Frontiers in neuroscience
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Frontiers in neuroscience · Jan 2014
ReviewGABAB receptor ligands for the treatment of alcohol use disorder: preclinical and clinical evidence.
The present paper summarizes the preclinical and clinical studies conducted to define the "anti-alcohol" pharmacological profile of the prototypic GABAB receptor agonist, baclofen, and its therapeutic potential for treatment of alcohol use disorder (AUD). Numerous studies have reported baclofen-induced suppression of alcohol drinking (including relapse- and binge-like drinking) and alcohol reinforcing, motivational, stimulating, and rewarding properties in rodents and monkeys. ⋯ The recent identification of a positive allosteric modulatory binding site, together with the synthesis of in vivo effective ligands, represents a novel, and likely more favorable, option for pharmacological manipulations of the GABAB receptor. Accordingly, data collected to date suggest that positive allosteric modulators of the GABAB receptor reproduce several "anti-alcohol" effects of baclofen and display a higher therapeutic index (with larger separation-in terms of doses-between "anti-alcohol" effects and sedation).
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Frontiers in neuroscience · Jan 2014
Neural correlates of short-term memory in primate auditory cortex.
Behaviorally-relevant sounds such as conspecific vocalizations are often available for only a brief amount of time; thus, goal-directed behavior frequently depends on auditory short-term memory (STM). Despite its ecological significance, the neural processes underlying auditory STM remain poorly understood. To investigate the role of the auditory cortex in STM, single- and multi-unit activity was recorded from the primary auditory cortex (A1) of two monkeys performing an auditory STM task using simple and complex sounds. ⋯ The data suggest that early match suppression occurs in both A1 and the dTP, whereas later match enhancement occurs first in the PFC, followed by A1 and later in dTP. Because match enhancement occurs first in the PFC, we speculate that enhancement observed in A1 and dTP may reflect top-down feedback. Overall, our findings suggest that A1 forms part of the larger neural system recruited during auditory STM.
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Brainstem and hypothalamic "orexigenic/anorexigenic" networks are thought to maintain body weight homeostasis in response to hormonal and metabolic feedback from peripheral sites. This approach has not been successful in managing over- and underweight patients. It is suggested that concept of homeostasis has been misinterpreted; rather than exerting control, the brain permits eating in proportion to the amount of physical activity necessary to obtain food. ⋯ As the physical price of food approaches zero, eating and body weight increase without constraints. Conversely, in anorexia nervosa body weight is homeostatically regulated, the high level of physical activity in anorexia is displaced hoarding for food that keeps body weight constantly low. A treatment based on this point of view, providing patients with computerized mealtime support to re-establish normal eating behavior, has brought 75% of patients with eating disorders into remission, reduced the rate of relapse to 10%, and eliminated mortality.
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Frontiers in neuroscience · Jan 2014
Single trial prediction of self-paced reaching directions from EEG signals.
Early detection of movement intention could possibly minimize the delays in the activation of neuroprosthetic devices. As yet, single trial analysis using non-invasive approaches for understanding such movement preparation remains a challenging task. We studied the feasibility of predicting movement directions in self-paced upper limb center-out reaching tasks, i.e., spontaneous movements executed without an external cue that can better reflect natural motor behavior in humans. ⋯ Comparison of the decoding accuracy across different frequency ranges (i.e., SCPs, delta, theta, alpha, and gamma) yielded the best accuracy using SCPs filtered between 0.1 to 1 Hz. Across all the subjects, including stroke subjects, the best selected features were obtained mostly from the fronto-parietal regions, hence consistent with previous neurophysiological studies on arm reaching tasks. In summary, we concluded that SCPs allow the possibility of single trial decoding of reaching directions at least 312.5 ms before onset of reach.
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Frontiers in neuroscience · Jan 2014
A neurochemical closed-loop controller for deep brain stimulation: toward individualized smart neuromodulation therapies.
Current strategies for optimizing deep brain stimulation (DBS) therapy involve multiple postoperative visits. During each visit, stimulation parameters are adjusted until desired therapeutic effects are achieved and adverse effects are minimized. However, the efficacy of these therapeutic parameters may decline with time due at least in part to disease progression, interactions between the host environment and the electrode, and lead migration. ⋯ In this manuscript, we summarize the current understanding of electrophysiological and electrochemical processing for control of neuromodulation therapies. Additionally, we describe a proof-of-principle closed-loop controller that characterizes DBS-evoked dopamine changes to adjust stimulation parameters in a rodent model of DBS. The work described herein represents the initial steps toward achieving a "smart" neuroprosthetic system for treatment of neurologic and psychiatric disorders.