Solute | TMS Resource Portal

Welcome to TMS Solutions' resource portal, Solute, where you will find the latest informative articles about mental health, neuromodulation techniques, and TMS.

Relevant Posts

Dec 31, 2021 11:12:00 AM

Transcranial Magnetic Stimulation (TMS) During Pregnancy: A Fetal Risk Factor

Source: Australasian Psychiatry. 29(2):226-229, 2021 04.

Authors: Pridmore S; Turnier-Shea Y; Rybak M; Pridmore W

OBJECTIVE: To examine reports of Transcranial Magnetic Stimulation (TMS) during pregnancy for evidence of fetal risk.

METHOD: PubMed was used to locate relevant literature for the years 1998-2020 and reference lists were examined for materials not located electronically.

RESULTS: Ten reports were located dealing with 67 births over 20 years. Stimulation was applied is all trimesters, at low and high frequency, and as intermittent theta-burst stimulation. No mother or baby experienced a serious event.

CONCLUSIONS: Certainty awaits large, standardized studies. However, the available reports provide no evidence that TMS to mother during pregnancy has detrimental effects on the fetus.

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Dec 31, 2021 11:10:00 AM

Cortical Mechanisms Underlying Variability in Intermittent Theta-burst Stimulation-Induced Plasticity: A TMS-EEG Study

Source: Clinical Neurophysiology. 132(10):2519-2531, 2021 10.

Authors: Leodori G; Fabbrini A; De Bartolo MI; Costanzo M; Asci F; Palma V; Belvisi
D; Conte A; Berardelli A

OBJECTIVE: To test the hypothesis that intermittent theta burst stimulation (iTBS) variability depends on the ability to engage specific neurons in the primary motor cortex (M1).

METHODS: In a sham-controlled interventional study on 31 healthy volunteers, we used concomitant transcranial magnetic stimulation (TMS) and electroencephalography (EEG). We compared baseline motor evoked potentials (MEPs), M1 iTBS-evoked EEG oscillations, and resting-state EEG (rsEEG) between subjects who did and did not show MEP facilitation following iTBS. We also investigated whether baseline MEP and iTBS-evoked EEG oscillations could explain inter and intraindividual variability in iTBS aftereffects.

RESULTS: The facilitation group had smaller baseline MEPs than the no-facilitation group and showed more iTBS-evoked EEG oscillation synchronization in the alpha and beta frequency bands. Resting-state EEG power was similar between groups and iTBS had a similar non-significant effect on rsEEG in both groups. Baseline MEP amplitude and beta iTBS-evoked EEG oscillation power explained both inter and intraindividual variability in MEP modulation following iTBS.

CONCLUSIONS: The results show that variability in iTBS-associated plasticity depends on baseline corticospinal excitability and on the ability of iTBS to engage M1 beta oscillations.

SIGNIFICANCE: These observations can be used to optimize iTBS investigational and therapeutic applications.

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Dec 30, 2021 11:39:00 AM

Clinical Response of Major Depressive Disorder Patients With Suicidal Ideation to Individual Target-Transcranial Magnetic Stimulation

Source: Frontiers in Psychiatry. 12 (no pagination), 2021. Article Number: 768819.

Date of Publication:
05 Nov 2021.

Tang N.; Sun C.; Wang Y.; Li X.; Liu J.; Chen Y.; Sun L.; Rao Y.; Li S.; Qi S.; Wang H.

Suicidal ideation increases precipitously in patients with depression,
contributing to the risk of suicidal attempts. Despite the recent advancement in transcranial magnetic stimulation, its effectiveness in depression disorder and its wide acceptance, the network mechanisms of the clinical response to suicidal ideation in major depressive disorder remain unclear. Independent component analysis for neuroimaging data allows the identification of functional network connectivity which may help to explore the neural basis of suicidal ideation in major depressive disorder. Resting-state functional magnetic resonance imaging data and clinical scales were collected from 30 participants (15 major depressive
patients with suicidal ideation and 15 healthy subjects). Individual target-transcranial magnetic stimulation (IT-TMS) was then used to decrease the subgenual anterior cingulate cortex activity through the left dorsolateral prefrontal cortex. Thirty days post IT-TMS therapy, seven of 15 patients (46.67%) met suicidal remission criteria, and 12 patients (80.00%) met depression remission criteria. We found that IT-TMS could restore the abnormal functional network connectivity between default mode network and precuneus network, left executive control network and sensory-motor network. Furthermore, the changes in functional network connectivity between the default mode network and precuneus network were associated with suicidal ideation, and depressive symptoms were related to
connectivity between left executive control network and sensory-motor network. These findings illustrate that IT-TMS is an effective protocol for the accurate restoration of impaired brain networks, which is consistent with clinical symptoms.

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Dec 30, 2021 11:06:00 AM

Influence of BDNF Val66Met Polymorphism on Excitatory-Inhibitory Balance and Plasticity in Human Motor Cortex

Source: Clinical Neurophysiology. 132(11):2827-2839, 2021 11.

Authors: Cash RFH; Udupa K; Gunraj CA; Mazzella F; Daskalakis ZJ; Wong AHC; Kennedy JL; Chen R

OBJECTIVE: While previous studies showed that the single nucleotide polymorphism (Val66Met) of brain-derived neurotrophic factor (BDNF) can impact neuroplasticity, the influence of BDNF genotype on cortical circuitry and relationship to neuroplasticity remain relatively unexplored in human.

METHODS: Using individualised transcranial magnetic stimulation (TMS) parameters, we explored the influence of the BDNF Val66Met polymorphism on
excitatory and inhibitory neural circuitry, its relation to I-wave TMS (ITMS) plasticity and effect on the excitatory/inhibitory (E/I) balance in 18 healthy individuals.

RESULTS: Excitatory and inhibitory indexes of neurotransmission were reduced in Met allele carriers. An E/I balance was evident, which was influenced by BDNF with higher E/I ratios in Val/Val homozygotes. Both long-term potentiation (LTP-) and depression (LTD-) like ITMS plasticity were greater in Val/Val homozygotes. LTP- but not LTD-like effects were restored in Met allele carriers by increasing stimulus intensity to compensate for reduced excitatory transmission.

CONCLUSIONS: The influence of BDNF genotype may extend beyond neuroplasticity to neurotransmission. The E/I balance was evident in human motor cortex, modulated by BDNF and measurable using TMS. Given the limited sample, these preliminary findings warrant further investigation.

SIGNIFICANCE: These novel findings suggest a broader role of BDNF genotype on neurocircuitry in human motor cortex.

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Dec 29, 2021 12:25:00 PM

Treatment of Mixed Depression with Theta-burst Stimulation (TBS): Results From a Double-Blind, Randomized, Sham-Controlled Clinical Trial

Source: Neuropsychopharmacology. 46(13):2257-2265, 2021 12.

Tavares DF; Suen P; Rodrigues Dos Santos CG; Moreno DH; Lane Valiengo LDC; Klein I; Borrione L; Marques Forte P; Brunoni AR; Alberto Moreno R

Mixed depression is probably different in terms of clinical course and
response to treatment. Repetitive transcranial magnetic stimulation (rTMS) is well established in non-mixed depression, and theta-burst stimulation (TBS) protocol is replacing conventional protocols because of noninferiority and reduced delivery time. However, TBS has not been adequately studied in mixed states. This study was a double-blind, six-week, sham-controlled, and randomized clinical trial of bilateral TBS targeting the right and left dorsolateral prefrontal cortex, respectively.
Adults with bipolar and major depressive disorder experiencing an acute mixed depression were eligible if they had not benefited from a first- or second-line treatment for acute unipolar or bipolar depression recommended by the Canadian Network for Mood and Anxiety Treatments. Out of 100 patients included, 90 composed modified intention-to-treat sample, which was patients that completed at least one week of the intervention. There were no significant differences in Montgomery-Asberg depression rating scale score changes (least squares mean difference between groups at week 3, -0.06 [95% CI, - 3.39 to 3.51; P = 0.97] in favor of sham TBS). Response and remission rates per MADRS were also not statistically
different among active and sham groups (35.7% vs. 43.7%, and 28.5% vs. 37.5% respectively at week 6, ps > 0.51). No other analyses from baseline to weeks 3 or 6 revealed significant time x group interaction or mean differences among groups in the mITT sample. Bilateral TBS targeting the DLPFC is not efficacious as an add-on treatment of acute bipolar and unipolar mixed depression.

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Dec 29, 2021 11:01:00 AM

Theta-burst Versus 20 Hz Repetitive Transcranial Magnetic Stimulation in Neuropathic Pain: A Head-to-Head Comparison

Source: Clinical Neurophysiology. 132(10):2702-2710, 2021 10.

Authors: Andre-Obadia N; Magnin M; Garcia-Larrea L

OBJECTIVE: High-frequency repetitive transcranial magnetic stimulation (rTMS) has been shown to reduce neuropathic pain, but intermittent "theta-burst" stimulation (iTBS) could be a better alternative because of shorter duration and greater ability to induce cortical plasticity. Here we compared head-to-head the pain-relieving efficacy of the two modalities when applied daily for 5 days to patients with neuropathic pain.

METHODS: Forty-six patients received 20 Hz-rTMS and/or iTBS protocols and 39 of them underwent the full two procedures in a random cross-over design. They rated pain intensity, sleep quality, fatigue and general health status daily during 5 consecutive weeks.

RESULTS: Pain relief during the month following stimulation was superior after 20 Hz-rTMS relative to iTBS (F(1,38) = 4.645; p = 0.037). Correlation between respective levels of maximal relief showed a significant deviation toward the 20 Hz-rTMS effect. A greater proportion of individuals responded to 20 Hz-rTMS (52% vs 32%, 95 %CI[0.095-3.27]; p = 0.06), and reports of fatigue significantly improved after 20 Hz-rTMS relative to iTBS (p = 0.01). General health and sleep quality scores did not differentiate both techniques.

CONCLUSIONS: High-frequency rTMS appeared superior to iTBS for neuropathic pain relief.

SIGNIFICANCE: Adequate matching between the oscillatory activity of motor cortex and that of rTMS may increase synaptic efficacy, thus enhancing functional connectivity of motor cortex with distant structures involved in pain regulation.

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Dec 28, 2021 11:36:00 AM

The Effects of Non-Invasive Brain Stimulation on Sleep Disturbances Among Different Neurological and Neuropsychiatric Conditions: A Systematic Review [Review]

Source: Sleep Medicine Reviews. 55:101381, 2021 02.

Herrero Babiloni A; Bellemare A; Beetz G; Vinet SA; Martel MO; Lavigne GJ;
De Beaumont L


Sleep disturbances (e.g., difficulty to initiate or maintain sleep) and poor sleep quality are major health concerns that accompany several neurological and neuropsychiatric clinical conditions where different brain circuitries are affected (e.g., chronic pain, Parkinson's disease or depression), having a great impact in the individual's well-being, quality of life, and the socioeconomic system. Sleep disturbances in absence of breathing or neurological disorders are mainly treated with medications (e.g., benzodiazepines, hypnotics, etc.) and cognitive behavioral therapy, which are associated with side-effects and adherence issues, respectively.
Moreover, these therapies do not seem to work effectively for some individuals. Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are non-invasive stimulation techniques used to treat several conditions and symptoms. Results from this systematic review indicate that rTMS and tDCS are safe and have potential to improve insomnia symptoms and sleep disturbances across different types of neurological and neuropsychiatric diseases.
However, uncontrolled and quasi experimental studies with high risk of bias were included. Thus, although these results can help developing the field, caution in interpreting them is advised. Additional research efforts are needed to reduce bias, improve quality, and characterize optimal brain stimulation parameters to promote their efficacy on sleep related outcomes.

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Dec 28, 2021 10:58:00 AM

Operculo-insular and Anterior Cingulate Plasticity Induced by Transcranial Magnetic Stimulation in the Human Motor Cortex: A Dynamic Casual Modeling Study

Source: Journal of Neurophysiology. 125(4):1180-1190, 2021 04 01.

Authors: Hodkinson DJ; Bungert A; Bowtell R; Jackson SR; Jung J

Abstract: The ability to induce neuroplasticity with noninvasive brain stimulation
techniques offers a unique opportunity to examine the human brain systems involved in pain modulation. In experimental and clinical settings, the primary motor cortex (M1) is commonly targeted to alleviate pain, but its mechanism of action remains unclear. Using dynamic causal modeling (DCM) and Bayesian model selection (BMS), we tested seven competing hypotheses about how transcranial magnetic stimulation (TMS) modulates the directed influences (or effective connectivity) between M1 and three distinct cortical areas of the medial and lateral pain systems, including the insular cortex (INS), anterior cingulate cortex (ACC), and parietal operculum cortex (PO). The data set included a novel fMRI acquisition collected synchronously with M1 stimulation during rest and while
performing a simple hand motor task. DCM and BMS showed a clear preference
for the fully connected model in which all cortical areas receive input directly from M1, with facilitation of the connections INS->M1, PO->M1, and ACC->M1, plus increased inhibition of their reciprocal connections. An additional DCM analysis comparing the reduced models only corresponding to networks with a sparser connectivity within the full model showed that M1 input into the INS is the second-best model of plasticity following TMS manipulations. The results reported here provide a starting point for investigating whether pathway-specific targeting involving M1INS improves analgesic response beyond conventional targeting. We eagerly await future empirical data and models that tests this hypothesis. NEW & NOTEWORTHY Transcranial magnetic stimulation of the primary motor cortex (M1) is a promising treatment for chronic pain, but its mechanism of action remains unclear. Competing dynamic causal models of effective connectivity between M1 and medial and lateral pain systems suggest direct input into the insular, anterior cingulate cortex, and parietal operculum. This supports the hypothesis that analgesia produced from M1 stimulation most likely acts through the activation of top-down processes associated with intracortical modulation.

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Dec 27, 2021 5:57:00 PM

Differences in Brain Structure and Theta-burst Stimulation-Induced Plasticity Implicate the Corticomotor System in Loss of Function After Musculoskeletal Injury

Source: Journal of Neurophysiology. 125(4):1006-1021, 2021 04 01.

Authors: Flanagan SD; Proessl F; Dunn-Lewis C; Sterczala AJ; Connaboy C; Canino MC; Beethe AZ; Eagle SR; Szivak TK; Onate JA; Volek JS; Maresh CM; Kaeding CC;
Kraemer WJ

Abstract: Traumatic musculoskeletal injury (MSI) may involve changes in corticomotor structure and function, but direct evidence is needed. To determine the corticomotor basis of MSI, we examined interactions among skeletomotor function, corticospinal excitability, corticomotor structure (cortical thickness and white matter microstructure), and intermittent theta burst stimulation (iTBS)-induced plasticity. Nine women with unilateral anterior cruciate ligament rupture (ACL) 3.2 +/- 1.1 yr prior to the study and 11 matched controls (CON) completed an MRI session followed by an offline plasticity-probing protocol using a randomized, sham-controlled, double-blind, cross-over study design. iTBS was applied to the injured (ACL) or nondominant (CON) motor cortex leg representation (M1LEG) with
plasticity assessed based on changes in skeletomotor function and corticospinal excitability compared with sham iTBS. The results showed persistent loss of function in the injured quadriceps, compensatory adaptations in the uninjured quadriceps and both hamstrings, and injury-specific increases in corticospinal excitability. Injury was associated with lateralized reductions in paracentral lobule thickness, greater centrality of nonleg corticomotor regions, and increased primary
somatosensory cortex leg area inefficiency and eccentricity. Individual responses to iTBS were consistent with the principles of homeostatic metaplasticity; corresponded to injury-related differences in skeletomotor function, corticospinal excitability, and corticomotor structure; and suggested that corticomotor adaptations involve both hemispheres. Moreover, iTBS normalized skeletomotor function and corticospinal excitability in ACL. The results of this investigation directly confirm corticomotor involvement in chronic loss of function after traumatic MSI, emphasize the sensitivity of the corticomotor system to skeletomotor events and behaviors, and raise the possibility that brain-targeted
therapies could improve recovery. NEW & NOTEWORTHY Traumatic musculoskeletal injuries may involve adaptive changes in the brain that contribute to loss of function. Our combination of neuroimaging and theta burst transcranial magnetic stimulation (iTBS) revealed distinct patterns of iTBS-induced plasticity that normalized differences in muscle and brain function evident years after unilateral knee ligament rupture. Individual responses to iTBS corresponded to injury-specific differences in brain structure and physiological activity, depended on skeletomotor deficit severity, and suggested that corticomotor adaptations involve both hemispheres.

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Dec 27, 2021 12:23:00 PM

Theta-burst Stimulation Over the Prefrontal Cortex: Effects on Cerebral Oximetry and Cardiovascular Measures in Healthy Humans

Source: Neuroscience Letters. 752:135792, 2021 05 01.

Pinto N; Goncalves H; Silva R; Duarte M; Gama J; Vaz Pato M

Theta Burst Stimulation (TBS) is a non-invasive neurophysiological
technique, able to induce changes in synaptic activity. Research suggests that TBS may induce changes in cerebral oxygenation, cerebral blood flow, blood pressure and heart rate but there are conflicting results across studies. Thus, the objective of our sham-controlled study is to evaluate if TBS applied to the dorsolateral prefrontal cortex (DLPFC) of healthy volunteers produces changes in cerebral oximetry, heart rate and blood pressure. Forty-nine volunteers of both sexes were randomly allocated to one of five stimulation groups. Before and after real TBS or sham stimulation, blood pressure, heart rate, and cerebral oxygenation of the
volunteers were measured. Cerebral oxygenation values were obtained with a near infra-red spectroscopy system. We found a significant reduction in left cortex oximetry after continuous TBS (cTBS) over the left DLPFC (p = 0.039) and a non-significant reduction in right cortex oximetry (p = 0.052). Right hemisphere inhibition (using cTBS) seemed to originate a significant reduction of 8 mmHg in systolic arterial pressure. No other changes were seen in oximetry, cardiac frequency and diastolic arterial pressure. In our group of normal subjects, cTBS applied to the left DLPFC was able to reduce oxygenation in the left cortex. Right hemisphere inhibition was associated with a significant reduction in systolic pressure.

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Dec 26, 2021 12:20:00 PM

The Role of Continuous Theta-burst TMS in the Neurorehabilitation of Subacute Stroke Patients: A Placebo-Controlled Study

Source: Frontiers in Neurology. 12 (no pagination), 2021. Article Number: 749798.

Date of Publication:
04 Nov 2021.

Dionisio A.; Gouveia R.; Castelhano J.; Duarte I.C.; Santo G.C.; Sargento-Freitas J.; Duecker F.; Castelo-Branco M.


Objectives: Transcranial magnetic stimulation, in particular continuous theta burst (cTBS), has been proposed for stroke rehabilitation, based on the concept that inhibition of the healthy hemisphere helps promote the recovery of the lesioned one. We aimed to study its effects on cortical excitability, oscillatory patterns, and motor function, the main aim being to identify potentially beneficial neurophysiological effects.

Material(s) and Method(s): We applied randomized real or placebo stimulation over the unaffected primary motor cortex of 10 subacute (7 +/- 3 days) post-stroke patients. Neurophysiological measurements were performed using electroencephalography and electromyography. Motor function was assessed with the Wolf Motor Function Test. We performed a repeated measure study with the recordings taken pre-, post-cTBS, and at 3 months' follow-up.

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Dec 23, 2021 5:51:00 PM

A Patient-Oriented Analysis of Pain Side Effect: A Step to Improve the Patient's Experience During rTMS

Source: Brain Stimulation. 14(5):1147-1153, 2021 Sep-Oct.

Authors: Humaira A; Gao S; Gregory E; Ridgway L; Blumberger DM; Downar J; Daskalakis ZJ; Ainsworth NJ; Wu L; Butterfield M; Vila-Rodriguez F

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an efficacious and well-tolerated intervention for treatment-resistant depression (TRD). A novel rTMS protocol, intermittent theta burst stimulation (iTBS) has been recently implemented in clinical practice, and it is essential to characterize the factors associated to pain and the trajectory of pain of iTBS compared to standard rTMS protocols.

OBJECTIVE: We aimed to characterize the side effect profile and the pain trajectories of High-Frequency Left (HFL) and iTBS in TRD patients in the THREE-D trial. We also investigated factors associated to pain and the relationship between pain and clinical outcomes.

METHODS: 414 patients were randomized to either HFL or iTBS. Severity of pain was measured after every treatment. General Estimating Equation was used to investigate factors associated with pain. Latent class linear mixed model was used to investigate latent classes of pain trajectories over the course of rTMS.

RESULTS: Higher level of pain was associated with older age, higher stimulation intensity, higher anxiety, female, and non-response. The severity of pain significantly declined over the course of treatments with a steeper decrease early on in the course of the treatment in both protocols, and four latent pain trajectories were identified. The less favorable pain trajectories were associated with non-response and higher stimulation intensity.

CONCLUSIONS: HFL and iTBS were associated with similar factors and pain trajectories, although iTBS was more uncomfortable. Response to rTMS was
associated with less pain and more favorable pain trajectories furthering the evince base of overlapping neurobiological underpinnings of mood and pain. We translated these results into patient-oriented information to aid in the decision-making process when considering rTMS.

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Dec 23, 2021 11:30:00 AM

Using Cortical Non-Invasive Neuromodulation as a Potential Preventive Treatment in Schizophrenia - A review [Review]

Source: Brain Stimulation. 14(3):643-651, 2021 May-Jun.

Authors: Edemann-Callesen H; Winter C; Hadar R

BACKGROUND: Evidence suggests that schizophrenia constitutes a neurodevelopmental disorder, characterized by a gradual emergence of behavioral and neurobiological abnormalities over time. Therefore, applying early interventions to prevent later manifestation of symptoms is appealing.

OBJECTIVE: This review focuses on the use of cortical neuromodulation in schizophrenia and its potential as a preventive treatment approach. We present clinical and preclinical findings investigating the use of neuromodulation in schizophrenia, including the current research focusing on cortical non-invasive stimulation and its possibility as a future preventive treatment.

METHODS: We performed a search in Medline (PubMed) in September 2020 using a combination of relevant medical subject headings (MeSH) and text words. The search included human and preclinical trials as well as existing systematic reviews and meta-analysis. There were no restrictions on language or the date of publication.

RESULTS: Neurodevelopmental animal models may be used to investigate how the disease progresses and thus which brain areas ideally should be targeted at a given time point. Here, abnormalities of the prefrontal cortex have been often identified as an early and persistent impairment in schizophrenia. Currently there is insufficient evidence to either support or refute the use of neuromodulation to the cortex in adult patients with already manifested symptoms. However, preclinical results show that early non-invasive neuromodulation to the prefrontal cortex of adolescent animals, sufficiently prevents later psychosis-relevant abnormalities in
adulthood. This points to the promising potential of cortical non-invasive neuromodulation as a preventive treatment when applied early in the course of the disease.

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Dec 22, 2021 5:48:00 PM

High-Frequency rTMS Over the Dorsolateral Prefrontal Cortex on Chronic and Provoked Pain: A Systematic Review and Meta-Analysis. [Review]

Source: Brain Stimulation. 14(5):1135-1146, 2021 Sep-Oct.

Authors: Che X; Cash RFH; Luo X; Luo H; Lu X; Xu F; Zang YF; Fitzgerald PB; Fitzgibbon BM

BACKGROUND: High-frequency rTMS over the dorsolateral prefrontal cortex (DLPFC) has demonstrated mixed effects on chronic and provoked pain.

OBJECTIVES/METHODS: In this study, a meta-analysis was conducted to characterise the potential analgesic effects of high-frequency rTMS over the DLPFC on both chronic and provoked pain.

RESULTS: A total of 626 studies were identified in a systematic search. Twenty-six eligible studies were included for the quantitative review, among which 17 modulated chronic pain and the remaining investigated the influence on provoked pain. The left side DLPFC was uniformly targeted in the chronic pain studies. While our data identified no overall effect of TMS across chronic pain conditions, there was a significant short-term analgesia in neuropathic pain conditions only (SMD = -0.87). In terms of long-lasting analgesia, there was an overall pain reduction in the midterm (SMD = -0.53, 24.6 days average) and long term (SMD = -0.63, 3 months
average) post DLPFC stimulation, although these effects were not observed within specific chronic pain conditions. Surprisingly, the number of sessions was demonstrated to have no impact on rTMS analgesia. In the analysis of provoked pain, our data also indicated a significant analgesic effect following HF-rTMS over the DLPFC (SMD = -0.73). Importantly, we identified a publication bias in the studies of provoked pain but not for chronic pain conditions.

CONCLUSIONS: Overall, our findings support that HF-DLPFC stimulation is able to induce an analgesic effect in chronic pain and in response to provoked pain. These results highlight the potential of DLPFC-rTMS in the management of certain chronic pain conditions and future directions are discussed to enhance the potential long-term analgesic effects.

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Dec 21, 2021 5:44:00 PM

Theta-burst Stimulation Entrains Frequency-Specific Oscillatory Responses

Source: Brain Stimulation. 14(5):1271-1284, 2021 Sep-Oct.

Authors: Solomon EA; Sperling MR; Sharan AD; Wanda PA; Levy DF; Lyalenko A; Pedisich I; Rizzuto DS; Kahana MJ

BACKGROUND: Brain stimulation has emerged as a powerful tool in human neuroscience, becoming integral to next-generation psychiatric and neurologic therapeutics. Theta-burst stimulation (TBS), in which electrical pulses are delivered in rhythmic bouts of 3-8 Hz, seeks to recapitulate neural activity seen endogenously during cognitive tasks. A growing literature suggests that TBS can be used to alter or enhance cognitive processes, but little is known about how these stimulation events influence underlying neural activity.

OBJECTIVE: Our study sought to investigate the effect of direct electrical TBS on mesoscale neural activity in humans by asking (1) whether TBS evokes persistent theta oscillations in cortical areas, (2) whether these oscillations occur at the stimulated frequency, and (3) whether stimulation events propagate in a manner consistent with underlying functional and structural brain architecture.

METHODS: We recruited 20 neurosurgical epilepsy patients with indwelling electrodes and delivered direct cortical TBS at varying locations and frequencies. Simultaneous iEEG was recorded from non-stimulated electrodes and analyzed to understand how TBS influences mesoscale neural activity.

RESULTS: We found that TBS rapidly evoked theta rhythms in widespread brain regions, preferentially at the stimulation frequency, and that these oscillations persisted for hundreds of milliseconds post stimulation offset. Furthermore, the functional connectivity between recording and stimulation sites predicted the strength of theta response, suggesting that underlying brain architecture guides the flow of stimulation through the brain.

CONCLUSIONS: By demonstrating that cortical TBS induces frequency-specific oscillatory responses, our results suggest this technology can be used to directly and predictably influence the activity of cognitively-relevant brain networks.

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Dec 21, 2021 5:41:00 PM

Stimulation of the Left Dorsolateral Prefrontal Cortex With Slow rTMS Enhances Verbal Memory Formation

Source: Plos Biology. 19(9):e3001363, 2021 09.

Authors: van der Plas M; Braun V; Stauch BJ; Hanslmayr S

Abstract: Encoding of episodic memories relies on stimulus-specific information
processing and involves the left prefrontal cortex. We here present an incidental finding from a simultaneous EEG-TMS experiment as well as a replication of this unexpected effect. Our results reveal that stimulating the left dorsolateral prefrontal cortex (DLPFC) with slow repetitive transcranial magnetic stimulation (rTMS) leads to enhanced word memory performance. A total of 40 healthy human participants engaged in a list learning paradigm. Half of the participants (N = 20) received 1 Hz rTMS to the left DLPFC, while the other half (N = 20) received 1 Hz rTMS to the vertex and served as a control group. Participants receiving left DLPFC
stimulation demonstrated enhanced memory performance compared to the control group. This effect was replicated in a within-subjects experiment where 24 participants received 1 Hz rTMS to the left DLPFC and vertex. In this second experiment, DLPFC stimulation also induced better memory performance compared to vertex stimulation. In addition to these behavioural effects, we found that 1 Hz rTMS to DLPFC induced stronger beta power modulation in posterior areas, a state that is known to be beneficial for memory encoding. Further analysis indicated that beta modulations did not have an oscillatory origin. Instead, the observed beta modulations were a result of a spectral tilt, suggesting inhibition of
these parietal regions. These results show that applying 1 Hz rTMS to DLPFC, an area involved in episodic memory formation, improves memory performance via modulating neural activity in parietal regions.

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Dec 21, 2021 11:27:00 AM

Neuromodulatory Treatments for Psychiatric Disease: A Comprehensive Survey of the Clinical Trial Landscape [Review]

Source: Brain Stimulation. 14(5):1393-1403, 2021 Sep-Oct.

Authors: Elias GJB; Boutet A; Parmar R; Wong EHY; Germann J; Loh A; Paff M; Pancholi A; Gwun D; Chow CT; Gouveia FV; Harmsen IE; Beyn ME; Santarnecchi E; Fasano A; Blumberger DM; Kennedy SH; Lozano AM; Bhat V

BACKGROUND: Numerous neuromodulatory therapies are currently under investigation or in clinical use for the treatment of psychiatric conditions.

OBJECTIVE/HYPOTHESIS: We sought to catalogue past and present human research studies on psychiatric neuromodulation and identify relevant trends in this field.

METHODS: ( and the International Clinical Trials Registry Platform ( were queried in March 2020 for trials assessing the outcome of neuromodulation for psychiatric disorders. Relevant trials were categorized by variables such as neuromodulation
modality, country, brain target, publication status, design, and funding source.

RESULTS: From 72,086 initial search results, 1252 unique trials were identified. The number of trials registered annually has consistently increased. Half of all trials were active and a quarter have translated to publications. The largest proportion of trials involved depression (45%), schizophrenia (18%), and substance use disorders (14%). Trials spanned 37 countries; China, the second largest contributor (13%) after the United States (28%), has increased its output substantially in recent years. Over
75% of trials involved non-convulsive non-invasive modalities (e.g., transcranial magnetic stimulation), while convulsive (e.g., electroconvulsive therapy) and invasive modalities (e.g., deep brain stimulation) were less represented. 72% of trials featured approved or cleared interventions. Characteristic inter-modality differences were observed with respect to enrollment size, trial design/phase, and funding. Dorsolateral prefrontal cortex accounted for over half of focal neuromodulation trial targets. The proportion of trials examining biological correlates of neuromodulation has increased.

CONCLUSION(S): These results provide a comprehensive overview of the state of psychiatric neuromodulation research, revealing the growing scope and internationalism of this field.

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Dec 20, 2021 5:37:00 PM

Two Forms of Short-Interval Intracortical Inhibition in Human Motor Cortex

Source: Brain Stimulation. 14(5):1340-1352, 2021 Sep-Oct.

Authors: Fong PY; Spampinato D; Rocchi L; Hannah R; Teng Y; Di Santo A; Shoura M;
Bhatia K; Rothwell JC

BACKGROUND: Pulses of transcranial magnetic stimulation (TMS) with a predominantly anterior-posterior (AP) or posterior-anterior (PA) current direction over the primary motor cortex appear to activate distinct excitatory inputs to corticospinal neurons. In contrast, very few reports have examined whether the inhibitory neurons responsible for short-interval intracortical inhibition (SICI) are sensitive to TMS current direction.

OBJECTIVES: To investigate whether SICI evaluated with AP and PA conditioning stimuli (CSPA and CSAP) activate different inhibitory pathways. SICI was always assessed using a PA-oriented test stimulus (TSPA).

METHODS: Using two superimposed TMS coils, CSPA and CSAP were applied at
interstimulus intervals (ISI) of 1-5 ms before a TSPA, and at a range of different intensities. Using a triple stimulation design, we then tested whether SICI at ISI of 3 ms using opposite directions of CS (SICICSPA3 and SICICSAP3) interacted differently with three other forms of inhibition, including SICI at ISI of 2 ms (SICICSPA2), cerebellum-motor cortex inhibition (CBI 5 ms) and short-latency afferent inhibition (SAI 22 ms). Finally, we compared the effect of tonic and phasic voluntary contraction on SICICSPA3 and SICICSAP3.

RESULTS: CSAP produced little SICI at ISIs = 1 and 2 ms. However, at ISI = 3 ms, both CSAP and CSPA were equally effective at the same percent of maximum stimulator output. Despite this apparent similarity, combining SICICSPA3 or SICICSAP3 with other forms of inhibition led to quite different results: SICICSPA3 interacted in complex ways with CBI, SAI and SICICSPA2, whereas the effect of SICICSAP3 appeared to be quite independent of them. Although SICICSPA and SICICSAP were both reduced by the same amount during voluntary tonic contraction compared with rest, in a simple reaction time task SICICSAP was disinhibited much earlier
following the imperative signal than SICICSPA.

CONCLUSIONS: SICICSPA appears to activate a different inhibitory pathway to that activated by SICICSAP. The difference is behaviorally relevant since the pathways are controlled differently during volitional contraction. The results may explain some previous pathological data and open the possibility of testing whether these pathways are differentially recruited in a range of tasks.

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Dec 19, 2021 12:16:00 PM

Theta-burst Stimulation Entrains Frequency-Specific Oscillatory Responses

Source: Brain Stimulation. 14(5):1271-1284, 2021 Sep-Oct.

Solomon EA; Sperling MR; Sharan AD; Wanda PA; Levy DF; Lyalenko A; Pedisich I; Rizzuto DS; Kahana MJ


BACKGROUND: Brain stimulation has emerged as a powerful tool in human neuroscience, becoming integral to next-generation psychiatric and neurologic therapeutics. Theta-burst stimulation (TBS), in which electrical pulses are delivered in rhythmic bouts of 3-8 Hz, seeks to recapitulate neural activity seen endogenously during cognitive tasks. A growing literature suggests that TBS can be used to alter or enhance cognitive processes, but little is known about how these stimulation events influence underlying neural activity.

OBJECTIVE: Our study sought to investigate the effect of direct electrical TBS on mesoscale neural activity in humans by asking (1) whether TBS evokes persistent theta oscillations in cortical areas, (2) whether these oscillations occur at the stimulated frequency, and (3) whether stimulation events propagate in a manner consistent with underlying functional and structural brain architecture.

METHODS: We recruited 20 neurosurgical epilepsy patients with indwelling electrodes and delivered direct cortical TBS at varying locations and frequencies. Simultaneous iEEG was recorded from non-stimulated electrodes and analyzed to understand how TBS influences mesoscale neural activity.

RESULTS: We found that TBS rapidly evoked theta rhythms in widespread brain regions, preferentially at the stimulation frequency, and that these oscillations persisted for hundreds of milliseconds post stimulation offset. Furthermore, the functional connectivity between recording and stimulation sites predicted the strength of theta response, suggesting that underlying brain architecture guides the flow of stimulation through the brain.

CONCLUSIONS: By demonstrating that cortical TBS induces frequency-specific oscillatory responses, our results suggest this technology can be used to directly and predictably influence the activity of cognitively-relevant brain networks.

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Dec 18, 2021 12:14:00 PM

Accelerated Theta-burst Stimulation for the Treatment of Depression: A Randomised Controlled Trial

Source: Brain Stimulation. 14(5):1095-1105, 2021 Sep-Oct.

Chen L; Thomas EHX; Kaewpijit P; Miljevic A; Hughes R; Hahn L; Kato Y;
Gill S; Clarke P; Ng F; Paterson T; Giam A; Sarma S; Hoy KE; Galletly C; Fitzgerald PB


INTRODUCTION: Theta burst pattern repetitive transcranial magnetic stimulation (TBS) is increasingly applied to treat depression. TBS's brevity is well-suited to application in accelerated schedules. Sizeable trials of accelerated TBS are lacking; and optimal TBS parameters such as stimulation intensity are not established.

METHODS: We conducted a three arm, single blind, randomised, controlled, multi-site trial comparing accelerated bilateral TBS applied at 80 % or 120 % of the resting motor threshold and left unilateral 10 Hz rTMS. 300  patients with treatment-resistant depression (TRD) were recruited. TBS arms applied 20 bilateral prefrontal TBS sessions over 10 days, while the rTMS arm applied 20 daily sessions of 10 Hz rTMS to the left prefrontal cortex over 4 weeks. Primary outcome was depression treatment response at week 4.

RESULTS: The overall treatment response rate was 43.7 % and the remission rate was 28.2 %. There were no significant differences for response (p = 0.180) or remission (p = 0.316) across the three groups. Response rates between accelerated bilateral TBS applied at sub- and supra-threshold intensities were not significantly different (p = 0.319). Linear mixed model analysis showed a significant effect of time (p < 0.01), but not rTMS type (p = 0.680).

CONCLUSION: This is the largest accelerated bilateral TBS study to date and provides evidence that it is effective and safe in treating TRD. The accelerated application of TBS was not associated with more rapid antidepressant effects. Bilateral sequential TBS did not have superior antidepressant effect to unilateral 10 Hz rTMS. There was no significant difference in antidepressant efficacy between sub- and supra-threshold accelerated bilateral TBS.

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Dec 17, 2021 5:34:00 PM

The Impact of 'Cluster Maintenance TMS' on Irritability Occurring in Major Depressive Disorder

Source: Australasian Psychiatry. 29(2):222-225, 2021 04.

Authors: Pridmore S; Turnier-Shea Y; Erger S; May T

OBJECTIVE: To determine the impact of clustered maintenance transcranial magnetic stimulation (TMS) on irritability occurring in treatment-resistant major depressive disorder (MDD).

METHOD: A naturalistic study of 106 courses that includes pre- and posttreatment assessments of subjective and objective depression and a subjective measure of irritability developed for this study.

RESULTS: Forty-six participants (35 females), mean age 43.2 years (14.3), completed 106 courses. There was a significant reduction in irritability and depression scores (p < .001). The change in irritability scores was significantly correlated with the change in depression scores, r = .40, p < .001.

CONCLUSION: TMS has the capacity to reduce the irritability co-occurring with treatment-resistant MDD, known to be responsive to TMS. This increases the possibility of using TMS in the treatment of irritability co-occurring with other disorders or standing alone (should irritability be categorized as a stand-alone disorder).

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Dec 17, 2021 11:22:00 AM

Day-to-Day Variability in Motor Threshold During rTMS Treatment for Depression: Clinical Implications

Source: Brain Stimulation. 14(5):1118-1125, 2021 Sep-Oct.

Authors: Cotovio G; Oliveira-Maia AJ; Paul C; Faro Viana F; Rodrigues da Silva D; Seybert C; Stern AP; Pascual-Leone A; Press DZ

BACKGROUND: When repetitive transcranial magnetic stimulation (rTMS) is used to treat medication refractory depression, the treatment pulse intensity is individualized according to motor threshold (MT). This measure is often acquired only on the first day of treatment, as per the protocol currently approved by Food and Drug Administration.

OBJECTIVE: Here, we aimed to assess daily MT variability across an rTMS treatment course and simulate the effects of different schedules of MT assessment on treatment intensity.

METHODS: We conducted a naturalistic retrospective study with 374 patients from a therapeutic rTMS program for depression that measures MT daily.

RESULTS: For each patient, in almost half the TMS sessions, MT varied on average more than 5% as compared to the baseline MT acquired in the first treatment day. Such variability was only minimally impacted by having different TMS technicians acquiring MT in different days. In a smaller cohort of healthy individuals, we confirmed that the motor hotspot localization method, a critical step for accurate MT assessment, was stable in different days, arguing that daily MT variability reflects physiological variability, rather than an artifact of measurement error. Finally, in simulations of the effect of one-time MT measurement, we found that half of sessions would have been 5% or more above or below target intensity, with almost 5% of sessions 25% above target intensity. The simulated effects of weekly MT measurements were significantly improved.

CONCLUSIONS: In conclusion, MT varies significantly across days, not fully dependent on methods of MT acquisition. This finding may have important implications for therapeutic rTMS practice regarding safety and suggests that regular MT assessments, daily or at least weekly, would ameliorate the effect.

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Dec 16, 2021 5:31:00 PM

TMS and CBT-I for Comorbid Depression and Insomnia. 

Exploring feasibility  and tolerability of transcranial magnetic stimulation (TMS) and cognitive behavioral therapy for insomnia (CBT-I) for comorbid major depressive disorder and insomnia during the COVID-19 pandemic

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Dec 15, 2021 5:23:00 PM

The Role of Expectation and Beliefs on the Effects of Non-Invasive Brain Stimulation

Source: Brain Sciences. 11(11) (no pagination), 2021. Article Number: 1526.

Date of Publication: November 2021.

Author: Braga M.; Barbiani D.; Andani M.E.; Villa-Sanchez B.; Tinazzi M.; Fiorio M.

Abstract: Non-invasive brain stimulation (NIBS) techniques are used in clinical and
cognitive neu-roscience to induce a mild magnetic or electric field in the brain to modulate behavior and cortical activation. Despite the great body of literature demonstrating promising results, unexpected or even paradoxical outcomes are sometimes observed. This might be due either to technical and methodological issues (e.g., stimulation parameters, stimulated brain area), or to participants' expectations and beliefs before and during the stimulation sessions. In this narrative review, we present some studies showing that placebo and nocebo effects, associated with positive and negative expectations, respectively, could be present in NIBS trials, both in experimental and in clinical settings. The lack of
systematic evaluation of subjective expectations and beliefs before and after stimulation could represent a caveat that overshadows the potential contribution of placebo and nocebo effects in the outcome of NIBS trials.

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Dec 15, 2021 11:19:00 AM

Targeting Repetitive Transcranial Magnetic Stimulation in Depression: Do We Really Know What We Are Stimulating and How Best to Do It? [Review]

Source: Brain Stimulation. 14(3):730-736, 2021 May-Jun.

Author: Fitzgerald PB

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an established treatment for patients with depression who have not achieved optimal outcomes with one or more trials of antidepressant medication. It is an effective antidepressant treatment but there remains considerable scope for improving clinical outcomes. One method to potentially enhance the efficacy of rTMS is through the improvement of methods of stimulation localization.

OBJECTIVE: The purpose of this paper is to review the literature pertaining to rTMS localization methods and approaches relevant to the treatment of major depressive disorder (MDD) and provide specific opinions on the state of the art in regards to targeting of rTMS treatment in depression.

METHODS: A targeted review of the literature on rTMS targeting in depression.

RESULTS: There is emerging evidence that optimal rTMS treatment outcomes are likely to be achieved with stimulation at a relatively anterior stimulation site in the left dorsolateral prefrontal cortex (DLPFC). However, some lines of research suggest that there may be two effective stimulation sites: one quite posterior, and one more anterior, in the DLPFC. The 'Beam F3' method provides reasonable localization to the anterior stimulation site and the posterior stimulation site corresponds to that typically used in studies using the '5 cm method'. Neuro-navigational methods are generally most likely to consistently ensure placement of the TMS coil such that it results in stimulation of a selected cortical site. fMRI - connectivity based approaches to targeting specific circuits in the DLPFC are intellectually attractive but it may not be possible to demonstrate differential effectiveness of these over the methods most commonly been used in clinical practice.

CONCLUSIONS: There is an emerging literature helping to improve our understanding of the optimal methods for targeting rTMS treatment for depression. However, we lack substantive prospective clinical trials demonstrating improved clinical outcomes with these techniques.

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Dec 14, 2021 5:20:00 PM

Reduction of Impulsivity in Patients Receiving Deep Transcranial Magnetic Stimulation Treatment for Obesity

Source: Endocrine. 74(3):559-570, 2021 12.

Authors: Luzi L; Gandini S; Massarini S; Bellerba F; Terruzzi I; Senesi P; Macri C; Ferrulli A

PURPOSE: Aims of the present study were to investigate a wide array of psychological symptoms through validated psychometric tests, before and after 5 weeks of deep Transcranial Magnetic Stimulation (dTMS) in individuals with obesity, and to identify possible relationships with neuroendocrine parameters.

METHODS: Forty-five patients with obesity (33 F, 12 M; age 48.8 +/- 9.9 years; body wt 97.6 +/- 14.2 Kg; BMI 36.2 +/- 4.2) were randomized into two groups: 26 received high frequency (HF) dTMS and 19 Sham stimulation for 5 weeks. At baseline and after the 5-week treatment, all patients underwent the following psychometric evaluations: Food Cravings Questionnaire-Trait (FCQ-T) and its subscales, Barratt Impulsiveness Scale-11 (BIS-11), State and Trait Anxiety Inventory (STAI-y1 and
STAI-y2), and Beck Depression Inventory (BDI). Hormonal and neuroendocrine
markers were assessed at the first and last dTMS session.

RESULTS: By adjusting for baseline variables and treatment arms, a significant decrease in body wt and BMI was found in HF group, both with univariate (p = 0.019) and multivariate analyses (p = 0.012). Impulsivity significantly decreased in HF group, both with univariate (p = 0.031) and multivariate analyses (p = 0.011). A positive association between the impulsivity score change and the leptin level variation (p = 0.031) was found.

CONCLUSION: The decrease of impulsivity together with the BMI reduction in individuals with obesity, treated with real stimulation, suggests that impulsivity may be a risk factor for obesity. Treatment with dTMS revealed to be effective in reducing both BMI and impulsivity by enhancing inhibitory capacity of Pre-Frontal Cortex

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Dec 14, 2021 12:02:00 PM

Subthreshold Stimulation Intensity is Associated with Greater Clinical Efficacy of Intermittent Theta-burst Stimulation Priming for Major Depressive Disorder

Source: Brain Stimulation. 14(4):1015-1021, 2021 Jul-Aug.

Lee JC; Corlier J; Wilson AC; Tadayonnejad R; Marder KG; Ngo D; Krantz DE; Wilke SA; Levitt JG; Ginder ND; Leuchter AF


BACKGROUND: Intermittent theta-burst stimulation priming (iTBS-P) can improve clinical outcome of patients with Major Depressive Disorder (MDD) who do not show early benefit from 10 Hz stimulation of left dorsolateral prefrontal cortex (DLPFC), also known as high-frequency left-sided (HFL) stimulation. The intensity and pulse number for iTBS-P needed to induce clinical benefit have not been systematically examined.

OBJECTIVE: To study the effect of intensity and pulse number on the clinical efficacy of iTBS-P.

METHODS: We conducted a retrospective review of 71 participants who received at least five sessions of HFL with limited clinical benefit and received iTBS-P augmentation for between 5 and 25 sessions. Intensity of iTBS-P priming stimuli ranged from 75 to 120% of motor threshold (MT) and pulse number ranged from 600 to 1800. Associations among intensity, pulse number, and clinical outcome were analyzed using a mixed methods linear model with change in IDS-SR as the primary outcome variable, priming stimulation intensity (subthreshold or suprathreshold), pulse number (<1200 or >1200 pulses), and gender as fixed factors, and number of iTBS-P treatments and age as continuous covariates.

RESULTS: Subjects who received subthreshold intensity iTBS-P experienced greater reduction in depressive symptoms than those who received suprathreshold iTBS-P (p = 0.011) with no effect of pulse number after controlling for stimulus intensity.

CONCLUSIONS: Subthreshold intensity iTBS-P was associated with greater clinical improvement than suprathreshold stimulation. This finding is consistent with iTBS-P acting through homeostatic plasticity mechanisms.

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Dec 13, 2021 5:13:00 PM

Diagnostic Contribution and Therapeutic Perspectives of Transcranial Magnetic Stimulation in Dementia. [Review]

Source: Clinical Neurophysiology. 132(10):2568-2607, 2021 10.

Authors: Di Lazzaro V; Bella R; Benussi A; Bologna M; Borroni B; Capone F; Chen KS;
Chen R; Chistyakov AV; Classen J; Kiernan MC; Koch G; Lanza G; Lefaucheur JP; Matsumoto H; Nguyen JP; Orth M; Pascual-Leone A; Rektorova I; Simko P; Taylor JP; Tremblay S; Ugawa Y; Dubbioso R; Ranieri F

Abstract: Transcranial magnetic stimulation (TMS) is a powerful tool to probe in
vivo brain circuits, as it allows to assess several cortical properties such asexcitability, plasticity and connectivity in humans. In the last 20 years, TMS has been applied to patients with dementia, enabling the identification of potential markers of the pathophysiology and predictors of cognitive decline; moreover, applied repetitively, TMS holds promise as a potential therapeutic intervention. The objective of this paper is to present a comprehensive review of studies that have employed TMS in dementia and to discuss potential clinical applications, from the
diagnosis to the treatment. To provide a technical and theoretical framework, we first present an overview of the basic physiological mechanisms of the application of TMS to assess cortical excitability, excitation and inhibition balance, mechanisms of plasticity and cortico-cortical connectivity in the human brain. We then review the insights gained by TMS techniques into the pathophysiology and predictors
of progression and response to treatment in dementias, including Alzheimer's disease (AD)-related dementias and secondary dementias. We show that while a single TMS measure offers low specificity, the use of a panel of measures and/or neurophysiological index can support the clinical diagnosis and predict progression. In the last part of the article, we discuss the therapeutic uses of TMS. So far, only repetitive TMS (rTMS) over the left dorsolateral prefrontal cortex and multisite rTMS associated with cognitive training have been shown to be, respectively, possibly (Level C of evidence) and probably (Level B of evidence) effective to improve cognition, apathy, memory, and language in AD patients, especially at a mild/early stage of the disease. The clinical use of this type of
treatment warrants the combination of brain imaging techniques and/or electrophysiological tools to elucidate neurobiological effects of neurostimulation and to optimally tailor rTMS treatment protocols in individual patients or specific patient subgroups with dementia or mild cognitive impairment.

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Dec 13, 2021 11:16:00 AM

Targeting Location Relates to Treatment Response in Active but Not Sham rTMS Stimulation

Source: Brain Stimulation. 14(3):703-709, 2021 May-Jun.

Authors: Rosen AC; Bhat JV; Cardenas VA; Ehrlich TJ; Horwege AM; Mathalon DH; Roach BJ; Glover GH; Badran BW; Forman SD; George MS; Thase ME; Yurgelun-Todd D; Sughrue ME; Doyen SP; Nicholas PJ; Scott JC; Tian L; Yesavage JA

BACKGROUND: Precise targeting of brain functional networks is believed critical for treatment efficacy of rTMS (repetitive pulse transcranial magnetic stimulation) in treatment resistant major depression.

OBJECTIVE: To use imaging data from a "failed" clinical trial of rTMS in Veterans to test whether treatment response was associated with rTMS coil location in active but not sham stimulation, and compare fMRI functional connectivity between those stimulation locations.

METHODS: An imaging substudy of 49 Veterans (mean age, 56 years; range, 27-78 years; 39 male) from a randomized, sham-controlled, double-blinded clinical trial of rTMS treatment, grouping participants by clinical response, followed by group comparisons of treatment locations identified by individualized fiducial markers on structural MRI and resting state fMRI derived networks.

RESULTS: The average stimulation location for responders versus nonresponders differed in the active but not in the sham condition (P = .02). The average responder location derived from the active condition showed significant negative functional connectivity with the subgenual cingulate (P < .001) while the nonresponder location did not (P = .17), a finding replicated in independent cohorts of 84 depressed and 35 neurotypical participants. The responder and nonresponder stimulation locations evoked different seed based networks (FDR corrected clusters, all P < .03), revealing additional brain regions related to rTMS treatment

CONCLUSION: These results provide evidence from a randomized controlled trial that clinical response to rTMS is related to accuracy in targeting the region within DLPFC that is negatively correlated with subgenual cingulate. These results support the validity of a neuro-functionally informed rTMS therapy target in Veterans.

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Dec 10, 2021 5:08:00 PM

Treatment of Mixed Depression With Theta-burst Stimulation (TBS): Results From a Double-Blind, Randomized, Sham-Controlled Clinical Trial

Source: Neuropsychopharmacology. 46(13):2257-2265, 2021 12.

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Dec 9, 2021 5:04:00 PM

Major Depressive Disorder: Validated Treatments and Future Challenges

Source: World Journal of Clinical Cases. 9(31) (pp 9350-9367), 2021.

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Dec 9, 2021 11:33:00 AM

Seizure Risk with Repetitive TMS: Survey Results From Over a Half-Million Treatment Sessions

Source: Brain Stimulation. 14(4):965-973, 2021 Jul-Aug.

Taylor JJ; Newberger NG; Stern AP; Phillips A; Feifel D; Betensky RA; Press DZ


BACKGROUND: Seizures are rare during repetitive transcranial magnetic stimulation (rTMS) treatment, but estimating risk is difficult because of study heterogeneity and sampling limitations. Moreover, there are few studies comparing rates between device manufacturers.

OBJECTIVE: The objective of this study was to calculate rTMS seizure rates across various FDA-cleared devices in naturalistic clinical settings.

METHODS: In July and August 2018, approximately 500 members of the Clinical TMS Society (CTMSS) were electronically surveyed about seizures in their practices. Seizures were distinguished from non-seizures by a remote semi-structured interview with a Board-certified neurologist and Co-Chair of the CTMSS Standards Committee. Exact Poisson calculations were used to estimate seizure rates and confidence intervals across the four most widely used manufacturers.

RESULTS: The survey was completed by 134 members, with 9 responses excluded because of data inconsistencies. In total, 18 seizures were reported in 586,656 sessions and 25,526 patients across all device manufacturers. The overall seizure rate was 0.31 (95% CI: 0.18, 0.48) per 10,000 sessions, and 0.71 (95% CI: 0.42, 1.11) per 1000 patients. The Brainsway H-coil seizure rate of 5.56 per 1000 patients (95% CI:
2.77,9.95) was significantly higher (p < 0.001) than the three most widely used figure- 8 coil devices' combined seizure rate of 0.14 per 1000 patients (95% CI: 0.01, 0.51).

CONCLUSION: The absolute risk of a seizure with rTMS is low, but generic Brainsway H-coil treatment appears to be associated with a higher relative risk than generic figure- 8 coil treatment. Well-designed prospective studies are warranted to further investigate this risk.

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Dec 8, 2021 4:59:00 PM

A Happiness Magnet? Reviewing the Evidence for Repetitive Transcranial Magnetic Stimulation in Major Depressive Disorder

Source: Australasian Psychiatry. 29(2):207-213, 2021 04.

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Dec 8, 2021 11:57:00 AM

Reproducibility of Cortical Response Modulation Induced by Intermittent and Continuous Theta-burst Stimulation of the Human Motor Cortex

Source: Brain Stimulation. 14(4):949-964, 2021 Jul-Aug.

Ozdemir RA; Boucher P; Fried PJ; Momi D; Jannati A; Pascual-Leone A; Santarnecchi E; Shafi MM


BACKGROUND: Over the past decade, the number of experimental and clinical studies using theta-burst-stimulation (TBS) protocols of transcranial magnetic stimulation (TMS) to modulate brain activity has risen substantially. The use of TBS is motivated by the assumption that these protocols can reliably and lastingly modulate cortical excitability despite their short duration and low number of stimuli. However, this assumption, and thus the experimental validity of studies using TBS, is challenged by recent work showing large inter- and intra-subject
variability in response to TBS protocols.

OBJECTIVES: To date, the reproducibility of TBS effects in humans has been exclusively assessed with motor evoked potentials (MEPs), which provide an indirect and limited measure of cortical excitability. Here we combined TMS with electroencephalography (TMS-EEG) and report the first comprehensive investigation of (1) direct TMS-evoked cortical responses to intermittent (iTBS) and continuous TBS (cTBS) of the human motor cortex, and (2) reproducibility of both iTBS- and cTBS-induced cortical response modulation against a robust sham control across repeat visits with commonly used cortical responsivity metrics.

RESULTS: We show that although single pulse TMS generates stable and reproducible cortical responses across visits, the modulatory effects of TBS vary substantially both between and within individuals. Overall, at the group level, most measures of the iTBS and cTBS-induced effects were not significantly different from sham-TBS. Most importantly, none of the significant TBS-induced effects observed in visit-1 were reproduced in visit-2.

CONCLUSIONS: Our findings suggest that the generally accepted mechanisms of TBS-induced neuromodulation, i.e. through changes in cortical excitability, may not be accurate. Future research is needed to determine the mechanisms underlying the established therapeutic effects of TBS in neuropsychiatry and examine reproducibility of TBS-induced neuromodulation through oscillatory response dynamics.

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Dec 7, 2021 4:55:00 PM

The Impact of Transcranial Magnetic Stimulation (TMS) on Irritability Occurring With Acute Major Depressive Disorder (MDD)

Source: Australasian Psychiatry. 29(2):218-221, 2021 04.

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Dec 6, 2021 4:51:00 PM

Transcranial Magnetic Stimulation Neurophysiology of Patients with Major Depressive Disorder: A Systematic Review and Meta-Analysis

Source: Psychological Medicine. 51(1):1-10, 2021 01.

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Dec 6, 2021 11:50:00 AM

Exploring and Optimizing the Neuroplastic Effects of Anodal Transcranial Direct Current Stimulation Over the Primary Motor Cortex of Older Humans

Source: Brain Stimulation. 14(3):622-634, 2021 May-Jun.

Farnad L; Ghasemian-Shirvan E; Mosayebi-Samani M; Kuo MF; Nitsche MA


BACKGROUND: tDCS modulates cortical plasticity and has shown potential to improve cognitive/motor functions in healthy young humans. However, age-related alterations of brain structure and functions might require an adaptation of tDCS-parameters to achieve a targeted plasticity effect in older humans and conclusions obtained from young adults might not be directly transferable to older adults. Thus, our study aimed to systematically explore the association between tDCS-parameters and induced aftereffects on motor cortical excitability to determine optimal stimulation protocols for older individuals, as well as to investigate age-related differences of motor cortex plasticity in two different age
groups of older adults.

METHODS: 32 healthy, volunteers from two different age groups of Young-Old (50-65 years, n = 16) and Old-Old (66-80 years, n = 16) participated in this study. Anodal tDCS was applied over the primary motor cortex, with respective combinations of three intensities (1, 2, and 3 mA) and durations (15, 20, and 30 min), in a sham-controlled cross-over design. Cortical excitability alterations were monitored by single-pulse TMS-induced MEPs until the next day morning after stimulation.

RESULTS: All active stimulation conditions resulted in a significant enhancement of motor cortical excitability in both age groups. The facilitatory aftereffects of anodal tDCS did not significantly differ between age groups. We observed prolonged plasticity in the late-phase range for two protocols with the highest stimulation intensity (i.e., 3 mA-20 min, 3 mA-30 min).

CONCLUSIONS: Our study highlights the role of stimulation dosage in tDCS-induced neuroplastic aftereffects in the motor cortex of healthy older adults and delivers crucial information about optimized tDCS protocols in the domain of the primary motor cortex. Our findings might set the grounds for the development of optimal stimulation protocols to reinstate neuroplasticity in different cortical areas and induce long-lasting, functionally relevant plasticity in normal aging and in pathological conditions, which would require however systematic tDCS titration studies over respective target areas.

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Dec 4, 2021 1:27:00 PM

Novel Method for Identification of Individualized Resonant Frequencies for Treatment of Major Depressive Disorder (MDD) Using rTMS: A Proof-of-Concept Study

Source: Brain Stimulation. 14(5):1373-1383, 2021 Sep-Oct.

Leuchter AF; Wilson AC; Vince-Cruz N; Corlier J


BACKGROUND: Repetitive Transcranial Magnetic Stimulation (rTMS) is an effective treatment for Major Depressive Disorder (MDD), but therapeutic benefit is highly variable. Clinical improvement is related to changes in brain circuits, which have preferred resonant frequencies (RFs) and vary across individuals.

OBJECTIVE: We developed a novel rTMS-electroencephalography (rTMS-EEG)
interrogation paradigm to identify RFs using the association of power/connectivity measures with symptom severity and treatment outcome.

METHODS: 35 subjects underwent rTMS interrogation at 71 frequencies ranging from 3 to 17 Hz administered to left dorsolateral prefrontal cortex (DLPFC). rTMS-EEG was used to assess resonance in oscillatory power/connectivity changes (phase coherence [PC], envelope correlation [EC], and spectral correlation coefficient [SCC]) after each frequency. Multiple regression was used to detect relationships between 10 Hz resonance and baseline symptoms as well as clinical improvement after 10 sessions of 10 Hz rTMS treatment.

RESULTS: Baseline symptom severity was significantly associated with SCC resonance in left sensorimotor (SM; p < 0.0004), PC resonance in fronto-parietal (p = 0.001), and EC resonance in centro-posterior channels (p = 0.002). Subjects significantly improved with 10 sessions of rTMS treatment. Only decreased SCC SM resonance was significantly associated with clinical improvement (r = 0.35, p = 0.04). Subjects for whom 10 Hz SM SCC was highly ranked as an RF among all stimulation frequencies had better outcomes from 10 Hz treatment.

CONCLUSIONS: Resonance of 10 Hz stimulation measured using SCC correlated
with both symptom severity and improvement with 10 Hz rTMS treatment. Research should determine whether this interrogation paradigm can identify individualized rTMS treatment frequencies.

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Dec 3, 2021 4:48:00 PM

Intermittent Theta-Burst Stimulation TMS Increases GABA in the Medial Prefrontal Cortex: A Preliminary Sham-Controlled Magnetic Resonance Spectroscopy Study in Acute Bipolar Depression

Source: Frontiers in Psychiatry. 12 (no pagination), 2021. Article Number: 665402.

Date of Publication: 11 May 2021.

Authors: Diederichs C.; DeMayo M.M.; Cole J.; Yatham L.N.; Harris A.D.; McGirr A.

Background: Magnetic resonance spectroscopy (MRS) has been used to identify gamma-aminobutyric acid (GABA) alterations in mood disorders, particularly in the medial prefrontal cortex (mPFC) where decreased concentrations have been associated with anhedonia. In major depressive disorder (MDD), prior work suggests that repetitive transcranial magnetic stimulation (rTMS) increases mPFC GABA concentrations proportional to antidepressant response. To our knowledge, this has not been examined in acute bipolar depression.

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Dec 2, 2021 4:39:00 PM

Repetitive Transcranial Magnetic Stimulation for Adolescent Major Depressive Disorder: A Focus on Neurodevelopment

Source: Frontiers in Psychiatry. 12 (no pagination), 2021. Article Number: 642847.

Date of Publication: 13 Apr 2021.

Authors: Oberman L.M.; Hynd M.; Nielson D.M.; Towbin K.E.; Lisanby S.H.; Stringaris

Adolescent depression is a potentially lethal condition and a leading cause of disability for this age group. There is an urgent need for novel efficacious treatments since half of adolescents with depression fail to respond to current therapies and up to 70% of those who respond will relapse within 5 years. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising treatment for major depressive disorder (MDD) in adults who do not respond to pharmacological or behavioral interventions. In contrast, rTMS has not demonstrated the same degree of efficacy in adolescent MDD. We argue that this is due, in part, to conceptual and methodological shortcomings in the existing literature. In our review, we first provide a neurodevelopmentally focused overview of adolescent depression. We then summarize the rTMS literature in adult and
adolescent MDD focusing on both the putative mechanisms of action and
neurodevelopmental factors that may influence efficacy in adolescents. We then identify limitations in the existing adolescent MDD rTMS literature and propose specific parameters and approaches that may be used to optimize efficacy in this uniquely vulnerable age group. Specifically, we suggest ways in which future studies reduce clinical and neural heterogeneity, optimize neuronavigation by drawing from functional brain imaging, apply current knowledge of rTMS parameters and neurodevelopment, and employ an experimental therapeutics platform to identify neural targets and biomarkers for response. We conclude that rTMS is worthy of further investigation. Furthermore, we suggest that following these recommendations in future studies will offer a more rigorous test of rTMS
as an effective treatment for adolescent depression.

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Dec 2, 2021 11:44:00 AM

Effect of Stimulus Orientation and Intensity on Short-Interval Intracortical Inhibition (SICI) and Facilitation (SICF): A Multi-Channel Transcranial Magnetic Stimulation Study

Source: PLoS ONE [Electronic Resource]. 16(9):e0257554, 2021.

Tugin S; Souza VH; Nazarova MA; Novikov PA; Tervo AE; Nieminen JO; Lioumis P; Ziemann U; Nikulin VV; Ilmoniemi RJ


Besides stimulus intensities and interstimulus intervals (ISI), the electric field (E-field) orientation is known to affect both short-interval intracortical inhibition (SICI) and facilitation (SICF) in paired-pulse transcranial magnetic stimulation (TMS). However, it has yet to be established how distinct orientations of the conditioning (CS) and test stimuli (TS) affect the SICI and SICF generation. With the use of a
multi-channel TMS transducer that provides electronic control of the stimulus orientation and intensity, we aimed to investigate how changes in the CS and TS orientation affect the strength of SICI and SICF. We hypothesized that the CS orientation would play a major role for SICF than for SICI, whereas the CS intensity would be more critical for SICI than for SICF. In eight healthy subjects, we tested two ISIs (1.5 and 2.7 ms), two CS and TS orientations (anteromedial (AM) and posteromedial (PM)), and four CS intensities (50, 70, 90, and 110% of the resting motor threshold (RMT)). The TS intensity was fixed at 110% RMT. The intensities were adjusted to the corresponding RMT in the AM and PM orientations. SICI and
SICF were observed in all tested CS and TS orientations. SICI depended on the CS intensity in a U-shaped manner in any combination of the CS and TS orientations. With 70% and 90% RMT CS intensities, stronger PM-oriented CS induced stronger inhibition than weaker AM-oriented CS. Similar SICF was observed for any CS orientation. Neither SICI nor SICF depended on the TS orientation. We demonstrated that SICI and SICF could be elicited by the CS perpendicular to the TS, which indicates that these stimuli affected either overlapping or strongly connected neuronal populations. We concluded that SICI is primarily sensitive to the CS intensity and that CS intensity adjustment resulted in similar SICF for different CS orientations.

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Dec 1, 2021 4:35:00 PM

Transcranial Magnetic Stimulation for the Treatment of Cocaine Addiction: A Systematic Review

Journal of Clinical Medicine. 10(23) (no pagination), 2021. Article
Number: 5595. Date of Publication: December-1 2021.

Torres-Castano A.; Rivero-Santana A.; Perestelo-Perez L.; Duarte-Diaz A.;
Toledo-Chavarri A.; Ramos-Garcia V.; Alvarez-Perez Y.; Cudeiro-Mazaira J.;
Padron-Gonzalez I.; Serrano-Perez P.

Long-term cocaine use is associated with cognitive deficits and neuro-psychiatric pathologies. Repetitive transcranial magnetic stimulation (rTMS) is an emerging therapeutic strategy relating to changes in brain activity. It stimulates the prefrontal cortex and is involved in inhibitory cognitive control, decision making and care. This systematic review aims to evaluate and synthesize the evidence on the safety,
effectiveness, and cost-effectiveness of rTMS for the treatment of cocaine addiction. A systematic review of the literature was carried out. The following electronic databases were consulted from inception to October 2020: MEDLINE, Embase, CINAHL, PsycINFO, Cochrane Central Register of Controlled Trials and Web of Science. Randomised controlled trials, non-randomised controlled trials and case-series and full economic evaluations were included. Twelve studies were included. No identified study reported data on cost-effectiveness. Significant results of the efficacy of TMS have been observed in terms of the reduction of craving to consume and the number of doses consumed. No serious adverse effects have been observed. Despite the low quality of the studies, the first results
were observed in terms of reduction of cocaine use and craving. In any case, this effect is considered moderate. Studies with larger sample sizes and longer follow-ups are required.

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Dec 1, 2021 11:53:00 AM

Estimation of Individually Induced E-Field Strength During Transcranial Electric Stimulation Using the Head Circumference

Source: Brain Stimulation. 14(5):1055-1058, 2021 Sep-Oct.

Antonenko D; Grittner U; Puonti O; Floel A; Thielscher A


BACKGROUND: Head and brain anatomy have been related to e-field strength induced by transcranial electrical stimulation (tES). Individualization based on anatomic factors require high-quality structural magnetic resonance images, which are not always available. Head circumference (HC) can serve as an alternative means, but its linkage to electric field strength has not yet been established.

METHODS: We simulated electric fields induced by tES based on individual T1w- and T2w-images of 47 healthy adults, for four conventional ("standard") and four corresponding focal ("4x1") electrode montages. Associations of electric field strength with individual HC were calculated using linear mixed models.

RESULTS: Larger HC was associated with lower electric field strength across montages. We provide mathematical equations to estimate individual electric field strength based on the HC.

CONCLUSION: HC can be used as an alternative to estimate interindividual differences of the tES-induced electric field strength and to prospectively individualize stimulation dose, e.g., in the clinical context.

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