03132nas a2200433 4500008004100000022001400041245013100055210006900186260001200255300001100267490000800278520179900286653000902085653001002094653001502104653001902119653003002138653002302168653001802191653001102209653002902220100001702249700001902266700002202285700001902307700001702326700002602343700001802369700002702387700002002414700002102434700001802455700002102473700001702494700002402511700001902535700002002554856012402574 2023 eng d a1095-957200aComparisons of electrophysiological markers of impaired executive attention after traumatic brain injury and in healthy aging.0 aComparisons of electrophysiological markers of impaired executiv c07/2023 a1201260 v2743 a

Executive attention impairments are a persistent and debilitating consequence of traumatic brain injury (TBI). To make headway towards treating and predicting outcomes following heterogeneous TBI, cognitive impairment specific pathophysiology first needs to be characterized. In a prospective observational study, we measured EEG during the attention network test aimed at detecting alerting, orienting, executive attention and processing speed. The sample (N = 110) of subjects aged 18-86 included those with and without traumatic brain injury: n = 27, complicated mild TBI; n = 5, moderate TBI; n = 10, severe TBI; n = 63, non-brain-injured controls. Subjects with TBI had impairments in processing speed and executive attention. Electrophysiological markers of executive attention processing in the midline frontal regions reveal that, as a group, those with TBI and elderly non-brain-injured controls have reduced responses. We also note that those with TBI and elderly controls have responses that are similar for both low and high-demand trials. In subjects with moderate-severe TBI, reductions in frontal cortical activation and performance profiles are both similar to that of controls who are ∼4 to 7 years older. Our specific observations of frontal response reductions in subjects with TBI and in older adults is consistent with the suggested role of the anterior forebrain mesocircuit as underlying cognitive impairments. Our results provide novel correlative data linking specific pathophysiological mechanisms underlying domain-specific cognitive deficits following TBI and with normal aging. Collectively, our findings provide biomarkers that may serve to track therapeutic interventions and guide development of targeted therapeutics following brain injuries.

10aAged10aAging10aBiomarkers10aBrain Injuries10aBrain Injuries, Traumatic10aExecutive Function10aHealthy Aging10aHumans10aNeuropsychological Tests1 aKim, Nayoung1 aJamison, Keith1 aJaywant, Abhishek1 aGaretti, Jacob1 aBlunt, Emily1 aRoyChoudhury, Arindam1 aButler, Tracy1 aDams-O'Connor, Kristen1 aKhedr, Shahenda1 aChen, Chun-Cheng1 aShetty, Teena1 aWinchell, Robert1 aHill, Jeremy1 aSchiff, Nicholas, D1 aKuceyeski, Amy1 aShah, Sudhin, A uhttps://www.neurotechcenter.org/publications/2023/comparisons-electrophysiological-markers-impaired-executive-attention02630nas a2200289 4500008004100000022001400041245009200055210006900147260001300216300001200229490000700241520171500248100001701963700002201980700001902002700001902021700001802040700002102058700001702079700002302096700001902119700002002138700002402158700001702182700002002199856012102219 2022 eng d a2163-040200aCognitive-Motor Dissociation Following Pediatric Brain Injury: What About the Children?0 aCognitiveMotor Dissociation Following Pediatric Brain Injury Wha c2022 Jun a248-2570 v123 a

BACKGROUND AND OBJECTIVES: Following severe brain injury, up to 16% of adults showing no clinical signs of cognitive function nonetheless have preserved cognitive capacities detectable via neuroimaging and neurophysiology; this has been designated cognitive-motor dissociation (CMD). Pediatric medicine lacks both practice guidelines for identifying covert cognition and epidemiologic data regarding CMD prevalence.

METHODS: We applied a diverse battery of neuroimaging and neurophysiologic tests to evaluate 2 adolescents (aged 15 and 18 years) who had shown no clinical evidence of preserved cognitive function following brain injury at age 9 and 13 years, respectively. Clinical evaluations were consistent with minimally conscious state (minus) and vegetative state, respectively.

RESULTS: Both participants' EEG, and 1 participant's fMRI, provided evidence that they could understand commands and make consistent voluntary decisions to follow them. Both participants' EEG demonstrated larger-than-expected responses to auditory stimuli and intact semantic processing of words in context.

DISCUSSION: These converging lines of evidence lead us to conclude that both participants had preserved cognitive function dissociated from their motor output. Throughout the 5+ years since injury, communication attempts and therapy had remained uninformed by such objective evidence of their cognitive abilities. Proper diagnosis of CMD is an ethical imperative. Children with covert cognition reflect a vulnerable and isolated population; the methods outlined here provide a first step in identifying such persons to advance efforts to alleviate their condition.

1 aKim, Nayoung1 aO'Sullivan, James1 aOlafson, Emily1 aCaliendo, Eric1 aNowak, Sophie1 aVoss, Henning, U1 aLowder, Ryan1 aWatson, William, D1 aIvanidze, Jana1 aFins, Joseph, J1 aSchiff, Nicholas, D1 aHill, Jeremy1 aShah, Sudhin, A uhttps://www.neurotechcenter.org/publications/2022/cognitive-motor-dissociation-following-pediatric-brain-injury-what02884nas a2200217 4500008004100000022001400041245008200055210006900137260001200206300001200218490000700230520217300237100001702410700002002427700001902447700001802466700002402484700002002508700001702528856012102545 2022 eng d a2163-040200aObjective Neurophysiologic Markers of Cognition After Pediatric Brain Injury.0 aObjective Neurophysiologic Markers of Cognition After Pediatric  c10/2022 a352-3640 v123 a

BACKGROUND AND OBJECTIVES: Following brain injury, clinical assessments of residual and emerging cognitive function are difficult and fraught with errors. In adults, recent American Academy of Neurology (AAN) practice guidelines recommend objective neuroimaging and neurophysiologic measures to support diagnosis. Equivalent measures are lacking in pediatrics-an especially great challenge due to the combined heterogeneity of both brain injury and pediatric development. Therefore, we aim to establish quantitative, clinically practicable measures of cognitive function following pediatric brain injury.

METHODS: Participants with and without brain injury were aged 8-18 years, clinically classified according to cognitive recovery state: N = 8 in disorders of consciousness (DoC), N = 7 in confusional state, N = 19 cognitively impaired, and N = 13 typically developing uninjured controls. We prospectively measured electroencephalographic markers of sensory processing and attention in an auditory oddball paradigm, and of covert movement attempts in a command-following paradigm.

RESULTS: In 3 participants with DoC, EEG markers of active attempted command following revealed cognitive function that clinical assessment had failed to detect. These same 3 individuals could also be distinguished from the rest of their group by 2 event-related potentials that correlate with sensory processing and orienting attention in the oddball paradigm. Considered across the whole participant group, magnitudes of these 2 ERP markers significantly increased as cognitive recovery progressed (ANOVA: each < 0.001); viewed jointly, the 2 ERP markers cleanly delineated the 4 cognitive states.

DISCUSSION: Despite heterogeneity of brain injuries and brain development, our objective EEG markers reflected cognitive recovery independent of motor function. Two of these markers required no active participation. Together, they allowed us to identify 3 individuals who meet the criteria for cognitive-motor dissociation. To diagnose, prognose, and track cognitive recovery accurately, such markers should be used in pediatrics.

1 aKim, Nayoung1 aWatson, William1 aCaliendo, Eric1 aNowak, Sophie1 aSchiff, Nicholas, D1 aShah, Sudhin, A1 aHill, Jeremy uhttps://www.neurotechcenter.org/publications/2022/objective-neurophysiologic-markers-cognition-after-pediatric-brain