Altered cortical visual processing in PD with hallucinations: An fMRI study
ABSTRACT To compare fMRI activation during two visual stimulation paradigms in Parkinson disease (PD) subjects with chronic visual hallucinations vs PD patients who had never hallucinated.
Twelve pairs of PD subjects, matched for age, PD duration, and dopaminergic drug exposure duration, participated in this study. The authors examined group differences in activation during stroboscopic (flashing) vs no visual stimulation and kinematic (apparent motion) vs stationary visual stimulation.
During stroboscopic stimulation, non-hallucinating PD subjects showed significantly greater activation in the parietal lobe and cingulate gyrus compared to hallucinating PD subjects. In contrast, the hallucinating subjects showed significantly greater activation in the inferior frontal gyrus and the caudate nucleus. During kinematic stimulation, non-hallucinating PD subjects showed significantly greater activation in area V5/MT, parietal lobe, and cingulate gyrus compared to hallucinating PD subjects. Hallucinating PD subjects showed significantly greater activation in the superior frontal gyrus.
PD patients with chronic visual hallucinations respond to visual stimuli with greater frontal and subcortical activation and less visual cortical activation than non-hallucinating PD subjects. Shifting visual circuitry from posterior to anterior regions associated primarily with attention processes suggests altered network organization may play a role in the pathophysiology of visual hallucinations in PD.
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ABSTRACT: Background: Visual hallucinations (VH) are one of the most striking nonmotor symptoms in Parkinson's disease (PD), and predict dementia and mortality. Aberrant default mode network (DMN) is associated with other psychoses. Here, we tested the hypothesis that DMN dysfunction contributes to VH in PD. Methods: Resting state functional data was acquired from individuals with PD with VH (PDVH) and without VH (PDnonVH), matched for levodopa drug equivalent dose, and a healthy control group (HC). Independent component analysis was used to investigate group differences in functional connectivity within the DMN. In addition, we investigated whether the functional changes associated with hallucinations were accompanied by differences in cortical thickness. Results: There were no group differences in cortical thickness but functional coactivation within components of the DMN was significantly lower in both PDVH and PDnonVH groups compared to HC. Functional coactivation within the DMN was found to be greater in PDVH group relative to PDnonVH group. Conclusion: Our study demonstrates, for the first time that, within a functionally abnormal DMN in PD, relatively higher "connectivity" is associated with VH. We postulate that aberrant connectivity in a large scale network affects sensory information processing and perception, and contributes to "positive" symptom generation in PD. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.Human Brain Mapping 11/2014; 35(11). DOI:10.1002/hbm.22577 · 6.92 Impact Factor
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ABSTRACT: Visual misperceptions and hallucinations represent a problematic symptom of Parkinson's disease. The pathophysiological mechanisms underlying these symptoms remain poorly understood, however, a recent hypothesis has suggested that visual misperceptions and hallucinations may arise from disrupted processing across attentional networks. To test the specific predictions of this hypothesis, 22 patients with Parkinson's disease underwent 3T fMRI while performing the Bistable Percept Paradigm, a task that has previously been shown to identify patients with hallucinations. Subjects are required to study a battery of randomly assigned "monostable" and "bistable" monochromatic images for the presence or absence of a bistable percept. Those patients who scored a high percentage of misperceptions and missed images on the task were less able to activate frontal and parietal hubs of the putative Dorsal Attention Network. Furthermore, poor performance on the task was significantly correlated with the degree of decreased activation in a number of these hubs. At the group level, the difference between processing a bistable versus a monostable cue was associated with increased recruitment of the anterior insula. In addition, those patients with impaired performance on the paradigm displayed decreased resting state functional connectivity between hubs of the Ventral and Dorsal Attention Networks. These same patients had significantly decreased gray matter in the insula bilaterally. In addition, a combined analysis of the separate neuroimaging approaches revealed significant relationships across the impaired networks. These findings are consistent with specific predictions from a recently proposed hypothesis that implicates dysfunction within attentional networks in Parkinsonian hallucinations. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.Human Brain Mapping 05/2014; 35(5). DOI:10.1002/hbm.22321 · 6.92 Impact Factor
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ABSTRACT: In Parkinson's disease, visual dysfunction is prominent. Visual hallucinations can be a major hallmark of late stage disease, but numerous visual deficits also occur in early stage Parkinson's disease. Specific retinopathy, deficits in the primary visual pathway and the secondary ventral and dorsal pathways, as well as dysfunction of the attention pathways have all been posited as causes of hallucinations in Parkinson's disease. We present data from patients with Parkinson's disease that contrast with a known neuro-ophthalmological syndrome, termed 'blindsight'. In this syndrome, there is an absence of conscious object identification, but preserved 'guess' of the location of a stimulus, preserved reflexive saccades and motion perception and preserved autonomical and expressive reactions to negative emotional facial expressions. We propose that patients with Parkinson's disease have the converse of blindsight, being 'blind to blindsight'. As such they preserve conscious vision, but show erroneous 'guess' localization of visual stimuli, poor saccades and motion perception, and poor emotional face perception with blunted autonomic reaction. Although a large data set on these deficits in Parkinson's disease has been accumulated, consolidation into one specific syndrome has not been proposed. Focusing on neuropathological and physiological data from two phylogenetically old and subconscious pathways, the retino-colliculo-thalamo-amygdala and the retino-geniculo-extrastriate pathways, we propose that aberrant function of these systems, including pathologically inhibited superior colliculus activity, deficient corollary discharges to the frontal eye fields, dysfunctional pulvinar, claustrum and amygdaloid subnuclei of the amygdala, the latter progressively burdened with Lewy bodies, underlie this syndrome. These network impairments are further corroborated by the concept of the 'silent amygdala'. Functionally being 'blind to blindsight' may facilitate the highly distinctive 'presence' or 'passage' hallucinations of Parkinson's disease and can help to explain handicaps in driving capacities and dysfunctional 'theory of mind'. We propose this synthesis to prompt refined neuropathological and neuroimaging studies on the pivotal nuclei in these pathways in order to better understand the networks underpinning this newly conceptualized syndrome in Parkinson's disease.Brain 04/2014; 137(6). DOI:10.1093/brain/awu094 · 10.23 Impact Factor