Single Stimulation Session Research Articles

The application of neuronavigated rTMS of the supplementary motor area and rhythmic speech training for stuttering intervention.

Stuttering, a neurodevelopmental speech fluency disorder, is associated with intermittent disruptions of speech-motor control. Behavioural treatments for adults who stutter (AWS) concentrate on adopting speech patterns that enhance fluency, such as speaking rhythmically or prolonging speech sounds. However, maintaining these treatment benefits can be challenging. Neuroimaging studies suggest that supplementary motor area (SMA) which play a crucial role in speech initiation, planning and internal timing shows aberrant activation in speech production of AWS and may contribute to stuttering. Preliminary evidence suggests that brain stimulation may impact responsiveness to behavioural treatments. The present study aims to investigate whether excitatory repetitive transcranial magnetic stimulation (rTMS) of the SMA and rhythmic speech can consistently reduce stuttering severity across various measures. Ten self-identified Cantonese-speaking AWS participated in this double-blinded, sham-controlled clinical trial study (NCT05472181). The participants underwent 10 sessions of rhythmic speech training across two phases, combined with either neuronavigated rTMS or sham, with a 2-week washout period between phases. The stuttering severity was assessed through various outcome measures, including the percentage of syllables stuttered, self-perceived stuttering severity, and the brief version of Unhelpful Thoughts and Beliefs About Stuttering before and after each treatment phase. Results demonstrated improved speech fluency in various speaking contexts, with no significant difference between rTMS and sham conditions immediately and 1 week post-treatment. Notably, rTMS specifically led to less stuttering in tongue twister production (d = -0.70). Both treatment conditions effectively reduced self-perceived stuttering severity and negative thoughts and beliefs about stuttering. The findings of this study indicate that stimulating the SMA reduced stuttering, only in the production of tongue twisters that may require greater motor control and coordination. Furthermore, it indicates that rhythmic speech might help alleviate negative beliefs and anxiety related to stuttering. This research contributes to our understanding of neuromodulation in stuttering treatment and the role of the SMA in speech motor control and emphasises the need for more research on the potential benefits and limitations of applying rTMS in this condition. What is already known on the subject Behavioural treatments for adults who stutter concentrate on adopting speech patterns that enhance fluency, such as speaking rhythmically or prolonging speech sounds. However, maintaining these treatment benefits can be challenging. Neuroimaging studies indicate that aberrant neural activation in speech production regions, like the supplementary motor area (SMA), is involved in stuttering. The SMA plays a crucial role in initiating, planning, and sequencing motor behaviours. Preliminary evidence suggests that brain stimulation (e.g., transcranial direct current stimulation or transcranial magnetic stimulation) may impact responsiveness to behavioural treatments. What this paper adds to existing knowledge There is limited knowledge regarding the potential effects of stimulating the SMA to enhance speech fluency in people who stutter. Existing research primarily consists of single case studies that lack proper control conditions or involve only a single stimulation session. Due to their limited scope and power, these studies may not provide sufficient evidence. The current study expands upon existing research by investigating whether multiple sessions of repetitive transcranial magnetic stimulation over the SMA, combined with rhythmic speech, improve speech fluency in adults who stutter. Furthermore, it addresses the limitations of brain stimulation methods and proposes directions for future research. What are the potential or actual clinical implications of this work? This study implies that the stimulation of SMA reduced stuttering only in speaking contexts that may require greater motor control and coordination such as tongue twisters. Additionally, the research suggests that using rhythmic speech could potentially alleviate negative beliefs and anxiety associated with stuttering.

Multi-session transcutaneous spinal cord stimulation prevents chloride homeostasis imbalance and the development of hyperreflexia after spinal cord injury in rat

Spasticity is a complex and multidimensional disorder that impacts nearly 75% of individuals with spinal cord injury (SCI) and currently lacks adequate treatment options. This sensorimotor condition is burdensome as hyperexcitability of reflex pathways result in exacerbated reflex responses, co-contractions of antagonistic muscles, and involuntary movements. Transcutaneous spinal cord stimulation (tSCS) has become a popular tool in the human SCI research field. The likeliness for this intervention to be successful as a noninvasive anti-spastic therapy after SCI is suggested by a mild and transitory improvement in spastic symptoms following a single stimulation session, but it remains to be determined if repeated tSCS over the course of weeks can produce more profound effects. Despite its popularity, the neuroplasticity induced by tSCS also remains widely unexplored, particularly due to the lack of suitable animal models to investigate this intervention. Thus, the basis of this work was to use tSCS over multiple sessions (multi-session tSCS) in a rat model to target spasticity after SCI and identify the long-term physiological improvements and anatomical neuroplasticity occurring in the spinal cord. Here, we show that multi-session tSCS in rats with an incomplete (severe T9 contusion) SCI (1) decreases hyperreflexia, (2) increases the low frequency-dependent modulation of the H-reflex, (3) prevents potassium-chloride cotransporter isoform 2 (KCC2) membrane downregulation in lumbar motoneurons, and (4) generally augments motor output, i.e., EMG amplitude in response to single pulses of tSCS, particularly in extensor muscles. Together, this work displays that multi-session tSCS can target and diminish spasticity after SCI as an alternative to pharmacological interventions and begins to highlight the underlying neuroplasticity contributing to its success in improving functional recovery.

Effect of regional intrinsic activity following two kinds of theta burst stimulation on precuneus.

Theta burst stimulation (TBS) has been widely used in the treatment of mental disorders, but the cerebral functional difference between intermittent TBS (iTBS) and continuous TBS (cTBS) after one single session of stimulation is not clear. Here we applied resting-state functional magnetic resonance imaging (RS-FMRI) to evaluate the alterations in intrinsic brain activity after iTBS and cTBS in the precuneus. We recruited 32 healthy young adults and performed a single session each of iTBS and cTBS at a 1-week interval. RS-fMRI was collected at baseline before and immediately after the stimulation. Parameters for regional brain activity (ALFF/fALFF/ReHo) and functional connectivity (FC) with the stimulated site of the precuneus after iTBS and cTBS were calculated and compared between each stimulation using a paired t-test. Correlation analysis among those parameters was calculated to explore whether changes in functional connectivity were associated with local spontaneous activity. After iTBS stimulation, fALFF increased in the bilateral precuneus, while fALFF decreased in the bilateral middle temporal gyrus. Reductions in precuneus FC were found in the bilateral cuneus, superior occipital gyrus, superior temporal gyrus, precentral gyrus, and postcentral gyrus, which correlated with regional activity. After cTBS, fALFF decreased in the bilateral insula, and precuneus FC was decreased in the bilateral inferior occipital gyrus and increased in the thalamus. In the current study, we observed that one session of iTBS or cTBS could cause inhibitory effects in remote brain regions, but only iTBS caused significant local activation in the target region.

The great reset: Transcranial pulse stimulation reduces global EEG-entropy in Alzheimer's Disease

Abstract Background: Transcranial Pulse Stimulation (TPS) is a new therapy that uses shockwaves for the treatment of Alzheimer's Disease (AD). In humans, there is first evidence for beneficial clinical effects after a series of six TPS sessions. Magnetic resonance imaging studies suggest up-regulation of memory networks as well as increased cortical thickness after stimulation. Effects on oscillatory electrical brain activity measured with resting state electroencephalography (EEG) have not been reported so far. Methods: A consecutive number of four pilot TPS-treated AD-patients was examined. TPS-naïve resting EEGs were recorded before treatment and compared with EEG-recordings directly after first stimulation. All patients received 4Hz TPS of about 6000 pulses of 0.2 mJ/mm2 (navigated bifrontally, biparietally, bitemporally and praecuneus) using the Neurolith System (Storz Medical). Frontal, parietal, central and temporal channel clusters were analyzed with regard to their alpha, theta delta and gamma power and for a measure of Tsallis entropy. Results: The immediate effect after first TPS on grand-average EEG resting state showed an increase of power in all frequency bands and for total power, although a significant difference between pre- and post-stimulation was not revealed due to power variability. However, the grand-average across patients and channels of Tsallis entropy showed a significant reduction after a single stimulation session. Discussion / Conclusion: Limited due to a high variability (and possibly due to underpower) we found power increase across frequency bands and channels which failed signifance. On the other hand Tsallis entropy was a more sensitive measure for change on EEG activity after stimulation. This might reflect a global reset of uncoordinated and thus pathological neural activity after TPS stimulation. More measurements should be added including longitudinal serial recordings over the treatment course of six sessions with correlations of clinical treatment effects. Keywords: transcranial pulse stimulation, shock wave , Alzheimer, EEG

Multi-session delivery of synchronous rTMS and sensory stimulation induces long-term plasticity

BackgroundCombining training or sensory stimulation with non-invasive brain stimulation has shown to improve performance in healthy subjects and improve brain function in patients after brain injury. However, the plasticity mechanisms and the optimal parameters to induce long-term and sustainable enhanced performance remain unknown. ObjectiveThis work was designed to identify the protocols of which combining sensory stimulation with repetitive transcranial magnetic stimulation (rTMS) will facilitate the greatest changes in fMRI activation maps in the rat's primary somatosensory cortex (S1). MethodsSeveral protocols of combining forepaw electrical stimulation with rTMS were tested, including a single stimulation session compared to multiple, daily stimulation sessions, as well as synchronous and asynchronous delivery of both modalities. High-resolution fMRI was used to determine how pairing sensory stimulation with rTMS induced short and long-term plasticity in the rat S1. ResultsAll groups that received a single session of rTMS showed short-term increases in S1 activity, but these increases did not last three days after the session. The group that received a stimulation protocol of 10 Hz forepaw stimulation that was delivered simultaneously with 10 Hz rTMS for five consecutive days demonstrated the greatest increases in the extent of the evoked fMRI responses compared to groups that received other stimulation protocols. ConclusionsOur results provide direct indication that pairing peripheral stimulation with rTMS induces long-term plasticity, and this phenomenon appears to follow a time-dependent plasticity mechanism. These results will be important to lead the design of new training and rehabilitation paradigms and training towards achieving maximal performance in healthy subjects.

The limited effect of neural stimulation on visual attention and social cognition in individuals with schizophrenia

BackgroundResearch demonstrates a relationship between faulty visual attention and poorer social cognition in schizophrenia. One potential explanatory model suggests abnormal neuromodulation in specific neural networks may result in reduced attention to socially important cues, leading to poorer understanding of another's emotional state or intentions. ObjectiveThe current study experimentally manipulated neural networks using tDCS to examine this potential causal mechanism. The primary aim was to determine whether stimulation to the right temporoparietal junction (rTPJ) improves visual attention, and secondary aims were to determine whether 1) stimulation improves social cognitive performance and 2) visual attention moderates this improved performance. MethodUsing a double-blind crossover design, 69 individuals with schizophrenia underwent both active and sham stimulation to either the rTPJ of the ventral attention network (n = 36) or the dorsomedial prefrontal cortex of the social brain network (dmPFC; n = 33). Following stimulation, participants completed tasks assessing emotion recognition and mentalizing. Concurrent eye tracking assessed visual attention, measuring proportion of time spent attending to areas of interest. ResultsFor emotion recognition, stimulation failed to impact either visual attention or social cognitive task accuracy. Similarly, neurostimulation failed to affect visual attention on the mentalizing task. However, exploratory analyses demonstrated that mentalizing accuracy significantly improved after stimulation to the active comparator, dmPFC, with no improvement after stimulation to rTPJ. ConclusionResults demonstrate limited effect of a single stimulation session on visual attention and emotion recognition accuracy but provide initial support for an alternate neural mechanism for mentalizing, highlighting the importance of executive functions over visual attention.

Combined Behavioral and Mismatch Negativity Evidence for the Effects of Long-Lasting High-Definition tDCS in Disorders of Consciousness: A Pilot Study.

ObjectiveTo evaluate the effects of long-term High-definition transcranial direct current stimulation (HD-tDCS) over precuneus on the level of consciousness (LOC) and the relationship between Mismatch negativity (MMN) and the LOC over the therapy period in patients with Disorders of consciousness (DOCs).MethodsWe employed a with-in group repeated measures design with an anode HD-tDCS protocol (2 mA, 20 min, the precuneus) on 11 (2 vegetative state and nine minimally conscious state) patients with DOCs. MMN and Coma Recovery Scale-Revised (CRS-R) scores were measured at four time points: before the treatment of HD-tDCS (T0), after a single session of HD-tDCS (T1), after the treatment of 7 days (T2) and 14 days (T3). A frequency-deviant oddball paradigm with two deviation magnitudes (standard stimulus: 1000 Hz, small deviant stimuli: 1050 Hz, large deviant stimuli: 1200 Hz) was adopted to elicit MMN.ResultsSignificant improvements of CRS-R score were found after 7-day (T2) and 14-day (T3) treatment compared with baseline (T0). Regarding the MMN, significant improvements of MMN amplitudes were observed after a single session of stimulation (T1), 7-day (T2) and 14-day treatment (T3) compared with baseline (T0). Additionally, there were significant negative correlations between CRS-R scores and MMN amplitudes elicited by both large and small deviant stimuli.ConclusionLong-term HD-tDCS over precuneus might improve signs of consciousness in patients with DOCs as measured by CRS-R total scores, and MMN could be an assistant assessment in the course of tDCS treatment.

Can theta burst stimulation safely influence auditory hearing thresholds in healthy young adults?

ObjectiveThis TBS sham-controlled study aimed to evaluate the effects of intermittent TBS (iTBS) and continuous TBS (cTBS) upon ipsilateral hearing thresholds after stimulation on the left auditory cortex. MethodsSixty healthy adults, aged between 19 and 32 years (median of 23 years), were randomly distributed into three groups and underwent iTBS, cTBS or sham stimulation. Each double-blind experimental session comprised two pure tone audiometric evaluations per subject, before and after stimulation. To assess volunteer safety, a follow-up of at least 48 hours was implemented. ResultsThe iTBS group mean thresholds displayed a tendency to decrease after stimulation, predominantly in the 500 Hz–6000 Hz interval and group comparisons revealed significant differences between the iTBS and sham groups for 500 Hz (p = 0.041) and between the iTBS and cTBS groups for 4000 Hz (p = 0.038). Neither relevant side effects nor any significant hearing threshold impairment after active or sham stimulation were found. ConclusionsA single stimulation session led to an effective neuromodulation of the auditory cortex, reflected in lower thresholds when using iTBS. SignificanceThese encouraging results with this safe noninvasive tool suggest that iTBS may have the potential to positively influence hearing thresholds.

Effects of Acute Transcranial Direct Current Stimulation on Gait Kinematics of Individuals With Parkinson Disease

Background: One of the most disabling problems in Parkinson disease (PD) is gait impairment. Noninvasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS), have been introduced as a therapeutic alternative for coping with PD motor problems. However, the effects of tDCS on gait performance in PD have not yet been fully established. Therefore, the main objective of this study was to evaluate whether a single session of tDCS modifies gait kinematics in individuals with PD. Methods: Twenty-one individuals with PD were included in this randomized, double-blinded, sham-controlled design study. They were randomly allocated in one real (N = 8) or sham (N = 9) tDCS group. Real tDCS comprises a 2-mA anodic current applied over 15 minutes in the supplementary motor area and medial areas of the primary motor cortices through a bipolar electrode montage. Gait kinematics and the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) were assessed before and immediately after a single stimulation session. Pre- minus poststimulation (Δ) values were computed and compared through a Mann-Whitney test. Data are shown as the median (lower, upper quartile). Results: There was a significant group difference with a large effect size for Δ values of gait cadence (P = .014, d = 0.87), indicating its reduction after anodic stimulation in the real (−0.28 [−1.16, 0.01] steps/s) compared with sham tDCS group (0.17 [0.00, 0.40] steps/s). No other significant effect was found. Conclusion: The findings of this study suggest that anodic tDCS administered in a single session improves gait cadence in PD individuals.

Effects of external trigeminal nerve stimulation (eTNS) on laser evoked cortical potentials (LEP): A pilot study in migraine patients and controls.

Background Transcutaneous external supraorbital nerve stimulation has emerged as a treatment option for primary headache disorders, though its action mechanism is still unclear. Study aim In this randomized, sham-controlled pilot study we aimed to test the effects of a single external transcutaneous nerve stimulation session on pain perception and cortical responses induced by painful laser stimuli delivered to the right forehead and the right hand in a cohort of migraine without aura patients and healthy controls. Methods Seventeen migraine without aura patients and 21 age- and sex-matched controls were selected and randomly assigned to a real or sham external transcutaneous nerve stimulation single stimulation session. The external transcutaneous nerve stimulation was delivered with a self-adhesive electrode placed on the forehead and generating a 60 Hz pulse at 16 mA intensity for 20 minutes. For sham stimulation, we used 2 mA intensity. Laser evoked responses were recorded from 21 scalp electrodes in basal condition (T0), during external transcutaneous nerve stimulation and sham stimulation (T1), and immediately after these (T2). The laser evoked responses were analyzed by LORETA software. Results The real external transcutaneous nerve stimulation reduced the trigeminal N2P2 amplitude in migraine and control groups significantly in respect to placebo. The real stimulation was associated with lower activity in the anterior cingulate cortex under trigeminal laser stimuli. The pattern of LEP-reduced habituation was reverted by real and sham transcutaneous stimulation in migraine patients. Conclusions The present results could suggest that the external transcutaneous nerve stimulation may interfere with the threshold and the extent of trigeminal system activation, with a mechanism of potential utility in the resolution and prevention of migraine attacks.

Neural signature of tDCS, tPCS and their combination: Comparing the effects on neural plasticity

Transcranial pulsed current stimulation (tPCS) and transcranial direct current stimulation (tDCS) are two noninvasive neuromodulatory brain stimulation techniques whose effects on human brain and behavior have been studied individually. In the present study we aimed to quantify the effects of tDCS and tPCS, individually and in combination, on cortical activity, sensitivity and pain-related assessments in healthy individuals in order to understand their neurophysiological mechanisms and potential applications in clinical populations. A total of 48 healthy individuals participated in this randomized double blind sham controlled study. Participants were randomized to receive a single stimulation session of either: active or sham tPCS and active or sham tDCS. Quantitative electroencephalography (qEEG), sensitivity and pain assessments were used before and after each stimulation session. We observed that tPCS had a higher effect on power, as compared to tDCS, in several bandwidths on various cortical regions: the theta band in the parietal region (p=0.021), the alpha band in the temporal (p=0.009), parietal (p=0.0063), and occipital (p<0.0001) regions. We found that the combination of tPCS and tDCS significantly decreased power in the low beta bandwidth of the frontal (p=0.0006), central (p=0.0001), and occipital (p=0.0003) regions, when compared to sham stimulation. Additionally, tDCS significantly increased power in high beta over the temporal (p=0.0015) and parietal (p=0.0007) regions, as compared to sham. We found no effect on sensitivity or pain-related assessments. We concluded that tPCS and tDCS have different neurophysiological mechanisms, elicit distinct signatures, and that the combination of the two leads to no effect or a decrease on qEEG power. Further studies are required to examine the effects of these techniques on clinical populations in which EEG signatures have been found altered.

Optimal random frequency range in transcranial pulsed current stimulation indexed by quantitative electroencephalography.

Given the recent results provided by previous investigations on transcranial pulsed current stimulation (tPCS) demonstrating its modulatory effects on cortical connectivity; we aimed to explore the application of different random pulsed frequencies. The utility of tPCS as a neuromodulatory technique for cognition performance will come as additional frequency ranges are tested with the purpose to find optimal operational parameters for tPCS. This study was designed to analyze the effects of tPCS using the following random frequencies; 1-5, 6-10, and 11-15 Hz compared with sham on quantitative electroencephalographic changes in the spectral power and interhemispheric coherence of each electroencephalographic frequency band. This was a parallel, randomized, double-blinded, sham-controlled trial. Forty healthy individuals older than 18 years were eligible to participate. The main outcomes were differences in the spectral power analysis and interhemispheric coherence as measured by quantitative electroencephalography. Participants were randomly allocated to four groups of random frequency stimulation and received a single session of stimulation for 20 min with a current intensity of 2 mA delivered by bilateral periauricular electrode clips. We found that a random pulsed frequency between 6-10 Hz significantly increased the power and coherence in frontal and central areas for the alpha band compared with sham stimulation, while 11-15 Hz tPCS decreased the power for the alpha and theta bandwidth. Our findings corroborate the hypothesis that a random frequency ranging into the boundaries of 6-10 Hz induces changes in the naturally occurring alpha oscillatory activity, providing additional data for further studies with tPCS.

Positive effects of tDCS cortical stimulation on the walking performance of chronic hemiplegic patients

To evaluate the effect of a single session of stimulation of the primary motor cortex (M1) with tDCS versus placebo (SHAM) on the walking performance of hemiplegic patients at a chronic stage. Randomized, cross-over, double-blind study. Eighteen patients (6 women, 12 men, mean age: 60 years) were included. They suffered an initially complete hemiplegia due to a single stroke older than 6 months (min: 14 months, max: 11 years). Each patient participated in a single anodal stimulation session (2 mA, 20 minutes) of the area of the lower limb ipsilesional M1 (STIM condition) and a pseudo-stimulation session (SHAM condition). The order of the two sessions was randomly assigned, with an 11-day interval between the two sessions. The anodal electrode was positioned on the hotspot previously identified with TMS. The cathode was placed above the contralesional orbit. The walking performances were evaluated with the Wade Test and the 6-Minute Walking Test (6MWT). These tests were performed during the stimulation and after 1 h, and 2 days before and 10 days after each session. The Wade Test and 6MWT showed a linear progression from the first pre-stimulation evaluation until the last evaluation (Wade average + 20% + 21% average 6MWT). To overcome this progression, comparisons were based on the linearly corrected data of each patient. The comparison between the 6MWT under STIM versus SHAM conditions demonstrated a significant positive effect of the stimulation by 11% during stimulation (Wilcoxon matched pairs, P = 0.019) and 6% 1 hour after stimulation (Wilcoxon matched pairs, P = 0.025). There is no significant difference regarding the Wade Test. These results show a significant positive effect of a single session of anodal tDCS of the M1 ipsilesional area of the lower limb in chronic hemiplegic patients. This improvement affects the endurance (6MWT) but not the walking speed (Wade Test). This proof of principle study supports a follow-up study assessing the training of walking under iterative tDCS stimulation.

High-Frequency Repetitive Transcranial Magnetic Stimulation over the Primary Foot Motor Area in Parkinson's Disease

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has been reported to be clinically effective for treating motor symptoms in Parkinson's disease (PD). Few studies have been performed reporting the effects of rTMS on non-motor symptoms such as depression and apathy in PD. ObjectiveWe assessed the effects of high-frequency (HF) rTMS over the primary motor (M1) foot area on motor symptoms, depression and apathy scales, and sensory symptoms in PD. MethodsWe investigated the efficacy of 3 consecutive days of HF-rTMS over the M1 foot area in 21 patients with PD using a randomized, double-blind cross-over trial compared with sham stimulation. Motor effects were evaluated using the Unified Parkinson's Disease Rating Scale part III (UPDRS-III), the self-assessment motor score, the visual analog scale (VAS), the 10-m walking test, and finger tapping. Non-motor effects were analyzed using the Montgomery Asberg Depression Rating Scale, the Apathy Scale, and quantitative sensory testing. ResultsHF-rTMS significantly improved UPDRS-III (P < 0.001), VAS (P < 0.001), the walking test (P = 0.014), self-assessment motor score (P = 0.010), and finger tapping measurement (P < 0.05) compared to sham stimulation. In contrast, no significant improvement was observed in depression and apathy scales. Consecutive days of rTMS did not significantly increase the improvement in motor symptoms. There were no adverse effects following rTMS on patients with PD. ConclusionsWe confirmed that HF-rTMS over the M1 foot area significantly improved motor symptoms in patients with PD. In addition, daily repeated stimulation was not significantly more effective than a single session of stimulation, but may be effective for maintaining the improvement in motor symptoms in patients with PD.

Non-invasive cerebral stimulation for the upper limb rehabilitation after stroke: A review

Numerous studies have recently been published on improving upper-limb motor function after stroke. There has been a particular interest in brain stimulation techniques, which could promote brain plasticity. In this review, transcranial Direct Current Stimulation (tDCS) and repetitive Transcranial Magnetic Stimulation (rTMS) are presented as techniques that could be relevant in Physical Medicine and Rehabilitation (PM&R) centers in the future. We are presenting a comprehensive literature review on the studies using tDCS or rTMS for upper-limb rehabilitation after a stroke. Both techniques have shown their ability to modify cortical excitability and to transitorily improve upper-limb function after one single stimulation session. The first placebo-controlled, blinded therapeutic trials, which included repeated daily sessions, seem quite promising, and deserve to be validated by further trials.

Transcranial Direct Current Stimulation Priming of Therapeutic Repetitive Transcranial Magnetic Stimulation

Repetitive transcranial magnetic stimulation (rTMS) has been shown to be a safe treatment of depression, and research efforts are now largely focused on strategies to enhance its efficacy. Motor cortex experiments suggest that the effects of rTMS can be enhanced by first priming the same cortical area with transcranial direct current stimulation (tDCS). We explored this approach in depressed subjects. Seven depressed subjects were given sessions of combined tDCS-rTMS to the left dorsolateral prefrontal cortex, exploring a range of tDCS and rTMS stimulation parameters and interstimulation intervals. Effects of repeated stimulation sessions on mood state and neuropsychological functioning were evaluated. Most of the subjects showed little improvement with cathodal tDCS followed by 10-Hz rTMS, although 2 subjects showed marked improvement, one after a single stimulation session. Anodal tDCS followed by rTMS did not lead to any improvement. Preconditioning with tDCS seemed to greatly exacerbate the pain of subsequent rTMS. No adverse effects on neuropsychological functioning were observed. Overall, preconditioning with cathodal tDCS followed by rTMS did not result in greater antidepressant efficacy than rTMS given at similar parameters in open trials, although the dramatic response in 1 subject is encouraging. Outcomes may be highly dependent on the exact stimulation paradigm in which tDCS and rTMS are combined. Researchers should be aware that preconditioning with tDCS may greatly increase the pain experienced with subsequent rTMS.

A single session of rTMS over the left dorsolateral prefrontal cortex influences attentional control in depressed patients

Depressed patients are impaired in the ability to shift their focus of attention. This attentional control process is related to dysfunctions in the dorsolateral prefrontal cortex (DLPFC). It has been proposed that a dorsal circuit plays an important role in the interaction between emotional and attentional information processing. However, because the different emphasis of fundamental cognitive neuroscience research and clinical research of repetitive transcranial magnetic stimulation (rTMS) over the DLPFC, little research has been done on the effects of rTMS on cognitive functioning after a single stimulation session to explore the neural systems underlying depression. This study was conducted as a double-blind, placebo-controlled, crossover, within subjects design. Sixteen depressed patients performed a modified task switching paradigm, before and after receiving high frequency (HF) versus placebo rTMS over the left DLPFC. One session of HF- rTMS over the left DLPFC had a specific beneficial effect on task-switching performance, whereas mood remained stable. Antidepressant effects of rTMS could be related to the same neurochemical changes that underlie cognitive functioning. Therefore, task switching performance may provide a unique window into the extent of antidepressant effects which can be considered as second-order long-term effects possibly related to primary alternations in cognitive functioning.

Effects of a 2- to 4-week course of repetitive transcranial magnetic stimulation (rTMS) on neuropsychologic functioning, electroencephalogram, and auditory threshold in depressed patients

Background: The safety of repetitive transcranial magnetic stimulation (rTMS) has only previously been formally studied in volunteers receiving a single session of stimulation or in a small number of depressed subjects receiving a 2-week treatment course. This study examined safety issues in depressed subjects receiving up to 4 weeks of rTMS. Efficacy results from this study have been previously reported. Methods: Eighteen subjects with DSM-IV major depression participated in a 2-week, parallel, double-blind, sham-controlled study of rTMS treatment. Twelve subjects then went on to receive 4 weeks active rTMS in an open follow-up. We examined the effects of rTMS on neuropsychologic function (up to 4 weeks), auditory threshold (up to 6 weeks exposure to rTMS noise), and an electroencephalogram (after 2 weeks). Data were analyzed by repeated measures analysis. Results: There were trends for improvement in neuropsychologic performance, probably due to practice effects. No mean changes in auditory threshold occurred, but two patients showed mild high-frequency hearing loss after several weeks of rTMS. Electroencephalograms in two patients, one of whom had sham stimulation, showed minor abnormality. Conclusions: No significant mean deficits were demonstrated in this cohort. Overall, rTMS for up to 4 weeks is safe, but individual results suggest caution and the need for further investigation of the safety of several weeks of rTMS.

Effect of functional continuous magnetic stimulation on urethral closure in healthy volunteers

Objectives. To study urodynamically the effect of functional continuous magnetic stimulation on urethral closure in normal volunteers. Methods. Ten volunteers (6 men and 4 women, 20 to 29 years old, mean age 24.5) were recruited for the study. Seven subjects were assigned to an active group and 3 to a sham group. An 8F transducer was inserted transurethrally, and the urethral pressure profile was monitored. Then the catheter was fixed so that the transducer could be positioned at the portion at which the highest pressure was recorded (maximum intraurethral pressure). In the active group, the stimulating intensity was gradually increased up to the tolerable limit. A 15-minute single session of stimulation was carried out at 20 Hz in an intermittent manner with 1-minute-on/30-second-off cycles. After stimulation, the urethral pressure profile was repeated. Results. In the active group, the greatest pressure difference between the on and off phases of the maximum intraurethral pressure was 62.4 ± 37.6 cm H 2O at 35% to 55% of maximum output (46 to 113 J). In the urethral pressure profile, the maximum urethral closure pressure increased significantly after stimulation ( P = 0.0280). In the sham group, no changes in these parameters were noted. All subjects tolerated the functional continuous magnetic stimulation well, and none experienced any adverse effect. Conclusions. Functional continuous magnetic stimulation safely and significantly increased maximum intraurethral pressure during stimulation and maximum urethral closure pressure after stimulation.