Assessment of Neural Dynamics in Severe Traumatic Brain Injured Patients with Disorders of Consciousness Casey S. Gilmore, Ph.D. Defense and Veterans Brain Injury Center Minneapolis VA Medical Center

Collaborators Giuseppe Pellizzer, Ph.D. Michelle Peterson, DPT, NCS Brian Fay, Ph.D. Charidimos Tzagarakis, M.D., Ph.D.

Consciousness

Disorders of Consciousness Arousal Awareness Coma Vegetative State Minimally Conscious State Consciousness Consciousness is defined by 2 elements: arousal and awareness Arousal is regulated by physiological functioning and consists of more primitive responses to the environment. (Predictable reflexive responses). It is maintained by the reticular activating system ( a network of structures and pathways) that include brainstem, medulla and thalamus. Awareness allows one to receive and process sensory information thus relating oneself to the environment. The psychological component is governed by cortical areas within the cerebral hemispheres. Coma-results when there is interference with the functioning of the cerebral cortex and the reticular activating system. There are no signs of arousal (eye opening) or awareness (interaction with the environment) Vegetative state-a coma-like state characterized by eye opening and the appearance of wakefulness in a state of partial arousal. No true awareness-reflexive activity. MCS-is distinguished from the VS by partial preservation of awareness. There is discernible behavioral evidence of self in relation to environment. Behaviors are inconsistent. Adapted from Laureys et al. 2004

Emergence from Altered Consciousness Interactive communication Functional object use Sense of self in the environment Challenges Clinical judgments concerning patients’ level of consciousness depend on inferences drawn from observed behavior. Sensory deficits, motor dysfunction or diminished drive may result in underestimation of cognitive capacity. This behavioral assessment is a challenging task given that DOC patients often have very limited or no ability to respond to stimuli or commands due to cognitive, sensory and motor disabilities. In addition, their level of consciousness may fluctuate in time and differ depending on the modality tested. ---------------------------------------------------------- Reliable and consistent interactive communication Accurate yes/no responses to six of six basic situational questions on 2 consecutive evaluations (can be via speech, writing, yes/no signals, or AAC) Aspen Criteria (Giacino J, 2002) Functional object use Appropriate use of at least 2 functional objects on 2 consecutive evaluations Consistent behavioral manifestation of a sense of self in the environment Those who are apraxic and aphasic

Objective Assessment of Levels of Consciousness Various brain imaging methods have their advantages EEG is a technique of choice as it provides high time-resolution data that capture the fast dynamics of neural activity. In addition, EEG can be used for bedside assessment, as well as in an examination room.

EEG Assessment of Levels of Consciousness Power in Frequency Bands Functional Connectivity Event Related Potential (ERP) Brain activity is characterized by dynamically interacting neural networks, and brain injuries interfere with those neural dynamics. Interestingly, despite the diversity of brain injuries across patients, there is evidence that characteristic neural dynamics are associated with different levels of consciousness VS is associated with less EEG activity in the high frequencies than MCS (Schiff et al., 2014) Measures of resting-state functional connectivity provided above chance distinction between MCS and VS patients (Holler et al., 2014) The neural dynamics of persistent VS patients are characterized by reduced interconnections of distant cortical networks relative to those of MCS patients (Wu et al., 2011). Measures of neural entropy, which assess neural networks complexity, were higher in MCS than in VS patients (Gosseries et al., 2011; Sitt et al., 2014) www.neurosky.com Hargrove et al, 2012 commons.wikimedia.org

Multidimensional classification of neural dynamics in Disorders of Consciousness Evaluate the neural dynamics of DOC patients Monitor changes of these neural dynamics across time Assess the prognostic value of EEG-based measures Evaluate: Using measures of power in different frequency bands, functional connectivity (phase coherence, both short-range and long-range), and ERPs Integrate behavioral and EEG assessment of DOC

Minneapolis VA Emerging Consciousness Program Preliminary Data Minneapolis VA Emerging Consciousness Program 2 patients in Minimally Conscious State (MCS) 21 and 31 year old males Motor Vehicle Accidents 2 healthy controls Resting State EEG

Differences in Power profiles between MCS and Controls The PSD profiles in MCS decreased progressively without noticeable characteristics. In contrast, the PSDs in Controls had a clearly defined alpha-band peak (~10 Hz).

Power profiles after Emergence from MCS (MCS+) The PSD profiles in MCS decreased progressively without noticeable characteristics. In contrast, the PSDs in MCS+ state had a strong beta-band peak (~20 Hz), whereas those of Controls had a clearly defined alpha-band peak (~10 Hz).   A large peak in the beta band has been observed in DOC patients in previous studies (Schiff et al., 2014), however to the best of our knowledge, it has never specifically been associated with emergence from MCS.   The peak of the beta band may indicate that MCS+ is associated with hyperactivity in the cortico-basal ganglia loops which is the main source of neural beta oscillations (Gatev, Darbin, & Wichmann, 2006).

Functional Connectivity lower in MCS, but higher after Emergence (MCS+) PLV for short-range interactions tended to be greater than for long-range interactions. More importantly, PLV changed as patients went from MCS to MCS+, and in both cases PLV was different than the Control group. Specifically, short-range and long range PLV was weaker in MCS than MCS+ and controls; whereas it was stronger in MCS+ condition than MCS and controls, which indicates a state of hypersynchrony during emergence from MCS.

Conclusions & Future Directions Contact: Casey.Gilmore2@va.gov Analysis of neural oscillatory activity with EEG can provide a sound basis for evaluating the level of consciousness of an individual, and monitoring changes in that level over time. This project will assess the effectiveness of several measures of brain activity in relation to the level of consciousness as measured by the clinical scales, and to their value as prognostic markers. A multidimensional approach of different measures reflecting neural activity will be used to increase effectiveness of short-term and long-term evaluation of patients. The development of an EEG assessment protocol would provide VA, and other, sites with advanced methodology to serve severely brain injured patients and their families. Analysis of neural oscillatory activity with EEG can provide a sound basis for evaluating the level of consciousness of an individual, and monitoring changes in that level over time. One goal of this project is to assess the effectiveness of several measures of willful brain activity in relation to the level of consciousness as measured by the clinical scales, and to their value as prognostic markers. We expect that a multidimensional approach of different measures reflecting neural complexity will most likely be needed for short-term evaluation of patients within a behavioral assessment session, as well as for long-term evaluation of patients across weeks.