Facial emotion recognition deficits are associated with hypomimia and related brain correlates in Parkinson's disease.

Hypomimia is a frequent manifestation in Parkinson's disease (PD) that can affect interpersonal relationships and quality of life. Recent studies have suggested that hypomimia is not only related to motor dysfunction but also to impairment in emotional processing networks. Therefore, we hypothesized that the severity of hypomimia could be associated with performance on a task aimed at assessing facial emotion recognition. In this study, we explored the association between hypomimia, recognition of facial expressions of basic emotions using the Ekman 60 Faces Test (EF), and brain correlates of both hypomimia and performance on the EF. A total of 94 subjects underwent clinical assessments (neurological and neuropsychological examinations), and 56 of them participated in the neuroimaging study. We found significant correlation between hypomimia, EF Disgust (r = -0.242, p = 0.022) and EF Happiness (r = -0.264, p = 0.012); an independent reduction in Cortical Thickness (Cth) in the postcentral gyrus, insula, middle and superior temporal gyri, supramarginal gyrus, banks of the superior temporal sulcus, bilateral fusiform gyri, entorhinal cortex, parahippocampal gyrus, inferior and superior parietal cortex, and right cuneus and precuneus; and multiple correlations between negative emotions such as EF Disgust or EF Anger and a reduced Cth in fronto-temporo-parietal regions. In conclusion, these results suggest that the association between hypomimia and emotion recognition deficits in individuals with PD might be mediated by shared circuits, supporting the concept that hypomimia is not only the result of the dysfunction of motor circuits, but also of higher cognitive functions.

Parkinson disease psychosis: from phenomenology to neurobiological mechanisms.

Parkinson disease (PD) psychosis (PDP) is a spectrum of illusions, hallucinations and delusions that are associated with PD throughout its disease course. Psychotic phenomena can manifest from the earliest stages of PD and might follow a continuum from minor hallucinations to structured hallucinations and delusions. Initially, PDP was considered to be a complication associated with dopaminergic drug use. However, subsequent research has provided evidence that PDP arises from the progression of brain alterations caused by PD itself, coupled with the use of dopaminergic drugs. The combined dysfunction of attentional control systems, sensory processing, limbic structures, the default mode network and thalamocortical connections provides a conceptual framework to explain how new incoming stimuli are incorrectly categorized, and how aberrant hierarchical predictive processing can produce false percepts that intrude into the stream of consciousness. The past decade has seen the publication of new data on the phenomenology and neurobiological basis of PDP from the initial stages of the disease, as well as the neurotransmitter systems involved in PDP initiation and progression. In this Review, we discuss the latest clinical, neuroimaging and neurochemical evidence that could aid early identification of psychotic phenomena in PD and inform the discovery of new therapeutic targets and strategies.

Predicting Impulse Control Disorders in Parkinson Disease through Incentive Biomarkers.

OBJECTIVE: This study was undertaken to evaluate whether the feedback-related negativity (FRN)-a neurophysiological marker of incentive processing-can be used to predict the development of impulse control disorders (ICDs) in Parkinson disease (PD). METHODS: The longitudinal cohort consisted of consecutive nondemented PD patients with no ICD history. We recorded FRN signals while they performed a gambling task. We calculated the mean amplitude difference between losses and gains (FRNdiff) to be used as a predictor of future ICD development. We performed prospective biannual follow-up assessments for 30 months to detect incident ICDs. Finally, we evaluated how basal FRNdiff was associated with posterior development of ICDs using survival models. RESULTS: Between October 7, 2015 and December 16, 2016, we screened 120 patients. Among them, 94 patients performed the gambling and 92 completed the follow-up. Eighteen patients developed ICDs during follow-up, whereas 74 remained free of ICDs. Baseline FRNdiff was greater in patients who developed ICDs than in those who did not (-2.33µV vs -0.84µV, p = 0.001). No other significant baseline differences were found. The FRNdiff was significantly associated with ICD development in the survival models both when not adjusted (hazard ratio [HR] = 0.73, 95% confidence interval [CI] = 0.58-0.91, p = 0.006) and when controlling for dopamine replacement therapy, sex, and age (HR = 0.74, 95% CI = 0.55-0.97, p = 0.035). None of the impulsivity measures evaluated was related to ICD development. INTERPRETATION: Reward-processing differences measured by FRN signals precede ICD development in PD. This neurophysiological marker permits identification of patients with high risk of ICD development. ANN NEUROL 2022;92:974-984.

The role of attentional control over interference in minor hallucinations in Parkinson's disease.

BACKGROUND: Minor hallucinations in Parkinson's disease are associated with connectivity changes in attentional networks and increased risk of structured hallucinations. However, the clinical translation of these abnormalities in attention processes is not well-defined, and commonly used neuropsychological tests are not able to detect significant deficits in Parkinson's disease patients with isolated minor hallucinations. OBJECTIVES: To analyze the behavioral and electrophysiological correlates of minor hallucinations in Parkinson's disease during an attentional task assessing response inhibition and interference control. METHODS: Fifty-five non-demented Parkinson's disease patients with (PD-mH; n = 27) and without minor hallucinations (PD-NH; n = 28) were included in the analysis. An Ericksen flanker task was performed to compare the effect of presenting congruent and incongruent stimuli on accuracy, reaction times and stimulus-locked event-related potentials morphology. RESULTS: Although both groups showed equivalent performance in a standard neuropsychological assessment, in the flanker task accuracy rates were lower in the PD-mH group in incongruent trials (p = 0.005). In the event-related potentials, PD-mH patients showed increased amplitude of the N2 at Fz [t(53); p < 0.05] and decreased amplitude of the P300 at Pz [t(53); p < 0.05] for the incongruent trials. CONCLUSIONS: Parkinson's disease patients with isolated minor hallucinations were more susceptible to interference mediated by irrelevant stimuli and had less cognitive control for suppressing these interferences. The failure of these systems could precipitate the intrusion and overrepresentation of peripheral irrelevant stimuli perceived as minor hallucinations. The Ericksen flanker task could be used as a sensitive clinical marker of the attentional defects leading to hallucinations in Parkinson's disease.

Clinical and structural brain correlates of hypomimia in early-stage Parkinson's disease.

BACKGROUND AND PURPOSE: Reduced facial expression of emotions is a very frequent symptom of Parkinson's disease (PD) and has been considered part of the motor features of the disease. However, the neural correlates of hypomimia and the relationship between hypomimia and other non-motor symptoms of PD are poorly understood. METHODS: The clinical and structural brain correlates of hypomimia were studied. For this purpose, cross-sectional data from the COPPADIS study database were used. Age, disease duration, levodopa equivalent daily dose, Unified Parkinson's Disease Rating Scale part III (UPDRS-III), severity of apathy and depression and global cognitive status were collected. At the imaging level, analyses based on gray matter volume and cortical thickness were used. RESULTS: After controlling for multiple confounding variables such as age or disease duration, the severity of hypomimia was shown to be indissociable from the UPDRS-III speech and bradykinesia items and was significantly related to the severity of apathy (ß = 0.595; p < 0.0001). At the level of neural correlates, hypomimia was related to motor regions brodmann area 8 (BA 8) and to multiple fronto-temporo-parietal regions involved in the decoding, recognition and production of facial expression of emotions. CONCLUSION: Reduced facial expressivity in PD is related to the severity of symptoms of apathy and is mediated by the dysfunction of brain systems involved in motor control and in the recognition, integration and expression of emotions. Therefore, hypomimia in PD may be conceptualized not exclusively as a motor symptom but as a consequence of a multidimensional deficit leading to a symptom where motor and non-motor aspects converge.

A Randomized Clinical Trial to Evaluate the Effects of Safinamide on Apathetic Non-demented Patients With Parkinson's Disease.

Background: Apathy is highly prevalent and disabling in Parkinson's disease (PD). Pharmacological options for its management lack sufficient evidence. Objective: We studied the effects of safinamide on apathy in PD. Methods: Prospective, 24-week, two-site, randomized, double-blind, placebo-controlled, parallel-group exploratory study in non-demented PD on stable dopaminergic therapy randomized 1:1 to adjunct safinamide (50 mg/day for 2 weeks and 100 mg/day for 22 weeks) or placebo. The primary endpoint was the mean change from baseline to week 24 on the Apathy Scale (AS) total score. Secondary endpoints included changes in cognition, activities of daily living, motor scores, the impression of change, and safety and tolerability measures. Results: In total, 30 participants (active treatment = 15; placebo = 15; 80% showing clinically significant apathetic symptoms according to the AS) were enrolled, and included in the intention-to-treat analysis. Change in AS (ANOVA) showed a trend to significance [p = 0.059] mediated by a more marked decrease in AS score with safinamide (-7.5 ± 6.9) than with placebo (-2.8 ± 5.7). Post-hoc analysis (paired t-test) showed a significant positive change in the AS score between 12-week and 24-week [p = 0.001] only in the active group. No significant or trend changes were found for any of the secondary outcome variables. Adverse events were few and only mild in both treatment groups. Conclusions: Safinamide was safe and well-tolerated, but failed to provide evidence of improved apathy. The positive trend observed in the post-hoc analyses deserves to be studied in depth in larger studies. Trial Registration: EudraCT 2017-003254-17.

Dissociable contribution of plasma NfL and p-tau181 to cognitive impairment in Parkinson's disease.

BACKGROUND: Cognitive dysfunction is a disabling complication in Parkinson's disease (PD). Accuracy of diagnosis of mild cognitive impairment in PD (PD-MCI) depends on the tests performed, which limits results generalization. Blood-based biomarkers could provide additional objective information for PD-MCI diagnosis and progression. Blood neurofilament light chain (NfL), a marker of neuronal injury, has shown good performance for PD disease stratification and progression. While NfL is not disease-specific, phosphorylated-tau at threonine-181 (p-tau181) in blood is a highly specific marker of concomitant brain amyloid-ß and tau pathology. METHODS: We investigated the potential of plasma NfL and p-tau181 levels as markers of cognitive impairment in a prospective cohort of 109 PD patients with and without PD-MCI (age 68.1 ± 7 years, education 12.2± 5 years), and 40 comparable healthy controls. After a follow-up of 4 years, we evaluated their predictive value for progression to dementia. RESULTS: Although NfL and p-tau181 levels were significantly increased in PD compared with healthy controls, only NfL levels were significantly higher in PD-MCI compared with PD with normal cognition (PD-NC) at baseline. After a follow-up of 4 years, only NfL predicted progression to dementia (HR 1.23, 95% CI 1.02-1.53; p = 0.038). Significant correlations between fluid biomarkers and neuropsychological examination were only found with NfL levels. CONCLUSIONS: Plasma NfL levels objectively differentiates PD-MCI from PD-NC patients, and may serve as a plasma biomarker for predicting progression to dementia in PD. Plasma levels of p-tau181 does not seem to help in differentiating PD-MCI or to predict future cognitive deterioration.

Increased homocysteine levels correlate with cortical structural damage in Parkinson's disease.

BACKGROUND: Blood homocysteine appears to be increased in Parkinson's disease (PD) and may play a role in the development and progression of this disorder. However, the specific contribution of abnormal homocysteine levels to cortical degeneration in PD remains elusive. OBJECTIVE: To characterize the cortical structural correlates of homocysteine levels in PD. METHODS: From the COPPADIS cohort, we identified a subset of PD patients and healthy controls (HC) with available homocysteine and imaging data. Surface-based vertex-wise multiple regression analyses were performed to investigate the cortical macrostructural (cortical thinning) and microstructural (increased intracortical diffusivity) correlates of homocysteine levels in this sample. RESULTS: A total of 137 PD patients and 43 HC were included. Homocysteine levels were increased in the PD group (t = -2.2, p = 0.03), correlating in turn with cognitive performance (r = -0.2, p = 0.03). Homocysteine in PD was also associated with frontal cortical thinning and, in a subset of patients with available DTI data, with microstructural damage in frontal and posterior-cortical regions (p < 0.05 Monte-Carlo corrected). CONCLUSIONS: Homocysteine in PD appears to be associated with cognitive performance and structural damage in the cerebral cortex. These findings not only reinforce the presence and importance of cortical degeneration in PD, but also suggest that homocysteine plays a role among the multiple pathological processes thought to be involved in its development.

Tipping the scales: how clinical assessment shapes the neural correlates of Parkinson's disease mild cognitive impairment.

Mild cognitive impairment in Parkinson's disease (PD-MCI) is associated with consistent structural and functional brain changes. Whether different approaches for diagnosing PD-MCI are equivalent in their neural correlates is presently unknown. We aimed to profile the neuroimaging changes associated with the two endorsed methods of diagnosing PD-MCI. We recruited 53 consecutive non-demented PD patients and classified them as PD-MCI according to comprehensive neuropsychological examination as operationalized by the Movement Disorders Task Force. Voxel-based morphometry, cortical thickness, functional connectivity and graph theoretical measures were obtained on a 3-Tesla MRI scanner. 18 patients (32%) were classified as PD-MCI with Level-II criteria, 19 (33%) with the Parkinson's disease Cognitive Rating Scale (PD-CRS) and 32 (60%) with the Montreal Cognitive Assessment (MoCA) scale. Though regions of atrophy differed across classifications, reduced gray matter in the precuneus was found using both Level-II and PD-CRS classifications in PD-MCI patients. Patients diagnosed with the PD-CRS also showed extensive changes in cortical thickness, concurring with the MoCA in regions of the cingulate cortex, and again with Level-II regarding cortical thinning in the precuneus. Functional connectivity analysis found higher coherence within salience network regions of interest, and decreased anticorrelations between salience/central executive and default-mode networks in the PD-CRS classification for PD-MCI patients. Graph theoretical metrics showed a widespread decrease in node degree for the three classifications in PD-MCI, whereas betweenness centrality was increased in select nodes of the default mode network (DMN). Clinical and neuroimaging commonalities between the endorsed methods of cognitive assessment suggest a corresponding set of neural correlates in PD-MCI: loss of structural integrity in DMN structures, mainly the precuneus, and a loss of weighted connections in the salience network that might be counterbalanced by increased centrality in the DMN. Furthermore, the similarity of the results between exhaustive Level-II and screening Level-I tools might have practical implications in the search for neuroimaging biomarkers of cognitive impairment in Parkinson's disease.

Identifying comorbidities and lifestyle factors contributing to the cognitive profile of early Parkinson's disease.

BACKGROUND: Identifying modifiable risk factors for cognitive impairment in the early stages of Parkinson's disease (PD) and estimating their impact on cognitive status may help prevent dementia (PDD) and the design of cognitive trials. METHODS: Using a standard approach for the assessment of global cognition in PD and controlling for the effects of age, education and disease duration, we explored the associations between cognitive status, comorbidities, metabolic variables and lifestyle variables in 533 PD participants from the COPPADIS study. RESULTS: Among the overall sample, 21% of participants were classified as PD-MCI (n = 114) and 4% as PDD (n = 26). The prevalence of hypertension, diabetes and dyslipidemia was significantly higher in cognitively impaired patients while no between-group differences were found for smoking, alcohol intake or use of supplementary vitamins. Better cognitive scores were significantly associated with regular physical exercise (p < 0.05) and cognitive stimulation (< 0.01). Cognitive performance was negatively associated with interleukin 2 (Il2) (p < 0.05), Il6 (p < 0.05), iron (p < 0.05), and homocysteine (p < 0.005) levels, and positively associated with vitamin B12 levels (p < 0.005). CONCLUSIONS: We extend previous findings regarding the positive and negative influence of various comorbidities and lifestyle factors on cognitive status in early PD patients, and reinforce the need to identify and treat potentially modifiable variables with the intention of exploring the possible improvement of the global cognitive status of patients with PD.

Neural signatures of predictive language processing in Parkinson's disease with and without mild cognitive impairment.

Cognitive deficits are common in Parkinson's disease (PD), with some PD patients meeting criteria for mild cognitive impairment (MCI). An unaddressed question is whether linguistic prediction is preserved in PD. This ability is nowadays deemed crucial for achieving fast and efficient comprehension, and it may be negatively impacted by cognitive deterioration in PD. To fill this gap of knowledge, we used event-related potentials (ERPs) to evaluate mechanisms of linguistic prediction in a sample of PD patients (on dopamine compensation) with and without MCI. To this end, participants read sentence contexts that were predictive or not about a sentence-final word. The final word appeared after one sec, matching or mismatching the prediction. The introduction of the interval allowed to capture neural responses both before and after sentence-final words, reflecting semantic anticipation and semantic processing. PD patients with normal cognition (N = 58) showed ERP responses comparable to those of matched controls. Specifically, in predictive contexts, a slow negative potential developed prior to sentence-final words, reflecting semantic anticipation. Later, expected words elicited reduced N400 responses (compared to unexpected words), indicating facilitated semantic processing. PD patients with MCI (N = 20) showed, in addition, a prolongation of the N400 congruency effect (compared to matched PD patients without MCI), indicating that further cognitive decline impacts semantic processing. Finally, lower verbal fluency scores correlated with prolonged N400 congruency effects and with reduced pre-word differences in all PD patients (N = 78). This relevantly points to a role of deficits in temporal-dependent mechanisms in PD, besides prototypical frontal dysfunction, in altered semantic anticipation and semantic processing during sentence comprehension.

Robot-induced hallucinations in Parkinson's disease depend on altered sensorimotor processing in fronto-temporal network.

Hallucinations in Parkinson's disease (PD) are disturbing and frequent non-motor symptoms and constitute a major risk factor for psychosis and dementia. We report a robotics-based approach applying conflicting sensorimotor stimulation, enabling the induction of presence hallucinations (PHs) and the characterization of a subgroup of patients with PD with enhanced sensitivity for conflicting sensorimotor stimulation and robot-induced PH. We next identify the fronto-temporal network of PH by combining MR-compatible robotics (and sensorimotor stimulation in healthy participants) and lesion network mapping (neurological patients without PD). This PH-network was selectively disrupted in an additional and independent cohort of patients with PD, predicted the presence of symptomatic PH, and associated with cognitive decline. These robotics-neuroimaging findings extend existing sensorimotor hallucination models to PD and reveal the pathological cortical sensorimotor processes of PH in PD, potentially indicating a more severe form of PD that has been associated with psychosis and cognitive decline.

Quantitative evaluation of oculomotor disturbances in progressive supranuclear palsy.

OBJECTIVES: To explore and quantify systematically the ocular abnormal movements present in progressive supranuclear palsy (PSP) from the early stages, to assess the ability of this standardized examination in the differential diagnosis of PSP from Parkinson's disease (PD), and to compare in more detail oculomotor disturbances between PSP variants. METHODS: Sixty-five consecutive PSP patients with <5 years of disease duration diagnosed according to MDS-PSP criteria, 25 PD patients and 25 controls comparable in age, education and disease duration were explored using a bedside battery of tests for the quantitative evaluation of oculomotor dysfunction in clinical practice. Other accepted scales were used for measurement of motor (PSPRS), cognitive (FAB) and behavioral (FBI) impairment. RESULTS: Measurement of oculomotor dysfunction significantly differentiated PSP from PD and controls (p < 0.001) and showed high accuracy in the differential diagnosis of early-to-mid stage PSP from PD. PSP-Parkinsonism and PSP-Progressive Gait Freezing phenotypes showed more preserved ocular motor function compared to PSP-Richardson Syndrome, although no differences were found between PSP subtypes in the number of square wave jerks, optokinetic nystagmus defects, degree of apraxia of eyelid opening, or presence of the "Round the Houses" sign. CONCLUSIONS: Using a bedside clinical instrument for quantifying oculomotor disturbances in PSP shows promising potential at differentiating PSP from PD, and it seems able to provide a qualitative and quantitative description of ocular motor function in parkinsonian disorders.

Cognitive and behavioral profile of progressive supranuclear palsy and its phenotypes.

BACKGROUND: Although several progressive supranuclear palsy (PSP) phenotypes have recently been described, studies identifying cognitive and neuropsychiatric differences between them are lacking. METHODS: An extensive battery of cognitive and behavioural assessments was administered to 63 PSP patients, 25 PD patients with similar sociodemographic characteristics, and 25 healthy controls. We analysed differences in phenomenology, frequency and severity of cognitive and neuropsychiatric symptoms between PSP, PD and HC, and between PSP subtypes. RESULTS: Regarding phenotypes, 64.6% met criteria for Richardson's syndrome (PSP-RS), 10.7% PSP with predominant Parkinsonism (PSP-P), 10.7% with PSP progressive gait freezing (PSP-PGF), and 10.7% PSP with predominant speech/language disorder (PSP-SL). Impairment was more severe in the PSP group than in the PD and HC groups regarding motor scores, cognitive testing and neuropsychiatric scales. Cognitive testing did not clearly differentiate between PSP phenotypes, but PSP-RS and PSP-SL appeared to have more cognitive impairment than PSP-PGF and PSP-P, mainly due to an increased impairment in frontal executive domains. Regarding neuropsychiatric disturbances, no specific behavior was more common in any of the PSP subtypes. CONCLUSION: Motor deficits delineate the phenotypes included in currently accepted MDS-PSP criteria. Cognition and behavioural disturbances are common in PSP and allow us to distinguish this disorder from other neurological diseases, but they do not differentiate between PSP phenotypes.

Subclinical affective and cognitive fluctuations in Parkinson's disease: a randomized double-blind double-dummy study of Oral vs. Intrajejunal Levodopa.

BACKGROUND: Chronic levodopa treatment in Parkinson's disease (PD) may promote undesirable motor and non-motor fluctuations. Compared to chronic oral levodopa treatment, continuous infusion of levodopa/carbidopa intestinal gel (LCIG) in advanced PD reduces motor fluctuations. However, differences in their effect on acute non-motor changes were not formally demonstrated. OBJECTIVE: We performed a randomized, double-blind, double-dummy, crossover study to compare acute non-motor changes between intermittent oral immediate-release carbidopa/levodopa (LC-IR) and LCIG. METHODS: After > 12-h OFF, thirteen PD patients chronically treated with LCIG and without history of non-motor swings, were allocated to receive first, LCIG infusion plus three oral doses of placebo, or placebo infusion plus three oral doses of LC-IR. Over-encapsulated oral medication (LC-IR or placebo) was administered every 2 h. We monitored plasmatic levels of levodopa, motor status (UPDRS-III), mood, anxiety, and frontal functions at baseline (0-h) and hourly after each oral challenge. RESULTS: Repeated-measures ANOVAs showed significant group by treatment interaction indicating more fluctuations of levodopa plasma levels with LC-IR. No significant interactions were seen in the temporal profile of motor status, anxiety, mood and cognition. However, point-to-point parametric and nonparametric tests showed a significant more marked and more sustained improvement in anxiety scores under LCIG. A significant improvement of mood and verbal fluency was seen a + 3-h only under LCIG. DISCUSSION: Our sample of advanced PD patients exhibited moderate but significant non-motor fluctuations. LCIG was associated with a more favorable profile of acute affective and cognitive fluctuations that was particularly expressed at the first part of the infusion curve.

The Free and Cued Selective Reminding Test in Parkinson's Disease Mild Cognitive Impairment: Discriminative Accuracy and Neural Correlates.

Introduction: Memory alterations are common in Parkinson's disease (PD) patients but the mechanisms involved in these deficits remain poorly understood. The study aims to explore the profile of episodic memory deficits in non-demented early PD patients. Methods: We obtained neurological, cognitive and behavioral data from 114 PD patients and 41 healthy controls (HC). PD participants were grouped as normal cognition (PD-NC) and mild cognitive impairment (PD-MCI) according to the Level II criteria of the Movement Disorders Society Task Force (MDS-TF). We evaluate the performance amongst groups on an episodic memory task using the Free and Cued Selective Reminding Test (FCSRT). Additionally, gray matter volume (GMV) voxel based morphometry, and mean diffusivity (MD) analyses were conducted in a subset of patients to explore the structural brain correlates of FCSRT performance. Results: Performance on all subscores of the FCSRT was significantly worse in PD-MCI than in PD-NC and HC. Delayed total recall (DTR) subscore was the best at differentiating PD-NC from PD-MCI. Using crosstabulation, DTR allowed identification of PD-MCI patients with an accuracy of 80%. Delayed free and cued recall was associated with decreased GMV and increased MD in multiple fronto-temporal and parietal areas. Conclusion: Encoding and retrieval deficits are a main characteristic of PD-MCI and are associated with structural damage in temporal, parietal and prefrontal areas.

Preservation of brain metabolism in recently diagnosed Parkinson's impulse control disorders.

BACKGROUND: Impulse control disorders (ICD) are a common and disrupting complication of Parkinson's disease (PD) treatment. Although their relationship with dopaminergic activity is well studied, their brain metabolic correlates are mostly unknown. METHODS: In this work we studied brain metabolism using brain 18F-FDG-PET. We performed a case-control study nested within a cohort of PD patients free of ICD at baseline to compare ICD patients right after ICD diagnosis and prior to any treatment modification with matched ICD-free patients. We also compared both PD groups with healthy controls. RESULTS: When compared with ICD-free PD patients, PD patients with recently diagnosed ICD showed higher glucose metabolism in widespread areas comprising prefrontal cortices, both amygdalae and default mode network hubs (p < 0.05, corrected). When compared to healthy controls, they did not show hypermetabolism, and the only hypometabolic region was the right caudate. In turn, ICD-free patients showed diffuse hypometabolism when compared to healthy controls. CONCLUSION: Our results suggest brain metabolism is more preserved in PD patients with ICD than patients without ICD. This metabolic preservation could be related to ICD development.

Minor hallucinations in Parkinson disease: A subtle symptom with major clinical implications.

OBJECTIVE: Psychosis is one of the most debilitating complications of Parkinson disease (PD). Although research on PD psychosis has been focused on the study of well-structured visual hallucinations (VH), currently accepted National Institute of Neurological Disorders and Stroke-National Institute of Mental Health diagnostic criteria emphasize minor hallucinations (MH) as the most common psychotic phenomena in PD. The objective of this review is to comprehensively describe the clinical and research advances on the understanding of MH and to provide future directions for obtaining further insights into their potential major implications for PD management and prognosis. METHODS: A PubMed search was done in November 2018 to identify articles on minor psychotic phenomena in PD. RESULTS: MH often precede the onset of well-structured VH and are associated with other nonmotor symptoms such as REM sleep behavior disorder and depression. The pattern of functional brain connectivity changes associated with MH involve visual-processing areas and attention control networks, which overlap with abnormalities described in patients with well-structured VH. The dysfunction of cortical networks in patients with MH may be an early indicator of a more widespread form of the disease. CONCLUSION: Although called "minor," MH may have major clinical and prognostic implications. Further research is needed to establish whether MH are associated with a higher risk of disabling psychotic complications, cognitive deterioration, or a more accelerated disease progression. Understanding the early neurobiological underpinnings of MH may provide the background for future studies to identify the progressive dysfunction of neural circuits leading to more severe forms of psychosis in PD.

A divergent breakdown of neurocognitive networks in Parkinson's Disease mild cognitive impairment.

Cognitive decline is a major disabling feature in Parkinson's disease (PD). Multimodal imaging studies have shown functional disruption in neurocognitive networks related to cognitive impairment. However, it remains unknown whether these changes are related to gray matter loss, or whether they outline network vulnerability in the early stages of cognitive impairment. In this work, we intended to assess functional connectivity and graph theoretical measures and their relation to gray matter loss in Parkinson's disease with mild cognitive impairment (PD-MCI). We recruited 53 Parkinson's disease patients and classified them for cognitive impairment using Level-1 Movement Disorders Society-Task Force Criteria. Voxel-based morphometry, functional connectivity and graph theoretical measures were obtained on a 3-Tesla MRI scanner. Loss of gray matter was observed in the default mode network (bilateral precuneus), without a corresponding disruption of functional or graph theoretical properties. However, functional and graph theoretical changes appeared in salience network nodes, without evidence of gray matter loss. Global cognition and executive scores showed a correlation with node degree in the right anterior insula. We also found a correlation between visuospatial scores and right supramarginal gyrus node degree. Our findings highlight the loss of functional connectivity and topological features without structural damage in salience network regions in PD-MCI. They also underline the importance of multimodal hubs in the transition to mild cognitive impairment. This functional disruption in the absence of gray matter atrophy suggests that the salience network is a key vulnerable system at the onset of mild cognitive impairment in PD.