Neural correlates of unstructured motor behaviors

Objective. We studied the relationship between uninstructed, unstructured movements and neural activity in three epilepsy patients with intracranial electroencephalographic (iEEG) recordings. Approach. We used a custom system to continuously record high definition video precisely time-aligned to clinical iEEG data. From these video recordings, movement periods were annotated via semi-automatic tracking based on dense optical flow. Main results. We found that neural signal features (8–32 Hz and 76–100 Hz power) previously identified from task-based experiments are also modulated before and during a variety of movement behaviors. These movement behaviors are coarsely labeled by time period and movement side (e.g. 'Idle' and 'Move', 'Right' and 'Left'); movements within a label can include a wide variety of uninstructed behaviors. A rigorous nested cross-validation framework was used to classify both movement onset and lateralization with statistical significance for all subjects. Significance. We demonstrate an evaluation framework to study neural activity related to natural movements not evoked by a task, annotated over hours of video. This work further establishes the feasibility to study neural correlates of unstructured behavior through continuous recording in the epilepsy monitoring unit. The insights gained from such studies may advance our understanding of how the brain naturally controls movement, which may inform the development of more robust and generalizable brain–computer interfaces

α-Ketoglutaramate: an overlooked metabolite of glutamine and a biomarker for hepatic encephalopathy and inborn errors of the urea cycle

Glutamine metabolism is generally regarded as proceeding via glutaminase-catalyzed hydrolysis to glutamate and ammonia, followed by conversion of glutamate to α-ketoglutarate catalyzed by glutamate dehydrogenase or by a glutamate-linked aminotransferase (transaminase). However, another pathway exists for the conversion of glutamine to α-ketoglutarate that is often overlooked, but is widely distributed in nature. This pathway, referred to as the glutaminase II pathway, consists of a glutamine transaminase coupled to ω-amidase. Transamination of glutamine results in formation of the corresponding α-keto acid, namely, α-ketoglutaramate (KGM). KGM is hydrolyzed by ω-amidase to α-ketoglutarate and ammonia. The net glutaminase II reaction is: L - Glutamine + α - keto acid + H2O → α - ketoglutarate + L - amino acid + ammonia. In this mini-review the biochemical importance of the glutaminase II pathway is summarized, with emphasis on the key component KGM. Forty years ago it was noted that the concentration of KGM is increased in the cerebrospinal fluid (CSF) of patients with hepatic encephalopathy (HE) and that the level of KGM in the CSF correlates well with the degree of encephalopathy. In more recent work, we have shown that KGM is markedly elevated in the urine of patients with inborn errors of the urea cycle. It is suggested that KGM may be a useful biomarker for many hyperammonemic diseases including hepatic encephalopathy, inborn errors of the urea cycle, citrin deficiency and lysinuric protein intolerance