Pathological claustrum activity drives aberrant cognitive network processing in human chronic pain.

Aberrant cognitive network activity and cognitive deficits are established features of chronic pain. However, the nature of cognitive network alterations associated with chronic pain and their underlying mechanisms require elucidation. Here, we report that the claustrum, a subcortical nucleus implicated in cognitive network modulation, is activated by acute painful stimulation and pain-predictive cues in healthy participants. Moreover, we discover pathological activity of the claustrum and a region near the posterior inferior frontal sulcus of the right dorsolateral prefrontal cortex (piDLPFC) in migraine patients during acute pain and cognitive task performance. Dynamic causal modeling suggests a directional influence of the claustrum on activity in this piDLPFC region, and diffusion weighted imaging verifies their structural connectivity. These findings advance understanding of claustrum function during acute pain and provide evidence of a possible circuit mechanism driving cognitive impairments in chronic pain.

Pathological claustrum activity drives aberrant cognitive network processing in human chronic pain.

Aberrant cognitive network activity and cognitive deficits are established features of chronic pain. However, the nature of cognitive network alterations associated with chronic pain and their underlying mechanisms require elucidation. Here, we report that the claustrum, a subcortical nucleus implicated in cognitive network modulation, is activated by acute painful stimulation and pain-predictive cues in healthy participants. Moreover, we discover pathological activity of the claustrum and a lateral aspect of the right dorsolateral prefrontal cortex (latDLPFC) in migraine patients. Dynamic causal modeling suggests a directional influence of the claustrum on activity in this latDLPFC region, and diffusion weighted imaging (DWI) verifies their structural connectivity. These findings advance understanding of claustrum function during acute pain and provide evidence of a possible circuit mechanism driving cognitive impairments in chronic pain.

Insula-cingulate structural and functional connectivity: an ultra-high field MRI study.

The insula and the cingulate are key brain regions with many heterogenous functions. Both regions are consistently shown to play integral roles in the processing of affective, cognitive, and interoceptive stimuli. The anterior insula (aINS) and the anterior mid-cingulate cortex (aMCC) are two key hubs of the salience network (SN). Beyond the aINS and aMCC, previous 3 Tesla (T) magnetic resonance imaging studies have suggested both structural connectivity (SC) and functional connectivity (FC) between other insular and cingulate subregions. Here, we investigate the SC and FC between insula and cingulate subregions using ultra-high field 7T diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rs-fMRI). DTI revealed strong SC between posterior INS (pINS) and posterior MCC (pMCC), and rs-fMRI revealed strong FC between the aINS and aMCC that was not supported by SC, indicating the likelihood of a mediating structure. Finally, the insular pole had the strongest SC to all cingulate subregions, with a slight preference for the pMCC, indicative of a potential relay node of the insula. Together these finding shed new light on the understanding of insula-cingulate functioning, both within the SN and other cortical processes, through a lens of its SC and FC.