Abstract
Hemispheric differences in emotional processing have been observed for over half a century, leading to multiple theories classifying differing roles for the right and left hemisphere in emotional processing. Conventional acceptance of these theories has had lasting clinical implications for the treatment of mood disorders. The theory that the left hemisphere is broadly associated with positively valenced emotions, while the right hemisphere is broadly associated with negatively valenced emotions, drove the initial application of repetitive transcranial magnetic stimulation (rTMS) for the treatment of major depressive disorder (MDD). Subsequent rTMS research has led to improved response rates while adhering to the same initial paradigm of administering excitatory rTMS to the left prefrontal cortex (PFC) and inhibitory rTMS to the right PFC. However, accumulating evidence points to greater similarities in emotional regulation between the hemispheres than previously theorized, with potential implications for how rTMS for MDD may be delivered and optimized in the near future. This review will catalog the range of measurement modalities that have been used to explore and describe hemispheric differences, and highlight evidence that updates and advances knowledge of TMS targeting and parameter selection. Future directions for research are proposed that may advance precision medicine and improve efficacy of TMS for MDD.
Highlights
The implications of hemispheric laterality have been of interest to neuroscientists and the lay public alike for over half a century [1]
Despite numerous studies confirming that the left dorsolateral prefrontal cortex (DLPFC) is an efficacious target for HF-repetitive transcranial magnetic stimulation (rTMS) at the group level, response rates with these protocols remain between 25%
While a selective review of studies beyond the rTMS literature provides ample support for the conventional hemispheric paradigm [22], in consideration of the ongoing problem of treatment resistance in major depressive disorder (MDD) it is reasonable to ask whether treatment delivered outside the typical paradigm may benefit patients who do not response to rTMS
Summary
The implications of hemispheric laterality have been of interest to neuroscientists and the lay public alike for over half a century [1]. While a selective review of studies beyond the rTMS literature provides ample support for the conventional hemispheric paradigm [22], in consideration of the ongoing problem of treatment resistance in major depressive disorder (MDD) it is reasonable to ask whether treatment delivered outside the typical paradigm may benefit patients who do not response to rTMS Evidence for this possibility exists, as the neuroscientific literature is more equivocal than might be expected based on the focus of rTMS and MDD research to date, with theoretical and experimental work providing a rationale for reconsideration of early protocols and exploration of novel protocols, in the right hemisphere. 1996 study was the first evidence that the right hemisphere might respond oppositely to HF-rTMS compared to the left [8], setting the stage for numerous efficacy studies validating the left/excitatory, right/inhibitory paradigm [43]
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