Neurophysiological impact of theta burst stimulation followed by cognitive exercise in treatment of youth depression

Dhami, Prabhjot; Lee, Jonathan C.; Schwartzmann, Benjamin; Knyahnytska, Yuliya; Atluri, Sravya; Christie, Gregory J.; Croarkin, Paul E.; Blumberger, Daniel M.; Daskalakis, Zafiris J.; Moreno, Sylvain; Farzan, Faranak

doi:10.1016/j.jadr.2022.100439

Cited by 2 publications

(2 citation statements)

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“…2 ) was designed as an open label 4-week TBS treatment with engagement in a cognitive exercise. The treatment consisted of 20 bilateral DLPFC TBS followed by engagement in cognitive exercise sessions (i.e., once daily, 5 days a week, over the course of 4 weeks) 6 , 24 . Thirty youth MDD patients were randomized to receive active or sham cognitive exercise.…”

Section: Methodsmentioning

confidence: 99%

“…The IPLs were chosen as control sites as they were not the sites of stimulation but are still implicated in MDD due to belonging to the default mode network 21 . As magnetic-based brain stimulation treatments, including TBS, are believed to exert their therapeutic effect in part by acting upon inhibitory mechanisms 11,[22][23][24] , we hypothesized that TEPs that reflect similar mechanisms (i.e., N45 and N100) from the left and right DLPFC would be associated with treatment response. Specifically, we hypothesized that greater baseline cortical inhibition (as reflected by a greater negativity of the N45 and N100) at the sites of stimulation (i.e., bilateral DLPFC) would be associated with greater treatment response.…”

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confidence: 99%

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Baseline markers of cortical excitation and inhibition predict response to theta burst stimulation treatment for youth depression

Dhami,

Moreno,

Croarkin

et al. 2023

Sci Rep

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Theta burst stimulation (TBS), a specific form of repetitive transcranial magnetic stimulation (TMS), is a promising treatment for youth with Major Depressive Disorder (MDD) who do not respond to conventional therapies. However, given the variable response to TBS, a greater understanding of how baseline features relate to clinical response is needed to identify which patients are most likely to benefit from this treatment. In the current study, we sought to determine if baseline neurophysiology, specifically cortical excitation and/or inhibition, is associated with antidepressant response to TBS. In two independent open-label clinical trials, youth (aged 16–24 years old) with MDD underwent bilateral dorsolateral prefrontal cortex (DLPFC) TBS treatment. Clinical trial one and two consisted of 10 and 20 daily sessions of bilateral DLPFC TBS, respectively. At baseline, single-pulse TMS combined with electroencephalography was used to assess the neurophysiology of 4 cortical sites: bilateral DLPFC and inferior parietal lobule. Measures of cortical excitation and inhibition were indexed by TMS-evoked potentials (i.e., P30, N45, P60, N100, and P200). Depression severity was measured before, during and after treatment completion using the Hamilton Rating Scale for Depression—17. In both clinical trials, the baseline left DLPFC N45 and P60, which are believed to reflect inhibitory and excitatory mechanisms respectively, were predictors of clinical response. Specifically, greater (i.e., more negative) N45 and smaller P60 baseline values were associated with greater treatment response to TBS. Accordingly, cortical excitation and inhibition circuitry of the left DLPFC may have value as a TBS treatment response biomarker for youth with MDD.Clinical trial 1 registration number: NCT02472470 (June 15, 2015).Clinical trial 2 registration number: NCT03708172 (October 17, 2018).

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Baseline markers of cortical excitation and inhibition predict response to theta burst stimulation treatment for youth depression

Dhami,

Moreno,

Croarkin

et al. 2023

Sci Rep

Self Cite

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The Virtual Brain links transcranial magnetic stimulation evoked potentials and inhibitory neurotransmitter changes in major depressive disorder

Hofsähs,

Pille,

Kern

et al. 2024

Preprint

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Background: Transcranial magnetic stimulation evoked potentials (TEPs) show promise as a biomarker in major depressive disorder (MDD), but the origin of the increased TEP amplitude in these patients remains unclear. Gamma aminobutyric acid (GABA) may be involved, as TEP peak amplitude is known to increase with GABAergic activity, but paradoxically MDD patients exhibit reduced GABA levels. We employed a computational modeling approach to investigate this contradiction. Methods: Whole-brain simulations in 'The Virtual Brain' (thevirtualbrain.org), employing the Jansen and Rit neural mass model, were optimized to simulate TEPs of healthy individuals (N=20, 14 females, 24.5+/-4.9 years). To mimic MDD, a GABAergic deficit was introduced to the simulations by altering one of two selected inhibitory parameters, the inhibitory synaptic time constant b or the number of inhibitory synapses C4. The TEP amplitude was quantified and compared for all simulations. Results: Both parameters, the inhibitory synaptic time constant (r=-0.6, p<0.001) and the number of inhibitory synapses (r=-0.79, p<0.001), showed a significant negative linear correlation to the TEP amplitude. Thus, under local parameter changes, we were able to alter the TEP amplitude towards pathological levels, i.e. creating an MDD-like increase of the global mean field amplitude in line with empirical results. Conclusions: Our model suggests specific GABAergic deficits as the cause of increased TEP amplitude in MDD patients, which may serve as therapeutic targets. This work highlights the potential of whole-brain simulations in the investigation of neuropsychiatric diseases.

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Neurophysiological impact of theta burst stimulation followed by cognitive exercise in treatment of youth depression

Cited by 2 publications

References 67 publications

Baseline markers of cortical excitation and inhibition predict response to theta burst stimulation treatment for youth depression

Baseline markers of cortical excitation and inhibition predict response to theta burst stimulation treatment for youth depression

The Virtual Brain links transcranial magnetic stimulation evoked potentials and inhibitory neurotransmitter changes in major depressive disorder

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