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

Abstract

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

The Pharmacology of Visual Hallucinations in Synucleinopathies

“…in the 90s (Llinàs et al, 1999) and the development of the clinical symptoms exhibited by PD or DLB patients, an array ranging from cognitive fluctuations to VH. These findings have led to posit the current model of VH in synucleinopathies (Onofrj et al, 2019) which are considered to result from PPN-driven alterations of thalamic pacing due to the enhanced activity of TRN. The derangement of thalamocortical loops provokes the unleashing of the DMN that becomes disentangled from the control of the TPNs.…”

“…We and others have proposed that VH are generated by a synuclein-driven combination of thalamic-and PPN-driven dysfunctions (Henderson et al, 2000;Rub et al, 2002;Pimlott et al, 2006;Janzen et al, 2012;Onofrj et al, 2019). In the model, PPN alterations promote the TRN activation and the inhibition of the first-order nuclei of the thalamus, thereby ultimately generating pathological, "TCD-like," theta rhythms.…”

“…The phenomenon is commonly and more properly described as "illusions" or "pareidolia," events that are the result of distorted perceptions (Uchiyama et al, 2012). VH occurring in the early course of DLB and cognitively-preserved PD patients are perceived as extraneous to reality by the hallucinating subject and they suddenly appear in the form of complex images, animals, or miniature figures (Onofrj et al, 2013) that generally disappear when the patient, employing a coping strategy, refocuses his/her attention (Diederich et al, 2009). With the disease progression and the appearance of cognitive decline, early VH that are initially associated with preserved insight are then replaced by complex VH (Fénelon, 2006).…”

“…Complex VH are characterized by the loss of insight and the presence of a complex narrative structure (Onofrj et al, 2001;Fénelon, 2006). In complex VH, hallucinating images do interact and move across the visual field with kinetic properties, thereby generating enriched scenarios (i.e., fighting demons, marching warriors, multi-colored funerals, molesting presences) (Fénelon, 2006;Onofrj et al, 2006;Diederich et al, 2009;Onofrj et al, 2013). These complex VH are named paraphrenic hallucinations (Ey, 1973).…”

The Role of EEG in the Diagnosis, Prognosis and Clinical Correlations of Dementia with Lewy Bodies—A Systematic Review

“…Specifically, posterior slow-wave activity with periodic fluctuations in the pre-alpha/theta range on resting EEG was designated as a supportive biomarker in the 2017 DLB consortium diagnostic criteria [6]. Theta activities had been correlated with cognitive decline, cognitive fluctuations and hallucinations [7]. The clinical correlation of EEG enables it to be used as a biomarker for more difficult to evaluate clinical symptoms such as cognitive fluctuations.…”