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
Dopamine‐replacing therapies are an effective treatment for the motor aspects of Parkinson's disease. However, its precise effect over the cognitive resting‐state networks is not clear; whether ...dopaminergic treatment normalizes their functional connectivity‐as in other networks‐ and the links with cognitive decline are presently unknown. We recruited 35 nondemented PD patients and 16 age‐matched controls. Clinical and neuropsychological assessments were performed at baseline, and conversion to dementia was assessed in a 10 year follow‐up. Structural and functional brain imaging were acquired in both the ON and practical OFF conditions. We assessed functional connectivity in both medication states compared to healthy controls, connectivity differences within participants related to the ON/OFF condition, and baseline connectivity of PD participants that converted to dementia compared to those who did not convert. PD participants showed and increased frontoparietal connectivity compared to controls: a pattern of higher connectivity between salience (SN) and default‐mode (DMN) networks both in the ON and OFF states. Within PD patients, this higher SN‐DMN connectivity characterized the participants in the ON state, while within‐DMN connectivity prevailed in the OFF state. Interestingly, participants who converted to dementia also showed higher SN‐DMN connectivity in their baseline ON scans compared to nonconverters. To conclude, PD patients showed higher frontoparietal connectivity in cognitive networks compared to healthy controls, irrespective of medication status, but dopaminergic treatment specifically promoted SN‐DM hyperconnectivity.
In this work, Aracil‐Bolaños et al. investigate the effects of dopaminergic treatment over the large‐scale cognitive networks of nondemented Parkinson's disease patients and healthy controls. Baseline frontoparietal connectivity was higher in Parkinson's disease than in controls irrespective of medication, but dopaminergic treatment within patients specifically promoted salience network connectivity.
Background
Huntington's disease (HD) is a genetically determined disease with motor, cognitive, and neuropsychiatric disorders. However, the links between clinical progression and disruptions to ...dynamics in motor and cognitive large‐scale networks are not well established.
Objective
To investigate changes in dynamic and static large‐scale networks using an established tool of disease progression in Huntington's disease, the composite Unified Huntington's Disease Rating Scale (cUHDRS).
Methods
Sixty‐four mutation carriers were included. Static and dynamic baseline functional connectivity as well as topological features were correlated to 2‐year follow‐up clinical assessments using the cUHDRS.
Results
Decline in cUHDRS scores was associated with higher connectivity between frontal default‐mode and motor networks, whereas higher connectivity in posterior, mainly visuospatial regions was associated with a smaller decline in cUHDRS scores.
Conclusions
Structural disruptions in HD were evident both in posterior parietal/occipital and frontal motor regions, with reciprocal increases in functional connectivity. However, although higher visuospatial network connectivity was tied to a smaller cUHDRS decline, increased motor and frontal default‐mode connections were linked to a larger cUHDRS decreases. Therefore, divergent functional compensation mechanisms might be at play in the clinical evolution of HD.
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.
Objective Cognitive impairment in Parkinson's disease (PD) can show a very heterogeneous trajectory among patients. Here, we explored the mechanisms involved in the expression and prediction of ...different cognitive phenotypes over 4 years. Methods In 2 independent cohorts (total n = 475), we performed a cluster analysis to identify trajectories of cognitive progression. Baseline and longitudinal level II neuropsychological assessments were conducted, and baseline structural magnetic resonance imaging, resting electroencephalogram and neurofilament light chain plasma quantification were carried out. Linear mixed‐effects models were used to study longitudinal changes. Risk of mild cognitive impairment and dementia were estimated using multivariable hazard regression. Spectral power density from the electroencephalogram at baseline and source localization were computed. Results Two cognitive trajectories were identified. Cluster 1 presented stability (PD‐Stable) over time, whereas cluster 2 showed progressive cognitive decline (PD‐Progressors). The PD‐Progressors group showed an increased risk for evolving to PD mild cognitive impairment (HR 2.09; 95% CI 1.11–3.95) and a marked risk for dementia (HR 4.87; 95% CI 1.34–17.76), associated with progressive worsening in posterior‐cortical‐dependent cognitive processes. Both clusters showed equivalent clinical and sociodemographic characteristics, structural magnetic resonance imaging, and neurofilament light chain levels at baseline. Conversely, the PD‐Progressors group showed a fronto‐temporo‐occipital and parietal slow‐wave power density increase, that was in turn related to worsening at 2 and 4 years of follow‐up in different cognitive measures. Interpretation In the absence of differences in baseline cognitive function and typical markers of neurodegeneration, the further development of an aggressive cognitive decline in PD is associated with increased slow‐wave power density and with a different profile of worsening in several posterior‐cortical‐dependent tasks. ANN NEUROL 2024
Background
Frontal lobe signs in progressive supranuclear palsy (PSP) are prevalent and occur early in the disease. Although they are recognized in clinical practice, studies are needed to ...systematically investigate them for an in‐depth understanding of the neurological substrate and their potential prognostic implications in the disease.
Objectives
To study the predictive role of frontal lobe signs in PSP, as well as to describe their neuropsychological and anatomical correlations.
Methods
Nine recognized signs of frontal lobe dysfunction were assessed in 61 patients with PSP. Those signs able to predict PSP Rating Scale (PSPRS) score at baseline were selected, a survival analysis was performed and associations with neuropsychological tests and cortical thickness parameters in brain MRI were studied.
Results
Grasping, anosognosia and orobuccal apraxia predicted the PSPRS score independently of age, gender, clinical subtype and disease duration. The occurrence of groping in the first 4 years could be a predictor of survival. Grasping and anosognosia were associated with frontal cognitive dysfunction, whereas orobuccal apraxia and groping were related to a more widespread cognitive impairment, involving temporal–parietal areas. Presence of groping showed an extensive cortical atrophy, with predominant prefrontal, temporal and superior parietal cortical thinning.
Conclusions
Grasping, groping, anosognosia and orobuccal apraxia are easily evaluable bedside clinical signs that reflect distinct stages of disease progression. Grasping, anosognosia and orobuccal apraxia predict disease disability in patients with PSP, and early onset groping could be a survival predictor.
Oculomotor behavior can provide insight into the integrity of widespread cortical networks, which may contribute to the differential diagnosis between Alzheimer's disease and frontotemporal dementia. ...Three groups of patients with Alzheimer's disease, behavioral variant of frontotemporal dementia (bvFTD) and semantic variant of primary progressive aphasia (svPPA) and a sample of cognitively unimpaired elders underwent an eye-tracking evaluation. All participants in the discovery sample, including controls, had a biomarker-supported diagnosis. Oculomotor correlates of neuropsychology and brain metabolism evaluated with 18F-FDG PET were explored. Machine-learning classification algorithms were trained for the differentiation between Alzheimer's disease, bvFTD and controls. A total of 93 subjects (33 Alzheimer's disease, 24 bvFTD, seven svPPA, and 29 controls) were included in the study. Alzheimer's disease was the most impaired group in all tests and displayed specific abnormalities in some visually-guided saccade parameters, as pursuit error and horizontal prosaccade latency, which are theoretically closely linked to posterior brain regions. BvFTD patients showed deficits especially in the most cognitively demanding tasks, the antisaccade and memory saccade tests, which require a fine control from frontal lobe regions. SvPPA patients performed similarly to controls in most parameters except for a lower number of correct memory saccades. Pursuit error was significantly correlated with cognitive measures of constructional praxis and executive function and metabolism in right posterior middle temporal gyrus. The classification algorithms yielded an area under the curve of 97.5% for the differentiation of Alzheimer's disease vs. controls, 96.7% for bvFTD vs. controls, and 92.5% for Alzheimer's disease vs. bvFTD. In conclusion, patients with Alzheimer's disease, bvFTD and svPPA exhibit differentiating oculomotor patterns which reflect the characteristic neuroanatomical distribution of pathology of each disease, and therefore its assessment can be useful in their diagnostic work-up. Machine learning approaches can facilitate the applicability of eye-tracking in clinical practice.
Previous imaging studies in patients with borderline personality disorder (BPD) have detected functional brain dysfunctions. Mindfulness training may improve the symptoms of BPD, although the neural ...mechanisms involved remain poorly understood. This study had several key aims: a) to investigate the role of right anterior insula (rAI) functional connectivity in modulating baseline emotional status in BPD, b) to compare differences in connectivity changes after mindfulness training versus interpersonal effectiveness intervention, and c) to explore the correlation between longitudinal changes in imaging data and clinical indicators.
Thirty-eight patients with BPD underwent resting-state functional magnetic resonance imaging. Participants completed self-report clinical scales and participated in a dialectical-behavioral therapy (mindfulness versus interpersonal effectiveness modules). Changes in clinical and imaging variables were evaluated longitudinally after completion of the first 10-week sessions of psychotherapeutic intervention.
At baseline, the rAI was strongly connected with the other salience network nodes and anticorrelated with most core nodes of the default mode network (p < .05, corrected). The functional connectivity of the rAI correlated with emotional dysregulation and deficits in mindfulness capacities (p < .05, corrected). After completion of psychotherapeutic intervention, both groups (mindfulness and interpersonal effectiveness) showed divergent posttherapy functional connectivity changes, which were in turn associated with the clinical response.
The functional connectivity of the rAI seems to play an important role in emotion dysregulation and deficits in mindfulness capacities in individuals with BPD. Psychotherapy seems to modulate this functional connectivity, leading to beneficial changes in clinical variables.
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