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

2021 ◽  
Vol 12 ◽  
Author(s):  
Chad Diederichs ◽  
Marilena M. DeMayo ◽  
Jaeden Cole ◽  
Lakshmi N. Yatham ◽  
Ashley D. Harris ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Magnetic Stimulation ◽  
Rating Scale ◽  
Bipolar Depression ◽  
Resonance Spectroscopy ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
Theta Burst

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.Methods: As part of a multicentre 4-week randomized, double-blind, sham-controlled trial using intermittent theta-burst stimulation (iTBS) of the left dorsolateral prefrontal cortex (DLPFC) in individuals with acute bipolar depression, we quantified mPFC GABA and Glx (glutamate+glutamine) concentrations using a 3T MRS scan at baseline and after the intervention. Depressive symptoms were measured using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating Scale-17 (HRDS-17), and anhedonia was measured using the Snaith-Hamilton Pleasure Scale (SHAPS).Results: The trial was terminated for futility and magnetic resonance spectroscopy data was acquired for 18 participants. At baseline, there were no associations between GABA or Glx concentrations and anhedonia, however GABA was negative correlated with depressive symptom severity on the HRDS-17. Compared to the sham-iTBS group, participants receiving active-iTBS had a significant increase in mPFC GABA concentrations. This was unrelated to antidepressant outcomes or improvements in anhedonia.Conclusion: Our data suggests that iTBS targeting the DLPFC is associated with physiological changes in the mPFC. In acute bipolar depression, our preliminary data suggests that mPFC GABA is dissociated from antidepressant iTBS treatment outcomes and anhedonia.

scholarly journals Neurochemical Effects of Theta Burst Stimulation as Assessed by Magnetic Resonance Spectroscopy

2009 ◽  
Vol 101 (6) ◽  
pp. 2872-2877 ◽  
Author(s):  
C. J. Stagg ◽  
M. Wylezinska ◽  
P. M. Matthews ◽  
H. Johansen-Berg ◽  
P. Jezzard ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Primary Motor Cortex ◽  
Control Site ◽  
Significant Inhibition ◽  
Resonance Spectroscopy ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
New Hypothesis ◽  
Theta Burst

Continuous theta burst stimulation (cTBS) is a novel transcranial stimulation technique that causes significant inhibition of synaptic transmission for ≤1 h when applied over the primary motor cortex (M1) in humans. Here we use magnetic resonance spectroscopy to define mechanisms mediating this inhibition by noninvasively measuring local changes in the cortical concentrations of γ-aminobutyric acid (GABA) and glutamate/glutamine (Glx). cTBS to the left M1 led to an increase in GABA compared with stimulation at a control site without significant change in Glx. This direct evidence for increased GABAergic interneuronal activity is framed in terms of a new hypothesis regarding mechanisms underlying cTBS.

scholarly journals Reliability of transcranial magnetic stimulation evoked potentials to detect the effects of theta-burst stimulation of the prefrontal cortex

2021 ◽  
Author(s):  
Adriano Henrique de Matos Moffa ◽  
Stevan Nikolin ◽  
Donel Martin ◽  
Colleen Loo ◽  
Tjeerd W. Boonstra
Keyword(s):  
Prefrontal Cortex ◽  
Transcranial Magnetic Stimulation ◽  
Evoked Potentials ◽  
Magnetic Stimulation ◽  
Cortical Excitability ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
Neural Excitability ◽  
Dorsolateral Prefrontal ◽  
Theta Burst

Background: Transcranial magnetic stimulation (TMS) with simultaneous electroencephalography (EEG) is a novel method for assessing cortical properties outside the motor region. Theta burst stimulation (TBS), a form of repetitive TMS, can non-invasively modulate cortical excitability and has been increasingly used to treat psychiatric disorders by targetting the dorsolateral prefrontal cortex (DLPFC). The TMS-evoked potentials (TEPs) analysis has been used to evaluate cortical excitability changes after TBS. However, it remains unclear whether TEPs can detect the neuromodulatory effects of TBS. Objectives: To confirm the reliability of TEP components within and between sessions and to measure changes in neural excitability induced by intermittent (iTBS) and continuous TBS (cTBS) applied to the left DLPFC. Methods: Test-retest reliability of TEPs and TBS-induced changes in cortical excitability were assessed in twenty-four healthy participants by stimulating the DLPFC in five separate sessions, once with sham and twice with iTBS and cTBS. EEG responses were recorded of 100 single TMS pulses before and after TBS, and the reproducibility measures were quantified with the concordance correlation coefficient (CCC). Results: The N100 and P200 components presented substantial reliability within the baseline block (CCCs>0.8) and moderate concordance between sessions (CCCmax≈0.7). Both N40 and P60 TEP amplitudes showed little concordance between sessions. Changes in TEP amplitudes after iTBS were marginally reliable for N100 (CCCmax=0.52), P200 (CCCmax=0.47) and P60 (CCCmax=0.40), presenting only fair levels of concordance at specific time points. Conclusions: The present findings show that only the N100 and P200 components had good concordance between sessions. The reliability of earlier components may have been affected by TMS-evoked artefacts. The poor reliability to detect changes in neural excitability induced by TBS indicates that TEPs do not provide a precise estimate of the changes in excitability in the DLPFC or, alternatively, that TBS did not induce consistent changes in neural excitability.

scholarly journals Assessing neuromodulation effects of theta burst stimulation to the prefrontal cortex using TMS-evoked potentials

2021 ◽  
Author(s):  
Adriano Henrique de Matos Moffa ◽  
Stevan Nikolin ◽  
Donel Martin ◽  
Colleen Loo ◽  
Tjeerd W. Boonstra
Keyword(s):  
Prefrontal Cortex ◽  
Transcranial Magnetic Stimulation ◽  
Evoked Potentials ◽  
Effect Size ◽  
Repeated Measures ◽  
Magnetic Stimulation ◽  
Cortical Excitability ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
Theta Burst

Theta burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (TMS), is capable of non-invasively modulating cortical excitability. TBS is gaining popularity as a therapeutic tool for psychiatric disorders such as depression, in which the dorsolateral prefrontal cortex (DLPFC) is the main therapeutic target. However, the neuromodulatory effects of TBS on prefrontal regions remain unclear. An emerging tool to assess neuromodulation in non-motor regions is concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to measure TMS-evoked potentials (TEPs). We assessed twenty-four healthy participants (13 males, mean age 25.2±9.9 years) following intermittent TBS, continuous TBS, and sham applied to the left DLPFC using a double-blinded crossover design. TEPs were obtained at baseline and 2-, 15-, and 30-min post-stimulation. Four TEP components (N40, P60, N100 and P200) were analysed using mixed effects repeated measures models (MRMM). Results indicate no significant effects for any assessed components (all p>.05). The largest effect size (Cohens d = -0.5) comparing iTBS and sham was obtained for the N100 component at 15 minutes post-stimulation. This result was in the same direction but smaller than found in previous studies, suggesting that the true effect size may be lower than previously reported. Accurate estimates of the effects sizes and inter-individual heterogeneity will critically inform clinical applications using TEPs to assess the neuromodulatory effects of TBS.

scholarly journals Therapeutic Use of Cerebellar Intermittent Theta Burst Stimulation (iTBS) in a Sardinian Family Affected by Spinocerebellar Ataxia 38 (SCA 38)

2021 ◽  
Author(s):  
Angela Sanna ◽  
Paolo Follesa ◽  
Paolo Tacconi ◽  
Mariangela Serra ◽  
Maria Giuseppina Pisu ◽  
...  
Keyword(s):  
Spinocerebellar Ataxia ◽  
Rating Scale ◽  
Clinical Symptoms ◽  
Therapeutic Use ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
Motor Cortex Excitability ◽  
Before And After ◽  
Theta Burst ◽  
Serum Bdnf

AbstractSpinocerebellar ataxia 38 (SCA 38) is an autosomal dominant disorder caused by conventional mutations in the ELOVL5 gene which encodes an enzyme involved in the synthesis of very long fatty acids, with a specific expression in cerebellar Purkinje cells. Three Italian families carrying the mutation, one of which is of Sardinian descent, have been identified and characterized. One session of cerebellar intermittent theta burst stimulation (iTBS) was applied to 6 affected members of the Sardinian family to probe motor cortex excitability measured by motor-evoked potentials (MEPs). Afterwards, patients were exposed to ten sessions of cerebellar real and sham iTBS in a cross-over study and clinical symptoms were evaluated before and after treatment by Modified International Cooperative Ataxia Rating Scale (MICARS). Moreover, serum BDNF levels were evaluated before and after real and sham cerebellar iTBS and the role of BDNF Val66Met polymorphism in influencing iTBS effect was explored. Present data show that one session of cerebellar iTBS was able to increase MEPs in all tested patients, suggesting an enhancement of the cerebello-thalamo-cortical pathway in SCA 38. MICARS scores were reduced after ten sessions of real cerebellar iTBS showing an improvement in clinical symptoms. Finally, although serum BDNF levels were not affected by cerebellar iTBS when considering all samples, segregating for genotype a difference was found between Val66Val and Val66Met carriers. These preliminary data suggest a potential therapeutic use of cerebellar iTBS in improving motor symptoms of SCA38.

scholarly journals Theta burst stimulation for the acute treatment of major depressive disorder: A systematic review and meta-analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jeffrey D. Voigt ◽  
Andrew F. Leuchter ◽  
Linda L. Carpenter
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Rating Scale ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
High Frequency Stimulation ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
Major Depressive ◽  
Significant Difference ◽  
Theta Burst

AbstractPatients with major depressive disorder (MDD) may be refractory to or have contraindications that preclude treatment with antidepressant pharmacotherapies. Alternative therapies such as repetitive transcranial magnetic stimulation (rTMS) continue to evolve, and include theta burst stimulation (TBS), which has advantages over conventional rTMS. The aim of this study was to identify and meta-analyze efficacy data from all randomized controlled trials (RCTs) investigating TBS as a treatment for MDD. Published reports of RCTs (January 1, 2010 to October 23, 2020) were identified via systematic searches in computerized databases, followed by review of individual reports for inclusion. Inclusion criteria included primary diagnosis of MDD ≥ 1 week duration of therapy with ≥10 sessions, and treatment with any form of TBS. The Cochrane GRADE methodology and PRISMA criteria were used for evaluation of individual trials. Data from ten RCTs were included, representing 667 patients. Of these, 8 RCTs compared TBS to sham treatment and one compared TBS to standard rTMS (i.e., high frequency stimulation over left dorsolateral prefrontal cortex [HFL]). Quality of evidence assessment yielded high confidence in the finding of TBS being superior to sham on response measured by the Hamilton Depression Rating Scale (HRSD) (RR = 2.4; 95% CI: 1.27 to 4.55; P = 0.007; I2 = 40%). Comparison of HRSD response rates for TBS versus rTMS produced no statistically significant difference (RR = 1.02; 95% CI: 0.85 to 1.23; P = 0.80; I2 = 0%). The incidence of adverse events between TBS and rTMS was not statistically different. The findings of a positive effect of TBS vs. sham, and noninferiority of TBS vs. standard HFL rTMS support the continued development of TBS to treat depression.

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