Single-dose serotonergic stimulation shows widespread effects on functional brain connectivity

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.

Cognition in ESRD may be improved by kidney transplantation, but mechanisms are unclear. We explored patterns of resting-state networks with resting-state functional magnetic resonance imaging among patients with ESRD before and after kidney transplantation. Thirty-seven patients with ESRD scheduled for kidney transplantation and 22 age-, sex-, and education-matched healthy subjects underwent resting-state functional magnetic resonance imaging. Patients were imaged before and 1 and 6 months after kidney transplantation. Functional connectivity of seven resting-state subnetworks was evaluated: default mode network, dorsal attention network, central executive network, self-referential network, sensorimotor network, visual network, and auditory network. Mixed effects models tested associations of ESRD, kidney transplantation, and neuropsychological measurements with functional connectivity. Compared with controls, pretransplant patients showed abnormal functional connectivity in six subnetworks. Compared with pretransplant patients, increased functional connectivity was observed in the default mode network, the dorsal attention network, the central executive network, the sensorimotor network, the auditory network, and the visual network 1 and 6 months after kidney transplantation (P=0.01). Six months after kidney transplantation, no significant difference in functional connectivity was observed for the dorsal attention network, the central executive network, the auditory network, or the visual network between patients and controls. Default mode network and sensorimotor network remained significantly different from those in controls when assessed 6 months after kidney transplantation. A relationship between functional connectivity and neuropsychological measurements was found in specific brain regions of some brain networks. The recovery patterns of resting-state subnetworks vary after kidney transplantation. The dorsal attention network, the central executive network, the auditory network, and the visual network recovered to normal levels, whereas the default mode network and the sensorimotor network did not recover completely 6 months after kidney transplantation. Neural resting-state functional connectivity was lower among patients with ESRD compared with control subjects, but it significantly improved with kidney transplantation. Resting-state subnetworks exhibited variable recovery, in some cases to levels that were no longer significantly different from those of normal controls.

Thyroid-associated ophthalmopathy (TAO) is a prevalent autoimmune disease characterized by ocular symptoms like eyelid retraction and exophthalmos. Prior neuroimaging studies have revealed structural and functional brain abnormalities in TAO patients, along with central nervous system symptoms such as cognitive deficits. Nonetheless, the changes in the static and dynamic functional network connectivity of the brain in TAO patients are currently unknown. This study delved into the modifications in static functional network connectivity (sFNC) and dynamic functional network connectivity (dFNC) among thyroid-associated ophthalmopathy patients using independent component analysis (ICA). Thirty-two patients diagnosed with thyroid-associated ophthalmopathy and 30 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning. ICA method was utilized to extract the sFNC and dFNC changes of both groups. In comparison to the HC group, the TAO group exhibited significantly increased intra-network functional connectivity (FC) in the right inferior temporal gyrus of the executive control network (ECN) and the visual network (VN), along with significantly decreased intra-network FC in the dorsal attentional network (DAN), the default mode network (DMN), and the left middle cingulum of the ECN. On the other hand, FNC analysis revealed substantially reduced connectivity intra- VN and inter- cerebellum network (CN) and high-level cognitive networks (DAN, DMN, and ECN) in the TAO group compared to the HC group. Regarding dFNC, TAO patients displayed abnormal connectivity across all five states, characterized by notably reduced intra-VN connectivity and CN connectivity with high-level cognitive networks (DAN, DMN, and ECN), alongside compensatory increased connectivity between DMN and low-level perceptual networks (VN and basal ganglia network). No significant differences were observed between the two groups for the three dynamic temporal metrics. Furthermore, excluding the classification outcomes of FC within VN (with an accuracy of 51.61% and area under the curve of 0.35208), the FC-based support vector machine (SVM) model demonstrated improved performance in distinguishing between TAO and HC, achieving accuracies ranging from 69.35 to 77.42% and areas under the curve from 0.68229 to 0.81667. The FNC-based SVM classification yielded an accuracy of 61.29% and an area under the curve of 0.57292. In summary, our study revealed that significant alterations in the visual network and high-level cognitive networks. These discoveries contribute to our understanding of the neural mechanisms in individuals with TAO, offering a valuable target for exploring future central nervous system changes in thyroid-associated eye diseases.

Is schizophrenia a spatiotemporal disorder of the brain's resting state?

SEE BIGLER DOI101093/AWW277 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Post-traumatic amnesia is very common immediately after traumatic brain injury. It is characterized by a confused, agitated state and a pronounced inability to encode new memories and sustain attention. Clinically, post-traumatic amnesia is an important predictor of functional outcome. However, despite its prevalence and functional importance, the pathophysiology of post-traumatic amnesia is not understood. Memory processing relies on limbic structures such as the hippocampus, parahippocampus and parts of the cingulate cortex. These structures are connected within an intrinsic connectivity network, the default mode network. Interactions within the default mode network can be assessed using resting state functional magnetic resonance imaging, which can be acquired in confused patients unable to perform tasks in the scanner. Here we used this approach to test the hypothesis that the mnemonic symptoms of post-traumatic amnesia are caused by functional disconnection within the default mode network. We assessed whether the hippocampus and parahippocampus showed evidence of transient disconnection from cortical brain regions involved in memory processing. Nineteen patients with traumatic brain injury were classified into post-traumatic amnesia and traumatic brain injury control groups, based on their performance on a paired associates learning task. Cognitive function was also assessed with a detailed neuropsychological test battery. Functional interactions between brain regions were investigated using resting-state functional magnetic resonance imaging. Together with impairments in associative memory, patients in post-traumatic amnesia demonstrated impairments in information processing speed and spatial working memory. Patients in post-traumatic amnesia showed abnormal functional connectivity between the parahippocampal gyrus and posterior cingulate cortex. The strength of this functional connection correlated with both associative memory and information processing speed and normalized when these functions improved. We have previously shown abnormally high posterior cingulate cortex connectivity in the chronic phase after traumatic brain injury, and this abnormality was also observed in patients with post-traumatic amnesia. Patients with post-traumatic amnesia showed evidence of widespread traumatic axonal injury measured using diffusion magnetic resonance imaging. This change was more marked within the cingulum bundle, the tract connecting the parahippocampal gyrus to the posterior cingulate cortex. These findings provide novel insights into the pathophysiology of post-traumatic amnesia and evidence that memory impairment acutely after traumatic brain injury results from altered parahippocampal functional connectivity, perhaps secondary to the effects of axonal injury on white matter tracts connecting limbic structures involved in memory processing.

Despite advances in resting state functional magnetic resonance imaging investigations, clinicians remain with the challenge of how to implement this paradigm on an individualized basis. Here, we assessed the clinical relevance of resting state functional magnetic resonance imaging acquisitions in patients with disorders of consciousness by means of a systems-level approach. Three clinical centres collected data from 73 patients in minimally conscious state, vegetative state/unresponsive wakefulness syndrome and coma. The main analysis was performed on the data set coming from one centre (Liège) including 51 patients (26 minimally conscious state, 19 vegetative state/unresponsive wakefulness syndrome, six coma; 15 females; mean age 49 ± 18 years, range 11-87; 16 traumatic, 32 non-traumatic of which 13 anoxic, three mixed; 35 patients assessed >1 month post-insult) for whom the clinical diagnosis with the Coma Recovery Scale-Revised was congruent with positron emission tomography scanning. Group-level functional connectivity was investigated for the default mode, frontoparietal, salience, auditory, sensorimotor and visual networks using a multiple-seed correlation approach. Between-group inferential statistics and machine learning were used to identify each network's capacity to discriminate between patients in minimally conscious state and vegetative state/unresponsive wakefulness syndrome. Data collected from 22 patients scanned in two other centres (Salzburg: 10 minimally conscious state, five vegetative state/unresponsive wakefulness syndrome; New York: five minimally conscious state, one vegetative state/unresponsive wakefulness syndrome, one emerged from minimally conscious state) were used to validate the classification with the selected features. Coma Recovery Scale-Revised total scores correlated with key regions of each network reflecting their involvement in consciousness-related processes. All networks had a high discriminative capacity (>80%) for separating patients in a minimally conscious state and vegetative state/unresponsive wakefulness syndrome. Among them, the auditory network was ranked the most highly. The regions of the auditory network which were more functionally connected in patients in minimally conscious state compared to vegetative state/unresponsive wakefulness syndrome encompassed bilateral auditory and visual cortices. Connectivity values in these three regions discriminated congruently 20 of 22 independently assessed patients. Our findings point to the significance of preserved abilities for multisensory integration and top-down processing in minimal consciousness seemingly supported by auditory-visual crossmodal connectivity, and promote the clinical utility of the resting paradigm for single-patient diagnostics.

Impaired functional default mode network in patients with mild neurological Wilson’s disease

PurposeTo investigate the effect of sleep disorder (SD) on the changes of brain network dysfunction in mild cognitive impairment (MCI), we compared network connectivity patterns among MCI, SD, and comorbid MCI and sleep disorders (MCI-SD) patients using resting state functional magnetic resonance imaging (RS-fMRI).Patients and MethodsA total of 60 participants were included in this study, 20 each with MCI, SD, or MCI-SD. And all participants underwent structural and functional MRI scanning. The default-mode network (DMN) was extracted by independent component analysis (ICA), and regional functional connectivity strengths were calculated and compared among groups.ResultsCompared to MCI patients, The DMN of MCI-SD patients demonstrated weaker functional connectivity with left middle frontal gyrus, right superior marginal gyrus, but stronger connectivity with the left parahippocampus, left precuneus and left middle temporal gyrus. Compared to the SD group, MCI-SD patients demonstrated weaker functional connectivity with right transverse temporal gyrus (Heschl’s gyrus), right precentral gyrus, and left insula, but stronger connectivity with posterior cerebellum, right middle occipital gyrus, and left precuneus.ConclusionPatients with MCI-SD show unique changes in brain network connectivity patterns compared to MCI or SD alone, likely reflecting a broader functional disconnection and the need to recruit more brain regions for functional compensation.

The specific topological changes in dynamic functional networks and their role in cervical spondylotic myelopathy (CSM) brain function reorganization remain unclear. This study aimed to investigate the dynamic functional connection (dFC) of patients with CSM, focusing on the temporal characteristics of the functional connection state patterns and the variability of network topological organization. Eighty-eight patients with CSM and 77 healthy controls (HCs) were recruited for resting-state functional magnetic resonance imaging. We applied the sliding time window analysis method and K-means clustering analysis to capture the dFC variability patterns of the two groups. The graph-theoretical approach was used to investigate the variance in the topological organization of whole-brain functional networks. All participants showed four types of dynamic functional connection states. The mean dwell time in state 2 was significantly different between the two groups. Particularly, the mean dwell time in state 2 was significantly longer in the CSM group than in the healthy control group. Among the four states, switching of relative brain networks mainly included the executive control network (ECN), salience network (SN), default mode network (DMN), language network (LN), visual network (VN), auditory network (AN), precuneus network (PN), and sensorimotor network (SMN). Additionally, the topological properties of the dynamic network were variable in patients with CSM. Dynamic functional connection states may offer new insights into intrinsic functional activities in CSM brain networks. The variance of topological organization may suggest instability of the brain networks in patients with CSM.

Background: Irritable Bowel Syndrome (IBS), as a functional gastrointestinal disorder, is characterized by abdominal pain and distension. Recent studies have shown that acupuncture treatment improves symptoms of diarrhea-predominant irritable bowel syndrome (IBS-D) by altering networks in certain brain regions. However, few studies have used resting-state functional magnetic resonance imaging (fMRI) to compare altered resting-state inter-network functional connectivity in IBS-D patients before and after acupuncture treatment.Objective: To analyze altered resting-state inter-network functional connectivity in IBS-D patients before and after acupuncture treatment.Methods: A total of 74 patients with IBS-D and 31 healthy controls (HCs) were recruited for this study. fMRI examination was performed in patients with IBS-D before and after acupuncture treatment, but only at baseline in HCs. Data on the left frontoparietal network (LFPN), default mode network (DMN), salience network (SN), ventral attention network (VAN), auditory network (AN), visual network (VN), sensorimotor network (SMN), dorsal attention network (DAN), and right frontoparietal network (RFPN) were subjected to independent component analysis (ICA). The functional connectivity values of inter-network were explored.Results: Acupuncture decreased irritable bowel syndrome symptom severity score (IBS-SSS) and Hamilton Anxiety Scale (HAMA). It also ameliorated symptoms related to IBS-D. Notably, functional connectivity between AN and VAN, SMN and DMN, RFPN and VAN in IBS-D patients after acupuncture treatment was different from that in HCs. Furthermore, there were differences in functional connectivity between DMN and DAN, DAN and LFPN, DMN and VAN before and after acupuncture treatment. The inter-network changes in DMN-VAN were positively correlated with changes in HAMA, life influence degree, and IBS-SSS in IBS-D.Conclusion: Altered inter-network functional connectivity is involved in several important hubs in large-scale networks. These networks are altered by acupuncture stimulation in patients with IBS-D.

ObjectivesUnderstanding functional connectivity after consuming meat can be essential to fully understanding consumer’s preferences and the connection to certain flavor compounds. The objective of this study was to determine differences in the functional brain connectivity of consumers after consuming grass-fed beef, grain-fed beef and chicken while determining the different chemical and volatile components that differentiate the treatments.Materials and MethodsGrass-fed strip steaks, Grain-fed strip steaks and chicken breasts were collected, aged 21 d and cut into 1×1-inch consumer steaks. Each steak was vacuum sealed with a random identification number and frozen at –20°C. 23 volunteered consumers evaluated each treatment randomly followed by a Blood Oxygen Level-Dependent (BOLD) fMRI scan. Each consumer received a resting state scan and three scans following each sample. The beef was cooked to a medium degree of doneness (71°C) and the chicken was cooked to a well-done degree of doneness (75°C), followed by a 1-min resting period. The consumers were asked to complete a sensory ballot for each sample to quantify tenderness, juiciness, flavor, overall liking and quality. Each attribute was evaluated on a 100mm line scale. The sensory ballot, volatile and fatty acid data were analyzed by ANOVA and multiple means comparison using SAS while the fMRI data were analyzed using FSL’s FEAT software.ResultsThe results indicated all treatments were equal for tenderness and flavor, but the chicken was the least juicy (P < 0.05) and the grain-fed steak was ranked higher for overall liking (P < 0.05) in comparison to chicken. Furthermore, based on an independent component analysis, there was a significant difference in the functional connectivity (P < 0.05) from the resting state scan to all three treatments within the insular, medial prefrontal cortex, and amygdala regions. Additionally, there were significant differences in connectivity (P < 0.05) between the insula and orbitofrontal cortex in grass-fed compared to grain-fed beef. These areas are involved in processing sensory characteristics related to smell and taste and tend to track differences in preferences and stimulus value. Also, the samples were evaluated for volatile compounds with GC–MS and fatty acids using the FAMES method. Chicken and grass-fed beef was found to have a higher concentration (P < 0.05) of dimethyl sulfone in comparison to grain-fed beef, while the grass-fed steaks possessed a higher concentration (P < 0.05) of toluene in comparison to grain-fed steaks, but not differing from chicken. Dimethyl sulfone and toluene have been tied to grass-fed beef and chicken flavor profiles (Tansawat et al., 2013).ConclusionThe results from the functional brain connectivity in the reward pathways and the chemical components of the different treatments indicated a trend for grain-fed beef to be the most different from grass-fed beef and chicken. Moreover, tying brain activity to the flavor and chemical components in meat can be vital in understanding consumer’s preferences not observed in behavior alone. Therefore, these results can provide a basis to determine the ability to track reactions within the functional connectivity in the brain and the chemical aspects of different steaks to determine and understand consumer’s preferences and the true value of beef and chicken.

This study assessed brain structural and functional alterations in patients with Parkinson's disease and impulsive-compulsive behaviours (PD-ICB) compared with controls and PD no-ICB cases. Eighty-five PD patients (35 PD-ICB) and 50 controls were recruited. All subjects underwent three-dimensional T1-weighted, diffusion tensor (DT), and resting state functional magnetic resonance imaging (RS fMRI). We assessed cortical thickness with surface-based morphometry, subcortical volumes using FIRST, DT MRI metrics using region of interest and tractography approaches, and RS fMRI using a model free approach. Compared with controls, both PD groups showed a pattern of brain structural alterations in the basal ganglia (more evident in PD no-ICB patients), sensorimotor and associative systems. Compared with PD no-ICB, PD-ICB cases showed left precentral and superior frontal cortical thinning, and motor and extramotor white matter tract damage. Compared with controls, all patients had an increased functional connectivity within the visual network. Additionally, PD no-ICB showed increased functional connectivity of bilateral precentral and postcentral gyri within the sensorimotor network compared with controls and PD-ICB. Severity and duration of PD-ICB modulated the functional connectivity between sensorimotor, visual and cognitive networks. Relative to PD no-ICB, PD-ICB patients were characterised by a more severe involvement of frontal, meso-limbic and motor circuits. These data suggest ICB in PD as the result of a disconnection between sensorimotor, associative and cognitive networks with increasing motor impairment, psychiatric symptoms, and ICB duration. These findings may have important implications in understanding the neural substrates underlying ICB in PD.

White matter microstructure underlying default mode network connectivity in the human brain

Background and PurposeTemporomandibular disorders (TMD), especially pain-related TMD, are closely related to social and psychological factors. We aimed to measure changes in spontaneous brain activity and its related functional connectivity (FC), as well as FC characteristics within the mood-regulating circuits (MRC) in TMD patients by resting-state functional magnetic resonance imaging (RS-fMRI), and to analyze the relationship between these parameters and emotional symptoms.Materials and MethodsTwenty-one adult TMD patients and thirty demographically matched healthy controls (HCs) underwent clinical scale evaluation and RS-fMRI scanning. After processing RS-fMRI data, the values of the amplitude of low-frequency fluctuation (ALFF) between the two groups were compared. Regions with abnormal ALFF values were selected as areas of interest (ROIs) to compare the differences of whole-brain seed-based FC between groups. The FCs between regions within MRC were also analyzed and compared. In addition, the relationships between RS-fMRI characteristics and pain and mood were explored by correlation and mediation analyses.ResultsCompared with HCs, TMD patients showed increased ALFF in the right parahippocampal gyrus (PHG), the right supplementary motor area, and the bilateral precentral gyrus, with decreased ALFF in the right cerebelum_crus2. Patients showed enhanced right PHG-related FC in the vermis and posterior cingulate cortex, orbitofrontal cortex (OFC)-related FC in the striatal-frontal regions, while decreased dorsolateral prefrontal cortex-related FC in the amygdala. In TMD patients, ALFF values in the right PHG and FC values between the right PHG and the vermis were positively correlated with depressive symptoms. Abnormal FCs in the left striatal-orbitofrontal pathway were correlated with pain and depressive symptoms. More importantly, mediation analysis revealed that chronic pain mediates the relationship between FC of right PHG with vermis and depressive symptoms, and abnormal FC in the left striatal-orbitofrontal pathway can mediate the association between pain and depressive symptoms.ConclusionTMD patients have dysregulated spontaneous activity and FC in the default mode network, sensorimotor network and pain-related regions, as well as dysfunction of the fronto-striatal-limbic circuits. The development of negative emotions in TMD may be related to the dysfunction of components within the reward system (especially hippocampus complex, OFC, striatum) due to chronic pain.

To investigate the functional connectivity of the default-mode network (DMN) in patients with end-stage renal disease (ESRD) by using independent component analysis of resting-state functional magnetic resonance (MR) imaging and to correlate these DMN connectivity changes with neuropsychological test results and clinical biomarkers. Medical research ethics committee approval and written informed consent were obtained. Forty-six patients with ESRD, including 22 with minimal nephrotic encephalopathy (MNE) and 24 without nephrotic encephalopathy, and 23 healthy control subjects underwent resting-state functional MR imaging. All patients were asymptomatic and without history of neurologic or psychiatric disease. Independent component analysis was used to isolate the DMN. To display the voxels that contributed most strongly to an independent component, the intensity values in each spatial map were converted to z scores, which indirectly provided a measurement of functional connectivity in the DMN. Maps of the DMN were compared among the groups. Pearson correlation analysis was performed to correlate abnormal DMN functional connectivity with serum urea, creatinine, duration of dialysis, duration of disease, and neuropsychological test scores. Patients with ESRD showed significantly less functional connectivity in the posterior cingulate cortex, precuneus, and medial prefrontal cortex (MPFC) (P < .01) than did control subjects. Comparison of the two patient groups showed significantly reduced functional connectivity in the superior and MPFC in the MNE group (P < .01). The functional connectivity of the MPFC was positively correlated with digital symbol test score (R = 0.293, P = .048). Serum creatinine level was negatively correlated with functional connectivity of the posterior cingulate cortex and precuneus in patients with ESRD (R = -0.51, P = .002). Functional connectivity in the DMN was impaired in patients with ESRD, with further reduction in the MPFC with the development of MNE, which might explain the reduced performance of these patients on neurocognitive tests. Serum creatinine level might be associated with impairment of the DMN in patients with ESRD.