Effective Connectivity Network of Aberrant Prediction Error Processing in Auditory Phantom Perception.

Abstract

Introduction: Prediction error (PE) is key to perception in the predictive coding framework. However, previous studies indicated the varied neural activities evoked by PE in tinnitus patients. Here, we aimed to reconcile the conflict by (1) a more nuanced view of PE, which could be driven by changing stimulus (stimulus-driven PE [sPE]) and violation of current context (context-driven PE [cPE]) and (2) investigating the aberrant connectivity networks that are engaged in the processing of the two types of PEs in tinnitus patients. Methods: Ten tinnitus patients with normal hearing and healthy controls were recruited, and a local-global auditory oddball paradigm was applied to measure the electroencephalographic difference between the two groups during sPE and cPE conditions. Results: Overall, the sPE condition engaged bottom-up and top-down connections, whereas the cPE condition engaged mostly top-down connections. The tinnitus group showed decreased sensitivity to the sPE and increased sensitivity to the cPE condition. Particularly, the auditory cortex and posterior cingulate cortex were the hubs for processing cPE in the control and tinnitus groups, respectively, showing the orientation to an internal state in tinnitus. Furthermore, tinnitus patients showed stronger connectivity to the parahippocampus and pregenual anterior cingulate cortex for the establishment of the prediction during the cPE condition. Conclusion: These results begin to dissect the role of changes in stimulus characteristics versus changes in the context of processing the same stimulus in mechanisms of tinnitus generation. Impact Statement This study delves into the number dynamics of prediction error (PE) in tinnitus, proposing a dual framework distinguishing between stimulus-driven PE (sPE) and context-driven PE (cPE). Electroencephalographic data from tinnitus patients and controls revealed distinct connectivity patterns during sPE and cPE conditions. Tinnitus patients exhibited reduced sensitivity to sPE and increased sensitivity to cPE. The auditory cortex and posterior cingulate cortex emerged as pivotal regions for cPE processing in controls and tinnitus patients, indicative of an internal state orientation in tinnitus. Enhanced connectivity to the parahippocampus and pregenual anterior cingulate cortex underscores the role of context in tinnitus pathophysiology.