Utilizing Invasive Recording and Stimulating Opportunities in Humans to Advance Neural Circuitry Understanding of Mental Health Disorders

Presenter

Lizzy Ankudowich, Ph.D.
Division of Translational Research

Goal

The goal of this concept is to encourage research utilizing invasive neural recording opportunities in humans to study the neural circuity underlying mental health disorders.

Rationale

Invasive neural recordings provide an unparalleled window into the human brain by facilitating exploration of the neural circuitry underlying complex moods, emotions, cognitive functions, and behaviors with high spatial and temporal precision. Additionally, the ability to stimulate, via the same electrodes, allows for direct causal tests by modulating network dynamics. Elucidating the circuits underlying complex human behaviors and determining how to manipulate those circuits into desired states could inform both invasive and non-invasive brain stimulation therapies of the future. Although early deep brain stimulation (DBS) studies for treatment-refractory depressed patients showed potential, larger pivotal studies have been unable to demonstrate efficacy, highlighting the need to deepen our understanding of the neural circuitry of mental health disorders.

Invasive neural recordings provide an excellent opportunity to explore the circuitry underlying complex human behavior and to translate lessons from animal research. These opportunities arise during the normal treatment course of a variety of clinical conditions. These can include intra-operative micro-electrode or strip recordings during DBS surgery, sub-acute epilepsy monitoring electrocorticography (ECoG) or depth electrode recordings, or chronic deep brain stimulation/responsive neural stimulation (DBS/RNS) devices capable of recording and stimulating. Many of these opportunities arise in patients being implanted for non-mental health related conditions. However, many relevant clinical populations (e.g., epilepsy and Parkinson’s patients) represent patient cohorts with comorbid mental health disorders. Careful study of fluctuating mood, cognitive function, and behavior of patients both with and without mental disorders can provide unique insights into behavioral network dynamics.

Direct neural stimulation will complement invasive recordings by enabling researchers to test mechanistic hypotheses and explore therapeutic options. Networks correlated with mood, cognitive, and behavioral changes (using dense behavioral assessments) can be modulated to assess for behavioral improvements. While current DBS and non-invasive brain stimulation therapies target localized areas, this research may demonstrate the distributed nodes involved in disorders, and therefore inform the design of new devices and therapies.

This concept would target a gap in the scientific knowledge of neural circuits related to mental disorders. Research related to this concept may include, but is not limited to, studies of:

• Acute intra-operative recordings from single-unit or strip electrodes.
• Sub-acute recordings from the epilepsy monitoring unit or related situations.
• Chronic recordings from recording/stimulating DBS systems.
• Research Domain Criteria (RDoC)-based paradigms to assess the relevant neural circuits of cognitive, affective, and social domains at a high spatial and temporal precision.
• Novel technological approaches of neural or behavioral recording and stimulation.