Renal impairment as a possible side effect of gabapentin - A single case report

A bipolar I manic patient was treated successfully by adding gabapentin to perazine and clonazepam. Also initially tolerated well, an increase of creatinine after several weeks of GP (2000 mg) was observed which was reversible after discontinuation of GP. It is suggested that the possibility of renal dysfunction should be kept in mind with the usage of gabapentin

Modulating Brain Networks With Transcranial Magnetic Stimulation Over the Primary Motor Cortex: A Concurrent TMS/fMRI Study

Stimulating the primary motor cortex (M1) using transcranial magnetic stimulation (TMS) causes unique multisensory experience such as the targeted muscle activity, afferent/reafferent sensory feedback, tactile sensation over the scalp and “click” sound. Although the human M1 has been intensively investigated using TMS, the experience of the M1 stimulation has not been elucidated at the whole brain. Here, using concurrent TMS/fMRI, we investigated the acute effect of the M1 stimulation of functional brain networks during task and at rest. A short train of 1 Hz TMS pulses applied to individuals’ hand area in the M1 during motor execution or at rest. Employing the independent component analysis (ICA), we showed the M1 stimulation decreased the motor networks activity when the networks were engaged in the task and increased the deactivation of networks when the networks were not involved in the ongoing task. The M1 stimulation induced the activation in the key networks involved in bodily self-consciousness (BSC) including the insular and rolandic operculum systems regardless of states. The degree of activation in these networks was prominent at rest compared to task conditions, showing the state-dependent TMS effect. Furthermore, we demonstrated that the M1 stimulation modulated other domain-general networks such as the default mode network (DMN) and attention network and the inter-network connectivity between these networks. Our results showed that the M1 stimulation induced the widespread changes in the brain at the targeted system as well as non-motor, remote brain networks, specifically related to the BSC. Our findings shed light on understanding the neural mechanism of the complex and multisensory experience of the M1 stimulation

Vertex Stimulation as a Control Site for Transcranial Magnetic Stimulation: A Concurrent TMS/fMRI Study

AbstractBackgroundA common control condition for transcranial magnetic stimulation (TMS) studies is to apply stimulation at the vertex. An assumption of vertex stimulation is that it has relatively little influence over on-going brain processes involved in most experimental tasks, however there has been little attempt to measure neural changes linked to vertex TMS. Here we directly test this assumption by using a concurrent TMS/fMRI paradigm in which we investigate fMRI blood-oxygenation-level-dependent (BOLD) signal changes across the whole brain linked to vertex stimulation.MethodsThirty-two healthy participants to part in this study. Twenty-one were stimulated at the vertex, at 120% of resting motor threshold (RMT), with short bursts of 1 Hz TMS, while functional magnetic resonance imaging (fMRI) BOLD images were acquired. As a control condition, we delivered TMS pulses over the left primary motor cortex using identical parameters to 11 other participants.ResultsVertex stimulation did not evoke increased BOLD activation at the stimulated site. By contrast we observed widespread BOLD deactivations across the brain, including regions within the default mode network (DMN). To examine the effects of vertex stimulation a functional connectivity analysis was conducted.ConclusionThe results demonstrated that stimulating the vertex with suprathreshold TMS reduced neural activity in brain regions related to the DMN but did not influence the functional connectivity of this network. Our findings provide brain imaging evidence in support of the use of vertex simulation as a control condition in TMS but confirm that vertex TMS induces regional widespread decreases in BOLD activation

Reducing image artefacts in concurrent TMS/fMRI by passive shimming

A significant problem in the concurrent application of transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) is the image artefact caused by the effect of the TMS-coil on the homogeneity of the static magnetic field (B0). The resulting field inhomogeneity can lead to spatial distortions and local signal loss in echo-planar (EP) images. Here we demonstrate that passive shimming using thin patches of austenitic stainless steel can reduce the effect of the TMS-coil on B0 by ~ 80%, thus essentially eliminating the associated artefact. Initially the effect of the TMS-coil on B0 was measured using the phase of gradient echo images. Consequently the ideal distribution for the steel was simulated using the magnetic properties of the steel and the effects of the TMS-coil. Finally we demonstrate the effect of two different implementations of the passive shim on a spherical phantom and in vivo

Operculo-Insular and Anterior Cingulate Plasticity Induced by Transcranial Magnetic Stimulation in the Human Motor Cortex: A Dynamic Casual Modelling Study

The ability to induce neuroplasticity with non-invasive brain stimulation techniques offers a unique opportunity to examine the human brain systems involved in pain modulation. In experimental and clinical settings, the primary motor cortex (M1) is commonly targeted to alleviate pain, but its mechanism of action remains unclear. Using dynamic causal modelling (DCM) and Bayesian model selection (BMS), we tested seven competing hypotheses about how TMS modulates the directed influences (or effective connectivity) between M1 and three distinct cortical areas of the medial and lateral pain systems, including the insular (INS), anterior cingulate cortex (ACC), and parietal operculum (PO). The dataset included a novel fMRI acquisition collected synchronously with M1 stimulation during rest and while performing a simple hand motor task. DCM and BMS showed a clear preference for the fully connected model in which all cortical areas receive input directly from M1, with facilitation of the connections INS®M1, PO®M1, and ACC®M1, plus increased inhibition of their reciprocal connections. An additional DCM analysis comparing the reduced models only corresponding to networks with a sparser connectivity within the full model, showed that M1 input into the INS is the second-best model of plasticity following TMS manipulations. The results reported here provide a starting point forinvestigating whether pathway-specific targeting involving M1«INS improves analgesic response beyond conventional targeting. We eagerly await future empirical data and models that tests this hypothesis

TMS combined with fMRI

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On the importance of specialized radiofrequency filtering for concurrent TMS/MRI

The concurrent application of TMS and MRI is challenging due to the MR-image artifacts, which are produced by using the two techniques in combination. One such artifact arises from the introduction of radio frequency noise through the lead of the TMS-coil into the scanner. Here we describe four methods used in the literature to integrate TMS into the MR environment and quantify in detail the efficacy of one approach in filtering RF interference. We show that RF filtering has a dramatic effect on the overall signal-to-fluctuation-noise ratio (SfNR) of the acquired echo-planar imaging data. The reduction in SfNR when integrating a TMS system into the MR scanner varies from 20% up to 80% (compared with MR scanner in the absence of TMS system), depending on the configuration used. Using an RF-filter in-line with the TMS-coil eliminates much of this loss in SfNR. However the RF filter also causes a ∼7% decrease in the functional efficacy of TMS. Overall, this study highlights the importance of RF-filtering when designing and installing a concurrent TMS/MRI system

The Impact of Phase-Specific Macrophage Depletion on Intestinal Anastomotic Healing

Intestinal anastomotic healing (AH) is critical in colorectal surgery, since disruptive AH leads to anastomotic leakage, a feared postoperative complication. Macrophages are innate immune cells and are instrumental in orchestrating intestinal wound healing, displaying a functional dichotomy as effectors of both tissue injury and repair. The aim of this study was to investigate the phase-specific function and plasticity of macrophages during intestinal AH. Transgenic CD11b diphtheria toxin receptor (CD11b-DTR) mice were used to deplete intestinal macrophages in a temporally controlled manner. Distal colonic end-to-end anastomoses were created in CD11b-DTR, and wild-type mice and macrophages were selectively depleted during either the inflammatory (day 0–3), proliferative (day 4–10), or reparative (day 11–20) phase of intestinal AH, respectively. For each time point, histological and functional analysis as well as gene set enrichment analysis (GSEA) of RNA-sequencing data were performed. Macrophage depletion during the inflammatory phase significantly reduced the associated inflammatory state without compromising microscopic AH. When intestinal macrophages were depleted during the proliferative phase, AH was improved, despite significantly reduced perianastomotic neoangiogenesis. Lastly, macrophages were depleted during the reparative phase and GSEA revealed macrophage-dependent pathways involved in collagen remodeling, cell proliferation, and extracellular matrix composition. However, AH remained comparable at this late timepoint. These results demonstrate that during intestinal AH, macrophages elicit phase-specific effects, and that therapeutic interventions must critically balance their dual and timely defined role