Internal Representations Are Prioritized by Frontoparietal Theta Connectivity and Suppressed by alpha Oscillation Dynamics: Evidence from Concurrent Transcranial Magnetic Stimulation EEG and Invasive EEG.

Control over internal representations requires the prioritization of relevant information and suppression of irrelevant information. The frontoparietal network exhibits prominent neural oscillations during these distinct cognitive processes. Yet, the causal role of this network-scale activity is unclear. Here, we targeted theta-frequency frontoparietal coherence and dynamic alpha oscillations in the posterior parietal cortex using online rhythmic transcranial magnetic stimulation (TMS) in women and men while they prioritized or suppressed internally maintained working memory (WM) representations. Using concurrent high-density EEG, we provided evidence that we acutely drove the targeted neural oscillation and TMS improved WM capacity only when the evoked activity corresponded with the desired cognitive process. To suppress an internal representation, we increased the amplitude of lateralized alpha oscillations in the posterior parietal cortex contralateral to the irrelevant visual field. For prioritization, we found that TMS to the prefrontal cortex increased theta-frequency connectivity in the prefrontoparietal network contralateral to the relevant visual field. To understand the spatial specificity of these effects, we administered the WM task to participants with implanted electrodes. We found that theta connectivity during prioritization was directed from the lateral prefrontal to the superior posterior parietal cortex. Together, these findings provide causal evidence in support of a model where a frontoparietal theta network prioritizes internally maintained representations and alpha oscillations in the posterior parietal cortex suppress irrelevant representations.

Day one postoperative MRI findings following electrode placement for deep brain stimulation: analysis of a large case series.

Objective: This study sought to characterize postoperative day one MRI findings in deep brain stimulation (DBS) patients. Methods: DBS patients were identified by CPT and had their reviewed by a trained neuroradiologist and neurosurgeon blinded to MR sequence and patient information. The radiographic abnormalities of interest were track microhemorrhage, pneumocephalus, hematomas, and edema, and the occurrence of these findings in compare the detection of these complications between T1/T2 gradient-echo (GRE) and T1/T2 fluid-attenuated inversion recovery (FLAIR) magnetic resonance (MR) sequences was compared. The presence, size, and association of susceptibility artifact with other radiographic abnormalities was also described. Lastly, the association of multiple microelectrode cannula passes with each radiographic finding was evaluated. Ad-hoc investigation evaluated hemisphere-specific associations. Multiple logistic regression with Bonferroni correction (corrected p = 0.006) was used for all analysis. Results: Out of 198 DBS patients reviewed, 115 (58%) patients showed entry microhemorrhage; 77 (39%) track microhemorrhage; 44 (22%) edema; 69 (35%) pneumocephalus; and 12 (6%) intracranial hematoma. T2 GRE was better for detecting microhemorrhage (OR = 14.82, p < 0.0001 for entry site and OR = 4.03, p < 0.0001 for track) and pneumocephalus (OR = 11.86, p < 0.0001), while T2 FLAIR was better at detecting edema (OR = 123.6, p < 0.0001). The relatively common findings of microhemorrhage and edema were best visualized by T2 GRE and T2 FLAIR sequences, respectively. More passes intraoperatively was associated with detection of ipsilateral track microhemorrhage (OR = 7.151, p < 0.0001 left; OR = 8.953, p < 0.0001 right). Susceptibility artifact surrounding electrodes possibly interfered with further detection of ipsilateral edema (OR = 4.323, p = 0.0025 left hemisphere only). Discussion: Day one postoperative magnetic resonance imaging (MRI) for DBS patients can be used to detect numerous radiographic abnormalities not identifiable on a computed tomographic (CT) scan. For this cohort, multiple stimulating cannula passes intraoperatively was associated with increased microhemorrhage along the electrode track. Further studies should be performed to evaluate the clinical relevance of these observations.

Reducing Ataxic Side Effects from Ventral Intermediate Nucleus of the Thalamus Deep Brain Stimulation Implantation in Essential Tremor: Potential Advantages of Directional Stimulation.

OBJECTIVE: The aim of the study was to retrospectively evaluate the effect of directional deep brain stimulation (DBS) on ataxia in an essential tremor patient population. MATERIALS AND METHODS: A retrospective chart review of documented Scale for Assessment and Rating of Ataxia (SARA) scores were analyzed using a case-control design. All subjects we evaluated were treated at a single, tertiary care academic center. We reviewed 14 patients who underwent bilateral ventral intermediate nucleus of the thalamus (VIM) implantation with microelectrode recording, with electrodeposition and segmented contact orientation confirmed via postoperative computed tomography. The main outcome was to determine change in ataxia scores between directional versus monopolar circumferential stimulation. RESULTS: Fourteen patients (9 males, median age at implantation 69 [range 63-82]) underwent surgery between October 2017 and July 2020 at the UNC Movement Disorders Center. SARA scores between directional stimulation and monopolar circumferential stimulation demonstrated a significant reduction in total scores with best possible segmented stimulation (n = 13, p < 0.0001, 95% confidence interval [CI] -3.496 to -6.789). This difference remained statistically significant even after removing the SARA tremor subscore (n = 13, p < 0.0001, 95% CI -3.155 to -6.274). In line with prior reports, SARA score changes from the preoperative state were generally worsened when applying monopolar circumferential stimulation bilaterally (n = 13, p = 0.655; 95% CI -2.836 to 4.359), but improved with directional stimulation (n = 13, p = 0.010; 95% CI -1.216 to -7.547). CONCLUSION: This retrospective analysis appears to show evidence for improved outcomes through directional stimulation in bilateral VIM DBS implantation with reduction of ataxic side effects that have traditionally plagued postoperative results, all while providing optimized tremor reduction via stimulation.

Feasibility of stereo electroencephalogram (SEEG) with little to no scalp bone; a case report.

Stereo electroencephalogram (SEEG) electrode placement with cranially fixed guide bolts is recognized as one of the most accurate and safest implantation strategies to sample deep and buried cortex during certain clinical scenarios involving epilepsy surgery. Bone thickness of less than 2 mm is a relative contraindication to SEEG. Here, we describe a case drug-resistant focal epilepsy where prior craniotomies, infections and radiation therapy yielded limited skull bone requiring invasive EEG monitoring. Due to the inability to use bolts over areas with limited skull bone, we successfully utilized a combination of the standard and a modified SEEG techniques for implantation and stabilization of intracranial electrodes without complications. This strategy enabled optimal intracranial EEG monitoring and surgical management of the patient's drug-resistant focal seizures.

Mesial temporal resection following long-term ambulatory intracranial EEG monitoring with a direct brain-responsive neurostimulation system.

OBJECTIVE: To describe seizure outcomes in patients with medically refractory epilepsy who had evidence of bilateral mesial temporal lobe (MTL) seizure onsets and underwent MTL resection based on chronic ambulatory intracranial EEG (ICEEG) data from a direct brain-responsive neurostimulator (RNS) system. METHODS: We retrospectively identified all patients at 17 epilepsy centers with MTL epilepsy who were treated with the RNS System using bilateral MTL leads, and in whom an MTL resection was subsequently performed. Presumed lateralization based on routine presurgical approaches was compared to lateralization determined by RNS System chronic ambulatory ICEEG recordings. The primary outcome was frequency of disabling seizures at last 3-month follow-up after MTL resection compared to seizure frequency 3 months before MTL resection. RESULTS: We identified 157 patients treated with the RNS System with bilateral MTL leads due to presumed bitemporal epilepsy. Twenty-five patients (16%) subsequently had an MTL resection informed by chronic ambulatory ICEEG (mean = 42 months ICEEG); follow-up was available for 24 patients. After MTL resection, the median reduction in disabling seizures at last follow-up was 100% (mean: 94%; range: 50%-100%). Nine patients (38%) had exclusively unilateral electrographic seizures recorded by chronic ambulatory ICEEG and all were seizure-free at last follow-up after MTL resection; eight of nine continued RNS System treatment. Fifteen patients (62%) had bilateral MTL electrographic seizures, had an MTL resection on the more active side, continued RNS System treatment, and achieved a median clinical seizure reduction of 100% (mean: 90%; range: 50%-100%) at last follow-up, with eight of fifteen seizure-free. For those with more than 1 year of follow-up (N = 21), 15 patients (71%) were seizure-free during the most recent year, including all eight patients with unilateral onsets and 7 of 13 patients (54%) with bilateral onsets. SIGNIFICANCE: Chronic ambulatory ICEEG data provide information about lateralization of MTL seizures and can identify additional patients who may benefit from MTL resection.

Network-Targeted, Multi-site Direct Cortical Stimulation Enhances Working Memory by Modulating Phase Lag of Low-Frequency Oscillations.

Working memory is mediated by the coordinated activation of frontal and parietal cortices occurring in the theta and alpha frequency ranges. Here, we test whether electrically stimulating frontal and parietal regions at the frequency of interaction is effective in modulating working memory. We identify working memory nodes that are functionally connected in theta and alpha frequency bands and intracranially stimulate both nodes simultaneously in participants performing working memory tasks. We find that in-phase stimulation results in improvements in performance compared to sham stimulation. In addition, in-phase stimulation results in decreased phase lag between regions within working memory network, while anti-phase stimulation results in increased phase lag, suggesting that shorter phase lag in oscillatory connectivity may lead to better performance. The results support the idea that phase lag may play a key role in information transmission across brain regions. Thus, brain stimulation strategies to improve cognition may require targeting multiple nodes of brain networks.

Brain death in low-income countries: a report from Malawi.

Most low-income nations have no practice guidelines for brain death; data describing brain death in these regions is absent. Our retrospective study describes the prevalence of brain death among patients treated in an intensive care unit (ICU) at a referral hospital in Malawi. The primary outcome was designation of brain death in the medical chart. Of 449 ICU patients included for analysis between September 2016 and May 2018, 43 (9.6%) were diagnosed with brain death during the ICU admission. The most common diagnostic reasons for admission among these patients were trauma (49%), malaria (16%) and postoperative monitoring after general abdominal surgery (19%). All patients diagnosed with brain death were declared dead in the hospital, after cardiac death. In conclusion, the incidence of brain death in a Malawi ICU is substantially higher than that seen in high-income ICU settings. Brain death is not treated as clinical death in Malawi.

Low-frequency direct cortical stimulation of left superior frontal gyrus enhances working memory performance.

The neural substrates of working memory are spread across prefrontal, parietal and cingulate cortices and are thought to be coordinated through low frequency cortical oscillations in the theta (3-8 Hz) and alpha (8-12 Hz) frequency bands. While the functional role of many subregions have been elucidated using neuroimaging studies, the role of superior frontal gyrus (SFG) is not yet clear. Here, we combined electrocorticography and direct cortical stimulation in three patients implanted with subdural electrodes to assess if superior frontal gyrus is indeed involved in working memory. We found left SFG exhibited task-related modulation of oscillations in the theta and alpha frequency bands specifically during the encoding epoch. Stimulation at the frequency matched to the endogenous oscillations resulted in reduced reaction times in all three participants. Our results provide evidence for SFG playing a functional role in working memory and suggest that SFG may coordinate working memory through low-frequency oscillations thus bolstering the feasibility of using intracranial electric stimulation for restoring cognitive function.

Challenges and opportunities for effective data collection in global neurosurgery: traumatic brain injury surveillance experience in Malawi.

Global health research can transform clinical and surgical practice worldwide. Partnerships between US academic centers and hospitals in low- and middle-income counties can improve clinical care at the host institution hospital and give the visiting institution access to a large volume of valuable research data. Recognizing the value of these partnerships, the University of North Carolina (UNC) formed a partnership with Kamuzu Central Hospital (KCH) in Lilongwe, Malawi. The Department of Neurosurgery joined the partnership with KCH and designed a Head Trauma Surveillance Registry. The success of this registry depended on the development of methods to accurately collect head injury data at KCH. Since medical record documentation is often unreliable in this setting, data collection teams were implemented to capture data from head trauma patients on a 24-hours-a-day, 7-days-a-week basis. As data collection improved, pilot groups tested methods to collect new variables and the registry expanded. UNC provided onsite and remote oversight to strengthen the accuracy of the data. Data accuracy still remains a hurdle in global research. Data collection teams, oversight from UNC, pilot group testing, and meaningful collaboration with local physicians improved the accuracy of the head trauma registry. Overall, these methods helped create a more accurate epidemiological and outcomes-centered analysis of brain injury patients at KCH to date.

Using Lean Quality Improvement Tools to Increase Delivery of Evidence-Based Tobacco Use Treatment in Hospitalized Neurosurgical Patients.

BACKGROUND: Health care providers routinely undertreat tobacco dependence, indicating a need for innovative ways to increase delivery of evidence-based care. Lean, a set of quality improvement (QI) tools used increasingly in health care, can help streamline processes, create buy-in for use of evidence-based practices, and lead to the identification of solutions on the basis of a problem's root causes. To date, no published research has examined the use of Lean tools in tobacco dependence. A 12-month QI project using Lean tools was conducted to increase delivery of evidence-based tobacco use treatment (TUT) to hospitalized neurosurgical patients. METHODS: The study team developed a nicotine replacement therapy (NRT) and counseling protocol for neurosurgery inpatients who indicated current tobacco use and used Lean tools to increase protocol adherence. Rates of NRT prescription, referrals to counseling, and follow-up phone calls were compared pre- and postintervention. Secondary measures included patient satisfaction with intervention, quit rates, and reduction rates at 4 weeks postdischarge. RESULTS: Referrals to counseling doubled from 31.7% at baseline to 62.0% after implementation of the intervention, and rates of nicotine replacement therapy (NRT) prescriptions during hospitalization and at discharge increased from 15.3% to 28.5% and 9.0% to 19.3%, respectively. Follow-up phone call rates also dramatically increased. The majority of satisfaction survey respondents indicated that counseling had a positive or neutral impact on stress level and overall satisfaction. CONCLUSION: Lean tools can dramatically increase use of evidence-based TUT in hospitalized patients. This project is easily replicable by professionals seeking to improve delivery of tobacco treatment. These findings may be particularly helpful to inpatient surgical departments that have traditionally been reticent to prescribe NRT.

The effect of anatomic location of injury on mortality risk in a resource-poor setting.

INTRODUCTION: Injury is a significant cause of death, with approximately 4.7 million people mortalities each year. By 2030, injury is predicted to be among the top 20 causes of death worldwide. We sought to characterize and compare the mortality probability in trauma patients in a resource-poor setting based on anatomic location of injury. METHODS: We performed a retrospective analysis of prospectively collected data using the trauma database at Kamuzu Central Hospital (KCH) in Lilongwe, Malawi. We included all adult trauma patients (≥16years) admitted between 2011 and 2015. We stratified patients according to anatomic location of injury, and used descriptive statistics to compare characteristics and management of each group. Bivariate analysis by mortality was done to determine covariates for our adjusted model. A Cox proportional hazard model was performed, using upper extremity injury as the baseline comparator. Descriptive statistics were used to describe the trend in incidence and mortality of head and spine injuries over five years. RESULTS: Of the 76,984 trauma patients who presented to KCH from 2011 to 2015, 49,126 (63.8%) were adults, and 8569 (17.4%) were admitted. The most common injury was to the head or spine, seen in 3712 patients (43.6%). The highest unadjusted hazard ratio for mortality was in head and spine injury patients, at 3.685 (95% CI=2.50-5.44), which increased to 4.501 (95% CI=2.78-7.30) when adjusted for age, sex, injury severity, transfer status, injury mechanism, and surgical intervention. Abdominal trauma had the second highest adjusted hazard of mortality, at 3.62 (95% CI=1.92-6.84) followed by thoracic trauma (HR=1.3621, 95% CI=0.49-3.56). CONCLUSION: In our setting, head or spine injury significantly increases the hazard of mortality significantly compared to all other anatomic injury locations. The prioritization of timely operative and non-operative head injury management is imperative. The development of head injury units may help attenuate trauma- related mortality in resource poor settings.

Modulation of Cortical Oscillations by Low-Frequency Direct Cortical Stimulation Is State-Dependent.

Cortical oscillations play a fundamental role in organizing large-scale functional brain networks. Noninvasive brain stimulation with temporally patterned waveforms such as repetitive transcranial magnetic stimulation (rTMS) and transcranial alternating current stimulation (tACS) have been proposed to modulate these oscillations. Thus, these stimulation modalities represent promising new approaches for the treatment of psychiatric illnesses in which these oscillations are impaired. However, the mechanism by which periodic brain stimulation alters endogenous oscillation dynamics is debated and appears to depend on brain state. Here, we demonstrate with a static model and a neural oscillator model that recurrent excitation in the thalamo-cortical circuit, together with recruitment of cortico-cortical connections, can explain the enhancement of oscillations by brain stimulation as a function of brain state. We then performed concurrent invasive recording and stimulation of the human cortical surface to elucidate the response of cortical oscillations to periodic stimulation and support the findings from the computational models. We found that (1) stimulation enhanced the targeted oscillation power, (2) this enhancement outlasted stimulation, and (3) the effect of stimulation depended on behavioral state. Together, our results show successful target engagement of oscillations by periodic brain stimulation and highlight the role of nonlinear interaction between endogenous network oscillations and stimulation. These mechanistic insights will contribute to the design of adaptive, more targeted stimulation paradigms.

Initial experience in hybrid PET-MRI for evaluation of refractory focal onset epilepsy.

PURPOSE: We aim to evaluate the utility/improved accuracy of hybrid PET/MR compared to current practice separate 3T MRI and PET-CT imaging for localization of seizure foci. METHOD: In a pilot study, twenty-nine patients undergoing epilepsy surgery evaluation were imaged using PET/MR. This subject group had 29 previous clinical 3T MRI as well as 12 PET-CT studies. Prior clinical PET and MR images were read sequentially while the hybrid PET/MR was concurrently read. RESULTS: The median interval between hybrid PET/MR and prior imaging studies was 5 months (range 1-77 months). In 24 patients, there was no change in the read between the clinical exams and hybrid PET/MR while new anatomical or functional lesions were identified by hybrid PET/MR in 5 patients without significant clinical change. Four new anatomical MR lesions were seen with concordant PET findings. The remaining patient revealed a new abnormal PET lesion without an MR abnormality. All new PET/MR lesions were clinically significant with concordant EEG and/or SPECT results as potential epileptic foci. CONCLUSION: Our initial hybrid PET-MRI experience increased diagnostic yields for detection of potential epileptic lesions. This may be due to the unique advantage of improved co-registration and simultaneous review of both structural and functional data.

Triple pathological findings in a surgically amenable patient with mesial temporal lobe epilepsy.

Mesial temporal sclerosis (MTS) is a well-recognized cause of intractable epilepsy; however, coexistence with focal cortical dysplasia (FCD) is less common. Middle fossa epidermoid cysts are rare and may involve the temporal lobe. Most epidermoids are clinically silent, slow-growing, and seldom associated with overt symptomatology, including seizures. We describe a patient with multiple comorbidities including left MTS and a large epidermoid cyst involving the left quadrigeminal plate cistern compressing upon the cerebellar vermis and tail of the left hippocampus, resulting in refractory left temporal lobe epilepsy. The patient underwent left anterior temporal lobectomy. The surgical pathology demonstrated a third pathological finding of left temporal FCD type Ia. The patient has been seizure-free since the surgery. This case provides additional information with regard to the understanding of epileptogenicity and surgical planning in patients with MTS and epidermoid cysts.

Cost effectiveness of a clinical pharmacist on a neurosurgical team.

OBJECTIVE: In 1999, the Society of Critical Care Medicine formally recognized that pharmacists were essential for the provision of high quality care to the critically ill population. This study is a brief quantitative analysis of the benefit provided by a clinical pharmacist in a multidisciplinary neurosurgical setting. METHODS: Patients admitted to the neurosurgical service in the 2 years before and 2 years after the implementation of dedicated neurosurgical pharmacy services were retrospectively reviewed. The clinical pharmacist was responsible for monitoring and evaluating all adult patients on the service and rounding with the team 6 days a week. RESULTS: A total of 2156 patients were admitted during the study period. No significant differences were noted among severity of illness scores between the 2 groups. During this time, 11 250 interventions were recorded by the pharmacist. The average pharmacy and intravenous therapy cost per patient between the pre- and postimplementation groups decreased from $4833 to $3239, resulting in a total savings of $1,718,260 over the duration of the study period. The average hospital stay decreased from 8.56 to 7.24 days (P = 0.003). Early hospital mortality also decreased from 3.34% to 1.95% (P = 0.06). For those patients who were discharged from the hospital, there was a significant decrease in readmission rates between the 2 groups (P < 0.05) CONCLUSION: Having a dedicated clinical pharmacist with critical care training rounding routinely with a neurosurgical team significantly reduced hospital stay, readmission rates, and pharmacy costs. Clinical pharmacists can have a significant effect on clinical and economic measures in the intensive care unit, and their participation on a multidisciplinary critical care team should be a standard of care.

Posterior fossa neoplasm and PHACES syndrome: a case report.

A 4-year-old girl with PHACES syndrome (posterior fossa brain malformations, hemangiomas, arterial anomalies, cardiac anomalies/coarctation of the aorta, eye abnormalities, and sternal clefting/supraumbilical raphe) developed a cerebellar pilocytic astrocytoma 18 months after resolution of her neck, ear, and thoracic hemangiomas. Because cutaneous hemangiomas may have involuted by the time a patient is diagnosed with a central nervous system neoplasm, it seems possible that in other such patients the association may have gone unrecognized. Cerebellar pilocytic astrocytoma may be a rare manifestation of the posterior fossa malformations of PHACES.

Relative adrenal insufficiency in patients with acute spinal cord injury.

INTRODUCTION: Relative adrenal insufficiency has been shown to occur in the settings of critical illness and septic shock, impairing the body's ability to respond to stress. Studies have demonstrated that the treatment of adrenal insufficiency (AI) results in shock reversal, hemodynamic stability, and a subsequent decrease in mortality. Endocrine changes and AI have been reported in patients with spinal cord injuries during their extended courses of rehabilitation. DISCUSSION: We describe two cases of patients with cervical spine injuries who presented with acute adrenal insufficiency following their injuries. With the addition of low-dose corticosteroids, each patient had symptom resolution and demonstrated clinical improvement. CONCLUSION: Patients with spinal cord injuries are at risk for AI, both in the acute and chronic settings following injury prompting the need for an increased awareness of this condition. Although variability exists in the exact criteria for the diagnosis of AI, the combination of clinical symptoms, depressed serum cortisol concentrations, and responsiveness to exogenous steroid therapy should all contribute to the diagnosis of this condition.

Determinants of ictal epileptiform patterns in the hippocampal slice.

PURPOSE: The transition from an interictal to an ictal pattern of epileptiform activity is a strategic target for antiepileptic drug (AED) action. Both the muscarinic agonist pilocarpine and the selective group I metabotropic glutamate receptor (mGluR) agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) produce prolonged synchronous activity in the hippocampal slice that resembles ictal discharges. We evaluated the role of synaptic mechanisms and release of calcium from intracellular stores in the generation of prolonged ictal oscillations. METHODS: Pilocarpine (10 microM) in 7.5 mM[K+]o or DHPG (100 microM) in 5 mM[K+]o artificial cerebrospinal fluid (ACSF) were bath applied to hippocampal slices, and extracellular recordings were made from the CA3 region. The pattern of activity was characterized as ictal if prolonged oscillations of discharges occurred at >2 Hz lasting for >3 s. The pattern of epileptiform activity was characterized and compared with the pattern observed after bath application of pharmacologic agents. RESULTS: The AMPA/kainic acid (KA) glutamate receptor blocker DNQX (20 microM) dampened and stopped ictal oscillations; however, antagonism of N-methyl-d-aspartate (NMDA) or gamma-aminobutyric acid (GABAA) receptors had minimal effects on ictal patterns. Ictal discharges were suppressed by dantrolene (30-100 microM), which blocks release of calcium from intracellular stores, or thapsigargin (1-5 microM), which inhibits the adenosine triphosphatase (ATPase) that maintains intracellular calcium stores. The L-type calcium channel antagonist nifedipine (1 microM) blocked ictal activity produced by pilocarpine or DHPG. CONCLUSIONS: Ictal discharges produced by pilocarpine or DHPG depended on intact synaptic transmission mediated by AMPA/KA receptors, release of calcium from intracellular stores, and L-type calcium channel activation. The results suggest that muscarinic and group I mGluRs activate a positive-feedback system that creates calcium oscillations and prolonged neuronal synchronization mediated by recurrent excitatory synaptic connections in the CA3 region of the hippocampus.

Suppression of pilocarpine-induced ictal oscillations in the hippocampal slice.

Activation of muscarinic cholinergic receptors produces oscillations in the hippocampal slice that resemble the theta rhythm, but also may produce abnormal synchronous activity that is more characteristic of epileptiform activity. We used pilocarpine, a muscarinic agonist and convulsant, and an elevation in extracellular potassium (5-7.5 mM) to produce synchronous neuronal activity that was prolonged (>2 s) and mimicked synchronization noted during seizures in vivo (ictal activity). In the CA3 region of adult rat hippocampal slices, prolonged ictal oscillations consisted of rhythmic field potentials occurring at 4-10 Hz for up to 30 s (ictal duration) that occurred in a regular periodic pattern every 12-166 s (ictal interval). The duration and interval between ictal oscillations were measured before and after application of drugs to define determinants of ictal occurrence. High threshold calcium channel antagonists (nifedipine and verapamil) blocked ictal activity. Release of calcium from intracellular stores also appeared to be important for ictal synchronization because ictal activity was blocked by dantrolene, an inhibitor of calcium release from intracellular stores, and by thapsigargin which blocks the ATPase that maintains intracellular calcium stores. These suppressive effects appeared to be postsynaptic because nifedipine, dantrolene, and thapsigargin had no effect on evoked fEPSPs. Enhancement of presynaptic inhibition by activation of GABA(B) or adenosine A(1) receptors suppressed ictal activity and depressed the amplitude of evoked population synaptic potentials. The results point to an important role for high threshold calcium channels and release of calcium from intracellular stores in addition to strength of synaptic connections in generation of prolonged oscillations that underlie seizure activity.

Focal cortical dysplasias in eloquent cortex: functional characteristics and correlation with MRI and histopathologic changes.

PURPOSE: Focal cortical dysplasia (CD) is increasingly recognized as a common pathologic substrate of medically intractable epilepsy. As these lesions are often localized in the frontal lobe (therefore in potentially eloquent cortex), an understanding of the functional status of the involved region(s) and of its anatomic and pathologic correlates is of prime importance. The purpose of this study is to assess the function of focal CD in relation to magnetic resonance imaging (MRI) and histopathologic features. METHODS: Eight patients operated on for medically intractable epilepsy with histologically proven focal CD involving putative eloquent cortex in the frontal lobe (perirolandic and Broca's areas) were included in the study. Functional regions (motor and language) and epileptogenic areas were assessed by extraoperative electrocorticographic recording and electrical cortical mapping. Cortical functions were correlated with the extent of epileptogenicity on electrocorticographic recordings, MRI features, and histologic characteristics. RESULTS: Language or motor areas were colocalized with epileptogenic regions (n=6 of 8, 75%), but were not mapped in regions of increased signal on fluid-attenuated inversion recovery (FLAIR) MRI (when they were identified) on preoperative MRI (n=5 of 5, 100%). Histologically, balloon cells were almost exclusively found in nonfunctional regions with FLAIR MRI abnormalities. When resected, regions of motor cortex were characterized by cortical dyslamination, columnar disorganization, and dysmorphic neurons, but were devoid of balloon cells. CONCLUSIONS: We found an absence of language or motor functions in perirolandic and Broca's areas that showed decreased epileptogenicity, histopathological evidence of CD with balloon cells and FLAIR MRI signal increase. Language and motor functions were present in epileptogenic and dysplastic areas with no balloon cells and no FLAIR signal abnormalities. These findings have implications on options for epilepsy surgery in patients with CD.