Transcranial Direct Current Stimulation as a Treatment for Motor Function in Participants Living With Progressive Supranuclear Palsy, Corticalbasal Syndrome Degeneration, or Parkinson's Disease
Phase: NA
Conditions: Progressive Supranuclear Palsy, Cortical Basal Ganglionic Degeneration, Parkinson Disease
Sponsor: Baycrest

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Protocol for the project titled: 
 
Transcranial direct current stimulation as a treatment for motor function in participants living with Progressive 
Supranuclear Palsy, Corticalbasal syndrome degeneration, or Parkinson’s Disease 
 
Primary Investigators:  
Carlos Roncero: (tcroncero@gmail.com) 
 
Supporting Authors 
Howard Chertkow 
 
Initial Version:  March, 2018 
Revised Version: October, 2025 
Background and rationale 
 
In 2021, we published a case report (Roncero et al., 2021) where a participant with progressive 
supranuclear palsy completed a series of 20-minute walking sessions accompanied  with transcranial direct 
current stimulation (tDCS). Anode electrodes were placed over the motor cortex and cathode electrodes over the 
deltoid muscle to pass the tDCS current through midbrain areas. Using this setup, we began a longitudinal A-B-
A study with alternating real and sham sessions. The participant received eight 20-min sessions (4 mA) over 
two weeks while walking 24 m during stimulation and completing a computer-based Flanker task to engage 
motor systems. Walking speed improved significantly after stimulation. Monthly follow-ups without 
stimulation showed gradual slowing until a plateau, after which tDCS was reapplied—again improving walking 
speed. These results suggest tDCS can enhance gait in PSP. 
 Proposed Study 
 
Our preliminary results are sufficiently impressive to suggest that tDCS stimulation does have the 
potential to improve motor function when that ability is trained during stimulation. In the proposed study, we 
aim to conduct a study similar to the case study that we conducted, but with additional measures of motor 
function: gait, articulation, eye gaze, and motor dexterity. In addition, we wish to examine if such results can be 
replicated in people with other conditions, such as cortical basal syndrome (CBD), and Parkinson’s disease 
(PD). The rationale for including people living with these conditions is the overlap in motor and cortical 
network dysfunction observed across these disorders. Like PSP, both CBS and PD involve impairment of motor 
initiation, gait, coordination, and executive motor control due to degeneration in frontal–subcortical pathways. 

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Because our preliminary findings in PSP suggest that tDCS can enhance motor performance when combined 
with active task engagement, extending the protocol to CBS and PD will help determine whether these effects 
generalize to other neurodegenerative movement disorders that share similar pathophysiological mechanisms. 
This extension will also allow for comparison of stimulation responsiveness across related diagnostic groups 
and provide insight into disease-specific factors influencing motor recovery potential. 
 
Previous tDCS studies, including from our lab (Roncero et al., 2015) have found significant results with 
sample sizes between 10-20 participants for a two-round study comparing training sessions with real tDCS 
versus sessions done without tDCS. However, we plan to recruit 30 participants living with each condition as 
this will allow us to examine results per group, but also how the individual groups compare; for example, if 
improvements is seen for all three groups or only one diagnostic category (e.g. PSP).  
Methods 
The following is a flowchart displays the study schedule planned for each participant: 
Round 1 
 
Monday 
Tuesday 
Wednesday 
Thursday 
Baseline Evaluation 
Stimulation Session 
Stimulation Session 
Stimulation and Evaluation Session 
Stimulation Session 
Stimulation Session 
Stimulation Session 
Stimulation Session 
Stimulation Session 
Stimulation Session 
Stimulation Session 
Stimulation and Evaluation Session 
 
Two Weeks Later 
 
Monday 
Tuesday 
Wednesday 
Thursday 
 
 
 
Evaluation Session 
 
Two Months Later: Round 2 
 
Monday 
Tuesday 
Wednesday 
Thursday 
Baseline Evaluation 
Stimulation Session 
Stimulation Session 
Stimulation and Evaluation Session 
Stimulation Session 
Stimulation Session 
Stimulation Session 
Stimulation Session 
Stimulation Session 
Stimulation Session 
Stimulation Session 
Stimulation and Evaluation Session 
 
Two Weeks Later 
 
Monday 
Tuesday 
Wednesday 
Thursday 
 
 
 
Evaluation Session 
 
 
 

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Two Months Later 
 
Monday 
Tuesday 
Wednesday 
Thursday 
 
 
 
Evaluation Session 
 
 
Each participant will undergo two rounds of stimulation, two months apart, each consisting of twelve 
tDCS sessions over three weeks (four sessions a week). These sessions are planned from Monday to Thursday 
each week. We designed the schedule in this format so if a participant misses a session during the week, the 
participant will be allowed to have a make-up session on Friday of that week. In the first week of both rounds, 
sham tDCS (i.e., placebo) will be given to establish a pre-stimulation baseline. Scores obtained in the final 
session of that week (i.e., Thursday) will be used as the baseline scores. In this manner, we can obtain scores 
that already reflect some accumulated practice from having completed a few sessions, but before actual 
stimulation has begun. Real tDCS stimulation will be given in weeks two and three of each round. The scores 
obtained in the final session of the second week of stimulation will be recorded as the stimulation scores. These 
scores will be taken as the result of the tDCS effect because it represents two weeks of stimulation, which 
should be sufficient for producing a reliable effect. Thus, the scores from the final session of week 1 and the 
final session of week 3 will be compared to check for an immediate effect of stimulation on performance. This 
comparison will be observed as the immediate tDCS effect. To examine possible maintenance effects from 
stimulation, or delayed and continued improvement from stimulation, we will also ask participants in both 
rounds to return two weeks later to repeat the same tasks without stimulation, which can then also be compared 
to scores obtained in week 1, and it will be observed as the post tDCS effect.  An additional post-stimulation 
evaluation will happen two months later, again compared to week 1. At this time-point, we actually expect 
tDCS effects to have effectively washed-out, and the participant will have a condition similar to baseline (i.e. 
pre-stimulation). Comparing this result at two-months to week 1 will be observed as the wash-out tDCS effect. 
To make it convenient for participants, and reduce the amount of study time required from them, we will use 
scores recorded in the first session of week 1 of the second round (while participants are receiving SHAM 
stimulation) which is scheduled to occur approximately two-months post-stimulation. In the second round, 
because there is no third round, participants will simply return for a single session two months after their final 

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stimulation session to record their performance levels two months post-stimulation.  
 
Each round will effectively be identical (SHAM in Week 1, real tDCS in weeks 2 and 3), but a different 
montage will be different in each round (counter-balanced across participants). In one montage, two anode 
electrodes over the left and right deltoid muscles, and two cathode electrodes over the left and right motor 
cortex at C3 and C4. In the other montage, two anode electrodes placed over the left and right motor cortex at 
C3 and C4, and two cathode electrodes over the left and right deltoid muscles. In both montages, stimulation 
will be given at an intensity of 4 mA for 20 minutes; thus, the only difference between montages will be the 
relative position of the anode and cathode electrodes. In our case study, we had found the montage with the 
anode electrodes over the deltoid muscles and the cathode electrodes over the motor cortex at the top of the 
head was superior. Our explanation for this result is that when the anodes are placed on the deltoid muscles, the 
electricity better travels to the motor cortex via the spinal cord rather than entering through the skull, which 
shunts (reduces) a great of the electricity passing the skull bone. Indeed, when electricity must enter the brain 
via the skull, dispersion is expected first when it hits the bone matter, and again when the electricity reaches 
vascular fluid which typically surrounds the brain in older adults. This double dispersion leads to the electricity 
received being less intense and diluted when it reaches the key brain regions. By having electricity pass through 
the spinal cord, these dispersion effects are avoided and ensures a sufficient dose of electricity will reach the 
key brain regions. Furthermore, the electricity entering the brain will be driven towards the motor cortex due to 
the exit point being produced by the two cathode electrodes. This is our current hypothesis, and by having 
participants complete both rounds with different montages, we will be able to examine if one of the montages is 
superior.   
 
The tDCS stimulation will be administered via a Sortex tDCS device which allows the intensity of the 
stimulation to be amped up and down at any time during the session to the participants’ comfort. This machine 
also indicates the contact quality throughout the session. The current belief regarding tDCS is that its effect is 
more pronounced when performed with training. The training performed during tDCS stimulation produces 
neuronal oscillations in relevant brain areas, which in turn attracts the tDCS current to that area which then 
reduces the resting threshold of those neurons. In turn, these neurons begin to fire easier, which behaviorally 

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results in training being more effective and symptom reduction in that impaired behavior. These neurons are 
also prone to greater amounts of long-term potentiation and plasticity, leading to the consolidation of 
improvements in the tasks that were trained in the individual during stimulation. In other words, the 
improvements can be observed for a limited time post-stimulation. Consistent with these arguments, this study 
will have participants complete tasks while receiving tDCS or SHAM stimulation. First, they will be asked to 
walk from the half-way point of a 24m gait mat (i.e., at the 12m mark) to the end of the gait mat, and back 
again, which will measure the participant’s speed and additional gait-related measures. They will complete this 
task twice. Next, they will walk a 12m hallway from base to end and back again. For this second measure, only 
total time and interval times (every 3m) will be collected from the participant. They will also complete this task 
twice. In addition, stimulation will be continued when they walk from the gait mat to the hallway. This protocol 
is being used to maximize the amount of time participants are walking while receiving stimulation. However, if 
a participant wishes to do each activity once, this will be allowed to ensure participants aren’t feeling overly 
fatigued to complete the study. Also, during these walks, there will be two additional research assistants present 
whose only task will be standing near the participant, one at the side and one at the front that will walk with the 
participant to ensure they can catch the participant if they fear a fall is about to occur.  
 
Next, and while the tDCS stimulation completes (approximately the final 10 minutes of stimulation), the 
participants will be asked to do read words outload, followed by a FLANKER decision-making task. They will 
complete the FLANKER task twice: once where they verbally give the correct answer, and a second time where 
they will need to press one of two buttons depending on the image on the screen. Script rehearsal is done with 
the goal of improving articulation, while the FLANKER task is aimed at improving both articulation and motor 
dexterity. Finally, an eye gaze task will be administered where they will be asked to look in each cardinal 
direction, and then asked to maintain focus on an object while the experimenter moves their head in each 
cardinal direction. This task will allow us to check for improvement in eye motor control.  
Outcome measures.   
As previously mentioned, we have three critical time-points: immediate, post-stimulation, and wash-out 
tDCS effect. This time-points compare any improvement from tDCS to the baseline scores obtained on the final 

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sessions of week 1. In addition, there are two rounds representing two different montages. To examine these 
results, we will first use generalize estimation equations that compare the results for each time-point and the 
effect of round. In this manner, we can examine if results were significantly better at any time-point compared 
to the baseline, and if this result was affected by a particular montage. Our primary outcome measures will be 
those found for gait: compared to the baseline scores obtained in a round at the end of week 1, did scores 
improve (i.e., did they become faster) after receiving stimulation (measured at the end of week 3 in a round). As 
an exploratory analysis, we will also produce difference scores between baseline and the evaluation point where 
the walking speed was most improved (e.g., Eval 2 Score minus Baseline Score). A multiple regression will 
then be run with sex, age, and diagnosis as predictors to examine if these variables were predictive of the 
improvement observed. We may lack the numbers for the power required to examine these effects, but will still 
present means for groups by sex, age, and diagnosis to allow readers to examine the differences among the 
demographic groups (if any). A similar set of analyses will be done for the additional tasks (e.g., FLANKER), 
but these results represent secondary outcomes in the study as our primary focus is gait. 
Inclusion and Exclusion Criteria 
Participants must be able to walk unassisted, or with the assistance of a walker or cane, and be 
individuals who walk daily. To be clear, walking on a daily basis is defined as being able to walk around the 
house or surrounding area if desired. For example, a person who is unable to ever walk, even if assisted with a 
walker or cane, and effectively restrained to their wheelchair, would be excluded because the study is primarily 
focused on whether tDCS improves walking ability. Lastly, participants should have a sufficient level of 
English to be able to express themselves verbally to be included in this study. For safety reasons, participants 
need to inform us whether they are finding the tDCS received tolerable. Also, due to the reading tasks, 
participants should be able to read words in English.  Finally, as the study requires the passage of electricity 
through the participants’ brain, individuals with metal implants within the brain such as shunts will be excluded.  
Confidentiality 
A research study file as well as medical records identifying participants will be maintained within Dr. 
Howard Chertkow’s lab. Names and identifying information will be replaced with a code, and the information 

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will be kept on file for 10 years after the end of the study. Data collected from participants’ who withdraw from 
the study will also be kept, unless participants withdraw consent for its use.  
Feasability 
Participants will be studied in two rounds over the course of four months. Participants will be 
individuals with PSP or CBD recruited through the participant database at Baycrest or from individuals that 
receive our brochure. We will also be receiving referrals through colleagues at Toronto Western Hospital, via 
our brochure, who are otherwise not associated with our research. Our colleagues at Toronto Western have 
already received prior REB approval to give potential participants our brochure, and people then call or email 
our lab if they are interested. Colleagues at Toronto Western have no involvement other than distributing our 
brochure.  Due to these resources, we anticipate no difficulty in recruiting participants for this project 
Safety 
 
The tDCS protocol for this experiment was determined according to the best practices observed in 
previous research using tDCS stimulation (Kuo, Paulus & Nitsche, 2014). Furthermore, tDCS is safe, has 
virtually no side effects, is technically easy to carry out, and is not uncomfortable to undergo (Hsu et al, 2015; 
Freitas et al, 2011). Multiple studies have also reported that the administration of 4 ma tDCS has no more 
adverse effects than 2 ma tDCS (see Nitsche & Bikson, 2017). No incidence of seizure has been recorded, 
although side effects could include headache, drowsiness, itching sensation, nausea, and, in rare cases, 
disorientation.  One study reported a single incidence of a 1st degree burn (Auvichayapat et al., 2012).  Another 
single study of treating depression using tDCS treatment reported a single incidence of hypomania (Loo et al., 
2012), but it remains to be seen if this rare side effect has ever been observed in patients being treated for 
neurodegenerative diseases. In our experiences, the only observed and reported side-effect has been temporary 
redness post-stimulation where the sponge was placed, and the occasional report of headaches. For headaches, 
we recommend participants take Tylenol. As we will be working with a population that is susceptible to falls, 
the portion of the session that includes walking will be carried out in the presence of the experimenter and two 
assistants who will walk in front of and behind the patient. 
  

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Significance and Importance of the study 
Currently there is no effective symptomatic therapy available for PSP or CBD, while no therapy has 
been shown to effectively decrease freezing in Parkinson’s disease. Our preliminary data indicates that 10 
sessions of tDCS will produce improvement in motor function, especially for walking speed and walking 
stability, as well as less freezing (measured as stance %). Considering the extensive motor impairments present 
in these conditions, an improvement in motor function would be quite beneficial. Furthermore, we will also 
examine if tDCS can improve other areas of impairment known to be related to these conditions (i.e., 
articulation and eye-gaze), and undertake post-stimulation follow-ups to determine the durability of the 
stimulation effect. Ultimately, we hope to produce a novel therapy feasible for many individuals with PSP, 
CBD, or PD. 
Yours truly, Dr. Howard Chertkow, Dr. Carlos Roncero,  
 

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