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      Blast Exposure Impairs Sensory Gating: Evidence from Measures of Acoustic Startle and Auditory Event-Related Potentials

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          Abstract

          Many military service members and veterans who have been exposed to high-intensity blast waves experience traumatic brain injury (TBI), resulting in chronic auditory deficits despite normal hearing sensitivity. The current study sought to examine the neurological cause of this chronic dysfunction by testing the hypothesis that blast exposure leads to impaired filtering of sensory information at brainstem and early cortical levels. Groups of blast-exposed and non-blast-exposed participants completed self-report measures of auditory and neurobehavioral status, auditory perceptual tasks involving degraded and competing speech stimuli, and physiological measures of sensory gating, including pre-pulse inhibition and habituation of the acoustic startle reflex and electrophysiological assessment of a paired-click sensory gating paradigm. Blast-exposed participants showed significantly reduced habituation to acoustic startle stimuli and impaired filtering of redundant sensory information at the level the auditory cortex. Multiple linear regression analyses revealed that poorer sensory gating at the cortical level was primarily influenced by a diagnosis of TBI, whereas reduced habituation was primarily influenced by a diagnosis of post-traumatic stress disorder. A statistical model was created including cortical sensory gating and habituation to acoustic startle, which strongly predicted performance on a degraded speech task. These results support the hypothesis that blast exposure impairs central auditory processing via impairment of neural mechanisms underlying habituation and sensory gating.

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          The N1 wave of the human electric and magnetic response to sound: a review and an analysis of the component structure.

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            Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies.

            Since the mid-1970s, cross-species translational studies of prepulse inhibition (PPI) have increased at an astounding pace as the value of this neurobiologically informative measure has been optimized. PPI occurs when a relatively weak sensory event (the prepulse) is presented 30-500 ms before a strong startle-inducing stimulus, and reduces the magnitude of the startle response. In humans, PPI occurs in a robust, predictable manner when the prepulse and startling stimuli occur in either the same or different modalities (acoustic, visual, or cutaneous). This review covers three areas of interest in human PPI studies. First, we review the normal influences on PPI related to the underlying construct of sensori- (prepulse) motor (startle reflex) gating. Second, we review PPI studies in psychopathological disorders that form a family of gating disorders. Third, we review the relatively limited but interesting and rapidly expanding literature on pharmacological influences on PPI in humans. All studies identified by a computerized literature search that addressed the three topics of this review were compiled and evaluated. The principal studies were summarized in appropriate tables. The major influences on PPI as a measure of sensorimotor gating can be grouped into 11 domains. Most of these domains are similar across species, supporting the value of PPI studies in translational comparisons across species. The most prominent literature describing deficits in PPI in psychiatrically defined groups features schizophrenia-spectrum patients and their clinically unaffected relatives. These findings support the use of PPI as an endophenotype in genetic studies. Additional groups of psychopathologically disordered patients with neuropathology involving cortico-striato-pallido-pontine circuits exhibit poor gating of motor, sensory, or cognitive information and corresponding PPI deficits. These groups include patients with obsessive compulsive disorder, Tourette's syndrome, blepharospasm, temporal lobe epilepsy with psychosis, enuresis, and perhaps posttraumatic stress disorder (PTSD). Several pharmacological manipulations have been examined for their effects on PPI in healthy human subjects. In some cases, the alterations in PPI produced by these drugs in animals correspond to similar effects in humans. Specifically, dopamine agonists disrupt and nicotine increases PPI in at least some human studies. With some other compounds, however, the effects seen in humans appear to differ from those reported in animals. For example, the PPI-increasing effects of the glutamate antagonist ketamine and the serotonin releaser MDMA in humans are opposite to the PPI-disruptive effects of these compounds in rodents. Considerable evidence supports a high degree of homology between measures of PPI in rodents and humans, consistent with the use of PPI as a cross-species measure of sensorimotor gating. Multiple investigations of PPI using a variety of methods and parameters confirm that deficits in PPI are evident in schizophrenia-spectrum patients and in certain other disorders in which gating mechanisms are disturbed. In contrast to the extensive literature on clinical populations, much more work is required to clarify the degree of correspondence between pharmacological effects on PPI in healthy humans and those reported in animals.
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              White matter integrity and cognition in chronic traumatic brain injury: a diffusion tensor imaging study.

              Traumatic brain injury (TBI) is a serious public health problem. Even injuries classified as mild, the most common, can result in persistent neurobehavioural impairment. Diffuse axonal injury is a common finding after TBI, and is presumed to contribute to outcomes, but may not always be apparent using standard neuroimaging. Diffusion tensor imaging (DTI) is a more recent method of assessing axonal integrity in vivo. The primary objective of the current investigation was to characterize white matter integrity utilizing DTI across the spectrum of chronic TBI of all severities. A secondary objective was to examine the relationship between white matter integrity and cognition. Twenty mild, 17 moderate to severe TBI and 18 controls underwent DTI and neuropsychological testing. Fractional anisotropy, axial diffusivity and radial diffusivity were calculated from the DTI data. Fractional anisotropy was the primary measure of white matter integrity. Region of interest analysis included anterior and posterior corona radiata, cortico-spinal tracts, cingulum fibre bundles, external capsule, forceps minor and major, genu, body and splenium of the corpus callosum, inferior fronto-occipital fasciculus, superior longitudinal fasciculus and sagittal stratum. Cognitive domain scores were calculated from executive, attention and memory testing. Decreased fractional anisotropy was found in all 13 regions of interest for the moderate to severe TBI group, but only in the cortico-spinal tract, sagittal stratum and superior longitudinal fasciculus for the mild TBI group. White Matter Load (a measure of the total number of regions with reduced FA) was negatively correlated with all cognitive domains. Analysis of radial and axial diffusivity values suggested that all severities of TBI can result in a degree of axonal damage, while irreversible myelin damage was only apparent for moderate to severe TBI. The present data emphasize that white matter changes exist on a spectrum, including mild TBI. An index of global white matter neuropathology (White Matter Load) was related to cognitive function, such that greater white matter pathology predicted greater cognitive deficits. Mechanistically, mild TBI white matter changes may be primarily due to axonal damage as opposed to myelin damage. The more severe injuries impact both. DTI provides an objective means for determining the relationship of cognitive deficits to TBI, even in cases where the injury was sustained years prior to the evaluation.
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                Author and article information

                Journal
                J Neurotrauma
                J. Neurotrauma
                neu
                Journal of Neurotrauma
                Mary Ann Liebert, Inc., publishers (140 Huguenot Street, 3rd FloorNew Rochelle, NY 10801USA )
                0897-7151
                1557-9042
                01 March 2019
                09 February 2019
                09 February 2019
                : 36
                : 5
                : 702-712
                Affiliations
                [ 1 ]National Center for Rehabilitative Auditory Research , VA Portland Health Care System, Portland, Oregon.
                [ 2 ]Department of Otolaryngology Head and Neck Surgery, Oregon Health & Science University , Portland, Oregon.
                [ 3 ]Department of Neurology, Oregon Health & Science University , Portland, Oregon.
                [ 4 ]Department of Psychiatry, Oregon Health & Science University , Portland, Oregon.
                [ 5 ]Department of Medicine, Division of Pulmonary and Critical Care Medicine, Oregon Health & Science University , Portland, Oregon.
                [ 6 ]Department of Behavioral Neuroscience and Oregon Institute of Occupational Health Sciences, Oregon Health & Science University , Portland, Oregon.
                Author notes
                [*]Address correspondence to: Melissa A. Papesh, AuD, PhD, NCRAR, VA Portland Health Care System, 3710 SW US Veterans Hospital Road, Mailcode P5-NCRAR, Portland, OR 97239 Melissa.Papesh@ 123456va.gov
                Article
                10.1089/neu.2018.5801
                10.1089/neu.2018.5801
                6387566
                30113267
                42011c87-77aa-4849-92c4-b3d7d742eff8
                © Melissa A. Papesh et al., 2018; Published by Mary Ann Liebert, Inc.

                This Open Access article is distributed under the terms of the Creative Commons License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.

                History
                Page count
                Figures: 6, Tables: 3, References: 80, Pages: 11
                Categories
                Original Articles

                electrophysiology,hearing,post-traumatic stress,tbi,veteran
                electrophysiology, hearing, post-traumatic stress, tbi, veteran

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