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Default mode network alterations after intermittent theta burst stimulation in healthy subjects.

ABSTRACT: Understanding the mechanisms by which intermittent theta burst stimulation (iTBS) protocols exert changes in the default-mode network (DMN) is paramount to develop therapeutically more effective approaches in the future. While a full session (3000 pulses) of 10?Hz repetitive transcranial magnetic stimulation (HF-rTMS) reduces the functional connectivity (FC) of the DMN and the subgenual anterior cingulate cortex, the current understanding of the effects of a single session of iTBS on the DMN in healthy subjects is limited. Here, we use a previously validated target selection approach for an unprecedented investigation into the effects of a single session (1800 pulses) of iTBS over the DMN in healthy controls. Twenty-six healthy subjects participated in a double-blind, crossover, sham-controlled study. After iTBS to the personalized left dorsolateral prefrontal cortex (DLPFC) targets, we investigated the time lapse of effects in the DMN and its relationship to the harm avoidance (HA) personality trait measure (Temperament and Character Inventory/TCI). Approximately 25-30?min after stimulation, we observed reduced FC between the DMN and the rostral and dorsal anterior cingulate cortex (dACC). About 45?min after stimulation the FC of rostral and dACC strongly decreased further, as did the FC of right anterior insula (AI) with the DMN. Also, we report a positive correlation between the FC decrease in the rostral ACC and the HA domain of TCI, indicating that the HA scores can potentially predict iTBS response. Overall, our results show the time lapse by which iTBS at left-DLPFC targets reduces the FC between DMN and the dACC and right AI, regions typically described as nodes of the salience network.

SUBMITTER: Singh A

PROVIDER: S-EPMC7040002 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Default mode network alterations after intermittent theta burst stimulation in healthy subjects.

Singh Aditya A Erwin-Grabner Tracy T Sutcliffe Grant G Paulus Walter W Dechent Peter P Antal Andrea A Goya-Maldonado Roberto R

Translational psychiatry 20200224 1

Understanding the mechanisms by which intermittent theta burst stimulation (iTBS) protocols exert changes in the default-mode network (DMN) is paramount to develop therapeutically more effective approaches in the future. While a full session (3000 pulses) of 10 Hz repetitive transcranial magnetic stimulation (HF-rTMS) reduces the functional connectivity (FC) of the DMN and the subgenual anterior cingulate cortex, the current understanding of the effects of a single session of iTBS on the DMN in ...[more]

PMID: 32094326

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Project description:Introduction:Cognitive symptoms from Parkinson's disease cause severe disability and significantly limit quality of life. Little is known about mechanisms of cognitive impairment in PD, although aberrant oscillatory activity in basal ganglia-thalamo-prefrontal cortical circuits likely plays an important role. While continuous high-frequency deep brain stimulation (DBS) improves motor symptoms, it is generally ineffective for cognitive symptoms. Although we lack robust treatment options for these symptoms, recent studies with transcranial magnetic stimulation (TMS), applying intermittent theta-burst stimulation (iTBS) to dorsolateral prefrontal cortex (DLPFC), suggest beneficial effects for certain aspects of cognition, such as memory or inhibitory control. While TMS is non-invasive, its results are transient and require repeated application. Subcortical DBS targets have strong reciprocal connections with prefrontal cortex, such that iTBS through the permanently implanted lead might represent a more durable solution. Here we demonstrate safety and feasibility for delivering iTBS from the DBS electrode and explore changes in DLPFC electrophysiology. Methods:We enrolled seven participants with medically refractory Parkinson's disease who underwent DBS surgery targeting either the subthalamic nucleus (STN) or globus pallidus interna (GPi). We temporarily placed an electrocorticography strip over DLPFC through the DBS burr hole. After placement of the DBS electrode into either GPi (n = 3) or STN (n = 4), awake subjects rested quietly during iTBS (three 50-Hz pulses delivered at 5 Hz for 2 s, followed by 8 s of rest). We contrasted power spectra in DLPFC local field potentials during iTBS versus at rest, as well as between iTBS and conventional high-frequency stimulation (HFS). Results:Dominant frequencies in DLPFC at rest varied among subjects and along the subdural strip electrode, though they were generally localized in theta (3-8 Hz) and/or beta (10-30 Hz) ranges. Both iTBS and HFS were well-tolerated and imperceptible. iTBS increased theta-frequency activity more than HFS. Further, GPi stimulation resulted in significantly greater theta-power versus STN stimulation in our sample. Conclusion:Acute subcortical iTBS from the DBS electrode was safe and well-tolerated. This novel stimulation pattern delivered from the GPi may increase theta-frequency power in ipsilateral DLPFC. Future studies will confirm these changes in DLPFC activity during iTBS and evaluate whether they are associated with improvements in cognitive or behavioral symptoms from PD.

Project description:PurposeThe utility of transcranial magnetic stimulation (TMS) has been growing rapidly in both neurocognitive studies and clinical applications in decades. However, it remains unclear how the responses of the stimulated site and the site-related functional network to the external TMS manipulation dynamically change over time.MethodsA multi-session combining TMS-fMRI experiment was conducted to explore the spatiotemporal effects of TMS within the fronto-limbic network. Ten healthy volunteers were modulated by intermittent theta-burst stimulation (iTBS) at a precise site within the left dorsolateral prefrontal cortex (DLPFC, MNI coordinate [-44 36 20]), navigated by individual structural MRI image. Three-session resting-state fMRI images were acquired before iTBS (TP1), immediately after iTBS (TP2), and 15 min after iTBS (TP3) for each participant. Seventy-four regions of interests (ROIs) within the fronto-limbic network were chosen including the bilateral superior frontal gyrus (SFG), middle frontal gyrus (MidFG), inferior frontal gyrus (IFG), orbital gyrus (OrG), cingulate gyrus (CG), and subcortical nuclei (hippocampus and amygdala). Regional fractional amplitude of low-frequency fluctuation (fALFF) and ROI-to-ROI functional connectivity (FC) were compared among TP1, TP2, and TP3.ResultsThe immediate iTBS effect was observed at the stimulated site. FC between the left dorsolateral SFG and left dorsal IFG and between the left rostral IFG and right MidFG increased at TP2 as compared to at TP1 (all FDR-p < 0.05), while FC within the left OrG decreased. The relatively long-term iTBS effect transmitted with decreased FC between the left IFG and right amygdala, increased FC between the left MidFG and left OrG, and decreased FC between bilateral IFG and OrG at TP3 than at TP1 (all FDR-p < 0.05). Meanwhile, mean fALFF values over the left SFG, MidFG, ventral CG, and IFG were significantly increased at TP3 as compared to those at TP2 (all p < 0.05 with Bonferroni correction).ConclusionBy combining TMS and fMRI, it becomes possible to track the spatiotemporal dynamics of TMS after-effects within the fronto-limbic network. Our findings suggested that the iTBS effect dynamically changed over time from the local neural activation at the stimulated site to its connected remote regions within the fronto-limbic network.

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Default mode network alterations after intermittent theta burst stimulation in healthy subjects.

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Default mode network alterations after intermittent theta burst stimulation in healthy subjects.

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