Association between resting-state functional connectivity and empathizing/systemizing

SummaryHumans show a remarkable ability to discriminate others' gaze direction, even though a given direction can be conveyed by many physically dissimilar configurations of different eye positions and head views. For example, eye contact can be signaled by a rightward glance in a left-turned head or by direct gaze in a front-facing head. Such acute gaze discrimination implies considerable perceptual invariance. Previous human research found that superior temporal sulcus (STS) responds preferentially to gaze shifts [1], but the underlying representation that supports such general responsiveness remains poorly understood. Using multivariate pattern analysis (MVPA) of human functional magnetic resonance imaging (fMRI) data, we tested whether STS contains a higher-order, head view-invariant code for gaze direction. The results revealed a finely graded gaze direction code in right anterior STS that was invariant to head view and physical image features. Further analyses revealed similar gaze effects in left anterior STS and precuneus. Our results suggest that anterior STS codes the direction of another's attention regardless of how this information is conveyed and demonstrate how high-level face areas carry out fine-grained, perceptually relevant discrimination through invariance to other face features.

Patients with schizophrenia exhibit impairments in working memory that often appear in attenuated form in persons at high risk for the illness. The authors hypothesized that deviations in task-related brain activation and deactivation would occur in persons with an at-risk mental state performing a working memory task that entailed the maintenance and manipulation of letters. Participants at ultra high risk for developing psychosis (N=60), identified using the Comprehensive Assessment of At-Risk Mental States, and healthy comparison subjects (N=38) 14 to 29 years of age underwent functional MRI while performing a verbal working memory task. Group differences in brain activation were identified using analysis of covariance. The two groups did not show significant differences in speed or accuracy of performance, even after accounting for differences in education. Irrespective of task condition, at-risk participants exhibited significantly less activation than healthy comparison subjects in the left anterior insula. During letter manipulation, at-risk persons exhibited greater task-related deactivation within the default-mode network than comparison subjects. Region-of-interest analysis in the at-risk group revealed significantly greater right dorsolateral prefrontal cortex activation during manipulation of letters. Despite comparable behavioral performance, at-risk participants performing a verbal working memory task exhibited altered brain activation compared with healthy subjects. These findings demonstrate an altered pattern of brain activation in at-risk persons that contains elements of reduced function as well as compensation.

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.

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

Stress exposures and dysregulated responses to stress are implicated in psychiatric disorders of mood, anxiety, and cognition. Perceived stress, an individual's appraisal of experienced stress and ability for coping, relates to dysregulated functioning in resting state brain networks. Alterations in GABAergic function may underlie perceived stress-related functional dysregulation in resting state networks but this has not yet been explored. Therefore, the current study examined the association of perceived stress, via the Perceived Stress Scale (PSS), with prefrontal GABA levels and corresponding resting state functional connectivity (RSFC) alterations. Twelve women and five men, ages 35–61, participated. MR spectroscopy was used to measure brain GABA levels in the anterior cingulate cortex (ACC), left dorsolateral prefrontal cortex (DLPFC), and ventromedial prefrontal cortex (VMPFC). Resting state functional scans acquired at 3 Tesla were used to measure RSFC within and between the default mode (DMN), salience (SN), and central executive networks (CEN), hippocampus and amygdala. We observed significant negative correlations between total PSS scores and left DLPFC GABA levels (r = −0.62, p = 0.023). However, PSS scores were not significantly correlated with RSFC measures (all p > 0.148). These preliminary results support a relationship between perceived stress and GABAergic functioning in DLPFC, a core node of the CEN, an intrinsic network thought to underlie goal-directed attentional processes. Our findings extend previous work suggesting that functioning in the CEN is related to perceived stress and may inform treatment strategies to improve outcomes in stress-related conditions.

Auditory cortex hyperconnectivity before rTMS is correlated with tinnitus improvement

ObjectiveWe aimed to study the neural processing of emotion-denoting words based on a circumplex model of affect, which posits that all emotions can be described as a linear combination of two neurophysiological dimensions, valence and arousal. Based on the circumplex model, we predicted a linear relationship between neural activity and incremental changes in these two affective dimensions.MethodsUsing functional magnetic resonance imaging, we assessed in 10 subjects the correlations of BOLD (blood oxygen level dependent) signal with ratings of valence and arousal during the presentation of emotion-denoting words.ResultsValence ratings correlated positively with neural activity in the left insular cortex and inversely with neural activity in the right dorsolateral prefrontal and precuneus cortices. The absolute value of valence ratings (reflecting the positive and negative extremes of valence) correlated positively with neural activity in the left dorsolateral and medial pre-frontal cortex (PFC), dorsal anterior cingulate cortex, posterior cingulate cortex, and right dorsal PFC, and inversely with neural activity in the left medial temporal cortex and right amygdala. Arousal ratings and neural activity correlated positively in the left parahippocampus and dorsal anterior cingulate cortex, and inversely in the left dorsolateral PFC and dorsal cerebellum.ConclusionWe found evidence for two neural networks subserving the affective dimensions of valence and arousal. These findings clarify inconsistencies from prior imaging studies of affect by suggesting that two underlying neurophysiological systems, valence and arousal, may subserve the processing of affective stimuli, consistent with the circumplex model of affect.

Background:The cannabinoid cannabinoid type 1 (CB1) neutral antagonist tetrahydrocannabivarin (THCv) has been suggested as a possible treatment for obesity, but without the depressogenic side-effects of inverse antagonists such as Rimonabant. However, how THCv might affect the resting state functional connectivity of the human brain is as yet unknown.Method:We examined the effects of a single 10mg oral dose of THCv and placebo in 20 healthy volunteers in a randomized, within-subject, double-blind design. Using resting state functional magnetic resonance imaging and seed-based connectivity analyses, we selected the amygdala, insula, orbitofrontal cortex, and dorsal medial prefrontal cortex (dmPFC) as regions of interest. Mood and subjective experience were also measured before and after drug administration using self-report scales.Results:Our results revealed, as expected, no significant differences in the subjective experience with a single dose of THCv. However, we found reduced resting state functional connectivity between the amygdala seed region and the default mode network and increased resting state functional connectivity between the amygdala seed region and the dorsal anterior cingulate cortex and between the dmPFC seed region and the inferior frontal gyrus/medial frontal gyrus. We also found a positive correlation under placebo for the amygdala-precuneus connectivity with the body mass index, although this correlation was not apparent under THCv.Conclusion:Our findings are the first to show that treatment with the CB1 neutral antagonist THCv decreases resting state functional connectivity in the default mode network and increases connectivity in the cognitive control network and dorsal visual stream network. This effect profile suggests possible therapeutic activity of THCv for obesity, where functional connectivity has been found to be altered in these regions.

Background/Objectives: Mild cognitive impairment (MCI) has been associated with risk for Alzheimer's Disease (AD). Previous investigations have suggested that vascular risk factors (VRFs) were associated with cognitive decline and AD pathogenesis, and the intervention of VRFs may be a possible way to prevent dementia. However, in MCI, little is known about the potential impacts of VRFs on neural networks and their neural substrates, which may be a neuroimaging biomarker of the disease progression.Methods: 128 elderly Han Chinese participants (67 MCI subjects and 61 matched normal elderly) with or without VRFs (hypertension, diabetes mellitus, hypercholesterolemia, smoking and alcohol drinking) underwent the resting-state functional magnetic resonance imaging (fMRI) and neuropsychological tests. We obtained the default mode network (DMN) to identify alterations in MCI with the varying number of the VRF and analyzed the significant correlation with behavioral performance.Results: The effects of VRF on the DMN were primarily in bilateral dorsolateral prefrontal cortex (DLPFC) (i.e., middle frontal gyrus). Normal elderly showed the gradually increased functional activity of DLPFC, while a fluctuant activation of DLPFC was displayed in MCI with the growing number of the VRF. Interestingly, the left DLPFC further displayed significantly dynamic correlation with executive function as the variation of VRF loading. Initial level of compensation was observed in normal aging and none-vascular risk factor (NVRF) MCI, while these compensatory neural processes were suppressed in One-VRF MCI and were subsequently re-aroused in Over-One-VRF MCI.Conclusions: These findings suggested that the dose-dependent effects of VRF on DLPFC were highlighted in MCI, and the dynamic compensatory neural processes that fluctuated along with variations of VRF loading could be key role in the progression of MCI.

Unprecedented 4D spatiotemporal infant regional cerebral blood flow framework and region-specific physiology–function coupling across infancy were elucidated, highlighting strong physiology–function coupling specifically at the default-mode network to meet extraneuronal metabolic demand for network emergence.

The resting-state cerebro-cerebellar function connectivity and associations with verbal working memory performance

Autism spectrum disorder (ASD) is a neurodevelopmental disorder usually presenting as reduced social interaction, lessened verbal communication, and repetitive behavior. Diagnosing autism spectrum disorder is extremely difficult because of its wide variety of symptoms, so it can only be diagnosed through behavioral tests and analysis of developmental history. Resting-state functional magnetic resonance imaging (rs-fMRI) can help researchers discover a neural substrate for autism spectrum disorder to diagnose it earlier. One prominent fMRI database for autism spectrum disorder research is the Autism Brain Imaging Data Exchange, a large-scale collection of anonymized functional MRI scans subdivided by age, gender, handedness, and scores on behavioral assessments. This analysis focused on two brain networks: the default mode network (DMN), which is active when minds wander, and the executive network, which is active during the performance of tasks. The medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), and angular gyrus are nodes of the default mode network, and the dorsolateral prefrontal cortex (DLPFC) is the main node in the executive network. Both networks are affected by autism spectrum disorder. This research used preprocessed resting-state fMRI data to establish neurocognitive phenotypes for autism spectrum disorder. Bivariate correlation was used to compare connectivity in the default mode network and dorsolateral prefrontal cortex between autism spectrum disorder fMRI scans and control fMRI scans, and these differences were analyzed for correlations with each patient’s assessment scores. After the Benjamini-Hochberg procedure was applied to reduce the false discovery rate, analysis of these metrics revealed that in autism spectrum disorder patients there was underconnectivity between the right posterior cingulate cortex and the right medial prefrontal cortex, while in control patients there was overconnectivity between the right angular gyrus and left dorsolateral prefrontal cortex. Autism spectrum disorder is extremely heritable, so phenotypic research is absolutely necessary for discovering more about the genetic causes of autism spectrum disorder, which will speed up autism spectrum disorder diagnosis and help researchers develop more targeted treatments for autism spectrum disorder.

The default mode network (DMN) is often considered a functionally homogeneous system that is broadly associated with internally directed cognition (e.g. episodic memory, theory of mind, self-evaluation). However, few studies have examined how this network interacts with other networks during putative “default” processes such as episodic memory retrieval. Using fMRI, we investigated the topography and response profile of human parietal regions inside and outside the DMN, independently defined using task-evoked deactivations and resting state functional connectivity, during episodic memory retrieval. Memory retrieval activated posterior nodes of the DMN, particularly the angular gyrus, but also more anterior and dorsal parietal regions that were anatomically separate from the DMN. The two sets of parietal regions showed different resting-state functional connectivity and response profiles. During memory retrieval, responses in DMN regions peaked sooner than non-DMN regions, which in turn showed responses that were sustained until a final memory judgment was reached. Moreover, a parahippocampal region that showed strong resting-state connectivity with parietal DMN regions also exhibited a pattern of task-evoked activity similar to that exhibited by DMN regions. These results suggest that DMN parietal regions directly supported memory retrieval, whereas non-DMN parietal regions were more involved in post-retrieval processes such as memory-based decision making. Finally, a robust functional dissociation within the DMN was observed. While angular gyrus and posterior cingulate/precuneus were significantly activated during memory retrieval, an anterior DMN node in medial prefrontal cortex was strongly deactivated. This latter finding demonstrates functional heterogeneity rather than homogeneity within the DMN during episodic memory retrieval.

Functional neuroimaging studies of epilepsy patients often show, at the time of epileptic activity, deactivation in default mode network (DMN) regions, which is hypothesized to reflect altered consciousness. We aimed to study the metabolic and electrophysiological correlates of these changes in the DMN regions. We studied six epilepsy patients that underwent scalp EEG-fMRI and later stereotaxic intracerebral EEG (SEEG) sampling regions of DMN (posterior cingulate cortex, Pre-cuneus, inferior parietal lobule, medial prefrontal cortex and dorsolateral frontal cortex) as well as non-DMN regions. SEEG recordings were subject to frequency analyses comparing sections with interictal epileptic discharges (IED) to IED-free baselines in the IED-generating region, DMN and non-DMN regions. EEG-fMRI and SEEG were obtained at rest. During IEDs, EEG-fMRI demonstrated deactivation in various DMN nodes in 5 of 6 patients, most frequently the pre-cuneus and inferior parietal lobule, and less frequently the other DMN nodes. SEEG analyses demonstrated decrease in gamma power (50–150 Hz), and increase in the power of lower frequencies (<30 Hz) at times of IEDs, in at least one DMN node in all patients. These changes were not apparent in the non-DMN regions. We demonstrate that, at the time of IEDs, DMN regions decrease their metabolic demand and undergo an EEG change consisting of decreased gamma and increased lower frequencies. These findings, specific to DMN regions, confirm in a pathological condition a direct relationship between DMN BOLD activity and EEG activity. They indicate that epileptic activity affects the DMN, and therefore may momentarily reduce the consciousness level and cognitive reserve.

Existing literature outlines the quality and location of activation in the prefrontal cortex (PFC) during working memory (WM) tasks. However, the effects of individual differences on the underlying neural process of WM tasks are still unclear. In this functional near infrared spectroscopy study, we administered a visual and auditory n-back task to examine activation in the PFC while considering the influences of task performance, and preferred learning strategy (VARK score). While controlling for age, results indicated that high performance (HP) subjects (accuracy > 90%) showed task dependent lower activation compared to normal performance subjects in PFC region Specifically HP groups showed lower activation in left dorsolateral PFC (DLPFC) region during performance of auditory task whereas during visual task they showed lower activation in the right DLPFC. After accounting for learning style, we found a correlation between visual and aural VARK score and level of activation in the PFC. Subjects with higher visual VARK scores displayed lower activation during auditory task in left DLPFC, while those with higher visual scores exhibited higher activation during visual task in bilateral DLPFC. During performance of auditory task, HP subjects had higher visual VARK scores compared to NP subjects indicating an effect of learning style on the task performance and activation. The results of this study show that learning style and task performance can influence PFC activation, with applications toward neurological implications of learning style and populations with deficits in auditory or visual processing.