Cognitive impairments are a devastating long-term consequence following traumatic brain injury (TBI). This review provides an update on the quantitative mutimodal neuroimaging studies that attempt to ...elucidate the mechanism(s) underlying cognitive impairments and their recovery following TBI.
Recent studies have linked individual specific behavioural impairments and their changes over time to physiological activity and structural changes using EEG, PET and MRI. Multimodal studies that combine measures of physiological activity with knowledge of neuroanatomical and connectivity damage have also illuminated the multifactorial function-structure relationships that underlie impairment and recovery following TBI.
The combined use of multiple neuroimaging modalities, with focus on individual longitudinal studies, has the potential to accurately classify impairments, enhance sensitivity of prognoses, inform targets for interventions and precisely track spontaneous and intervention-driven recovery.
•Are there similarities in executive attention pathophysiology following TBI and in normal age-related decline?.•We derived a biomarker of executive attention pathophysiology that was common to both ...aging-related and post-TBI-related impairments, and in moderate-severe TBI.•Our findings identify biomarkers to track recovery, impact of interventions and guide development of targeted therapeutics following brain injuries.
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.
We review the history of efforts to apply central thalamic deep brain stimulation (CT/DBS) to restore consciousness in patients in a coma or vegetative state by changing the arousal state. Early ...experimental and clinical studies, and the results of a recent single‐subject human study that demonstrated both immediate behavioral facilitation and carry‐over effects of CT/DBS are reviewed. We consider possible mechanisms underlying CT/DBS effects on cognitively‐mediated behaviors in conscious patients in light of the anatomical connectivity and physiological specializations of the central thalamus. Immediate and carry‐over effects of CT/DBS are discussed within the context of possible effects on neuronal plasticity and gene expression. We conclude that CT/DBS should be studied as a therapeutic intervention to improve impaired cognitive function in severely brain‐injured patients who, in addition to demonstrating clinical evidence of consciousness and goal‐directed behavior, retain sufficient preservation of large‐scale cerebral networks within the anterior forebrain. Although available data provide evidence for proof‐of‐concept, very significant challenges for study design and development of CT/DBS for clinical use are identified.
To understand how methylphenidate (MPH) is used in youth with traumatic brain injury (TBI) during inpatient pediatric rehabilitation.
Inpatient pediatric rehabilitation.
In total, 234 children with ...TBI; 62 of whom received MPH and 172 who did not. Patients were on average 11.6 years of age (range, 2 months to 21 years); 88 of 234 were female; the most common mechanism of injury was motor vehicle collision (49%); median (IQR) acute hospital length of stay (LOS) and inpatient rehabilitation LOS were 16 (10-29) and 23 (14-39), respectively; 51 of 234 were in a disorder of consciousness cognitive state at time of inpatient rehabilitation admission.
Multicenter, retrospective medical record review.
Patient demographic data, time to inpatient pediatric rehabilitation admission (TTA), cognitive state, MPH dosing (mg/kg/day).
Patients who received MPH were older (P = .011); TTA was significantly longer in patients who received MPH than those who did not (P =.002). The lowest recorded dose range by weight was 0.05 to 0.89 mg/kg/d, representing an 18-fold difference; the weight-based range for the maximum dose was 0.11 to 0.97 mg/kg/d, a 9-fold difference. Patients in lower cognitive states at admission (P = .001) and at discharge (P = .030) were more likely to receive MPH. Five patients had side effects known to be associated with MPH; no serious adverse events were reported.
This multicenter study indicates that there is variable use of MPH during acute inpatient rehabilitation for children with TBI. Children who receive MPH tend to be older with lower cognitive states. Dosing practices are likely consistent with underdosing. Clinical indications for MPH use during inpatient pediatric rehabilitation should be better defined. The use of MPH, as well as its combination with other medications and treatments, during inpatient rehabilitation needs to be further explored.
Converging evidence indicates that impairments in executive function and information-processing speed limit quality of life and social reentry after moderate-to-severe traumatic brain injury (msTBI). ...These deficits reflect dysfunction of frontostriatal networks for which the central lateral (CL) nucleus of the thalamus is a critical node. The primary objective of this feasibility study was to test the safety and efficacy of deep brain stimulation within the CL and the associated medial dorsal tegmental (CL/DTTm) tract.Six participants with msTBI, who were between 3 and 18 years post-injury, underwent surgery with electrode placement guided by imaging and subject-specific biophysical modeling to predict activation of the CL/DTTm tract. The primary efficacy measure was improvement in executive control indexed by processing speed on part B of the trail-making test.All six participants were safely implanted. Five participants completed the study and one was withdrawn for protocol non-compliance. Processing speed on part B of the trail-making test improved 15% to 52% from baseline, exceeding the 10% benchmark for improvement in all five cases.CL/DTTm deep brain stimulation can be safely applied and may improve executive control in patients with msTBI who are in the chronic phase of recovery.ClinicalTrials.gov identifier: NCT02881151 .
To describe dosing practices for amantadine hydrochloride and related adverse effects among children and young adults with traumatic brain injury (TBI) admitted to pediatric inpatient rehabilitation ...units.
Eight pediatric acute inpatient rehabilitation units located throughout the United States comprising the Pediatric Brain Injury Consortium.
Two-hundred thirty-four children and young adults aged 2 months to 21 years with TBI.
Retrospective data revie.
Demographic variables associated with the use of amantadine, amantadine dose, and reported adverse effects.
Forty-nine patients (21%) aged 0.9 to 20 years received amantadine during inpatient rehabilitation. Forty-five percent of patients admitted to inpatient rehabilitation with a disorder of consciousness (DoC) were treated with amantadine, while 14% of children admitted with higher levels of functioning received amantadine. Children with DoC who were not treated with amantadine were younger than those with DoC who received amantadine (median 3.0 vs 11.6 years, P = .008). Recorded doses of amantadine ranged from 0.7 to 13.5 mg/kg/d; the highest total daily dose was 400 mg/d. Adverse effects were reported in 8 patients (16%); nausea/abdominal discomfort and agitation were most common, each reported in 3 patients. The highest reported dose without an adverse effect was 10.1 mg/kg/d.
During pediatric inpatient rehabilitation, amantadine was prescribed to children across a range of ages and injury severity and was most commonly prescribed to older children with DoC. Dosing varied widely, with weight-based dosing for younger/smaller children at both lower and higher doses than what had been previously reported. Prospective studies are needed to characterize the safety and tolerability of higher amantadine doses and optimize amantadine dosing parameters for children with TBI.
Background
We developed a gap analysis that examines the role of brain–computer interfaces (BCI) in patients with disorders of consciousness (DoC), focusing on their assessment, establishment of ...communication, and engagement with their environment.
Methods
The Curing Coma Campaign convened a Coma Science work group that included 16 clinicians and neuroscientists with expertise in DoC. The work group met online biweekly and performed a gap analysis of the primary question.
Results
We outline a roadmap for assessing BCI readiness in patients with DoC and for advancing the use of BCI devices in patients with DoC. Additionally, we discuss preliminary studies that inform development of BCI solutions for communication and assessment of readiness for use of BCIs in DoC study participants. Special emphasis is placed on the challenges posed by the complex pathophysiologies caused by heterogeneous brain injuries and their impact on neuronal signaling. The differences between one-way and two-way communication are specifically considered. Possible implanted and noninvasive BCI solutions for acute and chronic DoC in adult and pediatric populations are also addressed.
Conclusions
We identify clinical and technical gaps hindering the use of BCI in patients with DoC in each of these contexts and provide a roadmap for research aimed at improving communication for adults and children with DoC, spanning the clinical spectrum from intensive care unit to chronic care.
Traumatic brain injury (TBI) is a major cause of morbidity and mortality in children; survivors experience long-term cognitive and motor deficits. To date, studies predicting outcome following ...pediatric TBI have primarily focused on acute behavioral responses and proxy measures of injury severity; unsurprisingly, these measures explain very little of the variance following heterogenous injury. In adults, certain acute imaging biomarkers help predict cognitive and motor recovery following moderate to severe TBI. This multi-center, retrospective study, characterizes the day-of-injury computed tomographic (CT) reports of pediatric, adolescent, and young adult patients (2 months to 21 years old) who received inpatient rehabilitation services for TBI (
= 247). The study also determines the prognostic utility of CT findings for cognitive and motor outcomes assessed by the Pediatric Functional Independence Measure, converted to age-appropriate developmental functional quotient (DFQ), at discharge from rehabilitation. Subdural hematomas (66%), contusions (63%), and subarachnoid hemorrhages (59%) were the most common lesions; the majority of subjects had less severe Rotterdam CT scores (88%, ≤ 3). After controlling for age, gender, mechanism of injury, length of acute hospital stay, and admission DFQ in multivariate regression analyses, the highest Rotterdam score (β = -25.2,
< 0.01) and complete cisternal effacement (β = -19.4,
< 0.05) were associated with lower motor DFQ, and intraventricular hemorrhage was associated with lower motor (β = -3.7,
< 0.05) and cognitive DFQ (β = -4.9,
< 0.05). These results suggest that direct detection of intracranial injury provides valuable information to aid in prediction of recovery after pediatric TBI, and needs to be accounted for in future studies of prognosis and intervention.
Diffusion tensor imaging along perivascular spaces (DTI-ALPS) is a novel MRI method for assessing brain interstitial fluid dynamics, potentially indexing glymphatic function. Failed glymphatic ...clearance is implicated in Alzheimer's disease (AD) pathophysiology. We assessed the contribution of age and female sex (strong AD risk factors) to DTI-ALPS index in healthy subjects. We also for the first time assessed the effect of head size. In accord with prior studies, we show reduced DTI-ALPS index with aging, and in men compared to women. However, head size may be a major contributing factor to this counterintuitive sex difference.
Managing cognitive function in care homes is a significant challenge. Individuals in care have a variety of scores across standard clinical assessments, such as the Mini-Mental Status Exam (MMSE), ...and many of them have scores that fall within the range associated with dementia. A recent methodological advance, brain vital sign monitoring through auditory event-related potentials, provides an objective and sensitive physiological measurement to track abnormalities, differences, or changes in cognitive function. Taking advantage of point-of-care accessibility, the current study evaluated the methodological feasibility, the assessment of whether a particular research method can be successfully implemented, of quantitatively measuring cognition of care home residents using brain vital signs. Secondarily, the current study examined the relationship between brain vital signs, specifically the cognitive processing associated N400 component, and MMSE scores in care home residents.
Brain vital signs used the established N100 (auditory sensation), P300 (basic attention), and N400 (cognitive processing) event-related potential (ERP) components. A total of 52 residents were enrolled, with all participants evaluated using the MMSE. Participants were assigned into homogeneous groups based on their MMSE scores, and were categorized into low (n = 14), medium (n = 17), and high (n = 13) MMSE groups. Both brain vital sign measures and underlying ERP waveforms were examined. Statistical analyses used partial least squares correlation (PLS) analyses in which both MMSE and age were included as factors, as well as jackknife approaches, to test for significant brain vital sign changes.
The current study successfully measured and analyzed standardized, quantifiable brain vital signs in a care home setting. ERP waveform data showed specific N400 changes between MMSE groups as a function of MMSE score. PLS analyses confirmed significant MMSE-related and age-related differences in the N400 amplitude (p < 0.05, corrected). Similarly, the jackknife approach emphasized the N400 latency difference between the low and high MMSE groups.
It was possible to acquire brain vital signs measures in care home residents. Additionally, the current study evaluated brain vital signs relative to MMSE in this group. The comparison revealed significant decreasing in N400 response amplitude (cognitive processing) as a function of both MMSE score and age, as well as a slowing of N400 latency. The findings indicate that objective neurophysiological measures of impairment are detectable in care home residents across the span of MMSE scores. Direct comparison to MMSE- and age-related variables represents a critical initial step ahead of future studies that will investigate relative improvements in sensitivity, validity, reliability and related advantages of brain vital sign monitoring.
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