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Dysfunctional Timing in Traumatic Brain Injury Patients: Co-occurrence of Cognitive, Motor, and Perceptual Deficits

ABSTRACT: Timing is an essential part of human cognition and of everyday life activities, such as walking or holding a conversation. Previous studies showed that traumatic brain injury (TBI) often affects cognitive functions such as processing speed and time-sensitive abilities, causing long-term sequelae as well as daily impairments. However, the existing evidence on timing capacities in TBI is mostly limited to perception and the processing of isolated intervals. It is therefore open whether the observed deficits extend to motor timing and to continuous dynamic tasks that more closely match daily life activities. The current study set out to answer these questions by assessing audio motor timing abilities and their relationship with cognitive functioning in a group of TBI patients (n = 15) and healthy matched controls. We employed a comprehensive set of tasks aiming at testing timing abilities across perception and production and from single intervals to continuous auditory sequences. In line with previous research, we report functional impairments in TBI patients concerning cognitive processing speed and perceptual timing. Critically, these deficits extended to motor timing: The ability to adjust to tempo changes in an auditory pacing sequence was impaired in TBI patients, and this motor timing deficit covaried with measures of processing speed. These findings confirm previous evidence on perceptual and cognitive timing deficits resulting from TBI and provide first evidence for comparable deficits in motor behavior. This suggests basic co-occurring perceptual and motor timing impairments that may factor into a wide range of daily activities. Our results thus place TBI into the wider range of pathologies with well-documented timing deficits (such as Parkinson’s disease) and encourage the search for novel timing-based therapeutic interventions (e.g., employing dynamic and/or musical stimuli) with high transfer potential to everyday life activities.

SUBMITTER: Verga L

PROVIDER: S-EPMC8558219 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Traumatic brain injury in children commonly involves the frontal lobes and is associated with distinct structural and behavioral changes. Despite the clinical significance of injuries localized to this region during brain development, the mechanisms underlying secondary damage and long-term recovery are poorly understood. Here, we have characterized the first model of unilateral focal traumatic injury to the developing frontal lobe. Male C57Bl/6J mice at postnatal day (p)21, an age approximating a toddler-aged child, received a controlled cortical impact or sham surgery to the left frontal lobe and were euthanized 1 or 7 days later. A necrotic cavity and local inflammatory response were largely confined to the unilateral frontal lobe, dorsal corpus callosum and striatum anterior to the bregma. While cell death and accumulated ?-amyloid precursor protein were characteristic features of the pericontusional motor cortex, corpus callosum, cingulum and dorsal striatum, underlying structures including the hippocampus showed no overt pathology. To determine the long-term functional consequences of injury at p21, two additional cohorts were subjected to a battery of behavioral tests in adolescence (p35-45) or adulthood (p70-80). In both cohorts, brain-injured mice showed normal levels of anxiety, sociability, spatial learning and memory. The signature phenotypic features were deficits in motor function and motor learning, coincident with a reduction in ipsilateral cortical brain volumes. Together, these findings demonstrate classic morphological features of a focal traumatic injury, including early cell death and axonal injury, and long-term volumetric loss of cortical volumes. The presence of deficits in sensorimotor function and coordination in the absence of abnormal findings related to anxiety, sociability and memory likely reflects several variables, including the unique location of the injury and the emergence of favorable compensatory mechanisms during subsequent brain development.

Project description:BackgroundIn patients with severe brain injury, withdrawal of life-sustaining measures (WLSM) is common in intensive care units (ICU). WLSM constitutes a dilemma: instituting WLSM too early could result in death despite the possibility of an acceptable functional outcome, whereas delaying WLSM could unnecessarily burden patients, families, clinicians, and hospital resources. We aimed to describe the occurrence and timing of WLSM, and factors associated with timing of WLSM in European ICUs in patients with traumatic brain injury (TBI).MethodsThe CENTER-TBI Study is a prospective multi-center cohort study. For the current study, patients with traumatic brain injury (TBI) admitted to the ICU and aged 16 or older were included. Occurrence and timing of WLSM were documented. For the analyses, we dichotomized timing of WLSM in early (< 72 h after injury) versus later (≥ 72 h after injury) based on recent guideline recommendations. We assessed factors associated with initiating WLSM early versus later, including geographic region, center, patient, injury, and treatment characteristics with univariable and multivariable (mixed effects) logistic regression.ResultsA total of 2022 patients aged 16 or older were admitted to the ICU. ICU mortality was 13% (n = 267). Of these, 229 (86%) patients died after WLSM, and were included in the analyses. The occurrence of WLSM varied between regions ranging from 0% in Eastern Europe to 96% in Northern Europe. In 51% of the patients, WLSM was early. Patients in the early WLSM group had a lower maximum therapy intensity level (TIL) score than patients in the later WLSM group (median of 5 versus 10) The strongest independent variables associated with early WLSM were one unreactive pupil (odds ratio (OR) 4.0, 95% confidence interval (CI) 1.3-12.4) or two unreactive pupils (OR 5.8, CI 2.6-13.1) compared to two reactive pupils, and an Injury Severity Score (ISS) if over 41 (OR per point above 41 = 1.1, CI 1.0-1.1). Timing of WLSM was not significantly associated with region or center.ConclusionWLSM occurs early in half of the patients, mostly in patients with severe TBI affecting brainstem reflexes who were severely injured. We found no regional or center influences in timing of WLSM. Whether WLSM is always appropriate or may contribute to a self-fulfilling prophecy requires further research and argues for reluctance to institute WLSM early in case of any doubt on prognosis.

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Dysfunctional Timing in Traumatic Brain Injury Patients: Co-occurrence of Cognitive, Motor, and Perceptual Deficits

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