Towards precision well-being in medical education.

Medical trainee well-being is often met with generalized solutions that overlook substantial individual variations in mental health predisposition and stress reactivity. Precision medicine leverages individual environmental, genetic, and lifestyle factors to tailor preventive and therapeutic interventions. In addition, an exclusive focus on clinical mental illness tends to disregard the importance of supporting the positive aspects of medical trainee well-being. We introduce a novel precision well-being framework for medical education that is built on a comprehensive and individualized view of mental health, combining measures from mental health and positive psychology in a unified, data-driven framework. Unsupervised machine learning techniques commonly used in precision medicine were applied to uncover patterns within multidimensional mental health data of medical students. Using data from 3,632 US medical students, clusters were formulated based on recognized metrics for depression, anxiety, and flourishing. The analysis identified three distinct clusters. Membership in the 'Healthy Flourishers' well-being phenotype was associated with no signs of anxiety or depression while simultaneously reporting high levels of flourishing. Students in the 'Getting By' cluster reported mild anxiety and depression and diminished flourishing. Membership in the 'At-Risk' cluster was associated with high anxiety and depression, languishing, and increased suicidality. Nearly half (49%) of the medical students surveyed were classified as 'Healthy Flourishers', whereas 36% were grouped into the 'Getting-By' cluster and 15% were identified as 'At-Risk'. Findings show that a substantial portion of medical students report diminished well-being during their studies, with a significant number struggling with mental health challenges. This novel precision well-being framework represents an integrated empirical model that classifies individual medical students into distinct and meaningful well-being phenotypes based on their holistic mental health. This approach has direct applicability to student support and can be used to evaluate the effectiveness of personalized intervention strategies stratified by cluster membership.

Spatiotemporal dynamics of human high gamma discriminate naturalistic behavioral states.

In analyzing the neural correlates of naturalistic and unstructured behaviors, features of neural activity that are ignored in a trial-based experimental paradigm can be more fully studied and investigated. Here, we analyze neural activity from two patients using electrocorticography (ECoG) and stereo-electroencephalography (sEEG) recordings, and reveal that multiple neural signal characteristics exist that discriminate between unstructured and naturalistic behavioral states such as "engaging in dialogue" and "using electronics". Using the high gamma amplitude as an estimate of neuronal firing rate, we demonstrate that behavioral states in a naturalistic setting are discriminable based on long-term mean shifts, variance shifts, and differences in the specific neural activity's covariance structure. Both the rapid and slow changes in high gamma band activity separate unstructured behavioral states. We also use Gaussian process factor analysis (GPFA) to show the existence of salient spatiotemporal features with variable smoothness in time. Further, we demonstrate that both temporally smooth and stochastic spatiotemporal activity can be used to differentiate unstructured behavioral states. This is the first attempt to elucidate how different neural signal features contain information about behavioral states collected outside the conventional experimental paradigm.

Ongoing neural oscillations influence behavior and sensory representations by suppressing neuronal excitability.

The ability to process and respond to external input is critical for adaptive behavior. Why, then, do neural and behavioral responses vary across repeated presentations of the same sensory input? Ongoing fluctuations of neuronal excitability are currently hypothesized to underlie the trial-by-trial variability in sensory processing. To test this, we capitalized on intracranial electrophysiology in neurosurgical patients performing an auditory discrimination task with visual cues: specifically, we examined the interaction between prestimulus alpha oscillations, excitability, task performance, and decoded neural stimulus representations. We found that strong prestimulus oscillations in the alpha+ band (i.e., alpha and neighboring frequencies), rather than the aperiodic signal, correlated with a low excitability state, indexed by reduced broadband high-frequency activity. This state was related to slower reaction times and reduced neural stimulus encoding strength. We propose that the alpha+ rhythm modulates excitability, thereby resulting in variability in behavior and sensory representations despite identical input.

Microscale Physiological Events on the Human Cortical Surface.

Despite ongoing advances in our understanding of local single-cellular and network-level activity of neuronal populations in the human brain, extraordinarily little is known about their "intermediate" microscale local circuit dynamics. Here, we utilized ultra-high-density microelectrode arrays and a rare opportunity to perform intracranial recordings across multiple cortical areas in human participants to discover three distinct classes of cortical activity that are not locked to ongoing natural brain rhythmic activity. The first included fast waveforms similar to extracellular single-unit activity. The other two types were discrete events with slower waveform dynamics and were found preferentially in upper cortical layers. These second and third types were also observed in rodents, nonhuman primates, and semi-chronic recordings from humans via laminar and Utah array microelectrodes. The rates of all three events were selectively modulated by auditory and electrical stimuli, pharmacological manipulation, and cold saline application and had small causal co-occurrences. These results suggest that the proper combination of high-resolution microelectrodes and analytic techniques can capture neuronal dynamics that lay between somatic action potentials and aggregate population activity. Understanding intermediate microscale dynamics in relation to single-cell and network dynamics may reveal important details about activity in the full cortical circuit.

An Intracranial Electrophysiology Study of Visual Language Encoding: The Contribution of the Precentral Gyrus to Silent Reading.

Models of reading emphasize that visual (orthographic) processing provides input to phonological as well as lexical-semantic processing. Neurobiological models of reading have mapped these processes to distributed regions across occipital-temporal, temporal-parietal, and frontal cortices. However, the role of the precentral gyrus in these models is ambiguous. Articulatory phonemic representations in the precentral gyrus are obviously involved in reading aloud, but it is unclear if the precentral gyrus is recruited during reading silently in a time window consistent with participation in phonological processing contributions. Here, we recorded intracranial electrophysiology during a speeded semantic decision task from 24 patients to map the spatio-temporal flow of information across the cortex during silent reading. Patients selected animate nouns from a stream of nonanimate words, letter strings, and false-font stimuli. We characterized the distribution and timing of evoked high-gamma power (70-170 Hz) as well as phase-locking between electrodes. The precentral gyrus showed a proportion of electrodes responsive to linguistic stimuli (27%) that was at least as high as those of surrounding peri-sylvian regions. These precentral gyrus electrodes had significantly greater high-gamma power for words compared to both false-font and letter-string stimuli. In a patient with word-selective effects in the fusiform, superior temporal, and precentral gyri, there was significant phase-locking between the fusiform and precentral gyri starting at ∼180 msec and between the precentral and superior temporal gyri starting at ∼220 msec. Finally, our large patient cohort allowed exploratory analyses of the spatio-temporal reading network underlying silent reading. The distribution, timing, and connectivity results place the precentral gyrus as an important hub in the silent reading network.

Algebraic relationship between the structural network's Laplacian and functional network's adjacency matrix is preserved in temporal lobe epilepsy subjects.

The relationship between anatomic and resting state functional connectivity of large-scale brain networks is a major focus of current research. In previous work, we introduced a model based on eigen decomposition of the Laplacian which predicts the functional network from the structural network in healthy brains. In this work, we apply the eigen decomposition model to two types of epilepsy; temporal lobe epilepsy associated with mesial temporal sclerosis, and MRI-normal temporal lobe epilepsy. Our findings show that the eigen relationship between function and structure holds for patients with temporal lobe epilepsy as well as normal individuals. These results suggest that the brain under TLE conditions reconfigures and rewires the fine-scale connectivity (a process which the model parameters are putatively sensitive to), in order to achieve the necessary structure-function relationship.

Time-resolved neural reinstatement and pattern separation during memory decisions in human hippocampus.

Mnemonic decision-making has long been hypothesized to rely on hippocampal dynamics that bias memory processing toward the formation of new memories or the retrieval of old ones. Successful memory encoding may be best optimized by pattern separation, whereby two highly similar experiences can be represented by underlying neural populations in an orthogonal manner. By contrast, successful memory retrieval is thought to be supported by a recovery of the same neural pattern laid down during encoding. Here we examined how hippocampal pattern completion and separation emerge over time during memory decisions. We measured electrocorticography activity in the human hippocampus and posterior occipitotemporal cortex (OTC) while participants performed continuous recognition of items that were new, repeated (old), or highly similar to a prior item (similar). During retrieval decisions of old items, both regions exhibited significant reinstatement of multivariate high-frequency activity (HFA) associated with encoding. Further, the extent of reinstatement of encoding patterns during retrieval was correlated with the strength (HFA power) of hippocampal encoding. Evidence for encoding pattern reinstatement was also seen in OTC on trials requiring fine-grained discrimination of similar items. By contrast, hippocampal activity showed evidence for pattern separation during these trials. Together, these results underscore the critical role of the hippocampus in supporting both reinstatement of overlapping information and separation of similar events.

Forced conceptual thought induced by electrical stimulation of the left prefrontal gyrus involves widespread neural networks.

BACKGROUND: Early accounts of forced thought were reported at the onset of a focal seizure, and characterized as vague, repetitive, and involuntary intellectual auras distinct from perceptual or psychic hallucinations or illusions. Here, we examine the neural underpinnings involved in conceptual thought by presenting a series of 3 patients with epilepsy reporting intrusive thoughts during electrical stimulation of the left lateral prefrontal cortex (PFC) during invasive surgical evaluation. We illustrate the widespread networks involved through two independent brain imaging modalities: resting state functional magnetic resonance imaging (fMRI) (rs-fMRI) and task-based meta-analytic connectivity modeling (MACM). METHODS: We report the clinical and stimulation characteristics of three patients with left hemispheric language dominance who demonstrate forced thought with functional mapping. To examine the brain networks underlying this phenomenon, we used the regions of interest (ROI) centered at the active electrode pairs. We modeled functional networks using two approaches: (1) rs-fMRI functional connectivity analysis, representing 81 healthy controls and (2) meta-analytic connectivity modeling (MACM), representing 8260 healthy subjects. We also determined the overlapping regions between these three subjects' rs-fMRI and MACM networks through a conjunction analysis. RESULTS: We identified that left PFC was associated with a large-scale functional network including frontal, temporal, and parietal regions, a network that has been associated with multiple cognitive functions including semantics, speech, attention, working memory, and explicit memory. CONCLUSIONS: We illustrate the neural networks involved in conceptual thought through a unique patient population and argue that PFC supports this function through activation of a widespread network.

Sensory-motor transformations for speech occur bilaterally.

Historically, the study of speech processing has emphasized a strong link between auditory perceptual input and motor production output. A kind of 'parity' is essential, as both perception- and production-based representations must form a unified interface to facilitate access to higher-order language processes such as syntax and semantics, believed to be computed in the dominant, typically left hemisphere. Although various theories have been proposed to unite perception and production, the underlying neural mechanisms are unclear. Early models of speech and language processing proposed that perceptual processing occurred in the left posterior superior temporal gyrus (Wernicke's area) and motor production processes occurred in the left inferior frontal gyrus (Broca's area). Sensory activity was proposed to link to production activity through connecting fibre tracts, forming the left lateralized speech sensory-motor system. Although recent evidence indicates that speech perception occurs bilaterally, prevailing models maintain that the speech sensory-motor system is left lateralized and facilitates the transformation from sensory-based auditory representations to motor-based production representations. However, evidence for the lateralized computation of sensory-motor speech transformations is indirect and primarily comes from stroke patients that have speech repetition deficits (conduction aphasia) and studies using covert speech and haemodynamic functional imaging. Whether the speech sensory-motor system is lateralized, like higher-order language processes, or bilateral, like speech perception, is controversial. Here we use direct neural recordings in subjects performing sensory-motor tasks involving overt speech production to show that sensory-motor transformations occur bilaterally. We demonstrate that electrodes over bilateral inferior frontal, inferior parietal, superior temporal, premotor and somatosensory cortices exhibit robust sensory-motor neural responses during both perception and production in an overt word-repetition task. Using a non-word transformation task, we show that bilateral sensory-motor responses can perform transformations between speech-perception- and speech-production-based representations. These results establish a bilateral sublexical speech sensory-motor system.

Not All Predictions Are Equal: "What" and "When" Predictions Modulate Activity in Auditory Cortex through Different Mechanisms.

Using predictions based on environmental regularities is fundamental for adaptive behavior. While it is widely accepted that predictions across different stimulus attributes (e.g., time and content) facilitate sensory processing, it is unknown whether predictions across these attributes rely on the same neural mechanism. Here, to elucidate the neural mechanisms of predictions, we combine invasive electrophysiological recordings (human electrocorticography in 4 females and 2 males) with computational modeling while manipulating predictions about content ("what") and time ("when"). We found that "when" predictions increased evoked activity over motor and prefrontal regions both at early (∼180 ms) and late (430-450 ms) latencies. "What" predictability, however, increased evoked activity only over prefrontal areas late in time (420-460 ms). Beyond these dissociable influences, we found that "what" and "when" predictability interactively modulated the amplitude of early (165 ms) evoked responses in the superior temporal gyrus. We modeled the observed neural responses using biophysically realistic neural mass models, to better understand whether "what" and "when" predictions tap into similar or different neurophysiological mechanisms. Our modeling results suggest that "what" and "when" predictability rely on complementary neural processes: "what" predictions increased short-term plasticity in auditory areas, whereas "when" predictability increased synaptic gain in motor areas. Thus, content and temporal predictions engage complementary neural mechanisms in different regions, suggesting domain-specific prediction signaling along the cortical hierarchy. Encoding predictions through different mechanisms may endow the brain with the flexibility to efficiently signal different sources of predictions, weight them by their reliability, and allow for their encoding without mutual interference.SIGNIFICANCE STATEMENT Predictions of different stimulus features facilitate sensory processing. However, it is unclear whether predictions of different attributes rely on similar or different neural mechanisms. By combining invasive electrophysiological recordings of cortical activity with experimental manipulations of participants' predictions about content and time of acoustic events, we found that the two types of predictions had dissociable influences on cortical activity, both in terms of the regions involved and the timing of the observed effects. Further, our biophysical modeling analysis suggests that predictability of content and time rely on complementary neural processes: short-term plasticity in auditory areas and synaptic gain in motor areas, respectively. This suggests that predictions of different features are encoded with complementary neural mechanisms in different brain regions.

Cortical gray-white matter blurring and declarative memory impairment in MRI-negative temporal lobe epilepsy.

Magnetic resonance imaging (MRI)-negative temporal lobe epilepsy (TLE) may be a distinct syndrome from TLE with mesial temporal sclerosis (TLE-MTS). Imaging and neuropsychological features of TLE-MTS are well-known; yet, these features are only beginning to be described in MRI-negative TLE. This study examined whether a quantitative measure of cortical gray and white matter blurring (GWB) was elevated in the temporal lobes ipsilateral to the seizure onset zone of individuals with MRI-negative TLE relative to TLE-MTS and healthy controls (HCs) and whether GWB elevations were associated with neuropsychological comorbidity. Gray-white matter blurring from 34 cortical regions and hippocampal volumes were quantified and compared across 28 people with MRI-negative TLE, 15 people with TLE-MTS, and 51 HCs. Declarative memory was assessed with standard neuropsychological tests and the intracarotid amobarbital procedure (IAP). In the group with MRI-negative TLE (left and right onsets combined), hippocampal volumes were within normal range but GWB was elevated, relative to HCs, across several mesial and lateral temporal lobe regions ipsilateral to the seizure onset zone. Gray-white matter blurring did not differ between the groups with TLE-MTS and HC or between the groups with TLE-MTS and MRI-negative TLE. The group with MRI-negative TLE could not be distinguished from the group with TLE-MTS on any of the standard neuropsychological tests; however, ipsilateral hippocampal volumes and IAP memory scores were lower in the group with TLE-MTS than in the group with MRI-negative TLE. The group with left MRI-negative TLE had lower general cognitive abilities and verbal fluency relative to the HC group, which adds to the characterization of neuropsychological comorbidities in left MRI-negative TLE. In addition, ipsilateral IAP memory performance was reduced relative to contralateral memory performance in MRI-negative TLE, indicating some degree of ipsilateral memory dysfunction. There was no relationship between hippocampal volume and IAP memory scores in MRI-negative TLE; however, decreased ipsilateral IAP memory scores were correlated with elevated GWB in the ipsilateral superior temporal sulcus of people with left MRI-negative TLE. In sum, GWB elevations in the ipsilateral temporal lobe of people with MRI-negative TLE suggest that GWB may serve as a marker for reduced structural integrity in regions in or near the seizure onset zone. Although mesial temporal abnormalities might be the major driver of memory dysfunction in TLE-MTS, a loss of structural integrity in lateral temporal lobe regions may contribute to IAP memory dysfunction in MRI-negative TLE.

Focal Cortical Anomalies and Language Impairment in 16p11.2 Deletion and Duplication Syndrome.

Individuals with copy number variants (CNV) in the 16p11.2 chromosomal region are at high risk for language disorders. We investigate whether the extent and location of focal cortical anomalies are associated with language impairment in individuals with 16p11.2 CNVs. High-resolution T1-weighted MRI scans from 30 16p11.2 deletion (16p-del), 25 16p11.2 duplication (16p-dup), and 90 noncarrier controls (NCC) were analyzed to derive personalized cortical anomaly maps through single-case cortical thickness (CT) comparison to age-matched normative samples. Focal cortical anomalies were elevated in both 16p-del and 16p-dup and their total extent was inversely correlated with Full-Scale IQ. Clusters of abnormally thick cortex were more extensive in the 16p-del group and clusters of abnormally thin cortex were more extensive in the 16p-dup group. Abnormally thick clusters were more extensive in left lateral temporal and bilateral postcentral and mesial occipital regions in 16p-del. Focal cortical anomalies in the left middle temporal region and pars opercularis (Broca's region) of children with 16-del were associated with lower scores on a comprehensive language evaluation. Results extend neuroanatomical findings in 16p11.2 syndrome to include spatially heterogenous focal cortical anomalies that appear to disrupt language ability in accordance with the functional specialization of left frontotemporal regions.

Functional brain connectivity is predictable from anatomic network's Laplacian eigen-structure.

How structural connectivity (SC) gives rise to functional connectivity (FC) is not fully understood. Here we mathematically derive a simple relationship between SC measured from diffusion tensor imaging, and FC from resting state fMRI. We establish that SC and FC are related via (structural) Laplacian spectra, whereby FC and SC share eigenvectors and their eigenvalues are exponentially related. This gives, for the first time, a simple and analytical relationship between the graph spectra of structural and functional networks. Laplacian eigenvectors are shown to be good predictors of functional eigenvectors and networks based on independent component analysis of functional time series. A small number of Laplacian eigenmodes are shown to be sufficient to reconstruct FC matrices, serving as basis functions. This approach is fast, and requires no time-consuming simulations. It was tested on two empirical SC/FC datasets, and was found to significantly outperform generative model simulations of coupled neural masses.

Parahippocampal and Entorhinal Resection Extent Predicts Verbal Memory Decline in an Epilepsy Surgery Cohort.

The differential contribution of medial-temporal lobe regions to verbal declarative memory is debated within the neuroscience, neuropsychology, and cognitive psychology communities. We evaluate whether the extent of surgical resection within medial-temporal regions predicts longitudinal verbal learning and memory outcomes. This single-center retrospective observational study involved patients with refractory temporal lobe epilepsy undergoing unilateral anterior temporal lobe resection from 2007 to 2015. Thirty-two participants with Engel Class 1 and 2 outcomes were included (14 left, 18 right) and followed for a mean of 2.3 years after surgery (±1.5 years). Participants had baseline and postsurgical neuropsychological testing and high-resolution T1-weighted MRI scans. Postsurgical lesions were manually traced and coregistered to presurgical scans to precisely quantify resection extent of medial-temporal regions. Verbal learning and memory change scores were regressed on hippocampal, entorhinal, and parahippocampal resection volume after accounting for baseline performance. Overall, there were no significant differences in learning and memory change between patients who received left and right anterior temporal lobe resection. After controlling for baseline performance, the extent of left parahippocampal resection accounted for 27% (p = .021) of the variance in verbal short delay free recall. The extent of left entorhinal resection accounted for 37% (p = .004) of the variance in verbal short delay free recall. Our findings highlight the critical role that the left parahippocampal and entorhinal regions play in recall for verbal material.

Resting-state functional MRI distinguishes temporal lobe epilepsy subtypes.

OBJECTIVE: We assessed whether presurgical resting state functional magnetic resonance imaging (fMRI) provides information for distinguishing temporal lobe epilepsy (TLE) with mesial temporal sclerosis (TLE-MTS) from TLE without MTS (TLE-noMTS). METHODS: Thirty-four patients with TLE and 34 sex-/age-matched controls consented to a research imaging protocol. MTS status was confirmed by histologic evaluation of surgical tissue (TLE-MTS = 16; TLE-noMTS = 18). The fractional amplitude of low-frequency fluctuations (fALFFs) in the blood oxygen level-dependent (BOLD) resting-state fMRI signal, a marker of local metabolic demand at rest, was averaged at five regions of interest (ROIs; hippocampus, amygdala, frontal, occipital, and temporal lobe), along with corresponding volume and cortical thickness estimates. ROIs were labeled ipsilateral or contralateral according to seizure lateralization and compared across TLE-MTS, TLE-noMTS, and healthy controls (HCs). MTS status was regressed on ipsilateral hippocampal volume and fALFF to test for independent contributions. RESULTS: The TLE-MTS group had reduced fALFF in the ipsilateral amygdala and hippocampus; whereas, the TLE-noMTS group had marginally reduced fALFF in the ipsilateral amygdala but not hippocampus. These results were consistently obtained with and without application of global signal regression (GSR). Ipsilateral hippocampal volume contributed to 37% of the variance in MTS status (p < 0.001) and fALFF contributed an additional 10% (p = 0.021). Two MTS cases were accurately classified with fALFF but not volume, and three were accurately classified with volume but not fALFF. At the lobar level, fALFF (with GSR) was reduced in the ipsilateral temporal and bilateral frontal lobes of patients with TLE-MTS and bilateral frontal lobes of patients with TLE-noMTS in the context of normal cortical thickness. SIGNIFICANCE: This study indicates that resting-state fMRI provides complementary functional information for MTS classification. Findings validate fALFF as a measure of regional brain integrity in TLE and highlight the value of using multi-modal imaging to provide independent diagnostic information in presurgical epilepsy evaluations.

Transient and chronic seizure-induced inflammation in human focal epilepsy.

In animal models, inflammation is both a cause and consequence of seizures. Less is known about the role of inflammation in human epilepsy. We performed positron emission tomography (PET) using a radiotracer sensitive to brain inflammation in a patient with frontal epilepsy ~36 h after a seizure as well as during a seizure-free period. When statistically compared to a group of 12 matched controls, both of the patient's scans identified a frontal (supplementary motor area) region of increased inflammation corresponding to his clinically defined seizure focus, but the postseizure scan showed significantly greater inflammation intensity and spatial extent. These results provide new information about transient and chronic neuroinflammation in human epilepsy and may be relevant to understanding the process of epileptogenesis and guiding therapy.

Exploring the efficacy of a 5-day course of transcranial direct current stimulation (TDCS) on depression and memory function in patients with well-controlled temporal lobe epilepsy.

INTRODUCTION: Depression and memory dysfunction significantly impact the quality of life of patients with epilepsy. Current therapies for these cognitive and psychiatric comorbidities are limited. We explored the efficacy and safety of transcranial direct current stimulation (TDCS) for treating depression and memory dysfunction in patients with temporal lobe epilepsy (TLE). METHODS: Thirty-seven (37) adults with well-controlled TLE were enrolled in a double-blinded, sham-controlled, randomized, parallel-group study of 5 days of fixed-dose (2 mA, 20 min) TDCS. Subjects were randomized to receive either real or sham TDCS, both delivered over the left dorsolateral prefrontal cortex. Patients received neuropsychological testing and a 20-minute scalp EEG at baseline immediately after the TDCS course and at 2- and 4-week follow-up. RESULTS: There was improvement in depression scores immediately after real TDCS, but not sham TDCS, as measured by changes in the Beck Depression Inventory (BDI change: -1.68 vs. 1.27, p<0.05) and NDDI-E (-0.83 vs. 0.9091, p=0.05). There was no difference between the groups at the 2- or 4-week follow-up. There was no effect on delayed or working memory performance. Transcranial direct current stimulation was well-tolerated and did not increase seizure frequency or interictal discharge frequency. Transcranial direct current stimulation induced an increase in delta frequency band power over the frontal region and delta, alpha, and theta band power in the occipital region after real stimulation compared to sham stimulation, although the difference did not reach statistical significance. DISCUSSION: This study provides evidence for the use of TDCS as a safe and well-tolerated nonpharmacologic approach to improving depressive symptoms in patients with well-controlled TLE. However, there were no changes in memory function immediately following or persisting after a stimulation course. Further studies may determine optimal stimulation parameters for maximal mood benefit.

Cortical Gray-White Matter Blurring and Cognitive Morbidity in Focal Cortical Dysplasia.

Focal cortical dysplasia (FCD) is a malformation of cortical development that is associated with high rates of cognitive morbidity. However, the degree to which specific irregularities of dysplastic tissue directly impact cognition remains unknown. This study investigates the relationship between blurring of the cortical gray and white matter boundary on magnetic resonance imaging (MRI) and global cognitive abilities in FCD. Gray-white blurring (GWB) is quantified by sampling the non-normalized T1 image intensity contrast above and below the gray and white matter interface along the cortical mantle. Spherical averaging is used to compare resulting GWB for patients with histopathologically verified FCD with matched controls. Whole-brain correlational analyses are used to investigate the relationship between blurring and general cognitive abilities, controlling for epilepsy duration. Results show that cognitive performance is reduced in patients with FCD relative to controls. Patients show increased GWB in bilateral temporal, parietal, and frontal regions. Furthermore, increased GWB in these regions is linearly related to decreased cognition and mediates group differences in cognitive performance. These findings demonstrate that GWB is a marker of reduced cognitive efficiency in FCD that can potentially be used to probe general and domain-specific cognitive functions in other neurological disorders.

Intracranial cortical responses during visual-tactile integration in humans.

Sensory integration of touch and sight is crucial to perceiving and navigating the environment. While recent evidence from other sensory modality combinations suggests that low-level sensory areas integrate multisensory information at early processing stages, little is known about how the brain combines visual and tactile information. We investigated the dynamics of multisensory integration between vision and touch using the high spatial and temporal resolution of intracranial electrocorticography in humans. We present a novel, two-step metric for defining multisensory integration. The first step compares the sum of the unisensory responses to the bimodal response as multisensory responses. The second step eliminates the possibility that double addition of sensory responses could be misinterpreted as interactions. Using these criteria, averaged local field potentials and high-gamma-band power demonstrate a functional processing cascade whereby sensory integration occurs late, both anatomically and temporally, in the temporo-parieto-occipital junction (TPOJ) and dorsolateral prefrontal cortex. Results further suggest two neurophysiologically distinct and temporally separated integration mechanisms in TPOJ, while providing direct evidence for local suppression as a dominant mechanism for synthesizing visual and tactile input. These results tend to support earlier concepts of multisensory integration as relatively late and centered in tertiary multimodal association cortices.

The corpus callosum and recovery of working memory after epilepsy surgery.

OBJECTIVE: For patients with medically intractable focal epilepsy, the benefit of epilepsy surgery must be weighed against the risk of cognitive decline. Clinical factors such as age and presurgical cognitive level partially predict cognitive outcome; yet, little is known about the role of cross-hemispheric white matter pathways in supporting postsurgical recovery of cognitive function. The purpose of this study is to determine whether the presurgical corpus callosum (CC) midsagittal area is associated with pre- to postsurgical change following epilepsy surgery. METHODS: In this observational study, we retrospectively identified 24 adult patients from an epilepsy resection series who completed preoperative high-resolution T1 -weighted magnetic resonance imaging (MRI) scans, as well as pre- and postsurgical neuropsychological testing. The total area and seven subregional areas of the CC were measured on the midsagittal MRI slice using an automated method. Standardized indices of auditory-verbal working memory and delayed memory were used to probe cognitive change from pre- to postsurgery. CC total and subregional areas were regressed on memory-change scores, after controlling for overall brain volume, age, presurgical memory scores, and duration of epilepsy. RESULTS: Patients had significantly reduced CC area relative to healthy controls. We found a positive relationship between CC area and change in working memory, but not delayed memory; specifically, the larger the CC, the greater the postsurgical improvement in working memory (ß = 0.523; p = 0.009). Effects were strongest in posterior CC subregions. There was no relationship between CC area and presurgical memory scores. SIGNIFICANCE: Findings indicate that larger CC area, measured presurgically, is related to improvement in working memory abilities following epilepsy surgery. This suggests that transcallosal pathways may play an important, yet little understood, role in postsurgical recovery of cognitive functions.