Selectively Disrupted Functional Connectivity Networks in Type 2 Diabetes Mellitus.
ABSTRACT: BACKGROUND:The high prevalence of type 2 diabetes mellitus (T2DM) in individuals over 65?years old and cognitive deficits caused by T2DM have attracted broad attention. The pathophysiological mechanism of T2DM-induced cognitive impairments, however, remains poorly understood. Previous studies have suggested that the cognitive impairments can be attributed not only to local functional and structural abnormalities but also to specific brain networks. Thus, our aim is to investigate the changes of global networks selectively affected by T2DM. METHODS:A resting state functional network analysis was conducted to investigate the intrinsic functional connectivity in 37 patients with diabetes and 40 healthy controls who were recruited from local communities in Beijing, China. RESULTS:We found that patients with T2DM exhibited cognitive function declines and functional connectivity disruptions within the default mode network, left frontal parietal network, and sensorimotor network. More importantly, the fasting glucose level was correlated with abnormal functional connectivity. CONCLUSION:These findings could help to understand the neural mechanisms of cognitive impairments in T2DM and provide potential neuroimaging biomarkers that may be used for early diagnosis and intervention in cognitive decline.
Project description:Although Type 2 diabetes mellitus (T2DM) is a well-recognized risk factor for dementia, the neural mechanisms that underlie cognitive impairment in T2DM remain unclear. This study uses resting-state functional magnetic resonance imaging (fMRI) to examine attention network alterations in T2DM and their relationships to impaired cognitive performance. Data-driven independent component analysis was applied to resting-state fMRI data from 38 T2DM patients and 32 healthy controls to identify the dorsal attention network (DAN) and ventral attention network (VAN). Correlations were then determined among the resting-state functional connectivity (rsFC), clinical data, and neuropsychological scores. The T2DM patients exhibited decreased rsFC in the left middle frontal gyrus (MFG) and bilateral inferior parietal lobe (IPL) of the DAN, as well as the left IPL and right MFG/IFG of the VAN. In addition, the rsFC of the left MFG was inversely correlated with the Trail Making Test-B scores; the rsFC of the left IPL was positively correlated with the Digit Span Test scores but negatively correlated with HbA1c; and the rsFC in the right precuneus was positively associated with cognitive performance (without Bonferroni correction). In conclusion, T2DM affects resting-state attentional networks, which may be related to reduced attention and a hyperglycemic state.
Project description:Cognitive impairment caused by subcortical ischemic vascular disease (SIVD) has been elucidated by many neuroimaging studies. However, little is known regarding the changes in brain functional connectivity networks in relation to the severity of cognitive impairment in SIVD. In the present study, 20 subcortical ischemic vascular cognitive impairment no dementia patients (SIVCIND) and 20 dementia patients (SIVaD) were enrolled; additionally, 19 normal controls were recruited. Each participant underwent a resting-state functional MRI scan. Whole-brain functional networks were analyzed with graph theory and network-based statistics (NBS) to study the functional organization of networks and find alterations in functional connectivity among brain regions. After adjustments for age, gender, and duration of formal education, there were significant group differences for two network functional organization indices, global efficiency and local efficiency, which decreased (NC?>?SIVCIND?>?SIVaD) as cognitive impairment worsened. Between-group differences in functional connectivity (NBS corrected, p?<?0.01) mainly involved the orbitofrontal, parietal, and temporal cortices, as well as the basal ganglia. The brain connectivity network was progressively disrupted as cognitive impairment worsened, with an increased number of decreased connections between brain regions. We also observed more reductions in nodal efficiency in the prefrontal and temporal cortices for SIVaD than for SIVCIND. These findings indicated a progressively disrupted pattern of the brain functional connectivity network with increased cognitive impairment and showed promise for the development of reliable biomarkers of network metric changes related to cognitive impairment caused by SIVD.
Project description:Research on brain activity in schizophrenia has shown that changes in the function of any single region cannot explain the range of cognitive and affective impairments in this illness. Rather, neural circuits that support sensory, cognitive, and emotional processes are now being investigated as substrates for cognitive and affective impairments in schizophrenia, a shift in focus consistent with long-standing hypotheses about schizophrenia as a disconnection syndrome. Our goal was to further examine alterations in functional connectivity within and between the default mode network and three cognitive control networks (frontal-parietal, cingulo-opercular, and cerebellar) as a basis for such impairments.Resting state functional magnetic resonance imaging was collected from 40 individuals with DSM-IV-TR schizophrenia, 31 siblings of individuals with schizophrenia, 15 healthy control subjects, and 18 siblings of healthy control subjects while they rested quietly with their eyes closed. Connectivity metrics were compared between patients and control subjects for both within- and between-network connections and were used to predict clinical symptoms and cognitive function.Individuals with schizophrenia showed reduced distal and somewhat enhanced local connectivity between the cognitive control networks compared with control subjects. Additionally, greater connectivity between the frontal-parietal and cerebellar regions was robustly predictive of better cognitive performance across groups and predictive of fewer disorganization symptoms among patients.These results are consistent with the hypothesis that impairments of executive function and cognitive control result from disruption in the coordination of activity across brain networks and additionally suggest that these might reflect impairments in normal pattern of brain connectivity development.
Project description:Cognitive control impairments in schizophrenia are thought to arise from dysfunction of interconnected networks of brain regions, but interrogating the functional dynamics of large-scale brain networks during cognitive task performance has proved difficult. We used functional magnetic resonance imaging to generate event-related whole-brain functional connectivity networks in participants with first-episode schizophrenia and healthy control subjects performing a cognitive control task.Functional connectivity during cognitive control performance was assessed between each pair of 78 brain regions in 23 patients and 25 control subjects. Network properties examined were region-wise connectivity, edge-wise connectivity, global path length, clustering, small-worldness, global efficiency, and local efficiency.Patients showed widespread functional connectivity deficits in a large-scale network of brain regions, which primarily affected connectivity between frontal cortex and posterior regions and occurred irrespective of task context. A more circumscribed and task-specific connectivity impairment in frontoparietal systems related to cognitive control was also apparent. Global properties of network topology in patients were relatively intact.The first episode of schizophrenia is associated with a generalized connectivity impairment affecting most brain regions but that is particularly pronounced for frontal cortex. Superimposed on this generalized deficit, patients show more specific cognitive-control-related functional connectivity reductions in frontoparietal regions. These connectivity deficits occur in the context of relatively preserved global network organization.
Project description:Type 2 diabetes mellitus (T2DM) is associated with cognitive impairment. We investigated whether alterations of intranetwork and internetwork functional connectivity with T2DM progression exist, by using resting-state functional MRI. MRI data were analysed from 19 T2DM patients with normal cognition (DMCN) and 19 T2DM patients with cognitive impairment (DMCI), 19 healthy controls (HC). Functional connectivity among 36 previously well-defined brain regions which consisted of 5 resting-state network (RSN) systems [default mode network (DMN), dorsal attention network (DAN), control network (CON), salience network (SAL) and sensorimotor network (SMN)] was investigated at 3 levels (integrity, network and connectivity). Impaired intranetwork and internetwork connectivity were found in T2DM, especially in DMCI, on the basis of the three levels of analysis. The bilateral posterior cerebellum, the right insula, the DMN and the CON were mainly involved in these changes. The functional connectivity strength of specific brain architectures in T2DM was found to be associated with haemoglobin A1c (HbA1c), cognitive score and illness duration. These network alterations in intergroup differences, which were associated with brain functional impairment due to T2DM, indicate that network organizations might be potential biomarkers for predicting the clinical progression, evaluating the cognitive impairment, and further understanding the pathophysiology of T2DM.
Project description:Type 2 diabetes mellitus (T2DM) is associated with cognitive impairment in many domains. There are several pieces of evidence that changes in neuronal neuropathies and metabolism have been observed in T2DM. Structural and functional MRI shows that abnormal connections and synchronization occur in T2DM brain circuits and related networks. Neuroplasticity and energy metabolism appear to be principal effector systems, which may be related to amyloid beta (Aβ) deposition, although there is no unified explanation that includes the complex etiology of T2DM with cognitive impairment. Herein, we assume that cognitive impairment in diabetes may lead to abnormalities in neuroplasticity and energy metabolism in the brain, and those reflected to MRI structural connectivity and functional connectivity, respectively.
Project description:Chronic disorders of consciousness (DOC) encompass unresponsive wakefulness syndrome and minimally conscious state. Their anatomo-functional correlates are not clearly defined yet, although impairments of functional cortical networks have been reported, as well as the implication of the thalamus and deep brain structures. However, the pallidal functional connectivity with the thalamus and the cortical networks has not been studied so far. Using resting-state functional MRI, we conducted a functional connectivity study between the pallidum, the thalamus and the cortical networks in 13 patients with chronic DOC and 19 healthy subjects. We observed in chronic DOC patients that the thalami were no longer connected to the cortical networks, nor to the pallidums. Concerning the functional connectivity of pallidums, we reported an abolition of the negative correlation with the default mode network, and of the positive correlation with the salience network. The disrupted functional connectivity observed in chronic DOC patients between subcortical structures and cortical networks could be related to the mesocircuit model. A better understanding of the DOC underlying physiopathology could provide food for thought for future therapeutic proposals.
Project description:Type 2 diabetes mellitus (T2DM) is related to cognitive impairments and increased risk for dementia. Neuroimaging studies have demonstrated T2DM-related brain structural and functional changes which are partly associated to the cognitive decline. However, few studies focused on the early neuroimaging findingsin T2DM patients. In this study, a data-driven whole-brain resting state functional connectivity strength (rsFCS) methodwas used to evaluate resting functional changes in 53 T2DM patients compared with 55 matched healthy controls (HCs), and to detect the associations between the rsFCSchanges and cognitive functions in T2DM patients. The T2DM patients exhibited weaker long-range rsFCS in the right insula and weaker short-range rsFCS in the right supramarginalgyrus (SG) compared with the HCs. Additionally, seed-based functional connectivity (FC) analysis revealed weaker FC between the right insula and the bilateral superior parietal lobule (SPL), and between the right SG and the bilateral supplementary motor area (SMA)/right SPL in T2DM patientscompared with the HCs. In T2DM patients, negative correlation was found between the long-range rsFCS in the right insula and HbA1c levels; and the FC between the right SG and the bilateral SMA negatively correlated with TMT-A scores. Our results indicated that the rsFCS alteration occurredbefore obvious cognitive deficits in T2DM patients, which might be helpful for understanding the neuromechanism of cognitive declines in T2DM patients.
Project description:BACKGROUND AND PURPOSE:Type 2 diabetes is associated with an increased risk of dementia. This study investigated the global connectivity patterns in the brains of patients with type 2 diabetes by using a functional MR imaging technique. MATERIALS AND METHODS:Forty patients and 43 age-, sex-, and education-matched healthy controls underwent resting-state functional imaging in a 3T MR imaging unit. Degree centrality, a commonly used measurement of global connectivity, was computed for a full-brain exploration of the regions influenced by type 2 diabetes. We then examined the functional connectivity of each region by using the seed-based approach. Finally, voxelwise correlation analyses were performed to explore the relationship among the connectivity changes, cognitive performance, and diabetes-related variables. RESULTS:Patients exhibited decreased degree centrality in the left lingual gyrus and increased centrality in the right insula and dorsal anterior cingulate cortex (corrected P < .05). The occipital network anchored in the lingual gyrus showed extensively reduced connectivity, while the network connectivity of the insula and cingulate cortex (mostly included in the salience network) was significantly elevated (corrected P < .05). Correlational analyses revealed that in the diabetic group, impaired visual memory and executive function performance were correlated with occipital hypoconnectivity, while higher fasting plasma glucose levels and better executive functioning were related to anterior cingulate cortex hyperconnectivity (all corrected P values < .05). Similar effects were not detected in the controls. CONCLUSIONS:This preliminary study shows that network connectivity is altered in patients with type 2 diabetes, which may provide critical insight into the neural substrate of diabetes-related cognitive decline.
Project description:Cognitive control is a cognitive and neural mechanism that contributes to managing the complex demands of day-to-day life. Studies have suggested that functional impairments in cognitive control associated brain circuitry contribute to a broad range of higher cognitive deficits in schizophrenia. To examine this issue, we assessed functional connectivity networks in healthy adults and individuals with schizophrenia performing tasks from two distinct cognitive domains that varied in demands for cognitive control, the RiSE episodic memory task and DPX goal maintenance task. We characterized general and cognitive control-specific effects of schizophrenia on functional connectivity within an expanded frontal parietal network (FPN) and quantified network topology properties using graph analysis. Using the network based statistic (NBS), we observed greater network functional connectivity in cognitive control demanding conditions during both tasks in both groups in the FPN, and demonstrated cognitive control FPN specificity against a task independent auditory network. NBS analyses also revealed widespread connectivity deficits in schizophrenia patients across all tasks. Furthermore, quantitative changes in network topology associated with diagnostic status and task demand were observed. The present findings, in an analysis that was limited to correct trials only, ensuring that subjects are on task, provide critical insights into network connections crucial for cognitive control and the manner in which brain networks reorganize to support such control. Impairments in this mechanism are present in schizophrenia and these results highlight how cognitive control deficits contribute to the pathophysiology of this illness.