Oscillatory Contributions to Working Memory and Attention

Study Overview
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Brief Summary
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The objectives are articulated in the proposal's specific aims: Aim 1: To test the hypothesis that the cognitive control of unattended memory items (UMI) is implemented by the same frontoparietal mechanisms that control spatial and nonspatial attention. Aim 2: To test the hypothesis that the selection of visual stimuli, whether from the environment or from WM, is accomplished, in part, by the hijacking of low-frequency oscillatory dynamics that are fundamental to the waking-state physiology of the corticothalamic circuitry of the visual system. Aim 3: To test the hypothesis that the function of context binding contributes to delay-period activity of the posterior parietal cortex (PPC).

Detailed Description
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4.2.a Narrative Study Description There are 11 distinct experiments proposed, and each is described in turn. Experiment 1.a.: Unconfounding cognitive state from the passage of time for UMI reactivation This experiment entails recording the EEG, and delivering spTMS, while healthy young adult subjects perform two types of WM trials: dual serial retrocuing (DSR) trials and single-retrocue trials. DSR trials begin with the presentation of two items (drawn from categories face, motion, word), followed by an initial Delay 1.1, then Cue 1 indicating which of the two will be probed by the first memory probe. After Probe 1, Cue 2 indicates which item will be tested by Probe 2. Both trial types will feature 3 types of probe: match (50% of trials); nonmatch/same-category (drawn from same category as retrocued sample, 30% of trials); and nonmatch/lure (probe is the uncued item, 20% of trials. spTMS will also be delivered, unpredictably on half of the delay periods, to IPS2. Prospective power analysis, using the results from PMC 5221753 (and taking into account that Exp. 1.a., unlike PMC 5221753, will use a repeated measures design), indicates that 360 trials per subject, and 12 subjects, are required to achieve 80% power for the critical behavioral comparison, which is the comparative influence of spTMS on the FAR to nonmatch/lure probes for dual serial- vs. single-retrocue trials, assessed with the contrast [(FAR nonmatch/lure, dual - FARnonmatch/same-category, dual) - (FAR nonmatch/lure, single - FARnonmatch/same-category, single)]. (To balance the number of match and nonmatch probes, there will be a total of 720 trials per subject.) Each subject will participate in two 2.5-hr experimental sessions. (Allowing for 15% attrition inflates the target n from 12 to 14.) Exp. 2.a. spTMS/EEG of the frontoparietal salience map. Study PMC 4893488 used n of 17 to achieve reliable single-trial regression results, which are least-powered analyses planned with this dataset; 18 subjects will allow for same number of subjects per targeted hemisphere. From the perspective of counterbalancing order of region targeted with spTMS, 12 subjects would be needed (2 hemispheres * 6 possible orders); once the 12 counterbalancing cells have been filled, the remaining 6 subjects will be selected two-at-a-time, and assigned the same randomly selected order-of-region, one to each hemisphere). (Allowing for 15% attrition inflates the target n from 18 to 21.) Exp. 2.b. 1 Hz rTMS of the frontoparietal salience map. Study PMC 5725229 recruited 27 subjects, based on its own power analysis based on the literature, to use a rTMS procedure comparable to what Exp. 2.b. will use to disrupt the function of PFC, one of the regions that will be targeted in this study. Because several previous studies using TMS to study attentional selection have found evidence of hemispheric asymmetries in the control of spatial attention, 27 subjects per hemisphere to be targeted will be recruited, yielding a total of 54. (Allowing for 15% attrition inflates the target n from 54 to 62.) Exp. 2.c.1 Hz rTMS of FEF and IFJ. Considerations are identical to those for Exp. 2.b. Experiment 3.a. Studying alpha-band dynamics of spatial and temporal attention with EEG. Study PMC 4500270 found reliable effects of temporal prediction-related frequency-shifting in the alpha band with 15 subjects. Sixteen (16) subjects will be recruited in order to achieve equal counterbalancing. (Allowing for 15% attrition inflates the target n from 16 to 18.) Exp. 4.a. Strategic control of alpha-band dynamics for perceptually unchallenging visual selection. Considerations are identical to those for Exp. 3.a. Exp. 4.b. Strategic control of alpha-band dynamics for selection in visual WM. Considerations are identical to those for Exp. 3.a. Experiment 5 (addressing Aim 3). Testing WM storage vs. context binding accounts of the CDA Power analyses, carried out with resampling of simulated data derived from the preliminary results of this study, indicate that 36 subjects are needed for 90% power to detect a load effect (i.e., CDA for 3C trials > CDA for 1C trials). (Allowing for 15% attrition inflates the target n from 36 to 41.) Experiment 6 (addressing Aim 3). Varying the domain of context. Considerations are identical to those for Exp. 5.

Official Title
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Oscillatory Contributions to Working Memory and Attention

Conditions
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Young Adults

Intervention / Treatment
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* Behavioral: working memory and attention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age of # 18 <36. - Right-handed. Be in good health determined by the investigator on basis of medical history, physical and neurological exam; for EEG-only sessions no physical or neurological exams will be performed; Female subjects must be two years past menopause, surgically sterile or practicing a medically acceptable method of birth control (does not apply to EEG-only sessions); Female subjects must not be pregnant. Able to understand and speak English. Able to provide written consent prior to admission Exclusion Criteria: History of epilepsy, stroke, brain surgery, cranial metal implants, structural brain lesion, devices that may be affected by TMS or tCS(pacemaker, medication pump, cochlear implant, implanted brain stimulator); - Women who are breast-feeding (self report)*; History of head trauma with loss of consciousness for greater than 5 minutes; Any history of seizures; Any family history of seizures*; Diabetes requiring insulin treatment*; A serious heart disorder or subjects who have had a heart attack within the last 3 months; Subjects who meet DSM-IV criteria for alcohol /drug abuse problems within the last six months; Any current Axis I or II diagnoses or past Axis I diagnoses; Required use of medication that affects CNS function; A subject with metallic implants, such as prostheses, shrapnel or aneurysm clip-S, or persons with electronic implants, such as cardiac pacemakers. The magnetic field generated by the MR machine can cause a displacement or malfunctioning of these devices*; The female subject who is pregnant or planning to become pregnant; or a female subject of child-bearing potential who is not practicing a medically acceptable form of birth control*; The subject has had a diagnosis of cancer in the past 3 years and/or has active neoplastic disease; The investigator anticipates that the subject will be unable to comply with the protocol. Prohibited Concomitant Treatment: Any investigational medication; antipsychotic, antidepressant; or ECT; Other psychotropic medications including sedative hypnotics (excluding chloral hydrate zaleplon); sumatriptan (and similar agents); anxiolytics and herbals (e.g., St. John's Wort, Kava Kava); an introduction or change in intensity of psychotherapy; any nonpsychopharmacologic drug with psychotropic effects (e.g., antihistamines, beta blockers). Colorblindness Poor or Uncorrected Vision History of fainting/syncope

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2016-0500-Healthy YoungAdults<br>working memory and attention | Behavioral: working memory and attention<br>* Behavioral tests of working memory and attention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Experiment 1.a. Behavioral accuracy | Mean percentage of responses that are correct | 3 hours | 
| Experiment 1.a. Reaction time | The time, measured in milliseconds, that it takes a subject to press the match or nonmatch button after the memory probe appears. | 3 hours | 
| Experiment 1.a. Changes in multivariate pattern classification of electroencephalography data in response to prioritization cues and in response to pulses of transcranial magnetic stimulation. | Multivariate pattern classification is a method from machine learning that can be used to assess the neural representation of stimulus information in electroencephalographic signal (i.e., to decode the signal). The outcome measure is how decoder performance will change as a function of a stimulus's priority status, and in response to a pulse of transcranial magnetic stimulation. Note that this method entails analysis of the broadband electroencephalographic signal (bandpass filtered from 1-100Hz) in each of two formats: time domain, and spectrally transformed. The spectrally transformed analysis does not entail the separate analysis of discrete functionally defined frequency bands (e.g., alpha, beta, etc.) Rather, spectral power values at every integer frequency from 2 to 20 Hz and every other integer from 22 to 50 Hz - yielding 34 frequencies per channel - are used as features in the analysis. | 3 hours | 
| Experiment 1.a. Spatially distributed phase coupling extraction-identified components of the transcranial magnetic stimulation-evoked electroencephalography signal | Spatially distributed phase coupling extraction-identified components of the transcranial magnetic stimulation-evoked electroencephalography signal will indicate whether the unattended memory item reactivation effect is carried by a de novo component in the electroencephalography signal or by a change in the power of one or more beta components that were present in the signal prior to the delivery of transcranial magnetic stimulation. Note that this method entails analysis of a spectral transformation of the broadband electroencephalographic signal that does not entail the separate analysis of discrete functionally defined frequency bands (e.g., alpha, beta, etc.) Rather, spectral power values at every integer frequency from 2 to 20 Hz and every other integer from frequency from 22 to 30 Hz - yielding 24 frequencies per channel - are entered into the analysis. No a priori assumptions are made about the frequency composition of components that the method will identify. | 3 hours | 
| Experiment 2.a. The amplitude of multivariate inverted encoding model-reconstructions of stimulus location, derived from the transcranial magnetic stimulation-evoked response | Multivariate inverted encoding modeling will be used to reconstruct the representation of stimulus locations from the electroencephalography data, and the strength of the representation will be compared across three stimulus conditions. Note that this method entails analysis of the broadband electroencephalographic signal (bandpass filtered from 1-100Hz) in each of two formats: time domain, and spectrally transformed. The spectrally transformed analysis does not entail the separate analysis of discrete functionally defined frequency bands (e.g., alpha, beta, etc.). Rather, spectral power values at every integer frequency from 2 to 20 Hz and at every other integer frequency from 22 to 50 Hz - yielding 34 frequencies per channel -- are used as features in the analysis. | 5 hours | 
| Experiment 2.a. Spatially distributed phase coupling extraction-identified components of the transcranial magnetic stimulation-evoked electroencephalography signal | Spatially distributed phase coupling extraction-identified components of the transcranial magnetic stimulation-evoked electroencephalography signal will indicate whether the unattended memory item reactivation effect is carried by a de novo component in the electroencephalographic signal, or by a change in the power of one or more components that were present in the signal prior to the delivery of transcranial magnetic stimulation. Note that this method entails analysis of a spectral transformation of the broadband electroencephalographic signal that does not entail the separate analysis of discrete functionally defined frequency bands (e.g., alpha, beta, etc.) Rather, spectral power values at every integer frequency from 2 to 20 Hz and every other integer from frequency from 22 to 30 Hz - yielding 24 frequencies per channel - are entered into the analysis. No a priori assumptions are made about the frequency composition of components that the method will identify. | 5 hours | 
| Experiment 2.a. Correlation of the amplitude of multivariate inverted encoding model-reconstructions of the location of the unattended memory item with alpha band power. | Correlation of the amplitude of multivariate inverted encoding model-reconstructions of the location of the unattended memory item, derived from the transcranial magnetic stimulation-evoked response, with alpha band power when targeting occipital cortex. | 5 hours | 
| Experiment 2.a. Correlation of the amplitude of multivariate inverted encoding model-reconstructions of the location of the unattended memory item with beta-band power | Correlation of the amplitude of multivariate inverted encoding model-reconstructions of the location of the unattended memory item, derived from the transcranial magnetic stimulation-evoked response, with beta-band power when targeting the intraparietal sulcus. | 5 hours | 
| Experiment 3.a. Power in the alpha band of the EEG as a function of retinotopic location | Power in the alpha band of the EEG as a function of retinotopic location | 4 hours | 
| Experiment 3.a. Frequency in the alpha band of the EEG as a function of retinotopic location | Frequency in the alpha band of the EEG as a function of retinotopic location | 4 hours | 
| Experiment 3.a. Spatially distributed phase coupling extraction-identified components of the electroencephalography signal from signals corresponding to the attended location | Spatially distributed phase coupling extraction-identified components of the electroencephalography signal from signals corresponding to the attended location to assess whether expectation-related shifts in alpha-band frequency are produced by a change in the frequency of one oscillator or by a change in the relative power of multiple oscillators. | 4 hours | 
| Experiment 4.a. Behavioral accuracy assessed as mean percentage correct responses. | Behavioral accuracy assessed as mean percentage correct responses. | 4 hours | 
| Experiment 4.a. Reaction time assess as latency to press response button after onset of critical stimulus. | Reaction time assess as latency to press response button after onset of critical stimulus. | 4 hours | 
| Experiment 4.a. Power in the alpha band of the EEG as a function of retinotopic location | Power in the alpha band of the EEG as a function of retinotopic location | 4 hours | 
| Experiment 4.a. Frequency in the alpha band of the EEG as a function of retinotopic location | Frequency in the alpha band of the EEG as a function of retinotopic location | 4 hours | 
| Experiment 4.a. Spatially distributed phase coupling extraction-identified alpha-band components of the electroencephalography signal from signals corresponding to the attended location | Spatially distributed phase coupling extraction-identified components of the electroencephalography signal from signals corresponding to the attended location to assess whether expectation-related shifts in alpha-band frequency are produced by a change in the frequency of one oscillator or by a change in the relative power of multiple oscillators. | 4 hours | 
| Experiment 5. The amplitude of the contralateral delay activity (CDA) slow component of the EEG during the time period from 1000-1600 milliseconds after stimulus array onset. | The amplitude of the CDA slow component of the EEG during the time period from 1000-1600 milliseconds after stimulus array onset. Note that this is an event-related potential analysis in which time-domain datas are trial averaged. The data are not spectrally transformed, so functionally defined frequency bands in the EEG (e.g., alpha, beta, etc.) are not relevant for this outcome. | 4 hours | 
| Experiment 5. Multivariate inverted encoding modeling of the EEG signal to determine whether or not stimulus information is carried in this signal. | Multivariate inverted encoding modeling of the EEG signal to determine whether or not stimulus information is carried in this signal. Note that this method entails analysis of the broadband electroencephalographic signal (bandpass filtered from 1-100Hz) in each of two formats: time domain, and spectrally transformed. The spectrally transformed analysis does not entail the separate analysis of discrete functionally defined frequency bands (e.g., alpha, beta, etc.). Rather, spectral power values at every integer frequency from 2 to 20 Hz and at every other integer frequency from 22 to 50 Hz - yielding 34 frequencies per channel -- are used as features in the analysis. | 4 hours | 
| Experiment 6. Multivariate inverted encoding modeling of the EEG signal to determine whether or not contextual information is carried in this signal | Multivariate inverted encoding modeling of the EEG signal to determine whether or not contextual information is carried in this signal. Note that this method entails analysis of the broadband electroencephalographic signal (bandpass filtered from 1-100Hz) in each of two formats: time domain, and spectrally transformed. The spectrally transformed analysis does not entail the separate analysis of discrete functionally defined frequency bands (e.g., alpha, beta, etc.). Rather, spectral power values at every integer frequency from 2 to 20 Hz and at every other integer frequency from 22 to 50 Hz - yielding 34 frequencies per channel -- are used as features in the analysis. | 4 hours |