Long-lasting effects of insufficient sleep on neurocognitive development in early adolescence

Importance: Adolescents nowadays often get insufficient sleep. Yet, the long-term adverse effects of sleep loss on developing brain and behavior remains unknown. Objective: To determine whether insufficient sleep leads to long-lasting impacts on mental health, cognition, and brain development in adolescents across two years. Design: This longitudinal study utilized a public dataset, the Adolescent Brain Cognitive Development (ABCD) study, which is an ongoing study starting from 2016. Setting: Data were collected from 21 research sites in the U.S. Participants: 11,875 9-10-year-olds were recruited using stratified sampling in order to reflect the diversity of the U.S. population. Intervention: Individuals with sufficient versus insufficient sleep (< 9 hours per day for adolescents) were compared after controlling for age (months), sex, race, puberty status, and other 7 covariates based on propensity score matching. Main Outcomes and Measures: Behavior problems, cognition, mental health assessments, resting-state functional connectivity, gray matter volume, cortical area, cortical thickness, and structural connectivity (Fractional anisotropy) were collected and preprocessed by the ABCD study. Independent-sample t-tests and meditation analysis were performed to investigate the effects of insufficient sleep. Results: 3021 matched pairs (50.7% male) were identified based on baseline assessment, with mean (SD) age of 119.5 (7.5) months. In baseline, sufficient sleep is associated less behavioral problems on 18 of 20 assessments, e.g. depress (95% CI of mean difference: -0.28 to -0.47, false discovery rate (FDR)-corrected p < .001, Cohen's d = -0.20), better cognitive performance on 7 of 10 assessments, such as crystal cognition (95% CI: 0.81 to 1.50, FDR-corrected p < .001, Cohen's d = 0.17), better functional connection between cortical regions and basal ganglia (all FDR-corrected p < .05, Cohen's d >0.15), and large structure in ACC and temporal pole (all FDR-corrected p < .05, Cohen's d >0.09). Similar patterns of effect of sufficient sleep were found in FL2 (749 pairs remained) e.g. Cohen's d of function connectivity at baseline was correlated with Cohen's d of that at FL2 (r = 0.54, 95% CI: 0.45 to 0.61, p < 1e-10). Mediation and longitudinal mediation analysis revealed that identified brain measures (e.g. gray matter volume of left temporal pole) at baseline mediated the effect of sufficient sleep on behavioral assessments (e.g. crystal cognition) at baseline and at FL2 (95% CI did not encompass 0, p < 0.05 on 100,000 random-generated bootstrapped samples). Conclusions and Relevance: These results provide strong population-level evidence for the long-lasting detrimental effects of insufficient sleep on mental health, cognition, and brain function and structure in adolescents. The current study identified potential neural mechanisms of adverse effect of insufficient sleep in adolescents, which might provide a theoretical grounding for sleep intervention programs to improve the long-term developmental outcomes in adolescents.

Temporal pole blurring in temporal lobe epilepsy revealed by 3D Edge-Enhancing Gradient Echo MRI

While abnormalities of the hippocampus have been well characterized in temporal lobe epilepsy, various additional temporal lobe abnormalities have also been described. One poorly understood entity, the so-called temporal pole blurring (TPB), is one of the more frequently described neocortical abnormalities in TLE and is thought to represent dysmyelination and axonal loss due to chronic electrical perturbations in early age-onset temporal lobe epilepsy. In this study, we describe the first reported cases of TPB diagnosed by a recently described MRI sequence known as 3D Edge-Enhancing Gradient Echo (3D-EDGE), which has an effective “myelin weighting” making it exquisitely sensitive to this temporal pole dysmyelination. The value of detection of TPB lies in lateralizing seizure onset, as well as predicting a lower baseline neuropsychological performance compared to temporal lobe epilepsy without TPB. Additionally, it is critical to not mistake TPB for alternative diagnoses, such as focal cortical dysplasia or neoplasm.

Histopathological Correlations of Qualitative and Quantitative Temporopolar MRI Analyses in Patients With Hippocampal Sclerosis

Hippocampal sclerosis (HS) is a common cause of pharmacoresistant focal epilepsy. Here, we (1) performed a histological approach to the anterior temporal pole of patients with HS to evaluate cortical and white matter (WM) cell populations, alteration of myelin integrity and markers of neuronal activity, and (2) correlated microscopic data with magnetic resonance imaging (MRI) findings. Our aim was to contribute with the understanding of neuroimaging and pathophysiological mechanisms of temporal lobe epilepsy (TLE) associated with HS. We examined MRIs and surgical specimens from the anterior temporal pole from TLE-HS patients (n = 9) and compared them with 10 autopsy controls. MRIs from healthy volunteers (n = 13) were used as neuroimaging controls. Histological techniques were performed to assess oligodendrocytes, heterotopic neurons, cellular proliferative index, and myeloarchitecture integrity of the WM, as well as markers of acute (c-fos) and chronic (ΔFosB) activities of neocortical neurons. Microscopic data were compared with neuroimaging findings, including T2-weighted/FLAIR MRI temporopolar blurring and values of fractional anisotropy (FA) from diffusion-weighed imaging (DWI). We found a significant increase in WM oligodendrocyte number, both in hematoxylin and eosin, and in Olig2-stained sections. The frequencies of oligodendrocytes in perivascular spaces and around heterotopic neurons were significantly higher in patients with TLE–HS compared with controls. The percentage of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase; a marker of myeloarchitecture integrity) immunopositive area in the WM was significantly higher in TLE-HS, as well as the numbers of c-fos- and ΔFosB-immunostained neocortical neurons. Additionally, we demonstrated a decrease in axonal bundle integrity on neuroimaging, with a significant reduction in the FA in the anterior temporal pole. No differences were detected between individuals with and without temporopolar blurring on visual MRI analysis, considering the number of oligodendroglial cells and percentage of WM CNPase-positive areas. Also, there was no relationship between T2 relaxometry and oligodendrocyte count. In conclusion, our histopathological data support the following: (1) the hypothesis that repetitive neocortical neuronal activity could induce changes in the WM cellular constitution and myelin remodeling in the anterior temporal pole from patients with TLE-HS, (2) that oligodendroglial hyperplasia is not related to temporal blurring or T2 signal intensity on MRI, and (3) that reduced FA is a marker of increase in Olig2-immunopositive cells in superficial temporopolar WM from patients with TLE-HS.

Alterations in Regional Brain Regional Volume Associated with Dioxin Exposure in Men Living in the Most Dioxin-Contaminated Area in Vietnam: Magnetic Resonance Imaging (MRI) Analysis Using Voxel-Based Morphometry (VBM)

To clarify the influence of dioxin exposure on brain morphometry, the present study investigated associations between dioxin exposure at high levels and brain structural irregularities in 32 Vietnamese men. Two exposure markers were used: blood dioxin levels, as a marker of exposure in adulthood, and perinatal dioxin exposure, estimated by maternal residency in a dioxin-contaminated area during pregnancy. All subjects underwent brain magnetic resonance imaging (MRI) scans. We analyzed correlations between regional gray matter volumes and blood dioxin levels, and compared regional volumes between men with and without perinatal dioxin exposure using the voxel-based morphometry (VBM) tool from Statistical Parametric Mapping 12 (SPM12). Blood 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was associated with low volume of the medial temporal pole and fusiform gyrus. Toxic equivalency (TEQ)-PCDDs were correlated with low medial temporal pole volume. However, 1,2,3,4,7,8-HxCDD was associated with high middle frontal gyrus and cerebellum volume. In men with perinatal dioxin exposure, the left inferior frontal gyrus pars orbitalis volume was significantly lower than in those without perinatal exposure. These results suggest that dioxin exposure during the perinatal period and in adulthood may alter regional brain volume, which might lead to cognitive deficits and unusual social emotional behavior in Vietnamese men living in dioxin-contaminated areas.

Hippocampus-Based Static Functional Connectivity Mapping within White Matter in Mild Cognitive Impairment

Mild cognitive impairment (MCI), as the early important stage of Alzheimer’s disease (AD), is clinically characterized by memory loss and cognitive impairment closely associated with the hippocampus. Accumulating studies have confirmed the presence of neural signal changes within white matter (WM) in resting-state fMRI. However, how the abnormal hippocampus affects the WM regions remained unclear in MCI. The current study employed 43 MCI, 71 very MCI (VMCI) and 87 matched healthy controls (HC) participants from the public OASIS 3 dataset. Adopting left and right hippocampus (HIP.R) as seed points respectively, whole-brain functional connectivity (FC) maps were obtained for each subject. Subsequently, one-way ANOVA was performed to explore the abnormal FC regions with hippocampus within gray matter (GM)/WM. Further probabilistic tracking was performed to explore whether the abnormal FC corresponded to structural connectivity. Compared to HC, MCI and VMCI groups exhibited common reduced static FC (SFC) in the middle temporal gyrus within GM, and temporal pole and inferior frontal gyrus within WM. Specific dysconnectivity was shown in the cerebellum_crus2 and inferior temporal gyrus within GM, and frontal gyrus within WM. In addition, the fiber bundle connecting the HIP.R and temporal pole within WM showed abnormally increased mean diffusion in MCI. The current study extended a new functional imaging direction for exploring the mechanism of memory decline, and promoted the understanding for pathophysiological mechanism in different early stages of AD.

Increase in Right Temporal Cortex Thickness Is Related to Decline of Overall Cognitive Function in Patients With Hypertension

Background: Hypertension is associated with poorer cognitive functions, but the mechanisms are unclear.Objective: This research aims to explore the cognitive status of elderly patients with hypertension and the possible mechanisms of hypertension affecting cognitive function.Methods: Data were obtained from the China Longitudinal Aging Study (CLAS), and a total of 128 residents, aged 60 years and above, were recruited in this study. Based on whether they had hypertension, these 128 people were divided into the hypertension (n = 64) and non-hypertension groups (n = 64). The Beijing version of the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to assess the overall cognitive function of the subjects, while digit span, language fluency, Wechsler mapping, and Wechsler wood block were used to assess their domain-specific cognitive function (both at baseline and follow-up stages). At the same time, we also examined baseline blood biochemical indicators (such as total protein, fasting plasma glucose (FPG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), cholesterol, and triglyceride) and baseline MRI data of hippocampus and amygdala volume and temporal polar cortex thickness.Results: The total protein and thickness of temporal polar cortex in patients with hypertension were significantly higher than those in normal controls, but the scores on MMSE, MoCA, digit span, Wechsler mapping and Wechsler wood block at baseline were significantly lower than those in normal controls (p &lt; 0.05). By linear regression analysis and correlation analysis (age and education were controlled), we found that baseline Wechsler mapping scores were negatively correlated with total protein (B = −0.243, t = −3,735, p &lt; 0.001, 95% confidence interval (CI): −0.371 to −0.114); and both the follow-up MMSE score (B = 2.657, t = 2.002, p = 0.049, 95% CI: 0.009~5.306) and the change score of MMSE (r = −0.025, p = 0.047) were related to the thickness of the right temporal pole cortex. Then, by linear regression analysis (mediating model), we found that hypertension may influence follow-up MMSE scores by influencing the cortical thickness of the right temporal pole (B = 1.727, p = 0.022, 95% CI: 0.261–3.193).Conclusions: Elderly patients with hypertension exhibit poorer overall cognitive function and executive function, and the mechanism may be related to the effect of hypertension on the cortical thickness of the right temporal pole.

Mapping connectivity fingerprints for presurgical evaluation of temporal lobe epilepsy

Background Surgery may render temporal lobe epilepsy (TLE) patients seizure-free. However, TLE is a heterogenous entity and surgical prognosis varies between patients. Network-based biomarkers have been shown to be altered in TLE patients and hold promise for classifying TLE subtypes and improving pre-surgical prognosis. The aim of the present study is to investigate a network-based biomarker, the weighted degree of connectivity (wDC), on an individual level, and its relation to TLE subtypes and surgical prognosis. Methods Thirty unilateral TLE patients undergoing the same surgical procedure (anterior temporal resection) and 18 healthy controls were included. All patients were followed-up in the same center for a mean time of 6.85 years and classified as seizure-free (SF) and non seizure-free (non-SF). Using pre-surgical resting state functional MRI, whole brain wDC values for patients and controls were calculated. Then, we divided both temporal lobes in three Regions-of-interest (ROIs) -mesial, pole and lateral- as these areas are known to behave differently in seizure onset and propagation, delimiting different TLE profiles. The wDC values for the defined ROIs of each individual patient were compared with the healthy group. Results After surgery, 14 TLE patients remained SF. As a group, patients had higher wDC than controls in both the temporal pole (p < 0.05) as well as in the mesial regions (p < 0.002) of the to-be-resected temporal lobe. When comparing between SF and non-SF patients, a step-wise binary logistic regression model including all the ROIs, showed that having an increased wDC of the temporal pole (p < 0.05) and the mesial area (p < 0.05) of the to-be-resected temporal lobe was associated with seizure freedom long-term after surgery. Conclusions This study provides a network-based presurgical biomarker that could pave the way towards personalized prediction. In patients with TLE undergoing anterior temporal resections, having an increased wDC at rest could be a signature of the epileptogenic area, and could help identifying those patients who would benefit most from surgery.

The Wernicke conundrum revisited: evidence from connectome-based lesion-symptom mapping in post-stroke aphasia

The classical assumption that word and sentence comprehension deficits in stroke aphasia follow from damage to Wernicke's area has been questioned following discrepant results in primary progressive aphasia. We tested the hypothesis of Mesulam et al. (2015; 2019) that word and sentence comprehension deficits in stroke aphasia result from 'double disconnection' due to white matter damage: word comprehension deficits resulting from disconnection of the anterior temporal lobe and sentence comprehension deficits resulting from disconnection of the frontal lobe. We performed lesion-deficit correlations, including connectome-based lesion-symptom mapping, in four large, partially overlapping groups of English-speaking chronic left hemisphere stroke survivors. After removing variance due to object recognition and associative semantic processing, the same middle and posterior temporal lobe regions were implicated both in word comprehension deficits (N = 180) and complex noncanonical sentence comprehension deficits (N = 131). Repetition deficits (N = 218) were associated with damage to the posterior temporal lobe and superior longitudinal fasciculus, and agrammatic production (N = 92) was associated with damage to the posterior middle frontal gyrus. Connectome lesion-symptom mapping revealed similar temporal-occipital white matter disconnections for impaired word and noncanonical sentence comprehension, including the temporal pole. We found additional significant temporal-parietal disconnections for noncanonical sentence comprehension deficits, which may indicate a role for phonological working memory in processing complex syntax, but no significant frontal-temporal or frontal-parietal disconnections. By contrast, repetition deficits were associated with a very large set of significant disconnections, including frontal-temporal disconnections, and agrammatic production was associated primarily with significant disconnections within the frontal lobe. Our results largely agree with the classical notion that damage to Wernicke's area causes both word and sentence comprehension deficits in stroke-based aphasia, suggest a supporting role for temporal pole in both word and sentence comprehension, and speak against the hypothesis that sentence comprehension deficits in Wernicke's aphasia result from frontal-temporal or frontal-parietal disconnections.

Abnormal Stability of Dynamic Functional Architecture in Amyotrophic Lateral Sclerosis: A Preliminary Resting-State fMRI Study

Purpose: Static and dynamic analyses for identifying functional connectivity (FC) have demonstrated brain dysfunctions in amyotrophic lateral sclerosis (ALS). However, few studies on the stability of dynamic FC have been conducted among ALS patients. This study explored the change of functional stability in ALS and how it correlates with disease severity.Methods: We gathered resting-state functional magnetic resonance data from 20 patients with ALS and 22 healthy controls (HCs). The disease severity was assessed with the Revised ALS Functional Rating Scale (ALSFRS-R). We used a sliding window correlation approach to identify dynamic FC and measured the concordance of dynamic FC over time to obtain the functional stability of each voxel. We assessed the between-group difference in functional stability by voxel-wise two-sample t-test. The correlation between the functional stability index and ALSFRS-R in ALS patients was evaluated using Spearman's correlation analysis.Results: Compared with the HC group, the ALS group had significantly increased functional stability in the left pre-central and post-central gyrus and right temporal pole while decreased functional stability in the right middle and inferior frontal gyrus. The results revealed a significant correlation between ALSFRS-R and the mean functional stability in the right temporal pole (r = −0.452 and P = 0.046) in the ALS patients.Conclusions: ALS patients have abnormal stability of brain functional architecture, which is associated with the severity of the disease.