Cognitive Dysfunction in Type 2 Diabetes Is Not a One-Way Process: Evidence From a Longitudinal Brain Connectivity Study.

Background: Cognitive dysfunction is an important comorbidity of diabetes characterized by brain functional hypo-connectivity. However, our recent study demonstrated an adaptive hyper-connectivity in young type 2 diabetes with cognitive decrements. This longitudinal study aimed to further explore the changes in functional connectivity and cognitive outcomes after regular glycemic control. Methods: At 18 months after recruitment, participants underwent a second cognitive assessment and magnetic resonance imaging. Three enhanced functional connectivities previously identified at baseline were followed up. Linear mixed-effects models were performed to compare the longitudinal changes of cognition and functional connectivity in patients with type 2 diabetes and non-diabetic controls. A linear regression model was used to investigate the association between changes in functional connectivity and changes in cognitive performance. Results: Improvements in multiple cognitive domains were observed in diabetes; however, the enhanced functional connectivity at baseline decreased significantly. Moreover, the decrease in hippocampal connectivity was correlated with an increase in the accuracy of Stroop task and the decrease in posterior cingulate cortex connectivity was correlated with an increase in Montreal Cognitive Assessment in diabetes. Conclusion: This study suggests diabetes-related cognitive dysfunction is not a one-way process and the early-stage enhancement of brain connectivity was a potential "window period" for cognitive reversal.

Compensatory Hippocampal Connectivity in Young Adults With Early-Stage Type 2 Diabetes.

CONTEXT: Middle-aged to elderly patients with type 2 diabetes mellitus (T2DM) exhibit reduced functional connectivity and brain atrophy underlying cognitive decrements; however, little is known about brain abnormalities in young patients. OBJECTIVE: To detect brain anatomical and functional changes in young patients with T2DM during the early disease stage. DESIGN: Case-control study. SETTING: Tertiary referral hospital. PARTICIPANTS: Thirty-five young patients with T2DM (<40 years of age) with no detectable microangiopathy and 32 nondiabetic control subjects. INTERVENTION: None. MAIN OUTCOME MEASURES: Subjects underwent neuropsychological assessments and structural and resting-state functional MRI. Both voxel-based morphometry and resting-state functional connectivity analyses were performed. RESULTS: No significant differences in brain volume were observed between the patients with T2DM and the controls after controlling for age, sex, education, and body mass index. Compared with the controls, the patients showed greater connectivity of the left hippocampus with the left inferior frontal gyrus and the left inferior parietal lobule. Moreover, the enhanced functional connectivity of left hippocampus with the left inferior frontal gyrus significantly correlated with disease severity (urinary albumin-to-creatinine ratio) (r = 0.613, P < 0.001) and executive function (completion time of Stroop Color and Word Test) (r = -0.461, P = 0.005) after false discovery rate correction. CONCLUSIONS: Our findings suggest an adaptive compensation of brain function to counteract the insidious cognitive decrements during the early stage of T2DM. Additionally, the functional alterations occurring before changes in brain structure and peripheral microangiopathy might serve as early biomarkers related to cognitive decrements.

Brain atrophy in middle-aged subjects with Type 2 diabetes mellitus, with and without microvascular complications.

BACKGROUND: The rapid rise in Type 2 diabetes mellitus (T2DM) among young adults makes it important to understand structural changes in the brain at a presenile stage. This study examined global and regional brain atrophy in middle-aged adults with T2DM, with a focus on those without clinical evidence of microvascular complications. METHODS: The study recruited 66 dementia-free middle-aged subjects (40 with T2DM, 26 healthy volunteers [HVs]). Patients were grouped according to the presence (T2DM-C; n = 20) or absence (T2DM-NC; n = 20) of diabetic microvascular complications. Global brain volume (including gray matter [GM] and white matter) was calculated based on voxel-based morphometry analysis. Regional GM volumes were further extracted using the anatomical automatic labeling template. RESULTS: There was a significant difference in global brain volume among groups (P = 0.003, anova). Global brain volume was lower in T2DM-C patients than in both T2DM-NC patients and HVs (mean [±SD] 0.720 ± 0.024 vs 0.736 ± 0.021 and 0.743 ± 0.019, respectively; P = 0.032 and P = 0.001, respectively). Regional analysis showed significant GM atrophy in the right Rolandic operculum (t = 3.42, P = 0.001) and right superior temporal gyrus (t = 2.803, P = 0.007) in T2DM-NC patients compared with age- and sex-matched HVs. CONCLUSIONS: Brain atrophy is present in dementia-free middle-aged adults with T2DM. Regional brain atrophy appears to be developing even in those with no clinical evidence of microvascular disturbances. The brain seems to be particularly vulnerable to metabolic disorders prior to peripheral microvascular pathologies associated with other target organs.

Differential mesolimbic and prefrontal alterations during reward anticipation and consummation in positive and negative schizotypy.

Schizotypy is associated with anhedonia. However, previous findings on the neural substrates of anhedonia in schizotypy are mixed. In the present study, we measured the neural substrates associated with reward anticipation and consummation in positive and negative schizotypy using functional MRI. The Monetary Incentive Delay task was administered to 33 individuals with schizotypy (18 positive schizotypy (PS),15 negative schizotypy (NS)) and 22 healthy controls. Comparison between schizotypy individuals and controls were performed using two-sample T tests for contrast images involving gain versus non-gain anticipation condition and gain versus non-gain consummation condition. Multiple comparisons were corrected using Monte Carlo Simulation correction of p<.05. The results showed no significant difference in brain activity between controls and schizotypy individuals as a whole during gain anticipation or consummation. However, during the consummatory phase, NS individuals rather than PS individuals showed diminished left amygdala and left putamen activity compared with controls. We observed significantly weaker activation at the left ventral striatum during gain anticipation in NS individuals compared with controls. PS individuals, however, exhibited enhanced right ventral lateral prefrontal activity. These findings suggest that different dimensions of schizotypy may be underlied by different neural dysfunctions in reward anticipation and consummation.

Multivariate Neural Representations of Value during Reward Anticipation and Consummation in the Human Orbitofrontal Cortex.

The role of the orbitofrontal cortex (OFC) in value processing is a focus of research. Conventional imaging analysis, where smoothing and averaging are employed, may not be sufficiently sensitive in studying the OFC, which has heterogeneous anatomical structures and functions. In this study, we employed representational similarity analysis (RSA) to reveal the multi-voxel fMRI patterns in the OFC associated with value processing during the anticipatory and the consummatory phases. We found that multi-voxel activation patterns in the OFC encoded magnitude and partial valence information (win vs. loss) but not outcome (favourable vs. unfavourable) during reward consummation. Furthermore, the lateral OFC rather than the medial OFC encoded loss information. Also, we found that OFC encoded values in a similar way to the ventral striatum (VS) or the anterior insula (AI) during reward anticipation regardless of motivated response and to the medial prefrontal cortex (MPFC) and the VS in reward consummation. In contrast, univariate analysis did not show changes of activation in the OFC. These findings suggest an important role of the OFC in value processing during reward anticipation and consummation.

Abnormal functional connectivity of the amygdala-based network in resting-state FMRI in adolescents with generalized anxiety disorder.

BACKGROUND: We aimed to investigate the disruptions of functional connectivity of amygdala-based networks in adolescents with untreated generalized anxiety disorder (GAD). MATERIAL AND METHODS: A total of 26 adolescents with first-episode GAD and 20 normal age-matched volunteers underwent resting-state and T1 functional magnetic resonance imaging (fMRI). We analyzed the correlation of fMRI signal fluctuation between the amygdala and other brain regions. The variation of amygdala-based functional connectivity and its correlation with anxiety severity were investigated. RESULTS: Decreased functional connectivity was found between the left amygdala and left dorsolateral prefrontal cortex. An increased right amygdala functional connectivity with right posterior and anterior lobes of the cerebellum, insula, superior temporal gyrus, putamen, and right amygdala were found in our study. Negative correlations between GAD scores and functional connectivity of the right amygdala with the cerebellum were also observed in the GAD adolescents. CONCLUSIONS: Adolescents with GAD have abnormalities in brain regions associated with the emotional processing pathways.

Neurobiological changes of schizotypy: evidence from both volume-based morphometric analysis and resting-state functional connectivity.

The current study sought to examine the underlying brain changes in individuals with high schizotypy by integrating networks derived from brain structural and functional imaging. Individuals with high schizotypy (n = 35) and low schizotypy (n = 34) controls were screened using the Schizotypal Personality Questionnaire and underwent brain structural and resting-state functional magnetic resonance imaging on a 3T scanner. Voxel-based morphometric analysis and graph theory-based functional network analysis were conducted. Individuals with high schizotypy showed reduced gray matter (GM) density in the insula and the dorsolateral prefrontal gyrus. The graph theoretical analysis showed that individuals with high schizotypy showed similar global properties in their functional networks as low schizotypy individuals. Several hubs of the functional network were identified in both groups, including the insula, the lingual gyrus, the postcentral gyrus, and the rolandic operculum. More hubs in the frontal lobe and fewer hubs in the occipital lobe were identified in individuals with high schizotypy. By comparing the functional connectivity between clusters with abnormal GM density and the whole brain, individuals with high schizotypy showed weaker functional connectivity between the left insula and the putamen, but stronger connectivity between the cerebellum and the medial frontal gyrus. Taken together, our findings suggest that individuals with high schizotypy present changes in terms of GM and resting-state functional connectivity, especially in the frontal lobe.

Analysis of central mechanism of cognitive training on cognitive impairment after stroke: Resting-state functional magnetic resonance imaging study.

OBJECTIVE: To investigate the central mechanism of cognitive training in patients with stroke, using resting state (RS) functional magnetic resonance imaging (fMRI). METHODS: Patients with stroke and executive function and memory deficit were randomized to receive computer-assisted cognitive training (treatment group; total 60 h training over 10 weeks) or no training (control group). All participants received neuropsychological assessment and RS fMRI at baseline and 10 weeks. RESULTS: Patients in the treatment group (n = 16) showed increased functional connectivity (FC) of the hippocampus with the frontal lobe (right inferior, right middle, left middle, left inferior and left superior frontal gyrus) and left parietal lobe at 10 weeks compared with baseline. Patients in the control group (n = 18) showed decreased FC of the left hippocampus-right occipital gyrus, and right hippocampus-right posterior lobe of cerebellum and left superior temporal gyrus. Significant correlations were found between improved neuropsychological scores and increased FC of the hippocampus with the frontal lobe and left parietal lobe in the treatment group only. CONCLUSIONS: Increased RS FC of the hippocampus with the frontal and parietal lobes may be an important mechanism of cognitive recovery after stroke.