Default mode network activity and connectivity was higher in PD with visual hallucinations and reduced in multiple system atrophy and PD without visual hallucinations. Cortical thickness comparisons suggest that functional, rather than structural, changes underlie the activity and connectivity differences.

Hallucinations, delusions, and functional neurological manifestations (conversion and somatic symptom disorders) of Parkinson's disease (PD) and dementia with Lewy bodies increase in frequency with disease progression, predict the onset of cognitive decline, and eventually blend with and are concealed by dementia. These symptoms share the absence of reality constraints and can be considered comparable elements of the PD‐dementia with Lewy bodies psychosis. We propose that PD‐dementia with Lewy bodies psychotic disorders depend on thalamic dysfunction promoting a theta burst mode and subsequent thalamocortical dysrhythmia with focal cortical coherence to theta electroencephalogram rhythms. This theta electroencephalogram activity, also called fast‐theta or pre‐alpha, has been shown to predict cognitive decline and fluctuations in Parkinson's disease with dementia and dementia with Lewy bodies. These electroencephalogram alterations are now considered a predictive marker for progression to dementia. The resulting thalamocortical dysrhythmia inhibits the frontal attentional network and favors the decoupling of the default mode network. As the default mode network is involved in integration of self‐referential information into conscious perception, unconstrained default mode network activity, as revealed by recent imaging studies, leads to random formation of connections that link strong autobiographical correlates to trivial stimuli, thereby producing hallucinations, delusions, and functional neurological disorders. The thalamocortical dysrhythmia default mode network decoupling hypothesis provides the rationale for the design and testing of novel therapeutic pharmacological and nonpharmacological interventions in the context of PD, PD with dementia, and dementia with Lewy bodies. © 2019 International Parkinson and Movement Disorder Society

Dementia with Lewy bodies (DLB) is characterized by fluctuation in cognition and attention. Thalamocortical connectivity and integrity of thalami are central to attentional function. We hypothesize that DLB patients with marked and frequent fluctuating cognition (flCog) have a loss of thalamocortical connectivity, an intrinsic disruption to thalamic structure and imbalances in thalamic neurotransmitter levels. To test this, magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) and proton MR spectroscopy on thalami were performed on 16 DLB, 16 Alzheimer's disease (AD) and 13 healthy subjects. MRI and DTI were combined to subdivide thalami according to their cortical connectivity and to investigate microstructural changes in connectivity-defined thalamic regions. Compared with controls, lower N-acetyl-aspartate/total creatine (NAA/tCr) and higher total choline/total creatine (tCho/tCr) values were observed within thalami of DLB patients. tCho/tCr increase was found within right thalamus of DLB patients as compared with AD. This increase correlated with severity and frequency of flCog. As compared with controls, DLB patients showed bilateral damage within thalamic regions projecting to prefrontal and parieto-occipital cortices, whereas AD patients showed bilateral alteration within thalamic region projecting to temporal cortex. We posit that microstructural thalamic damage and cholinergic imbalance may be central to the etiology of flCog in DLB.

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The amygdala–medial prefrontal cortex (mPFC) circuit plays a key role in emotional processing. GABA-ergic inhibition within the mPFC has been suggested to play a role in the shaping of amygdala activity. However, the functional and neurochemical interactions within the amygdala–mPFC circuits and their relevance to emotional processing remain unclear. To investigate this circuit, we obtained resting-state functional magnetic resonance imaging (rs-fMRI) and proton MR spectroscopy in 21 healthy subjects to assess the potential relationship between GABA levels within mPFC and the amygdala–mPFC functional connectivity. Trait anxiety was assessed using the State-Trait Anxiety Inventory (STAI-Y2). Partial correlations were used to measure the relationships among the functional connectivity outcomes, mPFC GABA levels and STAI-Y2 scores. Age, educational level and amount of the gray and white matters within 1H-MRS volume of interest were included as nuisance variables. The rs-fMRI signals of the amygdala and the vmPFC were significantly anti-correlated. This negative functional coupling between the two regions was inversely correlated with the GABA+/tCr level within the mPFC and the STAI-Y2 scores. We suggest a close relationship between mPFC GABA levels and functional interactions within the amygdala-vmPFC circuit, providing new insights in the physiology of emotion.

Visual hallucinations (VH) represent one of the core features in discriminating dementia with Lewy bodies (DLB) from Alzheimer’s Disease (AD). Previous studies reported that in DLB patients functional alterations of the parieto-occipital regions were correlated with the presence of VH. The aim of our study was to assess whether morphological changes in specific cortical regions of DLB could be related to the presence and severity of VH. We performed a cortical thickness analysis on magnetic resonance imaging data in a cohort including 18 DLB patients, 15 AD patients and 14 healthy control subjects. Relatively to DLB group, correlation analysis between the cortical thickness and the Neuropsychiatric Inventory (NPI) hallucination item scores was also performed. Cortical thickness was reduced bilaterally in DLB compared to controls in the pericalcarine and lingual gyri, cuneus, precuneus, superior parietal gyrus. Cortical thinning was found bilaterally in AD compared to controls in temporal cortex including the superior and middle temporal gyrus, part of inferior temporal cortex, temporal pole and insula. Inferior parietal and supramarginal gyri were also affected bilaterally in AD as compared to controls. The comparison between DLB and AD evidenced cortical thinning in DLB group in the right posterior regions including superior parietal gyrus, precuneus, cuneus, pericalcarine and lingual gyri. Furthermore, the correlation analysis between cortical thickness and NPI hallucination item scores showed that the structural alteration in the dorsal visual regions including superior parietal gyrus and precuneus closely correlated with the occurrence and severity of VH. We suggest that structural changes in key regions of the dorsal visual network may play a crucial role in the physiopathology of VH in DLB patients.

The structural connectivity within cortical areas and between cortical and subcortical structures was investigated in dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD). We hypothesized that white matter (WM) tracts, which are linked to visual, attentional, and mnemonic functions, would be differentially and selectively affected in DLB as compared to AD and age-matched control subjects. Structural tensor imaging and diffusion tensor imaging (DTI) were performed on 14 DLB patients, 14 AD patients, and 15 controls. DTI metrics related to WM damage were assessed within tracts reconstructed by FreeSurfer’s TRActs Constrained by UnderLying Anatomy pipeline. Correlation analysis between WM and gray matter (GM) metrics was performed to assess whether the structural connectivity alteration in AD and DLB could be secondary to GM neuronal loss or a consequence of direct WM injury. Anterior thalamic radiation (ATR) and cingulum-cingulate gyrus were altered in DLB, whereas cingulum-angular bundle (CAB) was disrupted in AD. In DLB patients, secondary axonal degeneration within ATR was found in relation to microstructural damage within medio-dorsal thalamus, whereas axonal degeneration within CAB was related to precuneus thinning. WM alteration within the uncinate fasciculus was present in both groups of patients and was related to frontal and to temporal thinning in DLB and AD, respectively. We found structural connectivity alterations within fronto-thalamic and fronto-parietal (precuneus) network in DLB whereas, in contrast, disruption of structural connectivity of mnemonic pathways was present in AD. Furthermore, the high correlation between GM and WM metrics suggests that the structural connectivity alteration in DLB could be linked to GM neuronal loss rather than by direct WM injury. Thus, this finding supports the key role of cortical and subcortical atrophy in DLB.

Introduction Subjective cognitive decline (SCD) is a risk factor for mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Although sleep has been shown to be altered in MCI and AD, little is known about sleep in SCD. Methods Seventy cognitively normal community-dwelling participants were classified as SCD (32) or controls (38) using the Subjective Cognitive Decline Questionnaire. Sleep was assessed using actigraphy and diaries. FreeSurfer was used for performing medial temporal lobes (MTLs) and brain cortical parcellation of 3T magnetic resonance images. Multiple regression models were used to assess the presence of sleep, MTL, or regional cortical differences between groups. Results Objective sleep was disrupted in SCD participants, which showed increased nighttime wakefulness and reduced sleep efficiency. No group differences emerged in subjective sleep or magnetic resonance imaging outcomes. Discussion Objective sleep resulted disrupted in community-dwelling SCD, without any subjective sleep or cortical change. Sleep assessment/intervention in SCD might help prevent/delay AD onset.