Late dominance of the right hemisphere during narrative comprehension.

PET and fMRI studies suggest that auditory narrative comprehension is supported by a bilateral multilobar cortical network. The superior temporal resolution of magnetoencephalography (MEG) makes it an attractive tool to investigate the dynamics of how different neuroanatomic substrates engage during narrative comprehension. Using beta-band power changes as a marker of cortical engagement, we studied MEG responses during an auditory story comprehension task in 31 healthy adults. The protocol consisted of two runs, each interleaving 7 blocks of the story comprehension task with 15 blocks of an auditorily presented math task as a control for phonological processing, working memory, and attention processes. Sources at the cortical surface were estimated with a frequency-resolved beamformer. Beta-band power was estimated in the frequency range of 16-24 Hz over 1-sec epochs starting from 400 msec after stimulus onset until the end of a story or math problem presentation. These power estimates were compared to 1-second epochs of data before the stimulus block onset. The task-related cortical engagement was inferred from beta-band power decrements. Group-level source activations were statistically compared using non-parametric permutation testing. A story-math contrast of beta-band power changes showed greater bilateral cortical engagement within the fusiform gyrus, inferior and middle temporal gyri, parahippocampal gyrus, and left inferior frontal gyrus (IFG) during story comprehension. A math-story contrast of beta power decrements showed greater bilateral but left-lateralized engagement of the middle frontal gyrus and superior parietal lobule. The evolution of cortical engagement during five temporal windows across the presentation of stories showed significant involvement during the first interval of the narrative of bilateral opercular and insular regions as well as the ventral and lateral temporal cortex, extending more posteriorly on the left and medially on the right. Over time, there continued to be sustained right anterior ventral temporal engagement, with increasing involvement of the right anterior parahippocampal gyrus, STG, MTG, posterior superior temporal sulcus, inferior parietal lobule, frontal operculum, and insula, while left hemisphere engagement decreased. Our findings are consistent with prior imaging studies of narrative comprehension, but in addition, they demonstrate increasing right-lateralized engagement over the course of narratives, suggesting an important role for these right-hemispheric regions in semantic integration as well as social and pragmatic inference processing.

Regional and global resting-state functional MR connectivity in temporal lobe epilepsy: Results from the Epilepsy Connectome Project.

Temporal lobe epilepsy (TLE) has been conceptualized as focal disease with a discrete neurobiological focus and can respond well to targeted resection or ablation. In contrast, the neuro-cognitive deficits resulting from TLE can be widespread involving regions beyond the primary epileptic network. We hypothesize that this seemingly paradoxical findings can be explained by differences in connectivity between the primary epileptic region which is hyper-connected and its secondary influence on global connectome organization. This hypothesis is tested using regional and global graph theory metrics where we anticipate that regional mesial-temporal hyperconnectivity will be found and correlate with seizure frequency while global networks will be disorganized and be more closely associated with neuro-cognitive deficits. Resting-state fMRI was used to examine temporal lobe regional connectivity and global functional connectivity from 102 patients with TLE and 55 controls. Connectivity matrices were calculated for subcortical volumes and cortical parcellations. Graph theory metrics (global clustering coefficient (GCC), degree, closeness) were compared between groups and in relation to neuropsychological profiles and disease covariates using permutation testing and causal analysis. In TLE there was a decrease in GCC (p = 0.0345) associated with a worse neuropsychological profile (p = 0.0134). There was increased connectivity in the left hippocampus/amygdala (degree p = 0.0103, closeness p = 0.0104) and a decrease in connectivity in the right lateral temporal lobe (degree p = 0.0186, closeness p = 0.0122). A ratio between the hippocampus/amygdala and lateral temporal lobe-temporal lobe connectivity ratio (TLCR) revealed differences between TLE and controls for closeness (left p = 0.00149, right p = 0.0494) and for degree on left p = 0.00169; with trend on right p = 0.0567. Causal analysis suggested that "Epilepsy Activity" (seizure frequency, anti-seizure medications) was associated with increase in TLCR but not in GCC, while cognitive decline was associated with decreased GCC. These findings support the hypothesis that in TLE there is hyperconnectivity in the hippocampus/amygdala and hypoconnectivity in the lateral temporal lobe associated with "Epilepsy Activity." While, global connectome disorganization was associated with worse neuropsychological phenotype.

Aberrant visual population receptive fields in human albinism.

Retinotopic organization is a fundamental feature of visual cortex thought to play a vital role in encoding spatial information. One important aspect of normal retinotopy is the representation of the right and left hemifields in contralateral visual cortex. However, in human albinism, many temporal retinal afferents decussate aberrantly at the optic chiasm resulting in partially superimposed representations of opposite hemifields in each hemisphere of visual cortex. Previous functional magnetic resonance imaging (fMRI) studies in human albinism suggest that the right and left hemifield representations are superimposed in a mirror-symmetric manner. This should produce imaging voxels which respond to two separate locations mirrored across the vertical meridian. However, it is not yet clear how retino-cortical miswiring in albinism manifests at the level of single voxel population receptive fields (pRFs). Here, we used pRF modeling to fit both single and dual pRF models to the visual responses of voxels in visual areas V1 to V3 of five subjects with albinism. We found that subjects with albinism (but not controls) have sizable clusters of voxels with unequivocal dual pRFs consistently corresponding to, but not fully coextensive with, regions of hemifield overlap. These dual pRFs were typically positioned at locations roughly mirrored across the vertical meridian and were uniquely clustered within a portion of the visual field for each subject.

Neuroticism in temporal lobe epilepsy is associated with altered limbic-frontal lobe resting-state functional connectivity.

Neuroticism, a core personality trait characterized by a tendency towards experiencing negative affect, has been reported to be higher in people with temporal lobe epilepsy (TLE) compared with healthy individuals. Neuroticism is a known predictor of depression and anxiety, which also occur more frequently in people with TLE. The purpose of this study was to identify abnormalities in whole-brain resting-state functional connectivity in relation to neuroticism in people with TLE and to determine the degree of unique versus shared patterns of abnormal connectivity in relation to elevated symptoms of depression and anxiety. Ninety-three individuals with TLE (55 females) and 40 healthy controls (18 females) from the Epilepsy Connectome Project (ECP) completed measures of neuroticism, depression, and anxiety, which were all significantly higher in people with TLE compared with controls. Resting-state functional connectivity was compared between controls and groups with TLE with high and low neuroticism using analysis of variance (ANOVA) and t-test. In secondary analyses, the same analytics were performed using measures of depression and anxiety and the unique variance in resting-state connectivity associated with neuroticism independent of symptoms of depression and anxiety identified. Increased neuroticism was significantly associated with hyposynchrony between the right hippocampus and Brodmann area (BA) 9 (region of prefrontal cortex (PFC)) (p < 0.005), representing a unique relationship independent of symptoms of depression and anxiety. Hyposynchrony of connection between the right hippocampus and BA47 (anterior frontal operculum) was associated with high neuroticism and with higher depression and anxiety scores (p < 0.05), making it a shared abnormal connection for the three measures. In conclusion, increased neuroticism exhibits both unique and shared patterns of abnormal functional connectivity with depression and anxiety symptoms between regions of the mesial temporal and frontal lobe.

The relationship between retinal cone density and cortical magnification in human albinism.

The human fovea lies at the center of the retina and supports high-acuity vision. In normal visual system development, the highest acuity is correlated with both a high density of cone photoreceptors in the fovea and a magnified retinotopic representation of the fovea in the visual cortex. Both cone density and the cortical area dedicated to each degree of visual space-the latter describing cortical magnification (CM)-steadily decrease with increasing eccentricity from the fovea. In albinism, peak cone density at the fovea and visual acuity are decreased, but seem to be within normal limits in the periphery, thus providing a model to explore the correlation between retinal structure, cortical structure, and behavior. Here, we used adaptive optics scanning light ophthalmoscopy to assess retinal cone density and functional magnetic resonance imaging to measure CM in the primary visual cortex of normal controls and individuals with albinism. We find that retinotopic organization is more varied among individuals with albinism than previously appreciated. Additionally, CM outside the fovea is similar to that in controls, but also more variable. CM in albinism and controls exceeds that which might be predicted based on cone density alone, but is more accurately predicted by retinal ganglion cell density. This finding suggests that decreased foveal cone density in albinism may be partially counteracted by nonuniform connectivity between cones and their downstream signaling partners. Together, these results emphasize that central as well as retinal factors must be included to provide a complete picture of aberrant structure and function in albinism.

Neuroanatomical correlates of personality traits in temporal lobe epilepsy: Findings from the Epilepsy Connectome Project.

Behavioral and personality disorders in temporal lobe epilepsy (TLE) have been a topic of interest and controversy for decades, with less attention paid to alterations in normal personality structure and traits. In this investigation, core personality traits (the Big 5) and their neurobiological correlates in TLE were explored using the Neuroticism Extraversion Openness-Five Factor Inventory (NEO-FFI) and structural magnetic resonance imaging (MRI) through the Epilepsy Connectome Project (ECP). NEO-FFI scores from 67 individuals with TLE (34.6 ±â€¯9.5 years; 67% women) were compared to 31 healthy controls (32.8 ±â€¯8.9 years; 41% women) to assess differences in the Big 5 traits (agreeableness, openness, conscientiousness, neuroticism, and extraversion). Individuals with TLE showed significantly higher neuroticism, with no significant differences on the other traits. Neural correlates of neuroticism were then determined in participants with TLE including cortical and subcortical volumes. Distributed reductions in cortical gray matter volumes were associated with increased neuroticism. Subcortically, hippocampal and amygdala volumes were negatively associated with neuroticism. These results offer insight into alterations in the Big 5 personality traits in TLE and their brain-related correlates.

The attentional field revealed by single-voxel modeling of fMRI time courses.

The spatial topography of visual attention is a distinguishing and critical feature of many theoretical models of visuospatial attention. Previous fMRI-based measurements of the topography of attention have typically been too crude to adequately test the predictions of different competing models. This study demonstrates a new technique to make detailed measurements of the topography of visuospatial attention from single-voxel, fMRI time courses. Briefly, this technique involves first estimating a voxel's population receptive field (pRF) and then "drifting" attention through the pRF such that the modulation of the voxel's fMRI time course reflects the spatial topography of attention. The topography of the attentional field (AF) is then estimated using a time-course modeling procedure. Notably, we are able to make these measurements in many visual areas including smaller, higher order areas, thus enabling a more comprehensive comparison of attentional mechanisms throughout the full hierarchy of human visual cortex. Using this technique, we show that the AF scales with eccentricity and varies across visual areas. We also show that voxels in multiple visual areas exhibit suppressive attentional effects that are well modeled by an AF having an enhancing Gaussian center with a suppressive surround. These findings provide extensive, quantitative neurophysiological data for use in modeling the psychological effects of visuospatial attention.

Atypical retinotopic organization of visual cortex in patients with central brain damage: congenital and adult onset.

It remains unclear to what extent retinotopic maps can undergo large-scale plasticity following damage to human visual cortex. The literature has predominately focused on retinotopic changes in patients with retinal pathologies or congenital brain malformations. Yet, damage to the adult visual cortex itself is common in cases such as stroke, tumor, or trauma. To address this issue, we used a unique database of fMRI vision maps in patients with adult-onset (n=25) and congenital (n=2) pathology of the visual cortex. We identified atypical retinotopic organization in three patients (two with adult-onset, and one with congenital pathology) consisting of an expanded ipsilateral field representation that was on average 3.2 times greater than healthy controls. The expanded representations were located at the vertical meridian borders between visual areas such as V1/V2. Additionally, two of the three patients had apparently an ectopic (topographically inconsistent) representation of the ipsilateral field within lateral occipital cortex that is normally associated with visual areas V3/V3A (and possibly other areas). Both adult-onset cases had direct damage to early visual cortex itself (rather than to the afferent drive only), resulting in a mostly nonfunctional hemisphere. The congenital case had severe cortical malformation of the visual cortex and was acallosal. Our results are consistent with a competitive model in which unilateral damage to visual cortex or disruption of the transcallosal connections removes interhemispheric suppression from retino-geniculate afferents in intact visual cortex that represent the vertical meridian and ipsilateral visual field.

An investigation of positive and inverted hemodynamic response functions across multiple visual areas.

Recent studies have demonstrated significant regional variability in the hemodynamic response function (HRF), highlighting the difficulty of correctly interpreting functional MRI (fMRI) data without proper modeling of the HRF. The focus of this study was to investigate the HRF variability within visual cortex. The HRF was estimated for a number of cortical visual areas by deconvolution of fMRI blood oxygenation level dependent (BOLD) responses to brief, large-field visual stimulation. Significant HRF variation was found across visual areas V1, V2, V3, V4, VO-1,2, V3AB, IPS-0,1,2,3, LO-1,2, and TO-1,2. Additionally, a subpopulation of voxels was identified that exhibited an impulse response waveform that was similar, but not identical, to an inverted version of the commonly described and modeled positive HRF. These voxels were found within the retinotopic confines of the stimulus and were intermixed with those showing positive responses. The spatial distribution and variability of these HRFs suggest a vascular origin for the inverted waveforms. We suggest that the polarity of the HRF is a separate factor that is independent of the suppressive or activating nature of the underlying neuronal activity. Correctly modeling the polarity of the HRF allows one to recover an estimate of the underlying neuronal activity rather than discard the responses from these voxels on the assumption that they are artifactual. We demonstrate this approach on phase-encoded retinotopic mapping data as an example of the benefits of accurately modeling the HRF during the analysis of fMRI data.

Are neuronal mechanisms of attention universal across human sensory and motor brain maps?

One's experience of shifting attention from the color to the smell to the act of picking a flower seems like a unitary process applied, at will, to one modality after another. Yet, the unique and separable experiences of sight versus smell versus movement might suggest that the neural mechanisms of attention have been separately optimized to employ each modality to its greatest advantage. Moreover, addressing the issue of universality can be particularly difficult due to a paucity of existing cross-modal comparisons and a dearth of neurophysiological methods that can be applied equally well across disparate modalities. Here we outline some of the conceptual and methodological issues related to this problem and present an instructive example of an experimental approach that can be applied widely throughout the human brain to permit detailed, quantitative comparison of attentional mechanisms across modalities. The ultimate goal is to spur efforts across disciplines to provide a large and varied database of empirical observations that will either support the notion of a universal neural substrate for attention or more clearly identify the degree to which attentional mechanisms are specialized for each modality.

BOLD Contrast Response Characteristics of Aberrant Voxels with Bilateral Visual Population Receptive Fields in Human Albinism.

Albinism is an inherited disorder characterized by disrupted melanin production in the eye, and often in the skin and hair. This retinal hypopigmentation is accompanied by pathological decussation of many temporal retinal afferents at the optic chiasm during development, ultimately resulting in partially superimposed representations of opposite visual hemifields in each cortical hemisphere. Within these aberrant regions of hemifield overlap, individual voxels have been shown to have bilateral, dual population receptive fields (pRFs) responding to roughly mirror-image locations across the vertical meridian. Nonetheless, how these two conflicting inputs combine to determine a voxel's response to image contrast is still unknown. To address this, we stimulated the right and left hemifields with separately controlled sinusoidal gratings, each having a variety of contrasts (0, 8, 20, 45, 100%), and extracted voxel-wise BOLD response amplitudes to each contrast combination in visual areas V1-V3. We then compared voxels' responses to each hemifield stimulated individually with conditions when both hemifields were stimulated simultaneously. We hypothesized that simultaneous stimulation of the two pRF components will result in either a suppressive or facilitative interaction. However, we found that BOLD responses to simultaneous stimulation appeared to reflect simple summation of the neural activity from the individual hemifield conditions. This suggests that the superimposed opposite hemifield representations do not interact. Thus, dual pRFs in albinism likely reflect two co-localized, but functionally independent populations of neurons each of which respond to a single hemifield. This finding is commensurate with psychophysical studies which have shown no clear perceptual interaction between opposite visual hemifields in human albinism.

T1-/T2-weighted ratio reveals no alterations to gray matter myelination in temporal lobe epilepsy.

Short-range functional connectivity in the limbic network is increased in patients with temporal lobe epilepsy (TLE), and recent studies have shown that cortical myelin content correlates with fMRI connectivity. We thus hypothesized that myelin may increase progressively in the epileptic network. We compared T1w/T2w gray matter myelin maps between TLE patients and age-matched controls and assessed relationships between myelin and aging. While both TLE patients and healthy controls exhibited increased T1w/T2w intensity with age, we found no evidence for significant group-level aberrations in overall myelin content or myelin changes through time in TLE.

Adaptive Kalman filtering for real-time mapping of the visual field.

This paper demonstrates the feasibility of real-time mapping of the visual field for clinical applications. Specifically, three aspects of this problem were considered: (1) experimental design, (2) statistical analysis, and (3) display of results. Proper experimental design is essential to achieving a successful outcome, particularly for real-time applications. A random-block experimental design was shown to have less sensitivity to measurement noise, as well as greater robustness to error in modeling of the hemodynamic impulse response function (IRF) and greater flexibility than common alternatives. In addition, random encoding of the visual field allows for the detection of voxels that are responsive to multiple, not necessarily contiguous, regions of the visual field. Due to its recursive nature, the Kalman filter is ideally suited for real-time statistical analysis of visual field mapping data. An important feature of the Kalman filter is that it can be used for nonstationary time series analysis. The capability of the Kalman filter to adapt, in real time, to abrupt changes in the baseline arising from subject motion inside the scanner and other external system disturbances is important for the success of clinical applications. The clinician needs real-time information to evaluate the success or failure of the imaging run and to decide whether to extend, modify, or terminate the run. Accordingly, the analytical software provides real-time displays of (1) brain activation maps for each stimulus segment, (2) voxel-wise spatial tuning profiles, (3) time plots of the variability of response parameters, and (4) time plots of activated volume.

Effects of Thresholding on Voxel-Wise Correspondence of Breath-Hold and Resting-State Maps of Cerebrovascular Reactivity.

Functional magnetic resonance imaging for presurgical brain mapping enables neurosurgeons to identify viable tissue near a site of operable pathology which might be at risk of surgery-induced damage. However, focal brain pathology (e.g., tumors) may selectively disrupt neurovascular coupling while leaving the underlying neurons functionally intact. Such neurovascular uncoupling can result in false negatives on brain activation maps thereby compromising their use for surgical planning. One way to detect potential neurovascular uncoupling is to map cerebrovascular reactivity using either an active breath-hold challenge or a passive resting-state scan. The equivalence of these two methods has yet to be fully established, especially at a voxel level of resolution. To quantitatively compare breath-hold and resting-state maps of cerebrovascular reactivity, we first identified threshold settings that optimized coverage of gray matter while minimizing false responses in white matter. When so optimized, the resting-state metric had moderately better gray matter coverage and specificity. We then assessed the spatial correspondence between the two metrics within cortical gray matter, again, across a wide range of thresholds. Optimal spatial correspondence was strongly dependent on threshold settings which if improperly set tended to produce statistically biased maps. When optimized, the two CVR maps did have moderately good correspondence with each other (mean accuracy of 73.6%). Our results show that while the breath-hold and resting-state maps may appear qualitatively similar they are not quantitatively identical at a voxel level of resolution.

Brain aging in temporal lobe epilepsy: Chronological, structural, and functional.

The association of epilepsy with structural brain changes and cognitive abnormalities in midlife has raised concern regarding the possibility of future accelerated brain and cognitive aging and increased risk of later life neurocognitive disorders. To address this issue we examined age-related processes in both structural and functional neuroimaging among individuals with temporal lobe epilepsy (TLE, N = 104) who were participants in the Epilepsy Connectome Project (ECP). Support vector regression (SVR) models were trained from 151 healthy controls and used to predict TLE patients' brain ages. It was found that TLE patients on average have both older structural (+6.6 years) and functional (+8.3 years) brain ages compared to healthy controls. Accelerated functional brain age (functional - chronological age) was mildly correlated (corrected P = 0.07) with complex partial seizure frequency and the number of anti-epileptic drug intake. Functional brain age was a significant correlate of declining cognition (fluid abilities) and partially mediated chronological age-fluid cognition relationships. Chronological age was the only positive predictor of crystallized cognition. Accelerated aging is evident not only in the structural brains of patients with TLE, but also in their functional brains. Understanding the causes of accelerated brain aging in TLE will be clinically important in order to potentially prevent or mitigate their cognitive deficits.

Network, clinical and sociodemographic features of cognitive phenotypes in temporal lobe epilepsy.

This study explored the taxonomy of cognitive impairment within temporal lobe epilepsy and characterized the sociodemographic, clinical and neurobiological correlates of identified cognitive phenotypes. 111 temporal lobe epilepsy patients and 83 controls (mean ages 33 and 39, 57% and 61% female, respectively) from the Epilepsy Connectome Project underwent neuropsychological assessment, clinical interview, and high resolution 3T structural and resting-state functional MRI. A comprehensive neuropsychological test battery was reduced to core cognitive domains (language, memory, executive, visuospatial, motor speed) which were then subjected to cluster analysis. The resulting cognitive subgroups were compared in regard to sociodemographic and clinical epilepsy characteristics as well as variations in brain structure and functional connectivity. Three cognitive subgroups were identified (intact, language/memory/executive function impairment, generalized impairment) which differed significantly, in a systematic fashion, across multiple features. The generalized impairment group was characterized by an earlier age at medication initiation (P < 0.05), fewer patient (P < 0.001) and parental years of education (P < 0.05), greater racial diversity (P < 0.05), and greater number of lifetime generalized seizures (P < 0.001). The three groups also differed in an orderly manner across total intracranial (P < 0.001) and bilateral cerebellar cortex volumes (P < 0.01), and rate of bilateral hippocampal atrophy (P < 0.014), but minimally in regional measures of cortical volume or thickness. In contrast, large-scale patterns of cortical-subcortical covariance networks revealed significant differences across groups in global and local measures of community structure and distribution of hubs. Resting-state fMRI revealed stepwise anomalies as a function of cluster membership, with the most abnormal patterns of connectivity evident in the generalized impairment group and no significant differences from controls in the cognitively intact group. Overall, the distinct underlying cognitive phenotypes of temporal lobe epilepsy harbor systematic relationships with clinical, sociodemographic and neuroimaging correlates. Cognitive phenotype variations in patient and familial education and ethnicity, with linked variations in total intracranial volume, raise the question of an early and persisting socioeconomic-status related neurodevelopmental impact, with additional contributions of clinical epilepsy factors (e.g., lifetime generalized seizures). The neuroimaging features of cognitive phenotype membership are most notable for disrupted large scale cortical-subcortical networks and patterns of functional connectivity with bilateral hippocampal and cerebellar atrophy. The cognitive taxonomy of temporal lobe epilepsy appears influenced by features that reflect the combined influence of socioeconomic, neurodevelopmental and neurobiological risk factors.

The representation of spatial attention in human parietal cortex dynamically modulates with performance.

The control and allocation of attention is an essential, ubiquitous neural process that gates our awareness of objects and events in the environment. Neural representations of the locus of spatial attention have been previously demonstrated in parietal cortex. However, the behavioral relevance of these neural representations is not known. While undergoing functional magnetic resonance imaging, subjects performed a covert spatial attention task that yielded a wide range of performance values. Voxels in parietal cortex selective for attended target location also dynamically modulated, becoming more or less responsive as performance levels changed. Surprisingly, this relationship was not linear. Responses peaked at intermediate performance levels and dropped both when performance was very high and when it was very low. Such dynamic modulation may represent a mechanism for organizing neural control signals according to behavioral task demands.

Cognitive slowing and its underlying neurobiology in temporal lobe epilepsy.

Cognitive slowing is a known but comparatively under-investigated neuropsychological complication of the epilepsies in relation to other known cognitive comorbidities such as memory, executive function and language. Here we focus on a novel metric of processing speed, characterize its relative salience compared to other cognitive difficulties in epilepsy, and explore its underlying neurobiological correlates. Research participants included 55 patients with temporal lobe epilepsy (TLE) and 58 healthy controls from the Epilepsy Connectome Project (ECP) who were administered a battery of tests yielding 14 neuropsychological measures, including selected tests from the NIH Toolbox-Cognitive Battery, and underwent 3T MRI and resting state fMRI. TLE patients exhibited a pattern of generalized cognitive impairment with very few lateralized abnormalities. Using the neuropsychological measures, machine learning (Support Vector Machine binary classification model) classified the TLE and control groups with 74% accuracy with processing speed (NIH Toolbox Pattern Comparison Processing Speed Test) the best predictor. In TLE, slower processing speed was associated predominantly with decreased local gyrification in regions including the rostral and caudal middle frontal gyrus, inferior precentral cortex, insula, inferior parietal cortex (angular and supramarginal gyri), lateral occipital cortex, rostral anterior cingulate, and medial orbital frontal regions, as well as three small regions of the temporal lobe. Slower processing speed was also associated with decreased connectivity between the primary visual cortices in both hemispheres and the left supplementary motor area, as well as between the right parieto-occipital sulcus and right middle insular area. Overall, slowed processing speed is an important cognitive comorbidity of TLE associated with altered brain structure and connectivity.

Effective Connectivity Within the Default Mode Network in Left Temporal Lobe Epilepsy: Findings from the Epilepsy Connectome Project.

The Epilepsy Connectome Project examines the differences in connectomes between temporal lobe epilepsy (TLE) patients and healthy controls. Using these data, the effective connectivity of the default mode network (DMN) in patients with left TLE compared with healthy controls was investigated using spectral dynamic causal modeling (spDCM) of resting-state functional magnetic resonance imaging data. Group comparisons were made using two parametric empirical Bayes (PEB) models. The first level of each PEB model consisted of each participant's spDCM. Two different second-level models were constructed: the first comparing effective connectivity of the groups directly and the second using the Rey Auditory Verbal Learning Test (RAVLT) delayed free recall index as a covariate at the second level to assess effective connectivity controlling for the poor memory performance of left TLE patients. After an automated search over the nested parameter space and thresholding parameters at 95% posterior probability, both models revealed numerous connections in the DMN, which lead to inhibition of the left hippocampal formation. Left hippocampal formation inhibition may be an inherent result of the left temporal epileptogenic focus as memory differences were controlled for in one model and the same connections remained. An excitatory connection from the posterior cingulate cortex to the medial prefrontal cortex was found to be concomitant with left hippocampal formation inhibition in TLE patients when including RAVLT delayed free recall at the second level.

Using Low-Frequency Oscillations to Detect Temporal Lobe Epilepsy with Machine Learning.

The National Institutes of Health-sponsored Epilepsy Connectome Project aims to characterize connectivity changes in temporal lobe epilepsy (TLE) patients. The magnetic resonance imaging protocol follows that used in the Human Connectome Project, and includes 20 min of resting-state functional magnetic resonance imaging acquired at 3T using 8-band multiband imaging. Glasser parcellation atlas was combined with the FreeSurfer subcortical regions to generate resting-state functional connectivity (RSFC), amplitude of low-frequency fluctuations (ALFFs), and fractional ALFF measures. Seven different frequency ranges such as Slow-5 (0.01-0.027 Hz) and Slow-4 (0.027-0.073 Hz) were selected to compute these measures. The goal was to train machine learning classification models to discriminate TLE patients from healthy controls, and to determine which combination of the resting state measure and frequency range produced the best classification model. The samples included age- and gender-matched groups of 60 TLE patients and 59 healthy controls. Three traditional machine learning models were trained: support vector machine, linear discriminant analysis, and naive Bayes classifier. The highest classification accuracy was obtained using RSFC measures in the Slow-4 + 5 band (0.01-0.073 Hz) as features. Leave-one-out cross-validation accuracies were ∼83%, with receiver operating characteristic area-under-the-curve reaching close to 90%. Increased connectivity from right area posterior 9-46v in TLE patients contributed to the high accuracies. With increased sample sizes in the near future, better machine learning models will be trained not only to aid the diagnosis of TLE, but also as a tool to understand this brain disorder.