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Objectives: Glutamate mediated excitotoxicity of the hyperactive subthalamic nucleus (STN) has been reported to contribute to nigral degeneration in Parkinson's disease (PD). Deep brain stimulation of the STN (STN DBS), in its role as a highly effective treatment of severe PD motor complications, has been thought to inhibit STN hyperactivity and therefore decrease progression of PD.Methods: In a prospective two centre study, disease progression was determined by means of serial (18)F-fluorodopa (F-dopa) positron emission tomography (PET) in 30 patients with successful STN DBS over the first 16 (SD 6) months after surgery.Results: Depending on the method of PET data analysis used in the two centres, annual progression rates relative to baseline were 9.5-12.4% in the caudate and 10.7-12.9% in the putamen.Conclusions: This functional imaging study is the first to demonstrate a continuous decline of dopaminergic function in patients with advanced PD under clinically effective bilateral STN stimulation. The rates of progression in patients with STN DBS were within the range of previously reported data from longitudinal imaging studies in PD. Therefore this study could not confirm the neuroprotective properties of DBS in the STN target. [ABSTRACT FROM AUTHOR]

This scientific commentary refers to 'Increased beta synchronization underlies perception-action hyperbinding in functional movement disorders', by Pastötter  et al . (https://doi.org/10.1093/braincomms/fcae301)., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Purpose: To give a comprehensive literature overview of alterations in regional cerebral glucose metabolism, measured using [ 18 F]FDG PET, in conditions associated with hyperkinetic movement disorders and ataxia. In addition, correlations between glucose metabolism and clinical variables as well as the effect of treatment on glucose metabolism are discussed., Methods: A systematic literature search was performed according to PRISMA guidelines. Studies concerning tremors, tics, dystonia, ataxia, chorea, myoclonus, functional movement disorders, or mixed movement disorders due to autoimmune or metabolic aetiologies were eligible for inclusion. A PubMed search was performed up to November 2021., Results: Of 1240 studies retrieved in the original search, 104 articles were included. Most articles concerned patients with chorea (n = 27), followed by ataxia (n = 25), dystonia (n = 20), tremor (n = 8), metabolic disease (n = 7), myoclonus (n = 6), tics (n = 6), and autoimmune disorders (n = 5). No papers on functional movement disorders were included. Altered glucose metabolism was detected in various brain regions in all movement disorders, with dystonia-related hypermetabolism of the lentiform nuclei and both hyper- and hypometabolism of the cerebellum; pronounced cerebellar hypometabolism in ataxia; and striatal hypometabolism in chorea (dominated by Huntington disease). Correlations between clinical characteristics and glucose metabolism were often described. [ 18 F]FDG PET-showed normalization of metabolic alterations after treatment in tremors, ataxia, and chorea., Conclusion: In all conditions with hyperkinetic movement disorders, hypo- or hypermetabolism was found in multiple, partly overlapping brain regions, and clinical characteristics often correlated with glucose metabolism. For some movement disorders, [ 18 F]FDG PET metabolic changes reflected the effect of treatment., (© 2023. The Author(s).)

Background: Hyperkinetic movement disorders (HMD) manifest as abnormal and uncontrollable movements. Despite reported involvement of several neural circuits, exact connectivity profiles remain elusive., Objectives: Providing a comprehensive literature review of resting-state brain connectivity alterations using resting-state fMRI (rs-fMRI). We additionally discuss alterations from the perspective of brain networks, as well as correlations between connectivity and clinical measures., Methods: A systematic review was performed according to PRISMA guidelines and searching PubMed until October 2022. Rs-fMRI studies addressing ataxia, chorea, dystonia, myoclonus, tics, tremor, and functional movement disorders (FMD) were included. The standardized mean difference was used to summarize findings per region in the Automated Anatomical Labeling atlas for each phenotype. Furthermore, the activation likelihood estimation meta-analytic method was used to analyze convergence of significant between-group differences per phenotype. Finally, we conducted hierarchical cluster analysis to provide additional insights into commonalities and differences across HMD phenotypes., Results: Most articles concerned tremor (51), followed by dystonia (46), tics (19), chorea (12), myoclonus (11), FMD (11), and ataxia (8). Altered resting-state connectivity was found in several brain regions: in ataxia mainly cerebellar areas; for chorea, the caudate nucleus; for dystonia, sensorimotor and basal ganglia regions; for myoclonus, the thalamus and cingulate cortex; in tics, the basal ganglia, cerebellum, insula, and frontal cortex; for tremor, the cerebello-thalamo-cortical circuit; finally, in FMD, frontal, parietal, and cerebellar regions. Both decreased and increased connectivity were found for all HMD. Significant spatial convergence was found for dystonia, FMD, myoclonus, and tremor. Correlations between clinical measures and resting-state connectivity were frequently described., Conclusion: Key brain regions contributing to functional connectivity changes across HMD often overlap. Possible increases and decreases of functional connections of a specific region emphasize that HMD should be viewed as a network disorder. Despite the complex interplay of physiological and methodological factors, this review serves to gain insight in brain connectivity profiles across HMD phenotypes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Brain imaging with [18F]FDG-PET can support the diagnostic work-up of patients with α-synucleinopathies. Validated data analysis approaches are necessary to evaluate disease-specific brain metabolism patterns in neurodegenerative disorders. This study compared the univariate Statistical Parametric Mapping (SPM) single-subject procedure and the multivariate Scaled Subprofile Model/Principal Component Analysis (SSM/PCA) in a cohort of patients with α-synucleinopathies., Methods: We included [18F]FDG-PET scans of 122 subjects within the α-synucleinopathy spectrum: Parkinson's Disease (PD) normal cognition on long-term follow-up (PD - low risk to dementia (LDR); n = 28), PD who developed dementia on clinical follow-up (PD - high risk of dementia (HDR); n = 16), Dementia with Lewy Bodies (DLB; n = 67), and Multiple System Atrophy (MSA; n = 11). We also included [18F]FDG-PET scans of isolated REM sleep behaviour disorder (iRBD; n = 51) subjects with a high risk of developing a manifest α-synucleinopathy. Each [18F]FDG-PET scan was compared with 112 healthy controls using SPM procedures. In the SSM/PCA approach, we computed the individual scores of previously identified patterns for PD, DLB, and MSA: PD-related patterns (PDRP), DLBRP, and MSARP. We used ROC curves to compare the diagnostic performances of SPM t-maps (visual rating) and SSM/PCA individual pattern scores in identifying each clinical condition across the spectrum. Specifically, we used the clinical diagnoses ("gold standard") as our reference in ROC curves to evaluate the accuracy of the two methods. Experts in movement disorders and dementia made all the diagnoses according to the current clinical criteria of each disease (PD, DLB and MSA)., Results: The visual rating of SPM t-maps showed higher performance (AUC: 0.995, specificity: 0.989, sensitivity 1.000) than PDRP z-scores (AUC: 0.818, specificity: 0.734, sensitivity 1.000) in differentiating PD-LDR from other α-synucleinopathies (PD-HDR, DLB and MSA). This result was mainly driven by the ability of SPM t-maps to reveal the limited or absent brain hypometabolism characteristics of PD-LDR. Both SPM t-maps visual rating and SSM/PCA z-scores showed high performance in identifying DLB (DLBRP = AUC: 0.909, specificity: 0.873, sensitivity 0.866; SPM t-maps = AUC: 0.892, specificity: 0.872, sensitivity 0.910) and MSA (MSARP: AUC: 0.921, specificity: 0.811, sensitivity 1.000; SPM t-maps: AUC: 1.000, specificity: 1.000, sensitivity 1.000) from other α-synucleinopathies. PD-HDR and DLB were comparable for the brain hypo and hypermetabolism patterns, thus not allowing differentiation by SPM t-maps or SSM/PCA. Of note, we found a gradual increase of PDRP and DLBRP expression in the continuum from iRBD to PD-HDR and DLB, where the DLB patients had the highest scores. SSM/PCA could differentiate iRBD from DLB, reflecting specifically the differences in disease staging and severity (AUC: 0.938, specificity: 0.821, sensitivity 0.941)., Conclusions: SPM-single subject maps and SSM/PCA are both valid methods in supporting diagnosis within the α-synucleinopathy spectrum, with different strengths and pitfalls. The former reveals dysfunctional brain topographies at the individual level with high accuracy for all the specific subtype patterns, and particularly also the normal maps; the latter provides a reliable quantification, independent from the rater experience, particularly in tracking the disease severity and staging. Thus, our findings suggest that differences in data analysis approaches exist and should be considered in clinical settings. However, combining both methods might offer the best diagnostic performance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: 2-Deoxy-2-[ 18 F]fluoroglucose (FDG) PET is an important tool for the identification of Alzheimer's disease (AD) patients through the characteristic neurodegeneration pattern that these patients present. Regional cerebral blood flow (rCBF) images derived from dynamic 11 C-labelled Pittsburgh Compound B (PIB) have been shown to present a similar pattern as FDG. Moreover, multivariate analysis techniques, such as scaled subprofile modelling using principal component analysis (SSM/PCA), can be used to generate disease-specific patterns (DP) that may aid in the classification of subjects. Therefore, the aim of this study was to compare rCBF AD-DPs with FDG AD-DP and their respective performances. Therefore, 52 subjects were included in this study. Fifteen AD and 16 healthy control subjects were used to generate four AD-DP: one based on relative cerebral trace blood (R 1 ), two based on time-weighted average of initial frame intervals (ePIB), and one based on FDG images. Furthermore, 21 subjects diagnosed with mild cognitive impairment were tested against these AD-DPs., Results: In general, the rCBF and FDG AD-DPs were characterized by a reduction in cortical frontal, temporal, and parietal lobes. FDG and rCBF methods presented similar score distribution., Conclusion: rCBF images may provide an alternative for FDG PET scans for the identification of AD patients through SSM/PCA., (© 2022. The Author(s).)

GTP-cyclohydrolase deficiency in dopa-responsive dystonia (DRD) patients impairs the biosynthesis of dopamine, but also of serotonin. The high prevalence of non-motor symptoms suggests involvement of the serotonergic pathway. Our study aimed to investigate the serotonergic system in vivo in the brain of`DRD patients and correlate this to (non-)motor symptoms. Dynamic [ 11 C]DASB PET scans, a marker of serotonin transporter availability, were performed. Ten DRD, 14 cervical dystonia patients and 12 controls were included. Univariate- and network-analysis did not show differences in binding between DRD patients compared to controls. Sleep disturbances were correlated with binding in the dorsal raphe nucleus (all participants: r s  = 0.45, p = 0.04; patients: r s  = 0.64, p = 0.05) and participants with a psychiatric disorder had a lower binding in the hippocampus (all participants: p = 0.00; patients: p = 0.06). Post-hoc analysis with correction for psychiatric co-morbidity showed a significant difference in binding in the hippocampus between DRD patients and controls (p = 0.00). This suggests that psychiatric symptoms might mask the altered serotonergic metabolism in DRD patients, but definite conclusions are difficult as psychiatry is considered part of the phenotype. We hypothesize that an imbalance between different neurotransmitter systems is responsible for the non-motor symptoms, and further research investigating multiple neurotransmitters and psychiatry in DRD is necessary., (© 2022. The Author(s).)

Background: Human bipedal gait benefits from arm swing, as it drives and shapes lower limb muscle activity in healthy participants as well as patients suffering from neurological impairment. Also during gait initiation, arm swing instructions were found to facilitate leg muscle recruitment., Research Question: The aim of the present study is to exploit the directional decomposition of coherence to examine to what extent forward and backward arm swing contribute to leg muscle recruitment during gait initiation., Methods: Ambulant electromyography (EMG) from shoulder muscles (deltoideus anterior and posterior) and upper leg muscles (biceps femoris and rectus femoris) was analysed during gait initiation in nineteen healthy participants (median age of 67 ± 12 (IQR) years). To assess to what extent either deltoideus anterior or posterior muscles were able to drive upper leg muscle activity during distinct stages of the gait initiation process, time dependent intermuscular coherence was decomposed into directional components based on their time lag (i.e. forward, reverse and zero-lag)., Results: Coherence from the forward directed components, representing shoulder muscle signals leading leg muscle signals, revealed that deltoideus anterior (i.e. forward arm swing) and deltoideus posterior (i.e. backward arm swing) equally drive upper leg muscle activity during the gait initiation process., Significance: The presently demonstrated time dependent directional intermuscular coherence analysis could be of use for future studies examining directional coupling between muscles or brain areas relative to certain gait (or other time) events. In the present study, this analysis provided neural underpinning that both forward and backward arm swing can provide neuronal support for leg muscle recruitment during gait initiation and can therefore both serve as an effective gait rehabilitation method in patients with gait initiation difficulties., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To explore to what extent neuronal coupling between upper and lower limb muscles during gait is preserved or affected in patients with Parkinson's Disease (PD)., Methods: Electromyography recordings were obtained from the bilateral deltoideus anterior and bilateral rectus femoris and biceps femoris muscles during overground gait in 20 healthy participants (median age 69 years) and 20 PD patients (median age 68.5 years). PD patients were able to walk independently (Hoehn and Yahr scale: Stage 2-3), had an equally distributed symptom laterality (6 left side, 7 both sides and 7 right side) and no cognitive problems or tremor dominant PD. Time-dependent directional intermuscular coherence analysis was employed to compare the neural coupling between upper and lower limb muscles between healthy participants and PD patients in three different directions: zero-lag (i.e. common driver), forward (i.e. shoulders driving the legs) and reverse component (i.e. legs driving the shoulders)., Results: Compared to healthy participants, PD patients exhibited (i) reduced intermuscular zero-lag coherence in the beta/gamma frequency band during end-of-stance and (ii) enhanced forward as well as reverse directed coherence in the alpha and beta/gamma frequency bands around toe-off., Conclusions: PD patients had a reduced common cortical drive to upper and lower limb muscles during gait, possibly contributing to disturbed interlimb coordination. Enhanced bidirectional coupling between upper and lower limb muscles on subcortical and transcortical levels in PD patients suggests a mechanism of compensation., Significance: These findings provide support for the facilitating effect of arm swing instructions in PD gait., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Spinocerebellar ataxia type 3 (SCA3) is a rare genetic neurodegenerative disease. The neurobiological basis of SCA3 is still poorly understood, and up until now resting-state fMRI (rs-fMRI) has not been used to study this disease. In the current study we investigated (multi-echo) rs-fMRI data from patients with genetically confirmed SCA3 (n = 17) and matched healthy subjects (n = 16). Using independent component analysis (ICA) and subsequent regression with bootstrap resampling, we identified a pattern of differences between patients and healthy subjects, which we coined the fMRI SCA3 related pattern (fSCA3-RP) comprising cerebellum, anterior striatum and various cortical regions. Individual fSCA3-RP scores were highly correlated with a previously published 18 F-FDG PET pattern found in the same sample (rho = 0.78, P = 0.0003). Also, a high correlation was found with the Scale for Assessment and Rating of Ataxia scores (r = 0.63, P = 0.007). No correlations were found with neuropsychological test scores, nor with levels of grey matter atrophy. Compared with the 18 F-FDG PET pattern, the fSCA3-RP included a more extensive contribution of the mediofrontal cortex, putatively representing changes in default network activity. This rs-fMRI identification of additional regions is proposed to reflect a consequence of the nature of the BOLD technique, enabling measurement of dynamic network activity, compared to the more static 18 F-FDG PET methodology. Altogether, our findings shed new light on the neural substrate of SCA3, and encourage further validation of the fSCA3-RP to assess its potential contribution as imaging biomarker for future research and clinical use., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The supplementary motor area (SMA) is implicated in stereotypic multi-limb movements such as walking with arm swing. Gait difficulties in Parkinson's Disease (PD) include reduced arm swing, which is associated with reduced SMA activity., Objective: To test whether enhanced arm swing improves Parkinsonian gait and explore the role of the SMA in such an improvement., Methods: Cortical activity and gait characteristics were assessed by ambulant EEG, accelerometers and video recordings in 27 PD patients with self-reported gait difficulties and 35 healthy participants when walking normally. Within these two groups, 19 PD patients additionally walked with enhanced arm swing and 30 healthy participants walked without arm swing. Power changes across the EEG frequency spectrum were assessed by Event Related Spectral Perturbation analysis of recordings from Fz over the putative SMA and gait analysis was performed., Results: Baseline PD gait, characterized by reduced arm swing among other features, exhibited reduced within-step Event Related Desynchronization (ERD)/Synchronization (ERS) alternation (Fz; 20-50Hz), accompanied by a reduced step length and walking speed. All became similar to normal gait when patients walked with enhanced arm swing. When healthy controls walked without arm swing, their alternating ERD-ERS pattern decreased, mimicking baseline PD gait., Conclusion: Enhanced arm swing may serve as a driving force to overcome impaired gait control in PD patients by restoring reduced ERD-ERS alternation over the putative SMA. Accompanied by increased step length and walking speed, this provides a neural underpinning of arm swing as an effective rehabilitation concept for improving Parkinsonian gait., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To explore changes in resting-state networks in patients with jerky and tremulous functional movement disorders (JT-FMD). Methods: Resting-state functional magnetic resonance imaging data from seventeen patients with JT-FMD and seventeen age-, sex-, and education-matched healthy controls (HC) were investigated. Independent component analysis was used to examine the central executive network (CEN), salience network, and default mode network (DMN). Frequency distribution of network signal fluctuations and intra- and internetwork functional connectivity were investigated. Symptom severity was measured using the Clinical Global Impression-Severity scale. Beck Depression Inventory and Beck Anxiety Inventory scores were collected to measure depression and anxiety in FMD, respectively. Results: Compared with HC, patients with JT-FMD had significantly decreased power of lower range (0.01-0.10 Hz) frequency fluctuations in a precuneus and posterior cingulate cortex component of the DMN and in the dorsal attention network (DAN) component of the CEN (false discovery rate-corrected p  < 0.05). No significant group differences were found for intra- and internetwork functional connectivity. In patients with JT-FMD, symptom severity was not significantly correlated with network measures. Depression scores were weakly correlated with intranetwork functional connectivity in the medial prefrontal cortex, while anxiety was not found to be related to network connectivity. Conclusions: Given the changes in the posterodorsal components of the DMN and DAN, we postulate that the JT-FMD-related functional alterations found in these regions could provide support for the concept that particularly attentional dysregulation is a fundamental disturbance in these patients. Impact statement In this study, we explored static brain network functional connectivity in patients with jerky and tremulous functional movement disorders (JT-FMD) and healthy controls. We studied network functioning by analyzing functional connectivity measures, and also time course frequency spectra, which is novel compared with previous studies. We discovered aberrations in the frequency distribution of a posterior component of the default mode network (precuneus/posterior cingulate) and the dorsal attention network in patients with JT-FMD relative to controls. Conclusively, our findings could provide support for impaired attentional control as a fundamental disturbance in JT-FMD and contribute to the growing conceptualization of this disorder.

Background: Walking is characterized by stable antiphase relations between upper and lower limb movements. Such bilateral rhythmic movement patterns are neuronally generated at levels of the spinal cord and brain stem, that are strongly interconnected with cortical circuitries, including the Supplementary Motor Area (SMA)., Objective: To explore cerebral activity associated with multi-limb phase relations in human gait by manipulating mutual attunement of the upper and lower limb antiphase patterns., Methods: Cortical activity and gait were assessed by ambulant EEG, accelerometers and videorecordings in 35 healthy participants walking normally and 19 healthy participants walking in amble gait, where upper limbs moved in-phase with the lower limbs. Power changes across the EEG frequency spectrum were assessed by Event Related Spectral Perturbation analysis and gait analysis was performed., Results: Amble gait was associated with enhanced Event Related Desynchronization (ERD) prior to and during especially the left swing phase and reduced Event Related Synchronization (ERS) at final swing phases. ERD enhancement was most pronounced over the putative right premotor, right primary motor and right parietal cortex, indicating involvement of higher-order organization and somatosensory guidance in the production of this more complex gait pattern, with an apparent right hemisphere dominance. The diminished within-step ERD/ERS pattern in amble gait, also over the SMA, suggests that this gait pattern is more stride driven instead of step driven., Conclusion: Increased four-limb phase complexity recruits distributed networks upstream of the primary motor cortex, primarily lateralized in the right hemisphere. Similar parietal-premotor involvement has been described to compensate impaired SMA function in Parkinson's disease bimanual antiphase movement, indicating a role as cortical support regions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Weersink, Maurits and de Jong.)

Key Points: Gait-related arm swing in humans supports efficient lower limb muscle activation, indicating a neural coupling between the upper and lower limbs during gait. Intermuscular coherence analyses of gait-related electromyography from upper and lower limbs in 20 healthy participants identified significant coherence in alpha and beta/gamma bands indicating that upper and lower limbs share common subcortical and cortical drivers that coordinate the rhythmic four-limb gait pattern. Additional directed connectivity analyses revealed that upper limb muscles drive and shape lower limb muscle activity during gait via subcortical and cortical pathways and to a lesser extent vice versa. The results provide a neural underpinning that arm swing may serve as an effective rehabilitation therapy concerning impaired gait in neurological diseases., Abstract: Human gait benefits from arm swing, as it enhances efficient lower limb muscle activation in healthy participants as well as patients suffering from neurological impairment. The underlying neuronal mechanisms of such coupling between upper and lower limbs remain poorly understood. The aim of the present study was to examine this coupling by intermuscular coherence analysis during gait. Additionally, directed connectivity analysis of this coupling enabled assessment of whether gait-related arm swing indeed drives lower limb muscles. To that end, electromyography recordings were obtained from four lower limb muscles and two upper limb muscles bilaterally, during gait, of 20 healthy participants (mean (SD) age 67 (6.8) years). Intermuscular coherence analysis revealed functional coupling between upper and lower limb muscles in the alpha and beta/gamma band during muscle specific periods of the gait cycle. These effects in the alpha and beta/gamma bands indicate involvement of subcortical and cortical sources, respectively, that commonly drive the rhythmic four-limb gait pattern in an efficiently coordinated fashion. Directed connectivity analysis revealed that upper limb muscles drive and shape lower limb muscle activity during gait via subcortical and cortical pathways and to a lesser extent vice versa. This indicates that gait-related arm swing reflects the recruitment of neuronal support for optimizing the cyclic movement pattern of the lower limbs. These findings thus provide a neural underpinning for arm swing to potentially serve as an effective rehabilitation therapy concerning impaired gait in neurological diseases., (© 2021 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Quantification of amyloid load with positron emission tomography can be useful to assess Alzheimer's Disease in-vivo. However, quantification can be affected by the image processing methodology applied. This study's goal was to address how amyloid quantification is influenced by different semi-automatic image processing pipelines. Images were analysed in their Native Space and Standard Space; non-rigid spatial transformation methods based on maximum a posteriori approaches and tissue probability maps (TPM) for regularisation were explored. Furthermore, grey matter tissue segmentations were defined before and after spatial normalisation, and also using a population-based template. Five quantification metrics were analysed: two intensity-based, two volumetric-based, and one multi-parametric feature. Intensity-related metrics were not substantially affected by spatial normalisation and did not significantly depend on the grey matter segmentation method, with an impact similar to that expected from test-retest studies (≤10%). Yet, volumetric and multi-parametric features were sensitive to the image processing methodology, with an overall variability up to 45%. Therefore, the analysis should be carried out in Native Space avoiding non-rigid spatial transformations. For analyses in Standard Space, spatial normalisation regularised by TPM is preferred. Volumetric-based measurements should be done in Native Space, while intensity-based metrics are more robust against differences in image processing pipelines., Competing Interests: The authors have declared that no competing interests exist.

Scaled subprofile model using principal component analysis (SSM/PCA) is a multivariate analysis technique used, mainly in [ 18 F]-2-fluoro-2-deoxy-d-glucose (FDG) PET studies, for the generation of disease-specific metabolic patterns (DP) that may aid with the classification of subjects with neurological disorders, like Alzheimer's disease (AD). The aim of this study was to explore the feasibility of using quantitative parametric images for this type of analysis, with dynamic [ 11 C]-labelled Pittsburgh Compound B (PIB) PET data as an example. Therefore, 15 AD patients and 15 healthy control subjects were included in an SSM/PCA analysis to generate four AD-DPs using relative cerebral blood flow (R 1 ), binding potential (BP ND ) and SUVR images derived from dynamic PIB and static FDG-PET studies. Furthermore, 49 new subjects with a variety of neurodegenerative cognitive disorders were tested against these DPs. The AD-DP was characterized by a reduction in the frontal, parietal, and temporal lobes voxel values for R 1 and SUVR-FDG DPs; and by a general increase of values in cortical areas for BP ND and SUVR-PIB DPs. In conclusion, the results suggest that the combination of parametric images derived from a single dynamic scan might be a good alternative for subject classification instead of using 2 independent PET studies., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Objective: Neurodegenerative diseases like Parkinson's disease often take several years before they can be diagnosed reliably based on clinical grounds. Imaging techniques such as MRI are used to detect anatomical (structural) pathological changes. However, these kinds of changes are usually seen only late in the development. The measurement of functional brain activity by means of [ 18 F]fluorodeoxyglucose positron emission tomography (FDG-PET) can provide useful information, but its interpretation is more difficult. The scaled sub-profile model principal component analysis (SSM/PCA) was shown to provide more useful information than other statistical techniques. Our objective is to improve the performance further by combining SSM/PCA and prototype-based generalized matrix learning vector quantization (GMLVQ)., Methods: We apply a combination of SSM/PCA and GMLVQ as a classifier. In order to demonstrate the combination's validity, we analyze FDG-PET data of Parkinson's disease (PD) patients collected at three different neuroimaging centers in Europe. We determine the diagnostic performance by performing a ten times repeated ten fold cross validation. Additionally, discriminant visualizations of the data are included. The prototypes and relevance of GMLVQ are transformed back to the original voxel space by exploiting the linearity of SSM/PCA. The resulting prototypes and relevance profiles have then been assessed by three neurologists., Results: One important finding is that discriminative visualization can help to identify disease-related properties as well as differences which are due to center-specific factors. Secondly, the neurologist assessed the interpretability of the method and confirmed that prototypes are similar to known activity profiles of PD patients., Conclusion: We have shown that the presented combination of SSM/PCA and GMLVQ can provide useful means to assess and better understand characteristic differences in FDG-PET data from PD patients and HCs. Based on the assessments by medical experts and the results of our computational analysis we conclude that the first steps towards a diagnostic support system have been taken successfully., Competing Interests: Declaration of Competing Interest The authors declare no competing or financial interest in this work., (Copyright © 2020. Published by Elsevier B.V.)

Functional impairment of spatially distributed brain regions in Parkinson's disease (PD) suggests changes in integrative and segregative network characteristics, for which novel analysis methods are available. To assess underlying structural network differences between PD patients and controls, we employed MRI T1 gray matter segmentation and diffusion MRI tractography to construct connectivity matrices to compare patients and controls with data originating from two different centers. In the Dutch dataset (Data-NL), 14 PD patients, and 15 healthy controls were analyzed, while 19 patients and 18 controls were included in the Canadian dataset (Data-CA). All subjects underwent T1 and diffusion-weighted MRI. Patients were assessed with Part 3 of the Unified Parkinson's Disease Rating Scale (UPDRS). T1 images were segmented using FreeSurfer, while tractography was performed using ExploreDTI. The regions of interest from the FreeSurfer segmentation were combined with the white matter streamline sets resulting from the tractography, to construct connectivity matrices. From these matrices, both global and local efficiencies were calculated, which were compared between the PD and control groups and related to the UPDRS motor scores. The connectivity matrices showed consistent patterns among the four groups, without significant differences between PD patients and control subjects, either in Data-NL or in Data-CA. In Data-NL, however, global and local efficiencies correlated negatively with UPDRS scores at both the whole-brain and the nodal levels [false discovery rate (FDR) 0.05]. At the nodal level, particularly, the posterior parietal cortex showed a negative correlation between UPDRS and local efficiency, while global efficiency correlated negatively with the UPDRS in the sensorimotor cortex. The spatial patterns of negative correlations between UPDRS and parameters for network efficiency seen in Data-NL suggest subtle structural differences in PD that were below sensitivity thresholds in Data-CA. These correlations are in line with previously described functional differences. The methodological approaches to detect such differences are discussed., (Copyright © 2020 Kok, Leemans, Teune, Leenders, McKeown, Appel-Cresswell, Kremer and de Jong.)

Aim: L -3,4-dihydroxy-6-18F-fluorophenylalanine (18F-DOPA PET may be used to distinguish subjects with Parkinsonism from those with symptoms not originating from impaired dopaminergic transmission. However, it is not routinely utilized to discriminate Idiopathic Parkinson's disease (IPD) from Atypical Parkinsonian Disorders (APD). We investigated the potential of FDOPA PET to discriminate between IPD and APD, with a focus on the anterior-to-posterior decline in het striatum, considered to be more specific for IPD., Materials and Methods: 18F-DOPA PET data from a total of 58 subjects were retrospectively analyzed. 28 subjects had idiopathic Parkinson's disease (14 male, 14 female; age at scan 61 +- 11,5), 13 atypical Parkinsonian disease (7 male, 6 females; age at scan: 69,6 +- 6,4) and 17 were controls (6 male, 11 female; age at scan 65,3 +-8,6). Regional striatal-to-occipital ratio's (RSOR's) were calculated, as well as multiple in-line VOI's from the caudate nucleus to the posterior part of the putamen. The linearity of anteroposterior decline was determined by a linear regression fit and associated R squared values. ROC curves were calculated to assess the diagnostic performance of these measurements. Data contralateral to the clinically most affected side were used for analysis., Results: ROC curve analysis for differentiation between controls and Parkinsonism patients showed the highest AUC for the caudate nucleus-to-posterior putamen ratio (AUC = 0.930; p < 0.00) and for the R squared value for the linear regression fit (AUC = 0.948; p = 0.006). For discrimating IPD from APD, the highest AUC was found for the caudate nucleus-to-anterior putamen ratio (0.824; p < 0.001) CONCLUSIONS: Subregional analysis of the striatum in F-DOPA PET scans may provide additional diagnostic information in patients screened for a  presynaptic dopaminergic deficit. A more linear decrease from the head of the caudate nucleus to the posterior putamen was  present in patients with IPD, although this feature did not have additional diagnostic value over the RSOR analysis., Competing Interests: Declaration of Competing Interest The authors declare that thay have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

This exploratory study set out to investigate dynamic functional connectivity (dFC) in patients with jerky and tremulous functional movement disorders (JT-FMD). The focus in this work is on dynamic brain states, which represent distinct dFC patterns that reoccur in time and across subjects. Resting-state fMRI data were collected from 17 patients with JT-FMD and 17 healthy controls (HC). Symptom severity was measured using the Clinical Global Impression-Severity scale. Depression and anxiety were measured using the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI), respectively. Independent component analysis was used to extract functional brain components. After computing dFC, dynamic brain states were determined for every subject using k-means clustering. Compared to HC, patients with JT-FMD spent more time in a state that was characterized predominantly by increasing medial prefrontal, and decreasing posterior midline connectivity over time. They also tended to visit this state more frequently. In addition, patients with JT-FMD transitioned significantly more often between different states compared to HC, and incorporated a state with decreasing medial prefrontal, and increasing posterior midline connectivity in their attractor, i.e., the cyclic patterns of state transitions. Altogether, this is the first study that demonstrates altered functional brain network dynamics in JT-FMD that may support concepts of increased self-reflective processes and impaired sense of agency as driving factors in FMD., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The supplementary motor area (SMA) is implicated in both motor initiation and stereotypic multi-limb movements such as walking with arm swing. Gait in Parkinson's disease exhibits starting difficulties and reduced arm swing, consistent with reduced SMA activity., Objective: We tested whether enhanced arm swing could improve Parkinson gait initiation and assessed whether increased SMA activity during preparation might facilitate such improvement., Methods: Effects of instructed arm swing on cortical activity, muscle activity and kinematics were assessed by ambulant EEG, EMG, accelerometers and video in 17 Parkinson patients and 19 controls. At baseline, all participants repeatedly started walking after a simple auditory cue. Next, patients started walking at this cue, which now meant starting with enhanced arm swing. EEG changes over the putative SMA and leg motor cortex were assessed by event related spectral perturbation (ERSP) analysis of recordings at Fz and Cz., Results: Over the putative SMA location (Fz), natural PD gait initiation showed enhanced alpha/theta synchronization around the auditory cue, and reduced alpha/beta desynchronization during gait preparation and movement onset, compared to controls. Leg muscle activity in patients was reduced during preparation and movement onset, while the latter was delayed compared to controls. When starting with enhanced arm swing, these group differences virtually disappeared., Conclusion: Instructed arm swing improves Parkinson gait initiation. ERSP normalization around the cue indicates that the attributed information may serve as a semi-internal cue, recruiting an internalized motor program to overcome initiation difficulties.

Background: In clinical practice, visual assessment of glucose metabolism images is often used for the diagnosis of Alzheimer's disease (AD) through 2-[ 18 F]-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) scans. However, visual assessment of the characteristic AD hypometabolic pattern relies on the expertise of the reader. Therefore, user-independent pipelines are preferred to evaluate the images and to classify the subjects. Moreover, glucose consumption is highly correlated with cerebral perfusion. Regional cerebral blood flow (rCBF) images can be derived from dynamic 11 C-labelled Pittsburgh Compound B PET scans, which are also used for the assessment of the deposition of amyloid-β plaques on the brain, a fundamental characteristic of AD. The aim of this study was to explore whether these rCBF PIB images could be used for diagnostic purposes through the PMOD Alzheimer's Discrimination Tool., Results: Both tracer relative cerebral flow (R 1 ) and early PIB (ePIB) (20-130 s) uptake presented a good correlation when compared to FDG standardized uptake value ratio (SUVR), while ePIB (1-8 min) showed a worse correlation. All receiver operating characteristic curves exhibited a similar shape, with high area under the curve values, and no statistically significant differences were found between curves. However, R 1 and ePIB (1-8 min) had the highest sensitivity, while FDG SUVR had the highest specificity., Conclusion: rCBF images were suggested to be a good surrogate for FDG scans for diagnostic purposes considering an adjusted threshold value.

Emerging evidence suggests that Parkinson's disease (PD) results from disrupted oscillatory activity in cortico-basal ganglia-thalamo-cortical (CBGTC) and cerebellar networks which can be partially corrected by applying deep brain stimulation (DBS). The inherent dynamic nature of such oscillatory activity might implicate that is represents temporal aspects of motor control. While the timing of muscle activities in CBGTC networks constitute the temporal dimensions of distinct motor acts, these very networks are also involved in somatosensory processing. In this respect, a temporal aspect of somatosensory processing in motor control concerns matching predicted (feedforward) and actual (feedback) sensory consequences of movement which implies a distinct contribution to demarcating the temporal order of events. Emerging evidence shows that such somatosensory processing is altered in movement disorders. This raises the question how disrupted oscillatory activity is related to impaired temporal processing and how/whether DBS can functionally restore this. In this perspective article, the neural underpinnings of temporal processing will be reviewed and translated to the specific alternated oscillatory neural activity specifically found in Parkinson's disease. These findings will be integrated in a neurophysiological framework linking somatosensory and motor processing. Finally, future implications for neuromodulation will be discussed with potential implications for strategy across a range of movement disorders.

Background: Human gait benefits from arm swing, which requires four-limb co-ordination. The Supplementary Motor Area (SMA) is involved in multi-limb coordination. With its location anterior to the leg motor cortex and the pattern of its connections, this suggests a distinct role in gait control., Research Question: Is the SMA functionally implicated in gait-related arm swing?, Methods: Ambulant electroencephalography (EEG) was employed during walking with and without arm swing in twenty healthy subjects (mean age: 64.9yrs, SD 7.2). Power changes across the EEG frequency spectrum were assessed by Event Related Spectral Perturbation (ERSP) analysis over both the putative SMA at electrode position Fz and additional sensorimotor regions., Results: During walking with arm swing, midline electrodes Fz and Cz showed a step-related pattern of Event Related Desynchronization (ERD) followed by Event Related Synchronization (ERS). Walking without arm swing was associated with significant ERD-ERS power reduction in the high-beta/low-gamma band over Fz and a power increase over Cz. Electrodes C3 and C4 revealed a pattern of ERD during contralateral- and ERS during ipsilateral leg swing. This ERD power decreased in gait without arm swing (low-frequency band). The ERSP pattern during walking with arm swing was similar at CP1 and CP2: ERD was seen during double support and the initial swing phase of the right leg, while a strong ERS emerged during the second half of the left leg's swing. Walking without arm swing showed a significant power reduction of this ERD-ERS pattern over CP2, while over CP1, ERS during left leg's swing turned into ERD., Conclusion: The relation between arm swing in walking and a step-related ERD-ERS pattern in the high-beta/low-gamma band over the putative SMA, points at an SMA contribution to integrated cyclic anti-phase movements of upper- and lower limbs. This supports a cortical underpinning of arm swing support in gait control., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A reduction in goal-directed behavior, or apathy, occurs in neurological and psychiatric disorders, though its neural substrates remain unclear. Deficits in circuits connecting the prefrontal cortex to subcortical regions are considered to underlie apathy. Although apathy is empirically associated with widespread changes in these regions, studies across disorders also link apathy with the lateral parietal cortex. Such variety in regional involvement is consistent with the established role of prefrontal and subcortical regions in models of goal-directed behavior, and with the suggestion of subtypes of apathy. However, these models do not provide a basis for the involvement of the lateral parietal cortex with apathy. Here, we review the association between lateral parietal cortex dysfunction and apathy across disorders and analyze the putative cognitive functions that may link this region with goal-directed behavior. We suggest that neural processes in the angular and supramarginal gyri of the inferior parietal lobule may provide an interface enabling the transformation of internal goals to external actions through intentional initiation of action interrelated with mechanisms of primary sensorimotor transformation. Consequently, we propose that impairment in this process of embedding intended action in a 'body schema' facilitating adequate recruitment of an effector system, is the likely mechanism underlying the association between the lateral parietal cortex and apathy. Considering the evidence, we propose a revised neurocognitive model of apathy where deficient internal initiation of behavior mediated by the inferior parietal lobule may be sufficient, though not necessary, to reduce goal-directed behavior, and may constitute a volitional subtype of apathy., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Self-intended action implies an initial stage of assigning an external entity as target of action, with subsequent recruitment of body-scheme information serving the free selection of an appropriate effector system to achieve the action aim. This plurality underscores the concept that neuronal response freedom underlying the generation of such action is not necessarily restricted to a singular cerebral event at its initiation, but that such freedom is embedded in a series of successive processing steps. In this respect, action intention initially concerns the transition of a neutral object into a target of action, while the "will" to act further crystalizes with the recruitment of one's body scheme. The latter is a prerequisite for effector selection and indeed complements the emerging sense of agency. This temporal order of neuronal events fits a model of fronto-parietal interactions associated with volition. A concise behavioral experiment is additionally described, in which successively displayed balls represent either a recognizable object with distinct shape and color features, or a target of action. Instructions to write down the ball's characteristics were alternated by the command "action." When shifting from a neutral object to an action target, the ball was placed in one of three backgrounds: empty, an outdoor goal or indoor basket. In response to the action command, subjects reported intended actions such as kicking, seizing, throwing and heading, thus implicitly referring to the foot, hand, or head as chosen effector. For the latter the parietal cortex is strongly implicated, not only concerning predefined but also free selection. Although subjects were free to choose what to do with the ball, the environmental cues of the ball strongly influenced their choices. These results illustrate the temporal order in fronto-parietal processing associated with initial target assignment, instantly followed by the embodiment of will, i.e., the recruitment of body-scheme information for possible effector selection. Such multistage neuronal processing underlying free action selection underscores that the onset of brain signals prior to the perceived sense of free will is not a valid argument to reduce free will to an illusion.

In Alzheimer's Disease (AD) dual-tracer positron emission tomography (PET) studies with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) and 11C-labelled Pittsburgh Compound B (PIB) are used to assess metabolism and cerebral amyloid-β deposition, respectively. Regional cerebral metabolism and blood flow (rCBF) are closely coupled, both providing an index for neuronal function. The present study compared PIB-derived rCBF, estimated by the ratio of tracer influx in target regions relative to reference region (R1) and early-stage PIB uptake (ePIB), to FDG scans. Fifteen PIB positive (+) patients and fifteen PIB negative (-) subjects underwent both FDG and PIB PET scans to assess the use of R1 and ePIB as a surrogate for FDG. First, subjects were classified based on visual inspection of the PIB PET images. Then, discriminative performance (PIB+ versus PIB-) of rCBF methods were compared to normalized regional FDG uptake. Strong positive correlations were found between analyses, suggesting that PIB-derived rCBF provides information that is closely related to what can be seen on FDG scans. Yet group related differences between method's distributions were seen as well. Also, a better correlation with FDG was found for R1 than for ePIB. Further studies are needed to validate the use of R1 as an alternative for FDG studies in clinical applications., Competing Interests: The authors have declared that no competing interests exist.

Introduction: We aimed to uncover the pattern of network-level changes in neuronal function in Spinocerebellar ataxia type 3 (SCA3)., Methods: 17 genetically-confirmed SCA3 patients and 16 controls underwent structural MRI and static resting-state [ 18 F]‑Fluoro‑deoxyglucose Positron Emission Tomography (FDG-PET) imaging. A SCA3-related pattern (SCA3-RP) was identified using a multivariate method (scaled subprofile model and principal component analysis (SSM PCA)). Participants were evaluated with the Scale for Assessment and Rating of Ataxia (SARA) and with neuropsychological examination including tests for language, executive dysfunction, memory, and information processing speed. The relationships between SCA3-RP expression and clinical scores were explored. Voxel based morphology (VBM) was applied on MRI-T1 images to assess possible correlations between FDG reduction and grey matter atrophy., Results: The SCA3-RP disclosed relative hypometabolism of the cerebellum, caudate nucleus and posterior parietal cortex, and relatively increased metabolism in somatosensory areas and the limbic system. This topography, which was not explained by regional atrophy, correlated significantly with ataxia (SARA) scores (ρ = 0.72; P  = 0.001). SCA3 patients showed significant deficits in executive function and information processing speed, but only letter fluency correlated with SCA3-RP expression (ρ = 0.51; P  = 0.04, uncorrected for multiple comparisons)., Conclusion: The SCA3 metabolic profile reflects network-level alterations which are primarily associated with the motor features of the disease. Striatum decreases additional to cerebellar hypometabolism underscores an intrinsic extrapyramidal involvement in SCA3. Cerebellar-posterior parietal hypometabolism together with anterior parietal (sensory) cortex hypermetabolism may reflect a shift from impaired feedforward to compensatory feedback processing in higher-order motor control. The demonstrated SCA3-RP provides basic insight in cerebral network changes in this disease.

Objective: Posthypoxic myoclonus (PHM) in the first few days after resuscitation can be divided clinically into generalized and focal (uni- and multifocal) subtypes. The former is associated with a subcortical origin and poor prognosis in patients with postanoxic encephalopathy (PAE), and the latter with a cortical origin and better prognosis. However, use of PHM as prognosticator in PAE is hampered by the modest objectivity in its clinical assessment. Therefore, we aimed to obtain the anatomical origin of PHM with use of neurophysiological investigations, and relate these to its clinical presentation., Methods: This study included 20 patients (56 ± 18 y/o, 68% M, 2 survived, 1 excluded) with EEG-EMG-video recording. Three neurologists classified PHM into generalized or focal PHM. Anatomical origin (cortical/subcortical) was assessed with basic and advanced neurophysiology (Jerk-Locked Back Averaging, coherence analysis)., Results: Clinically assessed origin of PHM did not match the result obtained with neurophysiology: cortical PHM was more likely present in generalized than in focal PHM. In addition, some cases demonstrated co-occurrence of cortical and subcortical myoclonus. Patients that recovered from PAE had cortical myoclonus (1 generalized, 1 focal)., Interpretation: Hypoxic damage to variable cortical and subcortical areas in the brain may lead to mixed and varying clinical manifestations of myoclonus that differ of those patients with myoclonus generally encountered in the outpatient clinic. The current clinical classification of PHM is not adequately refined to play a pivotal role in guiding treatment decisions to withdraw care. Our neurophysiological characterization of PHM provides specific parameters to be used in designing future comprehensive studies addressing the potential role of PHM as prognosticator in PAE.

Purpose: Alterations of the central serotonergic system have been implicated in the pathophysiology of dystonia. In this molecular imaging study, we assessed whether altered presynaptic serotonin transporter (SERT) binding contributes to the pathophysiology of cervical dystonia (CD), concerning both motor and non-motor symptoms (NMS)., Methods: We assessed the non-displaceable binding potential (BP ND ) using the selective SERT tracer [ 11 C]DASB and positron emission tomography (PET) in 14 CD patients and 12 age- and gender-matched controls. Severity of motor symptoms was scored using the Toronto Western Spasmodic Torticollis Rating Scale and Clinical Global Impression jerks/tremor scale. NMS for depressive symptoms, anxiety, fatigue, and sleep disturbances were assessed with quantitative rating scales. The relationship between SERT binding and clinical patient characteristics was analyzed with the Spearman's rho test and multiple regression., Results: When comparing the CD patients with controls, no significant differences in BP ND were found. Higher BP ND in the dorsal raphe nucleus was statistically significantly correlated ( p  < 0.001) with motor symptom severity ( r s  = 0.65), pain ( r s  = 0.73), and sleep disturbances ( r s  = 0.73), with motor symptom severity being the most important predictor of SERT binding. Furthermore, fatigue was negatively associated with the BP ND in the medial raphe nucleus ( r s  = -0.61, p  = 0.045), and sleep disorders were positively associated with the BP ND in the caudate nucleus ( r s  = 0.58, p  = 0.03) and the hippocampus ( r s  = 0.56, p  = 0.02)., Conclusion: Motor symptoms, as well as pain, sleep disturbances, and fatigue in CD showed a significant relationship with SERT binding in the raphe nuclei. Moreover, fatigue showed a significant relationship with the medial raphe nucleus and sleep disorders with the caudate nucleus and hippocampus. These findings suggest that an altered serotonergic signaling in different brain areas in CD is related to different motor as well as NMS, which will further stimulate research on the role of serotonin in the pathogenesis of dystonia.

Background: We describe the phenomenon of crossed cerebellar diaschisis (CCD) in four subjects diagnosed with Alzheimer's disease (AD) according to the National Institute on Aging - Alzheimer Association (NIA-AA) criteria, in combination with 18F-FDG PET and 11C-PiB PET imaging., Methods: 18F-FDG PET showed a pattern of cerebral metabolism with relative decrease most prominent in the frontal-parietal cortex of the left hemisphere and crossed hypometabolism of the right cerebellum. 11C-PiB PET showed symmetrical amyloid accumulation, but a lower relative tracer delivery (a surrogate of relative cerebral blood flow) in the left hemisphere. CCD is the phenomenon of unilateral cerebellar hypometabolism as a remote effect of supratentorial dysfunction of the brain in the contralateral hemisphere. The mechanism implies the involvement of the cortico-ponto-cerebellar fibers. The pathophysiology is thought to have a functional or reversible basis but can also reflect in secondary morphologic change. CCD is a well-recognized phenomenon, since the development of new imaging techniques, although scarcely described in neurodegenerative dementias., Results: To our knowledge this is the first report describing CCD in AD subjects with documentation of both 18F-FDG PET and 11C-PiB PET imaging. CCD in our subjects was explained on a functional basis due to neurodegenerative pathology in the left hemisphere. There was no structural lesion and the symmetric amyloid accumulation did not correspond with the unilateral metabolic impairment., Conclusion: This suggests that CCD might be caused by non-amyloid neurodegeneration. The pathophysiological mechanism, clinical relevance and therapeutic implications of CCD and the role of the cerebellum in AD need further investigation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Aims: Heart failure (HF) is associated with tissue hypoperfusion and congestion leading to organ dysfunction. Although cerebral blood flow (CBF) is preserved over a wide range of perfusion pressures in healthy subjects, it is impaired in end-stage HF. We aimed to compare CBF, autoregulation, and cognitive function in patients with mild non-ischaemic HF with healthy controls., Methods and Results: Fifteen patients with mild idiopathic dilated cardiomyopathy and 15 matched healthy controls were studied. Co-existing cerebrovascular disease was excluded. All subjects, except five patients with an implantable cardioverter defibrillator, underwent magnetic resonance imaging for measurements of both CBF by arterial spin labelling and quantitative volume flow entering the brain. Cardiocerebral vascular function was assessed with Doppler techniques testing cerebral dynamic autoregulation and vasomotor reactivity. Cognitive analysis was performed by neuropsychological testing. Global and regional CBF did not differ between HF patients (44.3 mL/100 g.min) and controls (42.1 mL/100 g.min). Basilar but not carotid artery inflow was reduced in patients (1.95 mL/s vs. 2.51 mL/s, P = 0.009). Testing autoregulation revealed fewer dampened blood flow fluctuations in HF patients vs. controls (0.96% vs. 0.67%, P < 0.001). Vasomotor reactivity in HF patients showed a reduced CBF velocity (48.4% vs. 61.0%, P = 0.05) and regional cerebral oxygen saturation (18.3% vs. 23.8%, P = 0.02). Cognitive function overall was not affected., Conclusion: Although global CBF was unaffected in patients with mild HF, significant changes in basilar inflow volume, cerebral autoregulation and vasomotor reactivity were observed. We describe a model of dynamic cerebral mechanisms required to compensate for the impaired haemodynamics in early-stage HF., (© 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.)

This review focuses on recent human 18 F-FDG PET studies in Parkinson disease. First, an overview is given of the current analytic approaches to metabolic brain imaging data. Next, we discuss how 18 F-FDG PET studies have advanced understanding of the relation between distinct brain regions and associated symptoms in Parkinson disease, including cognitive decline. In addition, the value of 18 F-FDG PET studies in differential diagnosis, identifying prodromal patients, and the evaluation of treatment effects are reviewed. Finally, anticipated developments in the field are addressed., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)