Handedness is considered to be one of the more obvious functional asymmetries within the human brain. The neural representation of handedness can be visually confirmed using neuroimaging. Less obvious functional asymmetries, such as language, creative problem-solving, and executive decision making require further investigation to determine neurological lateralization. Language regions (e.g., Wernicke’s and Broca’s areas) as well as the dorsolateral prefrontal cortex (dlPFC) constitute key functional targets for various therapeutic interventions (Avissar, 2017). The dlPFC is predominantly associated with frontal-executive skills, such as working memory, decision-making, creativity, and motor planning, and is functionally and reciprocally related to deeper prefrontal areas involved in mood regulation (Miller, 2001). Hemispheric localization varies to some degree with handedness, however, no heuristic used to correlate handedness with language or dominant dlPFC provides certainty. For instance, among a majority of right-handed individuals, dominant language function is most often localized to the left hemisphere. For many left-handed individuals, language may be lateralized to the left hemisphere as well; however, in contrast to right-handers, many left-handed participants will actually show either right hemisphere or bilateral representation.
Effective localization is highly important for decreasing the functional risks associated with neurosurgery and may be useful for determining placement for effective non-invasive stimulation techniques (e.g., transcranial magnetic stimulation, TMS). Repetitive TMS (rTMS) has been shown to mitigate subgenual cingulate hyperactivity in patients with refractory depression, nearly toward levels of healthy patients (Hadas, 2019). However, most literature on the use of rTMS for patients with depression report rTMS application over the left dlPFC rather than the right, assuming that right-handers have a dominant dlPFC on the left hemisphere (George, et al., 2010; George, 2013; Eche, 2012; Perera, 2016). Importantly, it is not uncommon for patients to have a negative reaction to right dlPFC rTMS, yielding agitation or mania, requiring switching to the contralateral dlPFC to provide the desired therapeutic effects.
Early imaging experience suggested that depressed patients appear to have decreased activation of the dlPFC with inverse increased activation of the subgenual prefrontal region. Both neurosurgical navigation and rTMS targeting protocols have occasionally deployed seed analysis to determine stimulation sites or establish the bounds of a surgical field. For instance, one technique for localizing the dlPFC involves an anticorrelation seed analysis of the subgenual cingulate (Biver, 1994; Baxter Jr, 1989; Galynker II, 1998; Mayberg, 2005; Chen, 2013; Liston, 2014; Fox, 2012). These techniques have been used to attempt to improve treatment outcomes. In this vein, the present study attempted to use a method to optimize effective functional localization strategies for both language regions and the dlPFC using an fMRI task that combines elements of creative problem solving, executive decision making based on an internal rule set, and working memory.