Frequency-specific effects of low-intensity rTMS can persist for up to 2 weeks post-stimulation: A longitudinal rs-fMRI/MRS study in rats

Seewoo, Bhedita J.; Feindel, Kirk W.; Etherington, Sarah J.; Rodger, Jennifer

doi:10.1016/j.brs.2019.06.028

Cited by 27 publications

(53 citation statements)

References 97 publications

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“…Altered neurotransmitter concentrations within the striatal neuropil may reflect changes within intraneuronal sites and may not necessarily reflect changes in extracellular glutamate release following magnetic stimulation. In contrast, other studies have shown that glutamate levels were unaltered, although they were assessed in other brain regions (Keck et al, 2002;Seewoo et al, 2019). Despite the varied findings, it appears that glutamate release and concentration within the striatum (dorsal and NAc) are altered following rTMS; however, more research (e.g., electrophysiological recordings) is required to understand the effects of rTMS within this brain region.…”

Section: Glutamatergic Systemsmentioning

confidence: 92%

“…Reasons for how rTMS induces therapeutic effects in various neurological disorders remain unclear; however, a number of preclinical studies have identified mechanisms that could underlie the long-term effects. These mechanisms include alterations to neuron excitability (Sun et al, 2011;Hoppenrath et al, 2016;Tang et al, 2016) and Hebbiantype strengthening of synapses (Vlachos et al, 2012;Lenz et al, 2015), as well as alterations to gene expression (Ikeda et al, 2005;Grehl et al, 2015), trophic factors necessary for neuroplasticity (Gersner et al, 2011;Rodger et al, 2012;Makowiecki et al, 2014), activity within brain regions beyond the induced electrical field (Aydin-Abidin et al, 2008;Seewoo et al, 2018Seewoo et al, , 2019, and even changes to non-neuronal cells, which may contribute to plastic events (Clarke et al, 2017a,b;Cullen et al, 2019).…”

Section: Fundamentals Of Rtmsmentioning

confidence: 99%

“…The relevance of animal studies in understanding rTMS effects in humans has recently been highlighted by neuroimaging studies showing that rTMS can induce similar changes in functional connectivity in rats and in humans (Cocchi et al, 2016;Seewoo et al, 2018Seewoo et al, , 2019. More specifically, chronic rTMS in healthy rats was associated with changes to addiction-related networks such as the cortical-striatal-thalamic and basal-ganglia networks, with chronic HF-rTMS potentiating interoceptive/default mode network connectivity and attenuating connectivity in the salience network (Seewoo et al, 2019). Surprisingly, there have been no equivalent studies describing the effects of chronic rTMS on functional connectivity in addicted rodents or human populations.…”

Section: Animal Models Of Addictionmentioning

confidence: 99%

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rTMS-Induced Changes in Glutamatergic and Dopaminergic Systems: Relevance to Cocaine and Methamphetamine Use Disorders

2020

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Cocaine use disorder and methamphetamine use disorder are chronic, relapsing disorders with no US Food and Drug Administration-approved interventions. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation tool that has been increasingly investigated as a possible therapeutic intervention for substance use disorders. rTMS may have the ability to induce beneficial neuroplasticity in abnormal circuits and networks in individuals with addiction. The aim of this review is to highlight the rationale and potential for rTMS to treat cocaine and methamphetamine dependence: we synthesize the outcomes of studies in healthy humans and animal models to identify and understand the neurobiological mechanisms of rTMS that seem most involved in addiction, focusing on the dopaminergic and glutamatergic systems. rTMS-induced changes to neurotransmitter systems include alterations to striatal dopamine release and metabolite levels, as well as to glutamate transporter and receptor expression, which may be relevant for ameliorating the aberrant plasticity observed in individuals with substance use disorders. We also discuss the clinical studies that have used rTMS in humans with cocaine and methamphetamine use disorders. Many such studies suggest changes in network connectivity following acute rTMS, which may underpin reduced craving following chronic rTMS. We suggest several possible future directions for research relating to the therapeutic potential of rTMS in addiction that would help fill current gaps in the literature. Such research would apply rTMS to animal models of addiction, developing a translational pipeline that would guide evidence-based rTMS treatment of cocaine and methamphetamine use disorder.

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Section: Glutamatergic Systemsmentioning

confidence: 92%

Section: Fundamentals Of Rtmsmentioning

confidence: 99%

Section: Animal Models Of Addictionmentioning

confidence: 99%

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rTMS-Induced Changes in Glutamatergic and Dopaminergic Systems: Relevance to Cocaine and Methamphetamine Use Disorders

2020

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“…To maximise the use of collected data, rs-fMRI data and T2-weighted images collected using the same acquisition and anaesthesia protocols from a previous study (Seewoo et al, 2019) in adult (6-8 weeks old, 150-250 g) male Sprague Dawley rats were also included in the analyses for baseline and control groups ( Table 2). These animals did not undergo any behavioural testing or intervention before the acquisition of MRI data.…”

Section: Rs-fmri Datamentioning

confidence: 99%

“…The interoceptive (Becerra et al, 2011;Seewoo et al, 2019) and salience (Bajic et al, 2016;Seewoo et al, 2019) networks were identified from baseline rs-fMRI data and used in dual regression analysis for detecting functional connectivity differences induced by CRS (Fig. 4).…”

Section: Changes In Resting-state Functional Connectivitymentioning

confidence: 99%

Validation of chronic restraint stress model in rats for the study of depression using longitudinal multimodal MR imaging

Seewoo

Hennessy

Feindel

et al. 2020

Preprint

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Prior research suggests that the neurobiological underpinnings of depression include disruptions in functional connectivity, neurometabolite levels, and hippocampal volume. This study examined the validity of a chronic restraint stress (CRS) paradigm in male Sprague Dawley rats for the study of depression using longitudinal behavioural tests and multiple 9.4 T MRI modalities (resting-state functional MRI, proton magnetic resonance spectroscopy, and volumetric studies). In the CRS protocol, rats were placed in individual transparent tubes for 2.5 h daily over 13 days. Elevated plus-maze test (EPM) and forced swim test (FST) confirmed the presence of anxiety-like and depression-like behaviours respectively post-restraint. Brain changes were also detected by MR. The rs-fMRI data revealed hypoconnectivity within the salience and interoceptive networks and hyperconnectivity of several brain regions to the cingulate cortex. The 1 H-MRS data revealed decreased sensorimotor cortical glutamate, glutamine and combined glutamate-glutamine levels. Volumetric analysis of T2-weighted images revealed decreased hippocampal volume, which was also correlated with salience network connectivity. Depression-like behaviours were correlated with salience and interoceptive network connectivity, glutamate and combined glutamate-glutamine levels and hippocampal volume. Anxiety-like behaviours were correlated with both hippocampus connectivity and interoceptive network connectivity. The present findings identify significant changes in brain connectivity, neurometabolites and structure that are correlated with abnormal behaviour in CRS rats. Importantly, these changes parallel those found in human depression, suggesting that the CRS rodent model has utility for translational studies and novel intervention development for depression.

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Hierarchical Bayesian modeling of the relationship between task‐related hemodynamic responses and cortical excitability

Cai

Pellegrino

Lina

et al. 2022

Human Brain Mapping

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Investigating the relationship between task-related hemodynamic responses and cortical excitability is challenging because it requires simultaneous measurement of hemodynamic responses while applying noninvasive brain stimulation. Moreover, cortical excitability and task-related hemodynamic responses are both associated with inter-/intra-subject variability. To reliably assess such a relationship, we applied hierarchical Bayesian modeling. This study involved 16 healthy subjects who underwent simultaneous Paired Associative Stimulation (PAS10, PAS25, Sham) while monitoring brain activity using functional Near-Infrared Spectroscopy (fNIRS), targeting the primary motor cortex (M1). Cortical excitability was measured by Motor Evoked Potentials (MEPs), and the motor task-related hemodynamic responses were measured using fNIRS 3D reconstructions. We constructed three models to investigate: (1) PAS effects on the M1 excitability, (2) PAS effects on fNIRS hemodynamic responses to a finger tapping task, and (3) the correlation between PAS effects on M1 excitability and PAS effects on task-related hemodynamic responses. Significant increase in cortical excitability was found following PAS25, whereas a small reduction of the cortical excitability was shown after PAS10 and a subtle increase occurred after sham. Both HbO and HbR absolute amplitudes increased after PAS25 and decreased after PAS10. The probability of the positive correlation between modulation of cortical excitability and hemodynamic activity was 0.77 for HbO and 0.79 for HbR. We demonstrated that PAS stimulation modulates task-related cortical hemodynamic responses in addition to M1 excitability. Moreover, the positive correlation between

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Frequency-specific effects of low-intensity rTMS can persist for up to 2 weeks post-stimulation: A longitudinal rs-fMRI/MRS study in rats

Abstract: Please cite this article as: Seewoo BJ, Feindel KW, Etherington SJ, Rodger J, Frequency-specific effects of low-intensity rTMS can persist for up to 2 weeks post-stimulation: A longitudinal rs-fMRI/MRS study in rats, Brain Stimulation,

Cited by 27 publications

References 97 publications

rTMS-Induced Changes in Glutamatergic and Dopaminergic Systems: Relevance to Cocaine and Methamphetamine Use Disorders

rTMS-Induced Changes in Glutamatergic and Dopaminergic Systems: Relevance to Cocaine and Methamphetamine Use Disorders

Validation of chronic restraint stress model in rats for the study of depression using longitudinal multimodal MR imaging

Hierarchical Bayesian modeling of the relationship between task‐related hemodynamic responses and cortical excitability

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