Altered cortical visual processing in PD with hallucinations: An fMRI study

Department of Neurological Sciences, Rush University Medical Center, 1725 West Harrison Street, Suite 309, Chicago, IL 60612, USA.
Neurology (Impact Factor: 8.29). 11/2004; 63(8):1409-16. DOI: 10.1212/01.WNL.0000141853.27081.BD
Source: PubMed


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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    • "Our connectivity approach provides a useful counterpoint to previous studies of task-dependent activation patterns reported in previous functional MRI studies in PDVH. Some authors have found hemodynamic differences in DMN regions in PDVH [Ramirez-Ruiz et al., 2008; Stebbins et al., 2004], while others reported no differences [Holroyd and Wooten, 2006; Ibarretxe-Bilbao et al., 2011; Meppelink et al., 2009]. Our study, focused on connectivity related to resting activity, avoids some of the potential confounds arising from differences in task design and/or difficulty. "
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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.
    Full-text · Article · Nov 2014 · Human Brain Mapping
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    • "In our study, PD patients showed a greater activation of bilateral PPC, with a right predominance, compared to controls. This result has not been previously reported, except for a comparison between PD patients without hallucinations versus PD patients with hallucinations (60). Our finding can be explained by the specificity of the task performed and by the clinical aspects of our patients. "
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    ABSTRACT: Background: Visual perception deficits are a recurrent manifestation in Parkinson’s disease (PD). Recently, structural abnormalities of fronto-parietal areas and subcortical regions, implicated in visual stimuli analysis, have been observed in PD patients with cognitive decline and visual hallucinations. The aim of the present study was to investigate the salient aspects of visual perception in cognitively unimpaired PD patients. Methods: Eleven right-handed non-demented right-sided onset PD patients without visuospatial impairment or hallucinations and 11 healthy controls were studied with functional magnetic resonance imaging while performing a specific visuoperceptual/visuospatial paradigm that allowed to highlight the specific process underlying visuospatial judgment. Results: Significant changes in both cortical areas and subcortical regions involved in visual stimuli processing were observed. In particular, PD patients showed a reduced activation for the right insula, left putamen, bilateral caudate, and right hippocampus, as well as an over-activation of the right dorso-lateral prefrontal and of the posterior parietal cortices, particularly in the right hemisphere. Conclusions: We found that both loss of efficiency and compensatory mechanisms occur in PD patients, providing further insight into the pathophysiological role of the functional alterations of basal ganglia and limbic structures in the impairment of visuoperceptual and visuospatial functions observed in PD.
    Full-text · Article · Jul 2014 · Frontiers in Neurology
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    • "Magnetic Resonance Imaging (fMRI), which demonstrated reduced activation in occipital and temporal cortices in PD patients with VH when presented with visual stimuli [Meppelink et al., 2009]. A separate fMRI study has demonstrated that PD patients with chronic VH respond to the presentation of simple visual stimuli with greater frontal and caudate nucleus activation and less visual cortical activation than non-hallucinating PD subjects [Stebbins et al., 2004]. This finding suggests that impaired processing of visual information may trigger " higher order " frontal regions. "
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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.
    Full-text · Article · May 2014 · Human Brain Mapping
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