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.
Highlights
There is growing body of evidence that brain abnormalities in focal epilepsies such temporal lobe epilepsy (TLE) are not limited to the epileptogenic region, but extend into widespread areas of the whole brain
When comparing mesial TLE (mTLE) versus nTLE patients, the California Verbal Learning Test (CVLT) II-long delay free (LDF) as well as the Logical Memory (LM) II scores were lower for the left mTLE patients (p = 0.023 and p = 0.005, respectively)
For the right TLE patients, we found reduced gray matter (GM) volume in six clusters located in the right hippocampus, the right temporal pole, the left anterior cingular cortex (ACC), the left inferior parietal cortex (IPC), the left postcentral gyrus and the left cerebellum relative to the controls doi:10.1371/journal.pone.0154660.g001 (Fig 1B)
Summary
There is growing body of evidence that brain abnormalities in focal epilepsies such temporal lobe epilepsy (TLE) are not limited to the epileptogenic region, but extend into widespread areas of the whole brain These extra-temporal abnormalities have emerged from gray matter (GM)[1], white matter[2,3], metabolic[4,5], and, more recently, resting-state fMRI investigations (see review by [6]). In terms of structural abnormalities, voxel-based morphometry (VBM) studies in TLE have been effective in demonstrating reduced GM volume in multiple brain regions such as the mesial temporal lobe, thalami, insula, or sensory motor cortex[1,7,8] Using this approach, differences between right and left TLE patients[8,9] and between TLE patients with and without mesial temporal sclerosis (MTS)[10,11] have been established. Using a more direct assessment of brain network abnormalities, resting-state functional connectivity (FC) studies in TLE patients have demonstrated both temporal and extra-temporal functional connectivity abnormalities[14,15,16]
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