Mechanisms of Action Underlying the Effect of Repetitive Transcranial Magnetic Stimulation on Mood: Behavioral and Brain Imaging Studies

Abstract

In a set of experiments, we applied 10-Hz repetitive transcranial magnetic stimulation (rTMS) over the left mid-dorsolateral frontal cortex (MDLFC) to investigate rTMS-induced changes in affective state and neural activity in healthy volunteers. In Experiment 1, we combined 10-Hz rTMS with a speech task to examine rTMS-induced changes in paralinguistic aspects of speech production, an affect-relevant behavior strongly linked to the ACC. In Experiment 2, we combined 10-Hz rTMS with positron emission tomography (PET) and used partial least squares (PLS) to identify a pattern of brain regions whose connectivity with the site of stimulation varied as a function of rTMS. The results of Experiment 1 revealed that following stimulation of the left MDLFC, subjects reported having less positive affect and vitality and displayed more monotonous speech. In Experiment 2, results revealed that 10-Hz rTMS influenced the covariation between blood flow at the site of stimulation (ie the left MDLFC) and blood flow in a number of affect-relevant brain regions including the perigenual anterior cingulate gyrus, insula, thalamus, parahippocampal gyrus, and caudate nucleus. Taken together, our results suggest that changes in affect and affect-relevant behaviour following 10-Hz rTMS applied over the left MDLFC may be related to changes in neural activity in brain regions widely implicated in affective states, including a frontocingulate circuit.

Impact of tDCS on performance and learning of target detection: Interaction with stimulus characteristics and experimental design

“…Previous research by Barrett et al (2004) has demonstrated that stimulation near the areas we targeted in this study can result in changes in mood and affect, although stimulation parameters in the study by Barrett and colleagues (i.e. cathode location, specific anode location, electrode size, and current strength) were somewhat different from those used in our research.…”

Baseline ‘state anxiety’ influences HPA-axis sensitivity to one sham-controlled HF-rTMS session applied to the right dorsolateral prefrontal cortex

“…Current hypotheses on possible rTMS working mechanisms suggest that the neurobiological influence occurs at the subcortical level, such as the paraventricular nucleus (PVN) of the hypothalamus Keck, 2003). Prefrontal cortical stimulation not only results in enhanced neuronal activity under the stimulation coil locally, but spreads through transsynaptic transmission further to other prefrontal cortical areas, such as the anterior cingulate cortex (ACC), in subcortical structures implicated in the neurocircuitry of emotional processing (Paus et al, 2001;Nahas et al, 2001;Kimbrell et al, 2002;Barrett et al, 2004) and in the neurobiological mechanisms of controlling HPA-system responsiveness (Herman et al, 2005;Radley et al, 2006;Jankord and Herman, 2008). These cortico-subcortical innervations which project to the hypothalamus are branches of the basic loop that is connected to autonomic expression of emotion (Gray, 1999;Zahm, 2006).…”

A primer on the treatment of schizophrenia through repetitive transcranial magnetic stimulation

“…Previous research has linked schizophrenia with a failure to integrate activity in distributed neural circuits [47][48][49][50]. rTMS has the potential to induce changes in remote, functionally connected brain areas [51,52] in addition to local effects. The application of sequential stimulation, aimed at the areas of the PFC and temporoparietal cortex, seems to be an interesting approach, with some evidence for reduction in not only negative but also positive schizophrenia symptoms and potentially improved working memory [53].…”