Effects of chronic mild traumatic brain injury on white matter integrity in Iraq and Afghanistan war veterans.

Mild traumatic brain injury (TBI) is a common source of morbidity from the wars in Iraq and Afghanistan. With no overt lesions on structural MRI, diagnosis of chronic mild TBI in military veterans relies on obtaining an accurate history and assessment of behavioral symptoms that are also associated with frequent comorbid disorders, particularly posttraumatic stress disorder (PTSD) and depression. Military veterans from Iraq and Afghanistan with mild TBI (n = 30) with comorbid PTSD and depression and non-TBI participants from primary (n = 42) and confirmatory (n = 28) control groups were assessed with high angular resolution diffusion imaging (HARDI). White matter-specific registration followed by whole-brain voxelwise analysis of crossing fibers provided separate partial volume fractions reflecting the integrity of primary fibers and secondary (crossing) fibers. Loss of white matter integrity in primary fibers (P < 0.05; corrected) was associated with chronic mild TBI in a widely distributed pattern of major fiber bundles and smaller peripheral tracts including the corpus callosum (genu, body, and splenium), forceps minor, forceps major, superior and posterior corona radiata, internal capsule, superior longitudinal fasciculus, and others. Distributed loss of white matter integrity correlated with duration of loss of consciousness and most notably with "feeling dazed or confused," but not diagnosis of PTSD or depressive symptoms. This widespread spatial extent of white matter damage has typically been reported in moderate to severe TBI. The diffuse loss of white matter integrity appears consistent with systemic mechanisms of damage shared by blast- and impact-related mild TBI that involves a cascade of inflammatory and neurochemical events.

Tracking the temporal evolution of a perceptual judgment using a compelled-response task.

Choice behavior and its neural correlates have been intensely studied with tasks in which a subject makes a perceptual judgment and indicates the result with a motor action. Yet a question crucial for relating behavior to neural activity remains unresolved: what fraction of a subject's reaction time (RT) is devoted to the perceptual evaluation step, as opposed to executing the motor report? Making such timing measurements accurately is complicated because RTs reflect both sensory and motor processing, and because speed and accuracy may be traded. To overcome these problems, we designed the compelled-saccade task, a two-alternative forced-choice task in which the instruction to initiate a saccade precedes the appearance of the relevant sensory information. With this paradigm, it is possible to track perceptual performance as a function of the amount of time during which sensory information is available to influence a subject's choice. The result-the tachometric curve-directly reveals a subject's perceptual processing capacity independently of motor demands. Psychophysical data, together with modeling and computer-simulation results, reveal that task performance depends on three separable components: the timing of the motor responses, the speed of the perceptual evaluation, and additional cognitive factors. Each can vary quickly, from one trial to the next, or can show stable, longer-term changes. This novel dissociation between sensory and motor processes yields a precise metric of how perceptual capacity varies under various experimental conditions and serves to interpret choice-related neuronal activity as perceptual, motor, or both.

Incidental paranasal sinusitis on routine brain magnetic resonance scans: association with atherosclerosis.

BACKGROUND: Incidental paranasal sinusitis (IPS) is common on imaging for non-sinusitis disorders, usually without symptoms or obstructive features, and possibly arising from periodontitis (PD). PD associations with atherosclerosis have been widely reported. We test if IPS may also be associated with atherosclerosis. METHODS: IPS was scored retrospectively in a random sample of 180 magnetic resonance (MR) brain scans and compared with chart review for atherosclerosis (all subtypes), rhinosinusitis, and related factors (smoking, asthma, and relevant surgery). IPS was scored out of 30, from all sinuses, with maxillary sinuses weighted double volumetrically. Significant IPS (Sig IPS) was designated as 6 or more out of 30. Bivariate logistic regression was used to test for associations of Sig IPS to the clinical data, with multivariate analysis then testing for potential confounders. RESULTS: A total of 173 subjects were analyzed (7 exclusions). MR indications included suspected acute/prior stroke (22.0%). Sig IPS found in 20 (11.6%). Positive histories for atherosclerosis were cerebral, 57 (32.9%); coronary, 48 (27.7%); and peripheral arterial disease, 14 (8.1%). IPS ≥6 was strongly associated with cerebrovascular disease (odds ratio [OR] 6.0, p < 0.001), and less robustly to smoking (OR 2.9, p = 0.07) and rhinosinusitis (OR 2.4, p = 0.09). No associations with coronary or peripheral artery diseases were found. After controlling for smoking and rhinosinusitis, yielding significant subclinical sinusitis, the link of Sig IPS to cerebrovascular disease persisted (modified OR 5.2, p = 0.002). CONCLUSION: Significant incidental sinusitis, which is mostly subclinical sinusitis, is associated with cerebrovascular disease but not other atheroscleroses. This suggests possible common causation of both by PD.

Developmental changes underlying the formation of the specialized time coding circuits in barn owls (Tyto alba).

Barn owls are capable of great accuracy in detecting the interaural time differences (ITDs) that underlie azimuthal sound localization. They compute ITDs in a circuit in nucleus laminaris (NL) that is reorganized with respect to birds like the chicken. The events that lead to the reorganization of the barn owl NL take place during embryonic development, shortly after the cochlear and laminaris nuclei have differentiated morphologically. At first the developing owl's auditory brainstem exhibits morphology reminiscent of that of the developing chicken. Later, the two systems diverge, and the owl's brainstem auditory nuclei undergo a secondary morphogenetic phase during which NL dendrites retract, the laminar organization is lost, and synapses are redistributed. These events lead to the restructuring of the ITD coding circuit and the consequent reorganization of the hindbrain map of ITDs and azimuthal space.

Perceptual decision making in less than 30 milliseconds.

In perceptual discrimination tasks, a subject's response time is determined by both sensory and motor processes. Measuring the time consumed by the perceptual evaluation step alone is therefore complicated by factors such as motor preparation, task difficulty and speed-accuracy tradeoffs. Here we present a task design that minimizes these confounding factors and allows us to track a subject's perceptual performance with unprecedented temporal resolution. We find that monkeys can make accurate color discriminations in less than 30 ms. Furthermore, our simple task design provides a tool for elucidating how neuronal activity relates to sensory as opposed to motor processing, as demonstrated with neural data from cortical oculomotor neurons. In these cells, perceptual information acts by accelerating and decelerating the ongoing motor plans associated with correct and incorrect choices, as predicted by a race-to-threshold model, and the time course of these neural events parallels the time course of the subject's choice accuracy.

Contextual modulation of central thalamic delay-period activity: representation of visual and saccadic goals.

This study examines the influence of behavioral context on the activity of visuomotor neurons in primate central thalamus. Neurons that combine information about sensory stimuli and their behavioral relevance are thought to contribute to the decision mechanisms that link specific stimuli to specific responses. We reported in a previous study that neurons in central thalamus carry spatial information throughout the instructed delay period of a visually guided delayed saccade task. The goal of the current study was to determine whether the delay-period activity of thalamic neurons is modulated by behavioral context. Single neurons were evaluated during performance of visually guided and memory-guided variants of a saccadic choice task in which a cue designated the response field stimulus as the target of a rewarded saccade or as an irrelevant distracter. The relative influence of the physical stimulus and context on delay-period activity suggested a minimum of 3 neural groups. Some neurons signaled the locations of visible stimuli regardless of behavioral relevance. Other neurons preferentially signaled the locations of current saccadic goals and did so even in the absence of the physical stimulus. A third group signaled only the locations of currently visible saccadic goals. For the latter 2 groups, activity was the product of both stimulus and context, suggesting that central thalamic neurons play a role in the context-dependent linkage of sensory signals and saccadic commands. More generally, these data suggest that the anatomical substrate of sensorimotor decision making may include the cortico-subcortical loops for which central thalamus serves as the penultimate synapse.

Bigger brains or bigger nuclei? Regulating the size of auditory structures in birds.

Increases in the size of the neuronal structures that mediate specific behaviors are believed to be related to enhanced computational performance. It is not clear, however, what developmental and evolutionary mechanisms mediate these changes, nor whether an increase in the size of a given neuronal population is a general mechanism to achieve enhanced computational ability. We addressed the issue of size by analyzing the variation in the relative number of cells of auditory structures in auditory specialists and generalists. We show that bird species with different auditory specializations exhibit variation in the relative size of their hindbrain auditory nuclei. In the barn owl, an auditory specialist, the hindbrain auditory nuclei involved in the computation of sound location show hyperplasia. This hyperplasia was also found in songbirds, but not in non-auditory specialists. The hyperplasia of auditory nuclei was also not seen in birds with large body weight suggesting that the total number of cells is selected for in auditory specialists. In barn owls, differences observed in the relative size of the auditory nuclei might be attributed to modifications in neurogenesis and cell death. Thus, hyperplasia of circuits used for auditory computation accompanies auditory specialization in different orders of birds.

Quantitative assessment of the timing and tuning of visual-related, saccade-related, and delay period activity in primate central thalamus.

This study investigates the visuomotor properties of several nuclei within primate central thalamus. These nuclei, which might be considered components of an oculomotor thalamus (OcTh), are found within and at the borders of the internal medullary lamina. These nuclei have extensive anatomical links to numerous cortical and subcortical visuomotor areas including the frontal eye fields, supplementary eye fields, prefrontal cortex, posterior parietal cortex, caudate, and substantia nigra pars reticulata. Previous single-unit recordings have shown that neurons in OcTh respond during self-paced spontaneous saccades and to visual stimuli in the absence of any specific behavioral requirement, but a thorough account of the activity of these areas in association with voluntary, goal-directed movement is lacking. We recorded activity from single neurons in primate central thalamus during performance of a visually guided delayed saccade task. The sample consisted primarily of neurons from the centrolateral and paracentral intralaminar nuclei and paralaminar regions of the ventral anterior and ventral lateral nuclei. Neurons responsive to sensory, delay, and motor phases of the task were observed in each region, with many neurons modulated during multiple task periods. Across the population, variation in the quality and timing of saccade-contingent activity suggested participation in functions ranging from generating a saccade (presaccadic) to registering its consequences (e.g., efference copy). Finally, many neurons were found to carry spatial information during the delay period, suggesting a role for central thalamus in higher-order aspects of visuomotor control.