A Multi-sequence MRI Study in Parkinson's Disease: Association Between Rigidity and Myelin.

BACKGROUND: The pathophysiology of rigidity in Parkinson's disease (PD) is poorly understood. Multi-sequence functional and structural brain MRI may further clarify the origin of this clinical characteristic. PURPOSE: To examine both joint and unique relationships of MRI-based functional and structural imaging modalities to rigidity and other clinical features of PD. STUDY TYPE: Retrospective cross-sectional study. POPULATION: 31 PD subjects (aged 68.0 ± 5.9 years, 21 males) with average disease duration 9.3 ± 5.4 years. FIELD STRENGTH/SEQUENCE: Multi-echo GRASE, diffusion-weighted echo planar imaging (EPI), and blood oxygen level dependent contrast EPI T2*-weighted sequences on a 3T scanner. ASSESSMENT: Myelin water fraction (MWF) and fractional anisotropy (FA) of 20 white-matter regions of interest (ROIs), and functional connectivity derived from resting-state fMRI among 56 ROIs were assessed. The Unified Parkinson's Disease Rating Scale-Part III, Montreal Cognitive Assessment, Beck Depression Index, and Apathy Rating Scales were used to assess motor and non-motor symptoms. STATISTICAL TESTS: Multiset canonical correlation analysis (MCCA) and canonical correlation analysis (CCA) were utilized to examine the joint and unique relationships of multiple imaging measures with clinical symptoms of PD. A permutation test was used to determine statistical significance (P < 0.05). RESULTS: MCCA revealed a single significant component jointly linking MWF, FA, and functional connectivity to age, bradykinesia, and leg agility, non-motor symptoms of cognition, depression, and apathy, but not rigidity (P = 0.77), tremor (P = 0.50 and 0.67 on the left and right side), or sex (P = 0.54). After controlling for this joint component, CCA found a unique significant association between MWF and rigidity, but no other associations were detected, including with FA (P = 0.87). DATA CONCLUSION: MWF, FA, and functional connectivity can serve as multi-sequence imaging markers to characterize many PD symptoms. However, rigidity in PD is additionally associated with widespread myelin changes. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 3.

White matter myelin profiles linked to clinical subtypes of Parkinson's disease.

BACKGROUND: White matter (WM) microstructural integrity is important for effective brain functioning and alterations have been shown in many neurodegenerative diseases. PURPOSE: To investigate WM myelin profiles and their relation to clinical features of Parkinson's disease (PD). STUDY TYPE: Retrospective cross-sectional. POPULATION: In all, 29 PD subjects and 15 healthy controls. FIELD STRENGTH/SEQUENCE: Multiecho GRASE with 10 msec echo spacing and echo planar imaging (EPI) diffusion-weighted (b-value = 700 with 32 gradient directions) on a 3T scanner. ASSESSMENT: Myelin water fraction (MWF) and fractional anisotropy (FA) across 20 WM regions of interest (ROIs) were compared between groups. Partial least squares (PLS) was used to associate MWF and FA with clinical and behavioral measures. STATISTICAL TESTS: Group comparisons were done using two-sample t-tests. PLS was assessed with permutation tests. Bootstrapping was used to investigate the robustness of imaging features. RESULTS: No group differences in myelin content could be detected with univariate tests. A three-component PLS model linked MWF profiles to clinical phenotypes but no FA profiles. The three components appeared to follow along broad motor/nonmotor subtypes of "akinetic-rigid," "tremor-predominant," and "depression/apathy" subtypes, respectively. The first component showed associations between overall motor scores (r = -0.43, P = 0.0196) and cognitive performance (r = 0.44, P = 0.0171) with interhemispheric and long-range association fibers. A second component linked overall motor scores (r = -0.58, P = 0.0009) and tremor scores (r = -0.48, P = 0.0091) to predominantly projection fibers. The last component related depression (r = -0.60, P = 0.0006) and apathy scores (r = -0.66, P = 0.0001 and r = -49, P = 0.0072) to a mixture of association and projection fibers. DATA CONCLUSION: MWF was robustly linked to distinct clinical subtypes of PD and may serve as an additional tool to characterize the disease. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:164-174.

The brain frequency tuning function for facial emotion discrimination: An ssVEP study.

Steady-state visual evoked potentials have only been applied recently to the study of face perception. We used this method to study the spatial and temporal dynamics of expression perception in the human brain and test the prediction that, as in the case of identity perception, the optimal frequency for facial expression would also be in the range of 5-6 Hz. We presented facial expressions at different flickering frequencies (2-8 Hz) to human observers while recording their brain electrical activity. Our modified adaptation paradigm contrasted blocks with varying expressions versus blocks with a constant neutral expression, while facial identity was kept constant. The presentation of different expressions created a larger steady-state response only at 5 Hz, corresponding to a cycle of 200 ms, over right occipito-temporal electrodes. Source localization using a time-domain analysis showed that the effect localized to the right occipito-temporal cortex, including the superior temporal sulcus and fusiform gyrus.

Interactions between the perception of age and ethnicity in faces: an event-related potential study.

Face perception models propose that different facial attributes are processed by anatomically distinct neural pathways that partially overlap. Whether these attributes interact functionally is an open question. Our goal was to determine if there are interactions between age and ethnicity processing and, if so, at what temporal epoch these interactions are evident. We monitored event-related potentials on electroencephalography while subjects categorized faces by age or ethnicity in two conditions: a baseline in which the other of these two properties not being categorized was held constant and an interference condition in which it also varied, as modelled after the Garner interference paradigm. We found that, when participants were categorizing faces by age, variations in ethnicity increased the amplitude of the right face-selective N170 component. When subjects were categorizing faces by ethnicity, variations in age did not alter the N170. We concluded that there is an asymmetric pattern of influence between age and ethnicity on early face-specific stages of visual processing, which has parallels with behavioural evidence of asymmetric interactions between identity and expression processing of faces.

Apathy scores in Parkinson's disease relate to EEG components in an incentivized motor task.

Apathy is one of the most prevalent non-motor symptoms of Parkinson's disease and is characterized by decreased goal-directed behaviour due to a lack of motivation and/or impaired emotional reactivity. Despite its high prevalence, the neurophysiological mechanisms underlying apathy in Parkinson's disease, which may guide neuromodulation interventions, are poorly understood. Here, we investigated the neural oscillatory characteristics of apathy in Parkinson's disease using EEG data recorded during an incentivized motor task. Thirteen Parkinson's disease patients with apathy and 13 Parkinson's disease patients without apathy as well as 12 healthy controls were instructed to squeeze a hand grip device to earn a monetary reward proportional to the grip force they used. Event-related spectral perturbations during the presentation of a reward cue and squeezing were analysed using multiset canonical correlation analysis to detect different orthogonal components of temporally consistent event-related spectral perturbations across trials and participants. The first component, predominantly located over parietal regions, demonstrated suppression of low-beta (12-20 Hz) power (i.e. beta desynchronization) during reward cue presentation that was significantly smaller in Parkinson's disease patients with apathy compared with healthy controls. Unlike traditional event-related spectral perturbation analysis, the beta desynchronization in this component was significantly correlated with clinical apathy scores. Higher monetary rewards resulted in larger beta desynchronization in healthy controls but not Parkinson's disease patients. The second component contained gamma and theta frequencies and demonstrated exaggerated theta (4-8 Hz) power in Parkinson's disease patients with apathy during the reward cue and squeezing compared with healthy controls (HCs), and this was positively correlated with Montreal Cognitive Assessment scores. The third component, over central regions, demonstrated significantly different beta power across groups, with apathetic groups having the lowest beta power. Our results emphasize that altered low-beta and low-theta oscillations are critical for reward processing and motor planning in Parkinson's disease patients with apathy and these may provide a target for non-invasive neuromodulation.

Sex, myelin, and clinical characteristics of Parkinson's disease.

Objective: To determine if there are sex differences in myelin in Parkinson's disease, and whether these explain some of the previously-described sex differences in clinical presentation. Methods: Thirty-three subjects (23 males, 10 females) with Parkinson's disease underwent myelin water fraction (MWF) imaging, an MRI scanning technique of in vivo myelin content. MWF of 20 white matter regions of interest (ROIs) were assessed. Motor symptoms were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS). Principal component analysis, logistic and multiple linear regressions, and t-tests were used to determine which white matter ROIs differed between sexes, the clinical features associated with these myelin changes, and if overall MWF and MWF laterality differed between males and females. Results: Consistent with prior reports, tremor and bradykinesia were more likely seen in females, whereas rigidity and axial symptoms were more likely seen in males in our cohort. MWF of the thalamic radiation, cingulum, cingulum hippocampus, inferior fronto-occipital fasciculi, inferior longitudinal fasciculi, and uncinate were significant in predicting sex. Overall MWF and asymmetry of MWF was greater in males. MWF differences between sexes were associated with tremor symptomatology and asymmetry of motor performance. Conclusion: Sex differences in myelin are associated with tremor and asymmetry of motor presentation. While preliminary, our results suggest that further investigation of the role of biological sex in myelin pathology and clinical presentation in Parkinson's disease is warranted.

The Efficacy of Measurement-Based Care for Depressive Disorders: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objective: To determine the efficacy of measurement-based care (MBC), defined as routinely administered outcome measures with practitioner and patient review to inform clinical decision-making, for adults with depressive disorders.Data Sources: Embase, MEDLINE, PsycINFO, ClinicalTrials.gov, CNKI, and Wanfang Data were searched through July 1, 2020, using search terms for measurement-based care, depression, antidepressant or pharmacotherapy, and randomized controlled trials (RCTs), without language restriction.Study Selection: Of 8,879 articles retrieved, 7 RCTs (2,019 participants) evaluating MBC for depressive disorders, all involving pharmacotherapy, were included.Data Extraction: Two independent reviewers extracted data. The primary outcome was response rate (≥ 50% improvement from baseline to endpoint on a depression scale). Secondary clinical outcomes were remission rate (endpoint score in remission range), difference in endpoint severity, and medication adherence.Results: Meta-analysis with random-effects models found no significant difference between MBC and comparison groups in response rates (3 studies; odds ratio [OR] = 1.66; 95% CI, 0.66-4.17; P = .279). MBC was associated with significantly greater remission rates (5 studies; OR = 1.83; 95% CI, 1.12-2.97; P = .015), lower endpoint severity (5 studies; standardized mean difference = 0.53; CI 0.06-0.99; P = .026), and greater medication adherence (3 studies; OR = 1.68; 95% CI, 1.22-2.30; P = .001).Conclusions: Although benefits for clinical response are unclear, MBC is effective in decreasing depression severity, promoting remission, and improving medication adherence in patients with depressive disorders treated with pharmacotherapy. The results are limited by the small number of included trials, high risk of bias, and significant study heterogeneity.

Galvanic Vestibular Stimulation Improves Subnetwork Interactions in Parkinson's Disease.

Background: Activating vestibular afferents via galvanic vestibular stimulation (GVS) has been recently shown to have a number of complex motor effects in Parkinson's disease (PD), but the basis of these improvements is unclear. The evaluation of network-level connectivity changes may provide us with greater insights into the mechanisms of GVS efficacy. Objective: To test the effects of different GVS stimuli on brain subnetwork interactions in both health control (HC) and PD groups using fMRI. Methods: FMRI data were collected for all participants at baseline (resting state) and under noisy, 1 Hz sinusoidal, and 70-200 Hz multisine GVS. All stimuli were given below sensory threshold, blinding subjects to stimulation. The subnetworks of 15 healthy controls and 27 PD subjects (on medication) were identified in their native space, and their subnetwork interactions were estimated by nonnegative canonical correlation analysis. We then determined if the inferred subnetwork interaction changes were affected by disease and stimulus type and if the stimulus-dependent GVS effects were influenced by demographic features. Results: At baseline, interactions with the visual-cerebellar network were significantly decreased in the PD group. Sinusoidal and multisine GVS improved (i.e., made values approaching those seen in HC) subnetwork interactions more effectively than noisy GVS stimuli overall. Worsening disease severity, apathy, depression, impaired cognitive function, and increasing age all limited the beneficial effects of GVS. Conclusions: Vestibular stimulation has widespread system-level brain influences and can improve subnetwork interactions in PD in a stimulus-dependent manner, with the magnitude of such effects associating with demographics and disease status.

Altered EEG alpha and theta oscillations characterize apathy in Parkinson's disease during incentivized movement.

Apathy is a common non-motor symptom of Parkinson's disease (PD) that is difficult to quantify and poorly understood. Some studies have used incentivized motor tasks to assess apathy, as the condition is often associated with a reduction in motivated behavior. Normally event-related desynchronization, a reduction of power in specific frequency bands, is observed in the motor cortex during the peri-movement period. Also, alpha (8-12 Hz) and theta (4-7 Hz) oscillations are sensitive to rewards that are closely related to motivational states however these oscillations have not been widely investigated in relation to apathy in PD. Using EEG recordings, we investigated the neural oscillatory characteristics of apathy in PD during an incentivized motor task with interleaved rest periods. Apathetic and non-apathetic PD subjects on dopaminergic medication and healthy control subjects were instructed to squeeze a hand grip device for a monetary reward proportional to the subject's grip force and the monetary value attributed to that trial. Apathetic PD subjects exhibited higher alpha and theta powers in the pre-trial baseline rest period compared to non-apathetic PD subjects and healthy subjects. Further, we found that both resting power and relative power in alpha and theta bands during incentivized movement predicted PD subjects' apathy scores. Our results suggest that apathetic PD patients may need to overcome greater baseline alpha and theta oscillatory activity in order to facilitate incentivized movement. Clinically, resting alpha and theta power as well as alpha and theta event-related desynchronization during movement may serve as potential neural markers for apathy severity in PD.