Previous studies suggest that pain perception is greatly shaped by anticipation, with M1 and DLPFC involved in this process. We hypothesized that high-frequency rTMS targeting these regions could alter pain anticipation and thereby reduce pain perception. In a double-blind, sham-controlled study, healthy participants received 10 Hz rTMS to M1, DLPFC, or a sham treatment. Assessments were conducted before, immediately after, and 60 min after stimulation, including laser-evoked potentials, pain ratings, and anticipatory EEG. M1-rTMS immediately reduced laser-evoked P2 amplitude, increased sensorimotor high-frequency α-oscillation power, and accelerated peak alpha frequency in the midfrontal region during pain anticipation. In contrast, DLPFC-rTMS reduced the N2-P2 complex and pain ratings 60 min post-stimulation, an effect associated with prolonged microstate C duration during pain anticipation—a microstate linked to default mode network activity. Thus, M1-rTMS immediately modulates anticipatory α-oscillations and laser-evoked potentials, while DLPFC-rTMS induces delayed analgesic effects partially by modulating default mode network activity.

Reduced empathy and elevated alexithymia are observed in autism spectrum disorder (ASD), which has been linked to altered asymmetry in brain morphology. Here, we investigated whether trait autism, empathy, and alexithymia in the general population is associated with brain morphological asymmetry. We determined left–right asymmetry indexes for cortical thickness and cortical surface area (CSA) and applied these features to a support-vector regression model that predicted trait autism, empathy, and alexithymia. Results showed that less leftward asymmetry of CSA in the gyrus rectus (a subregion of the orbitofrontal cortex) predicted more difficulties in social functioning, as well as reduced cognitive empathy and elevated trait alexithymia. Meta-analytic decoding of the left gyrus rectus annotated functional items related to social cognition. Furthermore, the link between gyrus rectus asymmetry and social difficulties was accounted by trait alexithymia and cognitive empathy. These results suggest that gyrus rectus asymmetry could be a shared neural correlate among trait alexithymia, cognitive empathy, and social functioning in neurotypical adults. Left–right asymmetry of gyrus rectus influenced social functioning by affecting the cognitive processes of emotions in the self and others. Interventions that increase leftward asymmetry of the gyrus rectus might improve social functioning for individuals with ASD.

Brain dynamics can be modeled by a sequence of transient, nonoverlapping patterns of quasi-stable electrical potentials named “microstates.” While electroencephalographic (EEG) microstates among patients with chronic pain remained inconsistent in the literature, this study characterizes the temporal dynamics of EEG microstates among healthy individuals during experimental sustained pain. We applied capsaicin (pain condition) or control (no-pain condition) cream to 58 healthy participants in different sessions and recorded resting-state EEG 15 min after application. We identified 4 canonical microstates (A–D) that are related to auditory, visual, salience, and attentional networks. Microstate C had less occurrence, as were bidirectional transitions between microstate C and microstates A and B during sustained pain. In contrast, sustained pain was associated with more frequent and longer duration of microsite D, as well as more bidirectional transitions between microstate D and microstates A and B. Microstate D duration positively correlated with intensity of ongoing pain. Sustained pain improved global integration within microstate C functional network, but weakened global integration and efficiency within microstate D functional network. These results suggest that sustained pain leads to an imbalance between processes that load on saliency (microstate C) and processes related to switching and reorientation of attention (microstate D).

Transcranial direct current stimulation (tDCS) exhibits potential for pain management, yet its protective efficacy against persistent pain remains underexplored. This study investigates the protective effects of preemptive tDCS over the primary motor cortex (M1) and dorsolateral prefrontal cortex (dlPFC) on mitigating capsaicin-induced persistent pain. Eighty participants underwent M1- or dlPFC-targeted tDCS before capsaicin application, with electroencephalography recorded for 60 min. Both protocols comparably reduced pain intensity, anxiety, and sensorimotor β/γ-oscillation activity. Microstate analysis identified five canonical microstates (A − E) that have been linked to auditory, visual, default-mode, dorsal attention, and salience networks. M1-tDCS decreased microstate C (self-referential processing) while enhancing microstate D (cognitive control), whereas dlPFC-tDCS suppressed microstate D activity. Mechanistically, M1-tDCS alleviated anxiety via increased D ↔ E transitions (cognitive-emotional integration), while dlPFC-tDCS attenuated pain through reduced D ↔ C shifts (cognitive-self-referential integration). These findings highlight both shared and distinct neuromodulatory effects of M1/dlPFC-tDCS, supporting their potential as preemptive strategies for persistent pain management.