Selective enhancement of post-sleep visual motion perception by repetitive tactile stimulation during sleep.

Tactile sensations can bias visual perception in the awake state while visual sensitivity is known to be facilitated by sleep. It remains unknown, however, whether the tactile sensation during sleep can bias the visual improvement after sleep. Here, we performed nap experiments in human participants (n = 56, 18 males, 38 females) to demonstrate that repetitive tactile motion stimulation on the fingertip during slow wave sleep selectively enhanced subsequent visual motion detection. The visual improvement was associated with slow wave activity. The high activation at the high beta frequency was found in the occipital electrodes after the tactile motion stimulation during sleep, indicating a visual-tactile cross-modal interaction during sleep. Furthermore, a second experiment (n = 14, 14 females) to examine whether a hand- or head-centered coordination is dominant for the interpretation of tactile motion direction showed that the biasing effect on visual improvement occurs according to the hand-centered coordination. These results suggest that tactile information can be interpreted during sleep, and can induce the selective improvement of post-sleep visual motion detection.Significant statement:Tactile sensations can bias our visual perception as a form of cross-modal interaction. However, it was reported only in the awake state. Here we show that repetitive directional tactile motion stimulation on the fingertip during slow wave sleep selectively enhanced subsequent visual motion perception. Moreover, the visual improvement was positively associated with sleep slow wave activity. The tactile motion stimulation during slow wave activity increased the activation at the high beta frequency over the occipital electrodes. The visual improvement occurred in agreement with a hand-centered reference frame. These results suggest that our sleeping brain can interpret tactile information based on a hand-centered reference frame, which can cause the sleep-dependent improvement of visual motion detection.

Sleep disorders in people with type 2 diabetes and associated health outcomes: a review of the literature.

Sleep disorders are linked to development of type 2 diabetes and increase the risk of developing diabetes complications. Treating sleep disorders might therefore play an important role in the prevention of diabetes progression. However, the detection and treatment of sleep disorders are not part of standardised care for people with type 2 diabetes. To highlight the importance of sleep disorders in people with type 2 diabetes, we provide a review of the literature on the prevalence of sleep disorders in type 2 diabetes and the association between sleep disorders and health outcomes, such as glycaemic control, microvascular and macrovascular complications, depression, mortality and quality of life. Additionally, we examine the extent to which treating sleep disorders in people with type 2 diabetes improves these health outcomes. We performed a literature search in PubMed from inception until January 2021, using search terms for sleep disorders, type 2 diabetes, prevalence, treatment and health outcomes. Both observational and experimental studies were included in the review. We found that insomnia (39% [95% CI 34, 44]), obstructive sleep apnoea (55-86%) and restless legs syndrome (8-45%) were more prevalent in people with type 2 diabetes, compared with the general population. No studies reported prevalence rates for circadian rhythm sleep-wake disorders, central disorders of hypersomnolence or parasomnias. Additionally, several cross-sectional and prospective studies showed that sleep disorders negatively affect health outcomes in at least one diabetes domain, especially glycaemic control. For example, insomnia is associated with increased HbA1c levels (2.51 mmol/mol [95% CI 1.1, 4.4]; 0.23% [95% CI 0.1, 0.4]). Finally, randomised controlled trials that investigate the effect of treating sleep disorders in people with type 2 diabetes are scarce, based on a small number of participants and sometimes inconclusive. Conventional therapies such as weight loss, sleep education and cognitive behavioural therapy seem to be effective in improving sleep and health outcomes in people with type 2 diabetes. We conclude that sleep disorders are highly prevalent in people with type 2 diabetes, negatively affecting health outcomes. Since treatment of the sleep disorder could prevent diabetes progression, efforts should be made to diagnose and treat sleep disorders in type 2 diabetes in order to ultimately improve health and therefore quality of life.

International Multicenter Analysis of Brain Structure Across Clinical Stages of Parkinson's Disease.

BACKGROUND: Brain structure abnormalities throughout the course of Parkinson's disease have yet to be fully elucidated. OBJECTIVE: Using a multicenter approach and harmonized analysis methods, we aimed to shed light on Parkinson's disease stage-specific profiles of pathology, as suggested by in vivo neuroimaging. METHODS: Individual brain MRI and clinical data from 2357 Parkinson's disease patients and 1182 healthy controls were collected from 19 sources. We analyzed regional cortical thickness, cortical surface area, and subcortical volume using mixed-effects models. Patients grouped according to Hoehn and Yahr stage were compared with age- and sex-matched controls. Within the patient sample, we investigated associations with Montreal Cognitive Assessment score. RESULTS: Overall, patients showed a thinner cortex in 38 of 68 regions compared with controls (dmax  = -0.20, dmin  = -0.09). The bilateral putamen (dleft  = -0.14, dright  = -0.14) and left amygdala (d = -0.13) were smaller in patients, whereas the left thalamus was larger (d = 0.13). Analysis of staging demonstrated an initial presentation of thinner occipital, parietal, and temporal cortices, extending toward rostrally located cortical regions with increased disease severity. From stage 2 and onward, the bilateral putamen and amygdala were consistently smaller with larger differences denoting each increment. Poorer cognition was associated with widespread cortical thinning and lower volumes of core limbic structures. CONCLUSIONS: Our findings offer robust and novel imaging signatures that are generally incremental across but in certain regions specific to disease stages. Our findings highlight the importance of adequately powered multicenter collaborations. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Adverse events of repetitive transcranial magnetic stimulation in older adults with depression, a systematic review of the literature.

OBJECTIVE: In the last decade, repetitive transcranial magnetic stimulation (rTMS) has been introduced as a non-invasive neuromodulation therapy for depression. Little is known, however, about (serious) adverse events (AE) of rTMS in older adults with a depression. In this article, we want to study what is known about (serious) AE of rTMS in older adults (>60 years) with late-life depression (LLD). METHODS: A systematic search has been performed according to the PRISMA guidelines in PubMed, EMBase and PsycInfo. We have screened 622 articles for eligibility. Eleven studies, evaluating 353 patients in total, were included in this review. RESULTS: AE were reported in 12.4% of the older adults with a LLD treated with rTMS, serious AE in 1.5%. Headache (6.9%) and discomfort at the stimulation site (2.7%) are the most commonly reported AE. Serious AE reported are: psychiatric hospitalization (three times), a combination of posterior vitreous detachment and retinal tear, and increased suicide ideation (both once). CONCLUSIONS: rTMS in older adults with LLD was concluded overall to be safe due to the low frequency of AE reported in trials and observational studies. In case-reports, however, more serious AE have been described. To tailor use of rTMS in older adults with LLD, more research is needed in larger samples to optimize tolerance.

Resting-state and task-based centrality of dorsolateral prefrontal cortex predict resilience to 1 Hz repetitive transcranial magnetic stimulation.

Repetitive transcranial magnetic stimulation (rTMS) is used to investigate normal brain function in healthy participants and as a treatment for brain disorders. Various subject factors can influence individual response to rTMS, including brain network properties. A previous study by our group showed that "virtually lesioning" the left dorsolateral prefrontal cortex (dlPFC; important for cognitive flexibility) using 1 Hz rTMS reduced performance on a set-shifting task. We aimed to determine whether this behavioural response was related to topological features of pre-TMS resting-state and task-based functional networks. 1 Hz (inhibitory) rTMS was applied to the left dlPFC in 16 healthy participants, and to the vertex in 17 participants as a control condition. Participants performed a set-shifting task during fMRI at baseline and directly after a single rTMS session 1-2 weeks later. Functional network topology measures were calculated from resting-state and task-based fMRI scans using graph theoretical analysis. The dlPFC-stimulated group, but not the vertex group, showed reduced setshifting performance after rTMS, associated with lower task-based betweenness centrality (BC) of the dlPFC at baseline (p = .030) and a smaller reduction in task-based BC after rTMS (p = .024). Reduced repeat trial accuracy after rTMS was associated with higher baseline resting state node strength of the dlPFC (p = .017). Our results suggest that behavioural response to 1 Hz rTMS to the dlPFC is dependent on baseline functional network features. Individuals with more globally integrated stimulated regions show greater resilience to rTMS effects, while individuals with more locally well-connected regions show greater vulnerability.

The Effects of Cognitive Training on Brain Network Activity and Connectivity in Aging and Neurodegenerative Diseases: a Systematic Review.

Cognitive training (CT) is an increasingly popular, non-pharmacological intervention for improving cognitive functioning in neurodegenerative diseases and healthy aging. Although meta-analyses support the efficacy of CT in improving cognitive functioning, the neural mechanisms underlying the effects of CT are still unclear. We performed a systematic review of literature in the PubMed, Embase and PsycINFO databases on controlled CT trials (N > 20) in aging and neurodegenerative diseases with pre- and post-training functional MRI outcomes up to November 23rd 2018 (PROSPERO registration number CRD42019103662). Twenty articles were eligible for our systematic review. We distinguished between multi-domain and single-domain CT. CT induced both increases and decreases in task-related functional activation, possibly indicative of an inverted U-shaped curve association between regional brain activity and task performance. Functional connectivity within 'cognitive' brain networks was consistently reported to increase after CT while a minority of studies additionally reported increased segregation of frontoparietal and default mode brain networks. Although we acknowledge the large heterogeneity in type of CT, imaging methodology, in-scanner task paradigm and analysis methods between studies, we propose a working model of the effects of CT on brain activity and connectivity in the context of current knowledge on compensatory mechanisms that are associated with aging and neurodegenerative diseases.

Actigraphic multi-night home-recorded sleep estimates reveal three types of sleep misperception in Insomnia Disorder and good sleepers.

People with Insomnia Disorder tend to underestimate their sleep compared with polysomnography or actigraphy, a phenomenon known as paradoxical insomnia or sleep-state misperception. Previous studies suggested that night-to-night variability could be an important feature differentiating subtypes of misperception. This study aimed for a data-driven definition of misperception subtypes revealed by multiple sleep features including night-to-night variability. We assessed features describing the mean and dispersion of misperception and objective and subjective sleep duration from 7-night diary and actigraphy recordings of 181 people with Insomnia Disorder and 55 people without sleep complaints. A minimally collinear subset of features was submitted to latent class analysis for data-driven subtyping. Analysis revealed three subtypes, best discriminated by three of five selected features: an individual's shortest reported subjective sleep duration; and the mean and standard deviation of misperception. These features were on average 5.4, -0.0 and 0.5 hr in one subtype accommodating the majority of good sleepers; 4.1, -1.4 and 1.0 hr in a second subtype representing the majority of people with Insomnia Disorder; and 1.7, -2.2 and 1.5 hr in a third subtype representing a quarter of people with Insomnia Disorder and hardly any good sleepers. Subtypes did not differ on an individual's objective sleep duration mean (6.9, 7.2 and 6.9 hr) and standard deviation (0.8, 0.8 and 0.9 hr). Data-driven analysis of naturalistic sleep revealed three subtypes that markedly differed in misperception features. Future studies may include misperception subtype to investigate whether it contributes to the unexplained considerable individual variability in treatment response.

COGTIPS: a double-blind randomized active controlled trial protocol to study the effect of home-based, online cognitive training on cognition and brain networks in Parkinson's disease.

BACKGROUND: Cognitive dysfunction is highly prevalent in Parkinson's disease (PD) and a large proportion of patients eventually develops PD-related dementia. Currently, no effective treatment is available. Cognitive training is effective in relieving cognitive dysfunctions in several -neurodegenerative- diseases, and earlier small-scale trials have shown positive results for PD. In this randomized controlled trial, we assess the efficacy of online home-based cognitive training, its long-term effects, as well as the underlying neural correlates in a large group of PD patients. METHODS: In this double-blind randomized controlled trial we will include 140 non-demented patients with idiopathic PD that experience significant subjective cognitive complaints. Participants will be randomized into a cognitive training group and an active control group. In both groups, participants will individually perform an online home-based intervention for eight weeks, three times a week during 45 min. The cognitive training consists of thirteen games that focus on executive functions, attention and processing speed with an adaptive difficulty. The active control comprises three games that keep participants cognitively engaged without a training component. Participants will be subjected to extensive neuropsychological assessments at baseline and after the intervention, and at six months, one year and two years of follow-up. A subset of participants (40 in each treatment condition) will undergo structural and functional magnetic resonance imaging. The primary outcome of this study is the performance on the Tower of London task. Secondary outcomes are objective and subjective cognitive functioning, conversion to PD-related mild cognitive impairment or dementia, functional and structural connectivity and network topological indices measured with magnetic resonance imaging. None of the outcome measures are part of the cognitive training program. Data will be analyzed using multivariate mixed-model analyses and odds ratios. DISCUSSION: This study is a large-scale cognitive training study in PD patients that evaluates the efficacy in relieving cognitive dysfunction, and the underlying mechanisms. The strengths of this study are the large sample size, the long follow-up period and the use of neuroimaging in a large subsample. The study is expected to have a low attrition and a high compliance rate given the home-based and easily-accessible intervention in both conditions. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT02920632 . Registered September 30, 2016.

Slow dissolving of emotional distress contributes to hyperarousal.

The mechanisms underlying hyperarousal, the key symptom of insomnia, have remained elusive, hampering cause-targeted treatment. Recently, restless rapid-eye-movement (REM) sleep emerged as a robust signature of sleep in insomnia. Given the role of REM sleep in emotion regulation, we hypothesized that restless REM sleep could interfere with the overnight resolution of emotional distress, thus contributing to accumulation of arousal. Participants (n = 1,199) completed questionnaires on insomnia severity, hyperarousal, self-conscious emotional distress, and thought-like nocturnal mentation that was validated to be a specific proxy for restless REM sleep (selective fragmentation: R = 0.57, P < 0.001; eye movement density: R = 0.46, P < 0.01) in 32 polysomnographically assessed participants. The experience of distress lasting overnight increased with insomnia severity (ß = 0.29, P < 10(-23)), whereas short-lasting distress did not (ß = -0.02, P = 0.41). Insomnia severity was associated with hyperarousal (ß = 0.47, P < 10(-63)) and with the thought-like nocturnal mentation that is specifically associated with restless REM sleep (ß = 0.31, P < 10(-26)). Structural equation modeling showed that 62.4% of the association between these key characteristics of insomnia was mediated specifically by reduced overnight resolution of emotional distress. The model outperformed all alternative mediation pathways. The findings suggest that restless REM sleep reflects a process that interferes with the overnight resolution of distress. Its accumulation may promote the development of chronic hyperarousal, giving clinical relevance to the role of REM sleep in emotion regulation in insomnia, depression, and posttraumatic stress disorder.

Early Trajectory Prediction in Elite Athletes.

Cerebellar plasticity is a critical mechanism for optimal feedback control. While Purkinje cell activity of the oculomotor vermis predicts eye movement speed and direction, more lateral areas of the cerebellum may play a role in more complex tasks, including decision-making. It is still under question how this motor-cognitive functional dichotomy between medial and lateral areas of the cerebellum plays a role in optimal feedback control. Here we show that elite athletes subjected to a trajectory prediction, go/no-go task manifest superior subsecond trajectory prediction accompanied by optimal eye movements and changes in cognitive load dynamics. Moreover, while interacting with the cerebral cortex, both the medial and lateral cerebellar networks are prominently activated during the fast feedback stage of the task, regardless of whether or not a motor response was required for the correct response. Our results show that cortico-cerebellar interactions are widespread during dynamic feedback and that experience can result in superior task-specific decision skills.

Carbon-wire loop based artifact correction outperforms post-processing EEG/fMRI corrections--A validation of a real-time simultaneous EEG/fMRI correction method.

Simultaneous EEG-fMRI combines two powerful neuroimaging techniques, but the EEG signal suffers from severe artifacts in the MRI environment that are difficult to remove. These are the MR scanning artifact and the blood-pulsation artifact--strategies to remove them are a topic of ongoing research. Additionally large, unsystematic artifacts are produced across the full frequency spectrum by the magnet's helium pump (and ventilator) systems which are notoriously hard to remove. As a consequence, experimenters routinely deactivate the helium pump during simultaneous EEG-fMRI acquisitions which potentially risks damaging the MRI system and necessitates more frequent and expensive helium refills. We present a novel correction method addressing both helium pump and ballisto-cardiac (BCG) artifacts, consisting of carbon-wire loops (CWL) as additional sensors to accurately track unpredictable artifacts related to subtle movements in the scanner, and an EEGLAB plugin to perform artifact correction. We compare signal-to-noise metrics of EEG data, corrected with CWL and three conventional correction methods, for helium pump off and on measurements. Because the CWL setup records signals in real-time, it fits requirements of applications where immediate correction is necessary, such as neuro-feedback applications or stimulation time-locked to specific sleep oscillations. The comparison metrics in this paper relate to: (1) the EEG signal itself, (2) the "eyes open vs. eyes closed" effect, and (3) an assessment of how the artifact corrections impacts the ability to perform meaningful correlations between EEG alpha power and the BOLD signal. Results show that the CWL correction corrects for He pump artifact and also produces EEG data more comparable to EEG obtained outside the magnet than conventional post-processing methods.

Reduced task-related functional connectivity during a set-shifting task in unmedicated early-stage Parkinson's disease patients.

BACKGROUND: Patients with Parkinson's disease (PD) often suffer from cognitive impairments, including set-shifting deficits, in addition to the characteristic motor symptoms. It is hypothesized that the striatal dopamine depletion leads to a sub-optimal functional connectivity between task-related brain areas and consequently results in impaired task-performance. In this study, we aimed to examine this hypothesis by investigating the task-related functional connectivity of brain areas that are believed to be involved in set-shifting, such as the dorsolateral prefrontal cortex (DLPFC), posterior parietal cortex (PPC) and the superior frontal gyrus (SFG), during a set-shifting task. We obtained functional imaging data from 18 early-stage PD patients and 35 healthy controls, matched at the group level, using a newly developed rule-based set-shifting task that required participants to manually respond to arrow stimuli based on their location on the screen of their direction. RESULTS: We found that early stage PD patients, compared with controls, showed (1) a decrease in positive coupling between the left DLPFC and the right insular cortex, and the right SFG and anterior cingulate cortex, (2) an increase in negative coupling between the right SFG and the anterior cingulate cortex, primary motor cortex, precuneus, and PPC, and (3) an increase in negative coupling between the left DLPFC and the left and right SFG. These results indicate that important task-related areas of PD patients have decreased functional connectivity with task-related regions and increased connectivity with task-unrelated areas. CONCLUSIONS: The disruption of functional connectivity in early stage PD patients during set-shifting reported here is likely compensated for by the local hyperactivation we reported earlier, thereby forestalling behavioural deficits.

A smaller amygdala is associated with anxiety in Parkinson's disease: a combined FreeSurfer-VBM study.

BACKGROUND: Up to 50% of all patients with Parkinson's disease (PD) suffer from anxiety symptoms, a much higher percentage than in the general population. This suggests that PD associated pathological alterations partly underlie these symptoms, although empirical evidence is limited. METHODS: Here we investigated the association between anxiety symptoms measured with the Beck Anxiety Inventory (BAI) and hippocampal and amygdalar volume in 110 early-stage patients with PD. Measures of anxiety in PD are often obscured by overlap with the somatic symptoms. We therefore also used a subscale of the BAI, established by our recent factor analysis, that reflects 'psychological' anxiety symptoms and is independent of the severity of PD-related motor and autonomic symptoms. We used FreeSurfer and voxel-based morphometry for the volumetric analyses. RESULTS: Both software packages showed a negative correlation between the 'psychological' subscale of the BAI, but not total BAI and volume of the left amygdala, independent of the severity of motor symptoms, autonomic dysfunction and dopaminergic or anxiolytic medication status. CONCLUSIONS: These results confirm studies in non-PD samples showing lower left amygdalar volume in anxious patients. The results also indicate that the 'psychological' BAI subscale is a better reflection of neural correlates of anxiety in PD. Whether the left amygdalar volume decrease constitutes a premorbid trait, a PD-associated neurobiological susceptibility to anxiety or arises as a consequence of chronic anxiety symptoms remains to be determined by future prospective longitudinal studies. Nonetheless, we speculate that the Parkinson pathology is responsible for the reduction in amygdalar volume and the concomitant development of anxiety symptoms.

Hippocampal-cerebellar interaction during spatio-temporal prediction.

The hippocampus and cerebellum play a role in the process of temporal memory formation. The interaction between these brain regions during the prediction of motor executions nevertheless remains unclear. Using fMRI, we show here that the hippocampus and cerebellum are co-activated during a timing-dependent task that requires accurate prediction timing of finger movements following preceding visual cues, but not during 2 control tasks: a reaction task requiring identical coordination of individual and combined fingers without predicting the motor timing, or an imagery task. In addition, functional connectivity analyses reveal that the hippocampus showed increased functional connectivity with the bilateral hemispheres of the cerebellum. These results suggest that hippocampal-cerebellar interplay occurs during spatio-temporal prediction of movements on the basis of visuomotor integration.

A double-blind randomized controlled trial to assess the effect of bright light therapy on depression in patients with Parkinson's disease.

BACKGROUND: A disturbed circadian rhythm seems to be a causal factor in the occurrence of depressive disorders in patients with Parkinson's disease (PD). The circadian rhythm can be restored with light. Therefore, Bright Light Therapy (BLT) might be a new treatment option for depression in PD patients. METHODS/DESIGN: In this double-blind controlled trial, 84 subjects with idiopathic PD are randomized to either BLT or a control light condition. The BLT condition emits white light with an intensity of 10,000 Lux, while the control device emits dim white light of 200 Lux, which is presumed to be too low to influence the circadian rhythm. Subjects receive 30 min of home treatment twice daily for three months. Timing of treatment is based on the individual chronotype. After finishing treatment, subjects enter a follow-up period of six months. The primary outcome of the study is the severity of depressive symptoms, as measured with the Hamilton Depression Rating Scale. Secondary outcomes are alternative depression measures, objective and subjective sleep measures, and salivary melatonin and cortisol concentrations. For exploratory purposes, we also assess the effects on motor symptoms, global cognitive function, comorbid psychiatric disorders, quality of life and caregiver burden. Data will be analyzed using a linear mixed models analysis. DISCUSSION: Performing a placebo-controlled trial on the effects of BLT in PD patients is challenging, as the appearance of the light may provide clues on the treatment condition. Moreover, fixed treatment times lead to an improved sleep-wake rhythm, which also influences the circadian system. With our study design, we do not compare BLT to placebo treatment, i.e. an ineffective control treatment. Rather, we compare structuring of the sleep-wake cycle in both conditions with additional BLT in the experimental condition, and additional dim light in the control condition. Participants are not informed about the exact details of the two light devices and the expected therapeutic effect, and expectancies are rated prior to the start of treatment. Ideally, the design of a future study on BLT should include two extra treatment arms where BLT and control light are administered at random times. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov on May 17th 2012 (ClinicalTrials.gov Identifier: NCT01604876 ).

Memory traces of long-range coordinated oscillations in the sleeping human brain.

Cognition involves coordinated activity across distributed neuronal networks. Neuronal activity during learning triggers cortical plasticity that allows for reorganization of the neuronal network and integration of new information. Animal studies have shown post-learning reactivation of learning-elicited neuronal network activity during subsequent sleep, supporting consolidation of the reorganization. However, no previous studies, to our knowledge, have demonstrated reactivation of specific learning-elicited long-range functional connectivity during sleep in humans. We here show reactivation of learning-induced long-range synchronization of magnetoencephalography power fluctuations in human sleep. Visuomotor learning elicited a specific profile of long-range cortico-cortical synchronization of slow (0.1 Hz) fluctuations in beta band (12-30 Hz) power. The parieto-occipital part of this synchronization profile reappeared in delta band (1-3.5 Hz) power fluctuations during subsequent sleep, but not during the intervening wakefulness period. Individual differences in the reactivated synchronization predicted postsleep performance improvement. The presleep resting-state synchronization profile was not reactivated during sleep. The findings demonstrate reactivation of long-range coordination of neuronal activity in humans, more specifically of reactivation of coupling of infra-slow fluctuations in oscillatory power. The spatiotemporal profile of delta power fluctuations during sleep may subserve memory consolidation by echoing coordinated activation elicited by prior learning.

Impaired planning in Parkinson's disease is reflected by reduced brain activation and connectivity.

OBJECTIVE: Parkinson's disease (PD) often entails impairments of executive functions, such as planning. Although widely held that these impairments arise from dopaminergic denervation of the striatum, not all executive functions are affected early on, and the underlying neural dynamics are not fully understood. In a combined longitudinal and cross-sectional study, we investigated how planning deficits progress over time in the early stages of PD compared to matched healthy controls. We used functional magnetic resonance imaging (fMRI) to identify accompanying neural dynamics. METHODS: Seventeen PD patients and 20 healthy controls performed a parametric Tower of London task at two time points separated by ∼3 years (baseline and follow-up). We assessed task performance longitudinally in both groups; at follow-up, a subset of participants (14 patients, 19 controls) performed a parallel version of the task during fMRI. We performed meta-analyses to localize regions-of-interest (ROIs), that is, the bilateral dorsolateral prefrontal cortex (DLPFC), inferior parietal cortex, and caudate nucleus, and performed group-by-task analyses and within-group regression analyses of planning-related neural activation. We studied task-related functional connectivity of seeds in the DLPFC and caudate nucleus. RESULTS: PD patients, compared with controls, showed impaired task performance at both time-points, while both groups showed similar performance reductions from baseline to follow-up. Compared to controls, patients showed lower planning-related brain activation together with decreased functional connectivity. CONCLUSION: These findings support the notion that planning is affected early in the PD disease course, and that this impairment in planning is accompanied by decreases in both task-related brain activity and connectivity.