Ying-hui Chou

Investigation of long-term reproducibility of intrinsic connectivity network mapping: a resting-state fMRI study.

BACKGROUND AND PURPOSE: Connectivity mapping based on resting-state fMRI is rapidly developing, and this methodology has great potential for clinical applications. However, before resting-state fMRI can be applied for diagnosis, prognosis, and monitoring treatment for an individual patient with neurologic or psychiatric diseases, it is essential to assess its long-term reproducibility and between-subject variations among healthy individuals. The purpose of the study was to quantify the long-term test-retest reproducibility of ICN measures derived from resting-state fMRI and to assess the between-subject variation of ICN measures across the whole brain. MATERIALS AND METHODS: Longitudinal resting-state fMRI data of 6 healthy volunteers were acquired from 9 scan sessions during >1 year. The within-subject reproducibility and between-subject variation of ICN measures, across the whole brain and major nodes of the DMN, were quantified with the ICC and COV. RESULTS: Our data show that the long-term test-retest reproducibility of ICN measures is outstanding, with >70% of the connectivity networks showing an ICC > 0.60. The COV across 6 healthy volunteers in this sample was >0.2, suggesting significant between-subject variation. CONCLUSIONS: Our data indicate that resting-state ICN measures (eg, the correlation coefficients between fMRI signal-intensity profiles from 2 different brain regions) are potentially suitable as biomarkers for monitoring disease progression and treatment effects in clinical trials and individual patients. Because between-subject variation is significant, it may be difficult to use quantitative ICN measures in their current state as a diagnostic tool.

Effects of Repetitive Transcranial Magnetic Stimulation on Motor Symptoms in Parkinson Disease: A Systematic Review and Meta-analysis

IMPORTANCE Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique that has been closely examined as a possible treatment for Parkinson disease (PD). However, results evaluating the effectiveness of rTMS in PD are mixed, mostly owing to low statistical power or variety in individual rTMS protocols. OBJECTIVES To determine the rTMS effects on motor dysfunction in patients with PD and to examine potential factors that modulate the rTMS effects. DATA SOURCES Databases searched included PubMed, EMBASE, Web of Knowledge, Scopus, and the Cochrane Library from inception to June 30, 2014. STUDY SELECTION Eligible studies included sham-controlled, randomized clinical trials of rTMS intervention for motor dysfunction in patients with PD. DATA EXTRACTION AND SYNTHESIS Relevant measures were extracted independently by 2 investigators. Standardized mean differences (SMDs) were calculated with random-effects models. MAIN OUTCOMES AND MEASURES Motor examination of the Unified Parkinsons Disease Rating Scale. RESULTS Twenty studies with a total of 470 patients were included. Random-effects analysis revealed a pooled SMD of 0.46 (95% CI, 0.29-0.64), indicating an overall medium effect size favoring active rTMS over sham rTMS in the reduction of motor symptoms (P<.001). Subgroup analysis showed that the effect sizes estimated from high-frequency rTMS targeting the primary motor cortex (SMD, 0.77; 95% CI, 0.46-1.08; P<.001) and low-frequency rTMS applied over other frontal regions (SMD, 0.50; 95% CI, 0.13-0.87; P=.008) were significant. The effect sizes obtained from the other 2 combinations of rTMS frequency and rTMS site (ie, high-frequency rTMS at other frontal regions: SMD, 0.23; 95% CI, -0.02 to 0.48, and low primary motor cortex: SMD, 0.28; 95% CI, -0.23 to 0.78) were not significant. Meta-regression revealed that a greater number of pulses per session or across sessions is associated with larger rTMS effects. Using the Grading of Recommendations, Assessment, Development, and Evaluation criteria, we characterized the quality of evidence presented in this meta-analysis as moderate quality. CONCLUSIONS AND RELEVANCE The pooled evidence suggests that rTMS improves motor symptoms for patients with PD. Combinations of rTMS site and frequency as well as the number of rTMS pulses are key modulators of rTMS effects. The findings of our meta-analysis may guide treatment decisions and inform future research.

Effects of Optic Flow Speed and Lateral Flow Asymmetry on Locomotion in Younger and Older Adults: A Virtual Reality Study

The purpose of the study is to investigate whether there are age-related differences in locomotion due to changes in presence of vision, optic flow speed, and lateral flow asymmetry using virtual reality technology. Gait kinematics and heading direction were measured using a three-dimensional motion analysis system. Although older and younger adults were affected differentially by the availability of vision, a greater dependence on optic flow information in older adults during walking was not found. Linear relations were observed between walking performance and flow speed as well as heading direction and flow asymmetry. The findings suggest that the ability to integrate optic flow information into the multimodal system for assessment of walking speed and heading direction is comparable in older and younger adults.

Visuospatial Perception and Navigation in Parkinson’s Disease

A shifted field of view, an altered perception of optic flow speed, and gait asymmetries may influence heading direction in Parkinsons disease (PD). PD participants (left body-side onset, LPD, n=14; right body-side onset, RPD, n=9) and Healthy Control participants (n=17) walked a virtual hallway in which the optic flow speeds of the walls varied. Three-dimensional kinematics showed participants veered away from the faster moving wall. Although veering normally occurs toward the side with smaller step length, in both LPD and RPD this bias was overridden by a shifted field of view, which caused veering in the opposite direction, toward the side of the brain with more basal ganglia damage.

Association between increased magnetic susceptibility of deep gray matter nuclei and decreased motor function in healthy adults

In the human brain, iron is more prevalent in gray matter than in white matter, and deep gray matter structures, particularly the globus pallidus, putamen, caudate nucleus, substantia nigra, red nucleus, and dentate nucleus, exhibit especially high iron content. Abnormally elevated iron levels have been found in various neurodegenerative diseases. Additionally, iron overload and related neurodegeneration may also occur during aging, but the functional consequences are not clear. In this study, we explored the correlation between magnetic susceptibility--a surrogate marker of brain iron--of these gray matter structures with behavioral measures of motor and cognitive abilities, in 132 healthy adults aged 40-83 years. Latent variables corresponding to manual dexterity and executive functions were obtained using factor analysis. The factor scores for manual dexterity declined significantly with increasing age. Independent of gender, age, and global cognitive function, increasing magnetic susceptibility in the globus pallidus and red nuclei was associated with decreasing manual dexterity. This finding suggests the potential value of magnetic susceptibility, a non-invasive quantitative imaging marker of iron, for the study of iron-related brain function changes.

Functional brain connectivity and cognition: effects of adult age and task demands

Previous neuroimaging research has documented that patterns of intrinsic (resting state) functional connectivity (FC) among brain regions covary with individual measures of cognitive performance. Here, we examined the relation between intrinsic FC and a reaction time (RT) measure of performance, as a function of age group and task demands. We obtained filtered, event-related functional magnetic resonance imaging data, and RT measures of visual search performance, from 21 younger adults (19-29 years old) and 21 healthy, older adults (60-87 years old). Age-related decline occurred in the connectivity strength in multiple brain regions, consistent with previous findings. Among 8 pairs of regions, across somatomotor, orbitofrontal, and subcortical networks, increasing FC was associated with faster responding (lower RT). Relative to younger adults, older adults exhibited a lower strength of this RT-connectivity relation and greater disruption of this relation by a salient but irrelevant display item (color singleton distractor). Age-related differences in the covariation of intrinsic FC and cognitive performance vary as a function of task demands.

Hippocampal and Insular Response to Smoking-Related Environments: Neuroimaging Evidence for Drug-Context Effects in Nicotine Dependence

Environments associated with prior drug use provoke craving and drug taking, and set the stage for lapse/relapse. Although the neurobehavioral bases of environment-induced drug taking have been investigated with animal models, the influence of drug–environments on brain function and behavior in clinical populations of substance users is largely unexplored. Adult smokers (n=40) photographed locations personally associated with smoking (personal smoking environments; PSEs) or personal nonsmoking environment (PNEs). Following 24-h abstinence, participants underwent fMRI scanning while viewing PSEs, PNEs, standard smoking and nonsmoking environments, as well as proximal smoking (eg, lit cigarette) and nonsmoking (eg, pencil) cues. Finally, in two separate sessions following 6-h abstinence they viewed either PSEs or PNEs while cue-induced self-reported craving and smoking behavior were assessed. Viewing PSEs increased blood oxygen level-dependent signal in right posterior hippocampus (pHPC; F2,685=3.74, p<0.024) and bilateral insula (left: F2,685=6.87, p=0.0011; right: F2,685=5.34, p=0.005). In the laboratory, viewing PSEs, compared with PNEs, was associated with higher craving levels (F2,180=18.32, p<0.0001) and greater ad lib smoking (F1,36=5.01, p=0.032). The effect of PSEs (minus PNEs) on brain activation in right insula was positively correlated with the effect of PSEs (minus PNEs) on number of puffs taken from a cigarette (r=0.6, p=0.001). Our data, for the first time in humans, elucidates the neural mechanisms that mediate the effects of real-world drug-associated environments on drug taking behavior under conditions of drug abstinence. These findings establish targets for the development and evaluation of treatments seeking to reduce environment provoked relapse.

Effect of Repetitive Transcranial Magnetic Stimulation on fMRI Resting-State Connectivity in Multiple System Atrophy

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique that has been used to treat neurological and psychiatric conditions. Although results of rTMS intervention are promising, so far, little is known about the rTMS effect on brain functional networks in clinical populations. In this study, we used a whole-brain connectivity analysis of resting-state functional magnetic resonance imaging data to uncover changes in functional connectivity following rTMS intervention and their association with motor symptoms in patients with multiple system atrophy (MSA). Patients were randomized to active rTMS or sham rTMS groups and completed a 10-session 5-Hz rTMS treatment over the left primary motor area. The results showed significant rTMS-related changes in motor symptoms and functional connectivity. Specifically, (1) significant improvement of motor symptoms was observed in the active rTMS group, but not in the sham rTMS group; and (2) several functional links involving the default mode, cerebellar, and limbic networks exhibited positive changes in functional connectivity in the active rTMS group. Moreover, the positive changes in functional connectivity were associated with improvement in motor symptoms for the active rTMS group. The present findings suggest that rTMS may improve motor symptoms by modulating functional links connecting to the default mode, cerebellar, and limbic networks, inferring a future therapeutic candidate for patients with MSA.

Age mediation of frontoparietal activation during visual feature search.

Activation of frontal and parietal brain regions is associated with attentional control during visual search. We used fMRI to characterize age-related differences in frontoparietal activation in a highly efficient feature search task, detection of a shape singleton. On half of the trials, a salient distractor (a color singleton) was present in the display. The hypothesis was that frontoparietal activation mediated the relation between age and attentional capture by the salient distractor. Participants were healthy, community-dwelling individuals, 21 younger adults (19-29 years of age) and 21 older adults (60-87 years of age). Top-down attention, in the form of target predictability, was associated with an improvement in search performance that was comparable for younger and older adults. The increase in search reaction time (RT) associated with the salient distractor (attentional capture), standardized to correct for generalized age-related slowing, was greater for older adults than for younger adults. On trials with a color singleton distractor, search RT increased as a function of increasing activation in frontal regions, for both age groups combined, suggesting increased task difficulty. Mediational analyses disconfirmed the hypothesized model, in which frontal activation mediated the age-related increase in attentional capture, but supported an alternative model in which age was a mediator of the relation between frontal activation and capture.

Effects of Virtual Reality Immersion and Walking Speed on Coordination of Arm and Leg Movements

The present study focused on the impact of immersive virtual reality (VR) technology on the coordination dynamics of walking, because of VR-induced symptoms and effects (e.g., motion sickness, postural instability, and disorientation) reported in the literature. Subjects were instructed to walk on a treadmill in a virtual and a real environment, while walking speeds were systematically varied. The virtual laboratory environment closely resembled the real laboratory environment. A third experimental condition was included controlling for the restricted view of a head mounted display (HMD) of the VR system. Movement of arms and legs were recorded with an Optotrak system. The main finding was that, for all speed conditions, there was an increased stride frequency in the VR environment compared to the other conditions. At the lower walking speeds, this coincided with a stronger locking of the arm movements on the stride frequency, and an increased mean relative phase between left arm and right arm movements as well as between ipsilateral arm and leg movements. No significant differences in the stability of the walking patterns were observed. Most importantly though, the impact of VR immersion was not large, was primarily limited to the lower walking velocity range, and could be further reduced by correcting for the effects of increased stride frequency by applying dimensionless analysis. The restricted view of the HMD did not significantly influence walking coordination. On the basis of these findings, it is concluded that immersive VR is a suitable tool to investigate perception-action coupling during walking, allowing for a systematic manipulation of optic flow parameters.