Functional brain connectivity changes associated with day-to-day fluctuations in affective states.

Affective neuroscience has traditionally relied on cross-sectional studies to uncover the brain correlates of affects, emotions, and moods. Such findings obfuscate intraindividual variability that may reveal meaningful changing affect states. The few functional magnetic resonance imaging longitudinal studies that have linked changes in brain function to the ebbs and flows of affective states over time have mostly investigated a single individual. In this study, we explored how the functional connectivity of brain areas associated with affective processes can explain within-person fluctuations in self-reported positive and negative affects across several subjects. To do so, we leveraged the Day2day dataset that includes 40 to 50 resting-state functional magnetic resonance imaging scans along self-reported positive and negative affectivity from a sample of six healthy participants. Sparse multivariate mixed-effect linear models could explain 15% and 11% of the within-person variation in positive and negative affective states, respectively. Evaluation of these models' generalizability to new data demonstrated the ability to predict approximately 5% and 2% of positive and negative affect variation. The functional connectivity of limbic areas, such as the amygdala, hippocampus, and insula, appeared most important to explain the temporal dynamics of affects over days, weeks, and months.

Brain functional connectivity mirrors genetic pleiotropy in psychiatric conditions.

Pleiotropy occurs when a genetic variant influences more than one trait. This is a key property of the genomic architecture of psychiatric disorders and has been observed for rare and common genomic variants. It is reasonable to hypothesize that the microscale genetic overlap (pleiotropy) across psychiatric conditions and cognitive traits may lead to similar overlaps at the macroscale brain level such as large-scale brain functional networks. We took advantage of brain connectivity, measured by resting-state functional MRI to measure the effects of pleiotropy on large-scale brain networks, a putative step from genes to behaviour. We processed nine resting-state functional MRI datasets including 32 726 individuals and computed connectome-wide profiles of seven neuropsychiatric copy-number-variants, five polygenic scores, neuroticism and fluid intelligence as well as four idiopathic psychiatric conditions. Nine out of 19 pairs of conditions and traits showed significant functional connectivity correlations (rFunctional connectivity), which could be explained by previously published levels of genomic (rGenetic) and transcriptomic (rTranscriptomic) correlations with moderate to high concordance: rGenetic-rFunctional connectivity = 0.71 [0.40-0.87] and rTranscriptomic-rFunctional connectivity = 0.83 [0.52; 0.94]. Extending this analysis to functional connectivity profiles associated with rare and common genetic risk showed that 30 out of 136 pairs of connectivity profiles were correlated above chance. These similarities between genetic risks and psychiatric disorders at the connectivity level were mainly driven by the overconnectivity of the thalamus and the somatomotor networks. Our findings suggest a substantial genetic component for shared connectivity profiles across conditions and traits, opening avenues to delineate general mechanisms-amenable to intervention-across psychiatric conditions and genetic risks.

Disrupted functional connectivity of the brain reward system in substance use problems: A meta-analysis of functional neuroimaging studies.

Extensive literature suggests that the brain reward system is crucial in understanding the neurobiology of substance use disorders. However, evidence of reliable deficits in functional connectivity across studies on substance use problems remains limited. Therefore, a voxel-wise seed-based meta-analysis using brain regions of the reward system as seeds of interest was conducted on 96 studies representing 5757 subjects with substance use problems. The ventromedial prefrontal cortex exhibited hyperconnectivity with the ventral striatum and hypoconnectivity with the amygdala and hippocampus. The executive striatum showed hyperconnectivity with the motor thalamus and dorsolateral prefrontal cortex and hypoconnectivity with the anterior cingulate cortex and anterior insula. Finally, the limbic striatum was found to be hyperconnected to the orbitofrontal cortex and hypoconnected to the precuneus compared with healthy subjects. The current study provided meta-analytical evidence of deficient functional connectivity between brain regions of the reward system and cortico-striato-thalamocortical loops in addiction. These results are consistent with deficits in motivation and habit formation occurring in addiction, and they highlight alterations in brain regions involved in socio-emotional processing and attention salience.

Multivariate consistency of resting-state fMRI connectivity maps acquired on a single individual over 2.5 years, 13 sites and 3 vendors.

Studies using resting-state functional magnetic resonance imaging (rsfMRI) are increasingly collecting data at multiple sites in order to speed up recruitment or increase sample size. The main objective of this study was to assess the long-term consistency of rsfMRI connectivity maps derived at multiple sites and vendors using the Canadian Dementia Imaging Protocol (CDIP, www.cdip-pcid.ca). Nine to 10 min of functional BOLD images were acquired from an adult cognitively healthy volunteer scanned repeatedly at 13 Canadian sites on three scanner makes (General Electric, Philips and Siemens) over the course of 2.5 years. The consistency (spatial Pearson's correlation) of rsfMRI connectivity maps for seven canonical networks ranged from 0.3 to 0.8, with a negligible effect of time, but significant site and vendor effects. We noted systematic differences in data quality (i.e. head motion, number of useable time frames, temporal signal-to-noise ratio) across vendors, which may also confound some of these results, and could not be disentangled in this sample. We also pooled the long-term longitudinal data with a single-site, short-term (1 month) data sample acquired on 26 subjects (10 scans per subject), called HNU1. Using randomly selected pairs of scans from each subject, we quantified the ability of a data-driven unsupervised cluster analysis to match two scans of the same subjects. In this "fingerprinting" experiment, we found that scans from the Canadian subject (Csub) could be matched with high accuracy intra-site (>95% for some networks), but that the accuracy decreased substantially for scans drawn from different sites and vendors, even falling outside of the range of accuracies observed in HNU1. Overall, our results demonstrate good multivariate stability of rsfMRI measures over several years, but substantial impact of scanning site and vendors. How detrimental these effects are will depend on the application, yet our results demonstrate that new methods for harmonizing multisite analysis represent an important area for future work.

Brain properties predict proximity to symptom onset in sporadic Alzheimer's disease.

See Tijms and Visser (doi:10.1093/brain/awy113) for a scientific commentary on this article.Alzheimer's disease is preceded by a lengthy 'preclinical' stage spanning many years, during which subtle brain changes occur in the absence of overt cognitive symptoms. Predicting when the onset of disease symptoms will occur is an unsolved challenge in individuals with sporadic Alzheimer's disease. In individuals with autosomal dominant genetic Alzheimer's disease, the age of symptom onset is similar across generations, allowing the prediction of individual onset times with some accuracy. We extend this concept to persons with a parental history of sporadic Alzheimer's disease to test whether an individual's symptom onset age can be informed by the onset age of their affected parent, and whether this estimated onset age can be predicted using only MRI. Structural and functional MRIs were acquired from 255 ageing cognitively healthy subjects with a parental history of sporadic Alzheimer's disease from the PREVENT-AD cohort. Years to estimated symptom onset was calculated as participant age minus age of parental symptom onset. Grey matter volume was extracted from T1-weighted images and whole-brain resting state functional connectivity was evaluated using degree count. Both modalities were summarized using a 444-region cortical-subcortical atlas. The entire sample was divided into training (n = 138) and testing (n = 68) sets. Within the training set, individuals closer to or beyond their parent's symptom onset demonstrated reduced grey matter volume and altered functional connectivity, specifically in regions known to be vulnerable in Alzheimer's disease. Machine learning was used to identify a weighted set of imaging features trained to predict years to estimated symptom onset. This feature set alone significantly predicted years to estimated symptom onset in the unseen testing data. This model, using only neuroimaging features, significantly outperformed a similar model instead trained with cognitive, genetic, imaging and demographic features used in a traditional clinical setting. We next tested if these brain properties could be generalized to predict time to clinical progression in a subgroup of 26 individuals from the Alzheimer's Disease Neuroimaging Initiative, who eventually converted either to mild cognitive impairment or to Alzheimer's dementia. The feature set trained on years to estimated symptom onset in the PREVENT-AD predicted variance in time to clinical conversion in this separate longitudinal dataset. Adjusting for participant age did not impact any of the results. These findings demonstrate that years to estimated symptom onset or similar measures can be predicted from brain features and may help estimate presymptomatic disease progression in at-risk individuals.

State-dependent modulation of functional connectivity in early blind individuals.

Resting-state functional connectivity (RSFC) studies have provided strong evidences that visual deprivation influences the brain's functional architecture. In particular, reduced RSFC coupling between occipital (visual) and temporal (auditory) regions has been reliably observed in early blind individuals (EB) at rest. In contrast, task-dependent activation studies have repeatedly demonstrated enhanced co-activation and connectivity of occipital and temporal regions during auditory processing in EB. To investigate this apparent discrepancy, the functional coupling between temporal and occipital networks at rest was directly compared to that of an auditory task in both EB and sighted controls (SC). Functional brain clusters shared across groups and cognitive states (rest and auditory task) were defined. In EBs, we observed higher occipito-temporal correlations in activity during the task than at rest. The reverse pattern was observed in SC. We also observed higher temporal variability of occipito-temporal RSFC in EB suggesting that occipital regions in this population may play the role of a multiple demand system. Our study reveals how the connectivity profile of sighted and early blind people is differentially influenced by their cognitive state, bridging the gap between previous task-dependent and RSFC studies. Our results also highlight how inferring group-differences in functional brain architecture solely based on resting-state acquisition has to be considered with caution.

Statistical power and prediction accuracy in multisite resting-state fMRI connectivity.

Connectivity studies using resting-state functional magnetic resonance imaging are increasingly pooling data acquired at multiple sites. While this may allow investigators to speed up recruitment or increase sample size, multisite studies also potentially introduce systematic biases in connectivity measures across sites. In this work, we measure the inter-site effect in connectivity and its impact on our ability to detect individual and group differences. Our study was based on real, as opposed to simulated, multisite fMRI datasets collected in N=345 young, healthy subjects across 8 scanning sites with 3T scanners and heterogeneous scanning protocols, drawn from the 1000 functional connectome project. We first empirically show that typical functional networks were reliably found at the group level in all sites, and that the amplitude of the inter-site effects was small to moderate, with a Cohen's effect size below 0.5 on average across brain connections. We then implemented a series of Monte-Carlo simulations, based on real data, to evaluate the impact of the multisite effects on detection power in statistical tests comparing two groups (with and without the effect) using a general linear model, as well as on the prediction of group labels with a support-vector machine. As a reference, we also implemented the same simulations with fMRI data collected at a single site using an identical sample size. Simulations revealed that using data from heterogeneous sites only slightly decreased our ability to detect changes compared to a monosite study with the GLM, and had a greater impact on prediction accuracy. However, the deleterious effect of multisite data pooling tended to decrease as the total sample size increased, to a point where differences between monosite and multisite simulations were small with N=120 subjects. Taken together, our results support the feasibility of multisite studies in rs-fMRI provided the sample size is large enough.

Maximum Pseudolikelihood Estimation for Model-Based Clustering of Time Series Data.

Mixture of autoregressions (MoAR) models provide a model-based approach to the clustering of time series data. The maximum likelihood (ML) estimation of MoAR models requires evaluating products of large numbers of densities of normal random variables. In practical scenarios, these products converge to zero as the length of the time series increases, and thus the ML estimation of MoAR models becomes infeasible without the use of numerical tricks. We propose a maximum pseudolikelihood (MPL) estimation approach as an alternative to the use of numerical tricks. The MPL estimator is proved to be consistent and can be computed with an EM (expectation-maximization) algorithm. Simulations are used to assess the performance of the MPL estimator against that of the ML estimator in cases where the latter was able to be calculated. An application to the clustering of time series data arising from a resting state fMRI experiment is presented as a demonstration of the methodology.

Altered brain connectivity in patients with schizophrenia is consistent across cognitive contexts.

BACKGROUND: Schizophrenia has been defined as a dysconnection syndrome characterized by aberrant functional brain connectivity. Using task-based fMRI, we assessed to what extent the nature of the cognitive context may further modulate abnormal functional brain connectivity. METHODS: We analyzed data matched for motion in patients with schizophrenia and healthy controls who performed 3 different tasks. Tasks 1 and 2 both involved emotional processing and only slighlty differed (incidental encoding v. memory recognition), whereas task 3 was a much different mental rotation task. We conducted a connectome-wide general linear model analysis aimed at identifying context-dependent and independent functional brain connectivity alterations in patients with schizophrenia. RESULTS: After matching for motion, we included 30 patients with schizophrenia and 30 healthy controls in our study. Abnormal connectivity in patients with schizophrenia followed similar patterns regardless of the degree of similarity between cognitive tasks. Decreased connectivity was most notable in the medial prefrontal cortex, the anterior and posterior cingulate, the temporal lobe, the lobule IX of the cerebellum and the premotor cortex. LIMITATIONS: A more circumscribed yet significant context-dependent effect might be detected with larger sample sizes or cognitive domains other than emotional and visuomotor processing. CONCLUSION: The context-independence of functional brain dysconnectivity in patients with schizophrenia provides a good justification for pooling data from multiple experiments in order to identify connectivity biomarkers of this mental illness.

The Richness of Task-Evoked Hemodynamic Responses Defines a Pseudohierarchy of Functionally Meaningful Brain Networks.

Functional magnetic resonance imaging can measure distributed and subtle variations in brain responses associated with task performance. However, it is unclear whether the rich variety of responses observed across the brain is functionally meaningful and consistent across individuals. Here, we used a multivariate clustering approach that grouped brain regions into clusters based on the similarity of their task-evoked temporal responses at the individual level, and then established the spatial consistency of these individual clusters at the group level. We observed a stable pseudohierarchy of task-evoked networks in the context of a delayed sequential motor task, where the fractionation of networks was driven by a gradient of involvement in motor sequence preparation versus execution. In line with theories about higher-level cognitive functioning, this gradient evolved in a rostro-caudal manner in the frontal lobe. In addition, parcellations in the cerebellum and basal ganglia matched with known anatomical territories and fiber pathways with the cerebral cortex. These findings demonstrate that subtle variations in brain responses associated with task performance are systematic enough across subjects to define a pseudohierarchy of task-evoked networks. Such networks capture meaningful functional features of brain organization as shaped by a given cognitive context.

Impact of the resolution of brain parcels on connectome-wide association studies in fMRI.

A recent trend in functional magnetic resonance imaging is to test for association of clinical disorders with every possible connection between selected brain parcels. We investigated the impact of the resolution of functional brain parcels, ranging from large-scale networks to local regions, on a mass univariate general linear model (GLM) of connectomes. For each resolution taken independently, the Benjamini-Hochberg procedure controlled the false-discovery rate (FDR) at nominal level on realistic simulations. However, the FDR for tests pooled across all resolutions could be inflated compared to the FDR within resolution. This inflation was severe in the presence of no or weak effects, but became negligible for strong effects. We thus developed an omnibus test to establish the overall presence of true discoveries across all resolutions. Although not a guarantee to control the FDR across resolutions, the omnibus test may be used for descriptive analysis of the impact of resolution on a GLM analysis, in complement to a primary analysis at a predefined single resolution. On three real datasets with significant omnibus test (schizophrenia, congenital blindness, motor practice), markedly higher rate of discovery were obtained at low resolutions, below 50, in line with simulations showing increase in sensitivity at such resolutions. This increase in discovery rate came at the cost of a lower ability to localize effects, as low resolution parcels merged many different brain regions together. However, with 30 or more parcels, the statistical effect maps were biologically plausible and very consistent across resolutions. These results show that resolution is a key parameter for GLM-connectome analysis with FDR control, and that a functional brain parcellation with 30 to 50 parcels may lead to an accurate summary of full connectome effects with good sensitivity in many situations.

Label-based meta-analysis of functional brain dysconnectivity across mood and psychotic disorders.

BACKGROUND: Resting-state functional magnetic resonance imaging (rsfMRI) studies have revealed patterns of functional brain dysconnectivity in psychiatric disorders such as major depression disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ). Although these disorders have been mostly studied in isolation, there is mounting evidence of shared neurobiological alterations across them. METHODS: To uncover the nature of the relatedness between these psychiatric disorders, we conducted an innovative meta-analysis of dysconnectivity findings reported separately in MDD, BD and SZ. Rather than relying on a classical voxel level coordinate-based approach, our procedure extracted relevant neuroanatomical labels from text data and examined findings at the whole brain network level. Data were drawn from 428 rsfMRI studies investigating MDD (158 studies, 7429 patients/7414 controls), BD (81 studies, 3330 patients/4096 patients) and/or SZ (223 studies, 11,168 patients/11,754 controls). Permutation testing revealed commonalities and differences in hypoconnectivity and hyperconnectivity patterns across disorders. RESULTS: Hypoconnectivity and hyperconnectivity patterns of higher-order cognitive (default-mode, fronto-parietal, cingulo-opercular) networks were similarly observed across the three disorders. By contrast, dysconnectivity of lower-order (somatomotor, visual, auditory) networks in some cases differed between disorders, notably dissociating SZ from BD and MDD. CONCLUSIONS: Findings suggest that functional brain dysconnectivity of higher-order cognitive networks is largely transdiagnostic in nature while that of lower-order networks may best discriminate between mood and psychotic disorders, thus emphasizing the relevance of motor and sensory networks to psychiatric neuroscience.

Brain plasticity related to the consolidation of motor sequence learning and motor adaptation.

This study aimed to investigate, through functional MRI (fMRI), the neuronal substrates associated with the consolidation process of two motor skills: motor sequence learning (MSL) and motor adaptation (MA). Four groups of young healthy individuals were assigned to either (i) a night/sleep condition, in which they were scanned while practicing a finger sequence learning task or an eight-target adaptation pointing task in the evening (test) and were scanned again 12 h later in the morning (retest) or (ii) a day/awake condition, in which they were scanned on the MSL or the MA tasks in the morning and were rescanned 12 h later in the evening. As expected and consistent with the behavioral results, the functional data revealed increased test-retest changes of activity in the striatum for the night/sleep group compared with the day/awake group in the MSL task. By contrast, the results of the MA task did not show any difference in test-retest activity between the night/sleep and day/awake groups. When the two MA task groups were combined, however, increased test-retest activity was found in lobule VI of the cerebellar cortex. Together, these findings highlight the presence of both functional and structural dissociations reflecting the off-line consolidation processes of MSL and MA. They suggest that MSL consolidation is sleep dependent and reflected by a differential increase of neural activity within the corticostriatal system, whereas MA consolidation necessitates either a period of daytime or sleep and is associated with increased neuronal activity within the corticocerebellar system.

Genetic Heterogeneity Shapes Brain Connectivity in Psychiatry.

BACKGROUND: Polygenicity and genetic heterogeneity pose great challenges for studying psychiatric conditions. Genetically informed approaches have been implemented in neuroimaging studies to address this issue. However, the effects on functional connectivity of rare and common genetic risks for psychiatric disorders are largely unknown. Our objectives were to estimate and compare the effect sizes on brain connectivity of psychiatric genomic risk factors with various levels of complexity: oligogenic copy number variants (CNVs), multigenic CNVs, and polygenic risk scores (PRSs) as well as idiopathic psychiatric conditions and traits. METHODS: Resting-state functional magnetic resonance imaging data were processed using the same pipeline across 9 datasets. Twenty-nine connectome-wide association studies were performed to characterize the effects of 15 CNVs (1003 carriers), 7 PRSs, 4 idiopathic psychiatric conditions (1022 individuals with autism, schizophrenia, bipolar conditions, or attention-deficit/hyperactivity disorder), and 2 traits (31,424 unaffected control subjects). RESULTS: Effect sizes on connectivity were largest for psychiatric CNVs (estimates: 0.2-0.65 z score), followed by psychiatric conditions (0.15-0.42), neuroticism and fluid intelligence (0.02-0.03), and PRSs (0.01-0.02). Effect sizes of CNVs on connectivity were correlated to their effects on cognition and risk for disease (r = 0.9, p = 5.93 × 10-6). However, effect sizes of CNVs adjusted for the number of genes significantly decreased from small oligogenic to large multigenic CNVs (r = -0.88, p = 8.78 × 10-6). PRSs had disproportionately low effect sizes on connectivity compared with CNVs conferring similar risk for disease. CONCLUSIONS: Heterogeneity and polygenicity affect our ability to detect brain connectivity alterations underlying psychiatric manifestations.

Functional connectivity subtypes associate robustly with ASD diagnosis.

Our understanding of the changes in functional brain organization in autism is hampered by the extensive heterogeneity that characterizes this neurodevelopmental disorder. Data driven clustering offers a straightforward way to decompose autism heterogeneity into subtypes of connectivity and promises an unbiased framework to investigate behavioral symptoms and causative genetic factors. Yet, the robustness and generalizability of functional connectivity subtypes is unknown. Here, we show that a simple hierarchical cluster analysis can robustly relate a given individual and brain network to a connectivity subtype, but that continuous assignments are more robust than discrete ones. We also found that functional connectivity subtypes are moderately associated with the clinical diagnosis of autism, and these associations generalize to independent replication data. We explored systematically 18 different brain networks as we expected them to associate with different behavioral profiles as well as different key regions. Contrary to this prediction, autism functional connectivity subtypes converged on a common topography across different networks, consistent with a compression of the primary gradient of functional brain organization, as previously reported in the literature. Our results support the use of data driven clustering as a reliable data dimensionality reduction technique, where any given dimension only associates moderately with clinical manifestations.

[Functional brain plasticity associated with motor learning]. / Plasticité fonctionnelle du cerveau et apprentissage moteur - Imagerie et cognition (5).

This review presents the results of studies carried out in our laboratory that aim to investigate, through functional magnetic resonance imaging (fMRI), the brain plasticity associated with motor sequence learning, defined as our ability to integrate simple stereotyped movements into a single motor representation. Following a brief description of Doyon and colleagues' model (2002, 2005, 2009) of motor skill learning that has guided this work, we then describe the functional changes that occur at the different (rapid, slow, automatization) acquisition phases, and propose specific roles that the putamen, the cerebellum and their motor-related cortical areas, play in this form of motor behavior. Finally, we put forward evidence that post-training, non-REM sleep (and spindles in Stage 2 sleep, in particular) contributes to the consolidation of a motor sequence memory trace, and that increased activity within the striatum and/or the hippocampus mediates this mnemonic process.

[Improved Mental Health Clinical Practice Informed by Digital Phenotyping]. / Le phénotypage digital pour une pratique clinique en santé mentale mieux informée.

Objectives This review is motivated by the observation that clinical decision-making in mental health is limited by the nature of the measures obtained in conventional clinical interviews and the difficulty for clinicians to make accurate predictions about their patients' future mental states. Our objective is to offer a representative overview of the potential of digital phenotyping coupled with machine learning to address this limitation, while highlighting its own current weaknesses. Methods Through a non-systematic narrative review of the literature, we identify the technological developments that make it possible to quantify, moment by moment and in ecologically valid settings, the human phenotype in various psychiatric populations using the smartphone. Relevant work is also selected in order to determine the usefulness and limitations of machine learning to guide predictions and clinical decision-making. Finally, the literature is explored to assess current barriers to the adoption of such tools. Results Although emerging from a recent field of research, a large body of work already highlights the value of measurements extracted from smartphone sensors in characterizing the human phenotype in behavioral, cognitive, emotional and social spheres that are all impacted by mental disorders. Machine learning permits useful and accurate clinical predictions based on such measures, but suffers from a lack of interpretability that will hamper its use in clinical practice in the near future. Moreover, several barriers identified both on the patient and clinician sides currently hamper the adoption of this type of monitoring and clinical decision support tools. Conclusion Digital phenotyping coupled with machine learning shows great promise for improving clinical practice in mental health. However, the youth of these new technological tools requires a necessary maturation process to be guided by the various concerned actors so that these promises can be fully realized.

Converting scores between the PANSS and SAPS/SANS beyond the positive/negative dichotomy.

Previous work provided conversion equations for overall indices of positive and negative symptomatology between the Positive and Negative Syndrome Scale (PANSS) and the Scales for the Assessment of Positive/Negative Symptoms (SAPS/SANS). Our objective was to provide such conversion equations for subdomains of positive and negative symptomatology in order to better account for the diversity of symptom profiles in schizophrenia. Symptoms severity was assessed using both the PANSS and SAPS/SANS in 205 patients with schizophrenia. Two exploratory factor analyses combining items from both scales were first performed separately in the positive and negative symptom domains. Positive factors were termed 'Hallucinations', 'Delusions' and 'Disorganization', while negative factors were associated with 'Expressivity', 'Amotivation' and 'Cognition', consistent with current descriptions of symptom dimensions in schizophrenia. For each factor, linear regression analyses were conducted on 80% of the data to obtain conversion equations from the PANSS to the SAPS/SANS and vice versa. Reliability was then evaluated on the 20% remaining data, with good to excellent intra-class correlation coefficients between the original and predicted scores for all but the cognition factor. These findings show that symptom severity scores can be converted with good accuracy between clinical scales beyond the positive/negative symptom dichotomy.

Cerebral functional networks during sleep in young and older individuals.

Even though sleep modification is a hallmark of the aging process, age-related changes in functional connectivity using functional Magnetic Resonance Imaging (fMRI) during sleep, remain unknown. Here, we combined electroencephalography and fMRI to examine functional connectivity differences between wakefulness and light sleep stages (N1 and N2 stages) in 16 young (23.1 ± 3.3y; 7 women), and 14 older individuals (59.6 ± 5.7y; 8 women). Results revealed extended, distributed (inter-between) and local (intra-within) decreases in network connectivity during sleep both in young and older individuals. However, compared to the young participants, older individuals showed lower decreases in connectivity or even increases in connectivity between thalamus/basal ganglia and several cerebral regions as well as between frontal regions of various networks. These findings reflect a reduced ability of the older brain to disconnect during sleep that may impede optimal disengagement for loss of responsiveness, enhanced lighter and fragmented sleep, and contribute to age effects on sleep-dependent brain plasticity.

The multifaceted nature of the relationship between performance and brain activity in motor sequence learning.

The 'learning and performance' conundrum has for a long time puzzled the field of cognitive neuroscience. Deciphering the genuine functional neuroanatomy of motor sequence learning, among that of other skills, has thereby been hampered. The main caveat is that changes in neural activity that inherently accompany task practice may not only reflect the learning process per se, but also the basic motor implementation of improved performance. Previous research has attempted to control for a performance confound in brain activity by adopting methodologies that prevent changes in performance. However, blocking the expression of performance is likely to distort the very nature of the motor sequence learning process, and may thus represent a major confound in itself. In the present study, we postulated that both learning-dependent plasticity mechanisms and learning-independent implementation processes are nested within the relationship that exists between performance and brain activity. Functional magnetic resonance imaging (fMRI) was used to map brain responses in healthy volunteers while they either (a) learned a novel sequence, (b) produced a highly automatized sequence or (c) executed non-sequential movements matched for speed frequency. In order to dissociate between qualitatively distinct, but intertwined, relationships between performance and neural activity, our analyses focused on correlations between variations in performance and brain activity, and how this relationship differs or shares commonalities between conditions. Results revealed that activity in the putamen and contralateral lobule VI of the cerebellum most strongly correlated with performance during learning per se, suggesting their key role in this process. By contrast, activity in a parallel cerebellar network, as well as in motor and premotor cortical areas, was modulated by performance during learning and during one or both control condition(s), suggesting the primary contribution of these areas in motor implementation, either as a function or not of the sequential content of movements. Our findings thus highlight the multifaceted nature of the link between performance and brain activity, and suggest that different components of the striato-cortical and cerebello-cortical motor loops play distinct, but complementary, roles during early motor sequence learning.