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.

Locally stable brain states predict suppression of epileptic activity by enhanced cognitive effort.

Cognitive effort is known to play a role in healthy brain state organization, but little is known about its effects on pathological brain dynamics. When cortical stimulation is used to map functional brain areas prior to surgery, a common unwanted side effect is the appearance of afterdischarges (ADs), epileptiform and potentially epileptogenic discharges that can progress to a clinical seizure. It is therefore desirable to suppress this activity. Here, we analyze electrocorticography recordings from 15 patients with epilepsy. We show that a cognitive intervention in the form of asking an arithmetic question can be effective in suppressing ADs, but that its effectiveness is dependent upon the brain state at the time of intervention. By applying novel techniques from network analysis to quantify brain states, we find that the spatial organization of ADs with respect to coherent brain regions relates to the success of the cognitive intervention: if ADs are mainly localized within a single stable brain region, a cognitive intervention is likely to suppress the ADs. These findings show that cognitive effort is a useful tactic to modify unstable pathological activity associated with epilepsy, and suggest that the success of therapeutic interventions to alter activity may depend on an individual's brain state at the time of intervention.

GALACTIC COSMIC RAYS IN THE LOCAL INTERSTELLAR MEDIUM: VOYAGER 1 OBSERVATIONS AND MODEL RESULTS.

Since 2012 August Voyager 1 has been observing the local interstellar energy spectra of Galactic cosmic-ray nuclei down to 3 MeV nuc-1 and electrons down to 2.7 MeV. The H and He spectra have the same energy dependence between 3 and 346 MeV nuc-1, with a broad maximum in the 10-50 MeV nuc-1 range and a H/He ratio of 12.2 ± 0.9. The peak H intensity is ~15 times that observed at 1 AU, and the observed local interstellar gradient of 3-346 MeV H is -0.009 ± 0.055% AU-1, consistent with models having no local interstellar gradient. The energy spectrum of electrons (e - + e +) with 2.7-74 MeV is consistent with E -1.30±0.05 and exceeds the H intensity at energies below ~50 MeV. Propagation model fits to the observed spectra indicate that the energy density of cosmic-ray nuclei with >3 MeV nuc-1 and electrons with >3 MeV is 0.83-1.02 eV cm-3 and the ionization rate of atomic H is in the range of 1.51-1.64 × 10-17 s-1. This rate is a factor >10 lower than the ionization rate in diffuse interstellar clouds, suggesting significant spatial inhomogeneity in low-energy cosmic rays or the presence of a suprathermal tail on the energy spectrum at much lower energies. The propagation model fits also provide improved estimates of the elemental abundances in the source of Galactic cosmic rays.

Voyager 1 observes low-energy galactic cosmic rays in a region depleted of heliospheric ions.

On 25 August 2012, Voyager 1 was at 122 astronomical units when the steady intensity of low-energy ions it had observed for the previous 6 years suddenly dropped for a third time and soon completely disappeared as the ions streamed away into interstellar space. Although the magnetic field observations indicate that Voyager 1 remained inside the heliosphere, the intensity of cosmic ray nuclei from outside the heliosphere abruptly increased. We report the spectra of galactic cosmic rays down to ~3 × 10(6) electron volts per nucleon, revealing H and He energy spectra with broad peaks from 10 × 10(6) to 40 × 10(6) electron volts per nucleon and an increasing galactic cosmic-ray electron intensity down to ~10 × 10(6) electron volts.

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.

Subdural electrodes.

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

When is electrical cortical stimulation more likely to produce afterdischarges?

OBJECTIVE: To study when afterdischarges (ADs) are more likely to occur during cortical stimulation. METHODS: We examined 6250 electrical stimulation trials in 13 patients with subdural electrodes, studying whether AD occurrence during a trial was influenced by electrode pair stimulated or AD occurrence during the previous trial. In total 545 electrodes were stimulated, 119 frontal (pre-perirolandic), 289 perirolandic, 36 parietal (post-perirolandic), 95 temporal, and 6 occipital. RESULTS: When the same electrode pair was stimulated as the prior trial, 19% produced ADs compared to 5% of trials when a different electrodes pair was stimulated (p<0.0001). When trials showed ADs, and the next trial stimulated the same electrode pair, ADs occurred in 46% of cases, compared to 13% of trials following trials without ADs (p<0.0001). AD probability decreased with increased inter-trial interval length only when the prior trial was at the same electrode pair and had produced an AD (p=0.001). AD probability increased with stimulation duration, whether the trial followed a trial with (p<0.001) or without (p<0.0001) an AD. CONCLUSIONS: ADs were more likely to occur when an electrode pair showed ADs and was stimulated again, especially when stimulating after short inter-trial intervals or for longer duration. SIGNIFICANCE: When ADs occur, waiting about a minute before resuming stimulation might lessen the likelihood of AD recurrence.

Reorganisation of cortical motor and language distribution in human brain.

BACKGROUND: The locations of cortex controlling motor, sensory, or language functions can change in adult humans under some circumstances, such as expanding tumours, trauma or continuous focal seizures. It is not clear what other circumstances might result in changes in cortical functional maps. METHODS: The results of extraoperative cortical mappings of motor, sensory, and language functions were compared in two epilepsy patients who underwent cortical resections on two separate occasions and who did not have brain tumours. RESULTS: It was found that the locations of motor functions could differ between the first and second procedures, but the locations of language functions were quite similar. The changes were not necessarily in or adjacent to epileptogenic regions or adjacent to resection boundaries. CONCLUSIONS: These findings support previous evidence indicating that cortical functional representations can change over time in humans, and suggest that these changes cannot be explained solely by lesion effects.

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.

Voyager 1 explores the termination shock region and the heliosheath beyond.

Voyager 1 crossed the termination shock of the supersonic flow of the solar wind on 16 December 2004 at a distance of 94.01 astronomical units from the Sun, becoming the first spacecraft to begin exploring the heliosheath, the outermost layer of the heliosphere. The shock is a steady source of low-energy protons with an energy spectrum approximately E(-1.41 +/- 0.15) from 0.5 to approximately 3.5 megaelectron volts, consistent with a weak termination shock having a solar wind velocity jump ratio r=2.6(-0.2)(+0.4). However, in contradiction to many predictions, the intensity of anomalous cosmic ray (ACR) helium did not peak at the shock, indicating that the ACR source is not in the shock region local to Voyager 1. The intensities of approximately 10-megaelectron volt electrons, ACRs, and galactic cosmic rays have steadily increased since late 2004 as the effects of solar modulation have decreased.

Brief bursts of pulse stimulation terminate afterdischarges caused by cortical stimulation.

OBJECTIVE: To determine whether cortical electrical stimulation can terminate bursts of epileptiform activity in humans, we used afterdischarges (ADs) as a model of epileptiform activity. METHODS: Cortical stimulation was performed for clinical localization purposes using subdural electrodes implanted in patients undergoing preresection evaluations for treatment of medically intractable seizures. We used 0.3-millisecond pulses of alternating polarity, repeated at 50 pulses/second. When stimulation produced AD, we often applied short additional brief bursts of pulse stimulation (BPS). We examined the effectiveness of BPS in aborting ADs in 17 patients using survival analysis. RESULTS: With BPS, ADs stopped within 2 seconds in 115 cases, 2 to 5 seconds in 22 cases, and in more than 5 seconds in 89 cases. Without BPS, ADs stopped within 2 seconds in 21 cases, 2 to 5 seconds in 114 cases, and in more than 5 seconds in 340 cases. BPS was an effective method to abort ADs (Cox proportional hazards model: p<0.0001). At any time during the course of ADs, the instantaneous rate of stopping ADs within 2 seconds after BPS was applied was 4.6 times greater than when BPS was not applied (95% CI = 3.7, 5.7). In eight cases, ADs progressed to the occurrence of clinical seizures, always when BPS was not applied. CONCLUSIONS: Afterdischarges significantly decreased in duration after we applied brief bursts of pulse stimulation. Although afterdischarges are not identical to spontaneous epileptiform activity, these results support the idea that electrical stimulation, applied in an appropriate manner at seizure onset, could abort seizures in humans.

Enhancing the detection of seizures with a clustering algorithm.

Automated detection algorithms of EEG seizures or similar clinical events typically analyze a finite epoch a given channel at a time, producing a probability or a weight estimating how likely it is for the event to resemble a clinical pattern. Epochs are normally shorter than the duration of a seizure, which may spread to more than one electrode. This may result in a weak correspondence between the seizure pattern in the record and its calculated detector event counterpart. As a result, such algorithms suffer from a high rate of false detections. We show that the weights/probabilities of a generic detector can be described as a weight function embedded in a directed graph (digraph). Extended objects such as seizures therefore correspond to the connected components of the digraph. We introduce a clustering algorithm that accounts for the shortcomings of a generic detector of the type described above. By correlating detector results with respect to both time and channel, we effectively extend the detection to an unlimited number of electrodes over an indefinite time. The algorithm is fast (linear - O(m)) and may be implemented in real time. We argue that the algorithm enhances the detection of seizure onset and lowers the rate of false detections. Preliminary results demonstrate a strong correlation between the seizure and the cluster's boundaries and over 50% reduction of false detection rate.