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      Neuroimaging after mild traumatic brain injury: Review and meta-analysis

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          This paper broadly reviews the study of mild traumatic brain injury (mTBI), across the spectrum of neuroimaging modalities. Among the range of imaging methods, however, magnetic resonance imaging (MRI) is unique in its applicability to studying both structure and function. Thus we additionally performed meta-analyses of MRI results to examine 1) the issue of anatomical variability and consistency for functional MRI (fMRI) findings, 2) the analogous issue of anatomical consistency for white-matter findings, and 3) the importance of accounting for the time post injury in diffusion weighted imaging reports. As we discuss, the human neuroimaging literature consists of both small and large studies spanning acute to chronic time points that have examined both structural and functional changes with mTBI, using virtually every available medical imaging modality. Two key commonalities have been used across the majority of imaging studies. The first is the comparison between mTBI and control populations. The second is the attempt to link imaging results with neuropsychological assessments. Our fMRI meta-analysis demonstrates a frontal vulnerability to mTBI, demonstrated by decreased signal in prefrontal cortex compared to controls. This vulnerability is further highlighted by examining the frequency of reported mTBI white matter anisotropy, in which we show a strong anterior-to-posterior gradient (with anterior regions being more frequently reported in mTBI). Our final DTI meta-analysis examines a debated topic arising from inconsistent anisotropy findings across studies. Our results support the hypothesis that acute mTBI is associated with elevated anisotropy values and chronic mTBI complaints are correlated with depressed anisotropy. Thus, this review and set of meta-analyses demonstrate several important points about the ongoing use of neuroimaging to understand the functional and structural changes that occur throughout the time course of mTBI recovery. Based on the complexity of mTBI, however, much more work in this area is required to characterize injury mechanisms and recovery factors and to achieve clinically-relevant capabilities for diagnosis.


          • mTBI neuroimaging literature review and meta-analyses of fMRI and DTI.

          • fMRI meta-analysis revealed differences between mTBI and controls in 13 regions.

          • mTBI anisotropy findings are statistically more frequently reported in anterior regions.

          • Anisotropy is elevated in acute mTBI, but depressed in chronic mTBI.

          • We hypothesize a statistical interaction between anisotropy, cognitive score, and time.

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          Most cited references 81

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          The role of prefrontal cortex in working-memory capacity, executive attention, and general fluid intelligence: An individual-differences perspective

          We provide an "executive-attention" framework for organizing the cognitive neuroscience research on the constructs of working-memory capacity (WMC), general fluid intelligence, and prefrontal cortex (PFC) function. Rather than provide a novel theory of PFC function, we synthesize a wealth of single-cell, brain-imaging, and neuropsychological research through the lens of our theory of normal individual differences in WMC and attention control (Engle, Kane, & Tuholski, 1999; Engle, Tuholski, Laughlin, & Conway, 1999). Our critical review confirms the prevalent view that dorsolateral PFC circuitry is critical to executive-attention functions. Moreover, although the dorsolateral PFC is but one critical structure in a network of anterior and posterior "attention control" areas, it does have a unique executive-attention role in actively maintaining access to stimulus representations and goals in interference-rich contexts. Our review suggests the utility of an executive-attention framework for guiding future research on both PFC function and cognitive control.
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            Mnemonic coding of visual space in the monkey's dorsolateral prefrontal cortex.

            1. An oculomotor delayed-response task was used to examine the spatial memory functions of neurons in primate prefrontal cortex. Monkeys were trained to fixate a central spot during a brief presentation (0.5 s) of a peripheral cue and throughout a subsequent delay period (1-6 s), and then, upon the extinction of the fixation target, to make a saccadic eye movement to where the cue had been presented. Cues were usually presented in one of eight different locations separated by 45 degrees. This task thus requires monkeys to direct their gaze to the location of a remembered visual cue, controls the retinal coordinates of the visual cues, controls the monkey's oculomotor behavior during the delay period, and also allows precise measurement of the timing and direction of the relevant behavioral responses. 2. Recordings were obtained from 288 neurons in the prefrontal cortex within and surrounding the principal sulcus (PS) while monkeys performed this task. An additional 31 neurons in the frontal eye fields (FEF) region within and near the anterior bank of the arcuate sulcus were also studied. 3. Of the 288 PS neurons, 170 exhibited task-related activity during at least one phase of this task and, of these, 87 showed significant excitation or inhibition of activity during the delay period relative to activity during the intertrial interval. 4. Delay period activity was classified as directional for 79% of these 87 neurons in that significant responses only occurred following cues located over a certain range of visual field directions and were weak or absent for other cue directions. The remaining 21% were omnidirectional, i.e., showed comparable delay period activity for all visual field locations tested. Directional preferences, or lack thereof, were maintained across different delay intervals (1-6 s). 5. For 50 of the 87 PS neurons, activity during the delay period was significantly elevated above the neuron's spontaneous rate for at least one cue location; for the remaining 37 neurons only inhibitory delay period activity was seen. Nearly all (92%) neurons with excitatory delay period activity were directional and few (8%) were omnidirectional. Most (62%) neurons with purely inhibitory delay period activity were directional, but a substantial minority (38%) was omnidirectional. 6. Fifteen of the neurons with excitatory directional delay period activity also had significant inhibitory delay period activity for other cue directions. These inhibitory responses were usually strongest for, or centered about, cue directions roughly opposite those optimal for excitatory responses.(ABSTRACT TRUNCATED AT 400 WORDS)
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              The neural basis of the central executive system of working memory.

              Working memory refers to a system for temporary storage and manipulation of information in the brain, a function critical for a wide range of cognitive operations. It has been proposed that working memory includes a central executive system (CES) to control attention and information flow to and from verbal and spatial short-term memory buffers. Although the prefrontal cortex is activated during both verbal and spatial passive working memory tasks, the brain regions involved in the CES component of working memory have not been identified. We have used functional magnetic resonance imaging (fMRI) to examine brain activation during the concurrent performance of two tasks, which is expected to engage the CES. Activation of the prefrontal cortex was observed when both tasks are performed together, but not when they are performed separately. These results support the view that the prefrontal cortex is involved in human working memory.

                Author and article information

                Neuroimage Clin
                Neuroimage Clin
                NeuroImage : Clinical
                4 January 2014
                4 January 2014
                : 4
                : 283-294
                [a ]Virginia Tech Carilion Research Institute, 2 Riverside Circle, Roanoke, VA, USA
                [b ]Structural and Computational Biology & Molecular Biophysics Graduate Program, Baylor College of Medicine, Houston, TX 77030, USA
                [c ]Child Mind Institute, 445 Park Avenue, New York, NY, USA
                [d ]Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA
                [e ]Virginia Tech Carilion School of Medicine, 2 Riverside Circle, Roanoke, VA, USA
                [f ]Department of Psychology, Virginia Tech, Blacksburg, VA, USA
                [g ]School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
                [h ]Department of Emergency Medicine, Virginia Tech Carilion School of Medicine, Roanoke, VA, USA
                [i ]Department of Emergency Radiology, Virginia Tech Carilion School of Medicine, Roanoke, VA, USA
                Author notes
                [* ]Corresponding author at: Virginia Tech Carilion Research Institute, 2 Riverside Circle, Roanoke, VA 24016, USA. Tel.: + 1 540 526 2008; fax: + 1 540 985 3373. slaconte@ 123456vtc.vt.edu
                © 2013 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).



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