Publications by authors named "Leonardo Bonilha"

183 Publications

Risk models to predict late-onset seizures after stroke: A systematic review.

Epilepsy Behav 2021 May 21;121(Pt A):108003. Epub 2021 May 21.

Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA.

Background And Purpose: We performed a systematic review to evaluate available risk models to predict late seizure onset among stroke survivors.

Methods: We searched major databases (PubMed, SCOPUS, and Cochrane Library) from inception to October 2020 for articles on the development and/or validation of risk models to predict late seizures after a stroke. The impact of models to predict late-onset seizures was also assessed. We included seven articles in the final analysis. For each of these studies, we evaluated the study design and scope of predictors analyzed to derive each model. We assessed the performance of the models during internal and external validation in terms of discrimination and calibration.

Results: Three studies focused on ischemic stroke alone, with c-statistic values ranging from 0.73 to 0.77. The SeLECT model from Switzerland was externally validated in Italian, German, and Austrian cohorts where c-statistics ranged from 0.69 to 0.81. This model along with the PSEiCARe model, were internally validated and calibration performance was provided for both models. The CAVS and CAVE models reported on the risk of late-onset seizures in patients with hemorrhagic stroke. The CAVS model derivation cohort was racially diverse. The CAVS model's c-statistic was 0.76, while the CAVE model had a c-statistic of 0.81. Calibration and internal validation were not performed for either study. The CAVS model, created from a Finnish population, was externally validated in American and French cohorts, with c-statistics of 0.73 and 0.69, respectively. Finally, the two studies focusing on both types of stroke came from the PoSERS and INPOSE models. Neither model provided c-statistics, calibration metrics, internal or external validation information. We found no evidence of the presence of impact studies to assess the effect of adopting late-onset seizure risk models after stroke on clinical outcomes.

Conclusion: The SeLECT model was the only model developed in line with proposed guidelines for appropriate model development. The model, which was externally validated in a very similar and homogeneous population, may need to be tested in a more racially/ethnic diverse and younger population; testing the SeLECT model, accounting for overall brain health is likely to improve the identification of high-risk patients for late post stroke seizures.
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http://dx.doi.org/10.1016/j.yebeh.2021.108003DOI Listing
May 2021

Effect of Stroke on Contralateral Functional Connectivity.

Brain Connect 2021 May 13. Epub 2021 May 13.

Department of Psychology, University of South Carolina, Columbia, South Carolina, USA.

Stroke can induce large-scale functional reorganization of the brain; however, the spatial patterns of this reorganization remain largely unknown. Using a large ( = 116) sample of participants who were in the chronic stages of stroke, we present a systematic study of the association between brain damage and functional connectivity (FC) within the intact hemisphere. We computed correlations between regional cortical damage and contralateral FC. We identified left-hemisphere regions that had the most pronounced effect on the right-hemisphere FC, and, conversely, right-hemisphere connections where the effect of damage was particularly strong. Notably, the vast majority of significant correlations were positive: damage was associated with an increase in regional contralateral connectivity. These findings lend evidence of the reorganization of contralateral cortical networks as a response to brain damage, which is more pronounced in a set of well-connected regions where connectivity increases with the amount of damage.
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http://dx.doi.org/10.1089/brain.2020.0901DOI Listing
May 2021

Indirect White Matter Pathways Are Associated With Treated Naming Improvement in Aphasia.

Neurorehabil Neural Repair 2021 04 10;35(4):346-355. Epub 2021 Mar 10.

Medical University of South Carolina, Charleston, SC, USA.

Background: White matter disconnection of language-specific brain regions associates with worse aphasia recovery. Despite a loss of direct connections, many stroke survivors may maintain indirect connections between brain regions.

Objective: To determine (1) whether preserved direct connections between language-specific brain regions relate to better poststroke naming treatment outcomes compared to no direct connections and (2) whether for individuals with a loss of direct connections, preserved indirect connections are associated with better treatment outcomes compared to individuals with no connections.

Methods: We computed structural whole-brain connectomes from 69 individuals with chronic left-hemisphere stroke and aphasia who completed a 3-week-long language treatment that was supplemented by either anodal transcranial direct current stimulation (A-tDCS) or sham stimulation (S-tDCS). We determined differences in naming improvement between individuals with direct, indirect, and no connections using 1-way analyses of covariance and multivariable linear regressions.

Results: Independently of tDCS modality, direct or indirect connections between the inferior frontal gyrus pars opercularis and angular gyrus were both associated with a greater increase in correct naming compared to no connections ( = .027 and = .039, respectively). Participants with direct connections between the inferior frontal gyrus pars opercularis and middle temporal gyrus who received S-tDCS and participants with indirect connections who received A-tDCS significantly improved in naming accuracy.

Conclusions: Poststroke preservation of indirect white matter connections is associated with better treated naming improvement in aphasia even when direct connections are damaged. This mechanistic information can be used to stratify and predict treated naming recovery in individuals with aphasia.
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http://dx.doi.org/10.1177/1545968321999052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068606PMC
April 2021

High-Density EEG in Current Clinical Practice and Opportunities for the Future.

J Clin Neurophysiol 2021 Mar;38(2):112-123

Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, U.S.A.

Summary: High-density EEG (HD-EEG) recordings use a higher spatial sampling of scalp electrodes than a standard 10-20 low-density EEG montage. Although several studies have demonstrated improved localization of the epileptogenic cortex using HD-EEG, widespread implementation is impeded by cost, setup and interpretation time, and lack of specific or sufficient procedural billing codes. Despite these barriers, HD-EEG has been in use at several institutions for years. These centers have noted utility in a variety of clinical scenarios where increased spatial resolution from HD-EEG has been required, justifying the extra time and cost. We share select scenarios from several centers, using different recording techniques and software, where HD-EEG provided information above and beyond the standard low-density EEG. We include seven cases where HD-EEG contributed directly to current clinical care of epilepsy patients and highlight two novel techniques which suggest potential opportunities to improve future clinical care. Cases illustrate how HD-EEG allows clinicians to: case 1-lateralize falsely generalized interictal epileptiform discharges; case 2-improve localization of falsely generalized epileptic spasms; cases 3 and 4-improve localization of interictal epileptiform discharges in anatomic regions below the circumferential limit of standard low-density EEG coverage; case 5-improve noninvasive localization of the seizure onset zone in lesional epilepsy; cases 6 and 7-improve localization of the seizure onset zone to guide invasive investigation near eloquent cortex; case 8-identify epileptic fast oscillations; and case 9-map language cortex. Together, these nine cases illustrate that using both visual analysis and advanced techniques, HD-EEG can play an important role in clinical management.
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http://dx.doi.org/10.1097/WNP.0000000000000807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083969PMC
March 2021

Speech timing changes accompany speech entrainment in aphasia.

J Commun Disord 2021 Mar-Apr;90:106090. Epub 2021 Feb 11.

Department of Communication Sciences and Disorders, University of South Carolina, Columbia, SC, 29208, USA. Electronic address:

Background: Prior speech entrainment studies, where individuals with non-fluent aphasia mimic an audio-visual model, suggest speech entrainment improves speech fluency, as indexed by various linguistic measures (e.g., the total number of different words produced per minute). Here, more precise speech timing adjustments accompanying entrained speech were studied and compared to spontaneous speech to determine how these temporal variables relate to the fluency inducing effects of speech entrainment in aphasia.

Methods: Thirty-one left hemisphere stroke survivors classified with fluent or non-fluent speech were audio-video recorded as they described a picture and during speech entrainment. Speech fluency was documented using the Western Aphasia Battery-Revised. Acoustic measures of speech timing included total number of syllables, speech rate, articulatory rate, silent pause frequency and duration. Standard descriptive statistics and a two-factor mixed model analysis of variance were used to investigate group, task, and 'group x task' interaction effects.

Findings: All acoustic measures of speech timing differentiated the fluent and nonfluent groups except for silent pause frequency. Differences between speech entrainment and spontaneous speech were found for most acoustic measures of speech timing and speaker groups, yet the direction of the effect varied. Stroke survivors classified with non-fluent aphasia improved speech fluency such that speech entrainment elicited pause adjustments facilitating more typical speech timing in comparison to spontaneous speech.

Conclusion: Overall, findings provide further evidence of the impact of speech entrainment on measures of speech timing to help individuals with non-fluent aphasia to practice speaking more fluently. Practicing speaking more fluently may ultimately impact perceptual judgments of speech naturalness and social acceptance for persons with aphasia.
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http://dx.doi.org/10.1016/j.jcomdis.2021.106090DOI Listing
February 2021

Fiber ball white matter modeling in focal epilepsy.

Hum Brain Mapp 2021 Jun 19;42(8):2490-2507. Epub 2021 Feb 19.

Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, UK.

Multicompartment diffusion magnetic resonance imaging (MRI) approaches are increasingly being applied to estimate intra-axonal and extra-axonal diffusion characteristics in the human brain. Fiber ball imaging (FBI) and its extension fiber ball white matter modeling (FBWM) are such recently described multicompartment approaches. However, these particular approaches have yet to be applied in clinical cohorts. The modeling of several diffusion parameters with interpretable biological meaning may offer the development of new, noninvasive biomarkers of pharmacoresistance in epilepsy. In the present study, we used FBI and FBWM to evaluate intra-axonal and extra-axonal diffusion properties of white matter tracts in patients with longstanding focal epilepsy. FBI/FBWM diffusion parameters were calculated along the length of 50 white matter tract bundles and statistically compared between patients with refractory epilepsy, nonrefractory epilepsy and controls. We report that patients with chronic epilepsy had a widespread distribution of extra-axonal diffusivity relative to controls, particularly in circumscribed regions along white matter tracts projecting to cerebral cortex from thalamic, striatal, brainstem, and peduncular regions. Patients with refractory epilepsy had significantly greater markers of extra-axonal diffusivity compared to those with nonrefractory epilepsy. The extra-axonal diffusivity alterations in patients with epilepsy observed in the present study could be markers of neuroinflammatory processes or a reflection of reduced axonal density, both of which have been histologically demonstrated in focal epilepsy. FBI is a clinically feasible MRI approach that provides the basis for more interpretive conclusions about the microstructural environment of the brain and may represent a unique biomarker of pharmacoresistance in epilepsy.
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http://dx.doi.org/10.1002/hbm.25382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090772PMC
June 2021

Patterns of seizure spread in temporal lobe epilepsy are associated with distinct white matter tracts.

Epilepsy Res 2021 Mar 5;171:106571. Epub 2021 Feb 5.

Medical University of South Carolina, Charleston, SC, USA. Electronic address:

Objective: It is commonly hypothesized that seizure spread patterns in patients with focal epilepsy are associated with structural brain pathways. However, this relationship is poorly understood and has not been fully demonstrated in patients with temporal lobe epilepsy. Here, we sought to determine whether directionality of seizure spread (DSS) is associated with specific cerebral white matter tracts in patients with temporal lobe epilepsy.

Methods: Thirty-three adult patients with temporal lobe epilepsy who underwent stereoelectroencephalography (sEEG) and magnetic resonance diffusion tensor imaging (MR-DTI) as part of their standard-of-care clinical evaluation were included in the study. DSS was defined as anterior-posterior (AP) or medial-lateral (ML) spread based upon sEEG evaluation by two independent specialists who demonstrated excellent inter-rater agreement (Cohen's kappa = .92). DTI connectometry was used to assess differences between seizure spread pattern groups along major fiber pathways regarding fractional anisotropy (FA).

Results: Twenty-four participants showed seizures with AP spread and nine participants showed seizures with ML spread. There were no significant differences between the groups on their demographic and clinical profile. Patients with ML seizures had higher FA along the corpus callosum and, to a lesser degree, some portions of the bilateral cingulate tracts. In contrast, patients with AP seizures had higher FA along several anterior-posterior white matter projections bundles, including the cingulate fasciculus and the inferior longitudinal, with significantly less involvement of the corpus callosum compared with ML seizures.

Significance: This study confirms the hypothesis that the anatomical pattern of electrophysiological ictal propagation is associated with the structural reinforcement of supporting pathways in temporal lobe epilepsy. This observation can help elucidate mechanisms of ictal propagation and may guide future translational approaches to curtail seizure spread.
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http://dx.doi.org/10.1016/j.eplepsyres.2021.106571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981262PMC
March 2021

Artificial intelligence to enhance the evaluation of refractory epilepsies.

Authors:
Leonardo Bonilha

Epilepsy Behav 2021 03 10;116:107776. Epub 2021 Feb 10.

Department of Neurology, Medical University of South Carolina, United States. Electronic address:

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http://dx.doi.org/10.1016/j.yebeh.2021.107776DOI Listing
March 2021

Machine learning-based multimodal prediction of language outcomes in chronic aphasia.

Hum Brain Mapp 2021 Apr 30;42(6):1682-1698. Epub 2020 Dec 30.

Center for the Study of Aphasia Recovery, University of South Carolina, Columbia, South Carolina, USA.

Recent studies have combined multiple neuroimaging modalities to gain further understanding of the neurobiological substrates of aphasia. Following this line of work, the current study uses machine learning approaches to predict aphasia severity and specific language measures based on a multimodal neuroimaging dataset. A total of 116 individuals with chronic left-hemisphere stroke were included in the study. Neuroimaging data included task-based functional magnetic resonance imaging (fMRI), diffusion-based fractional anisotropy (FA)-values, cerebral blood flow (CBF), and lesion-load data. The Western Aphasia Battery was used to measure aphasia severity and specific language functions. As a primary analysis, we constructed support vector regression (SVR) models predicting language measures based on (i) each neuroimaging modality separately, (ii) lesion volume alone, and (iii) a combination of all modalities. Prediction accuracy across models was subsequently statistically compared. Prediction accuracy across modalities and language measures varied substantially (predicted vs. empirical correlation range: r = .00-.67). The multimodal prediction model yielded the most accurate prediction in all cases (r = .53-.67). Statistical superiority in favor of the multimodal model was achieved in 28/30 model comparisons (p-value range: <.001-.046). Our results indicate that different neuroimaging modalities carry complementary information that can be integrated to more accurately depict how brain damage and remaining functionality of intact brain tissue translate into language function in aphasia.
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http://dx.doi.org/10.1002/hbm.25321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978124PMC
April 2021

Individualized Responses to Ipsilesional High-Frequency and Contralesional Low-Frequency rTMS in Chronic Stroke: A Pilot Study to Support the Individualization of Neuromodulation for Rehabilitation.

Front Hum Neurosci 2020 19;14:578127. Epub 2020 Nov 19.

Department of Research and Development, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, United States.

: In this pilot study, we examined the effects of ipsilesional high-frequency rTMS (iHF-rTMS) and contralesional low-frequency rTMS (cLF-rTMS) applied a double-cone coil on neurophysiological and gait variables in patients with chronic stroke. : To determine the group and individual level effects of two types of stimulation to better individualize neuromodulation for rehabilitation. : Using a randomized, within-subject, double-blind, sham-controlled trial with 14 chronic stroke participants iHF-rTMS and cLF-rTMS were applied a double-cone coil to the tibialis anterior cortical representation. Neurophysiological and gait variables were compared pre-post rTMS. : A small effect of cLF-rTMS indicated increased MEP amplitudes (Cohen's D; cLF-rTMS, = -0.30). Group-level analysis RMANOVA showed no significant group effects of stimulation ( > 0.099). However, secondary analyses of individual data showed a high degree of response variability to rTMS. Individual percent changes in resting motor threshold and normalized MEP latency correlated with changes in gait propulsive forces and walking speed (iHF-rTMS, nLAT:Pp, = 0.632 = 0.015; cLF-rTMS, rMT:SSWS, = -0.557, = 0.039; rMT:Pp, = 0.718, = 0.004). : Changes in propulsive forces and walking speed were seen in some individuals that showed neurophysiological changes in response to rTMS. The neurological consequences of stroke are heterogeneous making a "one type fits all" approach to neuromodulation for rehabilitation unlikely. This pilot study suggests that an individual's unique response to rTMS should be considered before the application/selection of neuromodulatory therapies. Before neuromodulatory therapies can be incorporated into standard clinical practice, additional work is needed to identify biomarkers of response and how best to prescribe neuromodulation for rehabilitation for post-stroke gait.
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http://dx.doi.org/10.3389/fnhum.2020.578127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717949PMC
November 2020

Network-based atrophy modeling in the common epilepsies: A worldwide ENIGMA study.

Sci Adv 2020 Nov 18;6(47). Epub 2020 Nov 18.

Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria 3010, Australia.

Epilepsy is increasingly conceptualized as a network disorder. In this cross-sectional mega-analysis, we integrated neuroimaging and connectome analysis to identify network associations with atrophy patterns in 1021 adults with epilepsy compared to 1564 healthy controls from 19 international sites. In temporal lobe epilepsy, areas of atrophy colocalized with highly interconnected cortical hub regions, whereas idiopathic generalized epilepsy showed preferential subcortical hub involvement. These morphological abnormalities were anchored to the connectivity profiles of distinct disease epicenters, pointing to temporo-limbic cortices in temporal lobe epilepsy and fronto-central cortices in idiopathic generalized epilepsy. Negative effects of age on atrophy further revealed a strong influence of connectome architecture in temporal lobe, but not idiopathic generalized, epilepsy. Our findings were reproduced across individual sites and single patients and were robust across different analytical methods. Through worldwide collaboration in ENIGMA-Epilepsy, we provided deeper insights into the macroscale features that shape the pathophysiology of common epilepsies.
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http://dx.doi.org/10.1126/sciadv.abc6457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673818PMC
November 2020

Neural correlates of within-session practice effects in mild motor impairment after stroke: a preliminary investigation.

Exp Brain Res 2021 Jan 1;239(1):151-160. Epub 2020 Nov 1.

Department of Exercise Science, University of South Carolina, 921 Assembly Street, Room 301D, Columbia, SC, 29208, USA.

While the structural integrity of the corticospinal tract (CST) has been shown to support motor performance after stroke, the neural correlates of within-session practice effects are not known. The purpose of this preliminary investigation was to examine the structural brain correlates of within-session practice effects on a functional motor task completed with the more impaired arm after stroke. Eleven individuals with mild motor impairment (mean age 57.0 ± 9.4 years, mean months post-stroke 37.0 ± 66.1, able to move ≥ 26 blocks on the Box and Blocks Test) due to left hemisphere stroke completed structural MRI and practiced a functional motor task that involved spooning beans from a start cup to three distal targets. Performance on the motor task improved with practice (p = 0.004), although response was variable. Baseline motor performance (Block 1) correlated with integrity of the CST (r = - 0.696) while within-session practice effects (change from Block 1 to Block 3) did not. Instead, practice effects correlated with degree of lesion to the superior longitudinal fasciculus (r = 0.606), a pathway that connects frontal and parietal brain regions previously shown to support motor learning. This difference between white matter tracts associated with baseline motor performance and within-session practice effects may have implications for understanding response to motor practice and the application of brain-focused intervention approaches aimed at improving hand function after stroke.
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http://dx.doi.org/10.1007/s00221-020-05964-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887039PMC
January 2021

The relationship between dorsal stream connections to the caudate and verbal fluency in Parkinson disease.

Brain Imaging Behav 2020 Oct 12. Epub 2020 Oct 12.

Department of Neurology, Medical University of South Carolina, 208b Rutledge Av., Charleston, SC, 29403, USA.

Performance in verbal fluency tasks are widely used as a marker of cognitive impairment in Parkinson disease. However, the anatomical substrate of its impairment remains undetermined. Based on the dual-stream language model, we hypothesized cortical input to the subcortical circuitry would be a crucial determinant of fluency. We performed a retrospective study using individual whole-brain structural connectomes derived from 135 individuals with PD and assessed the relationship between white matter integrity and verbal fluency tasks. Controlling for multiple factors, including dysarthria, we observed higher integrity of dorsal stream-caudate connectivity was associated with better letter fluency. This preliminary study indicates the possible dissociation between dorsal and ventral stream connectivity and letter fluency in PD. In addition, it suggests a non-motor role of the frontostriatal fibers in letter fluency.
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http://dx.doi.org/10.1007/s11682-020-00407-2DOI Listing
October 2020

Temporal Lobe Epilepsy Surgical Outcomes Can Be Inferred Based on Structural Connectome Hubs: A Machine Learning Study.

Ann Neurol 2020 11 10;88(5):970-983. Epub 2020 Sep 10.

Department of Neurology, Medical University of South Carolina, Charleston, SC, USA.

Objective: Medial temporal lobe epilepsy (TLE) is the most common form of medication-resistant focal epilepsy in adults. Despite removal of medial temporal structures, more than one-third of patients continue to have disabling seizures postoperatively. Seizure refractoriness implies that extramedial regions are capable of influencing the brain network and generating seizures. We tested whether abnormalities of structural network integration could be associated with surgical outcomes.

Methods: Presurgical magnetic resonance images from 121 patients with drug-resistant TLE across 3 independent epilepsy centers were used to train feed-forward neural network models based on tissue volume or graph-theory measures from whole-brain diffusion tensor imaging structural connectomes. An independent dataset of 47 patients with TLE from 3 other epilepsy centers was used to assess the predictive values of each model and regional anatomical contributions toward surgical treatment results.

Results: The receiver operating characteristic area under the curve based on regional betweenness centrality was 0.88, significantly higher than a random model or models based on gray matter volumes, degree, strength, and clustering coefficient. Nodes most strongly contributing to the predictive models involved the bilateral parahippocampal gyri, as well as the superior temporal gyri.

Interpretation: Network integration in the medial and lateral temporal regions was related to surgical outcomes. Patients with abnormally integrated structural network nodes were less likely to achieve seizure freedom. These findings are in line with previous observations related to network abnormalities in TLE and expand on the notion of underlying aberrant plasticity. Our findings provide additional information on the mechanisms of surgical refractoriness. ANN NEUROL 2020;88:970-983.
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http://dx.doi.org/10.1002/ana.25888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019146PMC
November 2020

White matter abnormalities across different epilepsy syndromes in adults: an ENIGMA-Epilepsy study.

Brain 2020 08;143(8):2454-2473

Department of Neurology, Medical University of South Carolina, Charleston 29425 SC, USA.

The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common epilepsy syndromes, including temporal lobe epilepsy, extratemporal epilepsy, and genetic generalized epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within syndromes in a multicentre sample of adult epilepsy patients. Diffusion-weighted MRI data were analysed from 1069 healthy controls and 1249 patients: temporal lobe epilepsy with hippocampal sclerosis (n = 599), temporal lobe epilepsy with normal MRI (n = 275), genetic generalized epilepsy (n = 182) and non-lesional extratemporal epilepsy (n = 193). A harmonized protocol using tract-based spatial statistics was used to derive skeletonized maps of fractional anisotropy and mean diffusivity for each participant, and fibre tracts were segmented using a diffusion MRI atlas. Data were harmonized to correct for scanner-specific variations in diffusion measures using a batch-effect correction tool (ComBat). Analyses of covariance, adjusting for age and sex, examined differences between each epilepsy syndrome and controls for each white matter tract (Bonferroni corrected at P < 0.001). Across 'all epilepsies' lower fractional anisotropy was observed in most fibre tracts with small to medium effect sizes, especially in the corpus callosum, cingulum and external capsule. There were also less robust increases in mean diffusivity. Syndrome-specific fractional anisotropy and mean diffusivity differences were most pronounced in patients with hippocampal sclerosis in the ipsilateral parahippocampal cingulum and external capsule, with smaller effects across most other tracts. Individuals with temporal lobe epilepsy and normal MRI showed a similar pattern of greater ipsilateral than contralateral abnormalities, but less marked than those in patients with hippocampal sclerosis. Patients with generalized and extratemporal epilepsies had pronounced reductions in fractional anisotropy in the corpus callosum, corona radiata and external capsule, and increased mean diffusivity of the anterior corona radiata. Earlier age of seizure onset and longer disease duration were associated with a greater extent of diffusion abnormalities in patients with hippocampal sclerosis. We demonstrate microstructural abnormalities across major association, commissural, and projection fibres in a large multicentre study of epilepsy. Overall, patients with epilepsy showed white matter abnormalities in the corpus callosum, cingulum and external capsule, with differing severity across epilepsy syndromes. These data further define the spectrum of white matter abnormalities in common epilepsy syndromes, yielding more detailed insights into pathological substrates that may explain cognitive and psychiatric co-morbidities and be used to guide biomarker studies of treatment outcomes and/or genetic research.
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http://dx.doi.org/10.1093/brain/awaa200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567169PMC
August 2020

Temporal lobe regions essential for preserved picture naming after left temporal epilepsy surgery.

Epilepsia 2020 09 11;61(9):1939-1948. Epub 2020 Aug 11.

Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

Objective: To define left temporal lobe regions where surgical resection produces a persistent postoperative decline in naming visual objects.

Methods: Pre- and postoperative brain magnetic resonance imaging data and picture naming (Boston Naming Test) scores were obtained prospectively from 59 people with drug-resistant left temporal lobe epilepsy. All patients had left hemisphere language dominance at baseline and underwent surgical resection or ablation in the left temporal lobe. Postoperative naming assessment occurred approximately 7 months after surgery. Surgical lesions were mapped to a standard template, and the relationship between presence or absence of a lesion and the degree of naming decline was tested at each template voxel while controlling for effects of overall lesion size.

Results: Patients declined by an average of 15% in their naming score, with wide variation across individuals. Decline was significantly related to damage in a cluster of voxels in the ventral temporal lobe, located mainly in the fusiform gyrus approximately 4-6 cm posterior to the temporal tip. Extent of damage to this region explained roughly 50% of the variance in outcome. Picture naming decline was not related to hippocampal or temporal pole damage.

Significance: The results provide the first statistical map relating lesion location in left temporal lobe epilepsy surgery to picture naming decline, and they support previous observations of transient naming deficits from electrical stimulation in the basal temporal cortex. The critical lesion is relatively posterior and could be avoided in many patients undergoing left temporal lobe surgery for intractable epilepsy.
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http://dx.doi.org/10.1111/epi.16643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722029PMC
September 2020

The ENIGMA-Epilepsy working group: Mapping disease from large data sets.

Hum Brain Mapp 2020 May 29. Epub 2020 May 29.

Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Mexico.

Epilepsy is a common and serious neurological disorder, with many different constituent conditions characterized by their electro clinical, imaging, and genetic features. MRI has been fundamental in advancing our understanding of brain processes in the epilepsies. Smaller-scale studies have identified many interesting imaging phenomena, with implications both for understanding pathophysiology and improving clinical care. Through the infrastructure and concepts now well-established by the ENIGMA Consortium, ENIGMA-Epilepsy was established to strengthen epilepsy neuroscience by greatly increasing sample sizes, leveraging ideas and methods established in other ENIGMA projects, and generating a body of collaborating scientists and clinicians to drive forward robust research. Here we review published, current, and future projects, that include structural MRI, diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI), and that employ advanced methods including structural covariance, and event-based modeling analysis. We explore age of onset- and duration-related features, as well as phenomena-specific work focusing on particular epilepsy syndromes or phenotypes, multimodal analyses focused on understanding the biology of disease progression, and deep learning approaches. We encourage groups who may be interested in participating to make contact to further grow and develop ENIGMA-Epilepsy.
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http://dx.doi.org/10.1002/hbm.25037DOI Listing
May 2020

Clinical Implementation of Transcranial Direct Current Stimulation in Aphasia: A Survey of Speech-Language Pathologists.

Am J Speech Lang Pathol 2020 08 20;29(3):1376-1388. Epub 2020 May 20.

Department of Communication Sciences and Disorders, University of South Carolina, Columbia.

Purpose The objectives of this study are to (a) identify speech-language pathologists' (SLPs') familiarity with transcranial direct current stimulation (tDCS), (b) quantify what SLPs consider necessary tDCS-related improvement in aphasia severity (i.e., tDCS enhancement; desired improvement above and beyond traditional behavioral therapy) to implement this adjuvant therapy for the clinical management of aphasia, and (c) identify concerns that could potentially hinder the clinical adoption of tDCS. Method A brief (14-question) survey was disseminated via e-mail and social media outlets targeting SLPs working with individuals with aphasia. Results Two hundred twenty-one individuals responded, and 155 valid surveys were analyzed. Seventy-one percent of participants reported familiarity with tDCS prior to taking the survey. Clinicians reported a desired mean enhancement of 22.9% additional points on the Western Aphasia Battery-Revised Aphasia Quotient. Importantly, 94.2% of SLPs reported concerns regarding the implementation of tDCS in clinical settings (i.e., safety, cost, administrative approval, reimbursement and training). Conclusions This is the first study to identify SLPs' perspectives regarding the clinical adoption of tDCS. Results suggest the majority of queried SLPs were familiar with tDCS prior to taking the survey. Although SLPs report a desired improvement of approximately 23% additional points on the Western Aphasia Battery-Revised Aphasia Quotient to consider adopting tDCS into practice, many SLPs reported concerns regarding clinical adoption. Responses from the current survey offer important preliminary evidence to begin bridging the research-to-practice gap as it relates to the clinical implementation of tDCS. Relatedly, these results will inform future clinical trials.
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http://dx.doi.org/10.1044/2020_AJSLP-19-00037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893518PMC
August 2020

Clinical utility of structural connectomics in predicting memory in temporal lobe epilepsy.

Neurology 2020 06 1;94(23):e2424-e2435. Epub 2020 May 1.

From the Center for Multimodal Imaging and Genetics (A.R.B., E.K., N.B., A.R., A.C.M., C.R.M.) and Department of Psychiatry (C.R.M.), University of California, San Diego; San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology (A.R., C.R.M.); Department of Neurology (S.L., B.M.P.), University of California, San Francisco; Department of Neurology (L.B.), Medical University of South Carolina, Charleston; and Boston University School of Medicine (A.R.B.), MA.

Objective: To determine the predictive power of white matter neuronal networks (i.e., structural connectomes [SCs]) in discriminating memory-impaired patients with temporal lobe epilepsy (TLE) from those with normal memory.

Methods: T1- and diffusion MRI (dMRI), clinical variables, and neuropsychological measures of verbal memory were available for 81 patients with TLE. Prediction of memory impairment was performed with a tree-based classifier (XGBoost) for 4 models: (1) a clinical model including demographic and clinical features, (2) a hippocampal volume (HCV) model, (3) a tract model including 5 temporal lobe white matter association tracts derived from a dMRI atlas, and (4) an SC model based on dMRI. SCs were derived by extracting cortical-cortical connections from a temporal lobe subnetwork with probabilistic tractography. Principal component (PC) analysis was then applied to reduce the dimensionality of the SC, yielding 10 PCs. Multimodal models were also tested combining SCs and tracts with HCV. Each model was trained on 48 patients from 1 epilepsy center and tested on 33 patients from a different center.

Results: Multimodal models that included the SC + HCV model yielded the highest classification accuracy (81%; 0.90 sensitivity; 0.67 specificity), outperforming the clinical model (61%; < 0.001) and HCV model (66%; < 0.001). In addition, the unimodal SC model (76% accuracy) and tract model (73% accuracy) outperformed the clinical model ( < 0.001) and HCV model ( < 0.001) for classifying patients with TLE with and without memory impairment. Furthermore, the SC identified that short-range temporal-temporal connections were important contributors to memory performance.

Conclusion: SCs and tract-based models are stronger predictors of memory impairment in TLE than HCVs and clinical variables. However, SCs may provide additional information about local cortical-cortical connectivity contributing to memory that is not captured in large association tracts.
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http://dx.doi.org/10.1212/WNL.0000000000009457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455364PMC
June 2020

NMDA receptor partial agonist, d-cycloserine, enhances 10 Hz rTMS-induced motor plasticity, suggesting long-term potentiation (LTP) as underlying mechanism.

Brain Stimul 2020 May - Jun;13(3):530-532. Epub 2020 Jan 8.

Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA; Ralph H. Johnson Veterans Administration Medical Center, Charleston, SC, USA.

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http://dx.doi.org/10.1016/j.brs.2020.01.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7224691PMC
January 2020

Changes in description naming for common and proper nouns after left anterior temporal lobectomy.

Epilepsy Behav 2020 05 13;106:106912. Epub 2020 Mar 13.

Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, United States of America.

Numerous studies have shown that surgical resection of the left anterior temporal lobe (ATL) is associated with a decline in object naming ability (Hermann et al., 1999). In contrast, few studies have examined the effects of left ATL surgery on auditory description naming (ADN) or category-specific naming. Compared with object naming, which loads heavily on visual recognition processes, ADN provides a more specific measure of concept retrieval. The present study examined ADN declines in a large group of patients who were tested before and after left ATL surgery, using a 2 × 2 × 2 factorial manipulation of uniqueness (common vs. proper nouns), taxonomic category (living vs. nonliving things), and time (pre- vs. postsurgery). Significant declines occurred across all categories but were substantially larger for proper living (PL) concepts, i.e., famous individuals. The disproportionate decline in PL noun naming relative to other conditions is consistent with the notion that the left ATL is specialized not only for retrieval of unique entity concepts, but also plays a role in processing social concepts and person-specific features.
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http://dx.doi.org/10.1016/j.yebeh.2020.106912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195239PMC
May 2020

The white matter connectome as an individualized biomarker of language impairment in temporal lobe epilepsy.

Neuroimage Clin 2020 13;25:102125. Epub 2019 Dec 13.

Center for Multimodal Imaging and Genetics, University of California, San Diego, CA, USA; San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA; Department of Psychiatry, University of California, San Diego, CA, USA. Electronic address:

Objective: The distributed white matter network underlying language leads to difficulties in extracting clinically meaningful summaries of neural alterations leading to language impairment. Here we determine the predictive ability of the structural connectome (SC), compared with global measures of white matter tract microstructure and clinical data, to discriminate language impaired patients with temporal lobe epilepsy (TLE) from TLE patients without language impairment.

Methods: T1- and diffusion-MRI, clinical variables (CVs), and neuropsychological measures of naming and verbal fluency were available for 82 TLE patients. Prediction of language impairment was performed using a robust tree-based classifier (XGBoost) for three models: (1) a CV-model which included demographic and epilepsy-related clinical features, (2) an atlas-based tract-model, including four frontotemporal white matter association tracts implicated in language (i.e., the bilateral arcuate fasciculus, inferior frontal occipital fasciculus, inferior longitudinal fasciculus, and uncinate fasciculus), and (3) a SC-model based on diffusion MRI. For the association tracts, mean fractional anisotropy was calculated as a measure of white matter microstructure for each tract using a diffusion tensor atlas (i.e., AtlasTrack). The SC-model used measurement of cortical-cortical connections arising from a temporal lobe subnetwork derived using probabilistic tractography. Dimensionality reduction of the SC was performed with principal components analysis (PCA). Each model was trained on 49 patients from one epilepsy center and tested on 33 patients from a different center (i.e., an independent dataset). Randomization was performed to test the stability of the results.

Results: The SC-model yielded a greater area under the curve (AUC; .73) and accuracy (79%) compared to both the tract-model (AUC: .54, p < .001; accuracy: 70%, p < .001) and the CV-model (AUC: .59, p < .001; accuracy: 64%, p < .001). Within the SC-model, lateral temporal connections had the highest importance to model performance, including connections similar to language association tracts such as links between the superior temporal gyrus to pars opercularis. However, in addition to these connections many additional connections that were widely distributed, bilateral and interhemispheric in nature were identified as contributing to SC-model performance.

Conclusion: The SC revealed a white matter network contributing to language impairment that was widely distributed, bilateral, and lateral temporal in nature. The distributed network underlying language may be why the SC-model has an advantage in identifying sub-components of the complex fiber networks most relevant for aspects of language performance.
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http://dx.doi.org/10.1016/j.nicl.2019.102125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953962PMC
December 2020

Brain-Derived Neurotrophic Factor Genotype-Specific Differences in Cortical Activation in Chronic Aphasia.

J Speech Lang Hear Res 2019 11 22;62(11):3923-3936. Epub 2019 Nov 22.

Department of Communication Sciences & Disorders, University of South Carolina, Columbia.

Purpose The brain-derived neurotrophic factor (BDNF) gene has been shown to be important for synaptic plasticity in animal models. Human research has suggested that BDNF genotype may influence stroke recovery. Some studies have suggested a genotype-specific motor-related brain activation in stroke recovery. However, recovery from aphasia in relation to BDNF genotype and language-related brain activation has received limited attention. We aimed to explore functional brain activation by BDNF genotype in individuals with chronic aphasia. Consistent with findings in healthy individuals and individuals with poststroke motor impairment, we hypothesized that, among individuals with aphasia, the presence of the Met allele of the BDNF gene is associated with reduced functional brain activation compared to noncarriers of the Met allele. Method Eighty-seven individuals with chronic stroke-induced aphasia performed a naming task during functional magnetic resonance imaging scanning and submitted blood or saliva samples for BDNF genotyping. The mean number of activated voxels was compared between groups, and group-based activation maps were directly compared. Neuropsychological testing was conducted to compare language impairment between BDNF genotype groups. The Western Aphasia Battery Aphasia Quotient (Kertesz, 2007) was included as a covariate in all analyses. Results While lesion size was comparable between groups, the amount of activation, quantified as the number of activated voxels, was significantly greater in noncarriers of the Met allele (whole brain: 98,500 vs. 28,630, < .001; left hemisphere only: 37,209 vs. 7,000, < .001; right hemisphere only: 74,830 vs. 30,630, < .001). This difference was most strongly expressed in the right hemisphere posterior temporal area, pre- and postcentral gyrus, and frontal lobe, extending into the white matter. Correspondingly, the atypical BDNF genotype group was found to have significantly less severe aphasia (Western Aphasia Battery Aphasia Quotient of 64.2 vs. 54.3, = .033) and performed better on a naming task (Philadelphia Naming Test [Roach, Schwartz, Martin, Grewal, & Brecher, 1996] score of 74.7 vs. 52.8, = .047). A region of interest analysis of intensity of activation revealed no group differences, and a direct comparison of average activation maps across groups similarly yielded null results. Conclusion BDNF genotype mediates cortical brain activation in individuals with chronic aphasia. Correspondingly, individuals carrying the Met allele present with more severe aphasia compared to noncarriers. These findings warrant further study into the effects of BDNF genotype in aphasia. Supplemental Material https://doi.org/10.23641/asha.10073147 Presentation Video https://doi.org/10.23641/asha.10257581.
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http://dx.doi.org/10.1044/2019_JSLHR-L-RSNP-19-0021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203521PMC
November 2019

Spectral Encoding of Seen and Attended Object Categories in the Human Brain.

J Neurosci 2020 01 6;40(2):327-342. Epub 2019 Nov 6.

Departments of Neuroscience, and

Local field potentials (LFPs) encode visual information via variations in power at many frequencies. These variations are complex and depend on stimulus and cognitive state in ways that have yet to be fully characterized. Specifically, the frequencies (or combinations of frequencies) that most robustly encode specific types of visual information are not fully known. To address this knowledge gap, we used intracranial EEG to record LFPs at 858 widely distributed recording sites as human subjects (six males, five females) indicated whether briefly presented natural scenes depicted one of three attended object categories. Principal component analysis applied to power spectra of the LFPs near stimulus onset revealed a broadband component (1-100 Hz) and two narrowband components (1-8 and 8-30 Hz, respectively) that encoded information about both seen and attended categories. Interestingly, we found that seen and attended categories were not encoded with the same fidelity by these distinct spectral components. Model-based tuning and decoding analyses revealed that power variations along the broadband component were most sharply tuned and offered more accurate decoding for seen than for attended categories. Power along the narrowband delta-theta (1-8 Hz) component robustly decoded information about both seen and attended categories, while the alpha-beta (8-30 Hz) component was specialized for attention. We conclude that, when viewing natural scenes, information about the seen category is encoded via broadband and sub-gamma (<30 Hz) power variations, while the attended category is most robustly encoded in the sub-gamma range. More generally, these results suggest that power variation along different spectral components can encode qualitatively different kinds of visual information. In this article, we characterize how changes in visual stimuli depicting specific objects (cars, faces, and buildings) and changes in attention to those objects affect the frequency content of local field potentials in the human brain. In contrast to many previous studies that have investigated encoding by variations in power at high (>30 Hz) frequencies, we find that the most important variation patterns are broadband (i.e., distributed across multiple frequencies) and narrowband, but in lower frequencies (<30 Hz). Interestingly, we find that seen and attended categories are not encoded with the same fidelity by these distinct spectral encoding patterns, suggesting that power at different frequencies can encode qualitatively different kinds of information.
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http://dx.doi.org/10.1523/JNEUROSCI.0900-19.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6948933PMC
January 2020

Investigating imaging network markers of cognitive dysfunction and pharmacoresistance in newly diagnosed epilepsy: a protocol for an observational cohort study in the UK.

BMJ Open 2019 10 16;9(10):e034347. Epub 2019 Oct 16.

Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.

Introduction: Epilepsy is one of the most common serious brain disorders, characterised by seizures that severely affect a person's quality of life and, frequently, their cognitive and mental health. Although most existing work has examined chronic epilepsy, newly diagnosed patients present a unique opportunity to understand the underlying biology of epilepsy and predict effective treatment pathways. The objective of this prospective cohort study is to examine whether cognitive dysfunction is associated with measurable brain architectural and connectivity impairments at diagnosis and whether the outcome of antiepileptic drug treatment can be predicted using these measures.

Methods And Analysis: 107 patients with newly diagnosed focal epilepsy from two National Health Service Trusts and 48 healthy controls (aged 16-65 years) will be recruited over a period of 30 months. Baseline assessments will include neuropsychological evaluation, structural and functional Magnetic Resonance Imaging (MRI), Electroencephalography (EEG), and a blood and saliva sample. Patients will be followed up every 6 months for a 24-month period to assess treatment outcomes. Connectivity- and network-based analyses of EEG and MRI data will be carried out and examined in relation to neuropsychological evaluation and patient treatment outcomes. Patient outcomes will also be investigated with respect to analysis of molecular isoforms of high mobility group box-1 from blood and saliva samples.

Ethics And Dissemination: This study was approved by the North West, Liverpool East Research Ethics Committee (19/NW/0384) through the Integrated Research Application System (Project ID 260623). Health Research Authority (HRA) approval was provided on 22 August 2019. The project is sponsored by the UoL (UoL001449) and funded by a UK Medical Research Council (MRC) research grant (MR/S00355X/1). Findings will be presented at national and international meetings and conferences and published in peer-reviewed journals.

Trial Registration Number: IRAS Project ID 260623.
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http://dx.doi.org/10.1136/bmjopen-2019-034347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797398PMC
October 2019

Mechanisms and Risk Factors Contributing to Visual Field Deficits following Stereotactic Laser Amygdalohippocampotomy.

Stereotact Funct Neurosurg 2019 16;97(4):255-265. Epub 2019 Oct 16.

Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA,

Selective laser amygdalohippocampotomy (SLAH) is a minimally invasive surgical treatment for medial temporal lobe epilepsy. Visual field deficits (VFDs) are a significant potential complication. The objective of this study was to determine the relationship between VFDs and potential mechanisms of injury to the optic radiations and lateral geniculate nucleus. We performed a retrospective cross-sectional analysis of 3 patients (5.2%) who developed persistent VFDs after SLAH within our larger series (n = 58), 15 healthy individuals and 10 SLAH patients without visual complications. Diffusion tractography was used to evaluate laser catheter penetration of the optic radiations. Using a complementary approach, we evaluated evidence for focal microstructural tissue damage within the optic radiations and lateral geniculate nucleus. Overablation and potential heat radiation were assessed by quantifying ablation and choroidal fissure CSF volumes as well as energy deposited during SLAH.SLAH treatment parameters did not distinguish VFD patients. Atypically high overlap between the laser catheter and optic radiations was found in 1/3 VFD patients and was accompanied by focal reductions in fractional anisotropy where the catheter entered the lateral occipital white matter. Surprisingly, lateral geniculate tissue diffusivity was abnormal following, but also preceding, SLAH in patients who subsequently developed a VFD (all p = 0.005).In our series, vision-related complications following SLAH, which appear to occur less frequently than following open temporal lobe -surgery, were not directly explained by SLAH treatment parameters. Instead, our data suggest that variations in lateral geniculate structure may influence susceptibility to indirect heat injury from transoccipital SLAH.
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http://dx.doi.org/10.1159/000502701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6979425PMC
March 2020

Serum Amyloid A-Mediated Inflammasome Activation of Microglial Cells in Cerebral Ischemia.

J Neurosci 2019 11 14;39(47):9465-9476. Epub 2019 Oct 14.

Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, Florida 33612,

Serum amyloid A (SAA) proteins are acute-phase reactant associated with high-density lipoprotein (HDL) particles and increase in the plasma 1000-fold during inflammation. Recent studies have implicated SAAs in innate immunity and various disorders; however, the precise mechanism eludes us. Previous studies have shown SAAs are elevated following stroke and cerebral ischemia, and our studies demonstrated that SAA-deficient mice reduce inflammation and infarct volumes in a mouse stroke model. Our studies demonstrate that SAA increases the cytokine interleukin-1β (IL-1β), which is mediated by Nod-like receptor protein 3 (NLRP3) inflammasome, cathepsin B, and caspase-1 and may play a role in the pathogenesis of neurological disorders. SAA induced the expression of NLRP3, which mediated IL-1β induction in murine BV-2 cells and both sex primary mouse microglial cells, in a dose- and time-dependent fashion. Inhibition or KO of the NLRP3 in microglia prevented the increase in IL-1β. -acetyl-l-cysteine and mito-TEMPO blocked the induction of IL-1β by inhibiting ROS with SAA treatment. In addition, inhibition of cathepsin B with different drugs or microglia from CatB-deficient mice attenuated inflammasome activation. Our studies suggest that the impact of SAA on inflammasome stimulation is mediated in part by the receptor for advanced glycation endproducts and Toll-like receptor proteins 2 and 4. SAA induced inflammatory cytokines and an M1 phenotype in the microglial cells while downregulating anti-inflammation M2 phenotype. These studies suggest that brain injury to can elicit a systemic inflammatory response mediated through SAA that contributes to the pathological outcomes. In the present study, serum amyloid A can induce that activation of the inflammasome in microglial cells and give rise to IL-1β release, which can further inflammation in the brain following neurological diseases. The also presents a novel target for therapeutic approaches in stroke.
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http://dx.doi.org/10.1523/JNEUROSCI.0801-19.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6867810PMC
November 2019

Predicting naming responses based on pre-articulatory electrical activity in individuals with aphasia.

Clin Neurophysiol 2019 11 26;130(11):2153-2163. Epub 2019 Aug 26.

Department of Neurology, Medical University of South Carolina, SC, USA.

Objective: To investigate whether pre-articulatory neural activity could be used to predict correct vs. incorrect naming responses in individuals with post-stroke aphasia.

Methods: We collected 64-channel high density electroencephalography (hdEEG) data from 5 individuals with chronic post-stroke aphasia (2 female/3 male, median age: 54 years) during naming of 80 concrete images. We applied machine learning on continuous wavelet transformed hdEEG data separately for alpha and beta energy bands (200 ms pre-stimulus to 1500 ms post-stimulus, but before articulation), and determined whether electrode/time-range/energy (ETE) combinations were predictive of correct vs incorrect responses for each participant.

Results: The five participants correctly named between 30% and 70% of the 80 stimuli correctly. We observed that pre-articulatory scalp EEG ETE combinations could predict correct vs incorrect responses with accuracies ranging from 63% to 80%. For all but one participant, the prediction accuracies were statistically better than chance.

Conclusions: Our findings indicate that pre-articulatory neural activity may be used to predict correct vs incorrect naming responses for some individuals with aphasia.

Significance: The individualized pre-articulatory neural pattern associated with correct naming responses could be used to both predict naming problems in aphasia and lead to the development of brain stimulation strategies for treatment.
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http://dx.doi.org/10.1016/j.clinph.2019.08.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935719PMC
November 2019

Neural structures supporting spontaneous and assisted (entrained) speech fluency.

Brain 2019 12;142(12):3951-3962

Department of Communications Sciences and Disorders, University of South Carolina, 915 Greene Street, Columbia, SC 29208, USA.

Non-fluent speech is one of the most common impairments in post-stroke aphasia. The rehabilitation of non-fluent speech in aphasia is particularly challenging as patients are rarely able to produce and practice fluent speech production. Speech entrainment is a behavioural technique that enables patients with non-fluent aphasia to speak fluently. However, its mechanisms are not well understood and the level of improved fluency with speech entrainment varies among individuals with non-fluent aphasia. In this study, we evaluated the behavioural and neuroanatomical factors associated with better speech fluency with the aid of speech entrainment during the training phase of speech entrainment. We used a lesion-symptom mapping approach to define the relationship between chronic stroke location on MRI and the number of different words per second produced during speech entrainment versus picture description spontaneous speech. The behavioural variable of interest was the speech entrainment/picture description ratio, which, if ≥1, indicated an increase in speech output during speech entrainment compared to picture description. We used machine learning (shallow neural network) to assess the statistical significance and out-of-sample predictive accuracy of the neuroanatomical model, and its regional contributors. We observed that better assisted speech (higher speech entrainment/picture description ratio) was achieved by individuals who had preservation of the posterior middle temporal gyrus, inferior fronto-occipital fasciculus and uncinate fasciculus, while exhibiting lesions in areas typically associated with non-fluent aphasia, such as the superior longitudinal fasciculus, precentral, inferior frontal, supramarginal and insular cortices. Our findings suggest that individuals with dorsal stream damage but preservation of ventral stream structures are more likely to achieve more fluent speech with the aid of speech entrainment compared to spontaneous speech. This observation provides insight into the mechanisms of non-fluent speech in aphasia and has potential implications for future research using speech entrainment for rehabilitation of non-fluent aphasia.
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http://dx.doi.org/10.1093/brain/awz309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885692PMC
December 2019

Characterizing Thalamo-Cortical Structural Connectivity in Essential Tremor with Diffusional Kurtosis Imaging Tractography.

Tremor Other Hyperkinet Mov (N Y) 2019 2;9. Epub 2019 Sep 2.

Department of Neurology, College of Medicine, Medical University of South Carolina, Charleston, SC, USA.

Background: Neuromodulation of the cerebello-thalamo-cortical (CTC) circuit via thalamic stimulation is an effective therapy for essential tremor (ET). In order to develop non-invasive neuromodulation approaches, clinically relevant thalamo-cortical connections must be elucidated.

Methods: Twenty-eight subjects (18 ET patients and 10 controls) underwent MRI diffusional kurtosis imaging (DKI). A deterministic fiber-tracking algorithm based on DKI was used, with a seeding region placed at the ventral intermediate nucleus (Vim-located based on intraoperative physiology) to the ending regions at the supplementary motor area (SMA), pre-SMA, or primary motor cortex. One-tailed -tests were performed to compare groups, and associations with tremor severity were determined by Pearson correlations. All p-values were adjusted for multiple comparisons using Bonferroni correction.

Results: There was a decrease in the mean diffusivity (MD) in patients compared to controls in all three tracts: Vim-M1 (ET 0.87, control 0.96, p < 0.01), Vim-SMA (ET 0.86, control 0.96, p < 0.05), and Vim-pre-SMA (ET 0.87, control 0.95, p < 0.05). There was a significant positive correlation between Tremor Rating Scale score and MK ( = 0.471, p = 0.033) and mean FA ( = 0.438, p = 0.045) for the Vim-SMA tract, and no significant correlation for the Vim-pre-SMA or Vim-M1 tracts was found.

Discussion: Patients with ET demonstrated a reinforcement of Vim-cortical connectivity, with higher Vim-SMA connectivity being associated with greater tremor severity. This finding suggests that the Vim-SMA connection is relevant to the underlying pathophysiology of ET, and inhibition of the SMA may be an effective therapeutic approach.
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http://dx.doi.org/10.7916/tohm.v0.690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727860PMC
March 2020