Microscopic dynamics underlying the stress relaxation of arrested soft materials.

Arrested soft materials such as gels and glasses exhibit a slow stress relaxation with a broad distribution of relaxation times in response to linear mechanical perturbations. Although this macroscopic stress relaxation is an essential feature in the application of arrested systems as structural materials, consumer products, foods, and biological materials, the microscopic origins of this relaxation remain poorly understood. Here, we elucidate the microscopic dynamics underlying the stress relaxation of such arrested soft materials under both quiescent and mechanically perturbed conditions through X-ray photon correlation spectroscopy. By studying the dynamics of a model associative gel system that undergoes dynamical arrest in the absence of aging effects, we show that the mean stress relaxation time measured from linear rheometry is directly correlated to the quiescent superdiffusive dynamics of the microscopic clusters, which are governed by a buildup of internal stresses during arrest. We also show that perturbing the system via small mechanical deformations can result in large intermittent fluctuations in the form of avalanches, which give rise to a broad non-Gaussian spectrum of relaxation modes at short times that is observed in stress relaxation measurements. These findings suggest that the linear viscoelastic stress relaxation in arrested soft materials may be governed by nonlinear phenomena involving an interplay of internal stress relaxations and perturbation-induced intermittent avalanches.

Edge-wise analysis reveals white matter connectivity associated with focal to bilateral tonic-clonic seizures.

OBJECTIVE: Focal to bilateral tonic-clonic seizures (FBTCS) represent a challenging subtype of focal temporal lobe epilepsy (TLE) in terms of both severity and treatment response. Most studies have focused on regional brain analysis that is agnostic to the distribution of white matter (WM) pathways associated with a node. We implemented a more selective, edge-wise approach that allowed for identification of the individual connections unique to FBTCS. METHODS: T1-weighted and diffusion-weighted images were obtained from 22 patients with solely focal seizures (FS), 43 FBTCS patients, and 65 age/sex-matched healthy participants (HPs), yielding streamline (STR) connectome matrices. We used diffusion tensor-derived STRs in an edge-wise approach to determine specific structural connectivity changes associated with seizure generalization in FBTCS compared to matched FS and HPs. Graph theory metrics were computed on both node- and edge-based connectivity matrices. RESULTS: Edge-wise analyses demonstrated that all significantly abnormal cross-hemispheric connections belonged to the FBTCS group. Abnormal connections associated with FBTCS were mostly housed in the contralateral hemisphere, with graph metric values generally decreased compared to HPs. In FBTCS, the contralateral amygdala showed selective decreases in the structural connection pathways to the contralateral frontal lobe. Abnormal connections in TLE involved the amygdala, with the ipsilateral side showing increases and the contralateral decreases. All the FS findings indicated higher graph metrics for connections involving the ipsilateral amygdala. Data also showed that some FBTCS connectivity effects are moderated by aging, recent seizure frequency, and longer illness duration. SIGNIFICANCE: Data showed that not all STR pathways are equally affected by the seizure propagation of FBTCS. We demonstrated two key biases, one indicating a large role for the amygdala in the propagation of seizures, the other pointing to the prominent role of cross-hemispheric and contralateral hemisphere connections in FBTCS. We demonstrated topographic reorganization in FBTCS, pointing to the specific WM tracts involved.

Task-based functional magnetic resonance imaging prediction of postsurgical cognitive outcomes in temporal lobe epilepsy: A systematic review, meta-analysis, and new data.

Task-based functional magnetic resonance imaging (tfMRI) has developed as a common alternative in epilepsy surgery to the intracarotid amobarbital procedure, also known as the Wada procedure. Prior studies have implicated tfMRI as a comparable predictor of postsurgical cognitive outcomes. However, the predictive validity of tfMRI has not been established. This preregistered systematic review and meta-analysis (CRD42020183563) synthesizes the literature predicting postsurgical cognitive outcomes in temporal lobe epilepsy (TLE) using tfMRI. The PubMed and PsycINFO literature databases were queried for English-language articles published between January 1, 2009 and December 31, 2020 associating tfMRI laterality indices or symmetry of task activation with outcomes in TLE. Their references were reviewed for additional relevant literature, and unpublished data from our center were incorporated. Nineteen studies were included in the meta-analysis. tfMRI studies predicted postsurgical cognitive outcomes in left TLE ( ρ ̂ = -.27, 95% confidence interval [CI] = -.32 to -.23) but not right TLE ( ρ ̂ = -.02, 95% CI = -.08 to .03). Among studies of left TLE, language tfMRI studies were more robustly predictive of postsurgical cognitive outcomes ( ρ ̂ = -.27, 95% CI = -.33 to -.20) than memory tfMRI studies ( ρ ̂ = -.27, 95% CI = -.43 to -.11). Further moderation by cognitive outcome domain indicated language tfMRI predicted confrontation naming ( ρ ̂ = -.32, 95% CI = -.41 to -.22) and verbal memory ( ρ ̂ = -.26, 95% CI = -.35 to -.17) outcomes, whereas memory tfMRI forecasted only verbal memory outcomes ( ρ ̂ = -.37, 95% CI = -.57 to -.18). Surgery type, birth sex, level of education, age at onset, disease duration, and hemispheric language dominance moderated study outcomes. Sensitivity analyses suggested the interval of postsurgical follow-up, and reporting and methodological practices influenced study outcomes as well. These findings intimate tfMRI is a modest predictor of outcomes in left TLE that should be considered in the context of a larger surgical workup.

Disrupted basal ganglia-thalamocortical loops in focal to bilateral tonic-clonic seizures.

Focal to bilateral tonic-clonic seizures are associated with lower quality of life, higher risk of seizure-related injuries, increased chance of sudden unexpected death, and unfavourable treatment outcomes. Achieving greater understanding of their underlying circuitry offers better opportunity to control these seizures. Towards this goal, we provide a network science perspective of the interactive pathways among basal ganglia, thalamus and cortex, to explore the imprinting of secondary seizure generalization on the mesoscale brain network in temporal lobe epilepsy. Specifically, we parameterized the functional organization of both the thalamocortical network and the basal ganglia-thalamus network with resting state functional MRI in three groups of patients with different focal to bilateral tonic-clonic seizure histories. Using the participation coefficient to describe the pattern of thalamocortical connections among different cortical networks, we showed that, compared to patients with no previous history, those with positive histories of focal to bilateral tonic-clonic seizures, including both remote (none for >1 year) and current (within the past year) histories, presented more uniform distribution patterns of thalamocortical connections in the ipsilateral medial-dorsal thalamic nuclei. As a sign of greater thalamus-mediated cortico-cortical communication, this result comports with greater susceptibility to secondary seizure generalization from the epileptogenic temporal lobe to broader brain networks in these patients. Using interregional integration to characterize the functional interaction between basal ganglia and thalamus, we demonstrated that patients with current history presented increased interaction between putamen and globus pallidus internus, and decreased interaction between the latter and the thalamus, compared to the other two patient groups. Importantly, through a series of 'disconnection' simulations, we showed that these changes in interactive profiles of the basal ganglia-thalamus network in the current history group mainly depended upon the direct but not the indirect basal ganglia pathway. It is intuitively plausible that such disruption in the striatum-modulated tonic inhibition of the thalamus from the globus pallidus internus could lead to an under-suppressed thalamus, which in turn may account for their greater vulnerability to secondary seizure generalization. Collectively, these findings suggest that the broken balance between basal ganglia inhibition and thalamus synchronization can inform the presence and effective control of focal to bilateral tonic-clonic seizures. The mechanistic underpinnings we uncover may shed light on the development of new treatment strategies for patients with temporal lobe epilepsy.

Flexible Cyclic-Poly(phthalaldehyde)/Poly(ε-caprolactone) Blend Fibers with Fast Daylight-Triggered Transience.

Cyclic-poly(phthalaldehyde) (cPPHA) exhibits photo-triggerable depolymerization on-demand for applications like the photolithography of microfabricated electronics. However, cPPHA is inherently brittle and thermally sensitive; both of these properties limit its usefulness as an engineering plastic. Prior to this report, small molecule plasticizers are added to cPPHA-based films to make the polymer more flexible. But plasticizers can eventually leach out of cPPHA, then leaving it increasingly more brittle throughout product lifetime. In this research, a new approach to fabricating flexible cPPHA blends for use as spun fibers is achieved through the incorporation of poly (ε-caprolactone) (PCL) by a modified wet spinning method. Among blend compositions, the 50/50 cPPHA/PCL fiber shows fast transience (<50 s) in response to daylight while retaining the flexibility of PCL and mechanical properties of an elastomer (i.e., tensile strength of ≈8 MPa, Young's modulus of ≈118 MPa, and elongation at break of ≈190%). Embedding 2 wt% gold nanoparticles to cPPHA can further improve the transience rate of fibers comprising less than 50% cPPHA. These flexible, daylight-triggerable cPPHA/PCL fibers can be applied to an extensive range of applications, such as wearable electronics, intelligent textiles, and zero waste packaging for which modest mechanical performance and fast transience are desired.

Consequences of mesial temporal sparing temporal lobe surgery in medically refractory epilepsy.

OBJECTIVE: We compared long-term seizure outcome, neuropsychological outcome, and occupational outcome of anterior temporal lobectomy (ATL) with and without sparing of mesial structures to determine whether mesial sparing temporal lobectomy prevents memory decline and thus disability, with acceptable seizure outcome. METHODS: We studied patients (n = 21) and controls (n = 21) with no evidence of mesial temporal sclerosis (MTS) on MRI who had surgery to treat drug-resistant epilepsy. Demographic and pre- and postsurgical clinical characteristics were compared. Patients had neuropsychological assessment before and after surgery. Neuropsychological analyses were limited to patients with left-sided surgery and available data (n = 14 in each group) as they were at risk of verbal memory impairment. The California Verbal Learning Test II (CVLT-II) (sum of trials 1-5, delayed free recall) and the Logical Memory subtest of the Wechsler Memory Scale III or IV (WMS-III or WMS-IV) (learning and delayed recall of prose passages) were used to assess verbal episodic learning and memory. Seizure and occupational outcomes were assessed. RESULTS: The chance of attaining seizure freedom was similar in the two groups, so sparing mesial temporal structures did not lessen the chance of stopping seizures. Sparing mesial temporal structures mitigated the extent of postoperative verbal memory impairment, though some of these individuals suffered decline as a consequence of surgery. Occupational outcome was similar in both groups. SIGNIFICANCE: Mesial temporal sparing resections provide a similar seizure outcome as ATL, while producing a better memory outcome. Anterior temporal lobectomy including mesial structure resection did not increase the risk of postoperative disability.

Neuroimaging and connectomics of drug-resistant epilepsy at multiple scales: From focal lesions to macroscale networks.

Epilepsy is among the most common chronic neurologic disorders, with 30%-40% of patients having seizures despite antiepileptic drug treatment. The advent of brain imaging and network analyses has greatly improved the understanding of this condition. In particular, developments in magnetic resonance imaging (MRI) have provided measures for the noninvasive characterization and detection of lesions causing epilepsy. MRI techniques can probe structural and functional connectivity, and network analyses have shaped our understanding of whole-brain anomalies associated with focal epilepsies. This review considers the progress made by neuroimaging and connectomics in the study of drug-resistant epilepsies due to focal substrates, particularly temporal lobe epilepsy related to mesiotemporal sclerosis and extratemporal lobe epilepsies associated with malformations of cortical development. In these disorders, there is evidence of widespread disturbances of structural and functional connectivity that may contribute to the clinical and cognitive prognosis of individual patients. It is hoped that studying the interplay between macroscale network anomalies and lesional profiles will improve our understanding of focal epilepsies and assist treatment choices.

Disrupted dynamic network reconfiguration of the language system in temporal lobe epilepsy.

Temporal lobe epilepsy tends to reshape the language system causing maladaptive reorganization that can be characterized by task-based functional MRI, and eventually can contribute to surgical decision making processes. However, the dynamic interacting nature of the brain as a complex system is often neglected, with many studies treating the language system as a static monolithic structure. Here, we demonstrate that as a specialized and integrated system, the language network is inherently dynamic, characterized by rich patterns of regional interactions, whose transient dynamics are disrupted in patients with temporal lobe epilepsy. Specifically, we applied tools from dynamic network neuroscience to functional MRI data collected from 50 temporal lobe epilepsy patients and 30 matched healthy controls during performance of a verbal fluency task, as well as during rest. By assigning 16 language-related regions into four subsystems (i.e. bilateral frontal and temporal), we observed regional specialization in both the probability of transient interactions and the frequency of such changes, in both healthy controls and patients during task performance but not rest. Furthermore, we found that both left and right temporal lobe epilepsy patients displayed reduced interactions within the left frontal 'core' subsystem compared to the healthy controls, while left temporal lobe epilepsy patients were unique in showing enhanced interactions between the left frontal 'core' and the right temporal subsystems. Also, both patient groups displayed reduced flexibility in the transient interactions of the left temporal and right frontal subsystems, which formed the 'periphery' of the language network. Importantly, such group differences were again evident only during task condition. Lastly, through random forest regression, we showed that dynamic reconfiguration of the language system tracks individual differences in verbal fluency with superior prediction accuracy compared to traditional activation-based static measures. Our results suggest dynamic network measures may be an effective biomarker for detecting the language dysfunction associated with neurological diseases such as temporal lobe epilepsy, specifying both the type of neuronal communications that are missing in these patients and those that are potentially added but maladaptive. Further advancements along these lines, transforming how we characterize and map language networks in the brain, have a high probability of altering clinical decision making in neurosurgical centres.10.1093/brain/awy042_video1awy042media15754656112001.

Quantification of Interface-Dependent Plasmon Quality Factors Using Single-Beam Nonlinear Optical Interferometry.

A method for quantification of plasmon mode quality factors using a novel collinear single-beam interferometric nonlinear optical (INLO) microscope is described. A collinear sequence of phase-stabilized femtosecond laser pulses generated by a series of birefringent optics is used for the INLO experiments. Our experimental designs allow for the creation of pulse replicas (800 nm carrier wave) that exhibit interpulse phase stability of 33 mrad (approximately 14 attoseonds), which can be incrementally temporally delayed from attosecond to picosecond time scales. This temporal tuning range allows for resonant electronic Fourier spectroscopy of plasmonic gold nanoparticles. The collinear geometry of the pulse pair facilitates integration into an optical microscopy platform capable of single-nanoparticle sensitivity. Analysis of the Fourier spectra in the frequency domain yields the sample plasmon resonant response and homogeneous line width; the latter provided quantification of the plasmon mode quality factor. We have applied this INLO approach to quantitatively determine the influence of encapsulation of gold nanorods with silica shells on plasmon quality factors. We have studied a series of three gold nanorod samples, distinguished by surface passivation. These include cetyltrimethylammonium bromide (CTAB)-passivated nanorods, as well as ones encapsulated by 5 and 20 nanometer-thick silica shells. The Q-factor results show a trend of increasing quality factor, increasing by 46% from 54 ± 8 to 79 ± 9, in going from CTAB- to 20 nm silica-coated AuNRs. The straightforward method of INLO enables analysis of plasmon responses to environmental influences, such as analyte binding and solvent effects, as well as quantification of structure-specific plasmon coherence dynamics.

Task activation and functional connectivity show concordant memory laterality in temporal lobe epilepsy.

OBJECTIVE: In epilepsy, asymmetries in the organization of mesial temporal lobe (MTL) functions help determine the cognitive risk associated with procedures such as anterior temporal lobectomy. Past studies have investigated the change/shift in a visual episodic memory laterality index (LI) in mesial temporal lobe structures through functional magnetic resonance imaging (fMRI) task activations. Here, we examine whether underlying task-related functional connectivity (FC) is concordant with such standard fMRI laterality measures. METHODS: A total of 56 patients with temporal lobe epilepsy (TLE) (Left TLE [LTLE]: 31; Right TLE [RTLE]: 25) and 34 matched healthy controls (HC) underwent fMRI scanning during performance of a scene encoding task (SET). We assessed an activation-based LI of the hippocampal gyrus (HG) and parahippocampal gyrus (PHG) during the SET and its correspondence with task-related FC measures. RESULTS: Analyses involving the HG and PHG showed that the patients with LTLE had a consistently higher LI (right-lateralized) than that of the HC and group with RTLE, indicating functional reorganization. The patients with RTLE did not display a reliable contralateral shift away from the pathology, with the mesial structures showing quite distinct laterality patterns (HG, no laterality bias; PHG, no evidence of LI shift). The FC data for the group with LTLE provided confirmation of reorganization effects, revealing that a rightward task LI may be based on underlying connections between several left-sided regions (middle/superior occipital and left medial frontal gyri) and the right PHG. The FCs between the right HG and left anterior cingulate/medial frontal gyri were also observed in LTLE. Importantly, the data demonstrate that the areas involved in the LTLE task activation shift to the right hemisphere showed a corresponding increase in task-related FCs between the hemispheres. SIGNIFICANCE: Altered laterality patterns based on mesial temporal lobe epilepsy (MTLE) pathology manifest as several different phenotypes, varying according to side of seizure onset and the specific mesial structures involved. There is good correspondence between task LI activation and FC patterns in the setting of LTLE, suggesting that reliable visual episodic memory reorganization may require both a shift in nodal activation and a change in nodal connectivity with mesial temporal structures involved in memory.

Ripple oscillations in the left temporal neocortex are associated with impaired verbal episodic memory encoding.

BACKGROUND: We sought to determine if ripple oscillations (80-120 Hz), detected in intracranial electroencephalogram (iEEG) recordings of patients with epilepsy, correlate with an enhancement or disruption of verbal episodic memory encoding. METHODS: We defined ripple and spike events in depth iEEG recordings during list learning in 107 patients with focal epilepsy. We used logistic regression models (LRMs) to investigate the relationship between the occurrence of ripple and spike events during word presentation and the odds of successful word recall following a distractor epoch and included the seizure onset zone (SOZ) as a covariate in the LRMs. RESULTS: We detected events during 58,312 word presentation trials from 7630 unique electrode sites. The probability of ripple on spike (RonS) events was increased in the SOZ (p < 0.04). In the left temporal neocortex, RonS events during word presentation corresponded with a decrease in the odds ratio (OR) of successful recall, however, this effect only met significance in the SOZ (OR of word recall: 0.71, 95% confidence interval (CI): 0.59-0.85, n = 158 events, adaptive Hochberg, p < 0.01). Ripple on oscillation (RonO) events that occurred in the left temporal neocortex non-SOZ also correlated with decreased odds of successful recall (OR: 0.52, 95% CI: 0.34-0.80, n = 140, adaptive Hochberg, p < 0.01). Spikes and RonS that occurred during word presentation in the left middle temporal gyrus (MTG) correlated with the most significant decrease in the odds of successful recall, irrespective of the location of the SOZ (adaptive Hochberg, p < 0.01). CONCLUSION: Ripples and spikes generated in the left temporal neocortex are associated with impaired verbal episodic memory encoding. Although physiological and pathological ripple oscillations were not distinguished during cognitive tasks, our results show an association of undifferentiated ripples with impaired encoding. The effect was sometimes specific to regions outside the SOZ, suggesting that widespread effects of epilepsy outside the SOZ may contribute to cognitive impairment.

From "rest" to language task: Task activation selects and prunes from broader resting-state network.

Resting-state networks (RSNs) show spatial patterns generally consistent with networks revealed during cognitive tasks. However, the exact degree of overlap between these networks has not been clearly quantified. Such an investigation shows promise for decoding altered functional connectivity (FC) related to abnormal language functioning in clinical populations such as temporal lobe epilepsy (TLE). In this context, we investigated the network configurations during a language task and during resting state using FC. Twenty-four healthy controls, 24 right and 24 left TLE patients completed a verb generation (VG) task and a resting-state fMRI scan. We compared the language network revealed by the VG task with three FC-based networks (seeding the left inferior frontal cortex (IFC)/Broca): two from the task (ON, OFF blocks) and one from the resting state. We found that, for both left TLE patients and controls, the RSN recruited regions bilaterally, whereas both VG-on and VG-off conditions produced more left-lateralized FC networks, matching more closely with the activated language network. TLE brings with it variability in both task-dependent and task-independent networks, reflective of atypical language organization. Overall, our findings suggest that our RSN captured bilateral activity, reflecting a set of prepotent language regions. We propose that this relationship can be best understood by the notion of pruning or winnowing down of the larger language-ready RSN to carry out specific task demands. Our data suggest that multiple types of network analyses may be needed to decode the association between language deficits and the underlying functional mechanisms altered by disease. Hum Brain Mapp 38:2540-2552, 2017. © 2017 Wiley Periodicals, Inc.

The Temporal Instability of Resting State Network Connectivity in Intractable Epilepsy.

OBJECTIVE: Focal epilepsies, such as temporal lobe epilepsy (TLE), are known to disrupt network activity in areas outside the epileptogenic zone [Tracy et al., 2015]. We devised a measure of temporal instability of resting state functional connectivity (FC), capturing temporal variations of BOLD correlations between brain regions that is less confounded than the "sliding window" approach common in the literature. METHODS: We investigated healthy controls and unilateral TLE patients (right and left seizure focus groups), utilizing group ICA to identify the default mode network (DMN), a network associated with episodic memory, a key cognitive deficit in TLE. Our instability analyses focused on: (1) connectivity between DMN region pairs, both within and between TLE patients and matched controls, (2) whole brain group differences between region pairs ipsilateral or contralateral to the epileptogenic temporal lobe. RESULTS: For both the whole brain and a more focused analysis of DMN region pairs, temporal stability appears to characterize the healthy brain. The TLE patients displayed more FC instability compared to controls, with this instability more pronounced for the right TLE patients. SIGNIFICANCE: Our findings challenge the view that the resting state signal is stable over time, providing a measure of signal coherence change that may generate insights into the temporal components of network organization. The precuneus was the region within the DMN consistently expressing this instability, suggesting this region plays a key role in large scale temporal dynamics of the DMN, with such dynamics disrupted in TLE, putting key cognitive functions at risk. Hum Brain Mapp 38:528-540, 2017. © 2016 Wiley Periodicals, Inc.

Probing biological nanotopology via diffusion of weakly constrained plasmonic nanorods with optical coherence tomography.

Biological materials exhibit complex nanotopology, i.e., a composite liquid and solid phase structure that is heterogeneous on the nanoscale. The diffusion of nanoparticles in nanotopological environments can elucidate biophysical changes associated with pathogenesis and disease progression. However, there is a lack of methods that characterize nanoprobe diffusion and translate easily to in vivo studies. Here, we demonstrate a method based on optical coherence tomography (OCT) to depth-resolve diffusion of plasmon-resonant gold nanorods (GNRs) that are weakly constrained by the biological tissue. By using GNRs that are on the size scale of the polymeric mesh, their Brownian motion is minimally hindered by intermittent collisions with local macromolecules. OCT depth-resolves the particle-averaged translational diffusion coefficient (DT) of GNRs within each coherence volume, which is separable from the nonequilibrium motile activities of cells based on the unique polarized light-scattering properties of GNRs. We show how this enables minimally invasive imaging and monitoring of nanotopological changes in a variety of biological models, including extracellular matrix (ECM) remodeling as relevant to carcinogenesis, and dehydration of pulmonary mucus as relevant to cystic fibrosis. In 3D ECM models, DT of GNRs decreases with both increasing collagen concentration and cell density. Similarly, DT of GNRs is sensitive to human bronchial-epithelial mucus concentration over a physiologically relevant range. This novel method comprises a broad-based platform for studying heterogeneous nanotopology, as distinct from bulk viscoelasticity, in biological milieu.

Imaging Extracellular Matrix Remodeling In Vitro by Diffusion-Sensitive Optical Coherence Tomography.

The mammary gland extracellular matrix (ECM) is comprised of biopolymers, primarily collagen I, that are created and maintained by stromal fibroblasts. ECM remodeling by fibroblasts results in changes in ECM fiber spacing (pores) that have been shown to play a critical role in the aggressiveness of breast cancer. However, minimally invasive methods to measure the spatial distribution of ECM pore areas within tissues and in vitro 3D culture models are currently lacking. We introduce diffusion-sensitive optical coherence tomography (DS-OCT) to image the nanoscale porosity of ECM by sensing weakly constrained diffusion of gold nanorods (GNRs). DS-OCT combines the principles of low-coherence interferometry and heterodyne dynamic light scattering. By collecting co- and cross-polarized light backscattered from GNRs within tissue culture, the ensemble-averaged translational self-diffusion rate, DT, of GNRs is resolved within ∼3 coherence volumes (10 × 5 µm, x × z). As GNRs are slowed by intermittent collisions with ECM fibers, DT is sensitive to ECM porosity on the size scale of their hydrodynamic diameter (∼46 nm). Here, we validate the utility of DS-OCT using pure collagen I gels and 3D mammary fibroblast cultures seeded in collagen/Matrigel, and associate differences in artificial ECM pore areas with gel concentration and cell seed density. Across all samples, DT was highly correlated with pore area obtained by scanning electron microscopy (R(2) = 0.968). We also demonstrate that DS-OCT can accurately map the spatial heterogeneity of layered samples. Importantly, DS-OCT of 3D mammary fibroblast cultures revealed the impact of fibroblast remodeling, where the spatial heterogeneity of matrix porosity was found to increase with cell density. This provides an unprecedented view into nanoscale changes in artificial ECM porosity over effective pore diameters ranging from ∼43 to 360 nm using a micron-scale optical imaging technique. In combination with the topical deposition of GNRs, the minimally invasive nature of DS-OCT makes this a promising technology for studying tissue remodeling processes.

Laser interstitial thermal therapy for medically intractable mesial temporal lobe epilepsy.

OBJECTIVE: To describe mesial temporal lobe ablated volumes, verbal memory, and surgical outcomes in patients with medically intractable mesial temporal lobe epilepsy (mTLE) treated with magnetic resonance imaging (MRI)-guided stereotactic laser interstitial thermal therapy (LiTT). METHODS: We prospectively tracked seizure outcome in 20 patients at Thomas Jefferson University Hospital with drug-resistant mTLE who underwent MRI-guided LiTT from December 2011 to December 2014. Surgical outcome was assessed at 6 months, 1 year, 2 years, and at the most recent visit. Volume-based analysis of ablated mesial temporal structures was conducted in 17 patients with mesial temporal sclerosis (MTS) and results were compared between the seizure-free and not seizure-free groups. RESULTS: Following LiTT, proportions of patients who were free of seizures impairing consciousness (including those with auras only) are as follows: 8 of 15 patients (53%, 95% confidence interval [CI] 30.1-75.2%) after 6 months, 4 of 11 patients (36.4%, 95% CI 14.9-64.8%) after 1 year, 3 of 5 patients (60%, 95% CI 22.9-88.4%) at 2-year follow-up. Median follow-up was 13.4 months after LiTT (range 1.3 months to 3.2 years). Seizure outcome after LiTT suggests an all or none response. Four patients had anterior temporal lobectomy (ATL) after LiTT; three are seizure-free. There were no differences in total ablated volume of the amygdalohippocampus complex or individual volumes of hippocampus, amygdala, entorhinal cortex, parahippocampal gyrus, and fusiform gyrus between seizure-free and non-seizure-free patients. Contextual verbal memory performance was preserved after LiTT, although decline in noncontextual memory task scores were noted. SIGNIFICANCE: We conclude that MRI-guided stereotactic LiTT is a safe alternative to ATL in patients with medically intractable mTLE. Individualized assessment is warranted to determine whether the reduced odds of seizure freedom are worth the reduction in risk, discomfort, and recovery time. Larger prospective studies are needed to confirm our preliminary findings, and to define optimal ablation volume and ideal structures for ablation.

Acute Traumatic Coagulopathy Accompanying Isolated Traumatic Brain Injury is Associated with Worse Long-Term Functional and Cognitive Outcomes.

BACKGROUND: Approximately one-third of patients with isolated traumatic brain injury (iTBI) present with acute traumatic coagulopathy (ATC). ATC is associated with increased morbidity and mortality. Its effects on long-term functional and cognitive outcomes are not as well characterized. METHODS: Data from the Citicoline Brain Injury Treatment Trial (COBRIT) were analyzed retrospectively. Exclusion criteria were renal failure or malignancy, and any extracranial injury severity score >3. ATC was defined as INR > 1.3, PTT > 38 s, or platelets < 100 K, determined at baseline, and during the first 7 days of hospitalization. RESULTS: Six hundred forty-seven patients were included; 21 % were found to have ATC. Highest incidence occurred at baseline, and Day Two. Forty-two percent of ATC patients had a GCS < 8, compared with 11.3 % of non-ATC patients (p < 0.001). A significantly higher proportion of ATC patients was transfused blood products, required greater than 4L of fluids, demonstrated hyperthermia and hypothermia, were hypotensive and demonstrated elevated lactate when compared to non-ATC patients. In-hospital mortality, mean hospital length of stay, incidence of DVT and seizures were also significantly higher in ATC patients. A significantly lower portion of ATC patients had good outcomes on the GOS-E (i.e., score > 6), and the DRS (i.e., score < 2) at 180 days, for which ATC was found to be an independent predictor with binary logistic regression. ATC patients also performed significantly worse on several components of the CVLT-II at 180 days. CONCLUSIONS: ATC accompanying iTBI is associated with worse functional and cognitive outcomes at 180 days.

Resting-state functional connectivity in epilepsy: growing relevance for clinical decision making.

PURPOSE OF REVIEW: Seizures produce dysfunctional, maladaptive networks, making functional connectivity an ideal technique for identifying complex brain effects of epilepsy. We review the current status of resting-state functional connectivity (rsFC) research, highlighting its potential added value to epilepsy surgery programs. RECENT FINDINGS: RsFC research has demonstrated that the brain impact of seizures goes beyond the epileptogenic zone, changing connectivity patterns in widespread cortical regions. There is evidence for abnormal connectivity, but the degree to which these represent adaptive or maladaptive plasticity responses is unclear. Empirical associations with cognitive performance and psychiatric symptoms have helped understand deleterious impacts of seizures outside the epileptogenic zone. Studies in the prediction of outcome suggest that there are identifiable presurgical patterns of functional connectivity associated with a greater likelihood of positive cognitive or seizure outcomes. SUMMARY: The role of rsFC remains limited in most clinical settings, but shows great promise for identifying epileptic circuits and foci, predicting outcomes following surgery, and explaining cognitive deficits and psychiatric symptoms of epilepsy. RsFC has demonstrated that even focal epilepsies constitute a network and brain systems disorder. By providing a tool to both identify and characterize the brain network impact of epileptiform activity, rsFC can make a strong contribution to presurgical algorithms in epilepsy.

Increased microstructural white matter correlations in left, but not right, temporal lobe epilepsy.

Microstructural white matter tract correlations have been shown to reflect known patterns of phylogenetic development and functional specialization in healthy subjects. The aim of this study was to establish intertract correlations in a group of controls and to examine potential deviations from normality in temporal lobe epilepsy (TLE). We investigated intertract correlations in 28 healthy controls, 21 left TLE (LTLE) and 23 right TLE (RTLE). Nine tracts were investigated, comprising the parahippocampal fasciculi, the uncinate fasciculi, the arcuate fasciculi, the frontoparietal tracts, and the fornix. An abnormal increase in tract correlations was observed in LTLE, while RTLE showed intertract correlations similar to controls. In the control group, tract correlations increased with increasing fractional anisotropy (FA), while in the TLE groups tract correlations increased with decreasing FA. Cluster analyses revealed agglomeration of bilateral pairs of homologous tracts in healthy subjects, with such pairs separated in our LTLE and RTLE groups. Discriminant analyses aimed at distinguishing LTLE from RTLE, revealing that tract correlations produce higher rates of accurate group classification than FA values. Our results confirm and extend previous work by showing that LTLE compared to RTLE patients display not only more extensive losses in microstructural orientation but also more aberrant intertract correlations. Aberrant correlations may be related to pathologic processes (i.e., seizure spread) or to adaptive processes aimed at preserving key cognitive functions. Our data suggest that tract correlations may have predictive value in distinguishing LTLE from RTLE, potentially moving diffusion imaging to a place of greater prominence in clinical practice.

Resting-state functional connectivity predicts the strength of hemispheric lateralization for language processing in temporal lobe epilepsy and normals.

In temporal lobe epilepsy (TLE), determining the hemispheric specialization for language before surgery is critical to preserving a patient's cognitive abilities post-surgery. To date, the major techniques utilized are limited by the capacity of patients to efficiently realize the task. We determined whether resting-state functional connectivity (rsFC) is a reliable predictor of language hemispheric dominance in right and left TLE patients, relative to controls. We chose three subregions of the inferior frontal cortex (pars orbitalis, pars triangularis, and pars opercularis) as the seed regions. All participants performed both a verb generation task and a resting-state fMRI procedure. Based on the language task, we computed a laterality index (LI) for the resulting network. This revealed that 96% of the participants were left-hemisphere dominant, although there remained a large degree of variability in the strength of left lateralization. We tested whether LI correlated with rsFC values emerging from each seed. We revealed a set of regions that was specific to each group. Unique correlations involving the epileptic mesial temporal lobe were revealed for the right and left TLE patients, but not for the controls. Importantly, for both TLE groups, the rsFC emerging from a contralateral seed was the most predictive of LI. Overall, our data depict the broad patterns of rsFC that support strong versus weak left hemisphere language laterality. This project provides the first evidence that rsFC data may potentially be used on its own to verify the strength of hemispheric dominance for language in impaired or pathologic populations.