Modulating functional connectivity between medial frontopolar cortex and amygdala by inhibitory and excitatory transcranial magnetic stimulation

Abstract

The prefrontal‐limbic network in the human brain plays a major role in social cognition, especially cognitive control of emotion. The medial frontopolar cortex (mFP; Brodmann Area 10) and the amygdala are part of this network and display correlated neuronal activity in time, as measured by functional magnetic resonance imaging (fMRI). This functional connectivity is dynamic, sensitive to training, and affected in mental disorders. However, the effects of neurostimulation on functional connectivity within this network have not yet been systematically investigated. Here, we investigate the effects of both low‐ and high‐frequency repetitive transcranial magnetic stimulation (rTMS) to the right mFP on functional connectivity between mFP and amygdala, as measured with resting state fMRI (rsfMRI). Three groups of healthy participants received either low‐frequency rTMS (1 Hz; N = 18), sham TMS (1 Hz, subthreshold; N = 18) or high‐frequency rTMS (20 Hz; N = 19). rsfMRI was acquired before and after (separate days). We hypothesized a modulation of functional connectivity in opposite directions compared to sham TMS through adjustment of the stimulation frequency. Groups differed in functional connectivity between mFP and amygdala after stimulation compared to before stimulation (low‐frequency: decrease, high‐frequency: increase). Motion or induced changes in neuronal activity were excluded as confounders. Results show that rTMS is effective for increasing and decreasing functional coherence between prefrontal and limbic regions. This finding is relevant for social and affective neuroscience as well as novel treatment approaches in psychiatry.

High-Frequency rTMS of the Motor Cortex Modulates Cerebellar and Widespread Activity as Revealed by SVM

“…The motor cortex is a widely used stimulation target for rTMS (Lefaucheur, 2019). Many studies have claimed that FC alters after rTMS on the motor cortex (Nettekoven et al, 2014;Esterman et al, 2017;Ji et al, 2017;Hawco et al, 2018;Riedel et al, 2019;Shang et al, 2019). The seed selection and candidate networks varied among these studies.…”

Questioning the role of amygdala and insula in an attentional capture by emotional stimuli task

“…A number of reviews highlight the importance of the amygdala for the processing of emotional stimuli (Armony, 2013; Iordan et al, 2013; LeDoux, 2003; Pessoa, 2010, 2017; Sander, Grafman, & Zalla, 2003; Sergerie, Chochol, & Armony, 2008; Zald, 2003). Functionally and structurally, the amygdala is connected with the prefrontal cortex (M. J. Kim et al, 2011; Riedel et al, 2019), and has been described as an integral part of the” hot emotional system” with inputs from the temporal, frontal and insular cortices (Dolcos et al, 2011; Iordan et al, 2013; Pessoa, 2017). Clinically, group differences in amygdala activity are, for example, observed for subjects with or without a family history of depression (Pilhatsch et al, 2014) or in subjects with major depressive disorder (Davidson, Pizzagalli, Nitschke, & Putnam, 2002; Sheline et al, 2001).…”

Combining transcranial magnetic stimulation with functional magnetic resonance imaging for probing and modulating neural circuits relevant to affective disorders

“…Even an electrical "sham" stimulation of the scalp will have a biological effect that needs to be ruled out. Comparing pre-to post-rTMS imaging data has shown clinically relevant findings such as an acute change in medial prefrontal to amygdala resting connectivity following a single round of rTMS (Riedel et al, 2019) as well as a change in subgenual cingulate to default mode connectivity after a clinical dose of rTMS treatment in depression (Liston et al, 2014). In the latter study, rTMS was applied to the dorsolateral prefrontal cortex (DLPFC) but the connectivity changes between the remote sgACC and DMN were associated with depression improvement.…”

“…Connectivity of distributed brain networks, best measured with online imaging, may be the most relevant mechanism of brain changes in response to rTMS that drive symptom improvement. Whether changes are found in the site of stimulation (e.g., Nettekoven et al, 2014) or in remote brain areas (Liston et al, 2014;Riedel et al, 2019), it is possible to conclude that the changes demonstrate brain areas that are part of the causal pathway of the stimulation site due to the knowledge of where stimulation was applied (with caveats for unmeasured confounds; see Box 1). Adding neuroimaging recordings following neuromodulation is the only way to know the extent to which brain networks responded to the neuromodulation.…”