The Effects of External Jugular Compression Applied during Head Impact Exposure on Longitudinal Changes in Brain Neuroanatomical and Neurophysiological Biomarkers: A Preliminary Investigation

Objectives: Utilize a prospective in vivo clinical trial to evaluate the potential for mild neck compression applied during head impact exposure to reduce anatomical and physiological biomarkers of brain injury. Methods: This project utilized a prospective randomized controlled trial to evaluate effects of mild jugular vein (neck) compression (collar) relative to controls (no collar) during a competitive hockey season (males; 16.3 ± 1.2 years). The collar was designed to mildly compress the jugular vein bilaterally with the goal to increase intracranial blood volume to reduce risk of brain slosh injury during head impact exposure. Helmet sensors were used to collect daily impact data in excess of 20 g (games and practices) and the primary outcome measures, which included changes in white matter (WM) microstructure, were assessed by diffusion tensor imaging (DTI). Specifically, four DTI measures: fractional anisotropy, mean diffusivity (MD), axial diffusivity, and radial diffusivity (RD) were used in the study. These metrics were analyzed using the tract-based Spatial Statistics (TBSS) approach – a voxel-based analysis. In addition, electroencephalography-derived event-related potentials were used to assess changes in brain network activation (BNA) between study groups. Results: For athletes not wearing the collar, DTI measures corresponding to a disruption of WM microstructure, including MD and RD, increased significantly from pre-season to mid-season (p 0.05). In addition to these anatomical findings, electrophysiological network analysis of the degree of congruence in the network electrophysiological activation pattern demonstrated concomitant changes in brain network dynamics in the non-collar group only (p < 0.05). Similar to the DTI findings, the increased change in BNA score in the non-collar relative to the collar group was statistically significant (p < 0.01). Changes in DTI outcomes were also directly correlated with altered brain network dynamics (r = 0.76; p < 0.05) as measured by BNA. Conclusion: Group differences in the longitudinal changes in both neuroanatomical and electrophysiological measures, as well as the correlation between the measures, provide initial evidence indicating that mild jugular vein compression may have reduced alterations in the WM response to head impacts during a competitive hockey season. The data indicate sport-related alterations in WM microstructure were ameliorated by application of jugular compression during head impact exposure. These results may lead to a novel line of research inquiry to evaluate the effects of protecting the brain from sports-related head impacts via optimized intracranial fluid dynamics

Auditory and Multisensory Responses in the Tectofugal Pathway of the Barn Owl

A common visual pathway in all amniotes is the tectofugal pathway connecting the optic tectum with the forebrain. The tectofugal pathway has been suggested to be involved in tasks such as orienting and attention, tasks that may benefit from integrating information across senses. Nevertheless, previous research has characterized the tectofugal pathway as strictly visual. Here we recorded from two stations along the tectofugal pathway of the barn owl: the thalamic nucleus rotundus (nRt) and the forebrain entopallium (E). We report that neurons in E and nRt respond to auditory stimuli as well as to visual stimuli. Visual tuning to the horizontal position of the stimulus and auditory tuning to the corresponding spatial cue (interaural time difference) were generally broad, covering a large portion of the contralateral space. Responses to spatiotemporally coinciding multisensory stimuli were mostly enhanced above the responses to the single modality stimuli, whereas spatially misaligned stimuli were not. Results from inactivation experiments suggest that the auditory responses in E are of tectal origin. These findings support the notion that the tectofugal pathway is involved in multisensory processing. In addition, the findings suggest that the ascending auditory information to the forebrain is not as bottlenecked through the auditory thalamus as previously thought.</jats:p

Interactions between Stimulus-Specific Adaptation and Visual Auditory Integration in the Forebrain of the Barn Owl

Neural adaptation and visual auditory integration are two well studied and common phenomena in the brain, yet little is known about the interaction between them. In the present study, we investigated a visual forebrain area in barn owls, the entopallium (E), which has been shown recently to encompass auditory responses as well. Responses of neurons to sequences of visual, auditory, and bimodal (visual and auditory together) events were analyzed. Sequences comprised two stimuli, one with a low probability of occurrence and the other with a high probability. Neurons in the E tended to respond more strongly to low probability visual stimuli than to high probability stimuli. Such a phenomenon is known as stimulus-specific adaptation (SSA) and is considered to be a neural correlate of change detection. Responses to the corresponding auditory sequences did not reveal an equivalent tendency. Interestingly, however, SSA to bimodal events was stronger than to visual events alone. This enhancement was apparent when the visual and auditory stimuli were presented from matching locations in space (congruent) but not when the bimodal stimuli were spatially incongruent. These findings suggest that the ongoing task of detecting unexpected events can benefit from the integration of visual and auditory information.</jats:p

Brain Network Activation Analysis Utilizing Spatiotemporal Features for Event Related Potentials Classification

The purpose of this study was to introduce an improved tool for automated classification of event-related potentials (ERPs) using spatiotemporally parcellated events incorporated into a functional brain network activation (BNA) analysis. The auditory oddball ERP paradigm was selected to demonstrate and evaluate the improved tool. Methods: The ERPs of each subject were decomposed into major dynamic spatiotemporal events. Then, a set of spatiotemporal events representing the group was generated by aligning and clustering the spatiotemporal events of all individual subjects. The temporal relationship between the common group events generated a network, which is the spatiotemporal reference BNA model. Scores were derived by comparing each subject’s spatiotemporal events to the reference BNA model and were then entered into a support vector machine classifier to classify subjects into relevant subgroups. The reliability of the BNA scores (test-retest repeatability using intraclass correlation) and their utility as a classification tool were examined in the context of Target-Novel classification. Results: BNA intraclass correlation values of repeatability ranged between 0.51 and 0.82 for the known ERP components N100, P200 and P300. Classification accuracy was high when the trained data were validated on the same subjects for different visits (AUCs 0.93 and 0.95). The classification accuracy remained high for a test group recorded at a different clinical center with a different recording system (AUCs 0.81, 0.85 for 2 visits). Conclusion: The improved spatiotemporal BNA analysis demonstrates high classification accuracy. The BNA analysis method holds promise as a tool for diagnosis, follow-up and drug development associated with different neurological conditions

“High Risk” Features of Differentiated Thyroid Cancer Are Commonly Found in Autopsy Studies: Implications for the ATA Guidelines

Abstract Background: While the popularity of lobectomy for differentiated thyroid cancer (DTC) has increased since the 2015 American Thyroid Association guidelines, several recent studies reported that “high risk” histological features may be found in up to half of lobectomy specimens, questioning the validity of this approach. In turn, the actual risk associated with some “high risk” features (multifocality, minimal extra-thyroidal extension (ETE), and small lymph node (LN) metastases) has been questioned in recent years. Aim: To assess the prevalence of “high risk” pathological features in occult DTC detected in autopsy studies. Methods: Meta-analysis of autopsy studies of the thyroid gland in subjects without history of thyroid cancer. Studies with DTC lesions and details on histological features were included. Results: Twenty nine studies including 8,750 subjects fulfilled the inclusion criteria, with incidentally discovered DTC in 740 autopsies (prevalence of 8.5%). Age was reported in 17 studies, with a median age of 61 years (range 41-68 years). Multifocality was reported in 27 studies with a calculated event rate of 28.2% (95%CI 23.1% to 33.8%, random effect), with bilateral involvement in 18% (95%CI 12.6%-25/1%). Minimal ETE was reported in five studies, with an event rate of 24.5% (95%CI 9.3% to 50.7%, random effect), and the presence of LN metastases was reported in 13 studies with an event rate of 11% (95%CI 6.1% to 19.1%, random effect). Vascular invasion was reported in seven studies with an event rate of 16% (95%CI 4% to 47%, random effect). Conclusions: “High risk” histological features are common in occult DTC found in autopsy studies, and do not seem to be markers of aggressive disease. These data support a less aggressive therapeutic approach in patients with microscopic “high risk” features which were not detected on pre-operative ultrasound.</jats:p