ABSTRACT
Aims and Objectives: To facilitate individualized assessment of unresponsive patients in the intensive care unit for signs of preserved consciousness after acute brain injury. Background: Physicians and neuroscientists are increasingly recognizing a disturbing dilemma: Brain-injured patients who appear entirely unresponsive at the bedside may show signs of covert consciousness when examined by functional MRI (fMRI) or electroencephalography (EEG). According to a recent meta-analysis, roughly 15% of behaviorally unresponsive brain-injured patients can participate in mental tasks by modifying their brain activity during EEG- or fMRI-based paradigms, suggesting that they are conscious and misdiagnosed. This has major ethical and practical implications, including prognosis, treatment, resource allocation, and end-of-life decisions. However, EEG- or fMRI-based paradigms have so far typically been tested in chronic brain injury. Hence, as a novel approach, CONNECT-ME will import the full range of consciousness paradigms into neurocritical care. Methods: We will assess intensive care patients with acute brain injury for preserved consciousness by serial and multimodal evaluation using active, passive and resting state fMRI and EEG paradigms, as well as state-of-the-art clinical techniques including pupillometry and sophisticated clinical rating scales such as the Coma Recovery Scale-Revised. In addition, we are establishing a biobank (blood, cerebrospinal fluid and brain tissue, where available) to facilitate future genomic and microbiomic research to search for signatures of consciousness recovery. Discussion: We anticipate that this multimodal approach will add vital clinical information, including detection of preserved consciousness in patients previously thought of as unconscious, and improved (i.e., personalized) prognostication of individual patients. Our aim is two-fold: We wish to establish a cutting-edge tertiary care clinical service for unresponsive patients in the intensive care unit and lay the foundation for a fruitful multidisciplinary research environment for the study of consciousness in acute brain injury. Of note, CONNECT-ME will not only enhance our understanding of consciousness disorders in acute brain injury but it will also raise awareness for these patients who, for obvious reasons, have lacked a voice so far. Trial registration: The study is registered with clinicaltrials.org (ClinicalTrials.gov Identifier: NCT02644265).
ABSTRACT
The Point Subtraction Aggression Paradigm (PSAP) measures aggressive behavior in response to provocations. The aim of the study was to implement the PSAP in a functional neuroimaging environment (fMRI) and evaluate aggression-related brain reactivity including response to provocations and associations with aggression within the paradigm. Twenty healthy participants completed two 12-min PSAP sessions within the scanner. We evaluated brain responses to aggressive behavior (removing points from an opponent), provocations (point subtractions by the opponent), and winning points. Our results showed significant ventral and dorsal striatal reactivity when participants won a point and removed one from the opponent. Provocations significantly activated the amygdala, dorsal striatum, insula, and prefrontal areas. Task-related aggressive behavior was positively correlated with neural reactivity to provocations in the insula, the dorsal striatum, and prefrontal areas. Our findings suggest the PSAP within an fMRI environment may be a useful tool for probing aggression-related neural pathways. Activity in the amygdala, dorsal striatum, insula, and prefrontal areas during provocations is consistent with the involvement of these brain regions in emotional and impulsive behavior. Striatal reactivity may suggest an involvement of reward during winning and stealing points.
