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      Significant Improvements in Cognitive Performance Post-Transcranial, Red/Near-Infrared Light-Emitting Diode Treatments in Chronic, Mild Traumatic Brain Injury: Open-Protocol Study

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          Abstract

          This pilot, open-protocol study examined whether scalp application of red and near-infrared (NIR) light-emitting diodes (LED) could improve cognition in patients with chronic, mild traumatic brain injury (mTBI). Application of red/NIR light improves mitochondrial function (especially in hypoxic/compromised cells) promoting increased adenosine triphosphate (ATP) important for cellular metabolism. Nitric oxide is released locally, increasing regional cerebral blood flow. LED therapy is noninvasive, painless, and non-thermal (cleared by the United States Food and Drug Administration [FDA], an insignificant risk device). Eleven chronic, mTBI participants (26-62 years of age, 6 males) with nonpenetrating brain injury and persistent cognitive dysfunction were treated for 18 outpatient sessions (Monday, Wednesday, Friday, for 6 weeks), starting at 10 months to 8 years post- mTBI (motor vehicle accident [MVA] or sports-related; and one participant, improvised explosive device [IED] blast injury). Four had a history of multiple concussions. Each LED cluster head (5.35 cm diameter, 500 mW, 22.2 mW/cm(2)) was applied for 10 min to each of 11 scalp placements (13 J/cm(2)). LEDs were placed on the midline from front-to-back hairline; and bilaterally on frontal, parietal, and temporal areas. Neuropsychological testing was performed pre-LED, and at 1 week, and 1 and 2 months after the 18th treatment. A significant linear trend was observed for the effect of LED treatment over time for the Stroop test for Executive Function, Trial 3 inhibition (p=0.004); Stroop, Trial 4 inhibition switching (p=0.003); California Verbal Learning Test (CVLT)-II, Total Trials 1-5 (p=0.003); and CVLT-II, Long Delay Free Recall (p=0.006). Participants reported improved sleep, and fewer post-traumatic stress disorder (PTSD) symptoms, if present. Participants and family reported better ability to perform social, interpersonal, and occupational functions. These open-protocol data suggest that placebo-controlled studies are warranted.

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          Most cited references49

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          Persistent activity in the prefrontal cortex during working memory.

          The dorsolateral prefrontal cortex (DLPFC) plays a crucial role in working memory. Notably, persistent activity in the DLPFC is often observed during the retention interval of delayed response tasks. The code carried by the persistent activity remains unclear, however. We critically evaluate how well recent findings from functional magnetic resonance imaging studies are compatible with current models of the role of the DLFPC in working memory. These new findings suggest that the DLPFC aids in the maintenance of information by directing attention to internal representations of sensory stimuli and motor plans that are stored in more posterior regions.
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            Anterior cingulate cortex and conflict detection: an update of theory and data.

            The dorsal anterior cingulate cortex (ACC) and associated regions of the medial frontal wall have often been hypothesized to play an important role in cognitive control. We have proposed that the ACC's specific role in cognitive control is to detect conflict between simultaneously active, competing representations and to engage the dorsolateral prefrontal cortex (DLPFC) to resolve such conflict. Here we review some of the evidence supporting this theory, from event-related potential (ERP) and fMRI studies. We focus on data obtained from interference tasks, such as the Stroop task, and review the evidence that trial-to-trial changes in control engagement can be understood as driven by conflict detection; the data suggest that levels of activation of the ACC and the DLPFC in such tasks do indeed reflect conflict and control, respectively. We also discuss some discrepant results in the literature that highlight the need for future research.
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              Salience network integrity predicts default mode network function after traumatic brain injury.

              Efficient behavior involves the coordinated activity of large-scale brain networks, but the way in which these networks interact is uncertain. One theory is that the salience network (SN)--which includes the anterior cingulate cortex, presupplementary motor area, and anterior insulae--regulates dynamic changes in other networks. If this is the case, then damage to the structural connectivity of the SN should disrupt the regulation of associated networks. To investigate this hypothesis, we studied a group of 57 patients with cognitive impairments following traumatic brain injury (TBI) and 25 control subjects using the stop-signal task. The pattern of brain activity associated with stop-signal task performance was studied by using functional MRI, and the structural integrity of network connections was quantified by using diffusion tensor imaging. Efficient inhibitory control was associated with rapid deactivation within parts of the default mode network (DMN), including the precuneus and posterior cingulate cortex. TBI patients showed a failure of DMN deactivation, which was associated with an impairment of inhibitory control. TBI frequently results in traumatic axonal injury, which can disconnect brain networks by damaging white matter tracts. The abnormality of DMN function was specifically predicted by the amount of white matter damage in the SN tract connecting the right anterior insulae to the presupplementary motor area and dorsal anterior cingulate cortex. The results provide evidence that structural integrity of the SN is necessary for the efficient regulation of activity in the DMN, and that a failure of this regulation leads to inefficient cognitive control.
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                Author and article information

                Journal
                Journal of Neurotrauma
                Journal of Neurotrauma
                Mary Ann Liebert Inc
                0897-7151
                1557-9042
                June 2014
                June 2014
                : 31
                : 11
                : 1008-1017
                Affiliations
                [1 ]VA Boston Healthcare System, Boston, Massachusetts.
                [2 ]Department of Neurology, Boston University School of Medicine, Boston, Massachusetts.
                [3 ]Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Charlestown, Massachusetts.
                [4 ]Massachusetts General Hospital, Brigham and Women's Hospital, Red Sox/MGH Home Base Program, Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, Massachusetts.
                [5 ]Wellman Center for Photomedicine, Massachusetts General Hospital, Department of Dermatology, Harvard Medical School, Harvard-MIT Division of Health Science and Technology, Cambridge, Massachusetts.
                [6 ]National Center for PTSD, VA Boston Healthcare System, Boston, Massachusetts.
                [7 ]Micheli Center for Sports Injury Prevention, Waltham, Massachusetts and Sports Concussion Clinic, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
                Article
                10.1089/neu.2013.3244
                24568233
                352fa2ad-3aac-42b9-83ca-bf9b86bdcdc1
                © 2014

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