Repetitive transcranial magnetic stimulation induces kf-1 expression in the rat brain

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive approach used for stimulating the brain, and has proven effective in the treatment of depression, however the mechanism of its antidepressant action is unknown. Recently, we have reported the induction of kf-1 in rat frontal cortex and hippocampus after chronic antidepressant treatment and repeated electroconvulsive treatment (ECT). In this study, we demonstrated the induction of kf-1 after rTMS in the rat frontal cortex and hippocampus, but not in hypothalamus. Our data suggest that kf-1 may be a common functional molecule that is increased after antidepressant treatment, ECT and rTMS. In conclusion, it is proposed that induction of kf-1 may be associated with the treatment induced adaptive neural plasticity in the brain, which is a long-term target for their antidepressant action.     

Listening to speech recruits specific tongue motor synergies as revealed by transcranial magnetic stimulation and tissue-Doppler ultrasound imaging

The activation of listener''s motor system during speech processing was first demonstrated by the enhancement of electromyographic tongue potentials as evoked by single-pulse transcranial magnetic stimulation (TMS) over tongue motor cortex. This technique is, however, technically challenging and enables only a rather coarse measurement of this motor mirroring. Here, we applied TMS to listeners’ tongue motor area in association with ultrasound tissue Doppler imaging to describe fine-grained tongue kinematic synergies evoked by passive listening to speech. Subjects listened to syllables requiring different patterns of dorso-ventral and antero-posterior movements (/ki/, /ko/, /ti/, /to/). Results show that passive listening to speech sounds evokes a pattern of motor synergies mirroring those occurring during speech production. Moreover, mirror motor synergies were more evident in those subjects showing good performances in discriminating speech in noise demonstrating a role of the speech-related mirror system in feed-forward processing the speaker''s ongoing motor plan.     

Changes in the brain spontaneous bioelectrical activity during transcranial electrical and electromagnetic stimulation

In order to study systemic brain reactions on transcranial electrical or electromagnetic medical stimulation and specify the neurophysiological criteria of its efficiency, comparative clinical and experimental examination was performed with the analysis of spontaneous bioelectric activity and behavioral or clinical parameters. We examined 6 patients with prolonged posttraumatic unconsciousness states treated with electrical stimulation and 17 intact Wistar rats subjected to electromagnetic stimulation of the brain. The effect of the transcranial stimulation was shown to depend on the initial level of the intercentral interactions of brain bioelectrical activity, estimated by the EEG coherence. Hypersynchronization of biopotentials as the main element of the brain reactivity can be the most useful for the rehabilitation of patients with cerebral pathology in cases of initially lowered level of the intercentral interactions in the absence of pathologically strengthened functional connections.     

Numerical modelling of plasticity induced by transcranial magnetic stimulation

We use neural field theory and spike-timing dependent plasticity to make a simple but biophysically reasonable model of long-term plasticity changes in the cortex due to transcranial magnetic stimulation (TMS). We show how common TMS protocols can be captured and studied within existing neural field theory. Specifically, we look at repetitive TMS protocols such as theta burst stimulation and paired-pulse protocols. Continuous repetitive protocols result mostly in depression, but intermittent repetitive protocols in potentiation. A paired pulse protocol results in depression at short ( < ～ 10 ms) and long ( > ～ 100 ms) interstimulus intervals, but potentiation for mid-range intervals. The model is sensitive to the choice of neural populations that are driven by the TMS pulses, and to the parameters that describe plasticity, which may aid interpretation of the high variability in existing experimental results. Driving excitatory populations results in greater plasticity changes than driving inhibitory populations. Modelling also shows the merit in optimizing a TMS protocol based on an individual’s electroencephalogram. Moreover, the model can be used to make predictions about protocols that may lead to improvements in repetitive TMS outcomes.     

Noninvasive ultrasound deep brain stimulation of nucleus accumbens induces behavioral avoidance

Ultrasound stimulation is an emerging noninvasive option in treating neuropsychiatric disorders. The present study investigates the behavioral alterations resulting from ultrasound stimulation on the nucleus accumbens(NAc) in freely moving mice. Our results show that an acute ultrasound stimulation on the NAc, rather than the visual cortex or auditory cortex, led to a pronounced avoidance behavior, while repeated NAc ultrasound stimulation resulted in an obvious conditioned place aversion with changes in synaptic protein(Glu A1/2 subunit) expression. Notably, NAc ultrasound stimulation suppressed the morphine-induced conditioned place preference. The results provide evidence that NAc ultrasound stimulation can be applied as a potential noninvasive therapeutic option in treating psychiatric disorders.     

Illusory sensation of movement induced by repetitive transcranial magnetic stimulation

Human movement sense relies on both somatosensory feedback and on knowledge of the motor commands used to produce the movement. We have induced a movement illusion using repetitive transcranial magnetic stimulation over primary motor cortex and dorsal premotor cortex in the absence of limb movement and its associated somatosensory feedback. Afferent and efferent neural signalling was abolished in the arm with ischemic nerve block, and in the leg with spinal nerve block. Movement sensation was assessed following trains of high-frequency repetitive transcranial magnetic stimulation applied over primary motor cortex, dorsal premotor cortex, and a control area (posterior parietal cortex). Magnetic stimulation over primary motor cortex and dorsal premotor cortex produced a movement sensation that was significantly greater than stimulation over the control region. Movement sensation after dorsal premotor cortex stimulation was less affected by sensory and motor deprivation than was primary motor cortex stimulation. We propose that repetitive transcranial magnetic stimulation over dorsal premotor cortex produces a corollary discharge that is perceived as movement.     

Pupillary reactions during transcranial magnetic stimulation

Pupillary reactions have been studied in healthy volunteers before, during, and after transcranial magnetic stimulation (TMS) of the primary visual cortex. During TMS in the projection of the primary visual cortex, a significant increase in pupil size was observed. Three minutes after the end of the TMS, a significant decrease in pupil size was recorded. These data point to a role of the primary visual cortex in the mechanisms of correcting pupillary reactions in humans.     

Noninvasive brain stimulation with transcranial magnetic or direct current stimulation (TMS/tDCS)-From insights into human memory to therapy of its dysfunction

Noninvasive stimulation of the brain by means of transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) has driven important discoveries in the field of human memory functions. Stand-alone or in combination with other brain mapping techniques noninvasive brain stimulation can assess issues such as location and timing of brain activity, connectivity and plasticity of neural circuits and functional relevance of a circumscribed brain area to a given cognitive task. In this emerging field, major advances in technology have been made in a relatively short period. New stimulation protocols and, especially, the progress in the application of tDCS have made it possible to obtain longer and much clearer inhibitory or facilitatory effects even after the stimulation has ceased. In this introductory review, we outline the basic principles, discuss technical limitations and describe how noninvasive brain stimulation can be used to study human memory functions in vivo. Though improvement of cognitive functions through noninvasive brain stimulation is promising, it still remains an exciting challenge to extend the use of TMS and tDCS from research tools in neuroscience to the treatment of neurological and psychiatric patients.     

Facilitate insight by non-invasive brain stimulation

Our experiences can blind us. Once we have learned to solve problems by one method, we often have difficulties in generating solutions involving a different kind of insight. Yet there is evidence that people with brain lesions are sometimes more resistant to this so-called mental set effect. This inspired us to investigate whether the mental set effect can be reduced by non-invasive brain stimulation. 60 healthy right-handed participants were asked to take an insight problem solving task while receiving transcranial direct current stimulation (tDCS) to the anterior temporal lobes (ATL). Only 20% of participants solved an insight problem with sham stimulation (control), whereas 3 times as many participants did so (p = 0.011) with cathodal stimulation (decreased excitability) of the left ATL together with anodal stimulation (increased excitability) of the right ATL. We found hemispheric differences in that a stimulation montage involving the opposite polarities did not facilitate performance. Our findings are consistent with the theory that inhibition to the left ATL can lead to a cognitive style that is less influenced by mental templates and that the right ATL may be associated with insight or novel meaning. Further studies including neurophysiological imaging are needed to elucidate the specific mechanisms leading to the enhancement.     

Influence of exercise on serotonergic neuromodulation in the brain

Summary. Implications of exercise on serotonergic neuromodulation in the brain have been investigated in two studies. Acute paroxetine (selective serotonin (5-HT) reuptake inhibitor) administration to endurance athletes, who performed a cycle ergometer test to exhaustion at moderate intensity, reduced time to exhaustion and post exercise cognitive performance in comparison to trials with placebo or BCAA administration. Furthermore, during a 3-week moderate endurance training of sedentary males basaline values of B_max of 5-HT transporters (5-HTT) and 5-HT_2A receptors (5-HT_2AR) on isolated platelet membranes increased while plasma prolactin (PRL) concentrations decreased as well as mood and physical efficiency improved. In contrast, after an excessive training program over four weeks, well-trained endurance athletes showed no change of B_max of 5-HTT, but a decline of 5-HT_2AR density and an increase in basal plasma PRL concentration. Mood was impaired and central fatigue increased. Thus, the impact of exercise on 5-HT neurotransmission may depend on training state of athletes and extent of exertion. The theoretical background of the implication of exercise and the effect of long lasting exhaustive exercise in athletes on mental and physical efficiency or central fatigue are evaluated. The significance of the primary disturbance of central neuromodulation and dysfunction of 5-HTT, 5-HT receptor subtypes and the phosphoinositol signal transduction as well as the limited modulation capacity of the 5-HT system in overstrain are also addressed. Received December 1, 1999 / Accepted February 1, 2000     

Modulation of monoamine transporter expression and function by repetitive transcranial magnetic stimulation

Repetitive transcranial magnetic stimulation (rTMS) is a new tool for the treatment of neuropsychiatric disorders. However, the mechanisms underlying the effects of rTMS are still unclear. In this study, we analyzed mRNA expression changes of monoamine transporter (MAT) genes, which are targets for antidepressants and psychostimulants. Following a 20-day rTMS treatment, these genes were found to be differentially expressed in the mouse brain. Down-regulation of serotonin transporter (SERT) mRNA levels and the subsequent decrease in serotonin uptake and binding were observed after chronic rTMS. In contrast to the SERT changes, increased mRNA levels of dopamine transporter (DAT) and norepinephrine transporter (NET) were observed. For NET, but not DAT, there were accompanying changes in uptake and binding. Similar effect on NET was observed in PC12 cells stimulated by rTMS for 15 days. These results indicate that modulation of MATs by chronic rTMS may be one therapeutic mechanism for the treatment of neuropsychiatric disorders.     

Spike suppression in a local cortical circuit induced by transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) noninvasively interferes with human cortical function, and is widely used as an effective technique for probing causal links between neural activity and cognitive function. However, the physiological mechanisms underlying TMS-induced effects on neural activity remain unclear. We examined the mechanism by which TMS disrupts neural activity in a local circuit in early visual cortex using a computational model consisting of conductance-based spiking neurons with excitatory and inhibitory synaptic connections. We found that single-pulse TMS suppressed spiking activity in a local circuit model, disrupting the population response. Spike suppression was observed when TMS was applied to the local circuit within a limited time window after the local circuit received sensory afferent input, as observed in experiments investigating suppression of visual perception with TMS targeting early visual cortex. Quantitative analyses revealed that the magnitude of suppression was significantly larger for synaptically-connected neurons than for isolated individual neurons, suggesting that intracortical inhibitory synaptic coupling also plays an important role in TMS-induced suppression. A conventional local circuit model of early visual cortex explained only the early period of visual suppression observed in experiments. However, models either involving strong recurrent excitatory synaptic connections or sustained excitatory input were able to reproduce the late period of visual suppression. These results suggest that TMS targeting early visual cortex disrupts functionally distinct neural signals, possibly corresponding to feedforward and recurrent information processing, by imposing inhibitory effects through intracortical inhibitory synaptic connections.     

Sleep deprivation in depression stabilizing antidepressant effects by repetitive transcranial magnetic stimulation

Partial sleep deprivation (PSD) has a profound and rapid effect on depressed mood. However, the transient antidepressant effect of PSD - most patients relapse after one night of recovery sleep - is limiting the clinical use of this method. Using a controlled, balanced parallel design we studied, whether repetitive transcranial magnetic stimulation (rTMS) applied in the morning after PSD is able to prevent this relapse. 20 PSD responders were randomly assigned to receive either active or sham stimulation during the following 4 days after PSD. Active stimulation prolonged significantly (p < 0.001) the antidepressant effect of PSD up to 4 days. This finding indicates that rTMS is an efficacious method to prevent relapse after PSD.