Abstract
Background:The neural substrates of visual hallucinations remain an enigma, due primarily to the difficulties associated with directly interrogating the brain during hallucinatory episodes.Aims:To delineate the functional patterns of brain network activity and connectivity underlying visual hallucinations in Parkinson’s disease.Methods:In this study, we combined functional magnetic resonance imaging (MRI) with a behavioral task capable of eliciting visual misperceptions, a confirmed surrogate for visual hallucinations, in 35 patients with idiopathic Parkinson’s disease. We then applied an independent component analysis to extract time series information for large-scale neuronal networks that have been previously implicated in the pathophysiology of visual hallucinations. These data were subjected to a task-based functional connectivity analysis, thus providing the first objective description of the neural activity and connectivity during visual hallucinations in patients with Parkinson’s disease.Results:Correct performance of the task was associated with increased activity in primary visual regions; however, during visual misperceptions, this same visual network became actively coupled with the default mode network (DMN). Further, the frequency of misperception errors on the task was positively correlated with the strength of connectivity between these two systems, as well as with decreased activity in the dorsal attention network (DAN), and with impaired connectivity between the DAN and the DMNs, and ventral attention networks. Finally, each of the network abnormalities identified in our analysis were significantly correlated with two independent clinical measures of hallucination severity.Conclusions:Together, these results provide evidence that visual hallucinations are due to increased engagement of the DMN with the primary visual system, and emphasize the role of dysfunctional engagement of attentional networks in the pathophysiology of hallucinations.
Highlights
Theoretical models have implicated sensory, attentional, and cognitive deficits in the development of visual hallucinations;[1,2,3,4,5,6,7] empirical evidence remains elusive, owing mainly to the obstacles inherent in eliciting hallucinatory phenomena experimentally
Consistent with the notion that visual hallucinations exist along a clinical spectrum, we observed strong positive correlations between the rate of misperceptions on the Bistable Percept Paradigm (BPP) and two independent clinical measures of visual hallucinations (UPDRS Q2: ρ = 0.733, P o 0.001; SCOPA–PC1–4: ρ = 0.469, P = 0.004)
Visual misperceptions were associated with the relative inability to recruit exogenous attention systems— namely, the dorsal attention network (DAN)—and a concomitant increase in endogenous systems, comprising the ventral attention network (VAN) and default mode network (DMN), the latter of which showed significant functional coupling with the visual network (VIS) during misperceptions (Figure 2)
Summary
Theoretical models have implicated sensory, attentional, and cognitive deficits in the development of visual hallucinations;[1,2,3,4,5,6,7] empirical evidence remains elusive, owing mainly to the obstacles inherent in eliciting hallucinatory phenomena experimentally. Most studies investigating hallucinations have been undertaken in psychiatric populations, e.g., in schizophrenia,[2] abnormal perceptual experiences are remarkably common in Parkinson’s disease, suggesting that Parkinson’s disease may represent an important model for probing visual hallucinations Despite this potential utility, initial strategies to investigate hallucinations in Parkinson’s disease have been reliant on either correlating brain activity with self-reported hallucinations[8,9,10,11] or interrogating impaired performance on basic visuoperceptual tasks.[12,13] such measures have provided insights into the pathophysiology of hallucinations, the utility of these approaches is limited by a lack of objective and concurrent assessment of the hallucinating brain. We applied an independent component analysis to extract time series information for large-scale neuronal networks that have been previously implicated in the pathophysiology of visual hallucinations These data were subjected to a task-based functional connectivity analysis, providing the first objective description of the neural activity and connectivity during visual hallucinations in patients with Parkinson’s disease. CONCLUSIONS: Together, these results provide evidence that visual hallucinations are due to increased engagement of the DMN with the primary visual system, and emphasize the role of dysfunctional engagement of attentional networks in the pathophysiology of hallucinations
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