Cognitive training in Parkinson’s disease induces local, not global, changes in white matter microstructure

ABSTRACTPrevious studies have shown that cognitive training can improve cognitive performance in various neurodegenerative diseases but relatively little is known about the effects of cognitive training on the brain. Here we investigated the effects of our cognitive training paradigm, COGTIPS, on regional white matter microstructure and topology of the structural network. We previously showed that COGTIPS has small, positive effects on processing speed. A subsample of 79 PD patients (N=40 cognitive training group, N=39 active control group) underwent multi-shell diffusion weighted imaging pre- and post-intervention. Our pre-registered analysis plan (osf.io/cht6g) entailed calculating white matter microstructural integrity in five tracts of interest, including the anterior thalamic radiation (ATR) and calculating the topology of the structural connectome. Training-induced changes were analyzed with linear mixed-models. Relative to the active control condition, cognitive training had no effect on network topology. Cognitive training did lead to a reduction in fractional anisotropy in the ATR (B[SE]: -0.32 [0.12], p=0.01). This reduction was associated with faster responses on the ToL task (r = 0.42, P = 0.007), but this just fell short of our statistical threshold (P<0.006). Post-hoc analyses showed that this was not due to changes in fiber density and cross-section, suggesting that that the observed effect in the ATR are due to training-induced alterations in neighboring fibers running through the same voxels, such as intra-striatal and thalamo-striatal fibers. These results indicate that eight weeks of cognitive training do not alter network topology, but can have subtle local effects on structural connectivity.

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Cognitive Training in Parkinson’s Disease Induces Local, Not Global, Changes in White Matter Microstructure

Neurotherapeutics ◽

10.1007/s13311-021-01103-9 ◽

2021 ◽

Author(s):

Chris Vriend ◽

Tim D. van Balkom ◽

Henk W. Berendse ◽

Ysbrand D. van der Werf ◽

Odile A. van den Heuvel

Keyword(s):

White Matter ◽

Fractional Anisotropy ◽

Active Control ◽

Cognitive Training ◽

Network Topology ◽

Control Group ◽

Whole Brain ◽

Positive Effects ◽

White Matter Microstructure ◽

Structural Network

AbstractPrevious studies showed that cognitive training can improve cognitive performance in various neurodegenerative diseases but little is known about the effects of cognitive training on the brain. Here, we investigated the effects of our cognitive training paradigm, COGTIPS, on regional white matter microstructure and structural network topology. We previously showed that COGTIPS has small, positive effects on processing speed. A subsample of 79 PD patients (N = 40 cognitive training group, N = 39 active control group) underwent multi-shell diffusion-weighted imaging pre- and post-intervention. Our pre-registered analysis plan (osf.io/cht6g) entailed investigating white matter microstructural integrity (e.g., fractional anisotropy) in five tracts of interest, including the anterior thalamic radiation (ATR), whole-brain tract-based spatial statistics (TBSS), and the topology of the structural network. Relative to the active control condition, cognitive training had no effect on topology of the structural network or whole-brain TBSS. Cognitive training did lead to a reduction in fractional anisotropy in the ATR (B [SE]: − 0.32 [0.12], P = 0.01). This reduction was associated with faster responses on the Tower of London task (r = 0.42, P = 0.007), but this just fell short of our statistical threshold (P < 0.006). Post hoc “fixel-based” analyses showed that this was not due to changes in fiber density and cross section. This suggests that the observed effect in the ATR is due to training-induced alterations in neighboring fibers running through the same voxels, such as intra-striatal and thalamo-striatal fibers. These results indicate that 8 weeks of cognitive training does not alter network topology, but has subtle local effects on structural connectivity.

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White Matter Changes on Diffusion Tensor Imaging in the FINGER Randomized Controlled Trial

Journal of Alzheimer s Disease ◽

10.3233/jad-200423 ◽

2020 ◽

Vol 78 (1) ◽

pp. 75-86

Author(s):

Ruth Stephen ◽

Alina Solomon ◽

Tiia Ngandu ◽

Esko Levälahti ◽

Juha O. Rinne ◽

...

Keyword(s):

White Matter ◽

Diffusion Tensor ◽

Controlled Trial ◽

Intervention Group ◽

Control Group ◽

Pathological Changes ◽

Cognitive Changes ◽

Randomized Controlled ◽

White Matter Microstructure ◽

Multidomain Intervention

Background: Early pathological changes in white matter microstructure can be studied using the diffusion tensor imaging (DTI). It is not only important to study these subtle pathological changes leading to cognitive decline, but also to ascertain how an intervention would impact the white matter microstructure and cognition in persons at-risk of dementia. Objectives: To study the impact of a multidomain lifestyle intervention on white matter and cognitive changes during the 2-year Finnish Geriatric Intervention Study to prevent Cognitive Impairment and Disability (FINGER), a randomized controlled trial in at-risk older individuals (age 60–77 years) from the general population. Methods: This exploratory study consisted of a subsample of 60 FINGER participants. Participants were randomized to either a multidomain intervention (diet, exercise, cognitive training, and vascular risk management, n = 34) or control group (general health advice, n = 26). All underwent baseline and 2-year brain DTI. Changes in fractional anisotropy (FA), diffusivity along domain (F1) and non-domain (F2) diffusion orientations, mean diffusivity (MD), axial diffusivity (AxD), radial diffusivity (RD), and their correlations with cognitive changes during the 2-year multidomain intervention were analyzed. Results: FA decreased, and cognition improved more in the intervention group compared to the control group (p < 0.05), with no significant intergroup differences for changes in F1, F2, MD, AxD, or RD. The cognitive changes were significantly positively related to FA change, and negatively related to RD change in the control group, but not in the intervention group. Conclusion: The 2-year multidomain FINGER intervention may modulate white matter microstructural alterations.

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White matter microstructure predicts foreign language learning in army interpreters

Bilingualism Language and Cognition ◽

10.1017/s1366728920000152 ◽

2020 ◽

Vol 23 (4) ◽

pp. 763-771 ◽

Cited By ~ 1

Author(s):

Johan Mårtensson ◽

Johan Eriksson ◽

Nils Christian Bodammer ◽

Magnus Lindgren ◽

Mikael Johansson ◽

...

Keyword(s):

White Matter ◽

Foreign Language ◽

Language Learning ◽

Language Proficiency ◽

Brain Structure ◽

Foreign Language Learning ◽

Control Group ◽

Final Test ◽

Foreign Language Acquisition ◽

White Matter Microstructure

AbstractAdult foreign language acquisition is challenging, and the degree of success varies among individuals. Anatomical differences in brain structure prior to training can partly explain why some learn more than others. We followed a sample of conscript interpreters undergoing intense language training to study learning-related changes in white-matter microstructure (FA, MD, RD and AD) and associations between differences in brain structure prior to training with acquired language proficiency. No evidence for changes in white matter microstructure relative to a control group was found. Starting values of RD, AD and MD were positively related to final test scores of language proficiency, corroborating earlier findings in the field and highlighting the need for further study of how initial brain structure influences and interacts with learning outcomes.

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Development of white matter microstructure and executive functions during childhood and adolescence: a review of diffusion MRI studies

10.31234/osf.io/kyxbq ◽

2020 ◽

Author(s):

Anne-Lise Goddings ◽

David Roalf ◽

Catherine Lebel ◽

Christian K. Tamnes

Keyword(s):

White Matter ◽

Executive Functions ◽

Structural Connectivity ◽

Child And Adolescent ◽

Childhood And Adolescence ◽

Cross Sectional ◽

Indirect Measures ◽

White Matter Microstructure ◽

P Diffusion ◽

The Brain

Diffusion magnetic resonance imaging (dMRI) provides indirect measures of white matter microstructure that can be used to make inferences about structural connectivity within the brain. Over the last decade, a growing literature of cross-sectional and longitudinal studies have documented relationships between dMRI indices and cognitive development. In this review, we provide a brief overview of dMRI methods and how they can be used to study white matter and connectivity, briefly discuss challenges with using dMRI in child and adolescent populations, and review the extant literature examining the links between dMRI indices and executive functions during development. We explore the links between white matter microstructure and specific executive functions: inhibition, working memory and cognitive shifting, as well as performance on complex executive function tasks. Where there is concordance in findings across studies, this is highlighted, and potential explanations for discrepancies between results are discussed. Finally, we explore future directions that are necessary to better understand the links between child and adolescent development of executive functions and structural connectivity of the brain.

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Longitudinal changes of ADHD symptoms in association with white matter microstructure: a tract-specific fixel-based analysis

10.1101/2021.11.19.469248 ◽

2021 ◽

Author(s):

Christienne G Damatac ◽

Sourena Soheili-Nezhad ◽

Guilherme Blazquez Freches ◽

Marcel P Zwiers ◽

Sanne de Bruijn ◽

...

Keyword(s):

White Matter ◽

Fiber Density ◽

Cross Sectional ◽

White Matter Microstructure ◽

Brain Structure And Function ◽

White Matter Development ◽

And Function ◽

Symptom Trajectory ◽

Over Time

Background: Variation in the longitudinal course of childhood attention deficit/hyperactivity disorder (ADHD) coincides with neurodevelopmental maturation of brain structure and function. Prior work has attempted to determine how alterations in white matter (WM) relate to changes in symptom severity, but much of that work has been done in smaller cross-sectional samples using voxel-based analyses. Using standard diffusion-weighted imaging (DWI) methods, we previously showed WM alterations were associated with ADHD symptom remission over time in a longitudinal sample of probands, siblings, and unaffected individuals. Here, we extend this work by further assessing the nature of these changes in WM microstructure by including an additional follow-up measurement (aged 18-34 years), and using the more physiologically informative fixel-based analysis (FBA). Methods: Data were obtained from 139 participants over 3 clinical and 2 follow-up DWI waves, and analyzed using FBA in regions-of-interest based on prior findings. We replicated previously reported significant models and extended them by adding another time-point, testing whether changes in combined and hyperactivity-impulsivity (HI) continuous symptom scores are associated with fixel metrics at follow-up. Results: Clinical improvement in HI symptoms over time was associated with more fiber density at follow-up in the left corticospinal tract (lCST) (tmax=1.092, standardized effect[SE]=0.044, pFWE=0.016), and improvement in combined symptoms over time was associated with more fiber cross-section at follow-up in the lCST (tmax=3.775, SE=0.051, pFWE=0.019). Conclusions: Aberrant white matter development involves both lCST micro- and macrostructural alterations and its path may be moderated by preceding symptom trajectory.

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Effects of Acupuncture on Cancer-Related Cognitive Impairment in Chinese Gynecological Cancer Patients: A Pilot Cohort Study

Integrative Cancer Therapies ◽

10.1177/1534735418777109 ◽

2018 ◽

Vol 17 (3) ◽

pp. 737-746 ◽

Cited By ~ 3

Author(s):

Yingchun Zeng ◽

Andy S. K. Cheng ◽

Ting Song ◽

Xiujie Sheng ◽

Shaojing Wang ◽

...

Keyword(s):

Cohort Study ◽

Cognitive Impairment ◽

White Matter ◽

Pilot Study ◽

Cancer Patients ◽

Gynecological Cancer ◽

Structural Connectivity ◽

Control Group ◽

Healthy Controls ◽

Neurocognitive Tests

Background: Among women in China, gynecological cancers are the second most common cancers after breast cancer. Cancer-related cognitive impairment (CRCI) has emerged as a significant problem affecting gynecological cancer survivors. While acupuncture has been used in different aspects of cancer care, the possible positive effects of acupuncture on cognitive impairment have received little attention. This study hypothesized that patients would demonstrate lower neurocognitive performance and lower structural connectivity compared to healthy controls. This pilot study also hypothesized that acupuncture may potentially be effective in treating CRCI of cancer patients by increasing brain structural connectivity and integrity. Methods: This prospective cohort study consisted of 3 stages: the first stage included a group of gynecological cancer patients and a group of age-matched healthy controls. This baseline stage used a core set of neurocognitive tests to screen patients with cognitive impairment and used a multimodal approach of brain magnetic resonance imaging (MRI) to explore the possible neurobiological mechanism of cognitive impairment in cancer patients, comparing the results with a group of noncancer controls. The second stage involved assigning CRCI patients into the acupuncture intervention group, while patients without CRCI were assigned into the cancer control group. The third stage was a postintervention assessment of neurocognitive function by the same set of neurocognitive tests at baseline. To explore the possible neurobiological basis of acupuncture for treating CRCI, this study also used a multimodal MRI approach to assess changes in brain structural connectivity, and neurochemical properties in patients at pre- and postacupuncture intervention. Results: This study found that the prevalence of cognitive impairment in Chinese gynecological cancer patients at diagnosis was 26.67%. When investigating the microstructural white matter in the brain, diffusion tensor imaging data in this study indicated that premorbid cognitive functioning (before clinical manifestations become evident) has already existed, as the global and local connectome properties in the entire patient group were lower than in the healthy control group. Using magnetic resonance spectroscopy, this study indicated there was a significant reduction of relative concentration of NAA ( N-acetyl aspartate) in the left hippocampus, comparing these results with healthy controls. Regarding the effects of acupuncture on reducing CRCI, patients in the acupuncture group reported better neurocognitive test performance after matching for age, menopausal status, cancer stage, and chemotherapy regimen dosage. On a microstructural level, acupuncture’s ability to reduce CRCI may be attributed to a reduction in demyelination and an enhancement of the neuronal viability of white matter in the hippocampus. Conclusion: This pilot study indicates that acupuncture is a promising intervention in treating CRCI in gynecological cancer patients undergoing chemotherapy; however, it requires evaluation in larger randomized controlled studies to definitively assess its benefit. By using a multimodal imaging approach, this pilot study also provides novel insights into the neurobiological basis of cognitive impairment on the human brain that has been induced by cancer and/or its treatment.

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Feasibility of a Cognitive Training Game in Parkinson’s Disease: The Randomized Parkin’Play Study

European Neurology ◽

10.1159/000509685 ◽

2020 ◽

Vol 83 (4) ◽

pp. 426-432 ◽

Cited By ~ 1

Author(s):

Sjors C.F. van de Weijer ◽

Annelien A. Duits ◽

Bastiaan R. Bloem ◽

Nienke M. de Vries ◽

Roy P.C. Kessels ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Training ◽

Controlled Trial ◽

Intervention Group ◽

Waiting List ◽

Control Group ◽

Positive Effects ◽

Home Based ◽

Global Cognition

Cognitive training (CT) shows modest positive effects on cognitive function in patients with Parkinson’s disease (PD). Gamification may enhance adherence to traditional CT, but this has not been studied yet. Here, we investigated the feasibility of a gamified CT. We performed a randomized controlled trial including PD patients with mild cognitive impairment. Participants were randomly allocated to a 12-week home-based gamified CT intervention or waiting-list control group. Assessments were performed at baseline and at weeks 12 and 24. Forty-one patients were included (21 intervention and 20 waiting-list controls). Sixty-three percent of the intervention group trained >50% of the recommended sessions, while 81% voluntarily continued training after 12 weeks. After 24 weeks, 87.5% graded the game to be satisfactory. Global cognition scores improved after 24 weeks. Home-based gamified CT shows acceptable feasibility in patients with PD, and we observed preliminary indications for efficacy. Larger trials are needed to establish this efficacy.

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Digital, mathematical and cognitive training: Evidence from a randomized trial

10.31234/osf.io/24ej7 ◽

2020 ◽

Author(s):

Carlos Guillermo Bozzoli ◽

Maria Luz Gonzalez-Gadea ◽

Maria Julia Hermida ◽

Lucía Navarro ◽

Tomás Alberto Olego ◽

...

Keyword(s):

Randomized Trial ◽

Cognitive Training ◽

Face Perception ◽

Primary Schools ◽

Digit Span ◽

Control Group ◽

Math Skills ◽

Positive Effects ◽

Percentage Points ◽

Visuospatial Reasoning

In this paper, we experimentally evaluate a cognitive training tool that aims to improve children’s mathematical ability through technology in rural primary schools in Argentina. We conducted a large cluster-randomized trial: schools in the treatment group used an app to train mathematical skills, while schools in the control group received a literacy book. We tested the math skills of 1,304 children in the 2nd through 6th grades from 80 rural schools and applied three cognitive tests: digit-span (working memory), face-perception (attention to objects), and block design (visuospatial reasoning), directly before and after the 10-week intervention period. In schools that received the treatment, we found no improvement in the digit-span or face-perception tests, but significant and positive effects in visuospatial reasoning and mathematical abilities. The improvement among students from treatment schools was 54 percentage points higher in math skills and 42 percentage points higher in visuospatial abilities than the gains by students in control schools. This study suggests this intervention is a feasible and effective way of enhancing the mathematical and cognitive abilities of children in rural areas.

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Fornix Microstructure and Memory Performance Is Associated with Altered Neural Connectivity during Episodic Recognition

Journal of the International Neuropsychological Society ◽

10.1017/s1355617715001216 ◽

2016 ◽

Vol 22 (2) ◽

pp. 191-204 ◽

Cited By ~ 10

Author(s):

Martina Ly ◽

Nagesh Adluru ◽

Daniel J. Destiche ◽

Sharon Y. Lu ◽

Jennifer M. Oh ◽

...

Keyword(s):

White Matter ◽

Diffusion Tensor ◽

Negative Impact ◽

Interaction Analysis ◽

Memory Performance ◽

Structural Connectivity ◽

Middle Frontal Gyrus ◽

Age Related ◽

White Matter Microstructure ◽

Psychophysiological Interaction

AbstractObjectives: The purpose of this study was to assess whether age-related differences in white matter microstructure are associated with altered task-related connectivity during episodic recognition. Methods: Using functional magnetic resonance imaging and diffusion tensor imaging from 282 cognitively healthy middle-to-late aged adults enrolled in the Wisconsin Registry for Alzheimer’s Prevention, we investigated whether fractional anisotropy (FA) within white matter regions known to decline with age was associated with task-related connectivity within the recognition network. Results: There was a positive relationship between fornix FA and memory performance, both of which negatively correlated with age. Psychophysiological interaction analyses revealed that higher fornix FA was associated with increased task-related connectivity amongst the hippocampus, caudate, precuneus, middle occipital gyrus, and middle frontal gyrus. In addition, better task performance was associated with increased task-related connectivity between the posterior cingulate gyrus, middle frontal gyrus, cuneus, and hippocampus. Conclusions: The findings indicate that age has a negative effect on white matter microstructure, which in turn has a negative impact on memory performance. However, fornix microstructure did not significantly mediate the effect of age on performance. Of interest, dynamic functional connectivity was associated with better memory performance. The results of the psychophysiological interaction analysis further revealed that alterations in fornix microstructure explain–at least in part–connectivity among cortical regions in the recognition memory network. Our results may further elucidate the relationship between structural connectivity, neural function, and cognition. (JINS, 2016, 22, 191–204)

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