Perceived Stress, Cortical GABA, and Functional Connectivity Correlates: A Hypothesis-Generating Preliminary Study

Association between function and structure of the triple network and catechol-O-methyltransferase val158met polymorphism in the first episode schizophrenia

Auditory cortex hyperconnectivity before rTMS is correlated with tinnitus improvement

Dysfunctional resting state network connectivity predicts postoperative delirium after major surgery.

Network-specific effects of age and in-scanner subject motion: A resting-state fMRI study of 238 healthy adults

Considerable efforts have been dedicated to developing effective treatments for post-stroke executive impairment (PSEI), among which repetitive transcranial magnetic stimulation (rTMS) has shown great potential. This study aimed to investigate the therapeutic effects of high-frequency rTMS on working memory (WM) and response inhibition (RI) of executive functions in PSEI patients and the potential neural mechanisms. In a randomized, double-blind trial, 10 Hz rTMS was applied to the left dorsolateral prefrontal cortex (DLPFC) in 32 PSEI patients for 10 days, who were divided into real and sham rTMS groups. The Stroop color-word test (SCWT), digit span test (DST), and functional near-infrared spectroscopy (fNIRS) were used for assessment before and after the intervention. Resting-state functional connectivity (rsFC) and graph theory methods were used to analyze changes in brain function. Compared to the sham rTMS group, the real rTMS group showed significant reductions in SCWT response time (F = 4.223, p = 0.049) and improvements in DST forward scores (F = 4.739, p = 0.037) after the intervention. Moreover, the real rTMS group demonstrated significant enhancements in rsFC from left DLPFC to the right DLPFC (F = 8.538, p = 0.007) and the right posterior parietal cortex (F = 9.905, p = 0.004), as well as in the Degree Centrality of the left DLPFC (F = 7.144, p = 0.012), which were respectively significantly correlated with reduced SCWT response time and increased DST forward scores. High-frequency rTMS effectively improves WM and RI performance in patients with PSEI, which may be attributed to the remodeling of specific connectivity patterns and enhancement of local communication efficiency within the frontoparietal network.

Dual Function of Primary Somatosensory Cortex in Cognitive Control of Language: Evidence from Resting State fMRI

P.2.049 - Fronto-parietal connectivity and its relation to frontal glutamate in patients suffering from schizophrenia

The therapeutic mechanism of repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD) may involve modulation of γ-aminobutyric acid (GABA) levels. We used proton magnetic resonance spectroscopy (MRS) to assess changes in GABA levels at the site of rTMS in the left dorsolateral prefrontal cortex (DLPFC). In 26 adults with TRD, we used Mescher–Garwood point-resolved spectroscopy (MEGA-PRESS) spectral-editing MRS to measure GABA in the left DLPFC before and after standard clinical treatment with rTMS. All participants but 1 were medicated, including 12 patients on GABA agonist agents. Mean GABA in the DLPFC increased 10.0% (p = 0.017) post-rTMS in the overall sample. As well, GABA increased significantly in rTMS responders (n = 12; 23.6%, p = 0.015) but not in nonresponders (n = 14; 4.1%, p = not significant). Changes in GABA were not significantly affected by GABAergic agonists, but clinical response was less frequent (p = 0.005) and weaker (p = 0.035) in the 12 participants who were receiving GABA agonists concomitant with rTMS treatment. This study had an open-label design in a population receiving naturalistic treatment. Treatment using rTMS was associated with increases in GABA levels at the stimulation site in the left DLPFC, and the degree of GABA change was related to clinical improvement. Participants receiving concomitant treatment with a GABA agonist were less likely to respond to rTMS. These findings were consistent with earlier studies showing the effects of rTMS on GABA levels and support a GABAergic model of depression.

Converging neuroimaging and patient data suggest that the dorsolateral prefrontal cortex (DLPFC) is involved in emotional processing. However, it is still not clear whether the DLPFC in the left and right hemisphere is differentially involved in emotion recognition depending on the emotion considered. Here we used transcranial magnetic stimulation (TMS) to shed light on the possible causal role of the left and right DLPFC in encoding valence of positive and negative emotional facial expressions. Participants were required to indicate whether a series of faces displayed a positive or negative expression, while TMS was delivered over the right DLPFC, the left DLPFC, and a control site (vertex). Interfering with activity in both the left and right DLPFC delayed valence categorization (compared to control stimulation) to a similar extent irrespective of emotion type. Overall, we failed to demonstrate any valence-related lateralization in the DLPFC by using TMS. Possible methodological limitations are discussed.

Association between resting-state functional connectivity and empathizing/systemizing

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 per day, 6 days per week) of enriched rehabilitation (ER) or conventional rehabilitation (CR). In addition, 20 age-matched healthy volunteers were enrolled as a control (HC) group. We assessed 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 (SMT), 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).

目的 探讨精神分裂症患者脑静息态默认网络、中心执行网络及突显网络的网络内及网络间的功能连接特点.方法 对74例精神分裂症患者(患者组)和79名相匹配的健康者(对照组)进行静息态fMRI扫描.采取功能连接分析方法,以内侧前额叶皮质及右侧前岛叶为感兴趣区域分别提取默认网络、中心执行网络及突显网络,分析3个网络内及网络间静息态功能连接情况;并对有差异的功能连接与精神症状及病程等进行偏相关分析.结果 与对照组相比,患者组内侧前额叶皮质与双侧背外侧前额叶皮质(左侧-0.02±0.18与-0.12±0.12,t=4.25,P＜0.01;右侧-0.02±0.11与-0.10±0.10,t=5.40,P＜0.01)、双侧豆状壳核(左侧0.14±0.12与0.04±0.10,t=5.03,P＜0.01;右侧0.13±0.11与0.03±0.98,t=4.96,P＜0.01)的功能连接增强;右侧前岛叶与左侧额中回(-0.05±0.17与-0.07±0.17,t=4.60,P＜0.01)及楔前叶/后扣带回(0.01±0.13与-0.09±0.14,t=4.01,P＜0.01)的功能连接增强(均采用高斯随机场理论校正,体素水平P＜0.01,簇水平P＜0.05);默认网络与中心执行网络、突显网络间的负向功能连接减小甚至消失(Bonferroni校正P＜0.05).患者组PANSS阳性症状分与右侧前岛叶与楔前叶/后扣带回皮质间的功能连接呈正相关(r=0.232,P=0.025);患者组病程与右侧前岛叶与左侧额中回(r=0.288,P=0.007)、楔前叶/后扣带回(r=0.196,P=0.049)间的功能连接呈正相关.结论 精神分裂症患者存在静息态默认网络、中心执行网络及突显网络3个网络间的连接异常,可能与精神分裂症的病理机制有关.

Previously, transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) has resulted in improved performance in simple motor tasks. For a complex bimanual movement, studies using functional magnetic resonance imaging and transcranial magnetic stimulation indicated the involvement of the left dorsolateral prefrontal cortex (DLPFC) as well as left M1. Here we investigated the relative effect of up-regulating the cortical function in left DLPFC and left M1 with tDCS. Participants practised a complex bimanual task over four days while receiving either of five stimulation protocols: anodal tDCS applied over M1, anodal tDCS over DLPFC, sham tDCS over M1, sham tDCS over DLPFC, or no stimulation. Performance was measured at the start and end of each training day to make a distinction between acquisition and consolidation. Although task performance improved over days, no significant difference between stimulation protocols was observed, suggesting that anodal tDCS had little effect on learning the bimanual task regardless of the stimulation sites and learning phase (acquisition or consolidation). Interestingly, cognitive performance as well as corticomotor excitability did not change following stimulation. Accordingly, we found no evidence for behavioural or neurophysiological changes following tDCS over left M1 or left DLPFC in learning a complex bimanual task.

Around one-third of people develop depression following ischaemic stroke, yet the underlying mechanisms are poorly understood. Post-stroke depression has been linked to frontal infarcts, mainly lesions in the left dorsolateral prefrontal cortex (DLPFC). But depression is a network disorder that cannot be fully characterised through lesion-symptom mapping. Researchers of depression in non-stroke populations have successfully tapped into the cognitive control network (CCN) using the bilateral DLPFC as a seed, and found that CCN resting-state connectivity is reduced in even mildly depressed subjects, compared to healthy controls. Hence, we aimed to investigate the association between post-stroke depressive features and the CCN resting-state connectivity in a stroke population. We analysed DLPFC resting-state connectivity in 64 stroke participants, 20 of whom showed depressive features assessed with the Patient Health Questionnaire (PHQ-9) at 3 months after stroke. We directly compared groups showing symptoms of depression with those who did not, and performed a regression with PHQ-9 scores in all participants, controlling for age, gender, lesion volume and stroke severity. Post-stroke depression was associated with lower connectivity between the left DLPFC and the right supramarginal gyrus (SMG) in both group and regression analyses. Neither the seed nor the results overlapped with stroke lesions. These findings confirm an important role of the left DLPFC in post-stroke depression, but now show that large-scale network disruptions following stroke associated with depressive features occur without lesions in the DLPFC.

Children born extremely preterm (EP; < 28 weeks of gestation) or extremely low birth weight (ELBW; < 1000 g) are at increased risk of working memory deficits compared with their term-born peers and may benefit from working memory training. This study aimed to determine whether Cogmed Working Memory Training®, compared with a placebo training program, was associated with changes in resting-state functional connectivity (rsfc) and whether these changes correlated with working memory performance in EP/ELBW children. Twenty-one 7-year-old EP/ELBW children were enrolled in a double-blinded randomized controlled trial and had magnetic resonance imaging (MRI) assessments (Cogmed, n = 12; placebo (a non-adaptive version of Cogmed), n = 9). Prior to training (baseline) and 2 weeks post-training, all children received a cognitive assessment, inclusive of immediate memory and working memory measures and an MRI. The Cogmed Improvement Index was used as a measure of improvement in trained activities in the Cogmed group. Resting-state functional MRI was used to measure training-related changes in intra- and inter-network rsfc. The networks assessed include the default mode network, the left and right central executive networks, the bilateral executive network, the dorsal attention network, and the salience network. rsfc data were compared between treatment groups and investigated in relation to changes in working memory performance. There was little evidence of differences in intra- or inter-network rsfc strength changes from baseline to post-training between treatment groups. In the Cogmed group, working memory performance was associated with increased rsfc from baseline to post-training within the precuneus network, but not in the placebo group. In the Cogmed group, results that did not survive multiple comparison correction further showed that improvement in trained activities was associated with increased rsfc between the left central and bilateral executive networks, and with decreased rsfc within the right central executive network and between the right central executive and salience networks. Changes in rsfc may facilitate working memory performance following Cogmed training. Further studies are needed to investigate how changes in rsfc are associated with behavioral changes to better support working memory in vulnerable groups.