scholarly journals Changes in structural network topology correlate with severity of hallucinatory behavior in Parkinson’s disease

2019 ◽  
Vol 3 (2) ◽  
pp. 521-538 ◽  
Author(s):  
Julie M. Hall ◽  
Claire O’Callaghan ◽  
Alana J. Muller ◽  
Kaylena A. Ehgoetz Martens ◽  
Joseph R. Phillips ◽  
...  

Inefficient integration between bottom-up visual input and higher order visual processing regions is implicated in visual hallucinations in Parkinson’s disease (PD). Here, we investigated white matter contributions to this perceptual imbalance hypothesis. Twenty-nine PD patients were assessed for hallucinatory behavior. Hallucination severity was correlated to connectivity strength of the network using the network-based statistic approach. The results showed that hallucination severity was associated with reduced connectivity within a subnetwork that included the majority of the diverse club. This network showed overall greater between-module scores compared with nodes not associated with hallucination severity. Reduced between-module connectivity in the lateral occipital cortex, insula, and pars orbitalis and decreased within-module connectivity in the prefrontal, somatosensory, and primary visual cortices were associated with hallucination severity. Conversely, hallucination severity was associated with increased between- and within-module connectivity in the orbitofrontal and temporal cortex, as well as regions comprising the dorsal attentional and default mode network. These results suggest that hallucination severity is associated with marked alterations in structural network topology with changes in participation along the perceptual hierarchy. This may result in the inefficient transfer of information that gives rise to hallucinations in PD.

2018 ◽  
Author(s):  
Julie M. Hall ◽  
Claire O’Callaghan ◽  
Alana. J. Muller ◽  
Kaylena A. Ehgoetz Martens ◽  
Joseph R. Phillips ◽  
...  

AbstractAn inefficient integration between bottom-up visual input and higher-order visual processing regions is implicated in the manifestation of visual hallucinations (VH) in Parkinson’s disease (PD). Using graph theory, the current study aimed to investigate white matter contributions to this perceptual imbalance hypothesis. Twenty-nine PD patients reported their hallucinatory behaviour on a questionnaire and performed a behavioural test that has been shown to elicit misperceptions. A composite score derived from these measures was used as a proxy for hallucinations severity and was correlated to connectivity strength of the network using the Network Based Statistic approach. The results showed that the severity of VH was associated with reduced connectivity within a large sub-network. This network included the majority of the diverse club and showed overall greater between- and within-module scores, compared to nodes not associated with hallucination severity. Furthermore, a reduction in between-module connectivity in the lateral occipital cortex, insula and pars orbitalis, as well as decreased within-module connectivity in the prefrontal, somatosensory and primary visual cortices were associated with VH severity. In contrast, the severity of VH was associated with an increase in between- and within-module connectivity in the orbitofrontal and temporal cortex, as well as regions comprising the dorsal attentional and DMN. These results suggest that the severity of VHs is associated with marked alterations in structural network topology, highlighted by a reduction in connectivity strength across a large sub-network, as well as changes in participation across top-down visual processing centres, visual and attentional networks. Therefore, impaired integration across the perceptual hierarchy may result in the inefficient transfer of information that gives rise to VHs in PD.


PLoS ONE ◽  
2017 ◽  
Vol 12 (3) ◽  
pp. e0172394 ◽  
Author(s):  
Robert Westphal ◽  
Camilla Simmons ◽  
Michel B. Mesquita ◽  
Tobias C. Wood ◽  
Steve C. R. Williams ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Carmen Gasca-Salas ◽  
Beatriz Fernández-Rodríguez ◽  
José A. Pineda-Pardo ◽  
Rafael Rodríguez-Rojas ◽  
Ignacio Obeso ◽  
...  

AbstractMR-guided focused ultrasound (MRgFUS), in combination with intravenous microbubble administration, has been applied for focal temporary BBB opening in patients with neurodegenerative disorders and brain tumors. MRgFUS could become a therapeutic tool for drug delivery of putative neurorestorative therapies. Treatment for Parkinson’s disease with dementia (PDD) is an important unmet need. We initiated a prospective, single-arm, non-randomized, proof-of-concept, safety and feasibility phase I clinical trial (NCT03608553), which is still in progress. The primary outcomes of the study were to demonstrate the safety, feasibility and reversibility of BBB disruption in PDD, targeting the right parieto-occipito-temporal cortex where cortical pathology is foremost in this clinical state. Changes in β-amyloid burden, brain metabolism after treatments and neuropsychological assessments, were analyzed as exploratory measurements. Five patients were recruited from October 2018 until May 2019, and received two treatment sessions separated by 2–3 weeks. The results are set out in a descriptive manner. Overall, this procedure was feasible and reversible with no serious clinical or radiological side effects. We report BBB opening in the parieto-occipito-temporal junction in 8/10 treatments in 5 patients as demonstrated by gadolinium enhancement. In all cases the procedures were uneventful and no side effects were encountered associated with BBB opening. From pre- to post-treatment, mild cognitive improvement was observed, and no major changes were detected in amyloid or fluorodeoxyglucose PET. MRgFUS-BBB opening in PDD is thus safe, reversible, and can be performed repeatedly. This study provides encouragement for the concept of BBB opening for drug delivery to treat dementia in PD and other neurodegenerative disorders.


2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Gajanan S Revankar ◽  
Noriaki Hattori ◽  
Yuta Kajiyama ◽  
Tomohito Nakano ◽  
Masahito Mihara ◽  
...  

Abstract In Parkinson’s disease, a precursor phenomenon to visual hallucinations presents as ‘pareidolias’ which make ambiguous forms appear meaningful. To evoke and detect pareidolias in patients, a noise pareidolia test was recently developed, although its task-dependent mechanisms are yet to be revealed. When subjected to this test, we hypothesized that patients exhibiting pareidolias would show altered top-down influence of visual processing allowing us to demonstrate the influence of pareidolic illusionary behaviour in Parkinson’s disease patients. To that end, we evaluated eye-movement strategies and fixation-related presaccadic activity on scalp EEG when participants performed the test. Twelve healthy controls and 21 Parkinson’s disease patients, evaluated for cognitive, visuo-spatial and executive functions, took a modified computer-based version of the noise pareidolia test in a free-viewing EEG eye-tracking experiment. Eye-tracking metrics (fixation-related durations and counts) documented the eye movement behaviour employed in correct responses (face/noise) and misperceptions (pareidolia/missed) during early and late visual search conditions. Simultaneously, EEG recorded the presaccadic activity in frontal and parietal areas of the brain. Based on the noise pareidolia test scores, we found certain Parkinson’s disease patients exhibited pareidolias whereas others did not. ANOVA on eye-tracking data showed that patients dwelled significantly longer to detect faces and pareidolias which affected both global and local search dynamics depending on their visuo-perceptual status. Presaccadic activity in parietal electrodes for the groups was positive for faces and pareidolias, and negative for noise, though these results depended mainly on saccade size. However, patients sensitive to pareidolias showed a significantly higher presaccadic potential on frontal electrodes independent of saccade sizes, suggesting a stronger frontal activation for pareidolic stimuli. We concluded with the following interpretations (i) the noise pareidolia test specifically characterizes visuo-perceptual inadequacies in patients despite their wide range of cognitive scores, (ii) Parkinson’s disease patients dwell longer to converge attention to pareidolic stimuli due to abnormal saccade generation proportional to their visuo-perceptual deficit during early search, and during late search, due to time-independent alteration of visual attentional network and (iii) patients with pareidolias show increased frontal activation reflecting the allocation of attention to irrelevant targets that express the pareidolic phenomenon. While the disease per se alters the visuo-perceptual and oculomotor dynamics, pareidolias occur in Parkinson’s disease due to an abnormal top-down modulation of visual processing that affects visual attention and guidance to ambiguous stimuli.


2021 ◽  
Author(s):  
Mathilde Salagnon ◽  
Sandrine Cremona ◽  
Marc Joliot ◽  
Francesco d'Errico ◽  
Emmanuel Mellet

It has been suggested that engraved abstract patterns dating from the Middle and Lower Palaeolithic served as means of representation and communication. Identifying the brain regions involved in visual processing of these engravings can provide insights into their function. In this study, brain activity was measured during perception of the earliest known Palaeolithic engraved patterns and compared to natural patterns mimicking human-made engravings. Participants were asked to categorise marks as being intentionally made by humans or due to natural processes (e.g. erosion, root etching). To simulate the putative familiarity of our ancestors with the marks, the responses of expert archaeologists and control participants were compared, allowing characterisation of the effect of previous knowledge on both behaviour and brain activity in perception of the marks. Besides a set of regions common to both groups and involved in visual analysis and decision-making, the experts exhibited greater activity in the inferior part of the lateral occipital cortex, ventral occipitotemporal cortex, and medial thalamic regions. These results are consistent with those reported in visual expertise studies, and confirm the importance of the integrative visual areas in the perception of the earliest abstract engravings. The attribution of a natural rather than human origin to the marks elicited greater activity in the salience network in both groups, reflecting the uncertainty and ambiguity in the perception of, and decision-making for, natural patterns. The activation of the salience network might also be related to the process at work in the attribution of an intention to the marks. The primary visual area was not specifically involved in the visual processing of engravings, which argued against its central role in the emergence of engraving production.


2021 ◽  
Vol 11 ◽  
Author(s):  
Nicholas Murphy ◽  
Alison Killen ◽  
Rajnish Kumar Gupta ◽  
Sara Graziadio ◽  
Lynn Rochester ◽  
...  

Visual hallucinations (VH) are a common symptom of Parkinson's disease with dementia (PDD), affecting up to 65% of cases. Integrative models of their etiology posit that a decline in executive control of the visuo-perceptual system is a primary mechanism of VH generation. The role of bottom-up processing in the manifestation of VH in this condition is still not clear although visual evoked potential (VEP) differences have been associated with VH at an earlier stage of PD. Here we compared the amplitude and latency pattern reversal VEPs in healthy controls (n = 21) and PDD patients (n = 34) with a range of VH severities. PDD patients showed increased N2 latency relative to controls, but no significant differences in VEP measures were found for patients reporting complex VH (CVH) (n = 17) compared to those without VH. Our VEP findings support previous reports of declining visual system physiology in PDD and some evidence of visual system differences between patients with and without VH. However, we did not replicate previous findings of a major relationships between the integrity of the visual pathway and VH.


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