Objective: Temporal lobe epilepsy (TLE) affects brain networks and is associated with impairment of episodic memory. Temporal and extratemporal reorganization of memory functions is described in functional magnetic resonance imaging (fMRI) studies. Functional reorganizations have been shown at the local activation level, but network-level alterations have been underinvestigated. We aim to investigate the functional anatomy of memory networks using memory fMRI and determine how this relates to memory function in TLE.

Individuals with temporal lobe epilepsy (TLE) may have significant language deficits. Language capabilities may further decline following temporal lobe resections. The language network, comprising dispersed gray matter regions interconnected with white matter fibers, may be atypical in individuals with TLE. This review explores the structural changes to the language network and the functional reorganization of language abilities in TLE. We discuss the importance of detailed reporting of patient's characteristics, such as, left‐ and right‐sided focal epilepsies as well as lesional and nonlesional pathological subtypes. These factors can affect the healthy functioning of gray and/or white matter. Dysfunction of white matter and displacement of gray matter function could concurrently impact their ability, in turn, producing an interactive effect on typical language organization and function. Surgical intervention can result in impairment of function if the resection includes parts of this structure‐function network that are critical to language. In addition, impairment may occur if language function has been reorganized and is included in a resection. Conversely, resection of an epileptogenic zone may be associated with recovery of cortical function and thus improvement in language function. We explore the abnormality of functional regions in a clinically applicable framework and highlight the differences in the underlying language network. Avoidance of language decline following surgical intervention may depend on tailored resections to avoid critical areas of gray matter and their white matter connections. Further work is required to elucidate the plasticity of the language network in TLE and to identify sub‐types of language representation, both of which will be useful in planning surgery to spare language function.

Background and Objectives:In medically refractory temporal lobe epilepsy (TLE), 30-50% of patients experience substantial language decline following resection in the language dominant hemisphere. Here, we investigate the contribution of white matter fiber bundle damage to language change at 3- and 12-months after surgery.Methods:We studied 127 patients who underwent TLE surgery from 2010–2019. Neuropsychological testing included picture naming, semantic, and phonemic verbal fluency, performed pre-operatively, 3- and 12-months post-operatively. Outcome was assessed using reliable change index (RCI; clinically significant decline) and change across timepoints (post- minus pre-operative scores).Functional MRI was used to determine language lateralization. The arcuate (AF), inferior fronto-occipital (IFOF), inferior longitudinal, middle longitudinal (MLF), and uncinate fasciculi were mapped using diffusion MRI probabilistic tractography. Resection masks, drawn comparing co-registered pre- and post-operative T1 MRI scans, were used as exclusion regions on pre-operative tractography to estimate the percentage of pre-operative tracts transected in surgery. Chi-squared assessments evaluated the occurrence of RCI-determined language decline. Independent samples T-tests and MM-estimator robust regressions were used to assess the impact of clinical factors and fiber transection on RCI and change outcomes, respectively.Results:Language dominant and non-dominant resections were treated separately for picture naming, as post-operative outcomes were significantly different between these groups. In language dominant hemisphere resections, greater surgical damage to the AF and IFOF was related to RCI-decline at 3 months. Damage to the inferior frontal sub-fasciculus of the IFOF was related to change at 3 months. In language non-dominant hemisphere resections, increased MLF resection was associated with RCI-decline at 3 months, and damage to the anterior sub-fasciculus was related to change at 3 months.Language dominant and non-dominant resections were treated as one cohort for semantic and phonemic fluency, as there were no significant differences in post-operative decline between these groups. Post-operative seizure freedom was associated with an absence of significant language decline 12 months after surgery for semantic fluency.Discussion:We demonstrate a relationship between fiber transection and naming decline after temporal lobe resection. Individualized surgical planning to spare white matter fiber bundles could help to preserve language function after surgery.

Around 50% of patients undergoing frontal lobe surgery for focal drug-resistant epilepsy become seizure free post-operatively; however, only about 30% of patients remain seizure free in the long-term. Early seizure recurrence is likely to be caused by partial resection of the epileptogenic lesion, whilst delayed seizure recurrence can occur even if the epileptogenic lesion has been completely excised. This suggests a coexistent epileptogenic network facilitating ictogenesis in close or distant dormant epileptic foci. As thalamic and striatal dysregulation can support epileptogenesis and disconnection of cortico-thalamostriatal pathways through hemispherotomy or neuromodulation can improve seizure outcome regardless of focality, we hypothesize that projections from the striatum and the thalamus to the cortex may contribute to this common epileptogenic network. To this end, we retrospectively reviewed a series of 47 consecutive individuals who underwent surgery for drug-resistant frontal lobe epilepsy. We performed voxel-based and tractography disconnectome analyses to investigate shared patterns of disconnection associated with long-term seizure freedom. Seizure freedom after 3 and 5 years was independently associated with disconnection of the anterior thalamic radiation and anterior cortico-striatal projections. This was also confirmed in a subgroup of 29 patients with complete resections, suggesting these pathways may play a critical role in supporting the development of novel epileptic networks. Our study indicates that network dysfunction in frontal lobe epilepsy may extend beyond the resection and putative epileptogenic zone. This may be critical in the pathogenesis of delayed seizure recurrence as thalamic and striatal networks may promote epileptogenesis and disconnection may underpin long-term seizure freedom.

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Anterior temporal lobe resection (ATLR) for temporal lobe epilepsy (TLE) has remission rates up to 80%, however is underutilised, in part because of the risk of language decline following surgery. Language decline occurs in up to 50% of ATLR in the language dominant side. This can occur despite careful planning with functional MRI (fMRI) language mapping. Several white matter bundles are close to the resection area which could contribute to language decline. Diffusion MRI-based fibre tracking to map the arcuate, uncinate, inferior fronto-occipital, inferior, and middle longitudinal fasciculus was performed on 43 patients. We extracted the left-sided bundles in those temporal lobe epilepsy patients who had left-dominant language based on verbal fluency functional MRI (fMRI) and a left-sided resection. Resection masks were manually drawn and used as exclusion regions. Changes from pre- to post-operative tractography and language ability were measured as percentages. Linear regression revealed that the McKenna Graded Naming test decline was predicted by the arcuate and middle longitudinal fasciculus resection (F(2,41)=5.562, p=0.007) with an adjusted R2 of 0.175. These findings demonstrate that damage to anterior arcuate extensions and the middle longitudinal fasciculus affects picture naming ability.lawrence.binding.19@ucl.ac.uk

Anterior temporal lobe resection (ATLR), while successful can result in lasting impairment of language function. White matter bundles have been shown to explain some of the variance seen in language decline after ATLR. Network analysis of the structural connectome has been shown superior in predicting preoperative language ability but remains unexplored in predicting postoperative ability.Diffusion MRI-based tractography was used to generate the preoperative connectome on 54 left-lat- eralised (as determined by functional MRI), left-hemisphere ATLR. Postoperative connectomes were estimated via manually drawn resection masks. Graded naming test (GNT), semantic, and letter fluency were binarised into significant decline or not (via their reliable change indices). Strength (sum of connec- tions) and betweenness centrality (interconnectivity) network changes were generated using pre- and postoperative connectomes as predictor variables. Each model was entered into a linear support vector machine incorporating synthetic minority over-sampling technique for class imbalances.Strength changes alone accurately predicted 81.6% of patients who had GNT decline. Betweenness centrality changes accurately predicted 73.3% of patients who had letter fluency decline. Patients with semantic decline were predicted equally as well by strength and betweenness centrality changes (accuracy=71.1%).These findings demonstrate the usefulness of the structural network in predicting and potentially prevent- ing postoperative language decline.

Perampanel, a noncompetitive antagonist of the postsynaptic a‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic (AMPA) receptor, is effective for controlling focal to bilateral tonic–clonic seizures but is also known to increase feelings of anger. Using statistical parametric mapping–derived measures of activation and task‐modulated functional connectivity (psychophysiologic interaction), we investigated 14 people with focal epilepsy who had verbal fluency functional magnetic resonance imaging (fMRI) twice, before and after the add‐on treatment of perampanel. For comparison, we included 28 people with epilepsy, propensity‐matched for clinical characteristics, who had two scans but no change in anti‐seizure medication (ASM) regimen in‐between. After commencing perampanel, individuals had higher task‐related activations in left orbitofrontal cortex (OFC), fewer task‐related activations in the subcortical regions including the left thalamus and left caudate, and lower task‐related thalamocaudate and caudate‐subtantial nigra connectivity. Decreased task‐related connectivity is observed between the left OFC and precuneus and left medial frontal lobe. Our results highlight the brain regions associated with the beneficiary therapeutic effects on focal to bilateral tonic–clonic seizures (thalamus and caudate) but also the undesired affective side effects of perampanel with increased anger and aggression (OFC).