Aberrant prefrontal-hippocampal connectivity of cross-modal associative memory impairment in schizophrenia

Associative memory (AM) impairment is considered as a core cognitive dysfunction and indicative of poor function in schizophrenia. Despite the robust findings of abnormalities in prefrontal-hippocampal network, yet the specific regions and definitive patterns have remained elusive. We adopted an innovative AM paradigm to disentangle the contributions of prefrontal-hippocampal network.

In this cross-sectional study, 30 schizophrenia patients and 30 matched healthy controls (HCs) were recruited, scheduled for an MRI session on a 3.0T Siemens, and completed clinical evaluations. We performed seed-based functional connectivity (FC) analyses using the bilateral hippocampus (Hipp) as seeds and conducted Pearson's correlation analyses between FC and the AM performance.

Compared to HCs, patients exhibited poorer AM functions in both same- and cross-domain conditions. Left Hipp exhibited decreased FC with clusters from medial and orbital superior frontal gyrus (SFG) bilaterally (p-FDR < 0.001), while enhanced FC with clusters from bilateral inferior frontal gyrus (IFG), pars opercularis and triangularis (p-FDR < 0.01) in the schizophrenia relative to HCs. Notably, decreased left Hipp-related FC was moderately positively correlated with cross-modal AM performance in HCs but not in the schizophrenia group. Conversely, a significant positive correlation was found between left Hipp-bilateral IFG FC values and cross-modal AM capacities in schizophrenia.

The current study demonstrated the disparities in AM deficits and substantiate correlative evidence for prefrontal-hippocampal network involvement in AM. These findings provide evidence for neuropathological mechanisms in schizophrenia, which potentially guiding relevant interventions and treatments.