Transcranial Magnetic Stimulation Protocol Research Articles

The Relationship of Anxious Arousal With Treatment of Dysphoria Using Virtual Reality Mindfulness and 2 Accelerated Transcranial Magnetic Stimulation Protocols

The Relationship of Anxious Arousal With Treatment of Dysphoria Using Virtual Reality Mindfulness and 2 Accelerated Transcranial Magnetic Stimulation Protocols

Use of transcranial magnetic stimulation (TMS) for studying cognitive control in depressed patients: A systematic review.

Major depressive disorder (MDD) is a debilitating mental disorder and the leading cause of disease burden. Major depressive disorder is associated with emotional impairment and cognitive deficit. Cognitive control, which is the ability to use perceptions, knowledge, and information about goals and motivations to shape the selection of goal-directed actions or thoughts, is a primary function of the prefrontal cortex (PFC). Psychotropic medications are one of the main treatments for MDD, but they are not effective for all patients. An alternative treatment is transcranial magnetic stimulation (TMS). Previous studies have provided mixed results on the cognitive-enhancing effects of TMS treatment in patients with MDD. Some studies have found significant improvement, while others have not. There is a lack of understanding of the specific effects of different TMS protocols and stimulation parameters on cognitive control in MDD. Thus, this review aims to synthesize the effectiveness of the TMS methods and a qualitative assessment of their potential benefits in improving cognitive functioning in patients with MDD. We reviewed 21 studies in which participants underwent a treatment of any transcranial magnetic stimulation protocol, such as repetitive TMS or theta-burst stimulation. One of the primary outcome measures was any change in the cognitive control process. Overall, the findings indicate that transcranial magnetic stimulation (TMS) may enhance cognitive function in patients with MDD. Most of the reviewed studies supported the notion of cognitive improvement following TMS treatment. Notably, improvements were predominantly observed in inhibition, attention, set shifting/flexibility, and memory domains. However, fewer significant improvements were detected in evaluations of visuospatial function and recognition, executive function, phonemic fluency, and speed of information processing. This review found evidence supporting the use of TMS as a treatment for cognitive deficits in patients with MDD. The results are promising, but further research is needed to clarify the specific TMS protocol and stimulation locations that are most effective.

Pilot study with randomised control of dual site theta burst transcranial magnetic stimulation (TMS) for methamphetamine use disorder: a protocol for the TARTAN study

BackgroundTranscranial magnetic stimulation (TMS) (including the theta burst stimulation (TBS) form of TMS used in this study) is a non-invasive means to stimulate nerve cells in superficial areas of the brain. In recent years, there has been a growth in the application of TMS to investigate the modulation of neural networks involved in substance use disorders. This study examines the feasibility of novel TMS protocols for the treatment of methamphetamine (MA) use disorder in an ambulatory drug and alcohol treatment setting.MethodsThirty participants meeting the criteria for moderate to severe MA use disorder will be recruited in community drug and alcohol treatment settings and randomised to receive active TMS or sham (control) intervention. The treatment is intermittent TBS (iTBS) applied to the left dorsolateral prefrontal cortex (DLPFC), then continuous TBS (cTBS) to the left orbitofrontal cortex (OFC). Twelve sessions are administered over 4 weeks with opt-in weekly standardized cognitive behaviour therapy (CBT) counselling and a neuroimaging sub-study offered to participants. Primary outcomes are feasibility measures including recruitment, retention and acceptability of the intervention. Secondary outcomes include monitoring of safety and preliminary efficacy data including changes in substance use, cravings (cue reactivity) and cognition (response inhibition).DiscussionThis study examines shorter TBS protocols of TMS for MA use disorder in real-world drug and alcohol outpatient settings where withdrawal and abstinence from MA, or other substances, are not eligibility requirements. TMS is a relatively affordable treatment and staff of ambulatory health settings can be trained to administer TMS. It is a potentially scalable and translatable treatment for existing drug and alcohol clinical settings. TMS has the potential to provide a much-needed adjuvant treatment to existing psychosocial interventions for MA use disorder. A limitation of this protocol is that the feasibility of follow-up is only examined at the end of treatment (4 weeks).Trial registrationAustralia New Zealand Clinical Trial Registry ACTRN12622000762752. Registered on May 27, 2022, and retrospectively registered (first participant enrolled) on May 23, 2022, with protocol version 7 on February 24, 2023.

Investigational applications of transcranial magnetic stimulation (TMS) in Mood Disorders: Studies from a tertiary care center in India

The investigational potential of TMS in psychiatry is largely underutilized. In the current article, we present the results of five studies with similar TMS protocols that looked at the investigative applications of TMS via measuring cortical reactivity as potential biomarkers in mood disorders. The first two studies, evaluate potential of TMS parameters and Motor neuron system (MNS) as state or trait markers of BD. Third and fourth studies evaluate these as endophenotypic markers of BD. The fifth study which is an RCT evaluating add-on yoga in UD, evaluates if markers of CI can index the therapeutic response of yoga. In study one MT1 was significantly greater in the SM (symptomatic-mania) group compared to HC (healthy-control) (P=0.032). The cortical inhibition measures SICI was reduced in SM(P=0.021) and BD (remitted Bipolar) (P=0.023) groups compared to HC. LICI was increased in the SM(0.021) and BD(P=0.06) groups compared to HC. In study two, a significant group x time interaction effect was observed indicating higher putative MNS-activity mediation in patients compared to HC on SlCl(P=0.024), LlCl(P=0.033). There were no significant group differences noted in the endophenotype studies. The fifth study showed a significant time X group interaction for CSP, favoring improvement in YG (yoga-group) (p<0.01).No significant change was observed for LICI(p=0.2), SICI(p=0.5). Limitations of these studies notwithstanding, we conclude that cortical reactivity measured using TMS is a potential biomarker across the course of mood disorders, starting from state and trait markers to understanding the therapeutic mechanism of a particular treatment modality in these disorders.

Safety and efficacy of repetitive stimulation of the left dorsolateral prefrontal cortex using transcranial focused ultrasound in treatment-resistant depressed patients: A non-inferiority randomized controlled trial protocol

BackgroundAbout 30% of patients diagnosed with major depressive disorder fail with the mainstream pharmacological treatment. Patients who do not achieve clinical remission of symptoms, even with two different antidepressants, are classified with treatment-resistant depression (TDR). This condition imposes an additional burden with increased Disability Adjusted Life Years. Therefore, complementary treatments, such as neuromodulation, are necessary. The transcranial focused ultrasound (tFUS) has emerged in the past few years as a reliable method for non-invasive neuromodulation in humans and may help treat TRD. This study aims to propose a research protocol for a non-inferiority randomized clinical trial of TDR with tFUS. MethodsPatients with documented TRD will be screened upon entering the TRD outpatient clinic at UFMG (Brazil). One hundred patients without a clinical history of other psychiatric illness, anatomical abnormalities on magnetic resonance imaging (MRI), or treatment with electroconvulsive therapy will be invited to participate. Patients will be randomized (1:1) into two groups: 1) treatment with a previously established protocol of transcranial magnetic stimulation; and 2) treatment with a similar protocol using the stimulation. Besides regular consultations in the outpatient clinic, both groups will attend 7 protocolled spaced days of brain stimulation targeted at the left dorsolateral prefrontal cortex. They will also be submitted to 4 sessions of image studies (2 MRIs, 2 positron-emission tomography), 3 of neuropsychological assessments (at baseline, 1 week and 2 months after treatment), the Montgomery-Åsberg Depression Rating Scale to analyze the severity of depressive symptoms. DiscussionThis clinical trial intends to verify the safety and clinical efficacy of tFUS stimulation of the dorsolateral prefrontal cortex of patients with TRD, compared with a previously established neuromodulation method.

Modulation of intracortical circuits in primary motor cortex during automatic action tendencies.

Humans display automatic action tendencies toward emotional stimuli, showing faster automatic behavior (i.e., approaching a positive stimulus and avoiding a negative stimulus) than regulated behavior (i.e., avoiding a positive stimulus and approaching a negative stimulus). Previous studies have shown that the primary motor cortex is involved in the processing of automatic actions, with higher motor evoked potential amplitudes during automatic behavior elicited by single-pulse transcranial magnetic stimulation. However, it is unknown how intracortical circuits are involved with automatic action tendencies. Here, we measured short-interval intracortical inhibition and intracortical facilitation within the primary motor cortex by using paired-pulse transcranial magnetic stimulation protocols during a manikin task, which has been widely used to explore approaching and avoiding behavior. Results showed that intracortical facilitation was stronger during automatic behavior than during regulated behavior. Moreover, there was a significant negative correlation between reaction times and intracortical facilitation effect during automatic behavior: individuals with short reaction times had stronger faciliatory activity, as shown by higher intracortical facilitation. By contrast, no significant difference was found for short-interval intracortical inhibition between automatic behavior and regulated behavior. The results indicated that the intracortical facilitation circuit, mediated by excitatory glutamatergic neurons, in the primary motor cortex, plays an important role in mediating automatic action tendencies. This finding further supports the link between emotional perception and the action system.

A meta-analysis of transcranial magnetic stimulation in Tourette syndrome

There is growing enthusiasm for the treatment of neuropsychiatric disorders using neuromodulation. While some reports claim that transcranial magnetic stimulation (TMS) can be used to treat Tourette Syndrome (TS), little research exists to support this assertion. This meta-analysis examined the efficacy of TMS to reduce tic severity in patients with TS. Additionally, it explored the effect of TMS to reduce premonitory urge severity—the primary mechanism implicated in the frontline evidence-based treatment of TS. Five treatment comparisons were selected using PRISMA guidelines. All studies included were required to be (1) a randomized controlled trial, (2) compare TMS to a sham condition, and (3) have all participants meet diagnostic criteria for a persistent tic disorder and/or TS. A random effects model meta-analysis examined the efficacy of using TMS to reduce tic severity and explored the effect of TMS to reduce premonitory urge severity. TMS did not significantly reduce tic severity (g = 0.44; 95% CI = −0.17, 1.05; z = 1.40; p = 0.16), but a moderate reduction in premonitory urge severity was found (g = 0.63; 95% CI = 0.9, 1.17; z = 2.27; p < 0.02). Trials with larger sample sizes and a preponderance of women were found to have greater therapeutic effects of TMS for tic severity. There is limited support for the use of TMS to reduce tic severity, though reductions in premonitory urge severity were observed. Major limitations of the existing literature are examined, with a call for research investigating newer TMS protocols and their use as a treatment augmentation strategy.

Frontal and cerebellar contributions to pitch and rhythm processing: a TMS study.

Music represents a salient stimulus for the brain with two key features: pitch and rhythm. Few data are available on cognitive analysis of music listening in musically naïve healthy participants. Beyond auditory cortices, neuroimaging data showed the involvement of prefrontal cortex in pitch and of cerebellum in rhythm. The present study is aimed at investigating the role of prefrontal and cerebellar cortices in both pitch and rhythm processing. The performance of fifteen participants without musical expertise was investigated in a listening discrimination task. The task required to decide whether two eight-element melodic sequences were equal or different according to pitch or rhythm characteristics. Before the task, we applied a protocol of continuous theta burst transcranial magnetic stimulation interfering with the activity of the left cerebellar hemisphere (lCb), right inferior frontal gyrus (rIFG), or vertex (Cz-control site), in a within cross-over design. Our results showed that participants were more accurate in pitch than rhythm tasks. Importantly, the reaction times were slower following rIFG or lCb stimulations in both tasks. Notably, frontal and cerebellar stimulations did not induce any motor effect in right and left hand. The present findings point to the role of the fronto-cerebellar network in music processing with a single mechanism for both pitch and rhythm patterns.

Exploring the Therapeutic Potential of Quadripulse rTMS over the Visual Cortex: A Proof-of-Concept Study in Healthy Volunteers and Chronic Migraine Patients with Medication Overuse Headache.

In chronic migraine with medication overuse (CM-MOH), sensitization of visual cortices is reflected by (i) increased amplitude of stimulus-evoked responses and (ii) habituation deficit during repetitive stimulation. Both abnormalities might be mitigated by inhibitory transcranial neurostimulation. Here, we tested an inhibitory quadripulse repetitive transcranial magnetic stimulation (rTMS-QPI) protocol to decrease durably visual cortex excitability in healthy subjects (HS) and explored its therapeutic potential in CM-MOH patients. Pattern-reversal visual evoked potentials (VEP) were used as biomarkers of effect and recorded before (T1), immediately after (T2), and 3 h after stimulation (T3). In HS, rTMS-QPI durably decreased the VEP 1st block amplitude (p < 0.05) and its habituation (p < 0.05). These changes were more pronounced for the P1N2 component that was modified already at T2 up to T3, while for N1P1 they were significant only at T3. An excitatory stimulation protocol (rTMS-QPE) tended to have an opposite effect, restricted to P1N2. In 12 CM-MOH patients, during a four-week treatment (2 sessions/week), rTMS-QPI significantly reduced monthly headache days (p < 0.01). In patients reversing from CM-MOH to episodic migraine (n = 6), VEP habituation significantly improved after treatment (p = 0.005). rTMS-QPI durably decreases visual cortex responsivity in healthy subjects. In a proof-of-concept study of CM-MOH patients, rTMS-QPI also has beneficial clinical and electrophysiological effects, but sham-controlled trials are needed.

The paired-pulse TMS paradigm of short intracortical inhibition is mediated by a reduction of repetitive motor neuron discharges.

Transcranial magnetic stimulation (TMS) causes repetitive spinal motoneuron discharges (repMNDs), but the effects of short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) on repMNDs remain unknown. Triple stimulation technique (TST) and the extended TST-protocols that include a fourth and fifth stimulation, the Quadruple (QuadS) and Quintuple (QuintS) stimulation, respectively, offer a precise estimate of cortical and spinal motor neuron discharges, including repMNDs. The objective of our study was to explore the effects of SICI and ICF on repMNDs. We explored conventional paired-pulse TMS protocols of SICI and ICF with the TMS, TST, the QuadS, and the QuintS protocols, in a randomized study design in 20 healthy volunteers. We found significantly less repMNDs in the SICI paradigm compared with a single-pulse TMS (SP-TMS). No significant difference was observed in the ICF paradigm. There was a significant inter- and intrasubject variability in both SICI and ICF. We demonstrate a significant reduction of repMNDs in SICI, which may result from the suppression of later I-waves and mediate the inhibition of motor-evoked potential (MEP). There is no increase in repMNDs in ICF suggesting another mechanism underlying facilitation. This study provides the proof that a reduction of repMNDs mediates the inhibition seen in SICI.NEW & NOTEWORTHY Significant reduction of repetitive motor neuron discharges (repMNDs) in short-interval intracortical inhibition (SICI) may result from the suppression of later I-waves and mediate the inhibition of motor-evoked potential (MEP). There is no change in the number of repMNDs in intracortical facilitation (ICF). There was a significant variability in SICI and ICF in healthy subjects.

A neuroimaging study of brain activity alterations in treatment-resistant depression after a dual target accelerated transcranial magnetic stimulation.

In this study, we designed a new transcranial magnetic stimulation (TMS) protocol using a dual-target accelerated transcranial magnetic stimulation (aTMS) for patients with treatment resistant depression (TRD). There are 58 TRD patients were recruited from the Second People's Hospital of Guizhou Province, who were, respectively, received dual-target (real continuous theta burst stimulation (cTBS) at right orbitofrontal cortex (OFC) and real repetitive transcranial magnetic stimulation (rTMS) at left dorsolateral prefrontal cortex (DLPFC)), single- target (sham cTBS at right OFC and real rTMS at left DLPFC), and sham stimulation (sham cTBS at right OFC and sham rTMS at left DLPFC). Resting-state functional magnetic resonance imaging (rs-fMRI) was acquired before and after aTMS treatment to compare characteristics of brain activities by use of amplitude of low-frequency fluctuations (ALFF), fractional low-frequency fluctuations (fALFF) and functional connectivity (FC). At the same time, Hamilton Depression Scale-24 (HAMD24) were conducted to assess the effect. HAMD24 scores reduced significantly in dual group comparing to the single and sham group. Dual-target stimulation decreased not only the ALFF values of right fusiform gyrus (FG) and fALFF values of the left superior temporal gyrus (STG), but also the FC between the right FG and the bilateral middle frontal gyrus (MFG), left triangular part of inferior frontal gyrus (IFG). Higher fALFF value in left STG at baseline may predict better reaction for bilateral arTMS. Dual-targe stimulation can significantly change resting-state brain activities and help to improve depressive symptoms.

Contribution of glial cells to the neuroprotective effects triggered by repetitive magnetic stimulation: a systematic review.

Repetitive transcranial magnetic stimulation has been increasingly studied in different neurological diseases, and although most studies focus on its effects on neuronal cells, the contribution of non-neuronal cells to the improvement triggered by repetitive transcranial magnetic stimulation in these diseases has been increasingly suggested. To systematically review the effects of repetitive magnetic stimulation on non-neuronal cells two online databases, Web of Science and PubMed were searched for the effects of high-frequency-repetitive transcranial magnetic stimulation, low-frequency-repetitive transcranial magnetic stimulation, intermittent theta-burst stimulation, continuous theta-burst stimulation, or repetitive magnetic stimulation on non-neuronal cells in models of disease and in unlesioned animals or cells. A total of 52 studies were included. The protocol more frequently used was high-frequency-repetitive magnetic stimulation, and in models of disease, most studies report that high-frequency-repetitive magnetic stimulation led to a decrease in astrocyte and microglial reactivity, a decrease in the release of pro-inflammatory cytokines, and an increase of oligodendrocyte proliferation. The trend towards decreased microglial and astrocyte reactivity as well as increased oligodendrocyte proliferation occurred with intermittent theta-burst stimulation and continuous theta-burst stimulation. Few papers analyzed the low-frequency-repetitive transcranial magnetic stimulation protocol, and the parameters evaluated were restricted to the study of astrocyte reactivity and release of pro-inflammatory cytokines, reporting the absence of effects on these parameters. In what concerns the use of magnetic stimulation in unlesioned animals or cells, most articles on all four types of stimulation reported a lack of effects. It is also important to point out that the studies were developed mostly in male rodents, not evaluating possible differential effects of repetitive transcranial magnetic stimulation between sexes. This systematic review supports that through modulation of glial cells repetitive magnetic stimulation contributes to the neuroprotection or repair in various neurological disease models. However, it should be noted that there are still few articles focusing on the impact of repetitive magnetic stimulation on non-neuronal cells and most studies did not perform in-depth analyses of the effects, emphasizing the need for more studies in this field.

The effect of functional magnetic resonance imaging connectivity on resting motor threshold transcranial magnetic stimulation in schizophrenia participants

Schizophrenia is a neurological disorder known to influence the motor region. Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique being investigated as a treatment for schizophrenia. Resting motor threshold (RMT) is the dosage parameter for TMS treatment protocols and is known to vary between participants with limited understanding of the drivers of this variance. Previous investigations have used functional magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and individual level neuroanatomy to explain RMT variability. Our previous investigation showed neuroanatomy influences RMT in both schizophrenia and healthy populations and this relationship was weakened by the presence of schizophrenia. In this study, 54 participants with schizophrenia-diagnosed, who were antipsychotic naive and 43 non-impaired controls underwent single pulse TMS, structural magnetic resonance imaging, and fMRI. An independent component analysis (ICA) was used to process fMRI data into 25 distinct channels where correlations were derived between channels. Linear and multiple regression models were used to evaluate first, the influence of these channel interactions on RMT followed by their influence when individual level neuroanatomy was also considered. We found that between-channel functional connectivity was altered in individuals with schizophrenia and that fMRI can contribute to prediction of RMT, but differently in both cohorts and to a lesser degree than individual level neuroanatomical measures. This suggests that functional connectivity influences TMS response and fMRI might help in dosage calculations of clinical TMS protocols.

The role of mirror system in influencing the valence evaluation of words: a TMS study

The mirror neuron system (MNS) has been a captivating area of research since its discovery in macaque monkeys [1]. Researchers have established the role and presence of the human auditory mirror system in both empathy [2] and musical creativity [3]. As well, the mirror system allows to learn new behaviors by observation, facilitating knowledge acquisition and action understanding. In addition, research has indicated the influence of stimulus valence on the human MNS [4]. The human brain is sensitive to the positive valence of words, and this reactivity may vary with the strength of the valence compared to negative words. Additionally, it can perceive differences in valence for negative stimuli and words. However, what about emotional words that are auditory? Do these words’ valence, whether positive, negative, or neutral, impact auditory mirror neurons and cortical excitability? The study examines how auditory words of different valences affect the MNS and cortical activity. This novel approach uses auditory stimuli to examine the role of mirror neurons in neuromodulation through a transcranial magnetic stimulation (TMS) protocol, which has not been done in previous investigations. The results of this study suggest that both positive and negative words will induce greater excitability [4], as evidenced by motor evoked potentials. The results of this study will have broad applications. Firstly, it will offer a new contribution to the investigation of mirror neurons through TMS protocol. Secondly, inferences can be drawn and applied in the field of therapeutics, where language is used as a tool to mediate the process. In general, it will increase personal awareness of language in daily communication, leading to an enhanced communication process. Furthermore, the study’s findings imply the existence of auditory mirror neurons and their pivotal role in comprehending the emotional valence of different words, thereby influencing our feelings. This will advance our understanding of the human brain and empower us to make informed decisions. The study is being conducted with the HSE Automated system for non-invasive brain stimulation, which allows for simultaneous recording of brain activity and eye movement.

Effects of sleep deprivation on cortical excitability: A threshold-tracking TMS study and review of the literature

ObjectiveInsufficient sleep is linked to several health problems. Previous studies on the effects of sleep deprivation on cortical excitability using conventional transcranial magnetic stimulation (TMS) included a limited number of modalities, and few inter-stimulus intervals (ISIs) and showed conflicting results. This study aimed to investigate the effects of sleep deprivation on cortical excitability through threshold-tracking TMS, using a wide range of protocols at multiple ISIs. MethodsFifteen healthy subjects (mean age ± SD: 36 ± 3.34 years) were included. The following tests were performed before and after 24 h of sleep deprivation using semi-automated threshold-tacking TMS protocols: short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) at 11 ISIs between 1 and 30 ms, short interval intracortical facilitation (SICF) at 14 ISIs between 1 and 4.9 ms, long interval intracortical inhibition (LICI) at 6 ISIs between 50 and 300 ms, and short-latency afferent inhibition (SAI) at 12 ISIs between 16 and 30 ms. ResultsNo significant differences were observed between pre- and post-sleep deprivation measurements for SICI, ICF, SICF, or LICI at any ISIs (p < 0.05). As for SAI, we found a difference at 28 ms (p = 0.007) and 30 ms (p = 0.04) but not at other ISIs. ConclusionsSleep deprivation does not affect cortical excitability except for SAI. SignificanceThis study confirms some of the previous studies while contradicting others.

Cerebellar transcranial magnetic stimulation in psychotic disorders: intermittent, continuous, and sham theta-burst stimulation on time perception and symptom severity.

The cerebellum contributes to the precise timing of non-motor and motor functions, and cerebellum abnormalities have been implicated in psychosis pathophysiology. In this study, we explored the effects of cerebellar theta burst stimulation (TBS), an efficient transcranial magnetic stimulation protocol, on temporal discrimination and self-reported mood and psychotic symptoms. We conducted a case-crossover study in which patients with psychosis (schizophrenias, schizoaffective disorders, or bipolar disorders with psychotic features) were assigned to three sessions of TBS to the cerebellar vermis: one session each of intermittent (iTBS), continuous (cTBS), and sham TBS. Of 28 enrolled patients, 26 underwent at least one TBS session, and 20 completed all three. Before and immediately following TBS, participants rated their mood and psychotic symptoms and performed a time interval discrimination task (IDT). We hypothesized that cerebellar iTBS and cTBS would modulate these measures in opposing directions, with iTBS being adaptive and cTBS maladaptive. Reaction time (RT) in the IDT decreased significantly after iTBS vs. Sham (LS-mean difference = -73.3, p = 0.0001, Cohen's d = 1.62), after iTBS vs. cTBS (LS-mean difference = -137.6, p < 0.0001, d = 2.03), and after Sham vs. cTBS (LS-mean difference = -64.4, p < 0.0001, d = 1.33). We found no effect on IDT accuracy. We did not observe any effects on symptom severity after correcting for multiple comparisons. We observed a frequency-dependent dissociation between the effects of iTBS vs. cTBS to the cerebellar midline on the reaction time of interval discrimination in patients with psychosis. iTBS showed improved (adaptive) while cTBS led to worsening (maladaptive) speed of response. These results demonstrate behavioral target engagement in a cognitive dimension of relevance to patients with psychosis and generate testable hypotheses about the potential therapeutic role of cerebellar iTBS in this clinical population. clinicaltrials.gov, identifier NCT02642029.

Somatosensory evoked potentials amplitude is enhanced after non-invasive brain stimulation in chronic ischemic stroke: Preliminary results from a randomised control trial

ObjectiveTo investigate the effects of transcranial electrical and magnetic non-invasive brain stimulation (NIBS) protocols on somatosensory evoked potential (SEP) in chronic ischemic stroke. Methods33 patients were randomly assigned to one of the four treatment groups of the transcranial direct current stimulation (tDCS) and/or repetitive transcranial magnetic stimulation (rTMS) protocol. SEP parameters were recorded before and after ten days of the treatment session. All the statistical analyses were carried out using SPSS version 19. ResultsIt was found that there is a statistically significant improvement in the N20-P22 mean amplitude after treatment sessions in all groups except the group where tDCS and rTMS groups were sham. On paired t-tests, the difference betweeen post and pre-stimulation SEP amplitudes for the real tDCS and real rTMS coupled group was 1.045 ± 0.732 (p value = 0.005). For sham tDCS+real rTMS group, 1.05 ± 0.96 (P = 0.04); for real tDCS+sham rTMS 0.543 ± 0.332 (P = 0.01) and for double sham stimulation, 0.204 ± 0.648 (P = 0.4) respectively ConclusionIn ischemic stroke patients, either or coupled true transcranial tDCS and rTMS was found to be safe and significantly enhanced the amplitude of cortical somatosensory potentials when combined with standard physiotherapy, in the interim analysis of an ongoing randomised controlled trial. Clinical Trial Registry of IndiaCTRI/2019/11/022009 SignificanceThe results of this research indicates the importance of RCTs in developing robust improved NIBS protocols coupled to physiotherapy to enhance the sensory-motor functional recovery following ischemic stroke.

Fast and accurate computational E-field dosimetry for group-level transcranial magnetic stimulation targeting

Transcranial magnetic stimulation (TMS) is used to study brain function and treat mental health disorders. During TMS, a coil placed on the scalp induces an E-field in the brain that modulates its activity. TMS is known to stimulate regions that are exposed to a large E-field. Clinical TMS protocols prescribe a coil placement based on scalp landmarks. There are inter-individual variations in brain anatomy that result in variations in the TMS-induced E-field at the targeted region and its outcome. These variations across individuals could in principle be minimized by developing a large database of head subjects and determining scalp landmarks that maximize E-field at the targeted brain region while minimizing its variation using computational methods. However, this approach requires repeated execution of a computational method to determine the E-field induced in the brain for a large number of subjects and coil placements. We developed a probabilistic matrix decomposition-based approach for rapidly evaluating the E-field induced during TMS for a large number of coil placements due to a pre-defined coil model. Our approach can determine the E-field induced in over 1 Million coil placements in 9.5 h, in contrast, to over 5 years using a brute-force approach. After the initial set-up stage, the E-field can be predicted over the whole brain within 2–3 ms and to 2% accuracy. We tested our approach in over 200 subjects and achieved an error of <2% in most and <3.5% in all subjects. We will present several examples of bench-marking analysis for our tool in terms of accuracy and speed. Furthermore, we will show the methods’ applicability for group-level optimization of coil placement for illustration purposes only. The software implementation link is provided in the appendix.

Dissociation of Centrally and Peripherally Induced Transcranial Magnetic Stimulation Effects in Nonhuman Primates.

Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation method that is rapidly growing in popularity for studying causal brain-behavior relationships. However, its dose-dependent centrally induced neural mechanisms and peripherally induced sensory costimulation effects remain debated. Understanding how TMS stimulation parameters affect brain responses is vital for the rational design of TMS protocols. Studying these mechanisms in humans is challenging because of the limited spatiotemporal resolution of available noninvasive neuroimaging methods. Here, we leverage invasive recordings of local field potentials in a male and a female nonhuman primate (rhesus macaque) to study TMS mesoscale responses. We demonstrate that early TMS-evoked potentials show a sigmoidal dose-response curve with stimulation intensity. We further show that stimulation responses are spatially specific. We use several control conditions to dissociate centrally induced neural responses from auditory and somatosensory coactivation. These results provide crucial evidence regarding TMS neural effects at the brain circuit level. Our findings are highly relevant for interpreting human TMS studies and biomarker developments for TMS target engagement in clinical applications.SIGNIFICANCE STATEMENT Transcranial magnetic stimulation (TMS) is a widely used noninvasive brain stimulation method to stimulate the human brain. To advance its utility for clinical applications, a clear understanding of its underlying physiological mechanisms is crucial. Here, we perform invasive electrophysiological recordings in the nonhuman primate brain during TMS, achieving a spatiotemporal precision not available in human EEG experiments. We find that evoked potentials are dose dependent and spatially specific, and can be separated from peripheral stimulation effects. This means that TMS-evoked responses can indicate a direct physiological stimulation response. Our work has important implications for the interpretation of human TMS-EEG recordings and biomarker development.

Accelerated transcranial magnetic stimulation for major depressive disorder: A quick path to relief?

Transcranial magnetic stimulation (TMS) is a safe, tolerable, and evidence-based intervention for major depressive disorder (MDD). However, even after decades of research, nearly half of the patients with MDD fail to respond to conventional TMS, with responding slowly and requiring daily attendance at the treatment site for 4-6 weeks. To intensify antidepressant efficacy and shorten treatment duration, accelerated TMS protocols, which involve multiple sessions per day over a few days, have been proposed and evaluated for safety and viability. We reviewed and summarized the current knowledge in accelerated TMS, including stimulation parameters, antidepressant efficacy, anti-suicidal efficacy, safety, and adverse effects. Limitations and suggestions for future directions are also addressed, along with a brief discussion on the application of accelerated TMS during the COVID-19 pandemic. This article is categorized under: Neuroscience > Clinical Neuroscience.