Gray Matter Abnormalities in Temporal Lobe Epilepsy: Relationships with Resting-State Functional Connectivity and Episodic Memory Performance

Abstract

Temporal lobe epilepsy (TLE) affects multiple brain regions through evidence from both structural (gray matter; GM) and functional connectivity (FC) studies. We tested whether these structural abnormalities were associated with FC abnormalities, and assessed the ability of these measures to explain episodic memory impairments in this population. A resting-state and T1 sequences were acquired on 94 (45 with mesial temporal pathology) TLE patients and 50 controls, using magnetic resonance imaging (MRI) technique. A voxel-based morphometry analysis was computed to determine the GM volume differences between groups (right, left TLE, controls). Resting-state FC between the abnormal GM volume regions was computed, and compared between groups. Finally, we investigated the relation between EM, GM and FC findings. Patients with and without temporal pathology were analyzed separately. The results revealed reduced GM volume in multiple regions in the patients relative to the controls. Using FC, we found the abnormal GM regions did not display abnormal functional connectivity. Lastly, we found in left TLE patients, verbal episodic memory was associated with abnormal left posterior hippocampus volume, while in right TLE, non-verbal episodic memory was better predicted by resting-state FC measures. This study investigated TLE abnormalities using a multi-modal approach combining GM, FC and neurocognitive measures. We did not find that the GM abnormalities were functionally or abnormally connected during an inter-ictal resting state, which may reflect a weak sensitivity of functional connectivity to the epileptic network. We provided evidence that verbal and non-verbal episodic memory in left and right TLE patients may have distinct relationships with structural and functional measures. Lastly, we provide data suggesting that in the setting of occult, non-lesional right TLE pathology, a coupling of structural and functional abnormalities in extra-temporal/non-ictal regions is necessary to produce reductions in episodic memory recall. The latter, in particular, demonstrates the complex structure/function interactions at work when trying to understand cognition in TLE, suggesting that subtle network effects can emerge bearing specific relationships to hemisphere and the type of pathology.

Grey matter volume in healthy and epileptic beagles using voxel-based morphometry – a pilot study

“…Statistically significant reduced GMV in cingulate gyrus could be found in our study in epileptic dogs which is in accordance with several findings in human TLE [ 45 , 46 , 69 ] as well as in epileptic humans with JME and juvenile AE [ 52 , 70 ]. On the other hand, in one study increased GMV in this part of the brain was described in patients with TLE compared to healthy controls [ 47 ].…”

“…The hippocampus of Beagles with IE had statistically significant reduced GMV that was even obvious, when all epileptic Beagles were calculated together. This finding is consistent with several human VBM studies about TLE [ 45 , 46 , 49 , 55 , 56 , 69 , 77 ]. Volumetric studies in veterinary medicine also showed hippocampal atrophy in epileptic dogs [ 24 , 44 ].…”

“…Current study even revealed statistically significant decreased GMV in cerebellum bilaterally. These findings are in accordance with results of several VBM studies of humans with TLE [ 45 , 48 , 49 , 55 , 69 , 85 ], JME [ 51 , 57 ] as well as GTCS [ 53 ]. The cerebellum has connections with a large number of other brain regions, especially the cerebral cortex [ 51 , 86 , 87 ] leading to the hypothesis that nerve cell injury and discharges spread to cerebellum and cause Purkinje cell loss [ 87 – 89 ].…”

Functional Connectivity Abnormalities of Brain Regions With Structural Deficits in Primary Insomnia Patients

“…Multimodal technical methods that combine structure and function may provide more useful information for clinical diagnosis. The combination of VBM and FC was used to study schizophrenia ( Zhang et al, 2015 ), Parkinson’s disease ( Canu et al, 2015 ), and temporal lobe epilepsy ( Doucet et al, 2016 ). To our knowledge, no previous study has investigated the neurobiological mechanisms of PI using a combination of VBM and FC analysis.…”

Common and distinct abnormal frontal-limbic system structural and functional patterns in patients with major depression and bipolar disorder

“…For example, by combining cortical thickness and functional connectivity (FC) analyses in MDD patients, Späti et al (2015) found indications that PFC thinning may impair the engagement of the ACC during depressive episodes, and Van Tol et al (2014) found that cortical thickness of the dmPFC could be used to predict the RSFC between the dmPFC and the default mode network (e.g., the precuneus). The combination of VBM and FC also has been adopted to study schizophrenia ( Zhang et al, 2015 ), temporal lobe epilepsy ( Doucet et al, 2016 ), and Parkinson's disease ( Canu et al, 2015 ). Until now, as far as we know, no prior study has investigated the brain abnormalities in BD or MDD patients by combining VBM and FC analyses.…”