Transcranial Direct Current Stimulation and Cognitive Remediation Therapy for Psychosis
Phase: NA
Conditions: Psychosis
Sponsor: University of Minnesota

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 1 of 51 
Revised: July 24, 2018 
PROTOCOL TITLE: 
Transcranial Direct Current Stimulation and Cognitive Remediation Therapy for 
Psychosis 
PRINCIPAL INVESTIGATOR or FACULTY ADVISOR: 
Ian Ramsay, PhD 
Psychiatry 
612-672-6805 
ramsa045@umn.edu 
VERSION NUMBER/DATE: 
 
Version 17.0 Date 27MAY2022 
REVISION HISTORY 
 
Revision # 
Version Date 
Summary of Changes 
Consent Change? 
2.0 
7FEB2018 
-Exchange WAIS assessment for 
WTAR 
-Updated EEG device, protocol 
description 
-Remove midpoint PANSS 
assessment 
-Change 3 month follow up 
appointment to a 1 month follow 
up appointment 
-Update Consent and HIPAA 
forms 
-Update Consent process: consents 
will now be digital and captured on 
an iPad 
-Update research storage process: 
all research forms (PANSS, MINI) 
will be scanned into the secure Box 
file and then shredded  
Yes 
3.0 
20APR2018 
- Change accepted diagnoses to 
Schizophrenia and 
Schizoaffective 
- Change MINI to abbreviated 
version consisting of mood, 
mania, and psychosis modules 
- Add PositScience FaceMorph 
assessment, to baseline, post, and 
1-month follow-up 
- Add Social Functioning Scale and 
Quality of Life Scale to baseline 
and 1-month visits 
- Added VRFCAT assessment 
Yes 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 2 of 51 
Revised: July 24, 2018 
- Remove Barratt Impulsivity 
Scales 
- Break baseline assessments into 
two visits 
- Updated compensation to $255 
- Adding new recruitment flyer and 
contact card  
4.0 
24JUL2018 
- Add questionnaire asking about 
participant blinding 
- Add a tolerability questionnaire 
- Add a handedness questionnaire 
- Allow WTAR/ Edinburgh 
Handedness Scale to be 
administered during consent or 
baseline assessments 
Yes 
5.0 
07AUG2018 
- Removed language allowing 
pregnant women 
No 
6.0 
07 DEC 2018 
-Changed appointment and 
payment schedules 
-Added MMN and ASSR 
assessments to EEG visits 
-Updated inclusion and exclusion 
criteria 
-Added risks of communicating via 
email 
-Updated recruitment poster and 
cards 
-Updated phone screen 
-Updated consent form 
-Cleaned up language in protocol, 
consent form, and phone screen 
 
Yes 
6.1 
07 JAN 2019 
-Removed sentence from Potential 
Benefits section, per IRB request 
-Clarified how emails will be de-
identified 
-Clarified data collection and 
storage procedures, including a 
data flow diagram 
 
7.0 
18 FEB 2019 
-Specified passing score for 
UBACC 
-Added compensation for parking 
expenses 
-Added DPX, Web-Surf, and PSS 
tasks/measures 
Yes 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 3 of 51 
Revised: July 24, 2018 
-Added ability to use diagnostic 
assessments from other studies 
-Updated Data Flow Diagram 
-Clarified means of completion for 
assessments on schedule of events 
-Added ability to text participants 
from a University-owned cell 
phone 
-Added text authorization form 
-Added un-encrypted email 
authorization form 
-Updated payment schedule 
-Updated data storage procedures 
-Updated recruitment materials 
7.1 
02 APR 2019 
-Specified a 12-month outer limit 
for recency of diagnostic data 
obtained from other studies 
-Specified collaborating labs 
-Clarified that text and email 
communication are optional 
elements on the consent form 
-Updated website study description 
 
8.0 
10 MAY 
2019 
-Changed Ian Ramsay to PI 
(reflected on relevant study 
documents) 
-Updated total enrollment goal in 
protocol and consent 
-Updated storage procedures for 
EEG data 
-Removed sentence in protocol 
DERXW³GDWHRIELUWK´VWRUDJHWKDW
contradicted another sentence in 
the protocol 
-Added language to the consent 
about excluding people who are 
pregnant or possibly pregnant 
-Edited language on website study 
description to be easier to 
understand by a non-academic 
audience 
-Updated withdrawal 
circumstances for hospitalizations 
-Updated exclusion criteria 
 
Yes 
8.1 
19 JUN 2019 
-Corrected total enrollment from 
30 to 85 
Yes 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 4 of 51 
Revised: July 24, 2018 
-Clarified reasoning behind 
exclusion of pregnant women in 
consent form 
9.0 
20 AUG 2019 -Removed Web Surf task 
-Added fMRI including structural 
T1/T2, Rest, N-back Task 
-Added risks of EEG 
Yes 
10.0 
18 MAR 2020 -Updated withdrawal procedures 
for on-study hospitalizations 
-Updated devices that can be used 
for some assessments 
-Updated times of appointments 
-Added ability to recruit and use 
data from the COPRR registry 
-Updated consent form to 
combined Consent/HIPAA 
-Updated phone screen 
-Added MSI as a location to 
analyze imaging data 
-Removed FaceMorph from all 
timepoints 
Yes 
11.0 
22 JUL 2020 
-COVID-19 adaptations 
-Allow for some remote research 
activities through Zoom or phone 
call, including consent procedures 
-Allow some research activities to 
be skipped if risk of COVID-19 
transmission becomes too great 
-Allow participants to complete 2 
tDCS/CRT sessions per visit to 
reduce total number of visits, if 
desired 
-Added information about crisis 
situations 
-Require mask use by participants 
during most in-person procedures 
-Added COVID-19 Stress Screener 
Survey 
-Added COVID-19 Screening Tool 
-Added risk of COVID-19 
infection and information about 
mitigation efforts that will be taken 
by staff 
-Update and correction to UBACC 
Yes 
12.0 
14 OCT 2020 
-Added third arm (tACS) 
Yes 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 5 of 51 
Revised: July 24, 2018 
-Increased target sample to 105 
individuals 
-Added Sound-Induced Flash 
Illusion 
-Updated electrode sponge size 
-Added participant-facing 
Cognitive Training Instructions 
document 
-Updated recruitment and consent 
materials to account for third arm 
13.0 
02 FEB 2021 
-Corrected Sound-Induced Flash 
Illusion Task to a Flash-Illusion 
Task 
-Softened language regarding long 
term risks of tDCS and tACS 
-Clarified protocol language about 
completing BAC remotely 
Yes 
14.0 
07 APR 2021 
-Updated sunrise plan to allow 
volunteers to safely return to in-
person work 
-Removed optional fMRI from all 
time points (and updated all 
relevant recruitment materials) 
-Added Binocular Surround 
Suppression task to Baseline and 
Post-Training time points 
-Updated COVID-19 screening to 
align with IRB guidance and new 
MN DOH guidelines 
Yes 
15.0 
25 JUN 2021 
- Added recruitment details with 
regard to recruiting through 
community mental health services 
and agencies 
- Updated study staff contact 
information on consent form and 
recruitment materials 
- Added ability to reimburse 
participants for costs related to 
transportation to study visits 
Yes 
16.0 
6 AUG 
2021 
-Update payment amount for 
stimulation sessions on protocol, 
consent, and recruitment materials 
-Removed Flash Illusion task from 
protocol 
-Updated COVID-19 Screening 
form 
Yes 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 6 of 51 
Revised: July 24, 2018 
17.0  
27  MAY 
2022 
-Added language stating that the 
study team would use 
remote/pencil/paper version of the 
BAC app. 
 
 
 
 
 
 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
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Table of Contents 
1.0 
102.0 103.0 164.0 165.0 176.0 237.0 298.0 299.0 2910.0 3011.0 3212.0
 
3213.0 3514.0 3615.0 3916.0 3917.0 4018.0 4119.0 4220.0 4321.0 4322.0 4523.0
 
4524.0 4625.0 4626.0 51 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
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ABBREVIATIONS/DEFINITIONS 
Ɣ ASSR: Auditory Steady State Response 
Ɣ BAA: Business Associates Agreement 
Ɣ BACS: Brief Assessment of Cognition in Schizophrenia (BACS) 
Ɣ COPRR: Consortium of Psychosis Research Recruitment 
Ɣ C-SSRS: Columbia Suicide Severity Rating Scale 
Ɣ CRT: Cognitive Remediation Therapy  
Ɣ DPX: Dot Pattern Expectancy Task 
Ɣ DUA: Data Use Agreement 
Ɣ EEG: Electroencephaologram 
Ɣ fMRI: Functional magnetic resonance imaging 
Ɣ NOS: Not otherwise specified 
Ɣ PANSS: Positive and Negative Syndrome Scale 
Ɣ MMN: Mismatch Negativity 
Ɣ PSS: Perceived Stress Scale 
Ɣ QoLS: Quality of Life Scale 
Ɣ SFS: Social Functioning Scale 
Ɣ SZ: Schizophrenia 
Ɣ tCS: Transcranial Current Stimulation  
Ɣ TCT: Targeted Cognitive Training 
Ɣ tACS: Transcranial Alternating Current Stimulation 
Ɣ tDCS: Transcranial Direct Current Stimulation  
Ɣ VRFCAT :Virtual Reality into the Assessment of Functioning in Clinical 
Trials 
Ɣ WTAR: Wechsler Test of Adult Reading 
 
 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
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Revised: July 24, 2018 
STUDY SUMMARY 
 
Study Title 
Transcranial Direct Current Stimulation and 
Cognitive Remediation Therapy for Psychosis 
Study Design 
Randomized Controlled Trial, Double Blind 
Primary Objective 
To investigate whether tDCS enhances the effect of 
cognitive remediation therapy on cognition and 
functional outcome by comparing active vs. sham 
testing on the BACS 
Secondary Objective(s) 
To determine if tDCS and CRT will enhance 
functional brain activation measured by EEG over 
sham tDCS and CRT 
Research 
Intervention(s)/Investigational 
Agents 
-Transcranial Direct Current Stimulation compared 
to sham stimulation 
-Cognitive remediation therapy  
IND/IDE # (if applicable) 
N/A 
Investigational Drug Services 
# (if applicable) 
N/A 
Study Population 
Outpatients diagnosed with Schizophrenia or 
Schizoaffective disorder 
Sample Size (number of 
participants) 
105 
Study Duration for Individual 
Participants 
Approximately 2 months 
 
 
 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
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1.0 
Objectives 
1.1 Purpose: The proposed pilot study is a randomized controlled study to assess 
the effectiveness of transcranial Direct Current Stimulation (tDCS) to 
enhance cognitive remediation therapy (CRT) in patients with schizophrenia 
and schizoaffective disorder. We will determine whether any observed 
changes in symptoms and cognition are greater in participants who receive 
concurrent tDCS and cognitive remediation therapy as compared to 
individuals who receive sham stimulation. Additionally, we will determine 
whether there are functional changes in participants who received active vs. 
sham tDCS by comparing EEG data from both groups. 
2.0 
Background 
2.1 Significance of Research Question/Purpose:  
Cognitive dysfunction is associated with disrupted prefrontal 
gamma in schizophrenia: Cognition in schizophrenia (SZ) is 
characterized by broad and pervasive deficits observed across most 
neurocognitive domains1, and is associated with poor functional 
outcomes2. Therefore, cognition is a treatment priority for 
individuals with SZ and related disorders, but the specific neural 
mechanisms that underlie this aspect of SZ pathology are not fully 
understood. Accumulating research has pointed to disruptions in 
prefrontal gamma oscillatory power that underlie a range of 
cognitive deficits in SZ, including early sensory processes3 and 
higher-order cognitive control operations4±6. Studies in both animals 
and healthy adults demonstrate that cortical circuit performance can 
be enhanced by neural synchronization in cortical networks driven 
by gamma oscillations7±10. This suggests that disrupted gamma may 
be a core pathophysiological mechanism underlying cognitive 
deficits in SZ, and therefore a crucial treatment target for improving 
outcomes.  
Targeted cognitive training (TCT) is a computerized behavioral 
intervention that seeks to mechanistically target the sensory 
processing and integration disruptions that underlie some of the 
hallmark cognitive deficits observed in SZ11. This treatment 
adaptively exercises basic auditory, visual, and working memory 
processes to harness plasticity in temporal12, prefrontal13, and 
thalamocortical circuitry14. Previous findings indicate that 40-50 
hours of TCT yields improvements in global cognition in patients 
with both early15 and chronic SZ16. Cognitive improvements have 
also been observed in as few as 20-40 hours of the intervention17,18. 
TCT has also been shown to influence functional, structural, and 
electrophysiological plasticity. 40 hours of training was associated 
with increased activation in prefrontal brain areas associated with 
working memory19 and social cognition20, as well as morphological 
changes observed in the thalamus that corresponded to 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 11 of 51 
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improvements in overall cognition (Ramsay et al. In Press). TCT has 
also been demonstrated to normalize physiologically measured 
sensory processing and attention (i.e. sensory gating) in SZ 18. 
Notably, in response to training, prefrontal high gamma oscillatory 
power increased and corresponded to cognitive improvements21,22.  
More efficient cognitive training strategies are necessary to develop 
a truly viable clinical treatment:  TCT is a promising treatment to 
target cognitive deficits via disruptions in oscillatory gamma, but 
remains limited due to the heavy participant burden. Despite efforts 
to embed motivational and rewarding stimuli into TCT, treatment 
remains a major challenge. In previous TCT trials, ~36% of 
participants dropped out of the active training condition23 (compared 
to 24% in the control condition), and those who did complete the 
study only achieved an average of 32.93 hours (out of 40 assigned) 
of training over the course of 2 months15. These participants self-
UHSRUWHG³VOLJKW´HQMR\PHQWLQUHVSRQVHWR7&7VXJJHVWLQJWKDWLQ
spite of the cognitive benefits, individuals may have difficulty 
engaging for 8-10 weeks in such a treatment. Additionally, null 
findings have been shown in response to TCT24,25, with further 
evidence suggesting that early behavioral and neural target 
engagement may be necessary to evoke cognitive gains26,27. In those 
who do show improvement in response to TCT, the durability of 
cognitive gains may be limited28, with some effects weakening six 
months following training, even for individuals who do receive a full 
WKHUDSHXWLF³GRVH´(YLGHQFHIURPRQJRLQJVWXGLHVLQRXUODERUDWRU\
indicates that treatment adherence is highest in the first 10-15 hours 
of training (even if required to complete the training in the 
laboratory), suggesting that novel interventions could capitalize on 
this early engagement to promote immediate and long-term cognitive 
improvement. Thus, in order to develop a fully viable clinical 
treatment, two critical goals must be attained: 1) lessen the duration 
of TCT necessary to achieve cognitive and neuroplastic gains; and 2) 
improve the durability of TCT such that cognitive gains may sustain 
beyond the duration of treatment, influencing long-term cognitive 
and functional outcomes. 
Neuromodulation has the capacity to enhance TCT:  Transcranial 
direct current stimulation (tDCS) is a viable neuromodulatory 
approach with promise for enhancing cognition in SZ. tDCS applies 
weak (1-2mA) electrical stimulation to the scalp, and is observed to 
evoke neural excitability and activity by influencing neural resting 
membrane potentials. Previous work has demonstrated that anodal 
tDCS reliably enhances motor-evoked potentials in healthy adults29, 
and can enhance prefrontal brain activation measured during a verbal 
fluency task30. In patients with SZ, prefrontal tDCS has been shown 
to elicit improvements in working memory31 that related to enhanced 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 12 of 51 
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prefrontal gamma oscillatory activity32, suggesting that such an 
intervention may evoke oscillatory neuroplasticity with pro-
cognitive effects in SZ. However, tDCS has also been shown to 
inhibit psychophysiological responses, which may be the result of 
³RIIOLQH´VWLPXODWLRQLHVWLPXODWLRQXQaccompanied by a task or 
goal-directed engagement). For example, a measure of auditory 
attention (mismatch negativity) and a measure of processing speed 
were both found to worsen in response to brief offline prefrontal 
tDCS33,34. This suggests that without placing effortful demands on 
the prefrontal system during stimulation, anodal tDCS could be 
reinforcing the inherent dysconnectivity consistently observed in 
SZ35.  
Both TCT and tDCS have independently shown a modulatory 
influence on prefrontal oscillatory gamma that coincides with 
cognitive improvement. Similar work in an animal model of SZ 
showed that cognitive inflexibility corresponded to deficient evoked 
prefrontal gamma oscillations, but recovered in response to direct 
prefrontal stimulation in the gamma frequency36. Based on this 
evidence, the current study will combine TCT and tDCS in human 
patients with SZ to test the hypotheses that: 1) individuals who 
undergo TCT+tDCS will show improvements in global cognition 
more rapidly than TCT alone (Aim 1), and 2) that TCT+tDCS will 
elicit increases in prefrontal oscillatory gamma power that coincide 
with improvements in global cognition (Aim 2). Though both 
interventions have demonstrated cognitive benefits independently, 
their synergistic effects remain unstudied. To date, one study has 
examined intermittent combined working memory-focused cognitive 
remediation and tDCS, demonstrating more rapid gains in working 
memory but no observed improvements in global cognition37. Also, 
previous work in our laboratory demonstrated that gains in auditory 
processing speed within the first 20 hours of TCT were predictive 
global cognitive improvement in SZ27, which may indicate a critical 
window for inducing long-term neuroplastic and behavioral gains. 
We will demonstrate that enhanced global cognition after a brief 
TCT+tDCS is more durable compared to TCT alone (Aim 3).  
Scientific Premise of Exploratory Aim: Computational approaches 
will be necessary to identify predictors of neuroplasticity: Cognitive 
deficits in SZ are characterized by disruptions spanning multiple 
biological and psychological levels of analysis, including genetic, 
molecular, circuit, system, and ultimately behavioral units38. 
Computational neuroscience approaches will be necessary to 
adequately model the complex mechanisms underlying the 
pathophysiology of SZ, as well as the targeted treatments that may 
seek to intervene at multiple biological and psychological levels39. 
Previous work has demonstrated that computational methods such as 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 13 of 51 
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machine learning have shown great promise for the diagnosis, 
prognosis, and personalized treatment of various psychiatric 
disorders40. For example, such an approach has been employed on 
EEG data to predict response to clozapine41; expanding on these 
findings will assist in the identification of biomarkers, and will be 
necessary to determine treatment efficacy in a personalized medicine 
approach. This exploratory aim seeks to utilize a similar approach to 
elucidate the viability of oscillatory biomarkers in addition to clinical 
characteristics in the prediction of a neuromodulation and cognitive 
training treatment response. In doing so we will explore whether a 
machine learning approach demonstrates that gamma oscillatory or 
functional connectivity patterns can predict treatment response to a 
TCT+tDCS intervention in individuals with SZ and related 
psychiatric disorders (Exploratory Aim). 
Significance of the Expected Research Contribution: This work 
has critically important implications for treatment in people with SZ 
and related psychiatric disorders, where cognitive deficits are shown 
to account for disruptions in functioning. If successful, these findings 
will elucidate a biological treatment target for cognition in SZ, and 
lay the groundwork for a new treatment that could be readily 
deployed in a clinical setting. 
Innovation: The proposed research is innovative as it examines the 
neural system and behavioral effects of TCT combined with tDCS. 
While previous outcomes have been mixed with regards to TCT and 
tDCS alone, findings from these literatures suggest both treatments 
may intervene on a common mechanism: prefrontal gamma 
oscillatory power and prefrontal functional activation. Given the 
SUHIURQWDOFRUWH[¶VFULWLFDOUROHLQERWKVHQVRU\DQGKLJKHU-order 
cognitive processes, as well as evidence from both the human and 
animal literatures indicating it may respond to neuroplasticity-based 
interventions, it serves as an ideal neural target for the treatment of 
cognition in SZ (though we acknowledge that changes in gamma 
may be governed by cross-frequency coupling with slower 
oscillatory patterns such as theta). This study is innovative in that it 
will use an experimental medicine framework to examine target 
engagement, and determine whether TCT+tDCS can improve the 
behavioral efficiency and sustainability over either intervention 
alone. Additionally, we propose exploratory analyses in which we 
will use a machine learning approach to assess whether baseline 
psychophysiology and behavior can predict treatment response. This 
computational psychiatry approach represents an innovative 
departure from previous work in this field, and will allow us to 
characterize and model both behavioral and neuropsychiatric 
mechanisms supporting cognitive recovery in SZ. 

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VERSION 17.0 DATE: 27MAY2022 
 
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2.2 Preliminary Data:  
Mobile cognitive training drives cognitive and symptom improvement 
in first-episode psychosis patients: 2XUODERUDWRU\¶VSUHYLRXVVWXG\DVNHG
patients with SZ (mean age 21 years) to undergo either 40 hours of TCT or 
computer games on laptops at home for 8 weeks15. TCT subjects showed 
significant gains in global cognition, processing speed, and verbal 
learning/memory, compared to controls (Figure 1, left). We show at 6-
month follow-up that the TCT group showed greater improvement in 
positive symptoms and trend-level improvement in total symptoms 
compared to controls (Under Review, Figure 1, right). In the current 
proposal, we aim to see similar effects in a shorter timeframe (20-hours of 
TCT; 10 hours tDCS; 3-month clinical follow-up).  
 
Cognitive training induces changes in prefrontal gamma power 
in patients with SZ: We have previously shown functional plasticity 
using fMRI and MEG in frontal cortex after training in patients with 
chronic illness (mean age 40 years)42,19,22,43. For example, prior to 
training, during a simple syllable-identification task, patients show a 
reduced M100 response in auditory cortex. After training, they show 
a significant increase in M100, as well as increases in high gamma 
power in prefrontal cortex (Figure 2).  Increased prefrontal high 
gamma power correlates with gains in M100, and both are associated 
with improvements in executive functioning. Thus, after training, 
significantly enhanced gamma-oscillatory power is observed in the 
prefrontal cortex. In this proposal we ask:  Does a TCT+tDCS 
intervention more rapidly induce changes in prefrontal gamma? Will 
changes in gamma correspond to changes in global cognition? 

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Gamma power is observed during resting EEG in patients with 
schizophrenia and their relatives: Findings from our partner group, 
the Sponheim Laboratory, has previously shown evidence of 
prefrontal gamma obtained during eyes-opened resting EEG in a 
sample of SZ patients, patients with bipolar disorder, and their 
relatives44 (Figure 3). A principal components analysis (PCA) 
limited to the 13-15 Hz frequency band was found to have 3 primary 
components, including gamma. The gamma signal was reliably 
observed in bilateral prefrontal cortex. For the current proposal, in 
addition to rest, we seek to measure pre- and post-treatment gamma 
power on a N-back working memory task, and in an auditory oddball 
paradigm. 
 

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Computational Model Selection and Outcome Prediction in SZ patients 
undergoing TCT: In support of the Exploratory Aim, we have employed a 
model selection and regression approach using the least absolute shrinkage 
and selection operator (LASSO)45 on 43 individuals who underwent TCT15. 
We carried out 10-fold cross validation of the LASSO using cognitive, 
behavioral, and demographic variables to predict cognitive outcomes in 
response to TCT. This procedure identified lower baseline global cognition, 
higher baseline education, and gender as variables predictive of increased 
global cognition following TCT (Ramsay et al., Under Review). We aim to 
use LASSO and related elastic net models for model selection in our 
machine-learning approach to determine whether baseline 
electrophysiology, in addition to cognition, behavior, and demographic 
variables, is predictive of response to TCT+tDCS. Such an approach has 
been previously used with EEG46,47. 
3.0 
Study Endpoints/Events/Outcomes 
3.1 Specific Aims:  
Ɣ To investigate whether tDCS or Alpha tACS enhances the effect of 
cognitive remediation therapy on cognition, symptoms, and functional 
outcomes 
Ɣ To determine if tDCS or Alpha tACS enhances functional brain 
activation measured by EEG 
3.2 Specific Hypotheses to be Tested:  
Ɣ tDCS and CRT will enhance cognitive gains measured by Brief 
Assessment of cognition in Schizophrenia (BACS) testing over sham 
tDCS and CRT. 
Ɣ Alpha tACS and CRT will enhance cognitive gains measured by Brief 
assessment of cognition in Schizophrenia (BACS) testing over sham 
tDCS and CRT. 
Ɣ tDCS and CRT will enhance functional brain activation and connectivity 
measured by EEG over sham tDCS and CRT 
Ɣ Alpha tACS will enhance functional brain activation and connectivity 
measured by EEG over sham tDCS and CRT. 
4.0 
Study Intervention(s)/Investigational Agent(s) 
4.1 Description: This protocol will utilize the StarStim Non-Invasive Wireless 
tCS Neurostimulator (Neuroelectrics, Spain). StarStim is a battery driven 
multi-channel direct current stimulator that delivers a low current to the 
outer cortex via small sponge electrodes (surface area of 25cm2), which are 
placed directly on the scalp. This device is supported for nonsignificant risk 
FOLQLFDOWULDOXVHLQDFFRUGDQFHZLWK)'$¶VUHJXODWRU\UHTXLUHPHQWVXQGHU
21 C.F.R. Part 812 for unapproved devices. For a full description of the tCS 

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VERSION 17.0 DATE: 27MAY2022 
 
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device, please refer to following documents (found in Supporting 
Documents): 
Ɣ StarStim User Manual 
Ɣ Electrodes User Manual 
Ɣ Safety & IRB Letter 
Ɣ FDA minimal risk letter 
Participants will wear a cap labeled with the 10-20 EEG system of electrode 
positioning. Prior to placing the cap, the stimulation electrodes will be 
soaked with a saline solution to minimize the risk of skin irritation. To 
stimulate the left DLPFC, the anode will be placed over F3, and its 
corresponding cathode over the right supraorbital region. The current 
intensity will be 2 mA (total current density over the stimulated area: 0.08 
mA/cm2) which is below the threshold for tissue damage. For the active 
stimulation, the current will be ramped up during the first 15 s to a 
maximum of 2 mA and maintained for the first 20 minutes of each cognitive 
remediation session. After the 20 minutes, participants will continue the 
remaining 40 minutes of training.  
A second condition will feature transcranial alternating current at an 
individualized alpha frequency (~10hz). Using the same electrode 
positioning (F3 and Fp2), subjects will receive 20 minutes of in-phase 
individual alpha +1hz sinusoidal stimulation at 1mA. 
For the sham stimulation, we will use the same electrode placement and the 
2mA tDCS current will be ramped down immediately after ramping up in 
order to achieve an effective blinding.  
The described electrode placement is consistent with previous protocols 
targeting working memory. (Fregni 2005, Andrews 2011, Gazzaley 2011). 
This procedure is also in accordance with other protocols that have outlined 
safe administration (Nitsche 2008).  These studies found that across more 
than 2000 subjects, no major side effects were reported. Minor side effects 
were found, which included itching under the electrode sponge and 
occasional occurrence of headache, fatigue, or nausea (Poreisz 2007).  
 
5.0 
Procedures Involved 
5.1 Study Design: This is a double-blind randomized controlled trial. 105 
participants, after signing informed consent and determining eligibility, will 
be randomized to receive either active tDCS, active tACS, or a sham tCS. 
Only 20 participants will be randomized to tACS. 
5.2 Study Procedures:  

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After the initial consent form has been signed, participants will undergo an 
abbreviated MINI, consisting of the mood, mania, suicide, and psychosis 
modules, to confirm diagnosis. The exception to this is if the participant has 
completed the MINI or Structured Clinical Interview for DSM-IV or DSM-5 
(SCID-IV or SCID-5) for another study within our lab or in a collaborating 
lab within the last year and has consented to sharing of data with other 
studies. Collaborating labs include those run by Drs. Sophia Vinogradov, 
Scott Sponheim, Kelvin Lim, and Angus MacDonald. If a participant is 
enrolled in the COPRR, study staff can also use diagnostic assessments from 
the COPRR. In these cases, the diagnosis can be confirmed from the 
previous diagnostic assessment. Re-evaluation of diagnosis will be made via 
the abbreviated MINI when the previous evaluation was more than 1 year 
earlier. They will complete the Columbia-Suicide Severity Rating Scale (C-
SSRS). They will also complete the WTAR. Inclusion of the WTAR allows 
cognitive gain to be analyzed against inherent intelligence. We will ask 
about handedness using the Edinburgh Handedness Inventory. Throughout 
one to three additional sessions, participants will complete the BACS, 
Positive and Negative Syndrome Scale (PANSS), Social Functioning Scale 
(SFS), Quality of Life Scale (QoLS), Perceived Stress Scale (PSS), COVID-
19 Stress Survey, Virtual Reality into the Assessment of Functioning in 
Clinical Trials (VRFCAT), Dot Pattern Expectancy (DPX), Binocular 
Surround Suppression, and an EEG evaluation including the N-back, 
Auditory Steady State Response (ASSR), Mismatch Negativity (MMN), and 
rest tasks. The WTAR, C-SSRS, and Edinburgh Handedness Scale may be 
completed during the additional sessions if there is not enough time during 
the consent visit. This proposed battery would assess cognitive control, 
cognitive gain, social functioning, working memory, changes in symptoms, 
and neural plasticity. Inclusion of PANSS and C-SSRS allows researchers to 
evaluate symptoms and monitor for adverse effects. Medications and 
substance use, including nicotine, will be recorded during initial evaluation 
as well. For the Binocular Surround Suppression task, participants will see a 
series of simple images (e.g., gray stripes) presented on a computer screen 
and will be asked to make basic judgments about their appearance (e.g., 
report which of the two images appears stronger). participants will make 
responses by pressing buttons on a response device (e.g., keyboard). Images 
will be viewed through a visual stereoscopic display device (like 3D 
glasses). Participants will be asked to keep their head position stable to 
focus their eyes at the center of the screen during the task. The task will take 
approximately 6 minutes. All intake/baseline tasks may be completed over 
2-YLVLWVGHSHQGLQJRQHDFKSDUWLFLSDQW¶VDYDLODELOLW\7RWDOLQWDNHEDVHOLQH
appointment time will be approximately 7-10 hours.  
 
The EEG acquisition will rely on a dedicated EEG system located within the 
ARC which utilizes ePRIME and Presentation software for data capture. 
EEG recording will be sampled at 1024 hz and carried out from 32 channels, 
including an array of frontal electrodes including F3, FZ, and F4. The EEG 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 19 of 51 
Revised: July 24, 2018 
assessment will examine prefrontal oscillatory activity during multiple 
tasks, including an Auditory Steady State Response (ASSR) task driving 
40hz and 20hz click trains, a Mismatch Negativity (MMN) task with 
duration and double deviant stimuli, eyes open and eyes closed rest, and the 
N-Back (2-back version described below). Preparation and recording will 
take approximately 2-3 hours in total. 
 
After baseline measurements are completed, all patients will participate in 
cognitive remediation therapy (CRT). Participants will complete between 2 
to 4 CRT sessions per week, each lasting approximately 60 to 90 minutes, 
for a total of 3 to 5 weeks. This study will utilize a commercially available 
CRT software system. The commercially available software will focus on 
enhancing sensory processing and working memory. Each CRT session 
involves an in-session assessment of skill acquisition (Bubble Pop and 
Sound Sweeps), as collected by the CRT software. The assessment will be 
completed prior to each CRT session and after its completion.  
 
Patients will be randomized into three arms: active tDCS vs. active tACS vs. 
sham tCS. In the tDCS condition, stimulation will be applied at a current of 
2mA via two saline soaked electrode sponges (25cm2) each CRT session. 
The anode will be placed over left DLPFC at F3, according to the 10-20 
international system for EEG electrode placement. The cathode will be 
placed over the contralateral supraorbital area. This placement is consistent 
with previous protocols targeting working memory. In the tACS condition, 
stimulation will have an identical electrode placement and will be applied at 
K]DERYHDQLQGLYLGXDO¶VLQGLYLGXDODOSKDSHDNIUHTXHQF\GHILQHGDVWKH
frequency with the highest power in the 7-13hz alpha range measured from 
resting EEG at baseline). Individual alpha tACS will be in-phase sinusoidal 
stimulation at 1mA. The sham condition will have an identical electrode 
placement as both the tDCS and tACS conditions. 
 
 
After electrodes have been placed, the participants will be instructed to 
complete their cognitive training via iPad for approximately 60 minutes.  
The tDCS will be applied at a current of 2mA via two saline soaked 
electrode sponges (25cm2) for the first 20 minutes of each CRT session in 
the active condition. In the sham condition, tDCS will be ramped up to 2 
mA via two saline soaked electrode sponges (25cm2) over the first 30 
seconds of each CRT session and then turned off. The tDCS device will 
remain in place throughout the CRT session. After completion of the 
training, the tDCS device will be removed.  
 
 
Participants will be asked to complete the C-SSRS at the completion of 5 
CRT sessions (Mid-Point assessment) and after 10 CRT sessions (End of 
Intervention assessment). At the End of Intervention assessment, 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 20 of 51 
Revised: July 24, 2018 
participants will additionally be asked to complete the EEG assessment 
(with N-Back, ASSR, MMN, and Rest), PANSS assessment, BACS, SFS, 
QoLS, PSS, COVID-19 Stress Survey, VRFCAT, Binocular Surround 
Suppression, and DPX. PANSS and C-SSRS evaluation will be used to 
determine any change in symptoms and safety for continuing in the study. If 
the study staff is concerned about an increase in symptoms, they may 
conduct an additional PANSS assessment at the mid-point assessment. The 
End of Intervention assessment will take approximately 5-8 hours over 2-4 
appointments. 
 
After the 10 sessions of training are completed, we will ask participants 
about the tolerability of the protocol. At the end of the 1-month follow-up 
visit we will ask participants if they thought they were in the active or sham 
condition. 
 
Participants may be asked to return to the ARC to re-administer sessions, if 
data was missing or of poor quality. If participants need to repeat a visit 
(e.g., readministration of EEG measures due to loss of data), they may be 
offered the same compensation for that visit a second time. Offering 
compensation for repeat visits will be at the discretion of the investigator 
and may be subject to reason for re-administration (e.g., the participant was 
intoxicated at their visit). Reasons for offering additional compensation will 
be documented with notes to file in the participant case files.  
 
Schedule of Events:  
Test / Means of 
Completion 
Consent 
Baseline 
Each 
Training 
After 5 
Sessions 
After 10 
Sessions 
1 Month 
Follow-
Up 
MINI / Researcher-
led 
X2 
 
 
 
 
 
WTAR / Researcher-
led 
X1 
X1 
 
 
 
 
Edinburgh 
Handedness Inventory 
/ Researcher-led 
X1 
X1 
 
 
 
 
CRT & tCS sessions 
/ On iPad* 
 
 
X 
 
 
 
PANSS / 
Researcher-led 
 
X 
 
 
X 
X 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 21 of 51 
Revised: July 24, 2018 
C-SSRS / 
Researcher-led 
 
X 
 
X 
X 
X 
BACS / On iPad 
 
X 
 
 
X 
X 
EEG (N-back, 
ASSR, MMN, & 
Rest) / On computer 
 
X 
 
 
X 
 
SFS & QoLS / Self-
report on iPad* 
 
X 
 
 
X 
X 
PSS / Self-report on 
iPad* 
 
X 
 
 
X 
X 
VRFCAT / On iPad 
 
X 
 
 
X 
X 
DPX / On computer 
 
X 
 
 
X 
X 
Tolerability 
Questionnaire / 
Researcher-led 
 
 
 
 
X 
 
Blinding Question / 
Researcher-led 
 
 
 
 
 
X 
Binocular Surround 
Suppression Task / 
On computer 
 
X 
 
 
X 
 
COVID-19 Stress 
Survey / Self-report 
on iPad* 
 
X 
 
 
X 
X 
1 WTAR and Edinburgh Handedness Scale will be completed at either the consent or 
baseline visit 
2 Unless able to confirm diagnosis from diagnostic assessment from previous study 
(within last 12 months) 
* Can be completed on an alternative device, if necessary. 
 
COVID-19 Adaptations: Due to the ongoing COVID-19 pandemic, the 
following modifications to study procedures may be used to mitigate 
pandemic-related risks while participating in this study. 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 22 of 51 
Revised: July 24, 2018 
Ɣ All study procedures that can be completed remotely will be 
completed remotely, if possible. Affected assessments are listed 
below. 
o MINI 
o WTAR 
o Edinburgh Handedness Inventory 
o PANSS 
o C-SSRS 
o SFS, QoLS, & PSS 
o COVID-19 Stress Survey 
o Tolerability Questionnaire 
o Blinding Question 
o Demographics 
o Some parts of the BAC (will primarily be done in person 
because some sub tests cannot be done remotely) 
Ɣ Certain in-person procedures may be forgone in certain cases. For 
example, if a participant becomes ill when they are well into the 
course of the study intervention, the remaining CRT sessions and in-
person Post-Training assessments can be forgone. If the PI deems it 
to be safe to collect those data at a later date, the participant may be 
asked to complete the missed assessments.  
Ɣ Study staff will allow participants to complete 2 CRT sessions at 
each appointment, if desired, in order to limit overall frequency of 
appointments. Participants will still be asked to complete 2-4 CRT 
sessions per week. These can be completed in 1-4 appointments per 
week, depending on the number of CRT sessions per appointment. 
Ɣ All participants will be screened for COVID-19 symptoms before 
any necessary in-person appointments. In general, the screening will 
assess risk through questions about symptoms, exposures to infected 
people, and high-risk behaviors (e.g., attending large events without 
precautions). Some questions will be optional, and will only be 
administered during high levels of community transmission (per 
CDC) or at staff discretion; the PI will make a determination 
whether the visit may continue if these optional questions are 
answered yes. The complete screening can be found in the COVID-
19 Screening document. Participant temperatures will also be taken 
before each EEG to confirm it is not higher than 100.4 degrees 
Fahrenheit. Documentation of a temperature =< 100.4 will be kept, 
but the exact temperature will not be recorded. 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 23 of 51 
Revised: July 24, 2018 
Ɣ As described in the Ramsay Lab Sunrise Plan, all participants will be 
required to wear a face mask during all in-person procedures. There 
will be some procedures that participants are not able to wear a mask 
(e.g., during an EEG). 
 
5.3 Follow-Up: Participants will return for repeat testing approximately one 
month after the end of treatment. Assessment with the BAC, SFS, QoLS, 
PSS, COVID-19 Stress Survey, VRFCAT, DPX, PANSS, and C-SSRS will 
occur at follow up. The final set of tasks should take approximately 3-4 
hours over 1-2 visits.  
5.4 Individually Identifiable Health Information: This protocol will involve the 
collection of Individually Identifiable Health Information.  
Ɣ Full names, phone numbers, and addresses will be collected to 
maintain contact with the research participants. 
Ɣ 7KHSDUWLFLSDQW¶VQDPHDQGPDLOLQJDGGUHVVZLOOEHXVHGIRU
compensation. 
Ɣ Email addresses will be collected from participants who consent to 
receiving either study related and/or compensation related 
communications via email.  
Ɣ Date of birth will be requested to determine eligibility for the trial. 
Age at time of participation will be used in data analysis. 
Ɣ Service dates for study appointments will be included in study 
records. 
Contact information will be stored in a secure dedicated folder in Box. Only 
qualified, trained study team members who require access to this file will be 
provided with access. Date of birth will be requested during the interview to 
confirm eligibility. Dates of study appointments will appear in the study 
files. All study data in binders and in REDCap will be completely de-
identified. Participants will be registered in OnCore, which will include their 
name and date of birth. If the participant is a Fairview patient, their Medical 
Record Number (MRN) will also be associated with their registration in the 
OnCore portal. 
6.0 
Data and Specimen Banking 
6.1 Storage and Access:  
All data management servers will meet all relevant privacy and security 
standards for electronic clinical trial data entry as storage, as well as HIPAA 
standards for confidentiality and privacy.  
Access to study data, particularly data with identifying information, will be 
limited to individuals listed on the delegation of authority log, or those who 
have authority to review study records. Identifying information will not be 
shared outside of the UMN study team unless required by law. Study staff 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 24 of 51 
Revised: July 24, 2018 
will only be provided with access to the study data that they need to perform 
their work duties. 
All identifying information will be maintained for a minimum of six years 
after the completion of the study in compliance with HIPAA regulations. 
Any data use agreements that allow for the sharing of study data will be 
maintained for a minimum of two years past their expiration.  
For a visual representation of the flow of study data, please refer to 
Appendix 1. 
Consent documents: Consent documents, including HIPAA Authorizations 
and UBACC assessments, will be collected and stored in REDCap. Historic 
consent documents that were previously collected on paper will be stored 
with the physical regulatory files in a locked cabinet in a locked office. If 
need be, participants may still complete paper consent documents. Copies of 
physical consents will be uploaded into a dedicated folder within Box. 
Locations of the consent forms will be documented within the regulatory 
files and OnCore system. These records will only be made available to study 
staff and will not be shared with any collaborators. Identifying information 
will not be shared outside of the UMN study team unless required by law.  
Assessment data: Some study data will be collected in physical forms, 
namely the MINI, PANSS, and miscellaneous notes captured during the 
assessment appointments. These documents will be kept in a locked drawer 
in a locked office space until they can be scanned to the Box folder. Each 
participant will have a separate folder in Box and all study files will follow a 
naming convention to identify participant, assessment, and time point.  
The DPX task may be completed on an AHC-IS supported laptop or the 
same computer listed in the EEG Data section below. The EEG-dedicated 
computers are not managed by AHC-IS, as the AHC-IS management 
software would potentially interfere with the sensitive communications 
between the devices and the EEG instruments. However, per the agreement 
with AHC-IS, these devices are not connected to the internet or another 
other devices, are not used for any purpose other than EEG collection, and 
do not process or store any PHI. If the DPX task is completed on an AHC-IS 
supported laptop, the data will be uploaded directly to Box for long-term 
storage. If the DPX task is completed during the EEG appointment on the 
psychophysiology lab computer, the data will be transferred via flash drive 
WRWKHVWXG\WHDP¶VGHVNWRSFRPSXWHUZKHUHLWZLOOEHXSORDGHGWR%R[IRU
long-term storage. After the data is uploaded to Box, it will be deleted from 
any devices it remains on (computers, flash drives, etc.). 
The Binocular Surround Suppression task will be completed on the same 
computer listed in the EEG Data section below. The EEG-dedicated 
computers are not managed by AHC-IS, as the AHC-IS management 
software would potentially interfere with the sensitive communications 
between the devices and the EEG instruments. However, per the agreement 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 25 of 51 
Revised: July 24, 2018 
with AHC-IS, these devices are not connected to the internet or other 
devices, are not used for any purpose other than EEG collection, and do not 
process or store any PHI. The data will be transferred via flash drive to the 
VWXG\WHDP¶VGHVNWRSFRPSXWHUZhere it will be uploaded to Box for long-
term storage. After the data is uploaded to Box, it will be deleted from any 
devices it remains on (computers, flash drives, etc.). 
Two assessments, the VRFCAT and BAC app, will be collected using 
technology developed by VeraSci (previously NeuroCog Trials). These 
assessment data will be stored directly onto servers maintained by VeraSci. 
The BAC App will be delivered on an iPad registered with AHC-IS, and the 
VRFCAT will be delivered on an iPad or a laptop managed by AHC-IS 
(depending on the version the developers provide access to). No assessment 
data will be stored on the devices. By design, the assessments will not 
collect direct identifiers, though it will store the date of data collection. All 
DVVHVVPHQWGDWDZLOOEHFROODWHGXQGHUQHDWKWKHSDUWLFLSDQW¶VXQLTXHVWXG\
ID number. Outcome data from the BAC and VRFCAT will be transcribed 
into a REDCap database in regular intervals by study staff. At the end of the 
trial and during interim analyses, study staff will extract all performance 
data for both the VRFCAT and BAC assessments for storage in Box. 
VeraSci will maintain records of all data generated during this study to use 
for their own purposes.  License Agreements and a DUA exist between the 
University of Minnesota and VeraSci to this end; as the instruments do not 
collect PHI by design, VeraSci declined to enter into a BAA with UMN.   
Performance data from BrainHQ cognitive assessments and training will be 
collected on the BrainHQ app and stored on secure servers hosted by Posit 
Science Corporation. Data will be collected on an iPad managed by AHC-
IS. No data will be stored on the device. All data will be collated using a 
unique study identification number and will not contain direct identifiers. 
Outcome data from the cognitive assessments will be entered into the 
REDCap database for this project. During interim analyses and at the end of 
the trial, study staff will extract the trial-by-trial and outcome data for both 
assessments and training from the BrainHQ website and store this data in 
Box for further analysis. Posit Science will maintain records of all data 
generated in this study to use for their own purposes. A BAA exists between 
Posit Science and the University of Minnesota Department of Psychiatry to 
allow sharing of this data.  
All other assessment data will be collected directly into the REDCap 
database during assessment appointments. AHC/HST-managed devices will 
be used to collect this data for in-person appointments. Any assessments 
collected in REDCap during a remote appointment will be completed using 
a participant-owned device. Data from the REDCap database will be 
extracted to Box during interim analyses and at the end of the project for 
final storage. The data will remain in Box indefinitely.  

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 26 of 51 
Revised: July 24, 2018 
All eCRFs will be reviewed by secondary staff to check for omitted data and 
data inconsistencies. Once data entry is confirmed correct, the record will be 
locked to prevent changes. Each data record will be evaluated regularly for 
errors. If errors are discovered, the record will be unlocked and the data 
corrected. An audit trail will be created and will allow recovery to any point 
in the change log if required. Once the data entered from scanned forms 
have been verified for accuracy and clarity, the documents will be shredded. 
Assessment data will contain no direct identifiers by design, though they 
will contain the date of data collection.  
If digital assessments are not available, paper/pencil or alternate online 
versions of the assessment will be used when possible. Study staff will 
upload or transcribe data to final storage location (e.g. REDcap) when 
available. Paper records will be kept in locked cabinet in locked office until 
date of destruction.  
 
EEG Data: EEG data will be collected on dedicated computers located in 
the Department of Psychiatry Ambulatory Research Center using E-PRIME 
software. These computers are not managed by AHC-IS, as the AHC-IS 
management software would potentially interfere with the sensitive 
communications between the devices and the EEG instruments. However, 
per the agreement with AHC-IS, these devices are not connected to the 
internet or any other devices, are not used for any purpose other than EEG 
collection, and do not process or store any PHI. Data from EEG assessments 
LVWDNHQIURPWKHVHGHYLFHVYLDIODVKGULYHWRWKHVWXG\WHDP¶VGHVNWRS
computer, where it is stored locally on the hard drive. The data will also be 
uploaded to the CMRR (Center for Magnetic Resonance Research) Secure 
Server. Both the dedicated EEG computers and the flash drive are regularly 
wiped of participant data. By design, the EEG assessment does not collect 
any direct identifiers, though it does store the date and time of assessment. 
The EEG computers, the flash drive, and the staff desktop computer are kept 
in locked offices in the Department of Psychiatry.  
 
fMRI Data: Previously collected fMRI data will be stored and analyzed at 
the Center for Magnetic Resonance Research (CMRR), which is part of 
AHC-IS. De-identified images are initially stored on the computers used to 
collect the data (these are routinely wiped of participant data), before being 
WUDQVIHUUHGWRWKH&055¶VVHFXUHVHUYHUV$OOORQJ-term data storage and 
analysis will be managed on the CMRR secure servers or MSI servers. Any 
additional behavioral data collected during the scans will also be stored in 
Box. 
Other Study Data: As part of the consent process, participants will be 
asked to share their contact information, including their full address, phone 
number, and email address with study staff. Participants will also be asked 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 27 of 51 
Revised: July 24, 2018 
whether study staff may contact their primary treating clinician to discuss 
their involvement with the study and safety concerns. This information will 
all be collected in a form in REDCap. Only qualified UMN study staff will 
have access to these forms.  
$QHQUROOPHQWORJFRQWDLQLQJWKHSDUWLFLSDQWV¶SHUVRQDOO\LGHQWLI\LQJ
information, including name and contact information, will be stored in Box 
in a dedicated study folder. Only qualified UMN study staff will have access 
to the study folder. This enrollment log will also maintain the key between 
subject ID numbers and personal identifiers. A separate randomization table 
will indicate which participant IDs were placed in each condition.  
Additionally, participant identities, date of birth, demographic data, and date 
of consent(s) will be maintained in OnCore. If the participant is a patient in 
the Fairview Clinics, their medical record number will also be associated 
with their account in OnCore. These records will be maintained for a 
minimum of six years after completion of the study. 
Text messages sent to and from participants will temporarily be stored on a 
8QLYHUVLW\FHOOSKRQH7KHFHOOSKRQHZLOOQRWVWRUHWKHSDUWLFLSDQW¶VQDPHLQ
WKHFRQWDFWOLVWRIWKHGHYLFHVWXG\VWDIIPD\VWRUHWKHSDUWLFLSDQW¶VQXPEHU
under their study ID code in order to recognize them during text 
conversations. When the participant has completed the study or withdraws, 
their contact information will be deleted from the phone. The cell phone will 
remain on University property, unless it is being taken home by a 
coordinator for the purpose of contacting a participant for an appointment 
scheduled outside of business hours (Mon-Fri 9AM-5PM). For example, if a 
coordinator had an appointment with a participant on Saturday, the 
coordinator could take the phone home with them on Friday night to 
FRQILUPWKHSDUWLFLSDQW¶VDWWHQGDQFHDWWKHDSSRLQWPHQWEHIRUHFRPPXWLQJWR
the University on Saturday. When the cell phone is not in use, it will be 
stored in a locked cabinet in a locked office. The phone will be locked with 
a passcode and will not have pop-up messages enabled on the locked screen; 
study staff will need to unlock the phone and navigate to the messages to 
read the contents of any texts received by participants. Text messages will 
be regularly deleted from the cell phone (at least weekly) to protect 
participant PHI. If the text messages are of significant concern (e.g., indicate 
a safety issue), the contents of the messages will be saved for future review, 
using screenshots of the conversation. The phone number/identification of 
the participant will be redacted from any transcripts. 
Participants may email study staff with questions or concerns, or to make 
arrangements for study visits. Emails with participants will be saved during 
the course of the study and will be deleted with other identifiable 
information. If deemed significant anGUHOHYDQWWRWKHSDUWLFLSDQW¶VVWXG\
record, de-LGHQWLILHGHPDLOVPD\EHVDYHGWRWKHSDUWLFLSDQW¶VVWXG\ILOHLQ
Box. To de-identify emails, all direct identifiers (name, email address, date 
of birth, etc.) will be redacted from the email in PDF format. Study staff will 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 28 of 51 
Revised: July 24, 2018 
place black bars over any directly identifying information. The redaction 
will be verified by a secondary staff member for accuracy and completion to 
ensure patient privacy prior to upload into Box for permanent storage. The 
dates of communication will be maintained in the emails to provide context 
for the conversation. 
6.2 Data:  
Ɣ 
Wechsler Test of Adult Reading (WTAR)  
Ɣ 
Edinburgh Handedness Inventory 
Ɣ 
Brief Assessment of Cognition in Schizophrenia (BACS) 
Ɣ 
Social Functioning Scale (SFS) 
Ɣ 
Quality of Life Scale (QoLS) 
Ɣ 
Perceived Stress Scale (PSS) 
Ɣ 
COVID-19 Stress Survey 
Ɣ 
Virtual Reality into the Assessment of Functioning in Clinical Trials 
(VRFCAT) 
Ɣ 
Dot Pattern Expectancy (DPX) 
Ɣ 
Binocular Surround Suppression 
Ɣ 
Positive and Negative Syndrome Scale (PANSS) 
Ɣ 
Columbia Suicide Severity Rating Scale (C-SSRS) 
Ɣ 
Cognitive Training Performance Data 
Ɣ 
EEG Data (with N-Back, ASSR, and MMN performance data) 
Ɣ 
fMRI Data (including structural and functional images) and related 
behavioral data (no longer collecting this data) 
Ɣ 
Protocol Tolerability Questionnaire 
Ɣ 
Blinding Reliability Question 
6.3 Release/Sharing: Data generated by Posit Science and VeriSci applications 
will be collected and maintained by these institutions and may be used to 
perform analyses in preparation of manuscripts, presentations, and other 
dissemination of results to the public, as well as for quality improvement 
and program development, as is seen fit by these companies. They will 
maintain these records indefinitely. Data collected by these applications will 
not contain direct identifiers by design, but will contain the date of data 
collection.  
Assessment data may be shared with outside collaborators, provided that 
there are appropriate data use agreements in place. Before sharing Posit 
Science or VeriSci data, the PI will verify that they approve the use of their 
data by another party, and help to establish any necessary agreements 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 29 of 51 
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between all parties. Any data that is shared with an outside collaborator will 
not contain any direct identifiers. Most likely a limited data set will be 
shared (e.g., assessment dates will still be included), but the data set may be 
completely de-identified if required by the data use agreements. Data will 
preferentially be shared via a data shelter managed by AHC-IE, but 
collaborators may be allowed to access the data in other means if necessary. 
The exact methods of access and data shared will be detailed in the data use 
agreements struck between the interested parties 
EEG data may be shared with outside collaborators, much like with 
assessment data. If necessary, the PI will enter into a data use agreement 
with the collaborators to ensure the participant data is protected. Participant 
identifiers will never be shared with the EEG data. Though the data will 
most likely be shared as a limited data set (e.g., date of assessments will be 
included), the data set may be completely de-identified if required by the 
agreements. Data will preferentially be shared via a data shelter managed by 
AHC-IE, but collaborators may be allowed to access the data in other means 
if necessary. The exact methods of access and data shared will be detailed in 
the data use agreements struck between the interested parties.   
 
7.0 
Sharing of Results with Participants 
7.1 Individual and group results will not be directly shared with research 
participants. Participants will be informed that they can learn more about the 
outcome of this study upon completion at clinicaltrials.gov or on the 
LQYHVWLJDWRUV¶SHUVRQDOODERUDWRU\Uesearch.  
8.0 
Study Duration 
8.1  
Ɣ 
An individual will be enrolled in the study for approximately two to 
three months total to provide complete data.  
Ɣ 
We anticipate requiring five years to enroll all subjects needed for this 
trial 
Ɣ 
After all subjects are enrolled, it will take approximately six months to 
finalize data collection and data entry. Data analysis will require 
another year to complete.  
9.0 
Study Population 
9.1 Inclusion Criteria:  
Ɣ 
Meet diagnostic criteria for schizophrenia or schizoaffective disorder 
Ɣ 
Are age 18-64 
Ɣ 
Fluent in written and spoken English 
Ɣ 
Have an outpatient status of at least 1 month prior to participation 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
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VERSION 17.0 DATE: 27MAY2022 
 
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Ɣ 
Has been on a stable dose of psychiatric medication for at least one 
month prior to participation (titration to a lower dose of psychotropic 
medications under supervision of a psychiatrist can be allowed at the 
discretion of the investigators) 
9.2 Exclusion Criteria: 
Ɣ 
History of seizures or epilepsy 
Ɣ 
Metallic cranial plates, screws, or implanted devices 
Ɣ 
History of craniotomy 
Ɣ 
History of stroke 
Ɣ 
History of eczema on scalp 
Ɣ 
Pre-existing sores or lesions at sites of tDCS electrode placement 
Ɣ 
Non-removable facial piercings  
Ɣ 
Current or possibility of current pregnancy 
Ɣ 
Active suicidal ideation at screening or baseline assessments, or 
previous intent to act on suicidal ideation with a specific plan, 
preparatory acts, or an actual suicide attempt within the last 3 months, 
as indicated by the C-SSRS 
Ɣ 
In the last 12 months, has received a clinically meaningful dose of a 
targeted cognitive training intervention as determined by the PI 
Ɣ 
WTAR standardized score below 70 
9.3 Screening: Individuals interested in participating will be screened using a 
series of questions probing for inclusion and exclusion criteria. The phone 
screen is included in the Recruitment Resources in ETHOS. Additionally, 
participants will undergo an exam of the scalp prior to tDCS administration 
to ensure that there are no lesions or sores at the stimulation site. 
10.0 Vulnerable Populations 
10.1 Vulnerable Populations:  
܆ Children 
܆ Pregnant women/Fetuses/Neonates 
܆ Prisoners 
܈ Adults lacking capacity to consent and/or adults with diminished 
capacity to consent, including, but not limited to, those with acute 
medical conditions, psychiatric disorders, neurologic disorders, 
developmental disorders, and behavioral disorders 
܆ Approached for participation in research during a stressful situation such 
as emergency room setting, childbirth (labor), etc. 
܆ Disadvantaged in the distribution of social goods and services such as 
income, housing, or healthcare 

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܆ Serious health condition for which there are no satisfactory standard 
treatments 
܆ Fear of negative consequences for not participating in the research (e.g. 
institutionalization, deportation, disclosure of stigmatizing behavior) 
܈ Any other circumstance/dynamic that could increase vulnerability to 
coercion or exploitation that might influence consent to research or 
decision to continue in research 
܆ Undervalued or disenfranchised social group 
܆ Members of the military 
܆ Non-English speakers 
܆ Those unable to read (illiterate) 
܆ Employees of the researcher 
܆ Students of the researcher 
܆ None of the above 
10.2 Adults lacking capacity to consent and/or adults with diminished capacity to 
consent: 
One of the hallmark features of psychotic illnesses is diminished cognitive 
functioning. Despite remarkable advances in psychiatry and neuroscience, 
there are relatively few treatments available for cognitive deficit. This 
research project is examining a potential treatment for cognition in 
psychotic illnesses; therefore, it is necessary to include individuals with 
diminished cognitive functioning to evaluate the effectiveness of the 
proposed therapy. This study is a minimal risk trial and those with 
diminished cognitive functioning will not face greater risks by participating. 
However, all participants must have capacity to provide informed consent at 
enrollment and throughout the study. Please refer to section 21.2 for the 
procedures to determine capacity to consent. 
10.3 Additional Safeguards:  
Some of the participants in this study may be patients of the investigators, 
Drs. Sophia Vinogradov and Ian Ramsay. Other participants may have this 
study introduced to them by their clinical care team at the partnered 
recruitment sites. To mitigate the possibility of coercion upon their patients, 
potential participants from the UMP Outpatient Psychiatry Clinic and 
Mental Health Neuromodulation Clinics interested in research opportunities 
PD\ILUVWFRPPXQLFDWHZLWKWKH'HSDUWPHQWRI3V\FKLDWU\¶V&OLQLFDO
Research Recruitment and Outreach Specialist, a neutral third party who 
will inform the patient of any study they potentially qualify for. If the 
patient is interested in learning more, the Outreach Specialist will introduce 
them to the study team, if possible, or collect their contact information to 
provide to the study team. If the Outreach Specialist is unable to meet with 
the interested party, another member of the research team will meet with 
them to discuss the study. All consent discussions will be conducted by 
study staff and not the investigator/clinicians. 

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11.0 Local Number of Participants 
11.1 Local Number of Participants to be Consented: Approximately 85 
participants will be enrolled. Approximately 68 participants are needed to 
support well-powered data.  
 
12.0 Local Recruitment Methods 
12.1 Recruitment Process: We will utilize recruitment flyers posted in the 
community and in the UMP Psychiatry Outpatient Clinic recruitment areas. 
We will also have postings on clinicaltrials.gov, Craigslist, 
vinogradovlab.com, the UMN Department of Psychiatry website, and 
StudyFinder that will allow participants to self-identify for this study.  
All outpatients seen at the UMP Psychiatry Clinic or Mental Health 
Neuromodulation Clinic are asked to complete a Consent to Contact for 
Research form to indicate if they are interested in being contacted for 
research opportunities. Study staff will request the contact information for 
those who have signed the consent form and meet basic inclusion criteria for 
the study, namely clinical diagnosis of a psychotic illness. Additionally, we 
have kept lists of previous participants or interested individuals who did not 
pass phone screens, who have consented to being contacted again in the 
future for further research opportunities. Individuals in both of these lists 
will be contacted by study staff, who will ask to describe the study to the 
individual on the phone and determine interest.  
When possible, study staff will place physical and electronic postings and 
make in-person and/or telephone announcements at community mental 
health support, advocacy, and service agencies. 
The Psychiatry Department has hired a Clinical Research Recruitment and 
Outreach Specialist who will be available to UMP clinic staff as a neutral 
party who can discuss research opportunities with patients. During a 
regularly scheduled clinic visit, the Specialist may briefly meet with the 
patient and ask them if they are interested in hearing about any research 
opportunities at the University of Minnesota. If the patient agrees, the 
Specialist will describe available studies which the patient may qualify for 
and if they are interested, provide contact information and recruitment 
materials to the patient. The Specialist may also ask if it would be okay to 
SURYLGHWKHSDWLHQW¶VFRQWDFWLQIRUPDWLRQWRthe study team or introduce 
them to study staff if they are available. The Specialist may also be 
responsible for asking patients to sign the consent form mentioned above 
which indicates if the patient may be contacted for research opportunities in 
the future. 
 

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Page 33 of 51 
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We will utilize the Consortium of Psychosis Research Recruitment 
(COPRR) in the Department of Psychiatry& Behavioral Sciences. COPRR 
provides research participants the opportunity to be added to a registry that 
contains their demographic and contact information, some assessment 
results, and study participation updates. The goal of COPRR is to reduce 
participant burden by centralizing recruitment and sharing assessment data 
that is collected in most studies. Data is stored in a secure REDCap 
database. Access WRWKHGDWDEDVHLVFRQWUROOHGE\WKHGHSDUWPHQW¶V5HVHDUFK
Recruitment & Outreach Specialist and is only granted after sufficient 
approval is confirmed. We will only use COPRR for its intended purposes 
and will follow guidelines from the COPRR PI for use of the database. 
 
Clinicians who see patients with psychotic illnesses within recruiting clinic 
locations may also discuss this study with their clients to see if they are 
interested in participating. If the client agrees, the provider may request that 
the client fill out a Consent to Contact for Research form, may ask to share 
their contact information with the study staff, or may provide them with IRB 
approved recruitment materials with contact information for the study. 
12.2 Source of Participants: 
Ɣ Current patients at the UMP Psychiatry Clinics 
Ɣ Patients entered into the Psychiatry Recruitment Registry 
Ɣ Participants entered into the COPRR 
Ɣ Former participants or individuals who failed phone screens who 
have agreed to be contacted for further research opportunities 
Ɣ Self-identifying individuals from the community 
Ɣ Patients from other partnered recruitment sites 
12.3 Identification of Potential Participants: 
Patients who are receiving clinical services for psychotic illness at UMP 
Psychiatry Clinics or other recruitment sites may be referred to this study if 
the treating clinician believes they are stable enough to participate in a 
research study. At UMP Clinics, patients will first be referred to the Clinical 
Research Recruitment and Outreach Specialist, who will make initial 
contact. At other partnering clinics, participants will be provided with 
contact information for the study staff, and the referring clinician may ask 
SHUPLVVLRQWRVKDUHWKHSDWLHQW¶VFRQWDFWLQIRUPDWLRQZLWKWKHVWXG\VWDII 
The Outreach Specialist has collected a list of patients who have signed the 
Consent to Contact for Research form, which includes their contact 
information and basic demographic data to determine eligibility. This list 
will be made available in Box for study staff involved with recruiting 
participants. First contact will be made by study staff.  

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VERSION 17.0 DATE: 27MAY2022 
 
Page 34 of 51 
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The lab has their own registry of former participants or individuals who 
failed phone screens, which includes basic demographic information. Any 
individual in this list who meets basic eligibility criteria may be contacted 
for this research by study staff.  
12.4 Recruitment Materials:  
Ɣ Flyer, Contact card 
Ɣ Clinicaltrials.gov and Study Finder posting 
Ɣ Website posting 
12.5 Payment: Compensation will be provided to participants in the form of 
reloadable gift cards hosted by ClinCard (GreenPhire). Participants will 
receive compensation when they have completed the assessment and 
training appointments. When a payment is uploaded to the card by research 
staff, participants will receive a notification by text and/or email if they have 
opted into this service. Participants will be notified that they will need to 
disclose personally identifying information, such as their name and address, 
in order to be registered in the ClinCard system. Participants will be 
compensated for their time and effort on the following schedule:  
Ɣ Consent and Diagnostic Assessment: $15 
Ɣ Baseline assessment completion: $85 
o Clinical assessment: $45 
o EEG assessment: $40 
Ɣ tDCS treatment sessions: $20 each @ 10 appointments = $200 
Ɣ End of Treatment assessment completion: $85 
o Clinical assessment: $45 
o EEG assessment: $40 
Ɣ 1 month follow up assessment: $45 
Ɣ Total compensation earned: $430 
If participants do not complete all of the Baseline or End of Treatment 
assessments, they will receive pro-rated payments based on the components 
they were able to complete. If participants are asked to re-do any 
appointments (e.g., re-administration of EEG due to poor signal quality), 
they may receive the same compensation for that visit a second time. 
Decisions to compensate for a visit the second time will be up to 
investigator discretion and may depend on the reason for readministration 
(e.g., the participant was intoxicated at their visit). 
 
Reimbursement for parking: 

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Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 35 of 51 
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Ɣ Participants may be offered discount tickets to pay for their 
appointment parking expenses if they park in the ramps at the 
Fairview hospital location. The vouchers dispensed to participants 
will be valid for time increments closest to, but not less than the 
length of their appointment, also accounting for time to get to and 
from their vehicle and time spent waLWLQJQHDUUHFHSWLRQHJ³8S
WRòKRXUV´YRXFKHUIRUDKRXUDSSRLQWPHQW6WXG\SHUVRQQHO
will not be able to compensate participants for any additional time 
spent parked in the ramps.  
Ɣ For other modes of transportation, up to $100 per participant can be 
reimbursed for public transportation or rides to appointments (taxi, 
Uber, Lyft, etc.) throughout the study. Receipts will be required for 
reimbursement of transportation costs and payments will be made 
on an as-needed basis, totaling up to $100 per participant. 
13.0 Withdrawal of Participants 
13.1 Withdrawal Circumstances:  
Ɣ ,IWKHSDUWLFLSDQW¶V3$1666FRUHLQFUHDVHVE\WKH\ZLOOUHTXLUH
clinical review before continuing. If their score increases by 50%, 
they will be removed from the study. A 25% PANSS change 
corresponds to a "minimal" change in CGI. A 50% PANSS score 
change corresponds to a "moderate" change in CGI. (Leucht et al, 
2005). 
Ɣ If at any time point a participant displays suicidal ideation with a 
rating of level of 4-5 on the C-SSRS, the participant will require a 
clinical evaluation. Should any suicidal behaviors emerge at any 
point during the study, the participant will also require a clinical 
evaluation. If in the opinion of the study team it is unsafe for them to 
continue in the trial, they will be removed. Crisis protocol will be 
followed, which may involve escorting the patient to the emergency 
room.  
Ɣ If the participant is unable to tolerate the tDCS stimulation, they will 
be withdrawn from the study.  
Ɣ If at any time the study staff or clinical care team of the participant 
believes that it is unsafe for the participant to continue in the study, 
they will be removed. 
Ɣ If the participant is incarcerated or hospitalized (deemed by the PI to 
be potentially related to study procedures) they will be removed 
from the study. 
Ɣ If the participant is not compliant with study procedures, they may 
be removed from the study at the discretion of the PI.  
13.2 Withdrawal Procedures: If participants are withdrawn from the study, the 
investigators will make a case-by-case determination as to whether they will 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 36 of 51 
Revised: July 24, 2018 
collect any final assessment data after terminating the intervention. If it is 
unsafe for the participant to continue participating in the study, follow up 
data will not be collected. Any previously collected data will continue to be 
used in the data analysis. 
14.0 Risks to Participants 
14.1 Foreseeable Risks: 
Ɣ Intervention risks: There are no known significant risks associated 
with the application of tDCS or tACS to date (Bikson et al. 2016; 
Brunoni 2011). Adverse effects of tDCS and tACS are minor and 
may include headache, nausea, fatigue, itching, discomfort, burning 
sensation, and dizziness, and a flashing sensation (phosphenes). 
 
Ɣ Risks of Assessments and Batteries: As with all assessments, there is 
the potential that we will ask questions that make the participant feel 
uncomfortable, embarrassed, or stressed. We will remind 
participants that they only need to provide the information that they 
are willing to answer and can ask to skip questions at any time. In 
addition, due to the length of the assessment visits, it is possible that 
participants can feel fatigued or stressed by the interview. We 
provide the option to split the assessment batteries over several visits 
in 1-2 week period to reduce the burden on the participant, and we 
will invite them to take short breaks in the middle of sessions to 
prevent fatigue.  
 
Ɣ Risks of Computerized Training: Participants may become frustrated 
or fatigued when participating in their computerized training 
program. To mitigate these risks, we limit the time to 60 minutes per 
training session. Additionally, they may take breaks in their training 
sessions if they need to. The programs are self-adaptive to adjust 
difficult level to approximately 80% success rates for individuals, 
which should help prevent feelings of frustration during the training 
programs. 
 
Ɣ EEG Risks: During electrode placement, the possibility of skin 
irritation from contact with the conductive gel exists. However, this 
is unlikely since the salt concentration of the gel is similar to that of 
human sweat. There is also a risk of abrasion to the scalp when 
applying the conductive gel to the electrodes. The gel applicator can 
feel rough and uncomfortable to sensitive skin. The administrator 
will check in with the participant regularly to make sure there is 
minimal discomfort during this process. 
 
Ɣ Randomization Risks: Since participants are randomly assigned to 
their treatment arm, they may receive treatment that is less effective 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
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VERSION 17.0 DATE: 27MAY2022 
 
Page 37 of 51 
Revised: July 24, 2018 
or has more side effects than the other study treatment, or other 
available treatments. However, the risks of randomization are 
minimal and not greater than minimal risk. 
 
Ɣ Confidentiality Risks: Participation in research will involve a loss of 
privacy due to the nature of the questions that are asked during 
assessment visits and data collected during training sessions. 
However, records will be handled as confidentially as possible. All 
participants will be assigned a unique study identifier that will be 
used to label all of their records. A link will be maintained on a 
private Box secure server accessible only to specific study staff 
listed in the Delegation of Authority log. This link will connect the 
SDUWLFLSDQW¶VLGHQWLI\LQJLQIRUPDWLRQVXFKDVQDPHHWFWRWKHLU
assigned ID number. No identifying information will be used in any 
report or publications that may result from this study. All study 
records will be kept in secure databases such as REDCap, OnCore, 
or Box. Paper records will be kept in locked cabinets in locked 
rooms. Data generated during training or assessments on Posit 
6FLHQFH¶VVHFXUHZHESDJHZLOOEHGH-identified and will be available 
for export for analysis. Identifying information will not be 
maintained with study records.  All members of the study team will 
be current with their HIPAA, CITI, GCP, and IRB trainings to 
ensure full compliance with confidentiality laws. 
 
Ɣ Email Risks: Participants will be able to opt-in to communicating 
with study staff via unencrypted email to arrange their appointments 
and receive study instructions. There are risks associated with email 
communication, and these risks increase when the emails are sent 
without an encryption service. Risks of sending or receiving emails 
without encryption include, but are not limited to: 
o Others can intercept messages 
o If messages are sent or received on an employer-owned 
device, the employer may have the right to save and read the 
messages. The internet or cell-phone provider may also have 
the right to save and read email messages. 
o A copy of the message may be saved on a device or computer 
system, even if it is deleted.  
o If an email address is not typed correctly, it can be sent to the 
wrong person 
o Emails can spread computer viruses. 
o Others may be able to access messages on devices that were 
lost, stolen, or thrown away. 
o If a user changes emails without notifying study staff, they 
may miss communications.  
 

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VERSION 17.0 DATE: 27MAY2022 
 
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Revised: July 24, 2018 
Emails that are sent to and by the study team will be saved as part of 
WKHSDUWLFLSDQW¶VVWXG\UHFRUG7KHHPDLOVZLOOEHSURWHFWHGDVWKH\
are with other study records. Emails will be redacted to remove 
personally identifying information if they are downloaded or saved 
from the original email account. All personally identifying 
information such as name and email address will be removed. A 
second individual will verify the removal of all personally 
identifying information prior to upload in Box for permanent 
storage. 
 
Participants do not have to opt-in to email communication in this 
study. If they change their mind about communicating via email at 
any time, they can notify study staff about their preferences to 
communication. If the participant would like to start using email 
during the study, they will need to sign an email communication 
consent form. 
 
Ɣ Risks of Text communication: Participants may opt in to communicating 
with study staff via texting a University-owned cell phone to arrange 
study appointments and receive other study updates. There are risks 
associated with text communication, including but not limited to:  
o Others can intercept messages 
o If messages are sent or received on an employer-owned 
device, the employer may have the right to save and read 
the messages. The internet or cell-phone provider may also 
have the right to save and read messages. 
o A copy of the message may be saved on a device, even if it 
is deleted 
o If the phone number is not typed correctly, it may be sent to 
the wrong person 
o Others may be able to access messages on devices that 
were lost, stolen, or thrown away 
o If a user changes phone numbers without notifying study 
staff, they may miss communications.  
Participants will be notified that the phone will only be monitored during 
business hours (Mon-Fri 9AM-5PM), unless they have an appointment 
scheduled outside of those hours. They will be informed that they should 
not use this phone as an emergency contact number as well. Texts that 
are sent to the study phone will be regularly deleted, unless they are 
IRXQGWREHVLJQLILFDQWWRWKHSDUWLFLSDQW¶VVWXG\UHFRUGRUVDIHW\,QWKLV
case, screen shots of the texts may be saved and redacted to protect 
privacy. StXG\VWDIIZLOOQRWVWRUHWKHSDUWLFLSDQW¶VQDPHLQWKHFRQWDFW
log. Their number will be saved with their study ID code so study staff 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 39 of 51 
Revised: July 24, 2018 
may identify them during conversations; once the participant completes 
participation in the study, their contact will be deleted.  
Participants do not have to opt into text communication in this study. 
If they change their mind about communicating via text, they can 
notify staff at any time about their communication preferences. If the 
participant would like to start using text during the study, they will 
need to sign a text communication consent form. 
 
Ɣ Some participants in the study may experience worsening psychotic 
symptoms during their participation. If a participant is hospitalized for 
psychiatric symptoms, their case will be individually reviewed by the PI. 
If the hospitalization does not appear to be caused by the study 
intervention, it will be considered a risk associated with a pre-existing 
condition and will not be reported to the IRB as an SAE. All 
hospitalizations will be recorded in the study files and will be available 
for review by study monitors. 
 
Ɣ COVID-19 Risk: We imagine the risk of COVID-19 infection while 
participating in this study to be no more than the risk presented during 
an average trip to the grocery store. Extensive precautions will be taken, 
including staff monitoring for risk factors (symptoms, exposures, high-
risk encounters, temperature checks), participant COVID-19 screening, 
required face mask use (participants and staff), required hand hygiene 
(participants and staff), required social distancing when possible, 
required additional PPE when social distancing is not possible (face 
shield, gloves, disposable gown [EEG only];staff only), and extensive 
disinfection procedures. More specific details about risk mitigation can 
be found in the Ramsay Lab Sunrise Plan and Recommendations for 
ARC EEG COVID-19 documents. 
15.0 Potential Benefits to Participants 
15.1 Potential Benefits: There are no direct potential benefits of this study to 
participants. If the experimental condition proves to be beneficial to 
schizophrenia subjects as a group, then this will be extremely helpful in the 
design of future remediation programs for patients. 
16.0 Data Management 
16.1 Data Analysis Plan: Our statistical analysis plan is to use a 2 (Between 
Group: Sham, Active) x 2 (Within Group: Time - pre-tx, post-tx) mixed 
ANOVA and test for a Group difference and an interaction between Group 
and Time. 
16.2 Power Analysis: To our knowledge, this is the first study to assess 
improvement in both cognitive measures and EEG when CRT is coupled 
with tDCS. A recruitment goal of 105 patients has been set.  In this pilot 

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VERSION 17.0 DATE: 27MAY2022 
 
Page 40 of 51 
Revised: July 24, 2018 
study, we propose to collect preliminary data to determine effect sizes for 
power calculations for future studies. 
16.3 Data Integrity: Missing data will be handled in two ways. First, any subject 
who discontinues the study prior to completion will be replaced by the next 
eligible subject. The number of subjects dropping from each treatment group 
will be analyzed at the end of the study to assess possible differences in 
retention rates between the three conditions. Other potential sources of bias 
will be assessed between-groups, such as differences in the adherence to 
treatment and baseline demographic characteristics. Second, if individual 
tests or interview items are not completed, multiple imputation techniques 
will be used to predict missing values. These will be based on methods 
appropriate for longitudinal responses (69). In our lab, schizophrenia 
subjects who have not dropped out of prior studies have had less than 5% of 
the above measures missing. For this reason, imputation of missing values 
has typically shown negligible effects on the means, variances, and 
correlations of outcome measures. In the case imputation is deemed 
necessary, results with and without imputation will be reported. 
17.0 Confidentiality 
17.1 Data Security:  
All digital records will require a username and password to access study 
information. The UMN will utilize a combination of Box, REDCap, and 
OnCore to store study data for this project, as well as AHC-IS managed 
devices. The servers maintained by Posit Science are HIPAA compliant, 
secure servers that will require permissions from the study team to access. 
VeriSci (formerly NeuroCog Trials) also operates on secure servers, but it is 
unknown if their servers meet HIPAA standards; however, by design, the 
data stored on this database will not contain any direct identifiers. The UMN 
has entered into agreements with both Posit Science (BAA) and VeriSci 
(DUA) to allow for the use of their software and the data generated.  
Any physical records will be maintained in locked cabinets in locked 
offices, until such time as the documents may be shredded in secure 
shredders. Access to these cabinets will be limited to the study team.  
Direct identifiers will not be included within assessment data or app 
performance data by design. Direct identifiers will be maintained in 
consents and participant registries, which will be maintained separately from 
study data. Date of birth will be captured in the REDCap database in 
demographics; however, it will be flagged as an identifier and will not be 
H[WUDFWHGIURPWKHGDWDEDVHIRUXVHLQDQ\DQDO\VHV2QO\SDUWLFLSDQW¶VDJH
at time of assessment will be extracted from the REDCap database.  
Participants will be registered within the ClinCard Greenphire payment 
system to receive their study compensation. Individually identifying 
LQIRUPDWLRQVXFKDVWKHSDUWLFLSDQW¶VQDPHDQGDGGUHVVZLOOEHLQFOXGHGLQ

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 41 of 51 
Revised: July 24, 2018 
this registration. ClinCard Greenphire is a HIPAA compliant system and is 
an approved payment method for the University of Minnesota. 
When participants are registered in OnCore using their Medical Record 
Number, their EPIC Medical Record will indicate that the participant is 
enrolled in this study. However, a copy of their consent form will not be 
placed in their medical record. Clinical staff can obtain contact information 
for the study staff using the enrollment information in EPIC, if need be. No 
VWXG\LQIRUPDWLRQZLOOEHLQFOXGHGLQWKHSDUWLFLSDQW¶VHPSOR\PHQWRU
education records.  
For a description of how data is collected, stored, and shared, please refer to 
Section 6.0 Data Banking.   
 
18.0 Provisions to Monitor the Data to Ensure the Safety of 
Participants  
18.1 Data Integrity Monitoring: Performance on all measures will be scored, 
submitted to the database, and monitored for accuracy and integrity. We will 
regularly conduct data audits to ensure the accuracy and completion of all 
data. Data sets will be locked once the information is verified as complete 
and accurate, and an audit trail will be available for all changes to data 
within the database with the capacity to restore to the original entry if 
necessary. 
 
18.2 Data Safety Monitoring: 
This is considered a minimal risk trial and we do not anticipate any adverse 
events from participation in the study. Nonetheless, we will review all 
unanticipated problems involving risk to participants, serious adverse 
events, and any participant deaths associated with the protocol. The PI will 
review all cases and make a determination as to the severity of the adverse 
event and its relation to study procedures, if any. Reports for events 
determined to be related to study procedures, those that are unanticipated, or 
those that are related to participant death will be promptly reported to the 
IRB. 
 
Study participants who become injured or ill as a direct result of the 
participation in the study will be able to seek regularly medical care, as 
needed. Should the study staff learn that a participant is experiencing 
suicidal ideation, or if they appear to have an increase in psychiatric 
symptoms, they may elect to make a mid-point assessment with the 
UBACC, C-SSRS, or PANSS to determine participant safety. If a 
participant makes study staff aware of active suicidal ideation (e.g., a score 
of 4-5 on the C-SSRS), study staff will inform Dr. Ramsay immediately, 
who will perform a safety evaluation (in-person or remotely, as appropriate) 
as soon as possible. If the Dr. Ramsay is not available or cannot be reached, 
study staff will reach out to Dr. Vinogradov. If deemed clinically necessary, 

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Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 42 of 51 
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the PI may elect to remove participants from the study if they find it is no 
ORQJHULQWKHSDUWLFLSDQW¶VEHVWLQWHUHVWVWRFRQWLQXHSDUWLFLSDWLRQLQWKH
study.  
 
We will follow guidelines for medical devices in the reporting of adverse 
events in this trial, which defines unanticipated adverse device effects 
(UADEs) in the Code of Federal Regulations in 21 CFR 812.3(s) as any 
serious adverse effect on health or safety associated with a device.  
 
19.0 Provisions to Protect the Privacy Interests of Participants 
19.1 Protecting Privacy: During all assessment appointments, participants will be 
reminded that their participation in this study is completely voluntary, which 
means that they can tell the study staff that they do not want to answer a 
question or complete a specific assessment if they do not want to. They will 
also be allowed to take breaks and will be offered refreshments during 
longer appointments. Participants are encouraged to break up assessments 
into multiple visits over 2-3 week periods to avoid fatigue and stress.  
When training new assessors, the research staff trainees must sit in on 
appointments to observe the assessments and then go over scoring after the 
appointment is complete as the first stage of their training. Participants will 
always be asked if it is okay to have an additional person sit in on their visit 
for training purposes prior to the appointment session. If the participant 
agrees, then the trainee will be invited into the room. 
 
The participant may choose to have a guest sit in on their appointments with 
them, if they would like. At the end of each appointment, particularly if 
sensitive questions are being asked (e.g., about sexual activity, drug use, 
etc.), the research staff may ask the guest to step out of the room to verify 
WKDWWKHUHZDVQ¶WDQ\IXUWKHULQIRUPDWLRQWKDWZDVQ¶WVKDUHGZLWKWKHJXHVW
present. 
 
Participants have the option to opt into un-encrypted emails from study staff 
to set up appointments or to discuss their study participation. Similarly, 
participants may opt into texting research staff on a University owned cell 
phone. If the participant does not give the study staff permission to contact 
via email or text, study staff will contact the participant by phone only. 
Participants will be able to indicate on their consent form which is their 
preferred method of contact: phone, email, or text. Participants may change 
their preferred method of contact at any point in the study, but if they have 
not already given permission for communication over email or text, they 
may be asked to sign an additional consent form for that mode of 
communication.  
 
Additionally, participants will have the ability to opt into both texts and 
emails from the ClinCard service to receive updates on the payments sent to 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 43 of 51 
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the reloadable gift cards. If participants do not agree to receive texts or 
emails from the ClinCard program, they will receive communication 
directly from the study staff for when their cards have been refilled. 
 
 
20.0 Compensation for Research-Related Injury 
N/A 
 
21.0 Consent Process 
21.1 Consent Process: 
Consenting will take place in a private office at the University of 
Minnesota Department of Psychiatry, Ambulatory Research Center. 
Prior to the appointment, research staff will send copies of the 
consent form and HIPAA Authorization, as available, via email. 
Only the staff obtaining consent, the subject, and any family 
members or friends invited by the subject will be present. The 
participant may be asked if they are willing to have training research 
team staff sit in on the consent appointment to observe the consent 
process; however, the participant may decline to have this person the 
consent session. The research coordinator or other trained research 
staff will explain the study to the participant. After explaining the 
study, the participant will be allowed as much time as needed to 
review the consent document and ask any questions that might arise 
before making the decision to participate. If necessary, the 
participant can delay participation and return to sign the consent 
form at a later time. The participant will be allowed to review the 
consent form in private for as long as they need. The participant will 
be encouraged to ask any and all questions prior to providing 
consent. Study personnel obtaining consent will emphasize first and 
foremost that the study is voluntary and will not influence that 
VXEMHFW¶VFOLQLFDOFDUHRUWKHLUUHODWLRQVKLSWRWKH8QLYHUVLW\RI
Minnesota. No participant will be under legal commitment at the 
time of their consent or during their participation in the study, and 
surrogate consent will not be allowed.  
Documentation of consent, assessment of capacity to consent, and 
the HIPAA authorization will be captured digitally on REDCap 
using an iPad. Participants will be offered a physical copy of the 
consent form and HIPAA authorization to read through during the 
consent discussion, or they may follow along with the digital copy. 
After the UBACC assessment is completed (section 21.2), the 
research staff will bring the participant to the signature block on the 
consent page and provide instructions to electronically sign the 
consent form. The participant will then be instructed similarly on 
how to electronically sign the HIPAA authorization. If necessary, 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 44 of 51 
Revised: July 24, 2018 
study staff can capture consent using paper forms. If consent is 
captured on a paper form, the copies will be scanned into a dedicated 
folder on Box, and the original forms will be kept in a locked drawer 
in a locked office.  
Consent to continue in the study will be addressed before each scheduled 
visit. The participant will be reminded that their participation in this study is 
completely voluntary and they do not have to continue unless they want to 
do so. In addition, if at any point during the study the staff has reason to 
suspect that WKHLQGLYLGXDO¶VFDSDFLW\WRSURYLGHFRQVHQWKDVGLPLQLVKHG
(e.g., the participant has increased psychotic symptoms), the study staff may 
choose to re-administer the capacity to consent assessment to confirm that 
the participant has capacity to provide ongoing consent. If the participant 
does not show capacity to consent, the PI will review their case and 
determine whether it would be best to withdraw them from the study 
completely or pause their participation until capacity to consent returns. 
In addition to the primary consent forms, we will have the subjects read and 
sign email communication and/or texting communication consent forms 
should they desire to opt into these types of communication. Participants 
currently enrolled in the study may also sign these consents at any time. 
 
COVID-19 Adaptations: Due to the ongoing COVID-19 pandemic, the 
following modifications to study procedures may be used to mitigate 
pandemic-related risks while participating in this study. 
Ɣ Consent procedures will be completed remotely through REDCap, 
while also using Zoom or a phone call to communicate. The consent 
form will be sent to the participant via email. Alternatively, study 
staff may be able to provide a web address and a survey code to open 
the consent survey. 
Ɣ The electronic versions of forms in REDCap may be formatted 
slightly different than the paper versions, due to limited formatting 
options in REDCap. 
Ɣ Participants will be prompted to enter a code during the consent 
procedures to ensure it is them completing the form. Study staff will 
provide the code through Zoom or by phone call. 
 
21.2 Cognitively Impaired Adults, or adults with fluctuating or diminished 
capacity to consent: 
To ensure that the potential participant has the capacity to provide 
informed consent, we will administer the UBACC prior to asking a 
participant to sign the consent documents. If the participant scores 
less than a 14 on the UBACC, the study staff obtaining consent may 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 45 of 51 
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review the study details in a single session of remedial education, 
and then administer the UBACC a second time. If the individual is 
still unable to score a 14 or higher on the UBACC after this remedial 
education, they will not be offered participation in the study. 
Individuals may be invited to participate at a later time if their 
cognitive status has improved in the opinion of their clinical care 
team and/or the PI. Participants who have had a medication change 
or hospitalization within one month of their consent appointment 
will be asked to wait to sign consent until they meet eligibility 
criteria. If participants sign consent before staff learn of medication 
changes or hospitalizations, they will be placed into a hold period 
until they are eligible to continue with baseline assessments.  
At times when the clinical care team or the study staff believe that the 
SDUWLFLSDQW¶VFDSDFLW\WRFRQVHQWPD\KDYHGLPLQLVKHGVWXG\VWDII
may redo the consent discussion and re-administer the assessment of 
capacity to consent to determine if the participant is still able to 
consent to participate. If the participant is determined unable to 
participate at that time, the investigators will make a decision as to 
whether the participant will be placed on temporary hold or 
withdrawn from the study. If the participant is placed on hold, they 
must successfully complete the UBACC assessment again before 
continuing with study procedures.  
Participants will not be invited for consent discussions during periods of greater 
impairment. Participants must have been in outpatient status for one month 
and on stable medications for one month prior to signing consent. If a 
participant is hospitalized for psychiatric reasons during the study, the PI 
will review the event and decide on a case-by-case basis if the participant 
should be withdrawn from the study. If the PI determines that the 
hospitalization is linked to study procedures or that continuing in the study 
could put the participant at greater risk, the participant will be withdrawn 
from the study treatment. Follow-up assessments may be completed on a 
case-by-case basis, as determined by the PI. 
22.0 Setting 
Research Sites: All research activities will take place in either the 
Department of Psychiatry Ambulatory Research Center or the Mental 
Health Neuromodulation Clinic in St. Louis Park. Remote study procedures 
may occur via Zoom teleconferencing or phone call. 
Recruitment will occur at the UMP Psychiatry Outpatient Clinic, UMP 
Mental Health Neuromodulation Clinic, other partnered clinics within the 
community, and online.  
23.0 Multi-Site Research 
N/A 
 

PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive 
Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 46 of 51 
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24.0 Resources Available 
24.1 Resources Available: 
Ɣ 
5HFUXLWPHQW:HZLOOEHUHFUXLWLQJIURPWKH3V\FKLDWU\&OLQLF¶V
Recruitment Registry, as well as contacting previous participants in 
our other research programs. Additionally, we will advertise locally 
within community settings.  
Ɣ 
Facilities: We have three facilities that can accommodate research 
visits. The primary location is the Department of Psychiatry 
Ambulatory Research Center. There are four dedicated appointment 
rooms available to meet participants for study visits, as well as 
overflow space. In the Mental Health Neuromodulation Clinic in St. 
Louis Park, study staff are able to reserve private rooms to conduct 
study appointments as needed. 
Ɣ 
Equipment: We have several iPads which can be used by research 
participants to complete their cognitive training during appointments. 
Our study staff are all equipped with desktop computers to conduct 
data entry and other study related tasks. All desktop computers are 
connected to dedicated secure Ethernet cords connected to the UMN 
secure networks and require passwords to log on. No identifying 
information will be stored on desktop computers. Additionally, we 
have two laptops for tDCS administration which will also be 
connected to the UMN secure networks via Ethernet. We have the 
necessary facilities to print subject binders. We have a StarStim tCS 
system..  
Ɣ 
Emergency facilities: In the case that the participant has an 
emergency, such as a heart attack, or if they express suicidal intent 
during an interview, rescue resources will be made available to them. 
At the Department of Psychiatry Ambulatory Research Center, the 
Emergency Department is located one floor below. In the case of a 
health emergency, study staff can call in a code to have emergency 
personnel come to the scene. If a participant is expressing suicidal 
intentions or has behavioral problems that warrant hospitalization, the 
study staff may either escort them to the emergency department or can 
call for security. At the St. Louis Park location, medical staff are on 
hand in the case of a medical emergency. For medical and psychiatric 
emergencies, study staff will call 911 for the participant to be brought 
to a hospital. 
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Remediation Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
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69. 
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VFKL]RSKUHQLD´Brain stimulation., vol:5 iss:3 pg:431-432. Jul 2011. 
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PROTOCOL TITLE: Transcranial Direct Current Stimulation and Cognitive Remediation 
Therapy for Psychosis 
VERSION 17.0 DATE: 27MAY2022 
 
Page 51 of 51 
Revised: July 24, 2018 
26.0 Appendix 1: Data Flow Diagram