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.

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.

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.

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.

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.

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.

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.

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.

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.

Stressful life event appraisal and coping in patients with psychogenic seizures and those with epilepsy.

Understanding stress and coping among individuals with psychogenic nonepileptic seizures (PNES) may have important treatment implications. 40 patients with PNES, 20 with epilepsy (EPIL), and 40 healthy control (HC) participants reported the frequency of various stressful life events (both positive and negative) and appraised the distress these events induced. They also described their habitual coping behaviors. PNES patients reported no more frequent stressful life events than EPIL patients or HC. In addition, the stressors they experienced are not objectively more severe. However, they reported more severe distress due to negative life events, especially in the domains of work, social functioning, legal matters, and health. PNES patients also engaged in less planning and active coping than HC. Neither of these two coping behaviors was associated with distress ratings. The PNES group did not engage in more denial than either group. However, greater denial among PNES patients was associated with greater perceived distress. Coping in PNES is characterized by elevated levels of perceived distress and fewer action strategies than are normally employed to reduce the impact of a stressor. These findings may inform cognitive behavioral therapy of PNES patients.

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.

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.