Overnight Thalamic TES-TI to Modulate Sleep Spindles in Individuals With Schizophrenia Spectrum Disorders and Matched Healthy Controls (ONSETS)

Inclusion Criteria (all participants):

• U.S. citizen or holding permanent resident status
• English-speaking

Inclusion Criteria (Participants with SSD):

• DSM-5 schizophrenia spectrum disorder (SSD) diagnosis, defined as schizophrenia, schizoaffective disorder, or schizophreniform disorder (confirmed by clinical interview and/or chart review)
• Chronic illness, defined as diagnosis of SSD for at least 1 year
• Clinically stable outpatient (no psychiatric hospitalization in past 6 months; no change in antipsychotic medication in the past 6 weeks)

Inclusion Criteria (Healthy Controls):

• Medically healthy (based on self-report and study team review)
• Matched to SSD participants on age (±5 years) and sex

Exclusion Criteria (all participants):

• Current or past history of clinically significant neurological disorder or acquired neurological disease (e.g., stroke, traumatic brain injury), including intracranial lesions (including clinically significant findings identified on the structural MRI)
• Active suicidal ideation, plan, or intent (assessed via PHQ-9 item 9 and follow-up Columbia-Suicide Severity Rating Scale (C-SSRS) Screener; see Safety Response Procedure)
• Inability to provide informed consent, including inadequate decisional capacity in the judgment of the study team and/or study psychiatrist
• History of head trauma resulting in prolonged loss of consciousness; or a history of >3 grade I concussions
• Current poorly controlled headaches, including intractable or frequent migraines
• Any systemic illness or unstable medical condition that may cause a medical emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.)
• History of seizures, diagnosis of epilepsy, history of abnormal (epileptiform) EEG, or family history of treatment resistant epilepsy except for a single seizure of benign etiology (e.g. febrile seizures) in the judgment of a board-certified neurologist
• Possible pregnancy or plan to become pregnant in the next 6 months (self reported)
• Any metal in the head
• Any medical devices or implants (i.e. cardiac pacemaker, medication infusion pump, cochlear implant, vagal nerve stimulator)
• Dental implants
• Permanent retainers
• Any hair braid, dreadlocks, hair pieces, or extensions which cannot be taken out before the study sessions
• Any head coverings or headdress that participant feels uncomfortable removing for the purposes of study sessions
• Current use of medications known to substantially lower seizure threshold, specifically chlorpromazine, clozapine, bupropion, clomipramine, or maprotiline; or other medications at doses known to substantially lower seizure threshold in the judgment of the PI or Study Psychiatrist
• Current use of medications known to directly and substantially enhance sleep spindle activity, including benzodiazepines; non-benzodiazepine "Z-drug" hypnotics (zolpidem, eszopiclone, zaleplon); barbiturates; and gabapentin or pregabalin, within 2 weeks of the overnight study visits. Other sedating medications used as sleep aids (e.g., trazodone, hydroxyzine, mirtazapine) are permitted provided the regimen is stable across the two overnight visits; dose and timing will be recorded as covariates
• Current moderate-to-severe alcohol or other substance use disorder (DSM-5) other than nicotine or caffeine
• Active scalp lesions, broken skin, or skin conditions at planned electrode sites that would preclude safe electrode application
• Claustrophobia (a fear of small or closed places)
• Back problems that would prevent lying flat for up to two hours
• Regular night-shift work (second or third shift)
• Sleep apnea or other sleep disorder (self-reported)

Exclusion Criteria (Healthy Controls):

• Self-reported history of inpatient psychiatric hospitalization
• Self-reported current or past diagnosis of schizophrenia or any other psychotic disorder
• Self-reported first-degree relative with schizophrenia or any other psychotic disorder
• Self-reported current or past diagnosis of bipolar disorder or major depressive disorder with psychotic features, or current treatment for any psychiatric disorder other than depression or anxiety (handled via the medication rule below)
• Current use of any psychotropic medication, with the exception of a single SSRI or SNRI taken at a stable dose for at least 6 weeks for depression or anxiety. Current use of antipsychotics, tricyclic antidepressants, mirtazapine, trazodone, lithium or other mood stabilizers, benzodiazepines, non-benzodiazepine hypnotics, other anxiolytics, or stimulants will result in exclusion.