Minimally invasive surgery for placement of a subcutaneous EEG implant.

Background: A new class of subcutaneous electroencephalography has enabled ultra long-term monitoring of people with epilepsy. The objective of this paper is to describe surgeons' experiences in an early series of implantations as well as discomfort or complications experienced by the participants. Methods: We included 38 implantation procedures from two trials on people with epilepsy and healthy adults. Questionnaires to assess surgeons' and participants' experience were analyzed as well as all recorded adverse events occurring up to 21 days post-surgery. Results: With training, the implantation could be performed in approximately 15 min. Overall, the implantation procedure was considered easy to perform with only 2 episodes where the implant got fixated in the introducing needle and a new implant had to be used. The explantation procedure was considered effortless. In 2 cases the silicone sheath covering the lead was damaged during the explantation, but it was possible to remove the entire implant without leaving any foreign body under the skin. Especially in the trial on healthy participants, a proportion experienced adverse events in the form of headache or implant-pain up to 21 days post-operatively. In 6 cases, adverse events contributed to the decision to explant and discontinue the study: Four of these cases involved implant pain or headache; One case involved a post-operative local infection; and in one case superficial lead placement resulted in skin perforation a few weeks after implantation. Conclusion: The implantation and explantation procedures are considered swift and easy to perform by both neurosurgeons and ENT surgeons. The implant is well tolerated by most participants. However, headache or pain around the implant can occur for up to 21 days post-operatively as anticipated with any such surgery. The expected benefits from the implant should always outweigh the potential disadvantages.

SLCO5A1 and synaptic assembly genes contribute to impulsivity in juvenile myoclonic epilepsy.

Elevated impulsivity is a key component of attention-deficit hyperactivity disorder (ADHD), bipolar disorder and juvenile myoclonic epilepsy (JME). We performed a genome-wide association, colocalization, polygenic risk score, and pathway analysis of impulsivity in JME (n = 381). Results were followed up with functional characterisation using a drosophila model. We identified genome-wide associated SNPs at 8q13.3 (P = 7.5 × 10-9) and 10p11.21 (P = 3.6 × 10-8). The 8q13.3 locus colocalizes with SLCO5A1 expression quantitative trait loci in cerebral cortex (P = 9.5 × 10-3). SLCO5A1 codes for an organic anion transporter and upregulates synapse assembly/organisation genes. Pathway analysis demonstrates 12.7-fold enrichment for presynaptic membrane assembly genes (P = 0.0005) and 14.3-fold enrichment for presynaptic organisation genes (P = 0.0005) including NLGN1 and PTPRD. RNAi knockdown of Oatp30B, the Drosophila polypeptide with the highest homology to SLCO5A1, causes over-reactive startling behaviour (P = 8.7 × 10-3) and increased seizure-like events (P = 6.8 × 10-7). Polygenic risk score for ADHD genetically correlates with impulsivity scores in JME (P = 1.60 × 10-3). SLCO5A1 loss-of-function represents an impulsivity and seizure mechanism. Synaptic assembly genes may inform the aetiology of impulsivity in health and disease.

First Human In Vivo Neuroelectrophysiology Recordings of Uncrossed Dentatothalamocortical White-Matter Connections: On the Fast Tract.

OBJECTIVES: We aim to demonstrate intraoperative recording of cerebellar to cortical pathways that have not been previously recorded in humans, though imaged. METHODS: We report 2 cases with intraoperative neurophysiologic mapping of cerebellocortical tracts. Direct electrical stimulation of subcortical cerebellum along with recordings of cortical evoked potential and motor muscle recordings was performed during surgery. MR tractography data from healthy participants were used to further illustrate the pathways. RESULTS: Neurophysiologic recordings showed large waveforms of evoked potentials in bilateral electrodes over premotor/motor cortices on stimulation of the dentate nucleus. EMG recordings showed responses in face and neck muscles on stimulation of the dentate nucleus at the motor threshold. We thus demonstrated first-in-human in vivo neurophysiologic evidence of cerebellum to cortex responses through an uncrossed dentatothalamocortical tract to the motor/premotor cortices. DISCUSSION: This technique provides a methodology for the direct mapping of the cerebellum and cerebello-cerebral connections. We hypothesize a direct structural connection from the dentate nucleus to the premotor and motor cortices, as well as to ipsilateral hemibody muscles, acting as a fast route of cerebellar output and back up for immediate motor responses. This will further help explain the modulatory effects of the cerebellum on motor, language, and cognitive functions.

Computational modelling in source space from scalp EEG to inform presurgical evaluation of epilepsy.

OBJECTIVE: The effectiveness of intracranial electroencephalography (iEEG) to inform epilepsy surgery depends on where iEEG electrodes are implanted. This decision is informed by noninvasive recording modalities such as scalp EEG. Herein we propose a framework to interrogate scalp EEG and determine epilepsy lateralization to aid in electrode implantation. METHODS: We use eLORETA to map source activities from seizure epochs recorded from scalp EEG and consider 15 regions of interest (ROIs). Functional networks are then constructed using the phase-locking value and studied using a mathematical model. By removing different ROIs from the network and simulating their impact on the network's ability to generate seizures in silico, the framework provides predictions of epilepsy lateralization. We consider 15 individuals from the EPILEPSIAE database and study a total of 62 seizures. Results were assessed by taking into account actual intracranial implantations and surgical outcome. RESULTS: The framework provided potentially useful information regarding epilepsy lateralization in 12 out of the 15 individuals (p=0.02, binomial test). CONCLUSIONS: Our results show promise for the use of this framework to better interrogate scalp EEG to determine epilepsy lateralization. SIGNIFICANCE: The framework may aid clinicians in the decision process to define where to implant electrodes for intracranial monitoring.

Quantification and Selection of Ictogenic Zones in Epilepsy Surgery.

Network models of brain dynamics provide valuable insight into the healthy functioning of the brain and how this breaks down in disease. A pertinent example is the use of network models to understand seizure generation (ictogenesis) in epilepsy. Recently, computational models have emerged to aid our understanding of seizures and to predict the outcome of surgical perturbations to brain networks. Such approaches provide the opportunity to quantify the effect of removing regions of tissue from brain networks and thereby search for the optimal resection strategy. Here, we use computational models to elucidate how sets of nodes contribute to the ictogenicity of networks. In small networks we fully elucidate the ictogenicity of all possible sets of nodes and demonstrate that the distribution of ictogenicity across sets depends on network topology. However, the full elucidation is a combinatorial problem that becomes intractable for large networks. Therefore, we combine computational models with a genetic algorithm to search for minimal sets of nodes that contribute significantly to ictogenesis. We demonstrate the potential applicability of these methods in practice by identifying optimal sets of nodes to resect in networks derived from 20 individuals who underwent resective surgery for epilepsy. We show that they have the potential to aid epilepsy surgery by suggesting alternative resection sites as well as facilitating the avoidance of brain regions that should not be resected.

Elevated Ictal Brain Network Ictogenicity Enables Prediction of Optimal Seizure Control.

Recent studies have shown that mathematical models can be used to analyze brain networks by quantifying how likely they are to generate seizures. In particular, we have introduced the quantity termed brain network ictogenicity (BNI), which was demonstrated to have the capability of differentiating between functional connectivity (FC) of healthy individuals and those with epilepsy. Furthermore, BNI has also been used to quantify and predict the outcome of epilepsy surgery based on FC extracted from pre-operative ictal intracranial electroencephalography (iEEG). This modeling framework is based on the assumption that the inferred FC provides an appropriate representation of an ictogenic network, i.e., a brain network responsible for the generation of seizures. However, FC networks have been shown to change their topology depending on the state of the brain. For example, topologies during seizure are different to those pre- and post-seizure. We therefore sought to understand how these changes affect BNI. We studied peri-ictal iEEG recordings from a cohort of 16 epilepsy patients who underwent surgery and found that, on average, ictal FC yield higher BNI relative to pre- and post-ictal FC. However, elevated ictal BNI was not observed in every individual, rather it was typically observed in those who had good post-operative seizure control. We therefore hypothesize that elevated ictal BNI is indicative of an ictogenic network being appropriately represented in the FC. We evidence this by demonstrating superior model predictions for post-operative seizure control in patients with elevated ictal BNI.

An optimal strategy for epilepsy surgery: Disruption of the rich-club?

Surgery is a therapeutic option for people with epilepsy whose seizures are not controlled by anti-epilepsy drugs. In pre-surgical planning, an array of data modalities, often including intra-cranial EEG, is used in an attempt to map regions of the brain thought to be crucial for the generation of seizures. These regions are then resected with the hope that the individual is rendered seizure free as a consequence. However, post-operative seizure freedom is currently sub-optimal, suggesting that the pre-surgical assessment may be improved by taking advantage of a mechanistic understanding of seizure generation in large brain networks. Herein we use mathematical models to uncover the relative contribution of regions of the brain to seizure generation and consequently which brain regions should be considered for resection. A critical advantage of this modeling approach is that the effect of different surgical strategies can be predicted and quantitatively compared in advance of surgery. Herein we seek to understand seizure generation in networks with different topologies and study how the removal of different nodes in these networks reduces the occurrence of seizures. Since this a computationally demanding problem, a first step for this aim is to facilitate tractability of this approach for large networks. To do this, we demonstrate that predictions arising from a neural mass model are preserved in a lower dimensional, canonical model that is quicker to simulate. We then use this simpler model to study the emergence of seizures in artificial networks with different topologies, and calculate which nodes should be removed to render the network seizure free. We find that for scale-free and rich-club networks there exist specific nodes that are critical for seizure generation and should therefore be removed, whereas for small-world networks the strategy should instead focus on removing sufficient brain tissue. We demonstrate the validity of our approach by analysing intra-cranial EEG recordings from a database comprising 16 patients who have undergone epilepsy surgery, revealing rich-club structures within the obtained functional networks. We show that the postsurgical outcome for these patients was better when a greater proportion of the rich club was removed, in agreement with our theoretical predictions.

Preoperative automated fibre quantification predicts postoperative seizure outcome in temporal lobe epilepsy.

Approximately one in every two patients with pharmacoresistant temporal lobe epilepsy will not be rendered completely seizure-free after temporal lobe surgery. The reasons for this are unknown and are likely to be multifactorial. Quantitative volumetric magnetic resonance imaging techniques have provided limited insight into the causes of persistent postoperative seizures in patients with temporal lobe epilepsy. The relationship between postoperative outcome and preoperative pathology of white matter tracts, which constitute crucial components of epileptogenic networks, is unknown. We investigated regional tissue characteristics of preoperative temporal lobe white matter tracts known to be important in the generation and propagation of temporal lobe seizures in temporal lobe epilepsy, using diffusion tensor imaging and automated fibre quantification. We studied 43 patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis and 44 healthy controls. Patients underwent preoperative imaging, amygdalohippocampectomy and postoperative assessment using the International League Against Epilepsy seizure outcome scale. From preoperative imaging, the fimbria-fornix, parahippocampal white matter bundle and uncinate fasciculus were reconstructed, and scalar diffusion metrics were calculated along the length of each tract. Altogether, 51.2% of patients were rendered completely seizure-free and 48.8% continued to experience postoperative seizure symptoms. Relative to controls, both patient groups exhibited strong and significant diffusion abnormalities along the length of the uncinate bilaterally, the ipsilateral parahippocampal white matter bundle, and the ipsilateral fimbria-fornix in regions located within the medial temporal lobe. However, only patients with persistent postoperative seizures showed evidence of significant pathology of tract sections located in the ipsilateral dorsal fornix and in the contralateral parahippocampal white matter bundle. Using receiver operating characteristic curves, diffusion characteristics of these regions could classify individual patients according to outcome with 84% sensitivity and 89% specificity. Pathological changes in the dorsal fornix were beyond the margins of resection, and contralateral parahippocampal changes may suggest a bitemporal disorder in some patients. Furthermore, diffusion characteristics of the ipsilateral uncinate could classify patients from controls with a sensitivity of 98%; importantly, by co-registering the preoperative fibre maps to postoperative surgical lacuna maps, we observed that the extent of uncinate resection was significantly greater in patients who were rendered seizure-free, suggesting that a smaller resection of the uncinate may represent insufficient disconnection of an anterior temporal epileptogenic network. These results may have the potential to be developed into imaging prognostic markers of postoperative outcome and provide new insights for why some patients with temporal lobe epilepsy continue to experience postoperative seizures.

Functional Connectome before and following Temporal Lobectomy in Mesial Temporal Lobe Epilepsy.

As mesial temporal lobe epilepsy (mTLE) has been recognized as a network disorder, a longitudinal connectome investigation may shed new light on the understanding of the underlying pathophysiology related to distinct surgical outcomes. Resting-state functional MRI data was acquired from mTLE patients before (n = 37) and after (n = 24) anterior temporal lobectomy. According to surgical outcome, patients were classified as seizure-free (SF, n = 14) or non-seizure-free (NSF, n = 10). First, we found higher network resilience to targeted attack on topologically central nodes in the SF group compared to the NSF group, preoperatively. Next, a two-way mixed analysis of variance with between-subject factor 'outcome' (SF vs. NSF) and within-subject factor 'treatment' (pre-operation vs. post-operation) revealed divergent dynamic reorganization in nodal topological characteristics between groups, in the temporoparietal junction and its connection with the ventral prefrontal cortex. We also correlated the network damage score (caused by surgical resection) with postsurgical brain function, and found that the damage score negatively correlated with postoperative global and local parallel information processing. Taken together, dynamic connectomic architecture provides vital information for selecting surgical candidates and for understanding brain recovery mechanisms following epilepsy surgery.

Hippocampal internal architecture and postoperative seizure outcome in temporal lobe epilepsy due to hippocampal sclerosis.

PURPOSE: Semi-quantitative analysis of hippocampal internal architecture (HIA) on MRI has been shown to be a reliable predictor of the side of seizure onset in patients with temporal lobe epilepsy (TLE). In the present study, we investigated the relationship between postoperative seizure outcome and preoperative semi-quantitative measures of HIA. METHODS: We determined HIA on high in-plane resolution preoperative T2 short tau inversion recovery MR images in 79 patients with presumed unilateral mesial TLE (mTLE) due to hippocampal sclerosis (HS) who underwent amygdalohippocampectomy and postoperative follow up. HIA was investigated with respect to postoperative seizure freedom, neuronal density determined from resected hippocampal specimens, and conventionally acquired hippocampal volume. RESULTS: HIA ratings were significantly related to some neuropathological features of the resected hippocampus (e.g. neuronal density of selective CA regions, Wyler grades), and bilaterally with preoperative hippocampal volume. However, there were no significant differences in HIA ratings of the to-be-resected or contralateral hippocampus between patients rendered seizure free (ILAE 1) compared to those continuing to experience seizures (ILAE 2-5). CONCLUSIONS: This work indicates that semi-quantitative assessment of HIA on high-resolution MRI provides a surrogate marker of underlying histopathology, but cannot prospectively distinguish between patients who will continue to experience postoperative seizures and those who will be rendered seizure free. The predictive power of HIA for postoperative seizure outcome in non-lesional patients with TLE should be explored.

Presurgical entorhinal cortex volume and postoperative seizure outcome in temporal lobe epilepsy.

BACKGROUND: Although temporal lobe surgery is an effective treatment for patients with intractable mesial temporal lobe epilepsy (mTLE), a third of patients will continue to experience seizures at 2 years after surgery. The reasons are unknown. One suggestion is that patients with abnormalities of the entorhinal cortex might have a subtype of mTLE that is resistant to surgery. We investigated the association between presurgical entorhinal cortex volume and postoperative outcome in patients with mTLE. METHODS: 78 patients with intractable mTLE and unilateral hippocampal sclerosis underwent comprehensive presurgical evaluation at the Department of Epileptology, University Hospital Bonn, Germany. Patients and 76 age-matched healthy controls received an MP-RAGE T1-weighted MRI. We determined left and right entorhinal cortex volume, masked to participant identity, using rigorous manual techniques. All patients had complex partial seizures, underwent amygdalohippocampectomy, and received postoperative outcome assessment. FINDINGS: There was a significant effect of group (controls, left mTLE, right mTLE) on the volume of the left (univariate ANOVA F=29·6, p<0·001) and right (F=8·3, p<0·001) entorhinal cortex, and entorhinal asymmetry (F=92·6, p<0·001). Post-hoc analysis with Bonferroni correction revealed that patients with left (p<0·001) and right (p=0·01) mTLE had significantly reduced volume of the ipsilateral entorhinal cortex relative to controls, and patients with right mTLE also had volume reduction of the contralateral entorhinal cortex (p=0·01). We found no significant differences in entorhinal cortex volumes and clinical data between patients (n=48, 62%) surgically rendered seizure free (ILAE I-II) and patients (n=30, 38%) with persistent seizures (ILAE III-VI). INTERPRETATION: These data indicate that gross atrophy of the entorhinal cortex is not a predictor of postoperative outcome in patients with intractable mTLE. We are evaluating whether alterations in entorhinal cortex connectivity and extent of resection are related to postoperative outcome in our series of patients. FUNDING: This work was supported by a UK Medical Research Council grant awarded to SSK.

Motor evoked potential polyphasia: a novel endophenotype of idiopathic generalized epilepsy.

OBJECTIVE: We compared the motor evoked potential (MEP) phases using transcranial magnetic stimulation in patients with idiopathic generalized epilepsy (IGE), their relatives, and healthy controls, hypothesizing that patients and their unaffected relatives may share a subtle pathophysiologic abnormality. METHODS: In a cross-sectional study, we investigated 23 patients with IGE, 34 first-degree relatives, and 30 matched healthy controls. Transcranial magnetic stimulation was performed to produce a series of suprathreshold single-pulse MEPs. A semiautomated method was used to count phases. We compared between groups the mean number of MEP phases, the stimulus-to-stimulus variability in MEP phases, and the proportion of polyphasic MEPs within subjects. RESULTS: Patients with IGE and their relatives had a significantly increased number of MEP phases (median for patients 2.24, relatives 2.17, controls 2.01) and a significantly higher proportion of MEPs with more than 2 phases than controls (median for patients 0.118, relatives 0.088, controls 0.013). Patients had a greater stimulus-to-stimulus variability in number of MEP phases than controls. There were no differences between patients and relatives. CONCLUSION: Increased MEP polyphasia in patients with IGE and their first-degree relatives may reflect transient abnormal evoked oscillations. The presence of polyphasic MEPs in relatives as well as patients suggests that MEP polyphasia is not related to treatment, and is in isolation insufficient to predispose to epilepsy. Polyphasic MEP may be a novel endophenotype in IGE.

Morphometric MRI alterations and postoperative seizure control in refractory temporal lobe epilepsy.

Refractory mesial temporal lobe epilepsy (mTLE) is a debilitating condition potentially amenable to resective surgery. However, between 40 and 50% patients continue to experience postoperative seizures. The development of imaging prognostic markers of postoperative seizure outcome is a crucial objective for epilepsy research. In the present study, we performed analyses of preoperative cortical thickness and subcortical surface shape on MRI in 115 of patients with mTLE and radiologically defined hippocampal sclerosis being considered for surgery, and 80 healthy controls. Patients with excellent (International League Against Epilepsy outcome (ILAE) I) and suboptimal (ILAE II-VI) postoperative outcomes had a comparable distribution of preoperative atrophy across the cortex, basal ganglia, and amygdala. Conventional volumetry of whole hippocampal and extrahippocampal subcortical structures, and of global gray and white matter, could not differentiate between patient outcome groups. However, surface shape analysis revealed localized atrophy of the thalamus bilaterally and of the posterior/lateral hippocampus contralateral to intended resection in patients with persistent postoperative seizures relative to those rendered seizure free. Data uncorrected for multiple comparisons also revealed focal atrophy of the ipsilateral hippocampus posterior to the margins of resection in patients with persistent seizures. This data indicates that persistent postoperative seizures after temporal lobe surgery are related to localized preoperative shape alterations of the thalamus bilaterally and the hippocampus contralateral to intended resection. Imaging techniques that have the potential to unlock prognostic markers of postoperative outcome in individual patients should focus assessment on a bihemispheric thalamohippocampal network in prospective patients with refractory mTLE being considered for temporal lobe surgery.

Thalamotemporal alteration and postoperative seizures in temporal lobe epilepsy.

OBJECTIVE: There are competing explanations for persistent postoperative seizures after temporal lobe surgery. One is that 1 or more particular subtypes of mesial temporal lobe epilepsy (mTLE) exist that are particularly resistant to surgery. We sought to identify a common brain structural and connectivity alteration in patients with persistent postoperative seizures using preoperative quantitative magnetic resonance imaging and diffusion tensor imaging (DTI). METHODS: We performed a series of studies in 87 patients with mTLE (47 subsequently rendered seizure free, 40 who continued to experience postoperative seizures) and 80 healthy controls. We investigated the relationship between imaging variables and postoperative seizure outcome. All patients had unilateral temporal lobe seizure onset, had ipsilateral hippocampal sclerosis as the only brain lesion, and underwent amygdalohippocampectomy. RESULTS: Quantitative imaging factors found not to be significantly associated with persistent seizures were volumes of ipsilateral and contralateral mesial temporal lobe structures, generalized brain atrophy, and extent of resection. There were nonsignificant trends for larger amygdala and entorhinal resections to be associated with improved outcome. However, patients with persistent seizures had significant atrophy of bilateral dorsomedial and pulvinar thalamic regions, and significant alterations of DTI-derived thalamotemporal probabilistic paths bilaterally relative to those patients rendered seizure free and controls, even when corrected for extent of mesial temporal lobe resection. INTERPRETATION: Patients with bihemispheric alterations of thalamotemporal structural networks may represent a subtype of mTLE that is resistant to temporal lobe surgery. Increasingly sensitive multimodal imaging techniques should endeavor to transform these group-based findings to individualize prediction of patient outcomes.

Memory fMRI in left hippocampal sclerosis: optimizing the approach to predicting postsurgical memory.

BACKGROUND: An optimal technique for clinical memory fMRI is not established. Previous studies suggest activity in right parahippocampal gyrus and right hippocampus shows the strongest difference between left hippocampal sclerosis (HS) patients and normal control subjects and that the difference in activity between left and right hippocampus predicts postoperative memory change. METHODS: The authors studied 30 patients with mesial temporal lobe epilepsy (mTLE) and left HS, 12 of whom subsequently underwent surgery, and 13 normal control subjects. The patients who had surgery underwent neuropsychometric evaluation pre- and postoperatively. All subjects underwent a verbal memory encoding event-related fMRI study. Activation maps were assessed visually. Subsequently, the brain regions involved in the memory task were revealed by group averaging; these regions were used to determine regions of interest (ROIs) for subsequent analysis. By use of stepwise discriminant function and stepwise multiple regression, the ROIs that optimally discriminated between patients and normal control subjects and that optimally predicted postoperative verbal memory outcome were determined. RESULTS: Visual inspection of individual patient activation statistic maps revealed noisy data that did not afford visual interpretation. Stepwise discriminant function revealed the difference between left and right hippocampal activity best discriminated between patients and normal control subjects. Stepwise multiple regression revealed left hippocampal activity was the strongest predictor of postoperative verbal memory outcome; greater left hippocampal activity predicted a greater postoperative decline in memory. CONCLUSIONS: Patients with left hippocampal sclerosis (HS) differ from normal control subjects in the distribution of memory-encoding activity between left and right hippocampus. Functional adequacy of left hippocampus best predicts postoperative memory outcome in left HS.

Pre-operative verbal memory fMRI predicts post-operative memory decline after left temporal lobe resection.

Functional MRI (fMRI) of cognitive tasks depends on technology widely available in the clinical sphere, but has yet to show a role in the investigation of patients. We report here the first demonstration of a clinically valuable role for cognitive fMRI. Temporal lobe epilepsy (TLE) is commonly caused by hippocampal sclerosis and is frequently resistant to drug treatment. Surgical resection of the left hippocampus in this setting can cure seizures, but may produce significant verbal memory decline, which is hard to predict. We report 10 right-handed TLE patients with left hippocampal sclerosis who underwent left hippocampal resection. We compared currently used data for the prediction of post-operative verbal memory decline in such patients with a novel fMRI assessment of verbal memory encoding. Multiple regression analyses showed that fMRI provided the strongest independent predictor of memory outcome after surgery. At the individual subject level, the fMRI data had high positive predictive value for memory decline.

Epilepsy and surgical mapping.

Drug treatment resistant epilepsy is an important public health problem. Patients with epilepsy of focal origin may have an excellent outcome following surgery that removes the source of seizures. Identification of the precise cortical region producing seizures is crucial to a good outcome; additionally, identification of eloquent cortical areas near the region to be resected is essential to prevent postoperative neurological deficit. A wide range of imaging techniques is valuable for imaging the epileptogenic zone, including high-resolution T1 MRI, T2 signal quantitation, MR spectroscopy, diffusion imaging, PET, SPECT and simultaneous EEG-fMRI. Eloquent cortex has in the past been mapped using highly invasive techniques; fMRI of motor and cognitive tasks holds great promise for future non-invasive mapping strategies.