Neuroscience
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Randomized Controlled Trial
Dissociable Effects of Subthalamic Stimulation in Obsessive Compulsive Disorder on Risky Reward and Loss Prospects.
Our daily decisions involve an element of risk, a behavioral process that is potentially modifiable. Here we assess the role of the associative-limbic subthalamic nucleus (STN) in obsessive compulsive disorder (OCD) testing on and off deep-brain stimulation (DBS) on anticipatory risk taking to obtain rewards and avoid losses. We assessed 12 OCD STN DBS in a randomized double-blind within-subject cross-over design. ⋯ We highlight a role for the STN in mediating dissociable valence prospects on risk seeking. STN stimulation decreases risk taking to rewards and impairs discrimination of loss magnitude. These findings may have implications for behavioral symptoms related to STN DBS and the potential for STN DBS for the treatment of psychiatric disorders.
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Recent studies have revealed that the ventral premotor cortex (PMv) of nonhuman primates plays a pivotal role in various behaviors that require the transformation of sensory cues to appropriate actions. Examples include decision-making based on various sensory cues, preparation for upcoming motor behavior, adaptive sensorimotor transformation, and the generation of motor commands using rapid sensory feedback. Although the PMv has frequently been regarded as a single entity, it can be divided into at least five functionally distinct regions: F4, a dorsal convexity region immediately rostral to the primary motor cortex (M1); F5p, a cortical region immediately rostral to F4, lying within the arcuate sulcus; F5c, a ventral convexity region rostral to F4; and F5a, located in the caudal bank of the arcuate sulcus inferior limb lateral to F5p. ⋯ F5p contains "mirror neurons" to understand others' actions based on visual and other types of information, and F4d and F5p work together as a functional complex involved in controlling forelimb and eye movements, most efficiently in the execution and completion of coordinated eye-hand movements for reaching and grasping under visual guidance. In contrast, F5c and F5a are hierarchically higher than the F4d, F5p, and F5v complexes, and play a role in decision-making based on various sensory discriminations. Hence, the PMv subregions form a hierarchically organized integral system from decision-making to eye-hand coordination under various behavioral circumstances.
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A major regulatory task of the organism is to keep brain functions relatively constant in spite of metabolic changes (e.g., hunger vs. satiety) or availability of energy (e.g., glucose administration). Resting-state functional magnetic resonance imaging (rs-fMRI) can reveal resulting changes in brain function but previous studies have focused mostly on the hypothalamus. Therefore, we took a whole-brain approach and examined 24 healthy normal-weight men once after 36 h of fasting and once in a satiated state (six meals over the course of 36 h). ⋯ This interaction was driven by a fALFF increase after glucose treatment in the hunger relative to the satiety condition. Our results indicate that fALFF analysis is the most sensitive measure to detect effects of metabolic states on resting-state brain activity. Moreover, we show that multimethod rs-fMRI provides an unbiased approach to identify spontaneous brain activity associated with changes in homeostasis and caloric intake.
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Clinical patients in a vegetative state or unresponsive wakefulness syndrome (VS/UWS) demonstrate distinct arousal-awareness dissociation; the neuropathological mechanisms underlying such dissociation remain poorly understood. Here, we systematically examined how functional connectivity from the brainstem areas regulating arousal to the cortical networks supporting internal and external awareness is disrupted in minimally conscious state (MCS) and VS/UWS patients. Resting-state functional imaging was conducted in 23 MCS patients, 31 VS/UWS patients, and 20 age-matched healthy individuals. ⋯ We show that functional connectivity from the PTA and caudal midbrain area to the cortical-awareness-supporting networks were significantly reduced in MCS and VS/UWS patients; importantly, as the clinical symptoms of consciousness disorders deepen from MCS to VS/UWS, functional connectivity strength became significantly reduced, changing from presenting no significant connections in MCS to widespread negative connections in VS/UWS. Additionally, we observed increased connectivity from the PTA and caudal midbrain area to limbic structures, the brainstem areas, and the cerebellum in MCS and VS/UWS patients, consistent with prior studies. These findings offer important insights into the neural network mechanisms underlying the long-observed arousal-awareness dissociation in VS/UWS patients and provide additional neuroimaging-based biomarkers for the clinical diagnosis of MCS and VS/UWS patients.
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Exposure to both sustained and intermittent hypoxia for as little as a day produces sustained augmentation of carotid chemoreceptor sensitivity; however, the molecular basis for this chemoreflex plasticity remains uncertain. We previously reported that NMDA receptor-dependent glutamatergic signaling in rat carotid body played a role in altered hypoxic sensitivity after exposure to cyclic intermittent hypoxia (CIH). Here we found that mRNAs of multiple AMPA and Kainate glutamate receptors were expressed in rat carotid body. ⋯ In addition, our results showed that multiple of vesicular glutamate transporters (VGLUTs) and excitatory amino acid transporters (EAATs) were expressed in the rat carotid body, indicating that glutamate might be as a neurotransmitter stored, released and uptake in the carotid body. Finally, we found that mRNAs of GluA1, GluA2 and GluA3 as well as PSD-95-like membrane-associated granulate kinase family members, PSD-95, PSD-93, and SAP97, were expressed in human carotid body. Our data suggest AMPA receptor-dependent glutamatergic signaling is present in the carotid body and might be involved in the carotid chemoreceptor response to hypoxia.