Identification of pre-spike network in patients with mesial temporal lobe epilepsy

Background: Seizures and interictal spikes in mesial temporal lobe epilepsy (MTLE) affect a network of brain regions rather than a single epileptic focus. Simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) studies have demonstrated a functional network in which hemodynamic changes are time-locked to spikes. However, whether this reflects the propagation of neuronal activity from a focus, or conversely the activation of a network linked to spike generation remains unknown. The functional connectivity (FC) changes prior to spikes may provide information about the connectivity changes that lead to the generation of spikes. We used EEG-fMRI to investigate FC changes immediately prior to the appearance of interictal spikes on EEG in patients with MTLE. Methods/principal findings: Fifteen patients with MTLE underwent continuous EEG-fMRI during rest. Spikes were identified on EEG and three 10 s epochs were defined relative to spike onset: spike (0–10 s), pre-spike (−10 to 0 s), and rest (−20 to −10 s, with no previous spikes in the preceding 45s). Significant spike-related activation in the hippocampus ipsilateral to the seizure focus was found compared to the pre-spike and rest epochs. The peak voxel within the hippocampus ipsilateral to the seizure focus was used as a seed region for FC analysis in the three conditions. A significant change in FC patterns was observed before the appearance of electrographic spikes. Specifically, there was significant loss of coherence between both hippocampi during the pre-spike period compared to spike and rest states. Conclusion/significance: In keeping with previous findings of abnormal inter-hemispheric hippocampal connectivity in MTLE, our findings specifically link reduced connectivity to the period immediately before spikes. This brief decoupling is consistent with a deficit in mutual (inter-hemispheric) hippocampal inhibition that may predispose to spike generation.

The N170 observed ‘in the wild’: robust event-related potentials to faces in cluttered dynamic visual scenes

As a social species in a constantly changing environment, humans rely heavily on the informational richness and communicative capacity of the face. Thus, understanding how the brain processes information about faces in real-time is of paramount importance. The N170 is a high temporal resolution electrophysiological index of the brain's early response to visual stimuli that is reliably elicited in carefully controlled laboratory-based studies. Although the N170 has often been reported to be of greatest amplitude to faces, there has been debate regarding whether this effect might be an artifact of certain aspects of the controlled experimental stimulation schedules and materials. To investigate whether the N170 can be identified in more realistic conditions with highly variable and cluttered visual images and accompanying auditory stimuli we recorded EEG 'in the wild', while participants watched pop videos. Scene-cuts to faces generated a clear N170 response, and this was larger than the N170 to transitions where the videos cut to non-face stimuli. Within participants, wild-type face N170 amplitudes were moderately correlated to those observed in a typical laboratory experiment. Thus, we demonstrate that the face N170 is a robust and ecologically valid phenomenon and not an artifact arising as an unintended consequence of some property of the more typical laboratory paradigm.

Examining the neural correlates of choice behavior in a gambling task using steady state topography

The present study investigated the behavioral and neuropsychological characteristics of decision-making behavior during a gambling task as well as how these characteristics may relate to the Somatic Marker Hypothesis and the Frequency of Gain model. The applicability to intertemporal choice was also discussed. Patterns of card selection during a computerized interpretation of the Iowa Gambling Task were assessed for 10 men and 10 women. Steady State Topography was employed to assess cortical processing throughout this task. Results supported the hypothesis that patterns of card selection were in line with both theories. As hypothesized, these 2 patterns of card selection were also associated with distinct patterns of cortical activity, suggesting that intertemporal choice may involve the recruitment of right dorsolateral prefrontal cortex for somatic labeling, left fusiform gyrus for object representations, and the left dorsolateral prefrontal cortex for an analysis of the associated frequency of gain or loss. It is suggested that processes contributing to intertemporal choice may include inhibition of negatively valenced options, guiding decisions away from those options, as well as computations favoring frequently rewarded options.

Functional neuroanatomy of auditory mismatch processing : an event-related fMRI study of duration-deviant oddballs

This study was designed to identify the neural networks underlying automatic auditory deviance detection in 10 healthy subjects using functional magnetic resonance imaging. We measured blood oxygenation level-dependent contrasts derived from the comparison of blocks of stimuli presented as a series of standard tones (50 ms duration) alone versus blocks that contained rare duration-deviant tones (100 ms) that were interspersed among a series of frequent standard tones while subjects were watching a silent movie. Possible effects of scanner noise were assessed by a “no tone” condition. In line with previous positron emission tomography and EEG source modeling studies, we found temporal lobe and prefrontal cortical activation that was associated with auditory duration mismatch processing. Data were also analyzed employing an event-related hemodynamic response model, which confirmed activation in response to duration-deviant tones bilaterally in the superior temporal gyrus and prefrontally in the right inferior and middle frontal gyri. In line with previous electrophysiological reports, mismatch activation of these brain regions was significantly correlated with age. These findings suggest a close relationship of the event-related hemodynamic response pattern with the corresponding electrophysiological activity underlying the event-related “mismatch negativity” potential, a putative measure of auditory sensory memory.

Wide-band spectral power fluctuations characterize the response of simulated cortical networks to increasing stimulus intensity

The hippocampus is an anatomically distinct region of the medial temporal lobe that plays a critical role in the formation of declarative memories. Here we show that a computer simulation of simple compartmental cells organized with basic hippocampal connectivity is capable of producing stimulus intensity sensitive wide-band fluctuations of spectral power similar to that seen in real EEG. While previous computational models have been designed to assess the viability of the putative mechanisms of memory storage and retrieval, they have generally been too abstract to allow comparison with empirical data. Furthermore, while the anatomical connectivity and organization of the hippocampus is well defined, many questions regarding the mechanisms that mediate large-scale synaptic integration remain unanswered. For this reason we focus less on the specifics of changing synaptic weights and more on the population dynamics. Spectral power in four distinct frequency bands were derived from simulated field potentials of the computational model and found to depend on the intensity of a random input. The majority of power occurred in the lowest frequency band (3-6 Hz) and was greatest to the lowest intensity stimulus condition (1% maximal stimulus). In contrast, higher frequency bands ranging from 7-45 Hz show an increase in power directly related with an increase in stimulus intensity. This trend continues up to a stimulus level of 15% to 20% of the maximal input, above which power falls dramatically. These results suggest that the relative power of intrinsic network oscillations are dependent upon the level of activation and that above threshold levels all frequencies are damped, perhaps due to over activation of inhibitory interneurons.

Memory and Epileptogenesis in Complex Biological and Simulated Systems

Oscillations of neural activity may bind widespread cortical areas into a neural representation that encodes disparate aspects of an event. In order to test this theory we have turned to data collected from complex partial epilepsy (CPE) patients with chronically implanted depth electrodes. Data from regions critical to word and face information processing was analyzed using spectral coherence measurements. Similar analyses of intracranial EEG (iEEG) during seizure episodes display HippoCampal Formation (HCF)—NeoCortical (NC) spectral coherence patterns that are characteristic of specific seizure stages (Klopp et al. 1996). We are now building a computational memory model to examine whether spatio-temporal patterns of human iEEG spectral coherence emerge in a computer simulation of HCF cellular distribution, membrane physiology and synaptic connectivity. Once the model is reasonably scaled it will be used as a tool to explore neural parameters that are critical to memory formation and epileptogenesis.

Neuroimaging and genetics: Exploring, searching, and finding

This issue on the genetics of brain imaging phenotypes is a celebration of the happy marriage between two of science's highly interesting fields: neuroscience and genetics. The articles collected here are ample evidence that a good deal of synergy exists in this marriage. A wide selection of papers is presented that provide many different perspectives on how genes cause variation in brain structure and function, which in turn influence behavioral phenotypes (including psychopathology). They are examples of the many different methodologies in contemporary genetics and neuroscience research. Genetic methodology includes genome-wide association (GWA), candidate-gene association, and twin studies. Sources of data on brain phenotypes include cortical gray matter (GM) structural/volumetric measures from magnetic resonance imaging (MRI); white matter (WM) measures from diffusion tensor imaging (DTI), such as fractional anisotropy; functional- (activity-) based measures from electroencephalography (EEG), and functional MRI (fMRI). Together, they reflect a combination of scientific fields that have seen great technological advances, whether it is the single-nucleotide polymorphism (SNP) array in genetics, the increasingly high-resolution MRI imaging, or high angular resolution diffusion imaging technique for measuring WM connective properties.

Partial epilepsy syndrome in a Gypsy family linked to 5q31.3-q32

PURPOSE The restricted genetic diversity and homogeneous molecular basis of Mendelian disorders in isolated founder populations have rarely been explored in epilepsy research. Our long-term goal is to explore the genetic basis of epilepsies in one such population, the Gypsies. The aim of this report is the clinical and genetic characterization of a Gypsy family with a partial epilepsy syndrome. METHODS Clinical information was collected using semistructured interviews with affected subjects and informants. At least one interictal electroencephalography (EEG) recording was performed for each patient and previous data obtained from records. Neuroimaging included structural magnetic resonance imaging (MRI). Linkage and haplotype analysis was performed using the Illumina IVb Linkage Panel, supplemented with highly informative microsatellites in linked regions and Affymetrix SNP 5.0 array data. RESULTS We observed an early-onset partial epilepsy syndrome with seizure semiology strongly suggestive of temporal lobe epilepsy (TLE), with mild intellectual deficit co-occurring in a large proportion of the patients. Psychiatric morbidity was common in the extended pedigree but did not cosegregate with epilepsy. Linkage analysis definitively excluded previously reported loci, and identified a novel locus on 5q31.3-q32 with an logarithm of the odds (LOD) score of 3 corresponding to the expected maximum in this family. DISCUSSION The syndrome can be classified as familial temporal lobe epilepsy (FTLE) or possibly a new syndrome with mild intellectual deficit. The linked 5q region does not contain any ion channel-encoding genes and is thus likely to contribute new knowledge about epilepsy pathogenesis. Identification of the mutation in this family and in additional patients will define the full phenotypic spectrum.

Diabetic ketoacidosis and electroencephalographic changes in newly diagnosed pediatric patients

Objective: To document electroencephalogram (EEG) changes and their correlation with clinical parameters in a newly diagnosed pediatric cohort of type 1 diabetes mellitus (T1DM) patients with and without diabetic ketoacidosis (DKA) and to define their medium term utility and significance. Research design and methods: Prospective longitudinal study of children presenting with T1DM. EEGs were performed within 24 h of diagnosis, day 5, and at 6 months post-diagnosis and reviewed by a neurologist blinded to clinical status. Severity of encephalopathy was graded from 1 to 5 using the Aoki and Lombroso encephalopathy scale. Cognitive abilities were assessed using standardized tests of attention, memory, and intelligence. Results: Eighty eight children were recruited; 34 presented with DKA. Abnormal background slowing was more often observed in the first 24 h in children with DKA (p = 0.01). Encephalopathy scores on day 1 correlated with initial pH, CO2, HCO3, base excess, respiratory rate, heart rate, diastolic blood pressure, and IV fluid intake (all parameters p < 0.05). EEG scores at day 1 did not correlate with contemporaneous mental state or cognition in the medium term. Conclusions: DKA was associated with significant clinical and neurophysiologic signs of brain dysfunction at presentation. While EEG is sensitive to the detection of encephalopathy in newly diagnosed T1DM, it has limited use in identifying children at risk of later cognitive deficits.

Cooperative game play with avatars and agents: Differences in brain activity and the experience of play

The current study sought to identify the impact of whether teammates in a cooperative videogame were controlled by other humans (avatars) or by the game (agents). The impact on player experience was explored through both subjective questionnaire measures and brain wave activity measurement (electroencephalography). Play with human teammates was associated with a greater sense of relatedness, but less competence and flow than play with other computer-controlled teammates. In terms of brain activity, play with human teammates was associated with greater activity in the alpha, theta and beta power bands than play with computer-controlled teammates. Overall, the results suggest that play with human teammates involves greater cognitive activity in terms of 'mentalising' than play with computer-controlled teammates. Additionally, the associations between subjective measures of player experience and brain activity are described. Limitations of the current study are identified and key directions for future research are discussed.

Early and late electrophysiological effects of distractor frequency in picture naming: Reconciling input and output accounts

The “distractor-frequency effect” refers to the finding that high-frequency (HF) distractor words slow picture naming less than low-frequency distractors in the picture–word interference paradigm. Rival input and output accounts of this effect have been proposed. The former attributes the effect to attentional selection mechanisms operating during distractor recognition, whereas the latter attributes it to monitoring/decision mechanisms operating on distractor and target responses in an articulatory buffer. Using high-density (128-channel) EEG, we tested hypotheses from these rival accounts. In addition to conducting stimulus- and response-locked whole-brain corrected analyses, we investigated the correct-related negativity, an ERP observed on correct trials at fronto-central electrodes proposed to reflect the involvement of domain general monitoring. The wholebrain ERP analysis revealed a significant effect of distractor frequency at inferior right frontal and temporal sites between 100 and 300-msec post-stimulus onset, during which lexical access is thought to occur. Response-locked, region of interest (ROI) analyses of fronto-central electrodes revealed a correct-related negativity starting 121 msec before and peaking 125 msec after vocal onset on the grand averages. Slope analysis of this component revealed a significant difference between HF and lowfrequency distractor words, with the former associated with a steeper slope on the time windowspanning from100 msec before to 100 msec after vocal onset. The finding of ERP effects in time windows and components corresponding to both lexical processing and monitoring suggests the distractor frequency effect is most likely associated with more than one physiological mechanism.