Objectives Research suggests that the majority of mild traumatic brain injury (mTBI) patients exhibit both cognitive and emotional dysfunction within the first weeks of injury, followed by symptom resolution 3–6 months post-injury. The neuronal correlates of said dysfunction are difficult to detect with standard clinical neuroimaging, complicating differential diagnosis and early identification of patients who may not recover. The current study examined whether resting state functional magnetic resonance imaging (FMRI) provides objective markers of injury and predicts cognitive, emotional and somatic complaints in mTBI patients semi-acutely (< 3 weeks post-injury) and in late recovery (3–5 month) phases. Methods Twenty seven semi-acute mTBI patients and 26 gender, age and education matched controls were studied. Fifteen out of 27 patients returned for a follow-up visit 3–5 months post-injury. The main dependent variables were spontaneous fluctuations (temporal correlation) in the default-mode (DMN) and fronto-parietal task-related (TRN) networks as measured by FMRI. Results Significant differences in self-reported cognitive, emotional and somatic complaints were observed (all p < .05), despite normal clinical (T1 and T2) imaging and neuropsychological testing results. Mild TBI patients demonstrated decreased functional connectivity within the DMN and hyper-connectivity between the DMN and lateral prefrontal cortex. Measures of functional connectivity exhibited high levels of sensitivity and specificity for patient classification and predicted cognitive complaints in the semi-acute injury stage. However, no changes in functional connectivity were observed across a four month recovery period. Conclusions Abnormal connectivity between the DMN and frontal cortex may provide objective biomarkers of mTBI and underlie cognitive impairment.

Objectives: Only a handful of studies have investigated the nature, functional significance, and course of white matter abnormalities associated with mild traumatic brain injury (mTBI) during the semi-acute stage of injury. The present study used diffusion tensor imaging (DTI) to investigate white matter integrity and compared the accuracy of traditional anatomic scans, neuropsychological testing, and DTI for objectively classifying mTBI patients from controls. Methods:Twenty-two patients with semi-acute mTBI (mean ϭ 12 days postinjury), 21 matched healthy controls, and a larger sample (n ϭ 32) of healthy controls were studied with an extensive imaging and clinical battery. A subset of participants was examined longitudinally 3-5 months after their initial visit.Results: mTBI patients did not differ from controls on clinical imaging scans or neuropsychological performance, although effect sizes were consistent with literature values. In contrast, mTBI patients demonstrated significantly greater fractional anisotropy as a result of reduced radial diffusivity in the corpus callosum and several left hemisphere tracts. DTI measures were more accurate than traditional clinical measures in classifying patients from controls. Longitudinal data provided preliminary evidence of partial normalization of DTI values in several white matter tracts.Conclusions: Current findings of white matter abnormalities suggest that cytotoxic edema may be present during the semi-acute phase of mild traumatic brain injury (mTBI). Initial mechanical damage to axons disrupts ionic homeostasis and the ratio of intracellular and extracellular water, primarily affecting diffusion perpendicular to axons. Diffusion tensor imaging measurement may have utility for objectively classifying mTBI, and may serve as a potential biomarker of recovery. Neurology® 2010;74:643-650 GLOSSARY ADC ϭ apparent diffusion coefficient; CC ϭ corpus callosum; CCI ϭ cortical impact injury model; CR ϭ corona radiata; DTI ϭ diffusion tensor imaging; EC ϭ external capsule; FA ϭ fractional anisotropy; FPI ϭ fluid percussion injury model; HC ϭ healthy controls; IC ϭ internal capsule; JHU ϭ Johns Hopkins University; MANCOVA ϭ multivariate analysis of covariance; mTBI ϭ mild traumatic brain injury; RD ϭ radial diffusivity; ROI ϭ region of interest; SCR ϭ superior corona radiata; SLF ϭ superior longitudinal fasciculus; UF ϭ uncinate fasciculus.Complex cognitive processes such as attention, executive functions, and memory depend on intact white matter tracts among frontal, parietal, and medial temporal lobes, 1 which are likely disrupted following mild traumatic brain injury (mTBI). Histologic evidence of white matter changes have been observed in both human autopsy 2,3 and animal 4 studies of mTBI. Although traditional neuroimaging sequences (i.e., T1-and T2-weighted imaging) are typically insensitive to these putative white matter changes, diffusion tensor imaging (DTI) is capable of measuring white matter pathology with histologic correlates in animal models of injury...

Deficits in working memory (WM) are a consistent neurocognitive marker for schizophrenia. Previous studies have suggested that WM is the product of coordinated activity in distributed functionally connected brain regions. Independent component analysis (ICA) is a data driven approach that can identify temporally coherent networks that underlie fMRI activity. We applied ICA to an fMRI dataset for 115 patients with chronic schizophrenia and 130 healthy controls performing the Sternberg Item Recognition Paradigm. Here, we describe the first results using ICA to identify differences in the function of WM networks in schizophrenia compared to controls. ICA revealed six networks that showed significant differences between schizophrenia patients and healthy controls. Four of these networks were negatively task-correlated and showed deactivation across the posterior cingulate, precuneus, medial prefrontal cortex, anterior cingulate, inferior parietal lobules, and parahippocampus. These networks comprise brain regions known as the default-mode network (DMN), a well-characterized set of regions shown to be active during internal modes of cognition and implicated in schizophrenia. Two networks were positively task- NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript correlated, with one network engaging WM regions such as bilateral DLPFC and inferior parietal lobules while the other network engaged primarily the cerebellum. Our results suggest that DLPFC dysfunction in schizophrenia might be lateralized to the left and intrinsically tied to other regions such as the inferior parietal lobule and cingulate gyrus. Furthermore, we found that DMN dysfunction in schizophrenia exists across multiple subnetworks of the DMN and that these subnetworks are individually relevant to the pathophysiology of schizophrenia. In summary, this large multsite study identified multiple temporally coherent networks which are aberrant in schizophrenia versus healthy controls and suggests both task correlated and task anticorrelated networks may serve as potential biomarkers.

Single-voxel proton magnetic resonance imaging (1H-MRS) and proton MR spectroscopic imaging (1H-MRSI) were used to compare brain metabolite levels in semi-acute mild traumatic brain injury (mTBI) patients (n = 10) and matched healthy controls (n = 9). The 1H-MRS voxel was positioned in the splenium, a region known to be susceptible to axonal injury in TBI, and a single 1H-MRSI slice was positioned above the lateral ventricles. To increase sensitivity to the glutamate (Glu) and the combined glutamate-glutamine (Glx) signal, an inter-pulse echo time shown to emphasize the major Glu signals was used along with an analysis method that reduces partial volume errors by using water as a concentration standard. Our preliminary findings indicate significantly lower levels of gray matter Glx and higher levels of white matter creatine-phosphocreatine (Cr) in mTBI subjects relative to healthy controls. Furthermore, Cr levels were predictive of executive function and emotional distress in the combined groups. These results suggest that perturbations in Cr, a critical component of the brain’s energy metabolism, and Glu, the brain’s major neurotransmitter, may occur following mTBI. Moreover, the different pattern of results for gray and white matter suggests tissue-specific metabolic responses to mTBI.

Deficits in the connectivity between brain regions have been suggested to play a major role in the pathophysiology of schizophrenia. A functional magnetic resonance imaging (fMRI) analysis of schizophrenia was implemented using independent component analysis (ICA) to identify multiple temporally cohesive, spatially distributed regions of brain activity that represent functionally connected networks. We hypothesized that functional connectivity differences would be seen in auditory networks comprised of regions such as superior temporal gyrus as well as executive networks that consisted of frontal-parietal areas. Eight networks were found to be implicated in schizophrenia during the auditory oddball paradigm. These included a bilateral temporal network containing the superior and middle temporal gyrus; a default-mode network comprised of the posterior cingulate, precuneus, and middle frontal gyrus; and multiple dorsal lateral prefrontal cortex networks that constituted various levels of between-group differences. Highly task-related sensory networks were also found. These results indicate that patients with schizophrenia show functional connectivity differences in networks related to auditory processing, executive control, and baseline functional activity. Overall, these findings support the idea that the cognitive deficits associated with schizophrenia are widespread and that a functional connectivity approach can help elucidate the neural correlates of this disorder.