Gault Lab

---

A major focus of the laboratory is developing objective measures of auditory hallucinations to complement traditional patient self-report. Current assessments rely heavily on subjective reporting, which can be limited by impaired insight, cognitive deficits, and fluctuating symptom awareness. To address this gap, Dr. Gault's team is developing multimodal approaches that integrate electroencephalography (EEG), deep brain stimulation recordings, video-based behavioral analysis, and artificial intelligence.

Preliminary findings identified a measurable "listening posture" during active hallucinations characterized by reduced facial expression, diminished head movement, and altered behavioral responsiveness. The proposed NIH R21 project will evaluate whether these behavioral patterns correspond with electrophysiological markers, including elevated beta-band oscillations and theta-gamma phase-amplitude coupling within language-processing networks. The ultimate goal is to establish objective biomarkers that can be used to monitor symptoms in real time, optimize neuromodulation therapies, and support development of adaptive DBS systems for schizophrenia.

Dr. Gault's neuromodulation research builds upon emerging evidence that the substantia nigra pars reticulata (SNr) may play a critical role in auditory hallucinations. Through collaborative clinical studies, the team has investigated DBS as a treatment for individuals with severe schizophrenia who remain symptomatic despite standard treatments. Findings from case studies and ongoing clinical work suggest that DBS targeting the SNr may substantially reduce or eliminate auditory hallucinations while normalizing abnormal neural activity in cortical language networks.

The laboratory is conducting translational research that combines clinical outcomes, electrophysiology, and machine learning to understand the neural mechanisms underlying symptom improvement and to identify biomarkers that can guide future personalized neuromodulation strategies.

In a widely cited analysis of neurosurgical outcomes, Dr. Gault and colleagues evaluated postsurgical morbidity and mortality associated with DBS and related procedures. This work demonstrated that the safety profile of modern DBS surgery compares favorably with many accepted neurosurgical interventions and supports further exploration of DBS for psychiatric conditions beyond current FDA-approved indications. The findings provide an evidence base for responsibly expanding DBS research into disorders such as schizophrenia and schizoaffective disorder.

A second major research area addresses ethical challenges associated with advanced neuromodulation technologies. While existing standards focus primarily on evaluating a patient's capacity to consent, many patients must choose among several complex treatment options that differ in risks, benefits, reversibility, and invasiveness.

To address this unmet need, Dr. Gault developed the proposed Direct Treatment Comparison Tool (DTCT), a novel framework designed to assess a patient's capacity to compare treatment options rather than simply consent to a single intervention. The DTCT builds upon the MacArthur Competence Assessment Tools and incorporates structured evaluation of understanding, appreciation, reasoning, and treatment choice across competing therapies

The proposed studies will evaluate the DTCT in patients considering DBS, responsive neurostimulation, Vagus Nerve Stimulation, surgical resection, and high-intensity focused ultrasound (HIFU) for epilepsy, essential tremor, and schizophrenia. This work seeks to improve patient autonomy, informed decision-making, and equitable access to advanced neurotechnology.

Complementing the capacity-to-consent research, Dr. Gault's work includes examination of stakeholder perspectives surrounding DBS for schizophrenia. Recent studies have explored how patients, caregivers, clinicians, and researchers evaluate the risks, benefits, and ethical considerations of invasive neuromodulation for severe psychiatric illness. These investigations help inform patient-centered clinical trial design and responsible implementation of emerging neurotechnologies.

Dr. Gault is also leading innovative work using large-scale electronic health record databases to better understand relationships among psychiatric, neurological, and medical disorders. Leveraging TriNetX, a global federated network containing more than 100 million patient records, her team has developed a novel Relative Frequency of Comorbidity (RFC) framework that estimates disease relatedness through real-world clinical data.

Current grant-supported research compares RFC-based disease networks with findings from modern genomic studies to identify shared biological and environmental risk factors across psychiatric disorders. The project extends beyond traditional psychiatric diagnoses to examine connections with hearing loss, tinnitus, autoimmune disorders, neurological diseases, aging-related conditions, and functional disorders. Results may improve disease classification, risk prediction, and identification of common therapeutic targets.

1. Age 22-70

2. Subject meets Structured Clinical Interview for DSM 5 (SCID 5) diagnostic criteria for schizophrenia or schizoaffective disorder determined by two psychiatrists. They have had residual symptoms (as described below) of schizophrenia or schizoaffective disorder for at least 5 years.

3. Subjects are determined to be treatment-resistant for at least one year prior to the Screening Visit as demonstrated by clinical evidence (determined by review of medical records and discussion with referring psychiatrist) of persistent AHs and/or delusions that have not responded to treatment with three adequate regimens of antipsychotic medication including one failed trial of clozapine as defined as follows:

• Adequate trials of two different antipsychotic drugs (not including clozapine) belonging to different classes of at least 12 weeks equivalent to at least 500 mg/day of chlorpromazine.
  
• A trial of clozapine of at least 12 weeks at a dose of at least 400 mg or a clozapine level of at least 350 ng/mL. Subjects unable to tolerate clozapine at this dose or for this duration because of intolerable side effects are also eligible.

4. Moderate to severe positive symptoms as assessed with five instruments:

• The core positive symptoms of the Brief Psychiatric Rating Scale (BPRS)
• The Psychotic Symptom Rating Scales (PSYRATS) with assessment of both hallucinations and delusions with 11 and 6 questions respectively
• Auditory Vocal Hallucination Rating Scale (AVHRS) interview of 16 questions with 5 responses to determine the  intensity, frequency, and characteristics of one’s AH’s
• Thought and Language Disorder (TALD);
• Scale for the Assessment of Positive Symptoms (SAPS).
  

5. Females must be postmenopausal, physically incapable of childbearing, or practicing an acceptable method of birth control. Acceptable methods of birth control include surgical sterilization, hormonal contraceptives, double-barrier methods (condom or diaphragm with a spermicidal agent or intrauterine device [IUD]), or abstinence. If practicing an acceptable method of birth control, a negative urine pregnancy test result has been obtained at baseline visits.

6. Subjects must have capacity to consent and be assessed by a psychiatrist who is not part of the investigative team.

7. Subject can read and understand English, communicates well with clinicians and is able to follow the recommended plan.

8. Medically able to safely undergo DBS procedure as determined by the study neurosurgeon.

9. Passing the pre-surgery work-up, including a history of reliable outpatient care follow-up, demonstration of reliable adherence to pre-surgery evaluation schedule, commitment to future follow-up, and approval by the study Ethics Board and pre-surgical evaluation.

10. Able to comply with all testing and follow-up requirements as defined by study protocol (including providing a home address and two local collateral contacts). Adequate outpatient follow-up history" be operationally defined (recommended: ≥75% of scheduled visits kept over the preceding 12 months with an established outpatient provider.

11. Has platelet count, PT/INR and PTT within normal laboratory limits.

1. Delusions or hallucinations or unusual thought content related to brain control by a device, or anything being implanted into their brain.

2. Pregnant or plans to become pregnant during the duration of the clinical trial.

3. The subject has a current or recent (last 6 months) history of illicit substance use disorder and is unable to abstain from illicit drug as demonstrated by a positive drug screen or divulged use history during any of the baseline visits. Alcohol, nicotine, or cannabis use is not an exclusion criterion unless use would interfere with the clinical trial as determined by the PI.

4. Subject has defibrillator or pacemaker or other implants that will interfere with MRI and functioning of the device. Subjects will be screened for the presence of any implanted metallic objects such as cardiac/neural pacemakers, defibrillators, aneurysm clips, certain heart valves, spinal nerve stimulators, artificial joints/limbs, shrapnel/bullets, metal fragments in their eyes, cochlear implants, hearing aids, dental implants, permanent orthodontic retainers, or mechanical birth control devices (women).

5. Unstable psycho-social conditions including lack of housing or poor support.

6. The presence of a condition or abnormality that in the opinion of the investigators would compromise the safety of the patient or the quality of the data. Examples include, a diagnosis of dementia, an uncontrolled seizure disorder for DBS in patients with epilepsy(59.2%))26, conditions requiring diathermy, a neurological condition that is a contraindication for DBS, or a history of traumatic brain injury associated with loss of consciousness of > 1 hour and/or intracranial/epidural/subdural bleeding.

7. Current imminent risk of suicide or serious self-harm as determined by a study psychiatrist.

8. Current imminent risk of violence as determined by a study psychiatrist.

9. Unresolved legal problems that could jeopardize continuation or completion of the study.

10. Known allergy to titanium, polyurethane, silicone, and nylon (the components of the device).

11. Unable to independently manage DBS device charging and do not have an identified support/caregiver plan.