Foot Surgery Using Resorbable Magnesium Screws.

The use of bioabsorbable magnesium (Mg) screws is new in foot surgery. Their relative merit over conventional titanium screws has not yet been proven. This prospective case series study was conducted to compare the clinical and radiological outcomes of bioabsorbable Mg screws and titanium screws. A consecutive series of patients (n = 60; 11 men and 49 women) underwent corrective hallux valgus surgery. The minimum follow-up period was 1 year. The assessment was based on a patient questionnaire, including the American Orthopedic Foot and Ankle Society (AOFAS) hallux valgus score, visual analog scale, patient's global impression of change (PGIC), and fifth metatarsus circumference (IF5C). The radiographic assessment included the intermetatarsal and hallux valgus angles, as well as time to osteotomy union and hardware failure. At 1 year, similar results were obtained radiographically. The healing of the osteotomies was significantly faster in the Mg group. Hardware failure was common in the Mg group (5/26) than in the TI group (0/34) but hardware removal was more common in the TI group (6/34) versus the MG group (0/26). IF5C increased by 8 ± 2 mm in the Mg group. The AOFAS and PGIC scores at 6 months were similar. Validated foot scores and radiographic analysis indicated that there was no detectable difference between the groups. The fast achievement of osteotomy union compensates for a high rate of hardware failure, resulting in patient satisfaction and avoiding reoperation for hardware removal.

Decoding human spontaneous spiking activity in medial temporal lobe from scalp EEG.

Linking scalp electroencephalography (EEG) signals and spontaneous firing activity from deep nuclei in humans is not trivial. To examine this, we analyzed simultaneous recordings of scalp EEG and unit activity in deeply located sites recorded overnight from patients undergoing pre-surgical invasive monitoring. We focused on modeling the within-subject average unit activity of two medial temporal lobe areas: amygdala and hippocampus. Linear regression model correlates the units' average firing activity to spectral features extracted from the EEG during wakefulness or non-REM sleep. We show that changes in mean firing activity in both areas and states can be estimated from EEG (Pearson r > 0.2, p≪0.001). Region specificity was shown with respect to other areas. Both short- and long-term fluctuations in firing rates contributed to the model accuracy. This demonstrates that scalp EEG frequency modulations can predict changes in neuronal firing rates, opening a new horizon for non-invasive neurological and psychiatric interventions.

Hemiarthroplasty for Hip Fractures: Posterior or Direct Lateral Approach? Advantages and Disadvantages.

BACKGROUND: Several approaches are used to access the hip joint; most common are the direct lateral and posterior. Little consensus exists on which to use when treating hip fractures. OBJECTIVES: To compare short-term complications, postoperative ambulation, and patient-reported outcome measures (PROMS) of direct lateral vs. posterior approaches in hemiarthroplasty for acute hip fractures. METHODS: We conducted a retrospective clinical trial with 260 patients who underwent bipolar hemiarthroplasty in the direct lateral or posterior approach (166 and 94, respectively) between January 2017 and December 2018. The clinical data included short-term complications: prosthetic dislocation, periprosthetic fractures, and infection. Postoperative ambulation was collected 6 weeks postoperatively; PROMS were collected for 173 patients at 2 years follow-up. RESULTS: There were six dislocations overall, average time to dislocation was 22 days postoperative (range 4-34). Five dislocations were after the posterior approach (5.3%) and one after direct lateral (0.6%) (P = 0.01). At 6 weeks follow-up, inability to walk was found in 16.9% of the direct lateral group and 6.4% of the posterior approach group (P = 0.02). In the posterior approach group, 76% could walk more than 20 meters; only half of the direct lateral group could (P = 0.0002). At 2 years follow-up, PROMS did not show a statistically significant difference between the groups. CONCLUSIONS: Posterior approach for hemiarthroplasty following femoral neck fractures allows superior ambulation to the direct lateral approach only for the short-term. However, no long-term clinical advantage was found. This short-term benefit does not justify the increased dislocation rate in the posterior approach.

Assessment of Hypertension Control Among Adults Participating in a Mobile Technology Blood Pressure Self-management Program.

Importance: It is unclear whether mobile technology hypertension self-management programs are associated with blood pressure (BP) control. Objective: To examine whether engagement with a hypertension self-management program with a BP monitor and connected smartphone application with clinically based digital coaching was associated with BP control during a follow-up period of as long as 3 years. Design, Setting, and Participants: This cohort study enrolled US adults with elevated BP or hypertension between January 1, 2015, and July 1, 2020. The hypertension self-management program was provided through the participant's (or their spouse's) employer health plan. Exposures: Program engagement, defined by average number of application sessions. Main Outcomes and Measures: Systolic and diastolic BP measured by a US Food and Drug Administration-cleared BP monitor, with categories defined as normal (systolic BP, <120 mm Hg), elevated (systolic BP, 120-129 mm Hg), stage 1 hypertension (systolic BP, 130-139 mm Hg), and stage 2 hypertension (systolic BP ≥140 mm Hg). Other measures included age, gender, depression, anxiety, diabetes, high cholesterol, smoking, geographic region, area deprivation index, self-reported weight, and device-measured physical activity (steps per day). Results: Among 28 189 participants (median [IQR] age, 51 [43-58] years; 9424 women [40.4%]; 13 902 men [59.6%]), median (IQR) baseline systolic BP was 129.5 mm Hg (120.5-139.6 mm Hg) and diastolic BP was 81.7 mm Hg (75.7-88.4 mm Hg). Median systolic BP at 1 year improved at least 1 category for 495 of 934 participants (53.0%) with baseline elevated BP, 673 of 966 (69.7%) with baseline stage 1 hypertension, and 920 of 1075 (85.7%) with baseline stage 2 hypertension. Participants in the program for 3 years had a mean (SEM) systolic BP reduction of 7.2 (0.4), 12.2 (0.7), and 20.9 (1.7) mm Hg compared with baseline for those starting with elevated, stage 1 hypertension, and stage 2 hypertension, respectively. Greater engagement was associated with lower systolic BP over time (high-engagement group: 131.2 mm Hg; 95% CI, 115.5-155.8 mm Hg; medium-engagement group: 133.4 mm Hg; 95% CI 116.3-159.5 mm Hg; low-engagement group: 135.5 mm Hg; 95% CI, 117.3-164.8 mm Hg; P < .001); these results persisted after adjusting for age, gender, depression, anxiety, diabetes, high cholesterol, smoking, area deprivation index rank, and US region, which was partially mediated by greater physical activity. A very high BP (systolic BP >180 mm Hg) was observed 11 637 times from 3778 participants. Greater engagement was associated with lower risk of very high BP; the estimated probability of a very high BP was greater in the low-engagement group (1.42%; 95% CI, 1.26%-1.59%) compared with the medium-engagement group (0.79%; 95% CI, 0.71%-0.87%; P < .001) and the high-engagement group (0.53%; 95% CI, 0.45%-0.60%; P < .001 for comparison with both groups). Conclusions and Relevance: The findings of this study suggest that a mobile technology hypertension self-management program can support long-term BP control and very high BP detection. Such programs may improve real-world BP monitoring and control.

Interictal Epileptiform Discharge Dynamics in Peri-sylvian Polymicrogyria Using EEG-fMRI.

Polymicrogyria (PMG) is a common malformation of cortical development associated with a higher susceptibility to epileptic seizures. Seizures secondary to PMG are characterized by difficult-to-localize cerebral sources due to the complex and widespread lesion structure. Tracing the dynamics of interictal epileptiform discharges (IEDs) in patients with epilepsy has been shown to reveal the location of epileptic activity sources, crucial for successful treatment in cases of focal drug-resistant epilepsy. In this case series IED dynamics were evaluated with simultaneous EEG-fMRI recordings in four patients with unilateral peri-sylvian polymicrogyria (PSPMG) by tracking BOLD activations over time: before, during and following IED appearance on scalp EEG. In all cases, focal BOLD activations within the lesion itself preceded the activity associated with the time of IED appearance on EEG, which showed stronger and more widespread activations. We therefore propose that early hemodynamic activity corresponding to IEDs may hold important localizing information potentially leading to the cerebral sources of epileptic activity. IEDs are suggested to develop within a small area in the PSPMG lesion with structural properties obscuring the appearance of their electric field on the scalp and only later engage widespread structures which allow the production of large currents which are recognized as IEDs on EEG.

Bilateral epileptic networks in congenital and acquired corpus callosum defects: EEG-fMRI study.

OBJECTIVES: Electroencephalography-correlated functional magnetic resonance imaging (EEG-fMRI) allows imaging of brain-wide epileptic networks, and demonstrates that focal interictal epileptic activity is sometimes accompanied by bilateral functional activations. The corpus callosum (CC) facilitates bilateral spread of epileptic activity and at times targeted surgically for drug-resistant epilepsy (DRE). We hypothesized that focal epileptic networks are more unilateral in patients lacking intact CC. METHODS: We included focal DRE patients who underwent pre-surgical EEG-fMRI and had CC agenesis (group A, n = 5), patients who previously underwent anterior callosotomy as treatment for drop attacks and continued having seizures (group B, n = 6), and control group of patients with focal epilepsy and intact CC (group C, n = 9). Blood-oxygenation-level-dependent (BOLD) signal maps were generated for interictal epileptic discharges. To quantify bi-hemispheric distribution of epileptic networks, laterality indices were compared between groups. Anatomical and diffusion-weighted imaging demonstrated white matter pathways. RESULTS: 96% of studies demonstrated bilateral activations. Laterality indices were similar in groups A and C, whereas group B demonstrated a more bilateral network than group C (p = 0.028). Diffusion-weighted and anatomical imaging showed aberrant white matter pathways and larger anterior commissure in groups A and B. 68% of studies showed maximal activation cluster concordant with the presumed epileptic focus, 28% showed non-maximal activation at presumed focus. SIGNIFICANCE: Focal epileptic activity is associated with bilateral functional activations despite lack of intact CC, and is associated with stronger contralateral activation in patients after anterior callosotomy compared to controls. These findings disprove our initial hypothesis, and combined with white matter structural imaging, may indicate that the CC is not a sole route of propagation of epileptic activity, which might spread via anterior commissure. Our study demonstrates the utility of EEG-fMRI in assessing epileptic networks and potentially aiding in tailoring surgical treatments in DRE patients with callosal anomalies, and in callosal surgeries.

Automatic segmentation, classification, and follow-up of optic pathway gliomas using deep learning and fuzzy c-means clustering based on MRI.

PURPOSE: Optic pathway gliomas (OPG) are low-grade pilocytic astrocytomas accounting for 3-5% of pediatric intracranial tumors. Accurate and quantitative follow-up of OPG using magnetic resonance imaging (MRI) is crucial for therapeutic decision making, yet is challenging due to the complex shape and heterogeneous tissue pattern which characterizes these tumors. The aim of this study was to implement automatic methods for segmentation and classification of OPG and its components, based on MRI. METHODS: A total of 202 MRI scans from 29 patients with chiasmatic OPG scanned longitudinally were retrospectively collected and included in this study. Data included T2 and post-contrast T1 weighted images. The entire tumor volume and its components were manually annotated by a senior neuro-radiologist, and inter- and intra-rater variability of the entire tumor volume was assessed in a subset of scans. Automatic tumor segmentation was performed using deep-learning method with U-Net+ResNet architecture. A fivefold cross-validation scheme was used to evaluate the automatic results relative to manual segmentation. Voxel-based classification of the tumor into enhanced, non-enhanced, and cystic components was performed using fuzzy c-means clustering. RESULTS: The results of the automatic tumor segmentation were: mean dice score = 0.736 ± 0.025, precision = 0.918 ± 0.014, and recall = 0.635 ± 0.039 for the validation data, and dice score = 0.761 ± 0.011, precision = 0.794 ± 0.028, and recall = 0.742 ± 0.012 for the test data. The accuracy of the voxel-based classification of tumor components was 0.94, with precision = 0.89, 0.97, and 0.85, and recall = 1.00, 0.79, and 0.94 for the non-enhanced, enhanced, and cystic components, respectively. CONCLUSION: This study presents methods for automatic segmentation of chiasmatic OPG tumors and classification into the different components of the tumor, based on conventional MRI. Automatic quantitative longitudinal assessment of these tumors may improve radiological monitoring, facilitate early detection of disease progression and optimize therapy management.

Author Correction: The role of mPFC and MTL neurons in human choice under goal-conflict.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Interaction of Temporal Lobe Epilepsy and Posttraumatic Stress Disorder: Network Analysis of a Single Case.

In this case study, we present a 21 years old female with long-standing Temporal Lobe Epilepsy (TLE) who, following a sexual assault, also developed Posttraumatic Stress Disorder (PTSD), leading to a change in her seizure semiology. The new seizures seemed to be a re-enactment of the sexual assault and accordingly were at first thought to be Psychogenic Non-Epileptic Seizures (PNES). Nevertheless, electroencephalography (EEG) recording at the Epilepsy Monitoring Unit (EMU) revealed ictal epileptic brain activity during these new attacks. In order to further explore the nature of the relation between epileptic seizures and PTSD symptomatology, a functional MRI (fMRI) scan was conducted focusing on neural response to threat (fearful faces). The results indicated that the response to threat elicited bilateral amygdala activation, as well as enhanced amygdala connectivity with the insula and anterior cingulate cortex (ACC), all central nodes of the fear circuitry. Accordingly, we suggest that this unique presentation of "pseudo" PNES might stem from the anatomical proximity of the epileptic network in this patient (temporal-insular-frontal) to the fear circuitry, allowing abnormal epileptic activity to "exploit" or activate the fear circuit or vice versa. We further propose that the traumatic experience may have changed the patient's ictal semiology by modifying the course of the spread of the ictal activity toward the PTSD network.

The role of mPFC and MTL neurons in human choice under goal-conflict.

Resolving approach-avoidance conflicts relies on encoding motivation outcomes and learning from past experiences. Accumulating evidence points to the role of the Medial Temporal Lobe (MTL) and Medial Prefrontal Cortex (mPFC) in these processes, but their differential contributions have not been convincingly deciphered in humans. We detect 310 neurons from mPFC and MTL from patients with epilepsy undergoing intracranial recordings and participating in a goal-conflict task where rewards and punishments could be controlled or not. mPFC neurons are more selective to punishments than rewards when controlled. However, only MTL firing following punishment is linked to a lower probability for subsequent approach behavior. mPFC response to punishment precedes a similar MTL response and affects subsequent behavior via an interaction with MTL firing. We thus propose a model where approach-avoidance conflict resolution in humans depends on outcome value tagging in mPFC neurons influencing encoding of such value in MTL to affect subsequent choice.

Preoperative localization of seizure onset zones by magnetic source imaging, EEG-correlated functional MRI, and their combination.

OBJECTIVE: Preoperative localization of seizure onset zones (SOZs) is an evolving field in the treatment of refractory epilepsy. Both magnetic source imaging (MSI), and the more recent EEG-correlated functional MRI (EEG-fMRI), have shown applicability in assisting surgical planning. The purpose of this study was to evaluate the capability of each method and their combination in localizing the seizure onset lobe (SL). METHODS: The study included 14 patients who underwent both MSI and EEG-fMRI before undergoing implantation of intracranial EEG (icEEG) as part of the presurgical planning of the resection of an epileptogenic zone (EZ) during the years 2012-2018. The estimated location of the SL by each method was compared with the location determined by icEEG. Identification rates of the SL were compared between the different methods. RESULTS: MSI and EEG-fMRI showed similar identification rates of SL locations in relation to icEEG results (88% ± 31% and 73% ± 42%, respectively; p = 0.281). The additive use of the coverage lobes of both methods correctly identified 100% of the SL, significantly higher than EEG-fMRI alone (p = 0.039) and nonsignificantly higher than MSI (p = 0.180). False-identification rates of the additive coverage lobes were significantly higher than MSI (p = 0.026) and EEG-fMRI (p = 0.027). The intersecting lobes of both methods showed the lowest false identification rate (13% ± 6%, p = 0.01). CONCLUSIONS: Both MSI and EEG-fMRI can assist in the presurgical evaluation of patients with refractory epilepsy. The additive use of both tests confers a high identification rate in finding the SL. This combination can help in focusing implantation of icEEG electrodes targeting the SOZ.

Functional MRI (fMRI) human mapping for indicating hippocampal content-specific responsivity and laterality.

OBJECTIVE: Presurgical memory functional MRI (fMRI) mapping for temporal lobe epilepsy surgery is important because of the excision of structures in the temporal lobe (e.g., hippocampus) that are relevant for intact memory. Although the American Academy of Neurology recommends the use of fMRI for presurgical mapping of epilepsy of verbal and nonverbal memory to predict memory outcome, there are still no specific recommendations about which tests to use. In the current study, we evaluate the potential for clinical utility of two established neuropsychological tests of memory adapted into the fMRI setting. METHOD: We used the Verbal Paired Associates (VPA) for assessment of verbal memory and the Object Learning and Location (OLL) task for assessment of visuospatial memory. To confirm that these tasks engage the hippocampus, we examined their neural underpinning and patterns of laterality in 20 healthy volunteers (mean age = 26.35). RESULTS: During fMRI of the VPA task of verbal memory, we found a strong left-lateralized posterior hippocampal activation. Remembering the location of objects in the OLL task of visuospatial memory elicited right-lateralized hippocampal activation. CONCLUSIONS: These findings demonstrate the utility of the VPA and OLL tests to delineate domain-specific activity and laterality and, as such, may provide supportive evidence to strengthen links between presurgical neuropsychological assessment and memory fMRI mapping for epilepsy surgery. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Ruminative Tendency Relates to Ventral Striatum Functionality: Evidence From Task and Resting-State fMRI.

BACKGROUND: Ruminative responding involves repetitive and passive thinking about one's negative affect. This tendency interferes with initiation of goal-directed rewarding strategies, which could alleviate depressive states. Such reward-directed response selection has been shown to be mediated by ventral striatum/nucleus accumbens (VS/NAcc) function. However, to date, no study has examined whether trait rumination relates to VS/NAcc functionality. Here, we tested whether rumination moderates VS/NAcc function both in response to reward and during a ruminative state. METHODS: Trait rumination was considered dimensionally using Rumination Response Scale (RRS) scores. Our sample (N = 80) consisted of individuals from a community sample and from patients diagnosed with major depressive disorder, providing a broad range of RRS scores. Participants underwent fMRI to assess two modes of VS/NAcc functionality: 1) in response to reward, and 2) during resting-state, as a proxy for ruminative state. We then tested for associations between RRS scores and VS/NAcc functional profiles, statistically controlling for overall depressive symptom severity. RESULTS: RRS scores correlated positively with VS/NAcc response to reward. Furthermore, we noted that higher RRS scores were associated with increased ruminative-dependent resting-state functional connectivity of the VS/NAcc with the left orbitofrontal cortex. CONCLUSIONS: These findings suggest that ruminative tendencies manifest in VS/NAcc reward- and rumination-related functions, providing support for a theoretical-clinical perspective of rumination as a habitual impairment in selection of rewarding, adaptive coping strategies.

Spatial distribution and hemispheric asymmetry of electrically evoked experiential phenomena in the human brain.

OBJECTIVE: Experiential phenomena (EP), such as illusions and complex hallucinations, are vivid experiences created in one's mind. They can occur spontaneously as epileptic auras or can be elicited by electrical brain stimulation (EBS) in patients undergoing presurgical evaluation for drug-resistant epilepsy. Previous work suggests that EP arise from activation of different nodes within interconnected neural networks mainly in the temporal lobes. Yet, the anatomical extent of these neural networks has not been described and the question of lateralization of EP has not been fully addressed. To this end, an extended number of brain regions in which electrical stimulation elicited EP were studied to test whether there is a lateralization propensity to EP phenomena. METHODS: A total of 19 drug-resistant focal epilepsy patients who underwent EBS as part of invasive presurgical evaluation and who experienced EP during the stimulation were included. Spatial dispersion of visual and auditory illusions and complex hallucinations in each hemisphere was determined by calculation of Euclidean distances between electrodes and their centroid in common space, based on (x, y, z) Cartesian coordinates of electrode locations. RESULTS: In total, 5857 stimulation epochs were analyzed; 917 stimulations elicited responses, out of which 130 elicited EP. Complex visual hallucinations were found to be widely dispersed in the right hemisphere, while they were tightly clustered in the occipital lobe of the left hemisphere. Visual illusions were elicited mostly in the occipital lobes bilaterally. Auditory illusions and hallucinations were evoked symmetrically in the temporal lobes. CONCLUSIONS: These findings suggest that complex visual hallucinations arise from wider spread in the right compared to the left hemisphere, possibly mirroring the asymmetry in the white matter organization of the two hemispheres. These results offer some insights into lateralized differences in functional organization and connectivity that may be important for functional mapping and planning of surgical resections in patients with epilepsy.

Conductive gel bridge sensor for motion tracking in simultaneous EEG-fMRI recordings.

EEG-fMRI allows the localization of the hemodynamic correlates of neural activity and has been shown to be useful as a diagnostic tool in pre-surgical evaluation of refractory epilepsy. However, EEG recordings may be highly contaminated by artifacts induced by movements inside the magnetic field thus rendering the scan difficult for interpretation. Existing methods for motion correction require additional equipment or hardware modification. We introduce a simple method for motion artifact detection, the conductive gel bridge sensor (CGBS), easily applicable using the standard setup. We report examples of CGBS use in two patients with epilepsy and demonstrate the method's ability to successfully differentiate between epochs of brain activity and those of movement.

Conflict monitoring mechanism at the single-neuron level in the human ventral anterior cingulate cortex.

Life requires monitoring and adjusting behavior in the face of conflicts. The conflict monitoring theory implicates the anterior cingulate cortex (ACC) in these processes; its ventral aspect (vACC) specializes in emotional conflict. To elucidate the underpinning neural mechanism, we recorded vACC extracellular activity from 12 patients with mood disorders or epilepsy who performed the face-emotional Stroop task. Behaviorally, both conflict detection and adaptation to conflict were evident. The firing rate of neurons in the vACC represented current conflict, i.e., current-congruency. The late onset of the effect is compatible with a role in monitoring. Additionally, early responses of some neurons represented the immediate history of conflicts, i.e., previous-trial-congruency. Finally, in some neurons the response to the current-trial was modulated by previous-trial-congruency, laying the ground for adjusting-to-conflicts. Our results uncover a single neuron level mechanism in the vACC that encodes and integrates past and present emotional conflicts, allowing humans to accommodate their responses accordingly.

Elaborate mapping of the posterior visual pathway in awake craniotomy.

OBJECTIVE Resection of intraaxial tumors adjacent to the optic radiation (OR) may be associated with postoperative visual field (VF) deficits. Intraoperative navigation using MRI-based tractography and electrophysiological monitoring of the visual pathways may allow maximal resection while preserving visual function. In this study, the authors evaluated the value of visual pathway mapping in a series of patients undergoing awake craniotomy for tumor resection. METHODS A retrospective analysis of prospectively collected data was conducted in 18 patients who underwent an awake craniotomy for resection of intraaxial tumors involving or adjacent to the OR. Preoperative MRI-based tractography was used for intraoperative navigation, and intraoperative acquisition of 3D ultrasonography images was performed for real-time imaging and correction of brain shift. Goggles with light-emitting diodes were used as a standard visual stimulus. Direct cortical visual evoked potential (VEP) recording, subcortical recordings from the OR, and subcortical stimulation of the OR were used intraoperatively to assess visual function and proximity of the lesion to the OR. VFs were assessed pre- and postoperatively. RESULTS Baseline cortical VEP recordings were available for 14 patients (77.7%). No association was found between preoperative VF status and baseline presence of cortical VEPs (p = 0.27). Five of the 14 patients (35.7%) who underwent subcortical stimulation of the OR reported seeing phosphenes in the corresponding contralateral VF. There was a positive correlation (r = 0.899, p = 0.04) between the subcortical threshold stimulation intensity (3-11.5 mA) and the distance from the OR. Subcortical recordings from the OR demonstrated a typical VEP waveform in 10 of the 13 evaluated patients (76.9%). These waveforms were present only when recordings were obtained within 10 mm of the OR (p = 0.04). Seven patients (38.9%) had postoperative VF deterioration, and it was associated with a length of < 8 mm between the tumor and the OR (p = 0.05). CONCLUSIONS Intraoperative electrophysiological monitoring of the visual pathways is feasible but may be of limited value in preserving the functional integrity of the posterior visual pathways. Subcortical stimulation of the OR may identify the location of the OR when done in proximity to the pathways, but such proximity may be associated with increased risk of postoperative worsening of the VF deficit.

Intra-operative multi-site stimulation: Expanding methodology for cortical brain mapping of language functions.

Direct cortical stimulation (DCS) is considered the gold-standard for functional cortical mapping during awake surgery for brain tumor resection. DCS is performed by stimulating one local cortical area at a time. We present a feasibility study using an intra-operative technique aimed at improving our ability to map brain functions which rely on activity in distributed cortical regions. Following standard DCS, Multi-Site Stimulation (MSS) was performed in 15 patients by applying simultaneous cortical stimulations at multiple locations. Language functioning was chosen as a case-cognitive domain due to its relatively well-known cortical organization. MSS, performed at sites that did not produce disruption when applied in a single stimulation point, revealed additional language dysfunction in 73% of the patients. Functional regions identified by this technique were presumed to be significant to language circuitry and were spared during surgery. No new neurological deficits were observed in any of the patients following surgery. Though the neuro-electrical effects of MSS need further investigation, this feasibility study may provide a first step towards sophistication of intra-operative cortical mapping.