Electrochemical and Electrophysiological Correlates of Human Cognition, Emotion, and Behavior

Dysfunction in neurotransmission and neurophysiology can result in a range of psychiatric conditions including depression, anxiety, chronic pain, addiction disorders, and problems with attention (attention deficit disorder) and arousal (narcolepsy). Despite the clear importance of these neuromodulatory systems, practically nothing is known about how these systems act in real time (at sub-second timescales) in the human brain. This temporal resolution has proven to be important in basic research in rodent model organisms, where it has been shown that the extracellular concentration of neurotransmitters and neural electrophysiology changes within 100s of milliseconds of interacting with relevant stimuli while navigating moment-to-moment changes in the environment. Measurements with this kind of precision are necessary to be able to investigate how rapid changes in each of these signals modulate brain function, cognition, learning, mood, and behavior in humans.

Clinical context of proposed research: Patients with treatment (medication) resistant epilepsy can become candidates for surgical ablation of the epileptic foci. To determine which region of the brain is the source of the seizures, patient undergo phase-I and, if necessary, phase-II epilepsy monitoring. Phase-I requires non-invasive electroencephalographic recordings using electrodes placed on the patient's scalp. If these recordings are inconclusive, a patient becomes a candidate for intracranial depth electrode mapping which requires brain surgery to place the depth electrodes to monitor for epileptic onset foci for consideration of future neuromodulation, resection, or ablation. This intracranial monitoring procedure is the platform for electrophysiological and neurochemical measurements and recordings we propose here. Importantly, we will only perform research recordings from sites that will necessarily be damaged by the clinical procedures, and due to the unknown epileptic foci, will later be deemed either healthy or epileptic tissue.

Cognitive processing occurs very rapidly over functionally organized networks that can be distributed among multiple brain areas. Consequently, understanding such complex functions requires the ability to map neuronal activity with high spatial and temporal resolution. Unfortunately, most noninvasive methodologies for recording neuronal activity have either high spatial or temporal resolution, but not both. However, electrocorticography (ECoG) offers the unique ability to record neuronal activity with both high spatial resolution (single-cell activity) and high temporal resolution (sub-millisecond time-scale).

Additionally, certain behaviors are uniquely human, including complex motor control, executive function, language processing, and speech generation. Many of these behaviors and their neural underpinnings are impossible to study in other species. If we are to improve treatments for human neurological and psychiatric conditions, it is critical to study them directly in humans. Patients already undergoing neurological surgery for functional brain mapping (Phase II epilepsy monitoring) offer the rare opportunity to test the neural underpinnings of these uniquely human behaviors via direct neurophysiological recordings. Moreover, ECoG and MER offer the ability to stimulate and record from multiple cortical and subcortical regions. Microstimulation allows for a more complete assessment of both the functional connectivity among isolated brain regions and the causal role(s) of these regions in cognition and behavior.

Similar work using intracranial recordings in humans has already enhanced our understanding of human cognition both in health and disease. For example, it has helped identify the neural correlates of human memory, language, error monitoring and behavioral adjustment and emotion. This work has helped to develop breakthroughs toward enhancing and restoring cognitive function in humans.