Beta Events and Sensory Perception

Brown University39 enrolled

Overview

Low-frequency brain rhythms in the alpha (8-14Hz) and beta (15-29Hz) bands are strong predictors of perception and functional performance in a range of tasks, and are disrupted in several disease states. The purpose of this study is to investigate a direct causal relationship between low-frequency brain rhythms and sensory perception, and to optimize commonly used TMS paradigms to impact sensory processing and perception in a similar manner as endogenous rhythms. To do so, this study combines human magnetic resonance imaging (MRI), electroencephalography (EEG), non-invasive brain stimulation (transcranial magnetic stimulation; TMS), and biophysically principled computational neural modeling.

Prior studies have shown that high power low-frequency brain rhythms in the alpha (8-14) and beta (15-29 Hz) bands in primary somatosensory cortex (SI) are associated with a decreased probability of perceiving tactile stimuli at perceptual threshold, and can be modulated with attention. Furthermore, high power beta activity in SI emerges as brief "events" (\<150ms) in un-averaged data, the rate and timing of which underlie the attentional and perceptual effects associated with high beta power. In this study, human electroencephalography (EEG) and a non-painful tactile detection task are used to assess if TMS that is hypothesized to mimic endogenous beta-frequency events impact touch perception in a similar manner. The TMS-EEG components of this study will use a within-subjects crossover design. In initial study sessions, all participants will have an MRI. In subsequent study sessions, participants will complete a tactile detection task while EEG data is recorded concurrent with online active, active control or sham control TMS. Analyses will focus on comparing detection probabilities of tactile stimuli presented at perceptual threshold and tactile evoked response potential waveforms between trials with and without concurrent TMS.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Interventions

Online Active SI-Hand TMSDEVICE

Online Sham SI-Hand TMSDEVICE

Single pulses of TMS will be delivered using a sham coil. One pulse will be delivered per trial (at least 5 seconds apart) "online" (during the tactile detection task), at 80% active motor threshold. TMS will target the hand area of primary somatosensory cortex (SI-Hand). This control condition is intended to mimic the peripheral (e.g. cranial/facial muscle and/or nerve activation, auditory evoked response), but not biological effects of TMS specifically related to somatosensory perception.

Online Active Control TMSDEVICE

Single pulses of TMS will be delivered using an active coil. One pulse will be delivered per trial (at least 5 seconds apart) "online" (during the tactile detection task), at 80% active motor threshold. TMS will target a control brain region, in a more superior and lateral location within SI. This control condition is intended to mimic the peripheral (e.g. cranial/facial muscle and/or nerve activation, auditory evoked response), but not biological effects of TMS specifically related to somatosensory perception.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Ability to provide informed consent/assent * Age: 18-65 years * English fluency: participants must be able to understand screening questionnaires and task instructions spoken/written in English. * Right handed: to reduce heterogeneity related to hand dominance, since our task involves touch perception on the hand, and examination of neural correlates in lateralized brain regions. Exclusion Criteria: * History of fainting spells of unknown or undetermined etiology that might constitute seizures * History of seizures, diagnosis of epilepsy, or immediate (1st degree relative) family history epilepsy * Any progressive (e.g., neurodegenerative) neurological disorder * Chronic medical conditions that may cause a medical emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.) * Metal implants (excluding dental fillings) * Pacemaker * Implanted medication pump or cochlear implant * Vagal nerve stimulator * Deep brain stimulator * TENS unit (unless removed completely for the study) * Ventriculo-peritoneal shunt * Signs of increased intracranial pressure * Intracranial lesion * History of head injury resulting in prolonged loss of consciousness * Pregnancy * Participants who have received prior TMS for medical treatment purposes. * Intellectual Disability or autism spectrum disorder (ASD) * Active psychosis, diagnosis of unipolar depression or bipolar disorder, active severe substance use disorders (within the last month), or active suicidal intent or ideations. * Conditions that may result in the inability to effectively carry out the tactile detection task, including loss of feeling, neuropathy or nerve damage in the hands or feet, chronic pain or fibromyalgia, and pain due to cancer, infection or arthritis. * If the participant is actively taking any of the medications that increase risk from TMS as indicated below, of if they have ingested any alcohol or any other drugs of abuse (see https://www.drugabuse.gov/drugs-abuse) on the day of the study session (prior to the session). Contraindicated medications: alcohol Amitriptyline Amphetamines ampicillin Anticholinergics Antihistamines aripiprazole BCNU \*\*bupropion\*\* cephalosporins chlorambucil chloroquine Chlorpromazine citalopram Clozapine Cocaine cyclosporine cytosine arabinoside Doxepine duloxetine fluoxetine fluphenazine fluvoxamine Foscarnet gamma-hydroxybutyrate (GHB) Ganciclovir haloperidol imipenem Imipramine isoniazid ketamine levofloxacin Lithium Maprotiline MDMA (ecstasy) mefloquine methotrexate metronidazole mianserin mirtazapine Nortriptyline olanzapine paroxetine penicillin phencyclidine (PCP, angel's dust) pimozide quetiapine reboxetine risperidone Ritonavir \*\*Sertraline\*\* Sympathomimetic theophylline venlafaxine vincristine ziprasidone

Outcomes

Primary Outcomes

Threshold-Level Tactile Detection Hit Rate

Participants receive one or zero tactile stimuli per trial and report detection or non-detection using a button press. Tactile stimuli are delivered at participants' individual perceptual threshold level (perceived roughly half the time). On a given trial, TMS may also be delivered 100 msec before the tap ('TMS100'), 25 msec after the tap ('TMS25'), or not at all ('TMS Null'), each for an equal number of trials. The 'hit rate' is defined as the number of trials with correctly detected tactile stimuli divided by the total number of trials on which a tactile stimulus was presented.

Time frame: Tactile detection was assessed between TMS and no TMS trials continuously during the TMS interventions - during the Active SI TMS session, and during either the Active Control TMS or Sham Control TMS session. The sessions were at least 1 week apart.

Secondary Outcomes

EEG Tactile Evoked Response Potential (ERP)

Participants receive one tactile stimulus per trial concurrent with EEG recording. The EEG-measured ERP immediately following each tactile stimulus is assessed and compared across conditions, with and without TMS at different latencies. 'TMS null' refers to trials in which no TMS was delivered, 'TMS100' refers to trials in which TMS was delivered 100 msec before the tactile stimulus, and 'TMS25' refers to trials in which TMS was delivered 25 msec after the tactile stimulus. 'Hit trials' are trials in which the tactile stimulus was delivered and corrected detected, and 'miss trials' are trials in which the tactile stimulus was delivered but incorrectly not detected. The outcome measure calculated here represents a time window between 78-161 msec after the tactile stimulus, where we expected to see a significant difference in signal amplitude between hit and miss trials based on prior publications.

Time frame: EEG measures were assessed between TMS and no TMS trials continuously during the TMS interventions - during the Active SI TMS session, and during either the Active Control TMS or Sham Control TMS session. The sessions were at least 1 week apart.