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.

Mapping thalamocortical network pathology in temporal lobe epilepsy.

OBJECTIVE: Although experimental work has provided evidence that the thalamus is a crucial relay structure in temporal lobe epilepsy (TLE), the relation of the thalamus to neocortical pathology remains unclear. To assess thalamocortical network pathology in TLE, we mapped pointwise patterns of thalamic atrophy and statistically related them to neocortical thinning. METHODS: We studied cross-sectionally 36 patients with drug-resistant TLE and 19 age- and sex-matched healthy control subjects using high-resolution MRI. To localize thalamic pathology, we converted manual labels into surface meshes using the spherical harmonic description and calculated local deformations relative to a template. In addition, we measured cortical thickness by means of the constrained Laplacian anatomic segmentation using proximity algorithm. RESULTS: Compared with control subjects, patients with TLE showed ipsilateral thalamic atrophy that was located along the medial surface, encompassing anterior, medial, and posterior divisions. Unbiased analysis correlating the degree of medial thalamic atrophy with cortical thickness measurements mapped bilateral frontocentral, lateral temporal, and mesiotemporal cortices. These areas overlapped with those of cortical thinning found when patients were compared with control subjects. Thalamic atrophy intensified with a longer duration of epilepsy and was more severe in patients with a history of febrile convulsions. CONCLUSION: The degree and distribution of thalamic pathology relates to the topography and extent of neocortical atrophy, lending support to the concept that the thalamus is an important hub in the pathologic network of TLE.

Thalamo-cortical network pathology in idiopathic generalized epilepsy: insights from MRI-based morphometric correlation analysis.

Epileptic activity underlying idiopathic generalized epilepsy (IGE) is related to abnormal thalamo-cortical interactions. Our purpose was to map in vivo the organization of the thalamo-cortical network in IGE. We measured cortical thickness and thalamic volumes on MRI in 23 IGE patients with generalized tonic-clonic seizures only and 46 healthy controls. Significant correlations between thalamic volumes and cortical thickness were interpreted as thalamo-cortical network connections. In controls, thickness of frontal, limbic, and occipital regions was positively correlated with the thalamic volumes, corresponding to known anatomical connections from sacrificial tracer studies in primates and human in vivo DTI data. In patients, thalamo-cortical network correlations increased in fronto-central and parietal regions, but decreased in limbic areas. Group analysis revealed that, compared to controls, IGE patients had bilateral thalamic atrophy and widespread cortical thinning that was most prominent in fronto-central areas, with a prevalence of up to 40%. Duration of epilepsy affected negatively thalamic volumes and thickness of fronto-central and limbic cortices. These effects were significantly different from aging in controls. Patients with poorly controlled seizures showed an even faster progression in these neocortical regions. Fronto-centro-parietal atrophy in IGE is likely the effect of generalized seizure activity inducing thalamo-cortical network remodeling. On the other hand, limbic abnormalities may take place secondary to thalamic disconnection.

MRI volumetry of the thalamus in temporal, extratemporal, and idiopathic generalized epilepsy.

OBJECTIVE: To examine the specificity of thalamic atrophy in epilepsy. METHODS: Thalamic volume measurements were carried out using high-resolution MRI in 40 patients with pharmacologically intractable temporal lobe epilepsy (TLE), 16 patients with extratemporal lobe epilepsy (ETE), and 17 with idiopathic generalized epilepsy (IGE). Thalamic volumes of patients were compared with those of 21 neurologically normal control subjects. Volumes were correlated with duration of epilepsy. The effect of prolonged febrile seizures and generalized seizures on thalamic volumes was examined. RESULTS: Compared with normal control subjects, patients with TLE had a reduction in thalamic volume ipsilateral to the seizure focus. Thalamic volumes in patients with ETE and IGE were not significantly different from those of normal control subjects. In TLE patients, thalamic volumes ipsilateral to the seizure focus were negatively correlated with duration of epilepsy. Patients with a history of prolonged febrile seizures had more severe thalamic atrophy ipsilateral to the seizure focus than those without febrile seizures. CONCLUSIONS: Thalamic atrophy ipsilateral to the seizure focus is found in TLE but not in other forms of focal epilepsy or IGE. In TLE, thalamic atrophy is correlated with duration of disease. Patients with a history of prolonged febrile seizures had smaller thalamic volumes ipsilateral to the seizure focus than those without.