Temporal assessment of behavior in Parkinson's visual hallucinations via a multidimensional analysis strategy.

Abstract

Visual hallucination (VH) is a common nonmotor symptom of Parkinson's disease (PD). However, the lack of reliable animal models and quantitative assessment tools poses significant challenges for mechanism and intervention research in this area. Here, we developed a novel PD-related visual hallucination (PDVH) model by administering benzhexol hydrochloride, which can induce hallucinatory phenotypes in PD model mice. On the basis of this model, we used a multidimensional behavioral analysis framework to identify a hallucination-related hunching state (HHS) that is strongly associated with hallucinatory episodes. This state is characterized by a sustained hunching posture accompanied by prolonged staring and embedded head twitching. By constructing a spontaneous behavior transition map, we found that the emergence of spontaneous behaviors is highly dependent on the immediately preceding state, revealing that the core hallucinatory features are structured and predictable at the level of spontaneous behavior. The relative fractions and transition probabilities of staring and head twitching allow high-throughput identification of PDVH mice and reflect temporal dynamics of the hallucination process. Our findings demonstrate that this approach enables high spatiotemporal resolution acquisition and analysis of behaviors associated with PDVH, offering a robust experimental framework for investigating PDVH mechanisms at the circuit level and developing targeted therapeutic strategies.