Cortical Responses to Input From Distant Areas are Modulated by Local Spontaneous Alpha/Beta Oscillations.

Any given area in human cortex may receive input from multiple, functionally heterogeneous areas, potentially representing different processing threads. Alpha (8-13 Hz) and beta oscillations (13-20 Hz) have been hypothesized by other investigators to gate local cortical processing, but their influence on cortical responses to input from other cortical areas is unknown. To study this, we measured the effect of local oscillatory power and phase on cortical responses elicited by single-pulse electrical stimulation (SPES) at distant cortical sites, in awake human subjects implanted with intracranial electrodes for epilepsy surgery. In 4 out of 5 subjects, the amplitudes of corticocortical evoked potentials (CCEPs) elicited by distant SPES were reproducibly modulated by the power, but not the phase, of local oscillations in alpha and beta frequencies. Specifically, CCEP amplitudes were higher when average oscillatory power just before distant SPES (-110 to -10 ms) was high. This effect was observed in only a subset (0-33%) of sites with CCEPs and, like the CCEPs themselves, varied with stimulation at different distant sites. Our results suggest that although alpha and beta oscillations may gate local processing, they may also enhance the responsiveness of cortex to input from distant cortical sites.

Proceedings of the Fifth International Workshop on Advances in Electrocorticography.

The Fifth International Workshop on Advances in Electrocorticography convened in San Diego, CA, on November 7-8, 2013. Advancements in methodology, implementation, and commercialization across both research and in the interval year since the last workshop were the focus of the gathering. Electrocorticography (ECoG) is now firmly established as a preferred signal source for advanced research in functional, cognitive, and neuroprosthetic domains. Published output in ECoG fields has increased tenfold in the past decade. These proceedings attempt to summarize the state of the art.

Pan-cortical electrophysiologic changes underlying attention.

We previously reported that pan-cortical effects occur when cognitive tasks end afterdischarges. For this report, we analyzed wavelet cross-coherence changes during cognitive tasks used to terminate afterdischarges studying multiple time segments and multiple groups of inter-electrode-con distances. We studied 12 patients with intractable epilepsy, with 970 implanted electrode contacts, and 39,871 electrode contact combinations. When cognitive tasks ended afterdischarges, coherence varied similarly across the cortex throughout the tasks, but there were gradations with time, distance, and frequency: (1) They tended to progressively decrease relative to baseline with time and then to increase toward baseline when afterdischarges ended. (2) During most time segments, decreases from baseline were largest for the closest inter-contact distances, moderate for intermediate inter-contact distances, and smallest for the greatest inter-contact distances. With respect to our patients' intractable epilepsy, the changes found suggest that future therapies might treat regions beyond those closest to regions of seizure onset and treat later in a seizure's evolution. Similar considerations might apply to other disorders. Our findings also suggest that cognitive tasks can result in pan-cortical coherence changes that participate in underlying attention, perhaps complementing the better-known regional mechanisms.

Therapeutic brain hypothermia, its mechanisms of action, and its prospects as a treatment for epilepsy.

Cooling the core body temperature to 32-35°C, is almost standard practice for conditions such as cardiac arrest in adults, and perinatal hypoxic ischemic encephalopathy in neonates. Limited clinical data, and more extensive animal experiments, indicate that hypothermia could help control seizures, and could be applied directly to the brain using implantable devices. These data have fostered further research to evaluate whether cooling would be a viable means to treat refractory epilepsy. Although the effect of temperature on cellular physiology has long been recognized, with possibly dual effects on pyramidal cells and interneurons, the exact mechanisms underlying its beneficial effects, in particular in epilepsy, are yet to be discovered. This article reviews currently available clinical and laboratory data with a focus on cellular mechanisms of action and prospects of hypothermia as a treatment for intractable seizures.

Connectivity between perisylvian and bilateral basal temporal cortices.

Language processing requires the orchestrated action of different neuronal populations, and some studies suggest that the role of the basal temporal (BT) cortex in language processing is bilaterally distributed. Our aim was to demonstrate connectivity between perisylvian cortex and both BT areas. We recorded corticocortical evoked potentials (CCEPs) in 8 patients with subdural electrodes implanted for surgical evaluation of intractable epilepsy. Four patients had subdural grids over dominant perisylvian and BT areas, and 4 had electrode strips over both BT areas and left posterior superior temporal gyrus (LPSTG). After electrocortical mapping, patients with grids had 1-Hz stimulation of language areas. Patients with strips did not undergo mapping but had 1-Hz stimulation of the LPSTG. Posterior language area stimulation elicited CCEPs in ipsilateral BT cortex in 3/4 patients with left hemispheric grids. CCEPs were recorded in bilateral BT cortices in 3/4 patients with strips upon stimulation of the LPSTG, and in the LPSTG in the fourth patient upon stimulation of either BT area. This is the first in vivo demonstration of connectivity between LPSTG and both BT cortices. The role of BT cortex in language processing may be bilaterally distributed and related to linking visual information with phonological representations stored in the LPSTG.

Timing of cognitive effects on afterdischarge termination.

OBJECTIVE: We previously studied efficacy of cognitive tasks on afterdischarge termination in patients undergoing cortical stimulation and found that diffuse wavelet cross-coherence changes on electrocorticography were associated with termination efficacy. We now report wavelet cross-coherence findings during different time segments of trials during which afterdischarges ended. METHODS: For 12 patients with implanted subdural electrodes, we compared wavelet cross-coherence findings among several 1-second portions of cognitive tasks, reflecting task presentation, patient replies, and afterdischarge termination. RESULTS: Coherence decreased significantly and progressively over time for 16.89, 22.53, and 30.03 Hz frequency ranges, but increased with afterdischarge termination. Coherence first increased, and then decreased for the 7.13 Hz frequency range. CONCLUSIONS: The findings suggest that cumulative but non-specific factors, likely related primarily to attention, influence the coherence results throughout the task, with a separate effect due to resolution of the afterdischarges at the end. SIGNIFICANCE: Task performance is well known to localize to specific brain regions and to be restricted in timing. In contrast, attention and overall mental activation might be due to emergent properties of brain as a whole and that are less circumscribed in space or time. Cognitive tasks might modify seizures and other neurological disorders.

Pan-cortical coordination underlying mental effort.

OBJECTIVE: It is well known that activity in, or coordination among, brain regions, can underlie movement, sensation, language, and cognition but there are observations that tasks unrelated to specific brain regions can nonetheless alter activity in those regions. These tasks might invoke activity in multiregional networks, but it also is possible that they are associated with changes beyond these networks. We therefore evaluated the possibility that more widespread, or even whole-cortical, mechanisms might complement or alter focal or multifocal cortical activity. METHODS: We assessed the extent of electroencephalographic changes occurring outside areas with epileptiform activity, but that were associated with termination of the epileptiform activity. To do this, we measured the distribution of wavelet cross-coherence changes based on electrocorticography from 15 patients who showed regional afterdischarges in response to electrical brain stimulation prior to epilepsy surgery and in whom cognitive tasks were used in attempts to end the afterdischarges. There were 1276 electrodes implanted in these patients, and we analyzed a total of 55,494 electrode combinations. We compared recordings when cognitive effort was versus when it was not successful in ending afterdischarges. RESULTS: We found that when afterdischarges were suppressed there were changes in electrocorticographic coherence that were similar throughout cortex, regardless of the distance between sites. CONCLUSIONS: The similarity implies coordination of the changes, and the similarity regardless of distance or location implies a pan-cortical effect. SIGNIFICANCE: Our results provide physical support for hypotheses that pan-cortical processes complement the well-known regional and multiregional networks. These processes may participate in, be recruited by, modify, or underlie the conative experiences of waking life.

Personality Assessment Inventory among patients with psychogenic seizures and those with epilepsy.

The Personality Assessment Inventory (PAI) is a widely used self-report questionnaire designed to detect and quantify dimensions of adult psychopathology. Previous studies that examined the ability of the PAI to differentiate between patients with psychogenic nonepileptic seizures (PNES) and those with epilepsy (EPIL) have yielded inconsistent results. We compared the full PAI profiles of 62 patients with PNES, 55 with EPIL, and 45 normal control (NC) participants to determine the diagnostic accuracy of the PAI. We also sought to highlight psychopathologic symptoms that may inform psychological treatment of patients with PNES or epilepsy. PNES and EPIL patients reported more somatic concerns and symptoms of anxiety and depression than did NC persons. PNES patients reported more unusual somatic symptoms, as well as greater physical symptoms of anxiety and depression than did patients with EPIL. Classification accuracy of the "NES Indicator" was not much better than chance, whereas the Conversion subscale alone had reasonable sensitivity (74%) and specificity (67%). Overall, the PAI demonstrated only moderate classification accuracy in an epilepsy monitoring unit sample. However, the inventory appears to identify specific psychopathological symptoms that may be targets of psychological/psychiatric intervention.

Using subdural electrodes to assess the safety of resections.

Subdural electrodes are frequently used to aid in the neurophysiological assessment of patients with intractable seizures. We review their use for localizing cortical regions supporting movement, sensation, and language.

Attention, Not Performance, Correlates With Afterdischarge Termination During Cortical Stimulation.

Cortical stimulation has been used for brain mapping for over a century, and a standard assumption is that stimulation interferes with task execution due to local effects at the stimulation site. Stimulation can however produce afterdischarges which interfere with functional localization and can lead to unwanted seizures. We previously showed that (a) cognitive effort can terminate these afterdischarges, (b) when termination thus occurs, there are electrocorticography changes throughout the cortex, not just at sites with afterdischarges or sites thought functionally important for the cognitive task used, and (c) thresholds for afterdischarges and functional responses can change among stimulation trials. We here show that afterdischarge termination can occur prior to overt performance of the cognitive tasks used to terminate them. These findings, taken together, demonstrate that task-related brain changes are not limited to one or a group of functional regions or a specific network, and not limited to the time directly surrounding overt task execution. Discrete locations, networks and times importantly underpin clinical behaviors. However, brain activity that is diffuse in location and extended in time also affect task execution and can affect brain mapping. This may in part reflect fluctuating levels of attention, engagement, or motivation during testing.

Short-term variations in response distribution to cortical stimulation.

Patterns of responses in the cerebral cortex can vary, and are influenced by pre-existing cortical function, but it is not known how rapidly these variations can occur in humans. We investigated how rapidly response patterns to electrical stimulation can vary in intact human brain. We also investigated whether the type of functional change occurring at a given location with stimulation would help predict the distribution of responses elsewhere over the cortex to stimulation at that given location. We did this by studying cortical afterdischarges following electrical stimulation of the cortex in awake humans undergoing evaluations for brain surgery. Response occurrence and location could change within seconds, both nearby to and distant from stimulation sites. Responses might occur at a given location during one trial but not the next. They could occur at electrodes adjacent or not adjacent to those directly stimulated or to other electrodes showing afterdischarges. The likelihood of an afterdischarge at an individual site after stimulation was predicted by spontaneous electroencephalographic activity at that specific site just prior to stimulation, but not by overall cortical activity. When stimulation at a site interrupted motor, sensory or language function, afterdischarges were more likely to occur at other sites where stimulation interrupted similar functions. These results show that widespread dynamic changes in cortical responses can occur in intact cortex within short periods of time, and that the distribution of these responses depends on local brain states and functional brain architecture at the time of stimulation. Similar rapid variations may occur during normal intracortical communication and may underlie changes in the cortical organization of function. Possibly these variations, and the occurrence and distribution of responses to cortical stimulation, could be predicted. If so, interventions such as stimulation might be used to alter spread of epileptogenic activity, accelerate learning or enhance cortical reorganization after brain injury.

Cognitive effort decreases beta, alpha, and theta coherence and ends afterdischarges in human brain.

OBJECTIVE: Mental activation has been reported to modify the occurrence of epileptiform activity. We studied its effect on afterdischarges. METHOD: In 15 patients with implanted electrodes we presented cognitive tasks when afterdischarges occurred. We developed a wavelet cross-coherence function to analyze the electrocorticography before and after the tasks and compared findings when cognitive tasks did or did not result in afterdischarge termination. Six patients returned for functional MRI (fMRI) testing, using similar tasks. RESULTS: Cognitive tasks often could terminate afterdischarges when direct abortive stimulation could not. Wavelet cross-coherence analysis showed that, when afterdischarges stopped, there was decreased coherence throughout the brain in the 7.13-22.53 Hz frequency ranges (p values 0.008-0.034). This occurred a) regardless of whether an area activated on fMRI and b) regardless of whether there were afterdischarges in the area. CONCLUSIONS: It is known that cognitive tasks can alter localized or network synchronization. Our results show that they can change activity throughout the brain. These changes in turn can terminate localized epileptiform activity. SIGNIFICANCE: Cognitive tasks result in diffuse brain changes that can modify focal brain activity. Combined with a seizure detection device, cognitive activation might provide a non-invasive method of terminating or modifying seizures.

Standardized computer-based organized reporting of EEG: SCORE - Second version.

Standardized terminology for computer-based assessment and reporting of EEG has been previously developed in Europe. The International Federation of Clinical Neurophysiology established a taskforce in 2013 to develop this further, and to reach international consensus. This work resulted in the second, revised version of SCORE (Standardized Computer-based Organized Reporting of EEG), which is presented in this paper. The revised terminology was implemented in a software package (SCORE EEG), which was tested in clinical practice on 12,160 EEG recordings. Standardized terms implemented in SCORE are used to report the features of clinical relevance, extracted while assessing the EEGs. Selection of the terms is context sensitive: initial choices determine the subsequently presented sets of additional choices. This process automatically generates a report and feeds these features into a database. In the end, the diagnostic significance is scored, using a standardized list of terms. SCORE has specific modules for scoring seizures (including seizure semiology and ictal EEG patterns), neonatal recordings (including features specific for this age group), and for Critical Care EEG Terminology. SCORE is a useful clinical tool, with potential impact on clinical care, quality assurance, data-sharing, research and education.

Termination of epileptiform activity by cooling in rat hippocampal slice epilepsy models.

Cooling has been shown to terminate experimentally induced epileptiform activity in models of epilepsy without causing injury to the cooled brain, suggesting that cooling could represent an approach to seizure control in intractable focal epilepsies. Here we sought to determine the most effective way to apply cooling to abort spontaneous epileptiform discharges in in vitro brain slice models. We induced spontaneous epileptiform activity in rat brain slices by exposure to 4-aminopyridine (4-AP), 4-AP plus bicuculline, and Mg(2+)-free artificial CSF (aCSF) at 28-34 degrees C. Extracellular field recordings were made at hippocampal or neocortical sites. Slice temperature was reduced by perfusion with cold aCSF. Rapid cooling at rates of 2-5 degrees C/s was compared to cooling at slower rates of 0.1-1 degrees C/s. Cooling at both rates reversibly aborted epileptiform discharges in all three models and at all recording sites. With rapid cooling, small temperature drops were highly effective in terminating discharges, an effect that was sustained for as long as the reduced temperature level was maintained. In contrast, slow cooling required much larger temperature drops to inhibit discharges. With slow cooling, absolute temperature drops to 21-22 degrees C caused a 90% reduction in event frequency, but cooling to 14-15 degrees C was required to terminate discharges. We conclude that rapid cooling as effectively aborts discharges in in vitro epilepsy models as does slow cooling, but the magnitude of the temperature change required is less. Practical devices to inhibit seizure activity may only need to induce small temperature drops, if the cooling can be applied sufficiently rapidly.

Electrocorticographic high gamma activity versus electrical cortical stimulation mapping of naming.

Subdural electrocorticographic (ECoG) recordings in patients undergoing epilepsy surgery have shown that functional activation is associated with event-related broadband gamma activity in a higher frequency range (>70 Hz) than previously studied in human scalp EEG. To investigate the utility of this high gamma activity (HGA) for mapping language cortex, we compared its neuroanatomical distribution with functional maps derived from electrical cortical stimulation (ECS), which remains the gold standard for predicting functional impairment after surgery for epilepsy, tumours or vascular malformations. Thirteen patients had undergone subdural electrode implantation for the surgical management of intractable epilepsy. Subdural ECoG signals were recorded while each patient verbally named sequentially presented line drawings of objects, and estimates of event-related HGA (80-100 Hz) were made at each recording site. Routine clinical ECS mapping used a subset of the same naming stimuli at each cortical site. If ECS disrupted mouth-related motor function, i.e. if it affected the mouth, lips or tongue, naming could not be tested with ECS at the same cortical site. Because naming during ECoG involved these muscles of articulation, the sensitivity and specificity of ECoG HGA were estimated relative to both ECS-induced impairments of naming and ECS disruption of mouth-related motor function. When these estimates were made separately for 12 electrode sites per patient (the average number with significant HGA), the specificity of ECoG HGA with respect to ECS was 78% for naming and 81% for mouth-related motor function, and equivalent sensitivities were 38% and 46%, respectively. When ECS maps of naming and mouth-related motor function were combined, the specificity and sensitivity of ECoG HGA with respect to ECS were 84% and 43%, respectively. This study indicates that event-related ECoG HGA during confrontation naming predicts ECS interference with naming and mouth-related motor function with good specificity but relatively low sensitivity. Its favourable specificity suggests that ECoG HGA can be used to construct a preliminary functional map that may help identify cortical sites of lower priority for ECS mapping. Passive recordings of ECoG gamma activity may be done simultaneously at all electrode sites without the risk of after-discharges associated with ECS mapping, which must be done sequentially at pairs of electrodes. We discuss the relative merits of these two functional mapping techniques.

Electroencephalography and Brain MRI Patterns in Encephalopathy.

INTRODUCTION: Using electroencephalography (EEG) and histology in patients with diffuse encephalopathy, Gloor et al reported that paroxysmal synchronous discharges (PSDs) on EEG required combined cortical gray (CG) and "subcortical" gray (SCG) matter pathology, while polymorphic delta activity (PDA) occurred in patients with white matter pathology. In patients with encephalopathy, we compared EEG findings and magnetic resonance imaging (MRI) to determine if MRI reflected similar pathological EEG correlations. METHODS: Retrospective case control study of 52 cases with EEG evidence of encephalopathy and 50 controls without evidence of encephalopathy. Review of clinical, EEG and MRI data acquired within 4 days of each other. RESULTS: The most common EEG finding in encephalopathy was background slowing, in 96.1%. We found PSDs in 0% of cases with the combination of CG and SCG abnormalities. Although 13.5% (n=7) had PSDs on EEG; 3 of these had CG and 4 had SCG abnormalities. A total of 73.1% (38/52) had white matter abnormalities-of these 28.9% (11/38) had PDA. CONCLUSION: PSDs were found with either CG or "SCG" MRI abnormalities and did not require a combination of the two. In agreement with Gloor et al, PDA occurred with white matter MRI abnormalities in the absence of gray matter abnormalities.

A Korean kindred with autosomal dominant nocturnal frontal lobe epilepsy and mental retardation.

BACKGROUND: A Korean family had distinctive clinical and neuroimaging features and carried the same genetic mutation that was found in a previously described Japanese kindred with autosomal dominant nocturnal frontal lobe epilepsy. OBJECTIVE: To describe the first Korean family with autosomal dominant nocturnal frontal lobe epilepsy. METHODS: Members of a large family, including 9 affected individuals from 3 generations, underwent a comprehensive genetic, clinical, electroencephalographic, neuropsychological, and neuroimaging evaluation. Affected members were tested for possible mutations in transmembrane regions 1 through 3 of the neuronal nicotinic acetylcholine receptor alpha4 subunit (CHRNA4) by direct sequencing and subsequent restriction analysis. RESULTS: Seizures began in childhood, presenting as nocturnal episodes of staring, confusion, shouting, perioral movements, unintelligible speech, and hand waving. Some patients had ictal or interictal epileptiform activity in the temporal and/or frontocentral areas. Neurological examination and brain magnetic resonance imaging results showed no abnormalities, except that all patients available for testing had mild to moderate mental retardation. Fluorodeoxyglucose F 18 with positron emission tomography showed mild decreased glucose uptake in the superior and middle frontal regions, more so on the left than on the right. Patient response to carbamazepine was poor. All affected members were heterozygous for the CHRNA4 Ser252Leu mutation. CONCLUSIONS: Disorders associated with mutations in the transmembrane region 2 of CHRNA4 are genetically and phenotypically heterogeneous. Distinctive features of this kindred include (1) mental retardation in all affected members available for testing, (2) abnormal brain findings on fluorodeoxyglucose F 18 with positron emission tomography, (3) poor response to carbamazepine, and (4) full penetrance.

Wavelet-crosscorrelation analysis can help predict whether bursts of pulse stimulation will terminate afterdischarges.

OBJECTIVE: Extraoperative cortical localizing stimulation (LS) is a standard clinical tool used to assess brain function before epilepsy surgery. However, LS can produce unwanted afterdischarges (ADs). We previously have shown that brief pulses of electrical stimulation (BPS) can terminate ADs caused by cortical stimulation. Our objective was to assess whether wavelet-crosscorrelation analysis could help predict the conditions under which BPS would be most likely to terminate ADs. METHODS: We used wavelet-crosscorrelation analysis to get wavelet-correlation coefficients (WCC), and determine time lag (TL) and absolute value of TL (ATL) between two electrodes. For Analysis-1, we compared WCC and ATL in epoch 1 which was before LS, epoch 2 which was after LS but before BPS, and epoch 3 which was after BPS. For Analysis 2, we compared WCC and ATL during epoch 1 under 4 conditions: epochs when ADs subsequently terminated within 2 s after the end of BPS (1A), terminated within 2-5 s (1B), did not terminate within 5 s (1C), and when ADs did not appear (1D). RESULTS: We found that BPS efficacy in terminating ADs was predicted by (1) low correlation and (2) slow propagation speed between electrode pairs in the 2-10 s period before stimulation. CONCLUSIONS: Wavelet-crosscorrelation analysis can help predict conditions during which BPS can abort ADs. It is possible that similar analyses could help predict when BPS or other interventions could abort clinical seizures.