Differential effects of long and short train theta burst stimulation on LTP induction in rat anterior cingulate cortex slices: Multi-electrode array recordings

Abstract INTRODUCTION Minimally invasive neuromodulation such as spinal cord stimulation (SCS) and occipital nerve stimulation (ONS) have shown to be successful for treatment of different types of pain such as chronic back or leg pain, complex regional pain syndrome (CRPS), and fibromyalgia. Recently, novel stimulation paradigm called burst stimulation was developed that suppresses pain to better extent than classical tonic stimulation. From clinical point of view, burst stimulation is very promising; however, little is known about its underlying mechanism. Hence, in this work we investigate mechanism of action for burst stimulation in different patient groups and controls using different neuroimaging multimodalities such as EEG, fMRI and PET. METHODS Control subjects and patients with chronic back or leg pain, CRPS, or fibromyalgia enrolled for study. Both controls and patients received SCS or ONS and sham, tonic, and burst stimulation in fMRI, PET, and EEG. RESULTS >EEG shows significant changes for burst stimulation compared to tonic and sham stimulation; evident by increased activity at dorsal anterior cingulate cortex (dACC), dorsolateral prefrontal cortex (dPFC), primary somatosensory cortex, and posterior cingulate cortex (PSC) in alpha frequency band. PET further confirmed by showing increased tracer capitation for burst in dACC, pregenual anterior cingulate cortex (pgACC), parahippocampus, and fusiform gyrus. Furthermore, fMRI showed burst changes in dACC, dPFC, pgACC, cerebellum, hypothalamus, and premotor cortex. A conjunction analysis between tonic and burst stimulation demonstrated theta activity is commonly modulated in somatosensory cortex and PSC. CONCLUSION Our data suggest that burst and tonic stimulation modulate ascending lateral and descending pain inhibitory pathways. Burst stimulation adds by modulating the medial pain pathway, possibly by direct modulation of spinothalamic pathway, as suggested by animal research. Burst normalizes an imbalance between ascending pain via medial system and descending pain inhibitory activity, which could be a plausible reason it's better than to tonic stimulation.

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Intermittent theta burst stimulation at personalized targets reduces the functional connectivity of the default mode network in healthy subjects

10.1101/646265 ◽

2019 ◽

Cited By ~ 1

Author(s):

Aditya Singh ◽

Tracy Erwin-Grabner ◽

Grant Sutcliffe ◽

Walter Paulus ◽

Peter Dechent ◽

...

Keyword(s):

Transcranial Magnetic Stimulation ◽

Functional Connectivity ◽

Default Mode Network ◽

Healthy Subjects ◽

Magnetic Stimulation ◽

Anterior Cingulate ◽

Single Session ◽

Theta Burst Stimulation ◽

Burst Stimulation ◽

Theta Burst

AbstractUnderstanding the mechanisms by which transcranial magnetic stimulation protocols exert changes in the default mode network (DMN) is paramount to develop therapeutically more effective approaches in the future. 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 but current understanding of the effects of a single session of intermittent theta burst stimulation (iTBS) on the DMN in healthy subjects is limited. To reduce the effects of inter-individual variability in functional architectures, we used a novel personalized target selection approach based on each subject’s resting state fMRI for an unprecedented investigation into the effects of a single session (1800 pulses) of iTBS over the DMN in healthy controls. 26 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). Approx. 25-30 minutes after stimulation, we observed reduced FC between the DMN and the rostral anterior cingulate cortex (rACC). About 45 minutes after stimulation the FC of rACC strongly decreased further, as did the FC of right anterior insula (rAI) with the DMN. We also report a positive correlation between the FC decrease in the rACC and the HA domain of TCI. Our results show how iTBS at personalized left-DLPFC targets reduces the FC between DMN and the rACC and rAI, regions typically described as nodes of the salience network. We find that HA scores can potentially predict iTBS response, as has been observed for HF-rTMS.

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Subgenual Anterior Cingulate–Medial Orbitofrontal Functional Connectivity in Medication-Resistant Major Depression: A Neurobiological Marker for Accelerated Intermittent Theta Burst Stimulation Treatment?

Biological Psychiatry Cognitive Neuroscience and Neuroimaging ◽

10.1016/j.bpsc.2017.01.001 ◽

2017 ◽

Vol 2 (7) ◽

pp. 556-565 ◽

Cited By ~ 18

Author(s):

Chris Baeken ◽

Romain Duprat ◽

Guo-Rong Wu ◽

Rudi De Raedt ◽

Kees van Heeringen

Keyword(s):

Major Depression ◽

Functional Connectivity ◽

Anterior Cingulate ◽

Theta Burst Stimulation ◽

Burst Stimulation ◽

Theta Burst

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Neuromodulation for Depression

Depression ◽

10.1093/med/9780190929565.003.0019 ◽

2019 ◽

pp. 318-342

Author(s):

John P. Coetzee ◽

Nolan Williams

Keyword(s):

Magnetic Stimulation ◽

Focused Ultrasound ◽

Anterior Cingulate ◽

Theta Burst Stimulation ◽

Burst Stimulation ◽

Subgenual Anterior Cingulate Cortex ◽

Low Intensity ◽

Dorsolateral Prefrontal ◽

Epidural Cortical Stimulation ◽

Theta Burst

Neuromodulation (also known as neurostimulation) is a growing and important category of treatments for depression. First-line treatments such as pharmacotherapy and counseling often fail to achieve remission, and neuromodulation can help many such patients. Neuromodulatory techniques can be broadly divided into invasive approaches, which include deep brain stimulation, epidural cortical stimulation, and vagal nerve stimulation, and noninvasive approaches, which include electroconvulsive therapy, transcranial magnetic stimulation, theta burst stimulation, and transcranial direct-current stimulation, among others. While efficacy varies among techniques, those with the most efficacy tend to be those that target nodes of a proposed tripartate functional connected circuit that includes left dorsolateral prefrontal cortex, subgenual anterior cingulate cortex, and vagus nerve. Treatments currently being developed that hold promise include accelerated intermittent theta burst stimulation and low-intensity focused ultrasound pulsation.

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Brain-Derived Neurotrophic Factor Produced Long-Term Synaptic Enhancement in The Anterior Cingulate Cortex of Adult Mice

10.21203/rs.3.rs-812346/v1 ◽

2021 ◽

Author(s):

Hui-Hui Miao ◽

Zhuang Miao ◽

Ji-Gang Pan ◽

Xu-Hui Li ◽

Min Zhuo

Keyword(s):

Anterior Cingulate Cortex ◽

Neurotrophic Factor ◽

Metabotropic Glutamate Receptors ◽

Electrode Array ◽

Cingulate Cortex ◽

Long Term Potentiation ◽

Brain Derived Neurotrophic Factor ◽

Anterior Cingulate ◽

Synaptic Responses

Abstract Previous studies show that brain-derived neurotrophic factor (BDNF) is one of diffusible messengers for enhancing synaptic transmission in the hippocampus. Less information is available for possible roles of BDNF in the anterior cingulate cortex (ACC). In the present study, we used 64-electrode array field recording system to investigate the effect of BDNF on ACC excitatory transmission. We found that BDNF enhanced synaptic responses in a dose-dependently manner in the ACC. The enhancement was long-lasting, and persisted for at least three hours. In addition to the enhancement, BDNF also recruited inactive synaptic responses in the ACC. Bath application of the tropomyosin receptor kinase B (TrkB) receptor antagonist K252a blocked BDNF-induced enhancement. L-type voltage-gated calcium channels (L-VGCC), metabotropic glutamate receptors (mGluRs), but not NMDA receptors were required for BDNF-produced enhancement. Moreover, calcium-stimulated adenylyl cyclase subtype 1 (AC1) but not AC8 was essential for the enhancement. A selective AC1 inhibitor NB001 completely blocked the enhancement. Furthermore, BDNF-produced enhancement occluded theta burst stimulation (TBS) induced long-term potentiation (LTP), suggesting that they may share similar signaling mechanisms. Finally, the expression of BDNF-induced enhancement depends on postsynaptic incorporation of calcium-permeable AMPA receptors (CP-AMPARs) and protein kinase Mζ (PKMζ). Our results demonstrate that cortical BDNF may contribute to synaptic potentiation in the ACC.

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