Beneficial Effects Of Stimulation Research Articles

Music combined with Transcranial Magnetic Stimulation for the treatment of depression

Depression can be disabling, and standard treatments are often ineffective. rTMS is a safe and effective brain stimulation modality. rTMS is often used in combination with other evidence-based strategies to improve treatment outcomes.We are introducing a novel combination approach of rTMS with music. Our goal is to present proof of concept and provide a theoretical framework on why this combination may be superior. We reviewed existing literature on music’s benefits in treating depression as well as evidence base on music’s effects on the brain. We have delivered the combination treatment of music and rTMS to 9 adult patients with severe treatment-resistant MDD. Hamilton Depression Rating Scale (HAM-D) was used to measure the response. Response and remission rates were 89% and 56%, respectively. The mean change in the total HAM-D score was -15.3 (SD=3.6). Music’s powerful effects on the brain make it an invaluable tool for using in combination with rTMS. In addition to being augmentative to the rTMS course, music can also provide a “priming effect,” whereby underlying brain activity is altered in a way that it improves beneficial effects of stimulation. This combination method is safe, convenient, and easy to set up and deliver.

Effects of alpha and gamma transcranial alternating current stimulation (tACS) on verbal creativity and intelligence test performance

Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation method that allows to directly modulate brain oscillations of a given frequency. Using this method, it was recently shown that increasing alpha (10Hz) oscillations improved creative ideation with figural material and that increasing gamma (40Hz) oscillations speeded up performance in a figural matrices intelligence task. The aim of the present study was to examine whether these findings generalize to verbal creativity and intelligence tasks. In addition, we explored whether the stimulation effects are moderated by individual differences in creative potential and intelligence. Twenty-two adults received 10Hz, 40Hz and sham tACS while they worked on a verbal creativity (alternate uses) task and a verbal intelligence (anagram) task. Analyses revealed that 10Hz stimulation had a marginally significant effect on ideational fluency in the alternate uses task, whereas originality was unaffected. The beneficial effect of stimulation on fluency tended to emerge mainly in the individuals with higher creative potential. In the verbal intelligence task, in contrast, 40Hz stimulation did neither impact on performance nor interacted with individual differences in intelligence. These findings provide first tentative evidence that enhancing alpha oscillations through tACS may improve creative thinking not only in the figural but also in the verbal domain. The previously reported beneficial effect of gamma tACS on figural intelligence, however, could not be observed in a verbal task. In sum, the present study further corroborates the causal link between alpha oscillations and creative thinking and suggests that tACS may be a promising tool to enhance cognitive processes.

Optogenetic neuronal stimulation of the lateral cerebellar nucleus promotes persistent functional recovery after stroke

Stroke induces network-wide changes in the brain, affecting the excitability in both nearby and remotely connected regions. Brain stimulation is a promising neurorestorative technique that has been shown to improve stroke recovery by altering neuronal activity of the target area. However, it is unclear whether the beneficial effect of stimulation is a result of neuronal or non-neuronal activation, as existing stimulation techniques nonspecifically activate/inhibit all cell types (neurons, glia, endothelial cells, oligodendrocytes) in the stimulated area. Furthermore, which brain circuit is efficacious for brain stimulation is unknown. Here we use the optogenetics approach to selectively stimulate neurons in the lateral cerebellar nucleus (LCN), a deep cerebellar nucleus that sends major excitatory output to multiple motor and sensory areas in the forebrain. Repeated LCN stimulations resulted in a robust and persistent recovery on the rotating beam test, even after cessation of stimulations for 2 weeks. Furthermore, western blot analysis demonstrated that LCN stimulations significantly increased the axonal growth protein GAP43 in the ipsilesional somatosensory cortex. Our results demonstrate that pan-neuronal stimulations of the LCN is sufficient to promote robust and persistent recovery after stroke, and thus is a promising target for brain stimulation.

Impact of 5-Hz rTMS over the primary sensory cortex is related to white matter volume in individuals with chronic stroke.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that may facilitate mechanisms of motor learning. In a recent single-blind, pseudo-randomized study, we showed that 5-Hz rTMS over ipsilesional primary somatosensory cortex followed by practice of a skilled motor task enhanced motor learning compared with sham rTMS + practice in individuals with chronic stroke. However, the beneficial effect of stimulation was inconsistent. The current study examined how differences in sensorimotor cortex morphology might predict rTMS-related improvements in motor learning in these individuals. High-resolution T1-weighted magnetic resonance images were acquired and processed in FreeSurfer using a newly developed automated, whole brain parcellation technique. Gray matter and white matter volumes of the ipsilesional primary somatosensory and motor cortices were extracted. A significant positive association was observed between the volume of white matter in the primary somatosensory cortex and motor learning-related change, exclusively in the group that received active 5-Hz rTMS. A regression model with age, gray matter and white matter volumes as predictors was significant for predicting motor learning-related change in individuals who received active TMS. White matter volume predicted the greatest amount of variance (47.6%). The same model was non-significant when volumes of the primary motor cortex were considered. We conclude that white matter volume in the cortex underlying the TMS coil may be a novel predictor for behavioral response to 5-Hz rTMS over the ipsilesional primary somatosensory followed by motor practice.

Direct visualization of Smad1/5/8‐mediated transcriptional activity identifies podocytes and collecting ducts as major targets of BMP signalling in healthy and diseased kidneys

Bone morphogenetic protein 7 (BMP7) is a key determinant of renal response to injury, exhibiting strong protective as well as regenerative potential in a variety of experimental models. In vitro, beneficial effects of stimulation with BMP7 and other BMPs have been observed in many renal cell types. Still, it remains poorly understood which cells in the native kidney actually respond to BMPs in health and disease. Here, we report the use of BRE:gfp mice expressing green fluorescent protein (GFP) under the control of a pSmad1/5/8-specific BMP-responsive element (BRE) to directly visualize the spatiotemporal distribution of transcriptional activity downstream of canonical BMP signalling in healthy kidneys and in two distinct models of kidney disease. BRE-GFP signal coincided with expression of endogenous BMP target genes but, surprisingly, it was much more restricted than expected from the widespread distribution of pSmad1/5/8, a classical component of canonical BMP signal tranduction. BRE-GFP was mainly present in podocytes and collecting duct cells, and both glomerular and medullary BRE-GFP decreased following ischaemia-reperfusion injury as well as following unilateral ureteric obstruction, together with decreased BMP7, pSmad1/5/8 and BMP target gene expression. Remarkably, however, BRE-GFP was increased in injured proximal tubules in association with up-regulation of BMP receptors ALK2 and ALK3. Thus, native BMP transcriptional activity is much more restricted than previously suggested based on pSmad1/5/8 detection alone, and its response to injury varies according to cell type and nephron segment.

Response to novelty, social and self-control behaviors, in rats exposed to neonatal anoxia: modulatory effects of an enriched environment

Perinatal asphyxia is a concern for public health and may promote subtle and long-lasting neuropsychiatric disorders. In the present study, newborn Wistar rat pups underwent a repeated 20-min exposure to a 100% N2 atmosphere (or air) on postnatal days (pnd) 1, 3, 5, and 7. Half of the animals were housed during adolescence (pnd 21-35) in an enriched environment. The consequences on behavior were assessed throughout adolescence to adulthood. When scored for social performance, adolescent rats exposed to neonatal asphyxia exhibited exaggerated levels of anogenital sniffing behavior, which was normalized by enriched living. In air-exposed controls, enriched living increased the expression of affiliative and novelty-seeking behaviors, as compared to standard housing. However, this enrichment-induced behavioral plasticity was not found in rats neonatally exposed to asphyxia. At adulthood, levels of impulsivity and 5-HT2A receptors in the striatum were markedly increased in neonatal-asphyxia rats kept in standard-housing conditions. Interestingly, impulsivity and receptor density were normalized by enriched rearing during adolescence. These findings indicate profound long-lasting behavioral alterations as a consequence of repeated neonatal asphyxia in rats. Beneficial effects of stimulation by an enriched environment during the still-plastic window of adolescence are suggested in these animals.

Epidural Electrical Stimulation on Neurogenic Bladder

In 1967 Shealy first used electrical stimulation of the spinal cord to treat spasticity and pain. This therapy proved to be effective for bladder dysfunction too. The effect of electrical stimulation of the spinal cord at thoracic level has been evaluated in 18 neurogenic patients suffering from hyperreflexia with detrusor-sphincter dyssynergia. Bladder function improved significantly in 13 (73%). Partial or complete relief of bladder hyperreflexia, marked increased of bladder capacity and reduction of residual urine were recorded. The beneficial effect of stimulation indicates that it is a safe and effective alternative treatment for the neuropathic bladder and careful trials with further investigations should be carried out.