Abrupt orientation to novel stimuli is a critical, memory-dependent task performed by the brain. In the present study, we examined two gaze control centers of the barn owl: the optic tectum (OT) and the arcopallium gaze fields (AGFs). Responses of neurons to long sequences of dichotic sound bursts comprised of two sounds differing in the probability of appearance were analyzed. We report that auditory neurons in the OT and in the AGFs tend to respond stronger to rarely presented sounds (novel sounds) than to the same sounds when presented frequently. This history-dependent phenomenon, known as stimulus-specific adaptation (SSA), was demonstrated for rare sound frequencies, binaural localization cues [interaural time difference (ITD) and level difference (ILD)] and sound amplitudes. The manifestation of SSA in such a variety of independent acoustic features, in the midbrain and in the forebrain, supports the notion that SSA is involved in sensory memory and novelty detection. To track the origin of SSA, we analyzed responses of neurons in the external nucleus of the inferior colliculus (ICX; the source of auditory input to the OT) to similar sequences of sound bursts. Neurons in the ICX responded stronger to rare sound frequencies, but did not respond differently to rare ITDs, ILDs, or sound amplitudes. We hypothesize that part of the SSA reported here is computed in high-level networks, giving rise to novelty signals that modulate tectal responses in a context-dependent manner.

Despite promising preliminary results in treating fibromyalgia (FM) pain, no neuromodulation technique has been adopted in clinical practice because of limited efficacy, low response rate, or poor tolerability. This phase II open-label trial aims to define a methodology for a clinically effective treatment of pain in FM by establishing treatment protocols and screening procedures to maximize efficacy and response rate. High-definition transcranial direct current stimulation (HD-tDCS) provides targeted subthreshold brain stimulation, combining tolerability with specificity. We aimed to establish the number of HD-tDCS sessions required to achieve a 50% FM pain reduction, and to characterize the biometrics of the response, including brain network activation pain scores of contact heat-evoked potentials. We report a clinically significant benefit of a 50% pain reduction in half (n = 7) of the patients (N = 14), with responders and nonresponders alike benefiting from a cumulative effect of treatment, reflected in significant pain reduction (P = .035) as well as improved quality of life (P = .001) over time. We also report an aggregate 6-week response rate of 50% of patients and estimate 15 as the median number of HD-tDCS sessions to reach clinically meaningful outcomes. The methodology for a pivotal FM neuromodulation clinical trial with individualized treatment is thus supported.

Zahar Y, Reches A, Gutfreund Y. Multisensory enhancement in the optic tectum of the barn owl: spike count and spike timing. J Neurophysiol 101: 2380 -2394, 2009. First published March 4, 2009 doi:10.1152/jn.91193.2008. Temporal and spatial correlations between auditory and visual stimuli facilitate the perception of unitary events and improve behavioral responses. However, it is not clear how combined visual and auditory information is processed in single neurons. Here we studied responses of multisensory neurons in the barn owl's optic tectum (the avian homologue of the superior colliculus) to visual, auditory, and bimodal stimuli. We specifically focused on responses to sequences of repeated stimuli. We first report that bimodal stimulation tends to elicit more spikes than in the responses to its unimodal components (a phenomenon known as multisensory enhancement). However, this tendency was found to be historydependent; multisensory enhancement was mostly apparent in the first stimulus of the sequence and to a much lesser extent in the subsequent stimuli. Next, a vector-strength analysis was applied to quantify the phase locking of the responses to the stimuli. We report that in a substantial number of multisensory neurons responses to sequences of bimodal stimuli elicited spike trains that were better phase locked to the stimulus than spike trains elicited by stimulating with the unimodal counterparts (visual or auditory). We conclude that multisensory enhancement can be manifested in better phase locking to the stimulus as well as in more spikes.

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.

ObjectivesUtilize 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.MethodsThis 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.ResultsFor 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). Athletes wearing the collar did not show a significant change in either MD or RD despite similar accumulated linear accelerations from head impacts (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.ConclusionGroup 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.