Neural Substrates of Reliability-Weighted Visual-Tactile Multisensory Integration

As sensory systems deteriorate in aging or disease, the brain must relearn the appropriate weights to assign each modality during multisensory integration. Using blood-oxygen level dependent functional magnetic resonance imaging of human subjects, we tested a model for the neural mechanisms of sensory weighting, termed “weighted connections.” This model holds that the connection weights between early and late areas vary depending on the reliability of the modality, independent of the level of early sensory cortex activity. When subjects detected viewed and felt touches to the hand, a network of brain areas was active, including visual areas in lateral occipital cortex, somatosensory areas in inferior parietal lobe, and multisensory areas in the intraparietal sulcus (IPS). In agreement with the weighted connection model, the connection weight measured with structural equation modeling between somatosensory cortex and IPS increased for somatosensory-reliable stimuli, and the connection weight between visual cortex and IPS increased for visual-reliable stimuli. This double dissociation of connection strengths was similar to the pattern of behavioral responses during incongruent multisensory stimulation, suggesting that weighted connections may be a neural mechanism for behavioral reliability weighting

Impact of Hypothyroidism and Heart Failure on Hospitalization Risk.

BackgroundPrior studies suggest that the relationship between hypothyroidism and mortality is dependent on underlying cardiovascular risk. Little is known about the association of hypothyroidism with hospitalization risk, and how these associations are modified by cardiovascular status.MethodsThis study examined the association of thyroid status, defined by serum thyrotropin (TSH), with hospitalization risk among patients who received care at a large university-based tertiary care center between 1990 and 2015. Thyroid status was categorized as hypothyroidism versus euthyroidism (TSH >4.7 vs. 0.3-4.7 mIU/L, respectively). The relationship between thyroid status and hospitalization risk stratified by cardiovascular status was examined using multivariable Cox models.ResultsAmong 52,856 patients who met eligibility criteria, 49,791 (94.2%) had euthyroidism and 3065 (5.8%) had hypothyroidism. In analyses stratified by congestive heart failure (CHF) status, compared to euthyroidism, hypothyroidism was associated with higher risk of hospitalization in those with CHF but slightly lower risk in those without CHF (adjusted hazard ratio [aHRs] = 1.86 [confidence interval (CI) 1.17-2.94] and HR = 0.95 [CI 0.92-0.99], respectively; p = 0.006). In sensitivity analyses accounting for death as a competing event, underlying coronary artery disease modified the hypothyroidism-hospitalization relationship, such that stronger associations were observed among those with versus without coronary artery disease. In competing risk analyses, hypothyroidism was associated with higher versus lower risk of hospitalization among those with versus without cerebrovascular disease, respectively.ConclusionsHypothyroidism is associated with higher hospitalization risk among patients with underlying cardiovascular disease. Future studies are needed to determine whether correction of thyroid status with replacement therapy ameliorates hospitalization risk in this population

Neural Substrates of Sound–Touch Synesthesia after a Thalamic Lesion

Neural plasticity induced by stroke can mediate positive outcomes, such as recovery of function, but can also result in the formation of abnormal connections with negative consequences for perception and cognition. In three experiments using blood-oxygen level dependent (BOLD) functional magnetic resonance imaging, we examined the neural substrates of acquired auditory-tactile synesthesia, in which certain sounds can produce an intense somatosensory tingling sensation in a patient with a thalamic lesion. Compared with nine normal controls, the first experiment showed that the patient had a threefold greater BOLD response to sounds in the parietal operculum, the location of secondary somatosensory cortex. We hypothesized that this abnormal opercular activity might be the neural substrate of the patient\u27s synesthesia. Supporting this hypothesis, the second experiment demonstrated that sounds that produced no somatosensation did not evoke a BOLD response in the operculum, while sounds that produced strong somatosensations evoked large BOLD responses. These abnormal responses may have resulted from plasticity induced by the loss of somatosensory inputs. Consistent with this idea, in the third experiment, BOLD responses to somatosensory stimulation were significantly weaker in the patient\u27s operculum than in normal controls. These experiments demonstrate a double dissociation in the patient\u27s secondary somatosensory cortex (increased responses to auditory stimulation and decreased responses to somatosensory stimulation), and suggest both that stroke-induced plasticity can result in abnormal connections between sensory modalities that are normally separate, and that synesthesia can be caused by inappropriate connections between nearby cortical territories

Sestrins are evolutionarily conserved mediators of exercise benefits.

Exercise is among the most effective interventions for age-associated mobility decline and metabolic dysregulation. Although long-term endurance exercise promotes insulin sensitivity and expands respiratory capacity, genetic components and pathways mediating the metabolic benefits of exercise have remained elusive. Here, we show that Sestrins, a family of evolutionarily conserved exercise-inducible proteins, are critical mediators of exercise benefits. In both fly and mouse models, genetic ablation of Sestrins prevents organisms from acquiring metabolic benefits of exercise and improving their endurance through training. Conversely, Sestrin upregulation mimics both molecular and physiological effects of exercise, suggesting that it could be a major effector of exercise metabolism. Among the various targets modulated by Sestrin in response to exercise, AKT and PGC1α are critical for the Sestrin effects in extending endurance. These results indicate that Sestrin is a key integrating factor that drives the benefits of chronic exercise to metabolism and physical endurance

An integrated model of care for neurological infections: the first six years of referrals to a specialist service at a university teaching hospital in Northwest England

Background A specialist neurological infectious disease service has been run jointly by the departments of infectious disease and neurology at the Royal Liverpool University Hospital since 2005. We sought to describe the referral case mix and outcomes of the first six years of referrals to the service. Methods Retrospective service review. Results Of 242 adults referred to the service, 231 (95 %) were inpatients. Neurological infections were confirmed in 155 (64 %), indicating a high degree of selection before referral. Viral meningitis (35 cases), bacterial meningitis (33) and encephalitis (22) accounted for 38 % of referrals and 61 % of confirmed neurological infections. Although an infrequent diagnosis (n = 19), neurological TB caused the longest admission (median 23, range 5 – 119 days). A proven or probable microbiological diagnosis was found in 100/155 cases (64.5 %). For the whole cohort, altered sensorium, older age and longer hospital stay were associated with poor outcome (death or neurological disability); viral meningitis was associated with good outcome. In multivariate analysis altered sensorium remained significantly associated with poor outcome, adjusted odds ratio 3.04 (95 % confidence interval 1.28 – 7.22, p = 0.01). Conclusions A service of this type provides important specialist care and a focus for training and clinical research on complex neurological infections

Human MST But Not MT Responds to Tactile Stimulation

Previous reports of tactile responses in human visual area MT/V5 have used complex stimuli, such as a brush stroking the arm. These complex moving stimuli are likely to induce imagery of visual motion, which is known to be a powerful activator of MT. The area described as “MT” in previous reports consists of at least two distinct cortical areas, MT and MST. Using functional magnetic resonance imaging, we separately localized human MT and MST and measured their response to vibrotactile stimuli unlikely to induce imagery of visual motion. Strong vibrotactile responses were observed in MST but not in MT. Vibrotactile responses in MST were approximately one-half as large as the response to visual motion and were distinct from those in another visual area previously reported to respond to tactile stimulation, the lateral occipital complex. To examine somatotopic organization, we separately stimulated the left and right hand and foot. No spatial segregation between hand and foot responses was observed in MST. The average response profile of MST was similar to that of somatosensory cortex, with a strong preference for the contralateral hand. These results offer evidence for the existence of somatosensory responses in MST, but not MT, independent of imagery of visual motion