Disruption of the default mode network and its intrinsic functional connectivity underlies minor hallucinations in Parkinson's disease

Abstract

Background Minor hallucinations and well‐structured hallucinations are considered in the severity continuum of the psychotic spectrum associated with Parkinson's disease. Although their chronological relationship is largely unknown, the spatial patterns of brain atrophy in these 2 forms of hallucinations partially overlap, suggesting they share similar pathophysiological processes. Functional connectivity studies show that disruption of functional networks involved in perception and attention could be relevant in the emergence of well‐structured hallucinations. However, functional neuroimaging studies in patients with isolated minor hallucinations are lacking. The objectives of this study were to explore the structural and functional changes underlying minor hallucinations. Methods We compared patients with (n = 18) and without (n = 14) minor hallucinations using a multimodal structural (gray‐matter volume voxel‐based morphometry) and functional (seed‐to‐whole‐brain resting‐state functional MRI) neuroimaging study. Results Coincident with previously described structural changes in well‐structured hallucinations in Parkinson's disease, patients with minor hallucinations exhibited gray‐matter atrophy with significant voxel‐wise differences in visuoperceptual processing areas and core regions of the default mode network. Functional connectivity changes consisted of altered connectivity within the default mode network, reduced negative correlation with task‐positive network, and aberrant connectivity between posterior regions of the default mode network and visual‐processing areas. These changes are in accordance with the attentional networks hypothesis proposed for well‐structured hallucinations. Conclusions Although longitudinal studies are needed to assess the potential role of minor hallucinations as an early clinical biomarker of progression to well‐structured hallucinations, the present findings show that the 2 phenomena share similar structural and functional brain correlates. © 2018 International Parkinson and Movement Disorder Society

Hallucinations, somatic‐functional disorders of PD‐DLB as expressions of thalamic dysfunction

“…In that conceptual framework, SFDs (with or without motor signs) represent a transient or stable break from reality, like what occurs with hallucinations and delusions. In the case of visual hallucinations, the notion that simple (eidolic) and complex (paraphrenic) hallucinations in PD‐DLB are part of a continuum is supported scientifically . We here propose that increased somatization scores on neuropsychological testing and complex somatic delusions are part of an SFD continuum occurring in PD‐DLB.…”

“…In the case of visual hallucinations, the notion that simple (eidolic) and complex (paraphrenic) hallucinations in PD-DLB are part of a continuum is supported scientifically. 1,97 We here propose that increased somatization scores on neuropsychological testing and complex somatic delusions are part of an SFD continuum occurring in PD-DLB. Along that line of thinking, it defies logic why a positive pareidolic test 36 should be interpreted as a valid sign of impending psychosis, and a positive somatic symptom test cannot predict the delusional progression of SFDs.…”

“…The positron emission tomography sign refers to the presence of a restricted area of preserved activity, localized in the PCC, that is embedded in hypoactive cortical regions. Further evidence is provided by several functional magnetic resonance imaging (fMRI) studies performed at rest and during tasks that show altered DMN activity and/or connectivity in PD and DLB patients that exhibit simpleor complex hallucinations (Table ). Moreover, structural MRI studies have lent support to the idea that altered activity/connectivity and decoupling of the DMN in PD‐DLB is of a functional rather than an anatomical character .…”

MRI of Motor and Nonmotor Therapy‐Induced Complications in Parkinson's Disease

“…In treated PD patients with visual hallucinations, structural MRI studies showed reduced GM volume in the visual associative areas, including the lingual gyrus and superior parietal regions, but also in the hippocampus and temporal cortex . Moreover, in these patients, Bejr‐Kasem and colleagues demonstrated the presence of an aberrant functional connectivity between posterior regions of the default mode network and the visual‐processing area. Further, from a neuropathological point of view, the degeneration of cholinergic brain structures, including the peduncolopontine nucleus, which results in altered cortical processing of visual perception, is believed to be involved in the development of visual hallucinations in PD .…”

Sensorimotor hallucinations in Parkinson’s disease

“…To assess the relevance of the cPH-network for PD patients' usual sPH in daily life, we analyzed resting state fMRI data in a new group of PD patients and investigated whether functional connectivity of the cPH-network (as defined in study2, projected bilaterally, (Supplementary S25-26, Tab.S11). Based on the disconnection hypothesis of hallucinations 52 , evidence of decreased connectivity for hallucinations of psychiatric origin 37 , and aberrant functional connectivity in PD patients with minor hallucinations including PH 24 , we predicted that the functional connectivity within the cPH-network differs between both PD patient groups and that the connectivity within the cPH-network is reduced in PD-PH vs. PD-nPH patients. We found that the functional connectivity within the cPH-network, predicted with 93.7% accuracy whether a patient was clinically classified as PD-PH (kappa:0.86, permutation p-value=0.0042).…”