Gabapentin Prescribing Practices Among Physicians: Clinical Indications and Reasoning

Gabapentin is an anticonvulsant and nerve pain medication with a variety of offlabel indications. There is at least some evidence that physicians have prescribed gabapentin to successfully treat several off-label conditions including alcohol dependence and withdrawal, brachioradial pruritus, chronic, refractory cough, diabetic neuropathy, fibromyalgia, hiccups (singultus), hot flashes, insomnia, neuropathic pain, adjunct therapy for postoperative pain, restless legs syndrome (RLS), anxiety disorders, and uremic pruritus. An observational cross-sectional study was used to determine the various reallife off-label uses of gabapentin and physicians’ perspectives with regard to particular advantages over other drugs and interventions, via an online survey. In addition, a secondary objective was to determine physicians’ perspectives regarding whether gabapentin is being misused. The most common off-label indications for prescribing gabapentin for Family Medicine and most other physicians surveyed were neuropathic pain, diabetic neuropathy, and fibromyalgia. Psychiatrists most commonly prescribed gabapentin for anxiety disorders and insomnia. With respect to misuse and overdose, six Emergency Medicine physicians felt that gabapentin was not leading to increased overdoses and/or intoxications while three felt that it was

The Functional Anatomy of Time: What and When in the Brain

This Opinion article considers the implications for functional anatomy of how we represent temporal structure in our exchanges with the world. It offers a theoretical treatment that tries to make sense of the architectural principles seen in mammalian brains. Specifically, it considers a factorisation between representations of temporal succession and representations of content or, heuristically, a segregation into when and what. This segregation may explain the central role of the hippocampus in neuronal hierarchies while providing a tentative explanation for recent observations of how ordinal sequences are encoded. The implications for neuroanatomy and physiology may have something important to say about how self-organised cell assembly sequences enable the brain to exhibit purposeful behaviour that transcends the here and now

Neural Dynamics in Parkinsonian Brain:The Boundary Between Synchronized and Nonsynchronized Dynamics

Synchronous oscillatory dynamics is frequently observed in the human brain. We analyze the fine temporal structure of phase-locking in a realistic network model and match it with the experimental data from parkinsonian patients. We show that the experimentally observed intermittent synchrony can be generated just by moderately increased coupling strength in the basal ganglia circuits due to the lack of dopamine. Comparison of the experimental and modeling data suggest that brain activity in Parkinson's disease resides in the large boundary region between synchronized and nonsynchronized dynamics. Being on the edge of synchrony may allow for easy formation of transient neuronal assemblies

Sleep Analytics and Online Selective Anomaly Detection

We introduce a new problem, the Online Selective Anomaly Detection (OSAD), to model a specific scenario emerging from research in sleep science. Scientists have segmented sleep into several stages and stage two is characterized by two patterns (or anomalies) in the EEG time series recorded on sleep subjects. These two patterns are sleep spindle (SS) and K-complex. The OSAD problem was introduced to design a residual system, where all anomalies (known and unknown) are detected but the system only triggers an alarm when non-SS anomalies appear. The solution of the OSAD problem required us to combine techniques from both machine learning and control theory. Experiments on data from real subjects attest to the effectiveness of our approach.Comment: Submitted to 20th ACM SIGKDD Conference on Knowledge Discovery and Data Mining 201

Place-selective firing contributes to the reverse-order reactivation of CA1 pyramidal cells during sharp waves in open-field exploration

On the linear track, the recent firing sequences of CA1 place cells recur during sharp wave/ripple patterns (SWRs) in a reverse temporal order [Foster & Wilson (2006) Nature, 440, 680–683]. We have found similar reverse-order reactivation during SWRs in open-field exploration where the firing sequence of cells varied before each SWR. Both the onset times and the firing patterns of cells showed a tendency for reversed sequences during SWRs. These effects were observed for SWRs that occurred during exploration, but not for those during longer immobility periods. Additionally, reverse reactivation was stronger when it was preceded by higher speed (> 5 cm/s) run periods. The trend for reverse-order SWR reactivation was not significantly different in familiar and novel environments, even though SWR-associated firing rates of both pyramidal cells and interneurons were reduced in novel environments as compared with familiar. During exploration-associated SWRs (eSWR) place cells retain place-selective firing [O'Neill et al. (2006) Neuron, 49, 143–155]. Here, we have shown that each cell's firing onset was more delayed and firing probability more reduced during eSWRs the further the rat was from the middle of the cell's place field; that is, cells receiving less momentary place-related excitatory drive fired later during SWR events. However, even controlling for place field distance, the recent firing of cells was still significantly correlated with SWR reactivation sequences. We therefore propose that both place-related drive and the firing history of cells contribute to reverse reactivation during eSWRs

A computational study on altered theta-gamma coupling during learning and phase coding

There is considerable interest in the role of coupling between theta and gamma oscillations in the brain in the context of learning and memory. Here we have used a neural network model which is capable of producing coupling of theta phase to gamma amplitude firstly to explore its ability to reproduce reported learning changes and secondly to memory-span and phase coding effects. The spiking neural network incorporates two kinetically different GABAA receptor-mediated currents to generate both theta and gamma rhythms and we have found that by selective alteration of both NMDA receptors and GABAA,slow receptors it can reproduce learning-related changes in the strength of coupling between theta and gamma either with or without coincident changes in theta amplitude. When the model was used to explore the relationship between theta and gamma oscillations, working memory capacity and phase coding it showed that the potential storage capacity of short term memories, in terms of nested gamma-subcycles, coincides with the maximal theta power. Increasing theta power is also related to the precision of theta phase which functions as a potential timing clock for neuronal firing in the cortex or hippocampus

Sex Commonalities and Differences in Obesity-Related Alterations in Intrinsic Brain Activity and Connectivity.

OBJECTIVE:This study aimed to characterize obesity-related sex differences in the intrinsic activity and connectivity of the brain's reward networks. METHODS:Eighty-six women (n = 43) and men (n = 43) completed a 10-minute resting functional magnetic resonance imaging scan. Sex differences and commonalities in BMI-related frequency power distribution and reward seed-based connectivity were investigated by using partial least squares analysis. RESULTS:For whole-brain activity in both men and women, increased BMI was associated with increased slow-5 activity in the left globus pallidus (GP) and substantia nigra. In women only, increased BMI was associated with increased slow-4 activity in the right GP and bilateral putamen. For seed-based connectivity in women, increased BMI was associated with reduced slow-5 connectivity between the left GP and putamen and the emotion and cortical regulation regions, but in men, increased BMI was associated with increased connectivity with the medial frontal cortex. In both men and women, increased BMI was associated with increased slow-4 connectivity between the right GP and bilateral putamen and the emotion regulation and sensorimotor-related regions. CONCLUSIONS:The stronger relationship between increased BMI and decreased connectivity of core reward network components with cortical and emotion regulation regions in women may be related to the greater prevalence of emotional eating. The present findings suggest the importance of personalized treatments for obesity that consider the sex of the affected individual

A cultured neuron probe

Work in progress toward the creation of a "cultured neuron probe" is described. This is a silicon structure similar to that for a multielectrode probe, but with embedded neurons which are intended to grow out and integrate with the neurons of a host nervous system into which the probe has been inserted. Each probe neuron is in close proximity to an electrode which is designed for extracellular estimation and recording from the probe neuron. In this way the probe neurons may provide a highly specific long-term communication link between external electronics and the host. Initial experiments to establish the feasibility of the concept will be done in rat hippocampus