Intracranial Investigation of Neural Circuity Underlying Human Mood

Summary

Depression is one of the most common disorders of mental health, affecting 7-8% of the population and causing tremendous disability to afflicted individuals and economic burden to society. In order to optimize existing treatments and develop improved ones, the investigators need a deeper understanding of the mechanistic basis of this complex disorder. Previous work in this area has made important progress but has two main limitations. (1) Most studies have used non-invasive and therefore imprecise measures of brain activity. (2) Black box modeling used to link neural activity to behavior remain difficult to interpret, and although sometimes successful in describing activity within certain contexts, may not generalize to new situations, provide mechanistic insight, or efficiently guide therapeutic interventions. To overcome these challenges, the investigators combine precise intracranial neural recordings in humans with a suite of new eXplainable Artificial Intelligence (XAI) approaches. The investigators have assembled a team of experimentalists and computational experts with combined experience sufficient for this task. Our unique dataset comprises two groups of subjects: the Epilepsy Cohort consists of patients with refractory epilepsy undergoing intracranial seizure monitoring, and the Depression Cohort consists of subjects in an NIH/BRAIN-funded research trial of deep brain stimulation for treatment-resistant depression (TRD). As a whole, this dataset provides precise, spatiotemporally resolved human intracranial recording and stimulation data across a wide dynamic range of depression severity. Our Aims apply a progressive approach to modeling and manipulating brain-behavior relationships. Aim 1 seeks to identify features of neural activity associated with mood states. Beginning with current state-of-the-art AI models and then uses a "ladder" approach to bridge to models of increasing expressiveness while imposing mechanistically explainable structure. Whereas Aim 1 focuses on self-reported mood level as the behavioral index of interest, Aim 2 uses an alternative approach of focusing on measurable neurobiological features inspired by the Research Domain Criteria (RDoC). These features, such as reward sensitivity, loss aversion, executive attention, etc. are extracted from behavioral task performance using a novel "inverse rational control" XAI approach.

Relating these measures to neural activity patterns provides additional mechanistic and normative understanding of the neurobiology of depression. Aim 3 uses recurrent neural networks to model the consequences of richly varied patterns of multi-site intracranial stimulation on neural activity. Then employing an innovative "inception loop" XAI approach to derive stimulation strategies for open- and closed-loop control that can drive the neural system towards a desired, healthier state. If successful, this project would enhance our understanding of the pathophysiology of depression and improve neuromodulatory treatment strategies. This can also be applied to a host of other neurological and psychiatric disorders, taking an important step towards XAI-guided precision neuroscience.

Conditions

• Depression
• Epilepsy

Interventions

DEVICE

Brain Stimulation

Both patients in the depression and epilepsy cohort will have implanted intracranial stereo-EEG (sEEG) electrodes as part of their clinical trial and regular clinical care, respectively, The depression cohort will also have deep brain stimulation (DBS) leads implanted as part of their trial. We will deliver stimulation via the DBS and sEEG electrodes. We will adhere to well known safety parameters.

DEVICE

sEEG Stimulation

Both patients in the depression and epilepsy cohort will have implanted intracranial stereo-EEG (sEEG) electrodes as part of their clinical trial and regular clinical care. We will deliver stimulation via the sEEG electrodes. We will adhere to well known safety parameters.

Sponsors & Collaborators

• University of Minnesota

  collaborator OTHER

• University of Texas

  collaborator OTHER

• Baylor College of Medicine

  lead OTHER

Study Design

Allocation

NON_RANDOMIZED

Purpose

HEALTH_SERVICES_RESEARCH

Masking

NONE

Model

FACTORIAL

Eligibility

Min Age

21 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-07-03

Primary Completion

2028-03-31

Completion

2028-03-31

FDA Device

Yes

Countries

• United States

Study Locations