Nicholas D. Davenport

Neural development of selective attention and response inhibition

Brain activation differences between 12 children (9- to 12-year-olds) and 12 adults (20- to 30-year-olds) were examined on two cognitive tasks during functional magnetic resonance imaging (fMRI). Spatial selective attention was measured with the visual search for a conjunction target (red triangle) in a field of distracters and response inhibition was measured with a go no-go task. There were small developmental differences in the selective attention task, with children showing greater activation than adults in the anterior cingulate and thalamus. There were large developmental differences in the response inhibition task, with children showing greater activation than adults in a fronto-striatal network including middle cingulate, medial frontal gyrus, medial aspects of bilateral superior frontal gyrus, and the caudate nucleus on the left. Children also showed greater bilateral activation for the response inhibition task in posterior cingulate, thalamus and the hippocampo-amygdaloid region. The extensive developmental differences on the response inhibition task are consistent with the prolonged maturation of the fronto-striatal network.

Diffuse and spatially variable white matter disruptions are associated with blast-related mild traumatic brain injury

Mild traumatic brain injury (mTBI) due to explosive blast is common among military service members and often associated with long term psychological and cognitive disruptions. Little is known about the neurological effects of blast-related mTBI and whether they differ from those of civilian, non-blast mTBI. Given that brain damage from blasts may be diffuse and heterogeneous, we tested the hypothesis that blast mTBI is associated with subtle white matter disruptions in the brain that are spatially inconsistent across individuals. We used diffusion tensor imaging to examine white matter integrity, as quantified by fractional anisotropy (FA), in a group of American military service members with (n=25) or without (n=33) blast-related mTBI who had been deployed as part of Operation Iraqi Freedom or Operation Enduring Freedom. History of civilian non-blast mTBI was equally common across groups, which enabled testing of both blast and non-blast mTBI effects on measures sensitive to (1) concentrated, spatially consistent (average FA within a region of interest [ROI]), (2) concentrated, spatially variable (number of ROIs with low average FA), and (3) diffuse (number of voxels with low FA) disruptions of white matter integrity. Blast mTBI was associated with a diffuse, global pattern of lower white matter integrity, and this pattern was not affected by previous civilian mTBI. Neither type of mTBI had an effect on the measures sensitive to more concentrated and spatially consistent white matter disruptions. Additionally, individuals with more than one blast mTBI tended to have a larger number of low FA voxels than individuals with a single blast injury. These results indicate that blast mTBI is associated with disrupted integrity of several white matter tracts, and that these disruptions are diluted by averaging across the large number of voxels within an ROI. The reported pattern of effects supports the conclusion that the neurological effects of blast mTBI are diffuse, widespread, and spatially variable.

Evidence of disrupted functional connectivity in the brain after combat-related blast injury

Non-impact blast-related mild traumatic brain injury (mTBI) appears to be present in soldiers returning from deployments to Afghanistan and Iraq. Although mTBI typically results in cognitive deficits that last less than a month, there is evidence that disrupted coordination of brain activity can persist for at least several months following injury (Thatcher et al., 1989, 2001). In the present study we examined whether neural communication may be affected in soldiers months after blast-related mTBI, and whether coordination of neural function is associated with underlying white matter integrity. The investigation included an application of a new time-frequency based method for measuring electroencephalogram (EEG) phase synchronization (Aviyente et al., 2010) as well as fractional anisotropy measures of axonal tracts derived from diffusion tensor imaging (DTI). Nine soldiers who incurred a blast-related mTBI during deployments to Afghanistan or Iraq were compared with eight demographically similar control subjects. Despite an absence of cognitive deficits, the blast-related mTBI group exhibited diminished EEG phase synchrony of lateral frontal sites with contralateral frontal brain regions suggesting diminished interhemispheric coordination of brain activity as a result of blast injury. For blast injured (i.e., blast-related mTBI) soldiers we found that EEG phase synchrony was associated with the structural integrity of white matter tracts of the frontal lobe (left anterior thalamic radiations and the forceps minor including the anterior corpus callosum). Analyses revealed that diminished EEG phase synchrony was not the consequence of combat-stress symptoms (e.g., post-traumatic stress and depression) and commonly prescribed medications. Results provide evidence for poor coordination of frontal neural function after blast injury that may be the consequence of damaged anterior white matter tracts.

Differential fractional anisotropy abnormalities in adolescents with ADHD or schizophrenia

Schizophrenia and Attention-Deficit/Hyperactivity Disorder (ADHD) are associated with similar deficits in working memory, attention, and inhibition. Both disorders also involve abnormalities of white matter integrity, possibly reflecting neural communication disruptions. There are likely some regional white matter abnormalities that underlie the common cognitive impairment, though also some regional abnormalities unique to each disorder. We used diffusion tensor imaging (DTI) to compare white matter integrity, as indicated by fractional anisotropy (FA), in adolescents with schizophrenia (n=15) or ADHD (n=14) and healthy controls (n=26). Schizophrenia patients had uniquely low FA, relative to the other two groups, in bilateral cerebral peduncles, anterior and posterior corpus callosum, right anterior corona radiata, and right superior longitudinal fasciculus. ADHD patients had uniquely high FA in left inferior and right superior frontal regions. Both clinical groups had lower FA than controls in left posterior fornix. The two disorders generally demonstrated distinct patterns of abnormal connectivity suggesting that common cognitive and behavioral deficits derive from distinct sources, though the posterior fornix may be involved in both disorders. Schizophrenia was associated with abnormally low FA in widespread circuitry indicative of general connectivity disruptions, whereas ADHD was associated with abnormally high FA in frontal networks that may indicate impaired branching of fibers.

Disruption of hippocampal connectivity in children and adolescents with schizophrenia--a voxel-based diffusion tensor imaging study.

INTRODUCTION One hypothesis that unifies the diversity of symptoms associated with schizophrenia involves the disruption of connectivity between brain regions. As white matter provides rapid and efficient communication between brain regions, this study was initiated to assess the early disruption of white matter pathways in children and adolescent with schizophrenia. MATERIALS AND METHODS Diffusion tensor images were acquired on 14 children and adolescents with schizophrenia, one subject with schizoaffective disorder, and 15 age and gender matched controls. The DTI images were acquired in twelve directions on a 3 T Siemens Trio scanner. The images were transformed into fractional anisotropy and mean diffusivity maps and a group analysis was performed using SPM2. RESULTS Children and adolescent patients with schizophrenia demonstrated a significant decrease in FA and associated increase in AD in the left posterior hippocampus (p<0.001, Bonferroni corrected on the cluster-level). These diffusion differences were not statistically significant when IQ was used as a covariate in the analysis. DISCUSSION These findings suggest hippocampal white matter abnormalities that present early in the development of schizophrenia. The lack of significant differences when IQ is used as a covariate suggests that this hippocampal region is associated with cognitive changes associated with schizophrenia.

Brain–Behavior Correlation in Children Depends on the Neurocognitive Network

We examined brain–behavior correlations in 12 children (age range 9.3 to 11.7 years) during a selective attention task that required the visual search of a conjunction of features and during a response inhibition task that required the inhibition of a pre‐potent response during “no‐go” blocks. We found that the association between performance in these tasks and brain activation as measured by functional magnetic resonance imaging (fMRI) depended on the neurocognitive network. Specifically, better performance during the no‐go task was associated with greater activation in the response inhibition network including the prefrontal cortex and basal ganglia. In contrast, better performance during the visual search task was associated with less activation in the selective attention network including superior parietal lobule and lateral premotor cortex. These results show that the relation of performance to the magnitude of neural activation is complex and may display differential relationships based on the cognitive domain, anatomical region, and perhaps also developmental stage. Hum Brain Mapping 23:99–108, 2004.

White matter abnormalities associated with military PTSD in the context of blast TBI

Mild traumatic brain injury (mTBI) and post‐traumatic stress disorder (PTSD) are common among recent military veterans and involve substantial symptom overlap, making clinical distinction and effective intervention difficult. Emerging evidence of cerebral white matter abnormalities associated with mTBI may provide a biological measure to inform diagnosis and treatment, but the potentially confounding effects between PTSD and mTBI have largely gone unexamined. We collected diffusion imaging data from 133 recently‐deployed American service members who developed PTSD and/or sustained mTBI, or had neither condition. Effects of PTSD and mTBI on traditional tensor‐based measures of cerebral white matter integrity (fractional anisotropy [FA] and mean diffusivity [MD]) were compared in anatomical regions of interest and individual voxels throughout the brain. Generalized FA (GFA), which allows for multiple fiber orientations per voxel, was also included to improve sensitivity in white matter areas containing crossing or diverging axon bundles. PTSD was consistently associated with high GFA in select brain regions, greater likelihood of regions and voxels with abnormally low MD, and a greater number of voxels with abnormally high FA, while mTBI was associated with fewer high MD regions. Overall, PTSD was associated with more restricted diffusion (low MD) and greater anisotropy (high GFA) in regions of crossing/diverging fibers poorly characterized by a single tensor (FA), suggesting that interstitial fibers may be involved. Contrary to earlier results in a sample without PTSD, mTBI was not associated with anisotropy abnormalities, perhaps indicating the cooccurrence of PTSD and mTBI requires special consideration with regard to structural brain connectivity. Hum Brain Mapp 36:1053–1064, 2015.

Neural anomalies during visual search in schizophrenia patients and unaffected siblings of schizophrenia patients

Schizophrenia patients and their unaffected first-degree relatives exhibit performance deficits on attention tasks, perhaps indicating genetic influence over attentional abnormalities in schizophrenia. To identify anomalous brain function associated with attention in individuals who likely have unexpressed genetic liability for schizophrenia, we studied electrophysiological characteristics of unaffected siblings of schizophrenia patients during a visual serial search task. We gathered behavioral and electrophysiological data from 19 schizophrenia patients, 18 unaffected biological siblings of schizophrenia patients, and 19 nonpsychiatric control participants during performance of the Span of Apprehension (Span) task and a control task. Schizophrenia patients had lower Span task accuracy than the other two groups. Schizophrenia and sibling groups exhibited diminished late positive potentials (P300) over parietal brain regions during Span trials. Compared to control task stimuli, attentional demands of Span stimuli elicited augmented early negative potentials (N1, P2) over posterior brain regions. The degree of augmentation was reduced in schizophrenia patients but not in siblings compared to control subjects. Unaffected siblings of schizophrenia patients appear to modulate early attentional functions of posterior brain regions more effectively than schizophrenia patients but show later electrophysiological anomalies suggestive of abnormal updating of task-relevant information. While the latter may reflect neural mechanisms predisposing performance deficits on attentional tasks, the former may reflect compensatory processes present in unaffected relatives of schizophrenia patients.

Deficits in Visual System Functional Connectivity after Blast‐Related Mild TBI are Associated with Injury Severity and Executive Dysfunction

Approximately, 275,000 American service members deployed to Iraq or Afghanistan have sustained a mild traumatic brain injury (mTBI), with 75% of these incidents involving an explosive blast. Visual processing problems and cognitive dysfunction are common complaints following blast‐related mTBI.

Personality and neuroimaging measures differentiate PTSD from mTBI in veterans

Mild traumatic brain injury (mTBI) is common among recent veterans and often is associated with chronic post-concussive symptoms (PCS). Elevated PCS may also be a consequence of post-traumatic stress disorder (PTSD) which shares symptoms with PCS. Identification of personality, biological, and psychopathology factors that contribute to the relationship between mTBI and PCS could help isolate the sources of chronic post concussive syndrome in veterans. Clinician rated diagnoses (PTSD, Major Depression, Alcohol Dependence), personality characteristics (Multidimensional Personality Questionnaire [MPQ] subscales), white matter brain imaging measures (Mean Diffusivity, Generalized Fractional Anisotropy), and diagnoses of mTBI were collected from 125 American military veterans of Iraq or Afghanistan. Linear and logistic regression models were tested to determine contributions to PCS and whether there were similar contributors to PTSD and mTBI. PCS score was associated with personality characteristics of high Stress Reaction and Traditionalism and low Control as well as mTBI. A diagnosis of PTSD was associated with low Social Closeness, PCS, Alcohol Dependence, and abnormal white matter mean diffusivity. Diagnosis of mTBI was associated with fewer white matter mean diffusivity abnormalities, PCS, and number of deployments. As commonly observed clinically, both PTSD and mTBI were associated with higher rates of PCS, though the contribution of PTSD appears to be secondary to personality traits, particularly Stress Reaction. Furthermore, the observation of factors that are uniquely associated with Blast mTBI (number of deployments) or with PTSD (Lifetime Alcohol Dependence and low Social Closeness), as well as a factor (region of abnormal MD) that had opposite effects on the likelihood of each diagnosis, indicates that the complex relationships between personality, psychopathology, and nature of mTBI need to be considered when interpreting chronic post-concussive symptoms.