Proteinopathy and longitudinal changes in functional connectivity networks in Parkinson disease

ObjectiveTo evaluate resting-state functional connectivity as a potential prognostic biomarker of Parkinson disease (PD) progression. The study examined longitudinal changes in cortical resting-state functional connectivity networks in participants with PD compared to controls as well as in relation to baseline protein measures and longitudinal clinical progression.MethodsIndividuals with PD without dementia (n = 64) and control participants (n = 27) completed longitudinal resting-state MRI scans and clinical assessments including full neuropsychological testing after overnight withdrawal of PD medications (“off”). A total of 55 participants with PD and 20 control participants also completed baseline β-amyloid PET scans and lumbar punctures for CSF protein levels of α-synuclein, β-amyloid, and tau. Longitudinal analyses were conducted with multilevel growth curve modeling, a type of mixed-effects model.ResultsFunctional connectivity within the sensorimotor network and the interaction between the dorsal attention network with the frontoparietal control network decreased significantly over time in participants with PD compared to controls. Baseline CSF α-synuclein protein levels predicted decline in the sensorimotor network. The longitudinal decline in the dorsal attention–frontoparietal internetwork strength correlated with the decline in cognitive function.ConclusionsThese results indicate that α-synuclein levels may influence longitudinal declines in motor-related functional connectivity networks. Further, the interaction between cortical association networks declines over time in PD prior to dementia onset and may serve as a prognostic marker for the development of dementia.

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Longitudinal changes of resting-state functional connectivity of amygdala following fear learning and extinction

International Journal of Psychophysiology ◽

10.1016/j.ijpsycho.2020.01.002 ◽

2020 ◽

Vol 149 ◽

pp. 15-24 ◽

Cited By ~ 2

Author(s):

Olga Martynova ◽

Alina Tetereva ◽

Vladislav Balaev ◽

Galina Portnova ◽

Vadim Ushakov ◽

...

Keyword(s):

Functional Connectivity ◽

Resting State ◽

Fear Learning ◽

Resting State Functional Connectivity ◽

Longitudinal Changes

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Vascular burden is associated with a decline in default-mode and global resting-state functional connectivity in individuals at risk for Alzheimer’s disease

10.1101/2020.04.10.036202 ◽

2020 ◽

Author(s):

Theresa Köbe ◽

Alexa Pichet Binette ◽

Jacob W. Vogel ◽

Pierre-François Meyer ◽

John C. S. Breitner ◽

...

Keyword(s):

Blood Pressure ◽

Functional Connectivity ◽

Diastolic Blood Pressure ◽

Resting State ◽

Ldl Cholesterol ◽

Resting State Functional Connectivity ◽

Cholesterol Levels ◽

Brain Functional Connectivity ◽

Vascular Burden ◽

Over Time

AbstractIntroductionCross-sectional studies suggest that cardiovascular risk factors and Alzheimer’s disease (AD) biomarkers are associated with abnormal brain resting-state functional connectivity in aging and AD; however, evidence is missing regarding longitudinal changes in functional connectivity. In this study, we investigate whether cholesterol levels and blood pressure are associated with changes in functional connectivity over time in asymptomatic individuals at risk for AD. The analyses were repeated with cerebral β-amyloid (Aβ) and tau deposition in a subset of the participants.MethodsThe study sample included 247 cognitively unimpaired individuals (185 women/ 62 men; mean [SD] age of 63 [5.3] years) of the PREVENT-AD cohort with a parental or multiple-sibling history of sporadic AD. Plasma total-, HDL-, and LDL-cholesterol and systolic and diastolic blood pressure were measured at baseline. Global brain functional connectivity, and connectivity from canonical functional networks, were computed from resting-state functional MRI obtained at baseline and up to four years of annual follow-ups, using a predefined functional parcellation. A subset of participants underwent tau-PET ([18F]Flortaucipir) and Aβ-PET ([18F]NAV4694). Vascular and AD measures were examined as predictors of brain functional connectivity changes in linear mixed-effects models.ResultsHigher total-cholesterol and LDL-cholesterol levels were associated with greater reduction of functional connectivity in the default-mode network over time. In addition, while overall whole-brain functional connectivity showed an increase over time across the entire sample higher diastolic blood pressure was associated with reduction in whole-brain functional connectivity. The associations were similar when the analyses were repeated using two other functional brain parcellations. The findings with total-cholesterol and diastolic blood pressure were also similar but attenuated when performed in a subsample of participants with PET (n=91), whereas AD biomarkers were not associated with changes in functional connectivity over time in this subsample.ConclusionThese findings provide evidence that vascular burden is associated with a decrease in brain functional connectivity over time in older adults with elevated risk for AD. The impact of vascular risk factors on functional brain changes might precede AD pathology-related changes.

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Cognitive correlates of cerebellar resting-state functional connectivity in Parkinson disease

Neurology ◽

10.1212/wnl.0000000000008754 ◽

2019 ◽

Vol 94 (4) ◽

pp. e384-e396 ◽

Cited By ~ 2

Author(s):

Baijayanta Maiti ◽

Jonathan M. Koller ◽

Abraham Z. Snyder ◽

Aaron B. Tanenbaum ◽

Scott A. Norris ◽

...

Keyword(s):

Cognitive Impairment ◽

Functional Connectivity ◽

Parkinson Disease ◽

Resting State ◽

Cognitive Status ◽

Association Cortex ◽

Resting State Functional Connectivity ◽

Clinical Dementia Rating ◽

Cross Sectional ◽

Global Cognition

ObjectiveTo investigate in a cross-sectional study the contributions of altered cerebellar resting-state functional connectivity (FC) to cognitive impairment in Parkinson disease (PD).MethodsWe conducted morphometric and resting-state FC-MRI analyses contrasting 81 participants with PD and 43 age-matched healthy controls using rigorous quality assurance measures. To investigate the relationship of cerebellar FC to cognitive status, we compared participants with PD without cognitive impairment (Clinical Dementia Rating [CDR] scale score 0, n = 47) to participants with PD with impaired cognition (CDR score ≥0.5, n = 34). Comprehensive measures of cognition across the 5 cognitive domains were assessed for behavioral correlations.ResultsThe participants with PD had significantly weaker FC between the vermis and peristriate visual association cortex compared to controls, and the strength of this FC correlated with visuospatial function and global cognition. In contrast, weaker FC between the vermis and dorsolateral prefrontal cortex was found in the cognitively impaired PD group compared to participants with PD without cognitive impairment. This effect correlated with deficits in attention, executive functions, and global cognition. No group differences in cerebellar lobular volumes or regional cortical thickness of the significant cortical clusters were observed.ConclusionThese results demonstrate a correlation between cerebellar vermal FC and cognitive impairment in PD. The absence of significant atrophy in cerebellum or relevant cortical areas suggests that this could be related to local pathophysiology such as neurotransmitter dysfunction.

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Longitudinal Changes of Caudate-Based Resting State Functional Connectivity in Mild Traumatic Brain Injury

Frontiers in Neurology ◽

10.3389/fneur.2018.00467 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 5

Author(s):

Hui Xu ◽

Xiaocui Wang ◽

Zhen Chen ◽

Guanghui Bai ◽

Bo Yin ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Functional Connectivity ◽

Mild Traumatic Brain Injury ◽

Resting State ◽

Resting State Functional Connectivity ◽

Longitudinal Changes

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3046 Reduced structural and functional connectivity in infants with prenatal opioid exposure

Journal of Clinical and Translational Science ◽

10.1017/cts.2019.123 ◽

2019 ◽

Vol 3 (s1) ◽

pp. 52-52

Author(s):

Stephanie Merhar ◽

Adebayo Braimah ◽

Traci Beiersdorfer ◽

Brenda Poindexter ◽

Nehal Parikh

Keyword(s):

White Matter ◽

Functional Connectivity ◽

Fractional Anisotropy ◽

Behavioral Problems ◽

Resting State ◽

Maternal Education ◽

Structural Connectivity ◽

Resting State Functional Connectivity ◽

Small Pilot Study ◽

Sensorimotor Network

OBJECTIVES/SPECIFIC AIMS:. This study aims to understand the effects of prenatal opioid exposure on structural and functional connectivity in the neonatal brain. Our central hypothesis is that infants with prenatal opioid exposure will have decreased structural and functional connectivity as compared to non-exposed controls. Our overarching goal is to improve neurodevelopmental and behavioral outcomes in infants with prenatal opioid exposure. METHODS/STUDY POPULATION:. Infants with prenatal opioid exposure were recruited from 2 birth hospitals in our area. Control infants were recruited from the larger community. Infants underwent MRI between 4-6 weeks of age in the Cincinnati Children’s Hospital Imaging Research Center. MRI sequences included 3D structural T1 and T2-weighted imaging, resting state functional connectivity MRI, and multi-shell DTI (36 directions at b=800 and 68 directions at b=2000). Tract-based spatial statistics (TBSS) was used to identify differences in fractional anisotropy (a measure of white matter integrity) between groups. Group independent component analysis was used to identify differences in resting-state networks between groups RESULTS/ANTICIPATED RESULTS:. There were 5 subjects enrolled in the study with evaluable imaging, 3 infants with prenatal opioid exposure and 2 unexposed controls. Structural MRI was normal in all cases. Infants with prenatal opioid exposure had reduced structural connectivity as measured by fractional anisotropy (FA) in the genu and splenium of the corpus callosum as compared with controls. The orange/red color represents areas in which the FA of the opioid-exposed group was lower than controls and green represents the white matter skeleton common to both groups. Infants with prenatal opioid exposure also had significantly reduced within-network functional connectivity strength (z-transformed partial correlation coefficient 0.358 vs 0.199, p = 0.03) in the sensorimotor network as compared with controls. DISCUSSION/SIGNIFICANCE OF IMPACT:. In this small pilot study, both structural and functional connectivity were reduced in opioid-exposed infants compared with controls. This data suggests that differences in structural and functional connectivity may underlie the later developmental and behavioral problems seen in opioid-exposed children. These findings must be validated in a larger population with correction for confounding factors such as maternal education

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Fatigue in multiple sclerosis: The contribution of resting-state functional connectivity reorganization

Multiple Sclerosis Journal ◽

10.1177/1352458517730932 ◽

2017 ◽

Vol 24 (13) ◽

pp. 1696-1705 ◽

Cited By ~ 23

Author(s):

Alvino Bisecco ◽

Federica Di Nardo ◽

Renato Docimo ◽

Giuseppina Caiazzo ◽

Alessandro d’Ambrosio ◽

...

Keyword(s):

Multiple Sclerosis ◽

Regression Analysis ◽

Functional Connectivity ◽

Motor Cortex ◽

Resting State ◽

Primary Motor Cortex ◽

Linear Regression Analysis ◽

Posterior Cingulate Cortex ◽

Resting State Functional Connectivity ◽

Sensorimotor Network

Objectives: To investigate resting-state functional connectivity (RS-FC) of the default-mode network (DMN) and of sensorimotor network (SMN) network in relapsing remitting (RR) multiple sclerosis (MS) patients with fatigue (F) and without fatigue(NF). Methods: In all, 59 RRMS patients and 29 healthy controls (HC) underwent magnetic resonance imaging (MRI) protocol including resting-state fMRI (RS-fMRI). Functional connectivity of the DMN and SMN was evaluated by independent component analysis (ICA). A linear regression analysis was performed to explore whether fatigue was mainly driven by changes observed in the DMN or in the SMN. Regional gray matter atrophy was assessed by voxel-based morphometry (VBM). Results: Compared to HC, F-MS patients showed a stronger RS-FC in the posterior cingulate cortex (PCC) and a reduced RS-FC in the anterior cingulated cortex (ACC) of the DMN. F-MS patients, compared to NF-MS patients, revealed (1) an increased RS-FC in the PCC and a reduced RS-FC in the ACC of the DMN and (2) an increased RS-FC in the primary motor cortex and in the supplementary motor cortex of the SMN. The regression analysis suggested that fatigue is mainly driven by RS-FC changes of the DMN. Conclusions: Fatigue in RRMS is mainly associated to a functional rearrangement of non-motor RS networks.

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