Brain connectivity and motor improvements after ballet intervention in multiple sclerosis: pilot

AbstractBackground and PurposeA pilot study to determine feasibility of detecting changes in structural connectivity (SC) and resting-state functional connectivity (RSFC) occur alongside motor improvements after participation in the Targeted Ballet Program (TBP) in adults with relapsing-remitting multiple sclerosis (RRMS).MethodsFive participants (four female) with RRMS between the ages of 38-64 with the following characteristics at baseline: Expanded Disability Status Scale 2.0-6.0, International Cooperative Ataxia Rating Scale (ICARS) > 7, Symbol-Digit Modality Test > 22, and no relapses or initiation of medications indicated to affect mobility within the past 30 days. Participants were asked to complete 12 weeks (one hour, twice per week) of the TBP. Magnetic resonance imaging data was collected pre- and post-intervention for SC and RSFC network analysis.ResultsIncreases in two RRMS-related graph theoretical measures (mean strength and mean clustering coefficient) for RSFC (p < 0.05) are detectable alongside significant reduction in ataxia (ICARS: p = 0.01012, Smoothness Index: p = 0.04995), and increase in balance (Mini-BESTest: p = 0.01474) following participation in the well-tolerated TBP.Discussion and ConclusionsSignificant increases in mean strength and mean clustering coefficient of RSFC suggest functional neurological improvements after participation in the TBP. The relationship between these network changes and clinical improvements in balance and amelioration of ataxia after participation in the TBP requires a larger randomized-controlled clinical trial of the TBP in persons with RRMS.

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Adjunctive Therapy to Manage Neuropsychiatric Symptoms in Moderate and Severe Dementia: Randomized Clinical Trial Using an Outpatient Version of Tailored Activity Program

Journal of Alzheimer s Disease ◽

10.3233/jad-210142 ◽

2021 ◽

pp. 1-12

Author(s):

Alexandra Martini Oliveira ◽

Marcia Radanovic ◽

Patricia Cotting Homem de Mello ◽

Patricia Cardoso Buchain ◽

Adriana Dias Barbosa Vizzotto ◽

...

Keyword(s):

Clinical Trial ◽

Sleep Disturbances ◽

Rating Scale ◽

Neuropsychiatric Symptoms ◽

Caregiver Training ◽

Controlled Clinical Trial ◽

Post Intervention ◽

Double Blind ◽

Activity Program ◽

Experimental Group

Background: Neuropsychiatric symptoms (NPS) such as aggression, apathy, agitation, and wandering may occur in up to 90%of dementia cases. International guidelines have suggested that non-pharmacological interventions are as effective as pharmacological treatments, however without the side effects and risks of medications. An occupational therapy method, called Tailored Activity Program (TAP), was developed with the objective to treat NPS in the elderly with dementia and has been shown to be effective. Objective: Evaluate the efficacy of the TAP method (outpatient version) in the treatment of NPS in individuals with dementia and in the burden reduction of their caregivers. Methods: This is a randomized, double-blind, controlled clinical trial for the treatment of NPS in dementia. Outcome measures consisted of assessing the NPS of individuals with dementia, through the Neuropsychiatric Inventory-Clinician rating scale (NPI-C), and assessing the burden on their caregivers, using the Zarit Scale. All the participants were evaluated pre-and post-intervention. Results: 54 individuals with dementia and caregivers were allocated to the experimental (n = 28) and control (n = 26) groups. There was improvement of the following NPS in the experimental group: delusions, agitation, aggressiveness, depression, anxiety, euphoria, apathy, disinhibition, irritability, motor disturbance, and aberrant vocalization. No improvement was observed in hallucinations, sleep disturbances, and appetite disorders. The TAP method for outpatient settings was also clinically effective in reducing burden between caregivers of the experimental group. Conclusion: The use of personalized prescribed activities, coupled with the caregiver training, may be a clinically effective approach to reduce NPS and caregiver burden of individuals with dementia.

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Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART): a multiarm phase IIb randomised, double-blind, placebo-controlled clinical trial comparing the efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis

BMJ Open ◽

10.1136/bmjopen-2018-021944 ◽

2018 ◽

Vol 8 (8) ◽

pp. e021944 ◽

Cited By ~ 20

Author(s):

Peter Connick ◽

Floriana De Angelis ◽

Richard A Parker ◽

Domenico Plantone ◽

Anisha Doshi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Unmet Need ◽

Dropout Rate ◽

Analysis Of Covariance ◽

Controlled Clinical Trial ◽

Imaging Data ◽

Secondary Progressive ◽

Link Type ◽

Oral Agents ◽

Neuroprotective Therapies

IntroductionThe major unmet need in multiple sclerosis (MS) is for neuroprotective therapies that can slow (or ideally stop) the rate of disease progression. The UK MS Society Clinical Trials Network (CTN) was initiated in 2007 with the purpose of developing a national, efficient, multiarm trial of repurposed drugs. Key underpinning work was commissioned by the CTN to inform the design, outcome selection and drug choice including animal models and a systematic review. This identified seven leading oral agents for repurposing as neuroprotective therapies in secondary progressive MS (SPMS). The purpose of the Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART) will be to evaluate the neuroprotective efficacy of three of these drugs, selected with distinct mechanistic actions and previous evidence of likely efficacy, against a common placebo arm. The interventions chosen were: amiloride (acid-sensing ion channel antagonist); fluoxetine (selective serotonin reuptake inhibitor) and riluzole (glutamate antagonist).Methods and analysisPatients with progressing SPMS will be randomised 1:1:1:1 to amiloride, fluoxetine, riluzole or matched placebo and followed for 96 weeks. The primary outcome will be the percentage brain volume change (PBVC) between baseline and 96 weeks, derived from structural MR brain imaging data using the Structural Image Evaluation, using Normalisation, of Atrophy method. With a sample size of 90 per arm, this will give 90% power to detect a 40% reduction in PBVC in any active arm compared with placebo and 80% power to detect a 35% reduction (analysing by analysis of covariance and with adjustment for multiple comparisons of three 1.67% two-sided tests), giving a 5% overall two-sided significance level. MS-SMART is not powered to detect differences between the three active treatment arms. Allowing for a 20% dropout rate, 110 patients per arm will be randomised. The study will take place at Neuroscience centres in England and Scotland.Ethics and disseminationMS-SMART was approved by the Scotland A Research Ethics Committee on 13 January 2013 (REC reference: 13/SS/0007). Results of the study will be submitted for publication in a peer-reviewed journal.Trial registration numbersNCT01910259; 2012-005394-31;ISRCTN28440672.

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Structural ‘connectomic’ alterations in the limbic system of multiple sclerosis patients with major depression

Multiple Sclerosis Journal ◽

10.1177/1352458514558474 ◽

2014 ◽

Vol 21 (8) ◽

pp. 1003-1012 ◽

Cited By ~ 27

Author(s):

Salvatore Nigro ◽

Luca Passamonti ◽

Roberta Riccelli ◽

Nicola Toschi ◽

Federico Rocca ◽

...

Keyword(s):

Multiple Sclerosis ◽

Major Depression ◽

Diffusion Tensor ◽

Negative Impact ◽

Brain Connectivity ◽

Strong Support ◽

Imaging Data ◽

Connectivity Patterns ◽

The Right ◽

Multiple Sclerosis Patients

Background: Major depression (MD) is a common psychiatric disorder in multiple sclerosis (MS). Despite the negative impact of MD on the quality of life of MS patients, little is known about its underlying brain mechanisms. Objective: We studied the whole-brain connectivity patterns that were associated with MD in MS. Alterations were mainly expected within limbic circuits. Methods: Diffusion tensor imaging data were collected in 20 MS patients with MD, 22 non-depressed MS patients and 16 healthy controls. We used deterministic tractography and graph analysis to study the white-matter connectivity patterns that characterized MS patients with MD. Results: We found that MD in MS was associated with increased local path length in the right hippocampus and right amygdala. Further analyses revealed that these effects were driven by an increased shortest distance between both the right hippocampus and right amygdala and a series of regions including the dorsolateral and ventrolateral prefrontal cortex, orbitofrontal cortex, sensory-motor cortices and supplementary motor area. Conclusion: Our data provide strong support for neurobiological accounts positing that MD in MS is mediated by abnormal ‘communications’ within limbic circuits. We also found evidence that MD in MS may be linked with connectivity alterations at the limbic-motor interface, a group of regions that translates emotions into survival-oriented behaviors.

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Anatomical brain connectivity can assess cognitive dysfunction in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458512474088 ◽

2013 ◽

Vol 19 (9) ◽

pp. 1161-1168 ◽

Cited By ~ 25

Author(s):

M Bozzali ◽

B Spanò ◽

GJM Parker ◽

G Giulietti ◽

M Castelli ◽

...

Keyword(s):

Multiple Sclerosis ◽

Grey Matter ◽

Brain Connectivity ◽

Structural Connectivity ◽

Grey Matter Volume ◽

Resonance Imaging ◽

Relapsing Remitting ◽

Weighted Magnetic Resonance Imaging ◽

Serial Addition ◽

New Perspective

Background: Brain disconnection plays a major role in determining cognitive disabilities in multiple sclerosis (MS). We recently developed a novel diffusion-weighted magnetic resonance imaging (DW-MRI) tractography approach, namely anatomical connectivitity mapping (ACM), that quantifies structural brain connectivity. Objective: Use of ACM to assess structural connectivity modifications in MS brains and ascertain their relationship with the patients’ Paced-Auditory-Serial-Addition-Test (PASAT) scores. Methods: Relapsing–remitting MS (RRMS) patients ( n = 25) and controls ( n = 25) underwent MRI at 3T, including conventional images, T1-weighted volumes and DW-MRI. Volumetric scans were coregistered to fractional anisotropy (FA) images, to obtain parenchymal FA maps for both white and grey matter. We initiated probabilistic tractography from all parenchymal voxels, obtaining ACM maps by counting the number of streamlines passing through each voxel, then normalizing by the total number of streamlines initiated. The ACM maps were transformed into standard space, for statistical use. Results: RRMS patients had reduced grey matter volume and FA, consistent with previous literature. Also, we showed reduced ACM in the thalamus and in the head of the caudate nucleus, bilaterally. In our RRMS patients, ACM was associated with PASAT scores in the corpus callosum, right hippocampus and cerebellum. Conclusions: ACM opens a new perspective, clarifying the contribution of anatomical brain disconnection to clinical disabilities in MS.

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Hippocampal-subregion functional alterations associated with antidepressant effects and cognitive impairments of electroconvulsive therapy

Psychological Medicine ◽

10.1017/s0033291718002684 ◽

2018 ◽

Vol 49 (08) ◽

pp. 1357-1364 ◽

Cited By ~ 8

Author(s):

Tongjian Bai ◽

Qiang Wei ◽

Wen Xie ◽

Anzhen Wang ◽

Jiaojian Wang ◽

...

Keyword(s):

Electroconvulsive Therapy ◽

Rating Scale ◽

Cognitive Impairments ◽

Structural Connectivity ◽

Angular Gyrus ◽

Resting State Functional Connectivity ◽

Antidepressant Effects ◽

Emotion And Memory ◽

Middle Occipital Gyrus ◽

The Relationship

AbstractBackgroundElectroconvulsive therapy (ECT), an effective antidepressive treatment, is frequently accompanied by cognitive impairment (predominantly memory), usually transient and self-limited. The hippocampus is a key region involved in memory and emotion processing, and in particular, the anterior-posterior hippocampal subregions has been shown to be associated with emotion and memory. However, less is known about the relationship between hippocampal-subregion alterations following ECT and antidepressant effects or cognitive impairments.MethodsResting-state functional connectivity (RSFC) based on the seeds of hippocampal subregions were investigated in 45 pre- and post-ECT depressed patients. Structural connectivity between hippocampal subregions and corresponding functionally abnormal regions was also conducted using probabilistic tractography. Antidepressant effects and cognitive impairments were measured by the Hamilton Depressive Rating Scale (HDRS) and the Category Verbal Fluency Test (CVFT), respectively. Their relationships with hippocampal-subregions alterations were examined.ResultsAfter ECT, patients showed increased RSFC in the hippocampal emotional subregion (HIPe) with the left middle occipital gyrus (LMOG) and right medial temporal gyrus (RMTG). Decreased HDRS was associated with increased HIPe-RMTG RSFC (r = −0.316, p = 0.035) significantly and increased HIPe-LMOG RSFC at trend level (r = −0.283, p = 0.060). In contrast, the hippocampal cognitive subregion showed decreased RSFC with the bilateral angular gyrus, and was correlated with decreased CVFT (r = 0.418, p = 0.015 for left; r = 0.356, p = 0.042 for right). No significant changes were found in structural connectivity.ConclusionThe hippocampal-subregions functional alterations may be specially associated with the antidepressant and cognitive effects of ECT.

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Resting-state functional connectivity and psychopathology in Klinefelter syndrome (47, XXY)

10.1101/2020.12.15.422868 ◽

2020 ◽

Author(s):

Ethan T. Whitman ◽

Siyuan Liu ◽

Erin Torres ◽

Allysa Warling ◽

Kathleen Wilson ◽

...

Keyword(s):

Functional Connectivity ◽

Resting State ◽

Genetic Risk ◽

Klinefelter Syndrome ◽

Brain Connectivity ◽

Brain Anatomy ◽

Imaging Data ◽

Resting State Functional Connectivity ◽

Dorsolateral Prefrontal ◽

Neuroimaging Study

Klinefelter syndrome (47, XXY; Henceforth: XXY syndrome) is a high impact but poorly understood genetic risk factor for neuropsychiatric impairment. Here, we provide the first neuroimaging study to map resting-state functional connectivity (rsFC) changes in XXY syndrome and ask how these might relate to brain anatomy and psychopathology. We collected resting state functional magnetic resonance imaging data from 75 individuals with XXY and 84 healthy XY males. We implemented a brain-wide screen to identify regions with altered global rsFC in XXY vs. XY males, and then used seed-based analysis to decompose these alterations. We further compared rsFC changes with regional changes in brain volume from voxel-based morphometry and tested for correlations between rsFC and symptom variation within XXY syndrome. We found that XXY syndrome was characterized by increased global rsFC in the left dorsolateral prefrontal cortex (DLPFC), associated with overconnectivity with diverse rsFC networks. Regional rsFC changes were partly coupled to regional volumetric changes in XXY syndrome. Within the precuneus, variation in DLPFC rsFC within XXY syndrome was correlated with the severity of psychopathology in XXY individuals. Our findings provide the first view of altered functional brain connectivity in XXY syndrome and delineate links between these alterations and those relating to both brain anatomy and psychopathology. Taken together, these insights advance biological understanding of XXY syndrome as a disorder in its own right, and as a model of genetic risk for psychopathology more broadly.

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Predicting MEG resting-state functional connectivity from microstructural information

Network Neuroscience ◽

10.1162/netn_a_00187 ◽

2021 ◽

pp. 1-42

Author(s):

Eirini Messaritaki ◽

Sonya Foley ◽

Simona Schiavi ◽

Lorenzo Magazzini ◽

Bethany Routley ◽

...

Keyword(s):

Functional Connectivity ◽

Fractional Anisotropy ◽

Shortest Path ◽

Resting State ◽

Path Length ◽

Structural Connectivity ◽

Imaging Data ◽

Resting State Functional Connectivity ◽

Brain Microstructure ◽

Functional Mechanisms

Understanding how human brain microstructure influences functional connectivity is an important endeavor. In this work, magnetic resonance imaging data from ninety healthy participants were used to calculate structural connectivity matrices using the streamline count, fractional anisotropy, radial diffusivity and a myelin measure (derived from multi-component relaxometry) to assign connection strength. Unweighted binarized structural connectivity matrices were also constructed. Magnetoencephalography resting-state data from those participants were used to calculate functional connectivity matrices, via correlations of the Hilbert envelopes of beamformer timeseries in the delta, theta, alpha and beta frequency bands. Non-negative matrix factorization was performed to identify the components of the functional connectivity. Shortest-path-length and search-information analyses of the structural connectomes were used to predict functional connectivity patterns for each participant. The microstructure-informed algorithms predicted the components of the functional connectivity more accurately than they predicted the total functional connectivity. This provides a methodology to understand functional mechanisms better. The shortest-path-length algorithm exhibited the highest prediction accuracy. Of the weights of the structural connectivity matrices, the streamline count and the myelin measure gave the most accurate predictions, while the fractional anisotropy performed poorly. Overall, different structural metrics paint very different pictures of the structural connectome and its relationship to functional connectivity.

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Altered brain structural and functional connectivity in schizotypy

Psychological Medicine ◽

10.1017/s0033291720002445 ◽

2020 ◽

pp. 1-10

Author(s):

Yong-ming Wang ◽

Xin-lu Cai ◽

Rui-ting Zhang ◽

Yi-jing Zhang ◽

Han-yu Zhou ◽

...

Keyword(s):

Functional Connectivity ◽

Default Mode Network ◽

Brain Connectivity ◽

Structural Connectivity ◽

Control Network ◽

Imaging Data ◽

Default Mode ◽

Task Control ◽

Brain White Matter ◽

Functional Connectivity Strength

Abstract Background Schizotypy refers to schizophrenia-like traits below the clinical threshold in the general population. The pathological development of schizophrenia has been postulated to evolve from the initial coexistence of ‘brain disconnection’ and ‘brain connectivity compensation’ to ‘brain connectivity decompensation’. Methods In this study, we examined the brain connectivity changes associated with schizotypy by combining brain white matter structural connectivity, static and dynamic functional connectivity analysis of diffusion tensor imaging data and resting-state functional magnetic resonance imaging data. A total of 87 participants with a high level of schizotypal traits and 122 control participants completed the experiment. Group differences in whole-brain white matter structural connectivity probability, static mean functional connectivity strength, dynamic functional connectivity variability and stability among 264 brain sub-regions of interests were investigated. Results We found that individuals with high schizotypy exhibited increased structural connectivity probability within the task control network and within the default mode network; increased variability and decreased stability of functional connectivity within the default mode network and between the auditory network and the subcortical network; and decreased static mean functional connectivity strength mainly associated with the sensorimotor network, the default mode network and the task control network. Conclusions These findings highlight the specific changes in brain connectivity associated with schizotypy and indicate that both decompensatory and compensatory changes in structural connectivity within the default mode network and the task control network in the context of whole-brain functional disconnection may be an important neurobiological correlate in individuals with high schizotypy.

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Predicting MEG resting-state functional connectivity using microstructural information

10.1101/2020.09.15.298307 ◽

2020 ◽

Cited By ~ 2

Author(s):

Eirini Messaritaki ◽

Sonya Foley ◽

Simona Schiavi ◽

Lorenzo Magazzini ◽

Bethany Routley ◽

...

Keyword(s):

Functional Connectivity ◽

Fractional Anisotropy ◽

Shortest Path ◽

Resting State ◽

Path Length ◽

Structural Connectivity ◽

Imaging Data ◽

Resting State Functional Connectivity ◽

Brain Microstructure ◽

Structural Metrics

AbstractUnderstanding how human brain microstructure influences functional connectivity is an important endeavor. In this work, magnetic resonance imaging data from ninety healthy participants were used to calculate structural connectivity matrices using the streamline count, fractional anisotropy, radial diffusivity and a myelin measure (derived from multi-component relaxometry) to assign connection strength. Unweighted binarized structural connectivity matrices were also constructed. Magnetoencephalography resting-state data from those participants were used to calculate functional connectivity matrices, via correlations of the Hilbert envelopes of beamformer timeseries at four frequency bands: delta (1 − 4 Hz), theta (3 − 8 Hz), alpha (8 − 13 Hz) and beta (13 − 30 Hz). Non-negative matrix factorization was performed to identify the components of the functional connectivity. Shortest-path-length and search-information analyses of the structural connectomes were used to predict functional connectivity patterns for each participant.The microstructurally-informed algorithms predicted the components of the functional connectivity more accurately than they predicted the total functional connectivity. The shortest-path-length algorithm exhibited the highest prediction accuracy. Of the weights of the structural connectivity matrices, the streamline count and the myelin measure gave the most accurate predictions, while the fractional anisotropy performed poorly. Different structural metrics paint very different pictures of the structural connectome and its relationship to functional connectivity.

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A double-blind, randomized, controlled study of oral pirfenidone for treatment of secondary progressive multiple sclerosis

Multiple Sclerosis Journal ◽

10.1191/1352458505ms1134oa ◽

2005 ◽

Vol 11 (2) ◽

pp. 149-158 ◽

Cited By ~ 31

Author(s):

Jonathan E Walker ◽

Shri N Giri ◽

Solomon B Margolin

Keyword(s):

Multiple Sclerosis ◽

Rating Scale ◽

Progressive Multiple Sclerosis ◽

Secondary Progressive Multiple Sclerosis ◽

Bladder Function ◽

Controlled Study ◽

Controlled Clinical Trial ◽

Double Blind ◽

Secondary Progressive ◽

Randomized Controlled

Currently, there are no approved treatments for secondary progressive multiple sclerosis (MS) that stabilize or reverse the neurological disabilities associated with this disease. Oral pirfenidone was found to stabilize and overcome the disabilities in two published independent open-label studies in secondary progressive MS. This led us to study pirfenidone in a phase II double-blind, randomized and controlled, clinical trial in patients with advanced secondary progressive MS for 12 months. Forty-three patients met the eligibility criteria approved by the IRB and accepted by the FDA. Of these patients, 18 were randomly assigned to placebo and 25 patients to oral pirfenidone groups. All eligible patients were included in the statistical analysis of the data according to intention-to-treat principles. Some patients on oral pirfenidone manifested mild drug-related adverse effects, but it was well tolerated overall. By one month, pirfenidone significantly (P<0.05) improved the Scripps Neurological Rating Scale (SNRS) scores, and scores remained significantly improved for 3, 6 and 12 months when compared to the baseline SNRS scores. In contrast, the SNRS scores of patients on oral placebo were not significantly improved at 1, 3, 6 or 12 months of the study, when compared with baseline scores. Oral pirfenidone significantly (P<0.04) reduced the incidence of relapses (27.8% on placebo versus 8.0% on pirfenidone). Furthermore, oral pirfenidone treatment was associated with a marked improvement in bladder dysfunction (40.0% on pirfenidone versus 16.7% on placebo). Expanded Disability Status Scale scores and MRI lesion count were not significantly different in the placebo and pirfenidone groups. These findings indicate a significant effect of pirfenidone on clinical disability and bladder function for secondary progressive MS patients. A major multicentre, double-blind, randomized, controlled trial is justified.

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