Traumatic brain injury alters the functional brain network mediating working memory.

PRIMARY OBJECTIVE: Investigation of the impact of traumatic brain injury (TBI) on the functional brain network that mediates working memory function. RESEARCH DESIGN: Functional magnetic resonance imaging (fMRI) during an n-back working memory task in nine chronic-stage patients with TBI and nine age-matched healthy controls. In addition to classical analyses investigating regional activity, the authors examined functional connectivity of the brain regions critical to working memory performance using psychophysiological interaction (PPI) analyses. MAIN OUTCOMES AND RESULTS: Patients with TBI made a greater percentage of errors than controls at high working memory load conditions. The fMRI data showed that the activation of the left inferior parietal gyrus (LIPG) was significantly reduced, whereas the activation of the right inferior frontal gyrus (RIFG) was significantly increased in patients compared with controls. Task performance accuracy was significantly associated with the activation of the LIPG in controls and the activation of the RIFG in patients. PPI analyses on fMRI data further suggested that the functional connectivity between the RIFG and LIPG was compromised in patients. CONCLUSION: The abnormal functional connectivity between LIPG and RIFG may underlie the observed working memory deficits and abnormal brain activation pattern in patients.

Heterogeneity in the patterns of neural abnormality in autistic spectrum disorders: evidence from ERP and MRI.

Autistic spectrum disorder (ASD) refers to a heterogeneous group of social communication problems. Research into the neural basis of ASD has revealed abnormalities in a number of different regions of the brain. However, the literature is highly inconsistent. One possible explanation for these discrepancies is differences in intelligence. Children with ASD and below average intelligence may be hypothesised to show additional or different neural abnormalities. This possibility was explored using structural magnetic resonance imaging (MRI) and event-related potentials (ERP). Two groups of children with ASD were studied, those with average or above average intelligence (high ASD group) and those with below average intelligence (low ASD group). The structural MRI data were analysed using voxel-based morphometry (VBM). Using the family-wise error threshold, results showed bilateral abnormality common to the two ASD groups in the cerebellum, fusiform gyrus and frontal cortex. In addition, a number of regions were found to be significantly different in the two ASD groups: regions of the cerebellum showed increased grey matter density bilaterally in the high ASD group, but decreased grey matter density bilaterally in the low ASD group. Further, compared to the high ASD group, additional bilateral abnormalities were found in the postcentral gyrus and regions of the dorsolateral prefrontal cortex in the low ASD group. Using the less stringent false discovery rate (FDR) threshold, differences were also seen in the medial temporal lobes. ERPs also showed differences between the two ASD groups. Whereas the ERPs of the high ASD group were not significantly different from those of the controls, the low ASD group had delayed novelty P3a responses and reduced amplitude target P3b components. These data provide convergent ERP and MRI evidence for the heterogeneity of neural abnormality in ASD in relation to variations in intelligence.

Cognitive reserve as a resilience factor against depression after moderate/severe head injury.

Depression is one of the most frequently reported and distressing residual complaints in survivors of head injury. Studies investigating the pattern of neuropathology associated with depression post head injury have found little consistency. One explanation for this is that cognitive reserve "protects" against depression either through more efficient processing or more effective compensation. An alternative explanation is that previous studies have used relatively gross measures of lesion location, and variable inclusion criteria and times between scan and injury. This study explored these possibilities in a cohort of survivors of moderate-severe head injury at least 6 months post-injury. Volunteers completed neuropsychological assessments and structural magnetic resonance imaging (MRI) scans. A significant difference between depressed and non-depressed survivors was found, with higher intelligence associated with lower rates of depression. No significant anatomical differences were found between depressed and non-depressed survivors. These results suggest that premorbid intelligence may provide a resilience factor against depression in head injury survivors.

Frontal cerebral vulnerability and executive deficits from raised intracranial pressure in child traumatic brain injury.

In severe pediatric traumatic brain injury (TBI), a common focus of treatment is raised intracranial pressure (ICP). The aim of this investigation was to test whether raised ICP is associated with later prefrontal executive deficits and regional brain tissue loss, consistent with an anterior vascular compartment syndrome. Thirty-three participants were assigned to one of two severe TBI groups based on whether or not they had increased ICP complicating their critical illness. At follow-up (average 3.9 years), the participants underwent magnetic resonance imaging and a battery of neuropsychological testing focused on prefrontal function. The ICP group had white matter loss that was diffuse as well as regional in the corpus callosum, periventricular tissue, and frontal region. Loss of gray matter in the ICP group was more regionally specific, with bilateral loss in the caudate nuclei and frontal regions, including the right dorsolateral region, right supplementary motor area, and the left orbitofrontal cortex. Both groups had normal intelligence quotients (IQs), but the ICP group showed long-term deficits on various measures of attention and executive function such as working memory, decision-making, and impulsivity. These findings suggest that raised ICP leads to diffuse brain injury and a predilection to hypoperfusion in, at least, the distribution of the anterior cerebral artery. Furthermore, since voxel-based morphometry (VBM) and measures of attention and executive function are sensitive to the phenomenon of raised ICP, we consider that these techniques warrant inclusion in trials assessing ICP-directed therapy.

The effects of methylphenidate on decision making in attention-deficit/hyperactivity disorder.

BACKGROUND: Children with attention-deficit/hyperactivity disorder (ADHD) frequently display poor judgment and risk taking in their everyday behavior, but there are little empirical data on decision-making cognition in this disorder. The objectives of the study were to assess the effects of stimulant medication on decision making in ADHD and compare performance on the Cambridge Gamble Task between boys with and without ADHD. METHODS: Twenty-one boys (aged 7-13) diagnosed with ADHD underwent a double-blind, placebo-controlled trial of methylphenidate (.5 mg/kg) during which they performed the Cambridge Gamble Task (CGT). A healthy age-matched control group was tested on two occasions off drug. RESULTS: The ADHD group bet more conservatively on the methylphenidate session than on the placebo session. In comparison with healthy control subjects, the ADHD group made more poor decisions, placed their bets more impulsively, and adjusted their bets less according to the chances of winning. Poor decision making was correlated with parent-reported symptoms and disruptive behavior in the ADHD group. CONCLUSIONS: Methylphenidate reduced risk-prone betting behavior on the CGT. Compared with control subjects, children with ADHD display a number of decision-making deficits on the task, and the measure of rational decision making may serve as an ecologically valid neuropsychological marker of impairment.

Impulsivity, reward sensitivity, and decision-making in subarachnoid hemorrhage survivors.

Subarachnoid hemorrhage (SAH) survivors often report psychosocial and emotional changes, including a diminished capacity for decision making. However, systematic investigations into the nature of the changes have been limited to those patients surviving SAH secondary to aneurysms of the anterior communicating artery. This study aimed to explore the nature of decision making in survivors of SAH secondary to aneurysms of the middle cerebral or posterior communicating artery using a series of computerized tasks. Twenty SAH survivors and 20 matched controls completed a battery of computerized decision-making tasks. These included tasks examining an individual's ability to make probabilistic choices and risk-taking behavior, as well as tasks examining aspects of impulsivity. The results revealed two key patterns of abnormal decision-making behavior in the SAH survivors: altered sensitivity to both reward and punishment, and impulsive responding. These complex deficits may contribute to difficulties in daily living resulting from apathy, poor judgment, or inhibition in SAH survivors.

Head circumference and brain and hippocampal volume after severe traumatic brain injury in childhood.

Vulnerability of the hippocampus to traumatic brain injury (TBI) in adults is related to severity of injury and white matter atrophy. The objectives of this study were to determine features of anthropometry and cerebral morphometry late after TBI in childhood and to assess whether hippocampal volume is related to severity of initial ictus and changes in white matter at follow-up. Thirty-three patients underwent magnetic resonance imaging 4.9 y after severe TBI that necessitated intensive care; 23 had mechanical ventilation and intracranial pressure monitoring longer than 3 d. Magnetic resonance imaging analyses included volume of brain, hemisphere, ventricles, and hippocampal and perihippocampal regions; spatial distribution of voxel-based morphometry differences in white matter; and eigenvalues of diffusion tensor imaging diffusivity. Patients with longer intensive care ictus had smaller-than-expected occipitofrontal head circumference. Eight of these, identified by voxel-based morphometry, had periventricular white matter loss and smaller-than-expected brain volume for OFC, suggesting "atrophy"; the remainder had expected volume for a smaller OFC, suggesting "growth disturbance." Ninety-three percent of the variation in right hippocampal volume was accounted for by factors related to severity of injury and white matter atrophy. It is concluded that anthropometry and cerebral morphometric measurements late after severe TBI in childhood provides useful outcome data and indicate that, despite adequate growth in stature, effects of TBI on brain growth and hippocampal volume may extend into adulthood.

Bilateral brain abnormalities associated with dominantly inherited verbal and orofacial dyspraxia.

The KE family is a large three-generational pedigree in which half of the members suffer from a verbal and orofacial dyspraxia in association with a point mutation in the FOXP2 gene. This report extends previous voxel-based morphometric analyses of magnetic resonance imaging (MRI) scans (Watkins et al. [2002] Brain 125:465-478) using a bilateral conjunction analysis. This searches specifically for areas of grey matter density that differ bilaterally in the affected members compared with both matched controls and the unaffected family members. 3-D T1-weighted MRI datasets of 17 family members (10 affected, 7 unaffected) and matched controls were compared. The most significant findings were reduced grey matter density bilaterally in the caudate nucleus, the cerebellum, and the left and right inferior frontal gyrus in the affected members. In addition, increased grey matter density was found bilaterally in the planum temporale. These results confirm that a point mutation in FOXP2 is associated with several bilateral grey matter abnormalities in both motor and language related regions. The results also demonstrate the advantages of using a conjunction analysis when bilateral abnormalities are suspected.