Causal structural covariance network revealing atrophy progression in Alzheimer's disease continuum.

The structural covariance network (SCN) has provided a perspective on the large-scale brain organization impairment in the Alzheimer's Disease (AD) continuum. However, the successive structural impairment across brain regions, which may underlie the disrupted SCN in the AD continuum, is not well understood. In the current study, we enrolled 446 subjects with AD, mild cognitive impairment (MCI) or normal aging (NA) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The SCN as well as a casual SCN (CaSCN) based on Granger causality analysis were applied to the T1-weighted structural magnetic resonance images of the subjects. Compared with that of the NAs, the SCN was disrupted in the MCI and AD subjects, with the hippocampus and left middle temporal lobe being the most impaired nodes, which is in line with previous studies. In contrast, according to the 194 subjects with records on CSF amyloid and Tau, the CaSCN revealed that during AD progression, the CaSCN was enhanced. Specifically, the hippocampus, thalamus, and precuneus/posterior cingulate cortex (PCC) were identified as the core regions in which atrophy originated and could predict atrophy in other brain regions. Taken together, these findings provide a comprehensive view of brain atrophy in the AD continuum and the relationships among the brain atrophy in different regions, which may provide novel insight into the progression of AD.

Community-informed connectomics of the thalamocortical system in generalized epilepsy.

OBJECTIVE: To study the intrinsic organization of the thalamocortical circuitry in patients with generalized epilepsy with tonic-clonic seizures (GTCS) via resting-state fMRI (rs-fMRI) connectome analysis and to evaluate its relation to drug response. METHODS: In a prospectively followed-up sample of 41 patients and 27 healthy controls, we obtained rs-fMRI and structural MRI. After 1 year of follow-up, 27 patients were classified as seizure-free and 14 as drug-resistant. We examined connectivity within and between resting-state communities in cortical and thalamic subregions. In addition to comparing patients to controls, we examined associations with seizure control. We assessed reproducibility in an independent cohort of 21 patients. RESULTS: Compared to controls, patients showed a more constrained network embedding of the thalamus, while frontocentral neocortical regions expressed increased functional diversity. Findings remained significant after regressing out thalamic volume and cortical thickness, suggesting independence from structural alterations. We observed more marked network imbalances in drug-resistant compared to seizure-free patients. Findings were similar in the reproducibility dataset. CONCLUSIONS: Our findings suggest a pathoconnectomic mechanism of generalized epilepsy centered on diverging changes in cortical and thalamic connectivity. More restricted thalamic connectivity could reflect the tendency to engage in recursive thalamocortical loops, which may contribute to hyperexcitability. Conversely, increased connectional diversity of frontocentral networks may relay abnormal activity to an extended bilateral territory. Network imbalances were observed shortly after diagnosis and related to future drug response, suggesting clinical utility.

Connectome Reorganization Associated With Surgical Outcome in Temporal Lobe Epilepsy.

To identify the distinct pattern of anatomical network reorganization in surgically refractory mesial temporal lobe epilepsy (MTLE) patients using a longitudinal design. We collected longitudinal diffusion-weighted images of 19 MTLE patients before and after anterior temporal lobectomy. Patients were classified as seizure-free (SF) or nonseizure-free (NSF) at least 1 year after surgery. We constructed whole-brain anatomical networks derived from white matter tractography and evaluated network connectivity measures by graph theoretical analysis. The reorganization trajectories of network measures in SF and NSF patients were investigated by two-way mixed analysis of variance, with factors "group" (SF vs NSF) and "treatment" (presurgery vs postsurgery). Widespread brain structures showed opposite reorganization trajectories in FS and NSF groups (interaction effect). Most of them showed group difference before surgery and then converge after surgery, suggesting that surgery remodeled these structures into a similar status. Conversly, contralateral amygdala-planum-temporale and thalamic-parietal tracts showed higher connectivity strength in NSF than in SF patients after surgery, indicating maladaptive neuroplastic responses to surgery in NSF patients. Our findings suggest that surgical outcomes are associated not only with the preoperative pattern of anatomical connectivity, but also with connectome reconfiguration following surgery. The reorganization of contralateral temporal lobe and corticothalamic tracts may be particularly important for seizure control in MTLE.

Frequency-dependent amplitude alterations of resting-state spontaneous fluctuations in idiopathic generalized epilepsy.

PURPOSE: Amplitude of low-frequency fluctuation (ALFF) of blood-oxygenation level-dependent (BOLD) has proven a promising way to detect disease-related local brain activity. However, routine approach employs an arbitrary frequency band of 0.01-0.08 Hz, which lacks frequency specificity and blinds to the information contained in other frequency bands. This study investigated the amplitude of fluctuations in full BOLD frequency bands, and addressed how amplitudes of fluctuations change in each specific frequency range in idiopathic generalized epilepsy (IGE). METHODS: Thirty-four IGE patients with generalized tonic-clonic seizure and the same number of age- and sex-matched healthy controls were included. Functional MRI data were acquired using a 2s repetition time. Routine amplitude of low-frequency fluctuation analysis was first performed. The regions showing group difference were set as Region-of-interest for analysis of amplitudes of full-frequency. The amplitudes of BOLD fluctuations were consecutively performed at each frequency bin of 0.002 Hz, and specific frequency amplitude analyses were performed in five different frequency ranges (0-0.01 Hz, 0.01-0.027 Hz, 0.027-0.073 Hz, 0.073-0.198 Hz, and 0.198-0.25 Hz). KEY FINDINGS: The thalamus and prefrontal cortex showed significant group differences in routine amplitude analysis. For amplitude of full-frequency analysis, a reverse pattern was found in the dynamic changes between the thalamus and prefrontal cortex in IGE. Moreover, the prefrontal cortex showed amplitude difference in the 0.01-0.027 Hz band, while the thalamus showed amplitude difference in the 0.027-0.073 Hz band. Both these two regions showed amplitude differences in 0.198-0.25 Hz band. SIGNIFICANCE: We demonstrated the characteristic alterations of amplitude of BOLD fluctuations in IGE in frequency domain. The amplitude analysis of full frequency may potentially help to select specific frequency range for detecting epilepsy-related brain activity, and provide insights into the pathophysiological mechanism of IGE.

Gray-matter volume reduction in the thalamus and frontal lobe in epileptic patients with generalized tonic-clonic seizures.

BACKGROUND AND PURPOSE: Generalized tonic-clonic seizures (GTCS) comprise a common subsyndrome of idiopathic generalized epilepsy (IGE). Previous studies found that patients with GTCS had structural abnormalities in a few specific brain regions. However, the underlying clinical cause leading to these abnormalities remains unclear. The present study aimed to explore the relationship between changes in gray-matter (GM) volume and duration of epilepsy, based on GM volume differences observed between GTCS patients and healthy controls. PATIENTS AND METHODS: Voxel-based morphometry (VBM) analysis with DARTEL (diffeomorphic anatomical registration through exponential Lie algebra) was used to investigate GM volume differences in 31 GTCS patients compared with 37 age- and gender-matched healthy controls. Voxel-based correlation analysis was used to explore the relationship between GM volume and duration of epilepsy in GTCS patients. RESULTS: Compared with healthy controls, GTCS patients showed significant decreases in GM volume in the bilateral thalami, frontal lobe, insula and cerebellum. In addition, GM volume in the bilateral thalami and left medial frontal gyrus had a negative correlation with duration of epilepsy. CONCLUSION: GM volume changes in the thalamus and frontal lobe were associated with progressive epileptic seizures. The results indicate the presence of an abnormal thalamocortical network, which may reflect an underlying pathophysiological mechanism of GTCS.