Enriched Rehabilitation Improves Gait Disorder and Cognitive Function in Parkinson’s Disease: A Randomized Clinical Trial

Background: Studies on non-pharmacological strategies for improving gait performance and cognition in Parkinson’s disease (PD) are of great significance. We aimed to investigate the effect of and mechanism underlying enriched rehabilitation as a potentially effective strategy for improving gait performance and cognition in early-stage PD.Methods: Forty participants with early-stage PD were randomly assigned to receive 12 weeks (2 h/day, 6 days/week) of enriched rehabilitation (ER; n = 20; mean age, 66.14 ± 4.15 years; 45% men) or conventional rehabilitation (CR; n = 20; mean age 65.32 ± 4.23 years; 50% men). In addition, 20 age-matched healthy volunteers were enrolled as a control (HC) group. We assessed the general motor function using the Unified PD Rating Scale—Part III (UPDRS-III) and gait performance during single-task (ST) and dual-task (DT) conditions pre- and post-intervention. Cognitive function assessments included the Montreal Cognitive Assessment (MoCA), the Symbol Digit Modalities Test (SDMT), and the Trail Making Test (TMT), which were conducted pre- and post-intervention. We also investigated alteration in positive resting-state functional connectivity (RSFC) of the left dorsolateral prefrontal cortex (DLPFC) in participants with PD, mediated by ER, using functional magnetic resonance imaging (fMRI).Results: Compared with the HC group, PD participants in both ER and CR groups performed consistently poorer on cognitive and motor assessments. Significant improvements were observed in general motor function as assessed by the UPDRS-III in both ER and CR groups post-intervention. However, only the ER group showed improvements in gait parameters under ST and DT conditions post-intervention. Moreover, ER had a significant effect on cognition, which was reflected in increased MoCA, SDMT, and TMT scores post-intervention. MoCA, SDMT, and TMT scores were significantly different between ER and CR groups post-intervention. The RSFC analysis showed strengthened positive functional connectivity between the left DLPFC and other brain areas including the left insula and left inferior frontal gyrus (LIFG) post-ER.Conclusion: Our findings indicated that ER could serve as a potentially effective therapy for early-stage PD for improving gait performance and cognitive function. The underlying mechanism based on fMRI involved strengthened RSFC between the left DLPFC and other brain areas (e.g., the left insula and LIFG).

Abnormal resting-state brain activity and connectivity of brain-bladder control network in overactive bladder syndrome

Background Neuroimaging studies have shown that the brain is involved in the mechanism of overactive bladder disease (OAB). Purpose To explorer spatial patterns of spontaneous neural activities and functional integration in patients with OAB. Material and Methods In total, 28 patients with OAB and 28 matched healthy controls (HC) underwent resting-state functional magnetic resonance imaging and completed questionnaires to assess clinical symptoms. The amplitude of low-frequency fluctuation (ALFF) and ROI-based functional connectivity (FC) within the brain-bladder control network (BBCN) were calculated and compared between the two groups using a two-sample t-test. Pearson correlation analysis was performed to investigate the relationship between ALFF and the clinical score of patients with OAB. Results Compared with HCs, patients with OAB exhibited significantly decreased ALFF in the left superior medial middle gyrus (SFGmed) and superior dorsal frontal gyrus (SFGdor), and increased ALFF in the right hippocampus. Furthermore, ALFF values in the left SFGmed were negatively correlated with OABSS scores. FC in patients with OAB was significantly increased between the bilateral caudate nucleus (CAU) and bilateral SFGdor, the bilateral CAU and bilateral supplementary motor area (SMA), the bilateral thalamus and SMA; the left CAU and bilateral SFGmed, the left CAU and bilateral anterior cingulate gyrus, and the left CAU and left insula. Additionally, decreased FC was found between the bilateral amygdala and bilateral SFGmed and the left SMA and left insula. Conclusion These abnormal activities and connectivities of BBCN may indicate impaired cortical control of micturition in OAB, suggesting a possible neural mechanism of OAB.

Structural and Functional Abnormalities in Knee Osteoarthritis Pain Revealed With Multimodal Magnetic Resonance Imaging

The knee osteoarthritis (KOA) pain is the most common form of arthritis pain affecting millions of people worldwide. Long-term KOA pain causes motor impairment and affects affective and cognitive functions. However, little is known about the structural and functional abnormalities induced by long-term KOA pain. In this work, high-resolution structural magnetic resonance imaging (sMRI) and resting-state functional MRI (rs-fMRI) data were acquired in patients with KOA and age-, sex-matched healthy controls (HC). Gray matter volume (GMV) and fractional amplitude of low-frequency fluctuation (fALFF) were used to study the structural and functional abnormalities in patients with KOA. Compared with HC, patients with KOA showed reduced GMV in bilateral insula and bilateral hippocampus, and reduced fALFF in left cerebellum, precentral gyrus, and the right superior occipital gyrus. Patients with KOA also showed increased fALFF in left insula and bilateral hippocampus. In addition, the abnormal GMV in left insula and fALFF in left fusiform were closely correlated with the pain severity or disease duration. These results indicated that long KOA pain leads to brain structural and functional impairments in motor, visual, cognitive, and affective functions that related to brain areas. Our findings may facilitate to understand the neural basis of KOA pain and the future therapy to relieve disease symptoms.

A review of functional and structural neuroimaging studies to investigate the inner speech model of auditory verbal hallucinations in schizophrenia

Although the pathophysiology of auditory verbal hallucinations remains uncertain, the inner speech model remains a prominent theory. A systematic review and meta-analyses of both functional and structural neuroimaging studies were performed to investigate the inner speech model. Of the 417 papers retrieved, 26 met the inclusion criteria. Meta-analyses found the left insula to be significantly active during auditory verbal hallucinations and to have a significantly reduced grey matter volume in hallucinators. Dysfunction of the left insula may contribute to the misattribution of inner speech due to its suggested roles in both inner speech production and the salience network. No significant activity was found at Broca’s area or Heschl’s gyrus during auditory verbal hallucinations. Furthermore, no structural abnormalities were found at these sites or in the arcuate fasciculi. Overall, evidence was found to both support and oppose the inner speech model. Further research should particularly include a systematic review of task-based trait studies with a focus on inner speech production and self-referential processing, and analyses of additional language-related white matter tracts.

Distinct neurostructural signatures of anxiety-, fear-related and depressive disorders: a comparative voxel-based meta-analysis

Internalizing disorders encompass anxiety, fear and depressive disorders. While the DSM-5 nosology conceptualizes anxiety and fear-related disorders as an entity, dimensional psychopathology models suggest that generalized anxiety disorders (GAD) and major depression originate from an overarching "anxious-misery" factor whereas fear-related disorders originate from the "fear" factor. Given that a neurobiological evaluation is lacking, we conducted a comparative neuroimaging meta-analysis of gray matter volume alterations to determine common and disorder-specific brain structural signatures in these disorders. The PubMed, Web of Knowledge, and Scopus databases were searched for case-control voxel-based morphometric studies through December, 2020 in GAD, fear-related anxiety disorders (FAD, i.e., social anxiety disorders, SAD; specific phobias, SP; panic disorders, PD; and agoraphobia, AG) and major depressive disorder (MDD). Neurostructural abnormalities were assessed within each disorder group followed by quantitative comparison and conjunction analyses using Seed-based d-Mapping (SDM-PSI). GAD (9 studies, 226 patients) showed disorder-specific decreased volumes in left insula (z=-2.98, pFWE-corrected <0.05) and lateral/medial prefrontal cortex (z=-2.10, pFWE-corrected<0.05,) as well as increased right putamen volume (z=1.86, pFWE-corrected<0.05) relative to FAD (10 SAD, 11 PD, 2 SP studies, 918 patients). Both GAD and MDD (46 studies, 2,575 patients) exhibited decreased prefrontal volumes compared to controls and FAD. While FAD showed less robust alterations in lingual gyrus (p < 0.0025, uncorrected), this group presented intact frontal integrity. No shared structural abnormalities were found. Unique clinical features characterizing anxiety-, fear-related and depressive disorders are reflected by disorder-specific neuroanatomical abnormalities. Targeting the disorder-specific neurostructural signatures could improve therapeutic efficacy.

The Self and Its Right Insula—Differential Topography and Dynamic of Right vs. Left Insula

Various studies demonstrate a special role of the right compared to the left anterior insula in mediating our self. However, the neural features of the right insula that allow for its special role remain unclear. Presupposing a spatiotemporal model of self—“Basis model of self-specificity” (BMSS)—we here address the following question: what spatial-topographic and temporal-dynamic features render neural activity in the right insula to be more suitable in mediating self-specificity than the left insula? First, applying fMRI, we demonstrate that the right insula (i) exhibits higher degrees of centrality in rest, and (ii) higher context-dependent functional connectivity in a self-specific task among regions of distinct layers of self (intero-, extero-proprioceptive, and mental). Second, using EEG in rest and task, we show that the right insula shows longer autocorrelation window (ACW) in its neural activity than both left insula and other regions of the different layers of self. Together, we demonstrate special topographic, i.e., high functional connectivity, and dynamic, i.e., long ACW, neural features of the right insula compared to both left insula and other regions of the distinct layers of self. This suits neural activity in the right insula ideally for high functional integration and temporal continuity as key features of the self including its intero-, extero-proprioceptive, and mental layers.

Different cerebral functional segregation in Sjogren’s syndrome with or without systemic lupus erythematosus revealed by amplitude of low-frequency fluctuation

Background Sjögren’s syndrome (SjS) associated with systemic lupus erythematosus (SjS-SLE) was considered a standalone but often-overlooked entity. Purpose To assess altered spontaneous brain activity in SjS-SLE and SjS using amplitude of low-frequency fluctuation (ALFF). Material and Methods Sixteen patients with SjS-SLE, 17 patients with SjS, and 17 matched controls underwent neuropsychological tests and subsequent resting-state functional magnetic resonance imaging (fMRI) examinations. The ALFF value was calculated based on blood oxygen level dependent (BOLD) fMRI. Statistical parametric mapping was utilized to analyze between-group differences and multiple comparison was corrected with Analysis of Functional NeuroImages 3dClustSim. Then, the ALFFs of brain regions with significant differences among the three groups were correlated to corresponding clinical and neuropsychological variables by Pearson correlation. Results ALFF differences in the bilateral precuneus/posterior cingulate cortex (PCC), right parahippocampal gyrus/caudate/insula, and left insula were found among the three groups. Both SjS-SLE and SjS displayed decreased ALFF in the right parahippocampal gyrus, right insula, and left insula than HC. Moreover, SjS-SLE showed wider decreased ALFF in the bilateral precuneus and right caudate, while the SjS group exhibited increased ALFF in the bilateral PCC. Additionally, patients with SjS-SLE exhibited lower ALFF values in the bilateral PCC and precuneus than SjS. Moreover, ALFF values in the right parahippocampal gyrus and PCC were negatively correlated to fatigue score and disease duration, respectively, in SjS-SLE. Conclusion SjS-SLE and SjS exhibited common and different alteration of cerebral functional segregation revealed by AlFF analysis. This result appeared to indicate that SjS-SLE might be different from SjS with a neuroimaging standpoint.

Reduced Brain Gray Matter Volume in Patients With First-Episode Major Depressive Disorder: A Quantitative Meta-Analysis

Background: The findings of many neuroimaging studies in patients with first-episode major depressive disorder (MDD), and even those of previous meta-analysis, are divergent. To quantitatively integrate these studies, we performed a meta-analysis of gray matter volumes using voxel-based morphometry (VBM).Methods: We performed a comprehensive literature search for relevant studies and traced the references up to May 1, 2021 to select the VBM studies between first-episode MDD and healthy controls (HC). A quantitative meta-analysis of VBM studies on first-episode MDD was performed using the Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) method, which allows a familywise error rate (FWE) correction for multiple comparisons of the results. Meta-regression was used to explore the effects of demographics and clinical characteristics.Results: Nineteen studies, with 22 datasets comprising 619 first-episode MDD and 707 HC, were included. The pooled and subgroup meta-analysis showed robust gray matter reductions in the left insula, the bilateral parahippocampal gyrus extending into the bilateral hippocampus, the right gyrus rectus extending into the right striatum, the right superior frontal gyrus (dorsolateral part), the left superior frontal gyrus (medial part) and the left superior parietal gyrus. Meta-regression analyses showed that higher HDRS scores were significantly more likely to present reduced gray matter volumes in the right amygdala, and the mean age of MDD patients in each study was negatively correlated with reduced gray matter in the left insula.Conclusions: The present meta-analysis revealed that structural abnormalities in the fronto-striatal-limbic and fronto-parietal networks are essential characteristics in first-episode MDD patients, which may become a potential target for clinical intervention.

Left Anterior Insular Lesions Result in Impaired Recognition of Facial Expressions of Negative Emotions

Single case studies about patients with unilateral insular lesions reported deficits in emotion recognition from facial expressions. However, there is no consensus about both the actual extent of impairments and the role of lesion lateralization. To investigate associations of brain lesions and impairments in a facial emotion recognition task, we used voxel-based lesion-symptom mapping (VLSM) in a group of 29 stroke patients in the chronic stage, 16 with left and 13 with right hemispheric lesion. Recognition accuracy was impaired for fearful and angry expressions in patients with left hemispheric lesions compared to 14 matched healthy controls. VLSM analyses revealed that lesions centered around the left insula were associated with impaired recognition of emotional facial expressions. We here demonstrate a critical role for the left insula in decoding unpleasant emotions from facial expressions and therefore present further evidence for a broader role for the insular cortex not restricted to disgust processing.