The Impact of Temporal Lobe Epilepsy Surgery on Picture Naming and its Relationship to Network Metric Change

Background: Anterior temporal lobe resection (ATLR) is a successful treatment for medically-refractory temporal lobe epilepsy (TLE). In the language-dominant hemisphere, 30%- 50% of individuals experience a naming decline which can impact upon daily life. Measures of structural networks are associated with language performance pre-operatively. It is unclear if analysis of network measures may predict post-operative decline. Methods: White matter fibre tractography was performed on preoperative diffusion MRI of 44 left lateralised and left resection individuals with TLE to reconstruct the preoperative structural network. Resection masks, drawn on co-registered pre- and post-operative T1-weighted MRI scans, were used as exclusion regions on pre-operative tractography to estimate the post-operative network. Changes in graph theory metrics, cortical strength, betweenness centrality, and clustering coefficient were generated by comparing the estimated pre- and post-operative networks. These were thresholded based on the presence of the connection in each patient, ranging from 75% to 100% in steps of 5%. The average graph theory metric across thresholds was taken. We incorporated leave-one-out cross-validation with smoothly clipped absolute deviation (SCAD) least absolute shrinkage and selection operator (LASSO) feature selection and a support vector classifier to assess graph theory metrics on picture naming decline. Picture naming was assessed via the Graded Naming Test preoperatively and at 3 and 12 months post-operatively and the outcome was classified using the reliable change index (RCI) to identify clinically significant decline. The best feature combination and model was selected using the area under the curve (AUC). The sensitivity, specificity and F1-score were also reported. Permutation testing was performed to assess the machine learning model and selected regions difference significance. Results: A combination of clinical and graph theory metrics were able to classify outcome of picture naming at 3 months with an AUC of 0.84. At 12 months, change in strength to cortical regions was best able to correctly classify outcome with an AUC of 0.86. Longitudinal analysis revealed that betweenness centrality was the best metric to identify patients who declined at 3 months, who will then continue to experience decline from 3-12 months. Both models were significantly higher AUC values than a random classifier. Conclusion: Our results suggest that inferred changes of network integrity were able to correctly classify picture naming decline after ATLR. These measures may be used to prospectively to identify patients who are at risk of picture naming decline after surgery and could potentially be utilised to assist tailoring the resection in order to prevent this decline

Contribution of White Matter Fiber Bundle Damage to Language Change After Surgery for Temporal Lobe Epilepsy.

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

The Impact of Temporal Lobe Epilepsy Surgery on Picture Naming and its Relationship to Network Metric Change

BackgroundAnterior temporal lobe resection (ATLR) is a successful treatment for medically-refractory temporal lobe epilepsy (TLE). In the language-dominant hemisphere, 30%- 50% of individuals experience a naming decline which can impact upon daily life. Measures of structural networks are associated with language performance pre-operatively. It is unclear if analysis of network measures may predict post-operative decline.MethodsWhite matter fibre tractography was performed on preoperative diffusion MRI of 44 left lateralised and left resection individuals with TLE to reconstruct the preoperative structural network. Resection masks, drawn on co-registered pre- and post-operative T1-weighted MRI scans, were used as exclusion regions on pre-operative tractography to estimate the post-operative network. Changes in graph theory metrics, cortical strength, betweenness centrality, and clustering coefficient were generated by comparing the estimated pre- and post-operative networks. These were thresholded based on the presence of the connection in each patient, ranging from 75% to 100% in steps of 5%. The average graph theory metric across thresholds was taken.We incorporated leave-one-out cross-validation with smoothly clipped absolute deviation (SCAD) least absolute shrinkage and selection operator (LASSO) feature selection and a support vector classifier to assess graph theory metrics on picture naming decline. Picture naming was assessed via the Graded Naming Test preoperatively and at 3 and 12 months post-operatively and the outcome was classified using the reliable change index (RCI) to identify clinically significant decline. The best feature combination and model was selected using the area under the curve (AUC). The sensitivity, specificity and F1-score were also reported. Permutation testing was performed to assess the machine learning model and selected regions difference significance.ResultsA combination of clinical and graph theory metrics were able to classify outcome of picture naming at 3 months with an AUC of 0.84. At 12 months, change in strength to cortical regions was best able to correctly classify outcome with an AUC of 0.86. Longitudinal analysis revealed that betweenness centrality was the best metric to identify patients who declined at 3 months, who will then continue to experience decline from 3-12 months. Both models were significantly higher AUC values than a random classifier.ConclusionOur results suggest that inferred changes of network integrity were able to correctly classify picture naming decline after ATLR. These measures may be used to prospectively to identify patients who are at risk of picture naming decline after surgery and could potentially be utilised to assist tailoring the resection in order to prevent this decline

Thalamostriatal disconnection underpins long-term seizure freedom in frontal lobe epilepsy 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