48 research outputs found
Resting-state functional brain netwoks in Parkinson's disease
The network approach is increasingly being applied to the investigation of normal brain function and its impairment. In the present review, we introduce the main methodological approaches employed for the analysis of resting-state neuroimaging data in Parkinson's disease studies. We then summarize the results of recent studies that used a functional network perspective to evaluate the changes underlying different manifestations of Parkinson's disease, with an emphasis on its cognitive symptoms. Despite the variability reported by many studies, these methods show promise as tools for shedding light on the pathophysiological substrates of different aspects of Parkinson's disease, as well as for differential diagnosis, treatment monitoring and establishment of imaging biomarkers for more severe clinical outcomes
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Cognitive Flexibility: A Default Mode Perspective
The intra/extradimensional set-shifting task (IED) provides a reliable assessment of cognitive flexibility, the shifting of attention to select behaviorally relevant stimuli in a given context. Impairments in this domain were previously reported in patients with altered neurotransmitter systems such as schizophrenia and Parkinson's disease. Consequently, corticostriatal connections were implicated in the mediation of this function. In addition, parts of the default mode network (DMN), namely the medial prefrontal and posterior cingulate/precuneus cortices, are also being progressively described in association with set-shifting paradigms. Nevertheless, a definitive link between cognitive flexibility and DMN connectivity remains to be established. To this end, we related resting state functional magnetic resonance imaging (fMRI)-based functional connectivity of DMN with IED task performance in a healthy population, measured outside the scanner. The results demonstrated that greater posterior cingulate cortex/precuneus (DMN) connectivity with the ventromedial striatopallidum at rest correlated with fewer total adjusted errors on the IED task. This finding points to a relationship between DMN and basal ganglia connectivity for cognitive flexibility, further highlighting this network's potential role in adaptive human cognition.The Evelyn Trust (RUAG/018) supported this research. Additionally, DV received funding from the Yousef Jameel Academic Program; DKM is funded by the NIHR Cambridge Biomedical Centre (RCZB/004), and an NIHR Senior Investigator Award (RCZB/014), and EAS is supported by the Stephen Erskine Fellowship Queens’ College, Cambridge. We would also like to thank Dr. Guy Williams and Victoria Lupson and the rest of the staff in the Wolfson Brain Imaging Centre (WBIC) at Addenbrooke’s Hospital for their assistance in scanning. Finally, we thank all the participants for their contribution to this studyThis is the author accepted manuscript. The final version is available from Mary Ann Liebert via http://dx.doi.org/10.1089/brain.2015.038
Modafinil treatment modulates functional connectivity in stroke survivors with severe fatigue
Post-stroke fatigue has a significant impact on stroke survivors’ mental and physical well-being. Our recent clinical trial showed significant reduction of post-stroke fatigue with modafinil treatment, however functional connectivity changes in response to modafinil have not yet been explored in stroke survivors with post-stroke fatigue. Twenty-eight participants (multidimensional fatigue inventory-20 ≥ 60) had MRI scans at baseline, and during modafinil and placebo treatment. Resting-state functional MRI data were obtained, and independent component analysis was used to extract functional networks. Resting-state functional connectivity (rsFC) was examined between baseline, modafinil and placebo treatment using permutation testing with threshold-free cluster enhancement. Overall twenty-eight participants (mean age: 6 +/-2 14.3, mean baseline MFI-20: 72.3 +/-9.24) were included. During modafinil treatment, increased rsFC was observed in the right hippocampus (p = 0.004, 11 voxels) compared to placebo. This coincided with lower rsFC in the left frontoparietal (inferior parietal lobule, p = 0.023, 13 voxels), somatosensory (primary somatosensory cortex; p = 0.009, 32 voxels) and mesolimbic network (temporal pole, p = 0.016, 35 voxels). In conclusion, modafinil treatment induces significant changes in rsFC in post-stroke fatigue. This modulation of rsFC may relate to a reduction of post-stroke fatigue; however, the relationship between sensory processing, neurotransmitter expression and fatigue requires further exploration
Interactive effects of dopamine transporter genotype and aging on resting-state functional networks
Aging and dopamine modulation have both been independently shown to influence the functional connectivity of brain networks during rest. Dopamine modulation is known to decline during the course of aging. Previous evidence also shows that the dopamine transporter gene (DAT1) influences the re-uptake of dopamine and the anyA9 genotype of this gene is associated with higher striatal dopamine signaling. Expanding these two lines of prior research, we investigated potential interactive effects between aging and individual variations in the DAT1 gene on the modular organization of brain acvitiy during rest. The graph-theoretic metrics of modularity, betweenness centrality and participation coefficient were assessed in 41 younger (age 20-30 years) and 37 older (age 60-75 years) adults. Age differences were only observed in the participation coefficient in carriers of the anyA9 genotype of the DAT1 gene and this effect was most prominently observed in the default mode network. Furthermore, we found that individual differences in the values of the participation coefficient correlated with individual differences in fluid intelligence and a measure of executive control in the anyA9 carriers. The correlation between participation coefficient and fluid intelligence was mainly shared with age-related differences, whereas the correlation with executive control was independent of age. These findings suggest that DAT1 genotype moderates age differences in the functional integration of brain networks as well as the relation between network characteristics and cognitive abilities
Cognitive impairment and resting-state network connectivity in Parkinson's disease
Previous functional MRI studies have revealed changes in the default-mode network (DMN) in Parkinson's disease (PD). The purpose of this work was to evaluate changes in the connectivity patterns of a set of cognitively relevant, dynamically interrelated brain networks in association with cognitive deficits in PD using resting-state functional MRI. Sixty-five non-demented PD patients and 36 matched healthy controls (HC) were included. Thirty-four percent of PD patients were classified as having mild cognitive impairment (MCI) based on performance in the three mainly-affected cognitive domains in Parkinson's disease (attention/executive, visuospatial/visuoperceptual and declarative memory). Data-driven analyses through independent-component analysis (ICA) was used to identify the DMN, the dorsal attention network (DAN) and the bilateral frontoparietal networks (FPN), which were compared between groups using a dual-regression approach. Additional seed-based analyses using a-priori defined regions of interest were used to characterize local changes in intra and inter-network connectivity. ICA results revealed reduced connectivity between the DAN and right frontoinsular cortical regions in MCI patients, which correlated with worse performance in attention/executive functions. The DMN, on the other hand, displayed increased connectivity with medial and lateral occipito-parietal regions in MCI patients; these increases correlated with worse visuospatial/visuoperceptual performance. In line with data-driven results, seed-based analyses mainly revealed reduced within-DAN, within-DMN and DAN-FPN connectivity, as well as increased DAN-DMN coupling in MCI patients. Our findings demonstrate differential connectivity changes affecting the networks evaluated, which we hypothesize to be related to the pathophysiological bases of different types of cognitive impairment in PD
NEUROTRANSMITTERS AND RESTING STATE NETWORKS: CLINICAL IMPLICATION FOR MAJOR PSYCHIATRIC DISORDER
Alterations in brain intrinsic activity \u2013 as organized in resting-state networks (RSNs) such as sensorimotor network (SMN), salience network (SN) and default-mode network (DMN) \u2013 and in neurotransmitters signaling \u2013 such as dopamine (DA) and serotonin (5-HT) \u2013 have been independently detected in psychiatric disorders like bipolar disorder and schizophrenia. Thus, the aim of this work was to investigate the relationship between such neurotransmitters and RSNs in healthy, by reviewing the relevant work on this topic and performing complementary analyses, in order to better understand their physiological link as well as their alterations in psychiatric disorders. According to the reviewed data, neurotransmitters nuclei diffusively project to subcortical and cortical regions of RSNs. In particular, the dopaminergic substantia nigra (SNc)-related nigrostriatal pathway is structurally and functionally connected with core regions of the SMN, while the ventral tegmental area (VTA)-related mesocorticolimbic pathway with core regions of the SN. The serotonergic raphe nuclei (RNi) connections involve regions of the SMN and DMN. Coherently, changes in neurotransmitters activity impact the functional configuration and level of activity of RSNs, as measured by functional connectivity (FC) and amplitude of low-frequency fluctuations/temporal variability of BOLD signal. Specifically, DA signaling is associated with increase in FC and activity in the SMN (hypothetically via the SNc-related nigrostriatal pathway) and SN (hypothetically via the VTA-related mesocorticolimbic pathway), as well as concurrent decrease in FC and activity in the DMN. By contrast, 5-HT signaling (via the RNi-related pathways) is associated with decrease in SMN activity along with increase in DMN activity. Complementally, our empirical data showed a positive correlation between SNc-related FC and SMN activity, while a negative correlation between RNi-related FC and SMN activity (along with tilting of networks balance toward the DMN). According to these data, we hypothesize that the activity of neurotransmitters-related neurons synchronize the low-frequency oscillations within different RSNs regions, thus affecting the baseline level of RSNs activity and their balancing. In our model, DA signaling favors the predominance of SMN-SN activity, while 5-HT signaling favors the predominance of DMN activity, manifesting in distinct behavioral patterns. In turn, alterations in neurotransmitters signaling (or its disconnection) may favor a correspondent functional reorganization of RSNs, manifesting in distinct psychopathological states. The here suggested model carries important implications for psychiatric disorders, providing novel and well testable hypotheses especially on bipolar disorder and schizophrenia
Intrinsic mesocorticolimbic connectivity is negatively associated with social amotivation in people with schizophrenia
Background: Social amotivation is a core element of the negative symptoms of schizophrenia. However, it is still largely unknown which neural substrates underpin social amotivation in people with schizophrenia, though deficiencies in the mesocorticolimbic dopamine system have been proposed. Methods: We examined the association between social amotivation and substantia nigra/ventral tegmental area-seeded intrinsic connectivity in 84 people with schizophrenia using resting state functional magnetic resonance imaging. Results: Spontaneous fluctuations of midbrain dopaminergic regions were positively associated with striatal and prefrontal fluctuations in people with schizophrenia. Most importantly, social amotivation was negatively associated with functional connectivity between the midbrain's substantia nigra/ventral tegmental area and medial-and lateral prefrontal cortex, the temporoparietal junction, and dorsal and ventral striatum. These associations were observed independently of depressive and positive symptoms. Conclusions: Our findings suggest that social amotivation in people with schizophrenia is associated with altered intrinsic connectivity of mesocorticolimbic pathways linked to cognitive control and reward processing. Dysconnectivity of dopaminergic neuronal ensembles that are fundamental to approach behavior and motivation may help explain the lack of initiative social behavior in people with social amotivation. (C) 2019 Elsevier B.V. All rights reserved
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Role of brain imaging in disorders of brain-gut interaction: a Rome Working Team Report.
Imaging of the living human brain is a powerful tool to probe the interactions between brain, gut and microbiome in health and in disorders of brain-gut interactions, in particular IBS. While altered signals from the viscera contribute to clinical symptoms, the brain integrates these interoceptive signals with emotional, cognitive and memory related inputs in a non-linear fashion to produce symptoms. Tremendous progress has occurred in the development of new imaging techniques that look at structural, functional and metabolic properties of brain regions and networks. Standardisation in image acquisition and advances in computational approaches has made it possible to study large data sets of imaging studies, identify network properties and integrate them with non-imaging data. These approaches are beginning to generate brain signatures in IBS that share some features with those obtained in other often overlapping chronic pain disorders such as urological pelvic pain syndromes and vulvodynia, suggesting shared mechanisms. Despite this progress, the identification of preclinical vulnerability factors and outcome predictors has been slow. To overcome current obstacles, the creation of consortia and the generation of standardised multisite repositories for brain imaging and metadata from multisite studies are required
A working model on large-scale spatio-temporal organization of brain functioning and its implications for bipolar disorder
A working model on large-scale spatio-temporal organization of brain functioning and its implications for bipolar disorde
Unravelling the effects of methylphenidate on the dopaminergic and noradrenergic functional circuits
Functional magnetic resonance imaging (fMRI) can be combined with drugs to investigate the system-level functional responses in the brain to such challenges. However, most psychoactive agents act on multiple neurotransmitters, limiting the ability of fMRI to identify functional effects related to actions on discrete pharmacological targets. We recently introduced a multimodal approach, REACT (Receptor-Enriched Analysis of functional Connectivity by Targets), which offers the opportunity to disentangle effects of drugs on different neurotransmitters and clarify the biological mechanisms driving clinical efficacy and side effects of a compound. Here, we focus on methylphenidate (MPH), which binds to the dopamine transporter (DAT) and the norepinephrine transporter (NET), to unravel its effects on dopaminergic and noradrenergic functional circuits in the healthy brain at rest. We then explored the relationship between these target-enriched resting state functional connectivity (FC) maps and inter-individual variability in behavioural responses to a reinforcement-learning task encompassing a novelty manipulation to disentangle the molecular systems underlying specific cognitive/behavioural effects. Our main analysis showed a significant MPH-induced FC increase in sensorimotor areas in the functional circuit associated with DAT. In our exploratory analysis, we found that MPH-induced regional variations in the DAT and NET-enriched FC maps were significantly correlated with some of the inter-individual differences on key behavioural responses associated with the reinforcement-learning task. Our findings show that main MPH-related FC changes at rest can be understood through the distribution of DAT in the brain. Furthermore, they suggest that when compounds have mixed pharmacological profiles, REACT may be able to capture regional functional effects that are underpinned by the same cognitive mechanism but are related to engagement of distinct molecular targets