Corticomotor control of the genioglossus in awake OSAS patients: a transcranial magnetic stimulation study

Background

Upper airway collapse does not occur during wake in obstructive sleep apnea patients. This points to wake-related compensatory mechanisms, and possibly to a modified corticomotor control of upper airway dilator muscles. The objectives of the study were to characterize the responsiveness of the genioglossus to transcranial magnetic stimulation during respiratory and non-respiratory facilitatory maneuvers in obstructive sleep apnea patients, and to compare it to the responsiveness of the diaphragm, with reference to normal controls.

Methods

Motor evoked potentials of the genioglossus and of the diaphragm, with the corresponding motor thresholds, were recorded in response to transcranial magnetic stimulation applied during expiration, inspiration and during maximal tongue protraction in 13 sleep apnea patients and 8 normal controls.

Main Results

In the sleep apnea patients: 1) combined genioglossus and diaphragm responses occurred more frequently than in controls (P < 0.0001); 2) the amplitude of the genioglossus response increased during inspiratory maneuvers (not observed in controls); 3) the latency of the genioglossus response decreased during tongue protraction (not observed in controls). A significant negative correlation was found between the latency of the genioglossus response and the apnea-hypopnea index; 4) the difference in diaphragm and genioglossus cortico-motor responses during tongue protraction and inspiratory loading differed between sleep apnea and controls.

Conclusion

Sleep apnea patients and control subjects differ in the response pattern of the genioglossus and of the diaphragm to facilitatory maneuvers, some of the differences being related to the frequency of sleep-related events.     

Phonological and lexical motor facilitation during speech listening: a transcranial magnetic stimulation study.

In the present study, we used transcranial magnetic stimulation (TMS) to investigate the influence of phonological and lexical properties of verbal items on the excitability of the tongue's cortical motor representation during passive listening. In particular, we aimed to clarify if the difference in tongue motor excitability found during listening to words and pseudo-words [Fadiga, L., Craighero, L., Buccino, G., Rizzolatti, G., 2002. Speech listening specifically modulates the excitability of tongue muscles: a TMS study. European Journal of Neuroscience 15, 399-402] is due to lexical frequency or to the presence of a meaning per se. In order to do this, we investigated the time-course of tongue motor-evoked potentials (MEPs) during listening to frequent words, rare words, and pseudo-words embedded with a double consonant requiring relevant tongue movements for its pronunciation. Results showed that at the later stimulation intervals (200 and 300 ms from the double consonant) listening to rare words evoked much larger MEPs than listening to frequent words. Moreover, by comparing pseudo-words embedded with a double consonant requiring or not tongue movements, we found that a pure phonological motor resonance was present only 100 ms after the double consonant. Thus, while the phonological motor resonance appears very early, the lexical-dependent motor facilitation takes more time to appear and depends on the frequency of the stimuli. The present results indicate that the motor system responsible for phonoarticulatory movements during speech production is also involved during speech listening in a strictly specific way. This motor facilitation reflects both the difference in the phonoarticulatory characteristics and the difference in the frequency of occurrence of the verbal material.     

Intrahemispheric dysfunction in primary motor cortex without corpus callosum: a transcranial magnetic stimulation study

Background  

The two human cerebral hemispheres are continuously interacting, through excitatory and inhibitory influences and one critical structure subserving this interhemispheric balance is the corpus callosum. Interhemispheric neurophysiological abnormalities and intrahemispheric behavioral impairments have been reported in individuals lacking the corpus callosum. The aim of this study was to examine intrahemispheric neurophysiological function in primary motor cortex devoid of callosal projections.     

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.     

Perceiving what is reachable depends on motor representations: evidence from a transcranial magnetic stimulation study

Background

Visually determining what is reachable in peripersonal space requires information about the egocentric location of objects but also information about the possibilities of action with the body, which are context dependent. The aim of the present study was to test the role of motor representations in the visual perception of peripersonal space.

Methodology

Seven healthy participants underwent a TMS study while performing a right-left decision (control) task or perceptually judging whether a visual target was reachable or not with their right hand. An actual grasping movement task was also included. Single pulse TMS was delivered 80% of the trials on the left motor and premotor cortex and on a control site (the temporo-occipital area), at 90% of the resting motor threshold and at different SOA conditions (50ms, 100ms, 200ms or 300ms).

Principal Findings

Results showed a facilitation effect of the TMS on reaction times in all tasks, whatever the site stimulated and until 200ms after stimulus presentation. However, the facilitation effect was on average 34ms lower when stimulating the motor cortex in the perceptual judgement task, especially for stimuli located at the boundary of peripersonal space.

Conclusion

This study provides the first evidence that brain motor area participate in the visual determination of what is reachable. We discuss how motor representations may feed the perceptual system with information about possible interactions with nearby objects and thus may contribute to the perception of the boundary of peripersonal space.     

Participation of the motor cortex in the bimanual unloading task: a study by transcranial magnetic stimulation

Motor potentials of m. biceps brachii evoked by transcranial magnetic stimulation of the contralateral motor cortex have been recorded in postural adjustment during arm unloading in humans. During active unloading, the amplitude of the motor evoked potential decreases simultaneously with the decreasing of the muscle activity. During load keeping, the muscle response changes simultaneously with the load changes. When the other arm has lifted the other load during load keeping, the amplitude of the motor evoked potential decreases in the m. biceps of the keeping arm without muscle activity changes. Passive unloading results in the same changes of the motor evoked potential as active unloading. A possible role of the direct corticospinal volley and the motor command mediated by some subcortical structures in the decrease of the muscle activity preceding active unloading (postural adjustment) is discussed.     

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.     

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.     

Post-lesional cerebral reorganisation: Evidence from functional neuroimaging and transcranial magnetic stimulation

Reorganisation of cerebral representations has been hypothesised to underlie the recovery from ischaemic brain infarction. The mechanisms can be investigated non-invasively in the human brain using functional neuroimaging and transcranial magnetic stimulation (TMS). Functional neuroimaging showed that reorganisation is a dynamic process beginning after stroke manifestation. In the acute stage, the mismatch between a large perfusion deficit and a smaller area with impaired water diffusion signifies the brain tissue that potentially enables recovery subsequent to early reperfusion as in thrombolysis. Single-pulse TMS showed that the integrity of the cortico-spinal tract system was critical for motor recovery within the first four weeks, irrespective of a concomitant affection of the somatosensory system. Follow-up studies over several months revealed that ischaemia results in atrophy of brain tissue adjacent to and of brain areas remote from the infarct lesion. In patients with hemiparetic stroke activation of premotor cortical areas in both cerebral hemispheres was found to underlie recovery of finger movements with the affected hand. Paired-pulse TMS showed regression of perilesional inhibition as well as intracortical disinhibition of the motor cortex contralateral to the infarction as mechanisms related to recovery. Training strategies can employ post-lesional brain plasticity resulting in enhanced perilesional activations and modulation of large-scale bihemispheric circuits.     

Electronically switchable sham transcranial magnetic stimulation (TMS) system

Transcranial magnetic stimulation (TMS) is increasingly being used to demonstrate the causal links between brain and behavior in humans. Further, extensive clinical trials are being conducted to investigate the therapeutic role of TMS in disorders such as depression. Because TMS causes strong peripheral effects such as auditory clicks and muscle twitches, experimental artifacts such as subject bias and placebo effect are clear concerns. Several sham TMS methods have been developed, but none of the techniques allows one to intermix real and sham TMS on a trial-by-trial basis in a double-blind manner. We have developed an attachment that allows fast, automated switching between Standard TMS and two types of control TMS (Sham and Reverse) without movement of the coil or reconfiguration of the setup. We validate the setup by performing mathematical modeling, search-coil and physiological measurements. To see if the stimulus conditions can be blinded, we conduct perceptual discrimination and sensory perception studies. We verify that the physical properties of the stimulus are appropriate, and that successive stimuli do not contaminate each other. We find that the threshold for motor activation is significantly higher for Reversed than for Standard stimulation, and that Sham stimulation entirely fails to activate muscle potentials. Subjects and experimenters perform poorly at discriminating between Sham and Standard TMS with a figure-of-eight coil, and between Reverse and Standard TMS with a circular coil. Our results raise the possibility of utilizing this technique for a wide range of applications.     

The continuous Wagon wheel illusion and the 'when' pathway of the right parietal lobe: a repetitive transcranial magnetic stimulation study

A continuous periodic motion stimulus can sometimes be perceived moving in the wrong direction. These illusory reversals have been taken as evidence that part of the motion perception system samples its inputs as a series of discrete snapshots -although other explanations of the phenomenon have been proposed, that rely on the spurious activation of low-level motion detectors in early visual areas. We have hypothesized that the right inferior parietal lobe ('when' pathway) plays a critical role in timing perceptual events relative to one another, and thus we examined the role of the right parietal lobe in the generation of this "continuous Wagon Wheel Illusion" (c-WWI). Consistent with our hypothesis, we found that the illusion was effectively weakened following disruption of right, but not left, parietal regions by low frequency repetitive transcranial magnetic stimulation (1 Hz, 10 min). These results were independent of whether the motion stimulus was shown in the left or the right visual field. Thus, the c-WWI appears to depend on higher-order attentional mechanisms that are supported by the 'when' pathway of the right parietal lobe.     

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.     

Calcium dependent plasticity applied to repetitive transcranial magnetic stimulation with a neural field model

The calcium dependent plasticity (CaDP) approach to the modeling of synaptic weight change is applied using a neural field approach to realistic repetitive transcranial magnetic stimulation (rTMS) protocols. A spatially-symmetric nonlinear neural field model consisting of populations of excitatory and inhibitory neurons is used. The plasticity between excitatory cell populations is then evaluated using a CaDP approach that incorporates metaplasticity. The direction and size of the plasticity (potentiation or depression) depends on both the amplitude of stimulation and duration of the protocol. The breaks in the inhibitory theta-burst stimulation protocol are crucial to ensuring that the stimulation bursts are potentiating in nature. Tuning the parameters of a spike-timing dependent plasticity (STDP) window with a Monte Carlo approach to maximize agreement between STDP predictions and the CaDP results reproduces a realistically-shaped window with two regions of depression in agreement with the existing literature. Developing understanding of how TMS interacts with cells at a network level may be important for future investigation.     

Effect of transcranial magnetic stimulation on treatment effect and immune function

To explore the effect of transcranial stimulation on the therapeutic effect and immune function of patients with post-stroke depression (PSD). Methods Selection in September 2020–April 2021 on the diagnosis of 70 patients with PSD as the research object, 35 patients were randomly divided into control group and intervention group and control group given conventional treatment, the intervention group in the control group on the basis of the application of transcranial magnetic stimulation treatment, compare the curative effect of two groups of patients after the treatment cycle and the effects on the immune function. Results After treatment, the levels of DA, NE, 5-HT in 2 groups were significantly increased, and those in the observation group were significantly higher than those in the control group (P < 0.05). After 8 weeks of treatment, serum Gly content in 2 groups was significantly increased and Glu content was significantly decreased compared with before treatment. Compared with the control group, serum Gly content in observation group was significantly increased and Glu content was significantly decreased after treatment (P < 0.05). After 8 weeks of treatment, the contents of IL-1β, IL-6 and TNF-α in serum of 2 groups were significantly decreased, compared with the control group, the contents of IL-1β, IL-6 and TNF-α in serum of observation group were significantly decreased (P < 0.05); Before treatment, there was no significant difference in PHQ-9 score and MBI score between the two groups (P > 0.05). After 8 weeks of treatment, PHQ-9 score and MBI score in the two groups were better than before treatment, and the observation group was better than the control group (P < 0.05). Conclusion Transcranial magnetic stimulation therapy can not only effectively promote the synthesis and release of monoamine neurotransmitters in patients with post-stroke depression, regulate the inhibitory/excitatory amino acid neurotransmitters, reduce inflammatory response, improve the clinical treatment effect and enhance the immune function of PSD patients, which has clinical application value.     

Repetitive transcranial magnetic stimulation and treatment of negative symptoms of schizophrenia

One of the fundamental prerequisites of the successful schizophrenia treatment is represented by an adequately significant impact on the negative symptoms of schizophrenia. Since the present pharmacotherapy has probably reached its limit in this area, there is a logical effort to utilize other, non-pharmacological methods. One of the most promising supplements that has been for a long time verified in the clinical practice is rTMS. Most of the studies have arrived at the conclusion that rTMS is an efficient method in the treatment of negative symptoms of schizophrenia. A valuable contribution to the assessment of the rTMS application in the treatment of negative symptoms is represented by meta-analyses. The meta-analyses indicate that the effect is mild to moderate (d=0.43 to 0.68). To sum it up, there will be higher probability of the rTMS effect on negative symptoms if 10?Hz stimulating frequency and a longer stimulation period in the extent at least three, ideally four to six weeks is used.