The role of the thalamus in modular functional networks in temporal lobe epilepsy with cognitive impairment.

OBJECTIVE: Cognitive deficit is common in patients with temporal lobe epilepsy (TLE). Here, we aimed to investigate the modular architecture of functional networks associated with distinct cognitive states in TLE patients together with the role of the thalamus in modular networks. METHODS: Resting-state functional magnetic resonance imaging scans were acquired from 53 TLE patients and 37 matched healthy controls. All patients received the Montreal Cognitive Assessment test and accordingly were divided into TLE patients with normal cognition (TLE-CN, n = 35) and TLE patients with cognitive impairment (TLE-CI, n = 18) groups. The modular properties of functional networks were calculated and compared including global modularity Q, modular segregation index, intramodular connections, and intermodular connections. Thalamic subdivisions corresponding to the modular networks were generated by applying a 'winner-take-all' strategy before analyzing the modular properties (participation coefficient and within-module degree z-score) of each thalamic subdivision to assess the contribution of the thalamus to modular functional networks. Relationships between network properties and cognitive performance were then further explored. RESULTS: Both TLE-CN and TLE-CI patients showed lower global modularity, as well as lower modular segregation index values for the ventral attention network and the default mode network. However, different patterns of intramodular and intermodular connections existed for different cognitive states. In addition, both TLE-CN and TLE-CI patients exhibited anomalous modular properties of functional thalamic subdivisions, with TLE-CI patients presenting a broader range of abnormalities. Cognitive performance in TLE-CI patients was not related to the modular properties of functional network but rather to the modular properties of functional thalamic subdivisions. CONCLUSIONS: The thalamus plays a prominent role in modular networks and potentially represents a key neural mechanism underlying cognitive impairment in TLE.

Temporal lobe epilepsy: decreased thalamic resting-state functional connectivity and their relationships with alertness performance.

OBJECTIVES: Studies have provided evidence regarding the pathology of the thalamus in patients with temporal lobe epilepsy (TLE). The thalamus, particularly the right thalamus, is one of the subcortical structures that are most uniformly accepted as being significantly involved in alertness. Moreover, alertness impairment in epilepsy has been reported. This study aimed to investigate alterations in thalamic resting-state functional connectivity (FC) and their relationships with alertness performance in patients with TLE; an issue that has not yet been addressed. METHODS: A total of 15 patients with right TLE (rTLE) and 16 healthy controls were recruited for the present study. All of the participants underwent a resting-state functional magnetic resonance imaging (fMRI) scan and the attention network test (ANT). Whole-brain voxel-wise FC analyses were applied to extract the thalamic resting-state functional networks in the patients with rTLE and healthy controls, and the differences between the two groups were evaluated. Correlation analyses were employed to examine the relationships between alterations in thalamic FC and alertness performance in patients with rTLE. RESULTS: Compared to the healthy controls, the FC within and between the bilateral thalamus was decreased in the patients with rTLE. Moreover, in the patient group, the bilateral anterior cingulate cortex (ACC) and subcortical regions, including the bilateral brainstem, cerebellum, putamen, right caudate nucleus, and amygdala, exhibited decreased FC with the ipsilateral thalamus (p<0.05, AlphaSim corrected, cluster size>44) but not with the contralateral thalamus (p<0.05, AlphaSim corrected, cluster size>43). The intrinsic and phasic alertness performances of the patients were impaired (p=0.001 and p<0.001, respectively) but not correlated with decreased thalamic FC. Meanwhile, the alertness performance was not altered in right TLE but was negatively correlated with decreased thalamic FC with ACC (p<0.05). CONCLUSIONS: Our findings highlight the functional importance of the thalamus in TLE pathology and suggest that damage to the thalamic resting-state functional networks, particularly ipsilateral to the epileptogenic focus, is present in patients with TLE.