Trends in alcohol use during moderate and severe traumatic brain injury: 18 years of neurotrauma in Pennsylvania.

PRIMARY OBJECTIVE: Alcohol is a known risk factor for TBI, yet little is known about how rates of alcohol use at time of injury differ across demographics and the stability of alcohol-related injury over time. Further, findings examining the relationship between alcohol and outcome are mixed. This study aimed to examine changes in alcohol-positive moderate-to-severe traumatic brain injury (+aTBI) over two decades with focus on demographic factors, changes in +aTBI frequency over time, mortality and acute outcome. METHODS: This retrospective study examined data collected from 1992-2009 by the Pennsylvania Trauma Outcome Study (PTOS). RESULTS: Results reveal that the proportion of +aTBI has been generally stable across years. However, there is an interaction of +aTBI incidence with mechanism of injury and age, with a downward trend in +aTBI within MVA and fall and individuals 18-30 and 71+ years. Further, consistent with several findings in the literature, alcohol was associated with higher rates of survival and better FSD scores during acute recovery. CONCLUSIONS: This study discusses findings in the context of a greater literature on TBI-related alcohol and outcome. The injury-alcohol profiles highlighted could be used to inform future allocation of resources toward prevention of, intervention for and care of individuals who sustain TBI.

The neural correlates of cognitive fatigue in traumatic brain injury using functional MRI.

PRIMARY OBJECTIVE: The present study used fMRI (functional magnetic resonance imaging) to objectively assess cognitive fatigue in persons with traumatic brain injury (TBI). It was hypothesized that while performing a cognitive task, TBI participants would show increased brain activity over time, indicative of increased cerebral 'effort' which might manifest as the subjective feeling of cognitive fatigue. METHODS AND PROCEDURES: Functional MRI was used to track brain activity across time while 11 TBI patients with moderate-severe injury and 11 age-matched healthy controls (HCs) performed a modified Symbol Digit Modalities Task (mSDMT). Cognitive fatigue was operationally defined as a relative increase in cerebral activation across time compared to that seen in HCs. ROIs were derived from the Chauduri and Behan model of cognitive fatigue. MAIN OUTCOMES AND RESULTS: While performing the mSDMT, participants with a TBI showed increased activity, while HCs subsequently showed decreased activity in several regions including the middle frontal gyrus, superior parietal cortex, basal ganglia and anterior cingulate. CONCLUSIONS: Increased brain activity exhibited by participants with a TBI might represent increased cerebral effort which may be manifested as cognitive fatigue. Functional MRI appears to be a potentially useful tool for understanding the neural mechanisms associated with cognitive fatigue in TBI.

Examining network dynamics after traumatic brain injury using the extended unified SEM approach.

The current study uses effective connectivity modeling to examine how individuals with traumatic brain injury (TBI) learn a new task. We make use of recent advancements in connectivity modeling (extended unified structural equation modeling, euSEM) and a novel iterative grouping procedure (Group Iterative Multiple Model Estimation, GIMME) in order to examine network flexibility after injury. The study enrolled 12 individuals sustaining moderate and severe TBI to examine the influence of task practice on connections between 8 network nodes (bilateral prefrontal cortex, anterior cingulate, inferior parietal lobule, and Crus I in the cerebellum). The data demonstrate alterations in networks from pre to post practice and differences in the models based upon distinct learning trajectories observed within the TBI sample. For example, better learning in the TBI sample was associated with diminished connectivity within frontal systems and increased frontal to parietal connectivity. These findings reveal the potential for using connectivity modeling and the euSEM to examine dynamic networks during task engagement and may ultimately be informative regarding when networks are moving in and out of periods of neural efficiency.

Changes in resting connectivity during recovery from severe traumatic brain injury.

In the present study we investigate neural network changes after moderate and severe traumatic brain injury (TBI) through the use of resting state functional connectivity (RSFC) methods. Using blood oxygen level dependent functional MRI, we examined RSFC at 3 and 6 months following resolution of posttraumatic amnesia. The goal of this study was to examine how regional off-task connectivity changes during a critical period of recovery from significant neurological disruption. This was achieved by examining regional changes in the intrinsic, or "resting", BOLD fMRI signal in separate networks: 1) regions linked to goal-directed (or external-state) networks and 2) default mode (or internal-state) networks. Findings here demonstrate significantly increased resting connectivity internal-state networks in the TBI sample during the first 6 months following recovery. The most consistent finding was increased connectivity in both internal and external state networks to the insula and medial temporal regions during recovery. These findings were dissociable from repeat measurements in a matched healthy control sample.

The influence of neuropathology on the FMRI signal: a measurement of brain or vein?

There is a rapidly growing literature using fMRI technology to investigate the various forms of behavioral impairment associated with brain injury and disease. Given this, surprisingly little work has been conducted to examine the influence of neuropathophysiological processes on the fMRI signal. This paper reviews the literature examining baseline alteration in cerebrovascular parameters associated with normal aging, brain injury, and brain disease. In addition, findings from three cases of individuals with severe brain trauma will be presented to show the influence of brain trauma on baseline cerebrovascular parameters measured by fMRI. The methods used here can be implemented by other investigators to accurately isolate specific hemodynamic changes that can influence the BOLD fMRI signal.

The relationship between neuropsychological measures and the Timed Instrumental Activities of Daily Living task in multiple sclerosis.

Multiple sclerosis (MS) can result in cognitive deficits and a loss of functional independence. To date, little research has linked the observed cognitive and behavioral deficits in MS, especially those in the processing speed domain, to performance on tasks of everyday functioning. The present study examined the relationship between neuropsychological test performance and performance on the Timed Instrumental Activities of Daily Living task (TIADL) in individuals with MS, and in healthy controls (HCs). The TIADL is a functional measure, which assesses both accuracy and speed in one's performance of everyday activities. The MS group performed significantly worse on the TIADL relative to the HC group. Additionally, TIADL scores of individuals with MS were significantly correlated with neuropsychological measures of processing speed. TIADL scores were not, however, correlated with neuropsychological measures of verbal episodic memory or working memory. These results indicate that the impairments in processing speed may contribute to impairments in activities of everyday living in persons with MS.

Examining lactate in severe TBI using proton magnetic resonance spectroscopy.

PRIMARY OBJECTIVE: Clinical management of acute traumatic brain injury (TBI) has emphasized identification of secondary mechanisms of pathophysiology. An important objective in this study is to use proton magnetic resonance spectroscopy (pMRS) to examine early metabolic disturbance due to TBI. RESEARCH DESIGN: The current design is a case study with repeated measures. METHOD AND PROCEDURE: Proton magnetic resonance imaging was used to examine neurometabolism in this case of very severe brain trauma at 9 and 23 days post-injury. MRI was performed on a clinical 1.5 Tesla scanner. MAIN OUTCOMES AND RESULTS: These data also reveal that pMRS methods can detect lactate elevations in an adult surviving severe head trauma and are sensitive to changes in basic neurometabolism during the first month of recovery. CONCLUSIONS: The current case study demonstrates the sensitivity of pMRS in detecting metabolic alterations during the acute recovery period. The case study reveals that lactate elevations may be apparent for weeks after severe neurotrauma. Further work in this area should endeavour to determine the ideal time periods for pMRS examination in severe TBI as well as the ideal locations of data acquisition (e.g. adjacent or distal to lesion sites).

Functionally activated brain imaging (O-15 PET and fMRI) in the study of learning and memory after traumatic brain injury.

Advances in functional imaging technology and cognitive neuropsychology have resulted in paradigms in which participants can perform cognitive tasks during functional image acquisition. We will discuss the application of two approaches (oxygen-15 positron emission tomography and functional magnetic resonance imaging) that have recently been used to examine components of learning and memory following traumatic brain injury (TBI). Activated functional brain imaging findings that we will discuss may suggest possible functional reallocation and reorganization of brain substrates involved in verbal learning and memory following brain injury. The findings also are clearly in line with other research that indicates a prominent role for the frontal lobes in learning and memory functioning, and support the concept of distributed neural networks for memory-related functions, cognitive load, and the potential for examining brain re-organization after injury.

Spacing of repetitions improves learning and memory after moderate and severe TBI.

Extensive research has determined that new learning in healthy individuals is significantly improved when trials are distributed over time (spaced presentation) compared to consecutive learning trials (massed presentation). This phenomenon known as the "spacing effect" (SE) has been shown to enhance verbal and nonverbal learning in healthy adults of different ages and in different memory paradigms (e.g., recognition, recall, etc.). The purpose of this study was to examine whether learning in adults with moderate and severe traumatic brain injury (TBI) is improved using a spacing-of-repetitions procedure. Using a within-groups design, participants with TBI (n = 20) were presented a list of 115 words that were presented either once (single condition), twice consecutively (massed condition), or twice with 11 words between presentations (spaced condition). Participants were required to rank each word from 1 to 10 according to their familiarity with the word; they were not asked to "memorize" words for a later test. Word list learning was measured with a free recall test immediately following list presentation and with free recall and recognition tests after a 30-min delay. Participants recalled and recognized significantly more spaced words than massed words during this word list learning task. These results strongly indicate that the spacing of repetitions improves learning and memory in individuals who have sustained moderate to severe TBI. Implications for rehabilitation are discussed.

An investigation of working memory rehearsal in multiple sclerosis using fMRI.

The present study examined patterns of cerebral activation during a working memory (WM) rehearsal task in individuals diagnosed with multiple sclerosis (MS) and in healthy adults. BOLD functional magnetic resonance imaging (fMRI) was performed using a 1.5 T GE scanner to assess activation during a WM task adapted from the Sternberg paradigm (Sternberg, 1969). Participants included 8 individuals diagnosed with MS, and 5 healthy controls (HCs) matched for age and education. Task difficulty was manipulated by increasing the length of time that strings of letters were to be rehearsed. Findings revealed increased right prefrontal cortex activation and increased right temporal lobe activation in individuals diagnosed with MS compared to HCs. The potential explanations for increased right hemisphere activation in persons with MS are discussed.