Mapping preserved real-world cognition in severely brain-injured patients.

Decoding the contents of consciousness from brain activity is one of most challenging frontiers of cognitive neuroscience. The ability to interpret mental content without recourse to behavior is most relevant for understanding patients who may be demonstrably conscious, but entirely unable to speak or move willfully in any way, precluding any systematic investigation of their conscious experience. Until recently, patient studies have used structured instructions to elicit willful modulation of brain activity according to command. Recent work has used a different approach, where the similarity of any given patient's brain activity to that of healthy controls during naturalistic paradigms can help detect high-level cognition and consciousness. This approach is easy to administer, brief, and does not require compliance with arbitrary task instructions. Therefore, it is suited to probing consciousness and revealing residual cognition in highly impaired comatose patients, thus helping to improve diagnosis and prognostication for this vulnerable patient group.

Detecting and interpreting conscious experiences in behaviorally non-responsive patients.

Decoding the contents of consciousness from brain activity is one of the most challenging frontiers of cognitive neuroscience. The ability to interpret mental content without recourse to behavior is most relevant for understanding patients who may be demonstrably conscious, but entirely unable to speak or move willfully in any way, precluding any systematic investigation of their conscious experience. The lack of consistent behavioral responsivity engenders unique challenges to decoding any conscious experiences these patients may have solely based on their brain activity. For this reason, paradigms that have been successful in healthy individuals cannot serve to interpret conscious mental states in this patient group. Until recently, patient studies have used structured instructions to elicit willful modulation of brain activity according to command, in order to decode the presence of willful brain-based responses in this patient group. In recent work, we have used naturalistic paradigms, such as watching a movie or listening to an audio-story, to demonstrate that a common neural code supports conscious experiences in different individuals. Moreover, we have demonstrated that this code can be used to interpret the conscious experiences of a patient who had remained non-responsive for several years. This approach is easy to administer, brief, and does not require compliance with task instructions. Rather, it engages attention naturally through meaningful stimuli that are similar to the real-world sensory information in a patient's environment. Therefore, it may be particularly suited to probing consciousness and revealing residual brain function in highly impaired, acute, patients in a comatose state, thus helping to improve diagnostication and prognostication for this vulnerable patient group from the critical early stages of severe brain-injury.

Western Database of Lipid Variants (WDLV): a catalogue of genetic variants in monogenic dyslipidemias.

BACKGROUND: Next-generation sequencing (NGS) is nearing routine clinical application, especially for diagnosis of rare monogenic cardiovascular diseases. But NGS uncovers so much variation in an individual genome that filtering steps are required to streamline data management. The first step is to determine whether a potential disease-causing variant has been observed previously in affected patients. METHODS: To facilitate this step for lipid disorders, we developed the Western Database of Lipid Variants (WDLV) of 2776 variants in 24 genes that cause monogenic dyslipoproteinemias, including conditions characterized primarily by either high or low low-density lipoprotein cholesterol, high or low high-density lipoprotein cholesterol, high triglyceride, and some miscellaneous disorders. We incorporated quality-control steps to maximize the likelihood that a listed mutation was disease causing. RESULTS: The details of each mutation found in a dyslipidemia, together with a mutation map of the causative genes, are shown in graphical display items. CONCLUSIONS: WDLV will help clinicians and researchers determine the potential pathogenicity of mutations discovered by DNA sequencing of patients or research participants with lipid disorders.