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Objective: Focal to bilateral tonic–clonic seizures (FBTCS) represent a challenging subtype of focal temporal lobe epilepsy (TLE) in terms of both severity and treatment response. Most studies have focused on regional brain analysis that is agnostic to the distribution of white matter (WM) pathways associated with a node. We implemented a more selective, edge‐wise approach that allowed for identification of the individual connections unique to FBTCS. Methods: T1‐weighted and diffusion‐weighted images were obtained from 22 patients with solely focal seizures (FS), 43 FBTCS patients, and 65 age/sex‐matched healthy participants (HPs), yielding streamline (STR) connectome matrices. We used diffusion tensor‐derived STRs in an edge‐wise approach to determine specific structural connectivity changes associated with seizure generalization in FBTCS compared to matched FS and HPs. Graph theory metrics were computed on both node‐ and edge‐based connectivity matrices. Results: Edge‐wise analyses demonstrated that all significantly abnormal cross‐hemispheric connections belonged to the FBTCS group. Abnormal connections associated with FBTCS were mostly housed in the contralateral hemisphere, with graph metric values generally decreased compared to HPs. In FBTCS, the contralateral amygdala showed selective decreases in the structural connection pathways to the contralateral frontal lobe. Abnormal connections in TLE involved the amygdala, with the ipsilateral side showing increases and the contralateral decreases. All the FS findings indicated higher graph metrics for connections involving the ipsilateral amygdala. Data also showed that some FBTCS connectivity effects are moderated by aging, recent seizure frequency, and longer illness duration. Significance: Data showed that not all STR pathways are equally affected by the seizure propagation of FBTCS. We demonstrated two key biases, one indicating a large role for the amygdala in the propagation of seizures, the other pointing to the prominent role of cross‐hemispheric and contralateral hemisphere connections in FBTCS. We demonstrated topographic reorganization in FBTCS, pointing to the specific WM tracts involved. [ABSTRACT FROM AUTHOR]

Objective: Stereo‐electroencephalography‐guided three‐dimensional radiofrequency thermocoagulation (SEEG‐3D RFTC) is a minimally invasive treatment for mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE‐HS). This study aimed to investigate the long‐term prognosis after SEEG‐3D RFTC treatment in patients with MTLE‐HS. Methods: This single‐center retrospective study included 28 patients with MTLE‐HS treated with SEEG‐3D RFTC from January 2016 to May 2018. Postoperative curative effects were evaluated using the Engel classification, and the patients were followed up for 5 years. Results: The proportions of patients categorized as Engel I between 1 and 5 years after surgery were 72.41% (12 months after surgery), 67.86% (18 months after surgery), 62.07% (24 months after surgery), 50.00% (36 months after surgery), 42.86% (48 months after surgery), and 42.86% (60 months after surgery), respectively. Regarding long‐term efficacy, based on the Engel classification, SEEG‐3D RFTC showed room for improvement. Significance: This was the first study to evaluate the efficacy of SEEG‐3D RFTC for MTLE‐HS with long‐term follow‐up. SEEG‐3D RFTC is a promising alternative for patients with MTLE‐HS. Plain Language Summary: This study explored the potential of stereoelectroencephalography‐guided three‐dimensional radiofrequency thermocoagulation, a minimally invasive approach, for treating medial temporal lobe epilepsy with hippocampal sclerosis. Involving 28 patients, the research tracked the treatment's success over five years using the Engel classification. Initial results were promising, with 72.41% of patients achieving the most favorable outcome (Engel I) at one year. While there was a gradual decrease in this proportion over time, 42.86% of patients maintained this positive outcome at five years, highlighting the treatment's potential for long‐term efficacy. [ABSTRACT FROM AUTHOR]

Cognitive impairment is a common comorbidity of epilepsy, and adversely impacts people with both frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE). While its neural substrates have been extensively investigated in TLE, functional imaging studies in FLE are scarce. In this study, we profiled the neural processes underlying cognitive impairment in FLE, and directly compared FLE and TLE to establish commonalities and differences. We investigated 172 adult participants (56 with FLE, 64 with TLE, and 52 controls) using neuropsychological tests and four functional MRI tasks probing expressive language (verbal fluency, verb generation) and working memory (verbal and visuo-spatial). Patient groups were comparable in disease duration and anti-seizure medication load. We devise a multiscale approach to map brain activation and deactivation during cognition, and track reorganization in FLE and TLE. Voxel-based analyses were complemented with profiling of task effects across established motifs of functional brain organization: (i) canonical resting-state functional systems, and (ii) the principal functional connectivity gradient, which encodes a continuous transition of regional connectivity profiles, anchoring lower-level sensory and transmodal brain areas at the opposite ends of a spectrum. We show that cognitive impairment in FLE is associated with reduced activation across attentional and executive systems, and reduced deactivation of the default mode system, indicative of a large-scale disorganization of task-related recruitment. The imaging signatures of dysfunction in FLE were broadly similar to those in TLE, but some patterns were syndrome-specific: altered default-mode deactivation was more prominent in FLE, while impaired recruitment of posterior language areas during a task with semantic demands was more marked in TLE. Functional abnormalities in FLE and TLE appeared overall modulated by disease load. On balance, our study elucidates neural processes underlying language and working memory impairment in FLE, identifies shared and syndrome-specific alterations in the two most common focal epilepsies, and sheds light on system behavior that may be amenable to future remediation strategies. [ABSTRACT FROM AUTHOR]

Focal to bilateral tonic-clonic seizures are associated with lower quality of life, higher risk of seizure-related injuries, increased chance of sudden unexpected death, and unfavourable treatment outcomes. Achieving greater understanding of their underlying circuitry offers better opportunity to control these seizures. Towards this goal, we provide a network science perspective of the interactive pathways among basal ganglia, thalamus and cortex, to explore the imprinting of secondary seizure generalization on the mesoscale brain network in temporal lobe epilepsy. Specifically, we parameterized the functional organization of both the thalamocortical network and the basal ganglia–thalamus network with resting state functional MRI in three groups of patients with different focal to bilateral tonic-clonic seizure histories. Using the participation coefficient to describe the pattern of thalamocortical connections among different cortical networks, we showed that, compared to patients with no previous history, those with positive histories of focal to bilateral tonic-clonic seizures, including both remote (none for >1 year) and current (within the past year) histories, presented more uniform distribution patterns of thalamocortical connections in the ipsilateral medial-dorsal thalamic nuclei. As a sign of greater thalamus-mediated cortico-cortical communication, this result comports with greater susceptibility to secondary seizure generalization from the epileptogenic temporal lobe to broader brain networks in these patients. Using interregional integration to characterize the functional interaction between basal ganglia and thalamus, we demonstrated that patients with current history presented increased interaction between putamen and globus pallidus internus, and decreased interaction between the latter and the thalamus, compared to the other two patient groups. Importantly, through a series of 'disconnection' simulations, we showed that these changes in interactive profiles of the basal ganglia–thalamus network in the current history group mainly depended upon the direct but not the indirect basal ganglia pathway. It is intuitively plausible that such disruption in the striatum-modulated tonic inhibition of the thalamus from the globus pallidus internus could lead to an under-suppressed thalamus, which in turn may account for their greater vulnerability to secondary seizure generalization. Collectively, these findings suggest that the broken balance between basal ganglia inhibition and thalamus synchronization can inform the presence and effective control of focal to bilateral tonic-clonic seizures. The mechanistic underpinnings we uncover may shed light on the development of new treatment strategies for patients with temporal lobe epilepsy. [ABSTRACT FROM AUTHOR]

Temporal lobe epilepsy tends to reshape the language system causing maladaptive reorganization that can be characterized by task-based functional MRI, and eventually can contribute to surgical decision making processes. However, the dynamic interacting nature of the brain as a complex system is often neglected, with many studies treating the language system as a static monolithic structure. Here, we demonstrate that as a specialized and integrated system, the language network is inherently dynamic, characterized by rich patterns of regional interactions, whose transient dynamics are disrupted in patients with temporal lobe epilepsy. Specifically, we applied tools from dynamic network neuroscience to functional MRI data collected from 50 temporal lobe epilepsy patients and 30 matched healthy controls during performance of a verbal fluency task, as well as during rest. By assigning 16 language-related regions into four subsystems (i.e. bilateral frontal and temporal), we observed regional specialization in both the probability of transient interactions and the frequency of such changes, in both healthy controls and patients during task performance but not rest. Furthermore, we found that both left and right temporal lobe epilepsy patients displayed reduced interactions within the left frontal 'core' subsystem compared to the healthy controls, while left temporal lobe epilepsy patients were unique in showing enhanced interactions between the left frontal 'core' and the right temporal subsystems. Also, both patient groups displayed reduced flexibility in the transient interactions of the left temporal and right frontal subsystems, which formed the 'periphery' of the language network. Importantly, such group differences were again evident only during task condition. Lastly, through random forest regression, we showed that dynamic reconfiguration of the language system tracks individual differences in verbal fluency with superior prediction accuracy compared to traditional activation-based static measures. Our results suggest dynamic network measures may be an effective biomarker for detecting the language dysfunction associated with neurological diseases such as temporal lobe epilepsy, specifying both the type of neuronal communications that are missing in these patients and those that are potentially added but maladaptive. Further advancements along these lines, transforming how we characterize and map language networks in the brain, have a high probability of altering clinical decision making in neurosurgical centres.10.1093/brain/awy042_video1awy042media15754656112001. [ABSTRACT FROM AUTHOR]

Resting-state networks (RSNs) show spatial patterns generally consistent with networks revealed during cognitive tasks. However, the exact degree of overlap between these networks has not been clearly quantified. Such an investigation shows promise for decoding altered functional connectivity (FC) related to abnormal language functioning in clinical populations such as temporal lobe epilepsy (TLE). In this context, we investigated the network configurations during a language task and during resting state using FC. Twenty-four healthy controls, 24 right and 24 left TLE patients completed a verb generation (VG) task and a resting-state fMRI scan. We compared the language network revealed by the VG task with three FC-based networks (seeding the left inferior frontal cortex (IFC)/Broca): two from the task (ON, OFF blocks) and one from the resting state. We found that, for both left TLE patients and controls, the RSN recruited regions bilaterally, whereas both VG-on and VG-off conditions produced more left-lateralized FC networks, matching more closely with the activated language network. TLE brings with it variability in both task-dependent and task-independent networks, reflective of atypical language organization. Overall, our findings suggest that our RSN captured bilateral activity, reflecting a set of prepotent language regions. We propose that this relationship can be best understood by the notion of pruning or winnowing down of the larger language-ready RSN to carry out specific task demands. Our data suggest that multiple types of network analyses may be needed to decode the association between language deficits and the underlying functional mechanisms altered by disease. Hum Brain Mapp 38:2540-2552, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objective Focal epilepsies, such as temporal lobe epilepsy (TLE), are known to disrupt network activity in areas outside the epileptogenic zone [Tracy et al., 2015]. We devised a measure of temporal instability of resting state functional connectivity (FC), capturing temporal variations of BOLD correlations between brain regions that is less confounded than the 'sliding window' approach common in the literature. Methods We investigated healthy controls and unilateral TLE patients (right and left seizure focus groups), utilizing group ICA to identify the default mode network (DMN), a network associated with episodic memory, a key cognitive deficit in TLE. Our instability analyses focused on: (1) connectivity between DMN region pairs, both within and between TLE patients and matched controls, (2) whole brain group differences between region pairs ipsilateral or contralateral to the epileptogenic temporal lobe. Results For both the whole brain and a more focused analysis of DMN region pairs, temporal stability appears to characterize the healthy brain. The TLE patients displayed more FC instability compared to controls, with this instability more pronounced for the right TLE patients. Significance Our findings challenge the view that the resting state signal is stable over time, providing a measure of signal coherence change that may generate insights into the temporal components of network organization. The precuneus was the region within the DMN consistently expressing this instability, suggesting this region plays a key role in large scale temporal dynamics of the DMN, with such dynamics disrupted in TLE, putting key cognitive functions at risk. Hum Brain Mapp 38:528-540, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective In temporal lobe epilepsy ( TLE), the thalamus is well known for its role in the propagation and spread of epileptiform activity. However, the integrity of thalamocortical functional connectivity ( FC) in TLE and its relation to specific seizure patterns have not yet been determined. We address these issues with resting-state functional magnetic resonance imaging (f MRI). Methods Resting-state f MRI was performed on two groups of unilateral TLE patients: those with focal seizures only (16 left TLE, 16 right TLE) and those with additional generalized seizures (16 left TLE, 10 right TLE), and 16 matched controls. A thalamic parcellation based on FC between five nonoverlapping cortical seeds (prefrontal, motor, somatosensory, parietal-occipital, and temporal) and the ipsilateral thalamus was carried out to parcel each thalamus into five corresponding segments. FCs between each segment and its ipsilateral cortical seed were extracted and compared across groups using analyses of variance ( ANOVAs). Results Compared to healthy controls, patients with TLE displayed decreased thalamocortical FC in multiple posterior and ventromedial thalamic segments of both the ictal and nonictal hemispheres. Our parcellation analysis revealed that these thalamic regions were functionally connected to the parietal/occipital and temporal lobes. In patients with TLE with focal seizures these regional thalamocortical FC decreases were limited to the ictal hemisphere. In contrast, TLE patients with both focal and generalized epileptiform activity displayed FC decreases in both the ictal and nonictal thalamus involving the dorsolateral pulvinar, a region preferentially connected to the parietal and occipital lobes. Significance Our data provide the first evidence of regional specific thalamocortical FC decreases in patients with unilateral TLE. Furthermore, our results demonstrate that patients with different seizure types present different thalamoparietal/occipital FC decrease patterns. While patients with focal seizures present thalamocortical FC decreases in the ictal hemisphere only, patients with additional generalized seizure activity also show thalamocortical FC decreases involving the thalamus in the nonictal hemisphere. [ABSTRACT FROM AUTHOR]

Objective In epilepsy, asymmetries in the organization of mesial temporal lobe (MTL) functions help determine the cognitive risk associated with procedures such as anterior temporal lobectomy. Past studies have investigated the change/shift in a visual episodic memory laterality index (LI) in mesial temporal lobe structures through functional magnetic resonance imaging (fMRI) task activations. Here, we examine whether underlying task-related functional connectivity (FC) is concordant with such standard fMRI laterality measures. Methods A total of 56 patients with temporal lobe epilepsy (TLE) (Left TLE [LTLE]: 31; Right TLE [RTLE]: 25) and 34 matched healthy controls (HC) underwent fMRI scanning during performance of a scene encoding task (SET). We assessed an activation-based LI of the hippocampal gyrus (HG) and parahippocampal gyrus (PHG) during the SET and its correspondence with task-related FC measures. Results Analyses involving the HG and PHG showed that the patients with LTLE had a consistently higher LI (right-lateralized) than that of the HC and group with RTLE, indicating functional reorganization. The patients with RTLE did not display a reliable contralateral shift away from the pathology, with the mesial structures showing quite distinct laterality patterns (HG, no laterality bias; PHG, no evidence of LI shift). The FC data for the group with LTLE provided confirmation of reorganization effects, revealing that a rightward task LI may be based on underlying connections between several left-sided regions (middle/superior occipital and left medial frontal gyri) and the right PHG. The FCs between the right HG and left anterior cingulate/medial frontal gyri were also observed in LTLE. Importantly, the data demonstrate that the areas involved in the LTLE task activation shift to the right hemisphere showed a corresponding increase in task-related FCs between the hemispheres. Significance Altered laterality patterns based on mesial temporal lobe epilepsy (MTLE) pathology manifest as several different phenotypes, varying according to side of seizure onset and the specific mesial structures involved. There is good correspondence between task LI activation and FC patterns in the setting of LTLE, suggesting that reliable visual episodic memory reorganization may require both a shift in nodal activation and a change in nodal connectivity with mesial temporal structures involved in memory. [ABSTRACT FROM AUTHOR]