Evidence for enhanced backward connectivity in the third visual pathway following cortico-cortical paired associative stimulation

The posterior superior temporal sulcus (pSTS) and early visual cortex (V1/V2) form part of a lateral occipito-temporal network - proposed as a "third" visual pathway - supporting the processing of socially and emotionally relevant information. Prior studies using cortico-cortical paired associative stimulation (ccPAS) applied from pSTS to V1/V2 have shown enhanced recognition of facial emotional expressions, interpreted as reflecting strengthened temporo-occipital backward connectivity. However, direct evidence that ccPAS can modulate pSTS-to-V1/V2 connectivity has been lacking. Here, we applied ccPAS consisting of repeated paired TMS pulses, with the first pulse delivered over pSTS and the second pulse over V1/V2 (ccPASSTS-V1). A reverse-order protocol (ccPASV1-STS) served as a control. Resting-state EEG was recorded before, immediately after, and 30 min post-stimulation to assess functional connectivity. Multivariate spectral Granger Causality analysis characterized the directionality and frequency-dependent dynamics of connectivity. Outdegree metrics revealed that ccPASSTS-V1 enhanced backward functional connectivity immediately after stimulation, with effects persisting after 30 min, possibly consistent with Hebbian-like associative plasticity in top-down pathways. In addition, an increase in forward connectivity was observed 30 min after ccPASV1-STS, and more weakly after ccPASSTS-V1, possibly reflecting broader compensatory mechanisms. These findings demonstrate that ccPAS can transiently and selectively modulate directional connectivity within the "third" visual pathway, providing insights into the physiological basis of ccPAS and suggesting that previously observed improvements in emotion recognition following ccPASSTS-V1 may arise from plastic changes in backward pSTS-to-V1/V2 connectivity. More broadly, they underscore the potential of ccPAS to probe and modulate the dynamics of higher-order visual circuits.