Recently, there has been renewed interest in the study of cognitive fatigue. It is known that fatigue is one of the most disabling symptoms in numerous neurological populations, including stroke, multiple sclerosis, Parkinson's disease, and traumatic brain injury. Behavioral studies of cognitive fatigue are hampered by lack of correlation of self-report measures with objective performance. Neuroimaging studies provide new insight about cognitive fatigue and its neural correlates. Impairment within the cortico-striatal network, involved in effort–reward calculation, has been suggested to be critically related to fatigue. The current review surveys the recent neuroimaging literature, and suggests promising avenues for future research. (JINS, 2013, 19, 1–5)

The theory of cognitive reserve attempts to explain why some individuals are more resilient to age-related brain pathology. Efforts to explore reserve have been hindered by measurement difficulties. Reed et al. (2010) proposed quantifying reserve as residual variance in episodic memory performance that remains after accounting for demographic factors and brain pathology (whole brain, hippocampal, and white matter hyperintensity volumes). This residual variance represents the discrepancy between an individual's predicted and actual memory performance. The goals of the present study were to extend these methods to a larger, community-based sample and to investigate whether the residual reserve variable is explained by age, predicts longitudinal changes in language, and predicts dementia conversion independent of age. Results support this operational measure of reserve. The residual reserve variable was associated with higher reading ability, lower likelihood of meeting criteria for mild cognitive impairment, lower odds of dementia conversion independent of age, and less decline in language abilities over 3 years. Finally, the residual reserve variable moderated the negative impact of memory variance explained by brain pathology on language decline. This method has the potential to facilitate research on the mechanisms of cognitive reserve and the efficacy of interventions designed to impart reserve. (JINS, 2013, 19, 1–9)

To study the natural recovery from sports concussion, 12 concussed high school football athletes and 12 matched uninjured teammates were evaluated with symptom rating scales, tests of postural balance and cognition, and an event-related fMRI study during performance of a load-dependent working memory task at 13 h and 7 weeks following injury. Injured athletes showed the expected postconcussive symptoms and cognitive decline with decreased reaction time (RT) and increased RT variability on a working memory task during the acute period and an apparent full recovery 7 weeks later. Brain activation patterns showed decreased activation of right hemisphere attentional networks in injured athletes relative to controls during the acute period with a reversed pattern of activation (injured > controls) in the same networks at 7 weeks following injury. These changes coincided with a decrease in self-reported postconcussive symptoms and improved cognitive test performance in the injured athletes. Results from this exploratory study suggest that decreased activation of right hemisphere attentional networks mediate the cognitive changes and postconcussion symptoms observed during the acute period following concussion. Conversely, improvement in cognitive functioning and postconcussive symptoms during the subacute period may be mediated by compensatory increases in activation of this same attentional network. (JINS, 2013, 19, 1–10)

It has been hypothesized that exposure to repetitive head trauma from contact sports over a long-playing career may eventuate in an increased risk of late-life cognitive impairment. There are currently two competing hypotheses about the possible mechanism underlying such impairment. One is the presence of a unique neurodegenerative disorder known as “chronic traumatic encephalopathy” (CTE). The other is diminished cerebral reserve leading to the earlier clinical expression of age-related neurodegenerative diseases such as mild cognitive impairment (MCI) and Alzheimer's disease (AD). The present study examined informant AD8 inventory data in a sample of 513 retired National Football League (NFL) players. These data were indicative of possible cognitive impairment in 35.1% of this relatively young sample. A comparison of neurocognitive profiles in a subsample of this group to a clinical sample of patients with a diagnosis of MCI due to AD revealed a highly similar profile of impairments. Overall, the data suggest that there may be an increased prevalence of late-life cognitive impairment in retired NFL players, which may reflect diminished cerebral reserve. The findings are considered preliminary, but emphasize the need for larger, controlled studies on this issue. (JINS, 2013, 19, 1–8)

Research reveals mixed results regarding the utility of standardized cognitive and academic tests to predict educational outcomes in youth following a traumatic brain injury (TBI). Yet, deficits in everyday school-based outcomes are prevalent after pediatric TBI. The current study used path modeling to test the hypothesis that parent ratings of adolescents’ daily behaviors associated with executive functioning (EF) would predict long-term functional educational outcomes following pediatric TBI, even when injury severity and patient demographics were included in the model. Furthermore, we contrasted the predictive strength of the EF behavioral ratings with that of a common measure of verbal memory. A total of 132 adolescents who were hospitalized for moderate to severe TBI were recruited to participate in a randomized clinical intervention trial. EF ratings and verbal memory were measured within 6 months of the injury; functional educational outcomes were measured 12 months later. EF ratings and verbal memory added to injury severity in predicting educational competence post injury but did not predict post-injury initiation of special education. The results demonstrated that measurement of EF behaviors is an important research and clinical tool for prediction of functional outcomes in pediatric TBI. (JINS, 2013, 19, 1–9)

Impulsive behaviors and poor inhibition performances are frequently described in patients with traumatic brain injury (TBI). However, few studies have examined impulsivity and associated inhibition impairments in these patients. Twenty-eight patients with moderate to severe TBI and 27 matched controls performed a stop-signal task designed to assess prepotent response inhibition (the ability to inhibit a dominant or automatic motor response) in a neutral or emotional context and a recent negative task to assess resistance to proactive interference (the ability to resist the intrusion into memory of information that was previously relevant but has since become irrelevant). Informants of each patient completed a short questionnaire designed to assess impulsivity. Patients showed a significant increase in current urgency, lack of premeditation, and lack of perseverance when retrospectively compared with the preinjury condition. Group comparisons revealed poorer prepotent response inhibition and resistance to proactive interference performances in patients with TBI. Finally, correlation analyses revealed a significant positive correlation between urgency (the tendency to act rashly when distressed) and prepotent response inhibition in patients with TBI. This study sheds new light on the construct of impulsivity after a TBI, its related cognitive mechanisms, and its potential role in problematic behaviors described after a TBI. (JINS, 2013, 19, 1–9)

Impairments of attention and executive functions are common sequelae of traumatic brain injury (TBI). The anterior cingulate is implicated in conflict-related task performance, such as the Stroop, and is susceptible to TBI-related injury due to its frontal location and proximity to the rough surface of the falx cerebri. We investigated the relationship between cingulate cortex volume and performance on tasks of selective attention and cognitive flexibility (single-trial Stroop and Auditory Consonant Trigrams [ACT]). Participants consisted of 12 adults with severe TBI and 18 controls. T1-weighted volumetric MRI data were analyzed using automated cortical reconstruction, segmentation, parcellation, and volume measurement. Cortical volume reductions were prominent bilaterally in frontal, temporal, and inferior parietal regions. Specific regional reduction of the cingulate cortex was observed only for cortical volume of right caudal anterior cingulate (cACC). The TBI group performed significantly worse than control participants on the Stroop and ACT tasks. Findings suggest that atrophy of the right cACC may contribute to reduced performance on executive function tasks, such as the Stroop and ACT, although this is likely but one node of an extensive brain network involved in these cognitive processes. (JINS, 2013, 19, 1–12)

Outcome of moderate to severe traumatic brain injury (TBI) includes impaired emotion regulation. Emotion regulation has been associated with amygdala and rostral anterior cingulate (rACC). However, functional connectivity between the two structures after injury has not been reported. A preliminary examination of functional connectivity of rACC and right amygdala was conducted in adolescents 2 to 3 years after moderate to severe TBI and in typically developing (TD) control adolescents, with the hypothesis that the TBI adolescents would demonstrate altered functional connectivity in the two regions. Functional connectivity was determined by correlating fluctuations in the blood oxygen level dependent (BOLD) signal of the rACC and right amygdala with that of other brain regions. In the TBI adolescents, the rACC was found to be significantly less functionally connected to medial prefrontal cortices and to right temporal regions near the amygdala (height threshold T = 2.5, cluster level p < .05, FDR corrected), while the right amygdala showed a trend in reduced functional connectivity with the rACC (height threshold T = 2.5, cluster level p = .06, FDR corrected). Data suggest disrupted functional connectivity in emotion regulation regions. Limitations include small sample sizes. Studies with larger sample sizes are necessary to characterize the persistent neural damage resulting from moderate to severe TBI during development. (JINS, 2013, 19, 1–14)

Improved understanding of the pattern of white matter changes in early and prodromal Alzheimer's disease (AD) states such as mild cognitive impairment (MCI) is necessary to support earlier preclinical detection of AD, and debate remains whether white matter changes in MCI are secondary to gray matter changes. We applied neuropsychologically based MCI criteria to a sample of normally aging older adults; 32 participants met criteria for MCI and 81 participants were classified as normal control (NC) subjects. Whole-head high resolution T1 and diffusion tensor imaging scans were completed. Tract-Based Spatial Statistics was applied and a priori selected regions of interest were extracted. Hippocampal volume and cortical thickness averaged across regions with known vulnerability to AD were derived. Controlling for cortical thickness, the MCI group showed decreased average fractional anisotropy (FA) and decreased FA in parietal white matter and in white matter underlying the entorhinal and posterior cingulate cortices relative to the NC group. Statistically controlling for cortical thickness, medial temporal FA was related to memory and parietal FA was related to executive functioning. These results provide further support for the potential role of white matter integrity as an early biomarker for individuals at risk for AD and highlight that changes in white matter may be independent of gray matter changes. (JINS, 2013, 19, 1–13)

The Relative Consequence Model proposes multiple sclerosis (MS) patients have a fundamental deficit in processing speed that compromises other cognitive functions. The present study examined the mediating role of processing speed, as well as working memory, in the MS-related effects on other cognitive functions for early relapsing-remitting patients. Seventy relapsing-remitting MS patients with disease duration not greater than 10 years and 72 controls completed tasks assessing processing speed, working memory, learning, and executive functioning. The possible mediating roles of speed and working memory in the MS-related effects on other cognitive functions were evaluated using structural equation modeling. Processing speed was not significantly related to group membership and could not have a mediating role. Working memory was related to group membership and functioned as a mediating/intervening factor. The results do not support the Relative Consequence Model in this sample and they challenge the notion that working memory impairment only emerges at later disease stages. The results do support a mediating/intervening role of working memory. These results were obtained for early relapsing-remitting MS patients and should not be generalized to the broader MS population. Instead, future research should examine the relations that exist at other disease stages. (JINS, 2013, 19, 1–12)