Publications by authors named "Jennifer Vannest"

86 Publications

Neuroimaging of the Syllable Repetition Task in Children With Residual Speech Sound Disorder.

J Speech Lang Hear Res 2021 Mar 11:1-11. Epub 2021 Mar 11.

Department of Communication Sciences and Disorders, University of Cincinnati, OH.

Purpose This study investigated phonological and speech motor neural networks in children with residual speech sound disorder (RSSD) during an overt Syllable Repetition Task (SRT). Method Sixteen children with RSSD with /ɹ/ errors (6F [female]; ages 8;0-12;6 [years;months]) and 16 children with typically developing speech (TD; 8F; ages 8;5-13;7) completed a functional magnetic resonance imaging experiment. Children performed the SRT ("SRT-Early Sounds") with the phonemes /b, d, m, n, ɑ/ and an adapted version ("SRT-Late Sounds") with the phonemes /ɹ, s, l, tʃ, ɑ/. We compared the functional activation and transcribed production accuracy of the RSSD and TD groups during both conditions. Expected errors were not scored as inaccurate. Results No between-group or within-group differences in repetition accuracy were found on the SRT-Early Sounds or SRT-Late Sounds tasks at any syllable sequence length. On a first-level analysis of the tasks, the TD group showed expected patterns of activation for both the SRT-Early Sounds and SRT-Late Sounds, including activation in the left primary motor cortex, left premotor cortex, bilateral anterior cingulate, bilateral primary auditory cortex, bilateral superior temporal gyrus, and bilateral insula. The RSSD group showed similar activation when correcting for multiple comparisons. In further exploratory analyses, we observed the following subthreshold patterns: (a) On the SRT-Early Sounds, greater activation was found in the left premotor cortex for the RSSD group, while greater activation was found in the left cerebellum for the TD group; (b) on the SRT-Late Sounds, a small area of greater activation was found in the right cerebellum for the RSSD group. No within-group functional differences were observed (SRT-Early Sounds vs. SRT-Late Sounds) for either group. Conclusions Performance was similar between groups, and likewise, we found that functional activation did not differ. Observed functional differences in previous studies may reflect differences in task performance, rather than fundamental differences in neural mechanisms for syllable repetition.
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http://dx.doi.org/10.1044/2020_JSLHR-20-00269DOI Listing
March 2021

Beta synchrony for expressive language lateralizes to right hemisphere in development.

Sci Rep 2021 Feb 17;11(1):3949. Epub 2021 Feb 17.

Neurosciences and Mental Health, Hospital for Sick Children, 686 Bay Street, Toronto, ON, M5G 0A4, Canada.

A left perisylvian network is known to support language in healthy adults. Low-beta (13-23 Hz) event-related desynchrony (ERD) has been observed during verb generation, at approximately 700-1200 ms post-stimulus presentation in past studies; the signal is known to reflect increased neuronal firing and metabolic demand during language production. In contrast, concurrent beta event-related synchrony (ERS) is thought to reflect neuronal inhibition but has not been well studied in the context of language. Further, while low-beta ERD for expressive language has been found to gradually shift from bilateral in childhood to left hemispheric by early adulthood, developmental lateralization of ERS has not been established. We used magnetoencephalography to study low beta ERS lateralization in a group of children and adolescents (n = 78), aged 4 to less than 19 years, who performed covert verb generation. We found that the youngest children had bilateral ERD and ERS. By adolescence, low-beta ERD was predominantly left lateralized in perisylvian cortex (i.e., Broca's and Wernicke's regions), while beta ERS was predominantly right lateralized. Increasing lateralization was significantly correlated to age for both ERD (Spearman's r = 0.45, p < 0.01) and ERS (Spearman's r =  - 0.44, p < 0.01). Interestingly, while ERD lateralized in a linear manner, ERS lateralization followed a nonlinear trajectory, suggesting distinct developmental trajectories. Implications to early-age neuroplasticity and neuronal inhibition are discussed.
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http://dx.doi.org/10.1038/s41598-021-83373-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889886PMC
February 2021

Altered functional network connectivity and working memory dysfunction in adolescents with epilepsy.

Brain Imaging Behav 2021 Feb 2. Epub 2021 Feb 2.

Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.

Adolescents with epilepsy are at risk for deficits in working memory, which could lead to learning difficulties and poor academic outcomes. We used task-based functional magnetic resonance imaging (fMRI) to examine potential disruption in working memory function in adolescents with epilepsy as compared to healthy controls. We recruited 29 adolescents (13-17 years) with non-lesional epilepsy and 20 healthy controls. All participants performed an N-back fMRI task and neuropsychological testing. A general linear model approach was used to create group activation maps of N-back fMRI for epilepsy and control groups and both groups combined (p < 0.05 corrected for multiple comparisons). Functionally defined regions of interest (ROIs) were identified based on clusters of combined group activation (z > 5). Subsets of these functional ROIs corresponding to cingulo-opercular and fronto-parietal networks were selected and differences in functional connectivity between the epilepsy and control groups were assessed. Adolescents with epilepsy had significantly poorer working memory scores compared to controls. For the N-back fMRI task, there were no significant differences in group activation. Functional connectivity was significantly reduced between the left frontal operculum and anterior cingulate gyrus (cingulo-opercular network) in adolescents with epilepsy compared to controls. This study demonstrates working memory deficits and an altered pattern of connectivity in brain networks supporting working memory in adolescents with epilepsy. Working memory performance was worse in adolescents with epilepsy; though scores were not directly correlated with reduced connectivity. These results suggest the neural substrates of working memory in adolescents with epilepsy may differ from those in typically-developing adolescents, and require further investigation to understand the reasons for poorer working memory performance.
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http://dx.doi.org/10.1007/s11682-021-00452-5DOI Listing
February 2021

Functional magnetic resonance brain imaging of imagined walking to study locomotor function after stroke.

Clin Neurophysiol 2021 Jan 21;132(1):167-177. Epub 2020 Nov 21.

Pediatric Neuroimaging Research Consortium, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Communication Sciences and Disorders, College of Allied Health Sciences, University of Cincinnati, OH, USA.

Objective: Imagined walking has yielded insights into normal locomotor control and could improve understanding of neurologic gait dysfunction. This study evaluated brain activation during imagined walking in chronic stroke.

Methods: Ten persons with stroke and 10 matched controls completed a walking test battery and a magnetic resonance imaging session including imagined walking and knee extension tasks. Brain activations were compared between tasks and groups. Associations between activations and composite gait score were also calculated, while controlling for lesion load.

Results: Stroke and worse gait score were each associated with lesser overall brain activation during knee extension but greater overall activation during imagined walking. During imagined walking, the stroke group significantly activated the primary motor cortex lower limb region and cerebellar locomotor region. Better walking function was associated with less activation of these regions and greater activation of medial superior frontal gyrus area 9.

Conclusions: Compared with knee extension, imagined walking was less sensitive to stroke-related deficits in brain activation but better at revealing compensatory changes, some of which could be maladaptive.

Significance: The identified associations for imagined walking suggest potential neural mechanisms of locomotor adaptation after stroke, which could be useful for future intervention development and prognostication.
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http://dx.doi.org/10.1016/j.clinph.2020.11.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856193PMC
January 2021

Longer Screen Vs. Reading Time is Related to Greater Functional Connections Between the Salience Network and Executive Functions Regions in Children with Reading Difficulties Vs. Typical Readers.

Child Psychiatry Hum Dev 2020 Sep 4. Epub 2020 Sep 4.

Educational Neuroimaging Center, Faculty of Biomedical Engineering, Technion, Israel.

An adverse relationship between screen exposure time and brain functional/structural connectivity was reported in typically developing children, specifically related to neurobiological correlates of reading ability. As children with reading difficulties (RD) suffer from impairments in reading and executive functions (EF), we sought to determine the association between the ratio of screen time duration to reading time duration and functional connectivity of EF networks to the entire brain in children with RD compared to typical readers (TRs) using resting state data. Screen/reading time ratio was related to reduced reading and EF abilities. A larger screen/reading time ratio was correlated with increased functional connectivity between the salience network and frontal-EF regions in children with RD compared to TRs. We suggest that whereas greater screen/reading time ratio is related to excessive stimulation of the visual processing system in TRs, it may be related to decreased efficiency of the cognitive control system in RDs.
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http://dx.doi.org/10.1007/s10578-020-01053-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930153PMC
September 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

Cortical and subcortical volume differences between Benign Epilepsy with Centrotemporal Spikes and Childhood Absence Epilepsy.

Epilepsy Res 2020 10 23;166:106407. Epub 2020 Jun 23.

Division of Neurology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave. Cincinnati, OH, 45229, USA; Pediatric Neuroimaging Research Consortium, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave. Cincinnati, OH, 45229, USA. Electronic address:

Objective: Benign Childhood Epilepsy with Centrotemporal Spikes (BECTS) and Childhood Absence Epilepsy (CAE) are the most common childhood epilepsy syndromes and they share a similar age-dependence. However, the two syndromes clearly differ in seizures and EEG patterns. The aim of this study is to investigate whether children of the same age with BECTS, CAE and typically-developing children have significant differences in grey matter volume that may underlie the different profiles of these syndromes.

Methods: Twenty one patients with newly-diagnosed BECTS and 18 newly diagnosed and drug naïve CAE were included and compared to 31 typically-developing children. Voxel-based morphometry was utilized to investigate grey matter volume differences among BECTS, CAE, and controls. We also examined the effect of age on grey matter volume in all three groups. In addition to the whole brain analysis, we chose regions of interest analysis based on previous literature suggesting the involvement of these regions in BECTS or CAE. The group differences of grey matter volume was tested with 2-sample t-test for between two groups' comparisons and ANOVA for three group comparisons.

Results: In the whole brain group comparisons, the grey matter volume in CAE was significantly decreased in the areas of right inferior frontal and anterior temporal compared to BECTS and controls (F  = 27.53, p < 0.001). In the control group, grey matter volume in bifrontal lobes showed a negative correlation with age (r=-0.54, p < 0.05), whereas no correlation was found in either CAE or BECTS. With ROI analyses, the grey matter volume of posterior thalami was increased in CAE compared to other 2 groups (p < 0.05).

Significance: This study shows that there are grey matter volume differences between CAE and BECTS. Our findings of grey matter volume differences may suggest that there may be localized, specific differences in brain structure between these two types of epilepsy.
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http://dx.doi.org/10.1016/j.eplepsyres.2020.106407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494623PMC
October 2020

Listening Difficulties in Children: Behavior and Brain Activation Produced by Dichotic Listening of CV Syllables.

Front Psychol 2020 16;11:675. Epub 2020 Apr 16.

Communication Sciences Research Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.

Listening difficulties (LiD) are common in children with and without hearing loss. Impaired interactions between the two ears have been proposed as an important component of LiD when there is no hearing loss, also known as auditory processing disorder (APD). We examined the ability of 6-13 year old (y.o.) children with normal audiometric thresholds to identify and selectively attend to dichotically presented CV syllables using the Bergen Dichotic Listening Test (BDLT; www.dichoticlistening.com). Children were recruited as typically developing (TD; = 39) or having LiD ( = 35) based primarily on composite score of the ECLiPS caregiver report. Different single syllables (ba, da, ga, pa, ta, ka) were presented simultaneously to each ear (6 × 36 trials). Children reported the syllable heard most clearly (non-forced, NF) or the syllable presented to the right [forced right (FR)] or left [forced left (FL)] ear. Interaural level differences (ILDs) manipulated bottom-up perceptual salience. Dichotic listening (DL) data [correct responses, laterality index (LI)] were analyzed initially by group (LiD, TD), age, report method (NF, FR, FL), and ILD (0, ± 15 dB) and compared with speech-in-noise thresholds (LiSN-S) and cognitive performance (NIH Toolbox). fMRI measured brain activation produced by a receptive speech task that segregated speech, phonetic, and intelligibility components. Some activated areas [planum temporale (PT), inferior frontal gyrus (IFG), and orbitofrontal cortex (OFC)] were correlated with dichotic results in TD children only. Neither group, age, nor report method affected the LI of right/left recall. However, a significant interaction was found between ear, group, and ILD. Laterality indices were small and tended to increase with age, as previously reported. Children with LiD had significantly larger mean LIs than TD children for stimuli with ILDs, especially those favoring the left ear. Neural activity associated with Speech, Phonetic, and Intelligibility sentence cues did not differ significantly between groups. Significant correlations between brain activity level and BDLT were found in several frontal and temporal locations for the TD but not for the LiD group. Overall, the children with LiD had only subtle differences from TD children in the BDLT, and correspondingly minor changes in brain activation.
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http://dx.doi.org/10.3389/fpsyg.2020.00675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177005PMC
April 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

Locomotor training intensity after stroke: Effects of interval type and mode.

Top Stroke Rehabil 2020 10 16;27(7):483-493. Epub 2020 Feb 16.

Department of Rehabilitation, Exercise and Nutrition Sciences, College of Allied Health Sciences, University of Cincinnati , Cincinnati, OH, USA.

: High-intensity interval training (HIIT) is a promising strategy for improving gait and fitness after stroke, but optimal parameters remain unknown. We tested the effects of short vs long interval type and over-ground vs treadmill mode on training intensity. : Using a repeated measures design, 10 participants with chronic hemiparesis performed 12 HIIT sessions over 4 weeks, alternating between short and long-interval HIIT sessions. Both protocols included 10 minutes of over-ground HIIT, 20 minutes of treadmill HIIT and another 10 minutes over-ground. Short-interval HIIT involved 30 second bursts at maximum safe speed and 30-60 second rest periods. Long-interval HIIT involved 4-minute bursts at ~90% of peak heart rate (HR) and 3-minute recovery periods at ~70% HR. : Compared with long-interval HIIT, short-interval HIIT had significantly faster mean overground speeds (0.75 vs 0.67 m/s) and treadmill speeds (0.90 vs 0.51 m/s), with similar mean treadmill HR (82.9 vs 81.8%HR) and session perceived exertion (16.3 vs 16.3), but lower overground HR (78.4 vs 81.1%HR) and session step counts (1481 vs 1672). For short-interval HIIT, training speeds and HR were significantly higher on the treadmill vs. overground. For long-interval HIIT, the treadmill elicited HR similar to overground training at significantly slower speeds. : Both short and long-interval HIIT elicit high intensities but emphasize different dosing parameters. From these preliminary findings and previous studies, we hypothesize that overground and treadmill short-interval HIIT could be optimal for improving gait speed and overground long-interval HIIT could be optimal for improving gait endurance.
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http://dx.doi.org/10.1080/10749357.2020.1728953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429314PMC
October 2020

The neural basis of executive functioning deficits in adolescents with epilepsy: a resting-state fMRI connectivity study of working memory.

Brain Imaging Behav 2021 Feb;15(1):166-176

Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229, USA.

Working memory deficits are common in youth with epilepsy and consistently associated with long-term negative outcomes. Existing research on the neural basis of working memory disruptions in pediatric epilepsy is limited. The question of whether differences in the functional connectivity of neural networks underlie working memory disruptions in pediatric patients with epilepsy remains unanswered. A total of 49 adolescents between the ages of 13-17 years participated in this study. Twenty-nine adolescents had confirmed epilepsy (n = 17 generalized epilepsy, n = 6 localization-related, n = 6 unclassified). The control group included 20 healthy adolescents. A total of 10-min resting state functional magnetic resonance imaging was obtained for all participants. NeuroSynth-derived regions of interest were used as nodes that comprise working memory neural networks. Group differences in resting state functional connectivity were examined between adolescents with epilepsy and controls. Functional connectivity was computed as the temporal correlation of functional magnetic resonance imaging signal fluctuations between any two regions of interest. Compared to controls, adolescents in the epilepsy group demonstrated both hypoconnectivity and hyperconnectivity in cortical areas that map onto fronto-parietal and cingulo-opercular networks, as well as cerebellar regions. Functional connectivity between pairs of regions of interest was also significantly associated with behavioral measures of working memory across epilepsy and control groups. This study demonstrates that the presence of abnormal patterns in resting state neural network connectivity may underlie the working memory disruptions that frequently characterize the neurocognitive profile of youth with epilepsy.
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http://dx.doi.org/10.1007/s11682-019-00243-zDOI Listing
February 2021

Reading in children with drug-resistant epilepsy was related to functional connectivity in cognitive control regions.

Acta Paediatr 2020 10 13;109(10):2105-2111. Epub 2020 Feb 13.

Division of General and Community Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Aim: This study aimed to define whether individuals with drug-resistant focal epilepsy also used regions related to cognitive control to facilitate reading.

Methods: We focused on patients with drug-resistant focal epilepsy in 2011-2014, who were aged 8-20 years and were being treated at the Cincinnati Children's Hospital, USA. They performed a verb generation functional magnetic resonance imaging task known to involve language and cognitive control, as well as a formal reading assessment. The reading scores were correlated with functional connectivity of the anterior cingulate cortex (ACC) using seed-to-voxel analysis.

Results: There were 81 potential patients and 13 (seven females) met the inclusion criteria. Their age at seizure onset was 0-13 years, and they had a mean age of 12.66 ± 3.17 years at the time of the study. Individuals with epilepsy demonstrated average intelligence and word reading ability. Their reading scores were positively correlated with functional connectivity between the ACC and regions related to emotional processing (right amygdala), learning and language processing (left cerebellum) and visual processing.

Conclusion: Our results support the role that the ACC plays in proficient reading among children with drug-resistant epilepsy, even in those with epileptogenic foci in areas related to language.
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http://dx.doi.org/10.1111/apa.15201DOI Listing
October 2020

Clinical and neural responses to cognitive behavioral therapy for functional tremor.

Neurology 2019 11 4;93(19):e1787-e1798. Epub 2019 Oct 4.

From the Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., E.N.); Mood Disorders Center (S.R., L.R.W.), University of Cincinnati Gardner Neuroscience Institute; Pediatric Neuroimaging Research Consortium (T.M., J.V.), Cincinnati Children's Hospital; Department of Pediatrics (J.V.), University of Cincinnati College of Medicine, OH; Department of Biomedical Sciences (A.K.D.), Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso; Department of Neurology (J.B.A., J.P.S.), University of Alabama at Birmingham; Division of Neuropsychiatry and Behavioral Neurology (W.C.L.), Rhode Island Hospital, Providence; and Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic (A.E.L.), Toronto Western Hospital, University of Toronto, Ontario, Canada.

Objectives: To evaluate changes in tremor severity and motor/emotion-processing circuits in response to cognitive behavioral therapy (CBT) delivered as treatment for functional tremor (FT), the most common functional movement disorder in adults.

Methods: Fifteen patients with FT underwent fMRI with motor, basic-emotion, and intense-emotion tasks before and after 12 weeks of CBT. Baseline fMRI was compared to those of 25 healthy controls (HCs). The main clinical endpoint was the tremor score (sum of severity, duration, and incapacitation subscores) adapted from the Rating Scale for Psychogenic Movement Disorders (PMDRS) assessed by a blinded clinician. CBT responders were defined as those with PMDRS score reduction >75%. Anatomic and functional brain images were obtained with a 4T MRI system. Generalized linear model and region-of-interest analyses were used to evaluate before-versus-after treatment-related changes in brain activation.

Results: CBT markedly reduced tremor severity ( < 0.01) with remission/near remission achieved in 73.3% of the cohort. Compared to HCs, in those with FT, a functionally defined fMRI region of interest in the anterior cingulate/paracingulate cortex showed increased activation at baseline and decreased activation after CBT during basic-emotion processing ( = 0.012 for CBT responders). Among CBT responders, the change in anterior cingulate/paracingulate was more significant in those with more severe baseline depression ( = 0.75, < 0.01).

Conclusions: Tremor severity improved significantly after CBT. The improvement was associated with changes in the anterior cingulate/paracingulate activity, which may represent a marker of emotional dysregulation in FT and a predictor of treatment response.

Classification Of Evidence: This study provides Class III evidence that CBT significantly improves tremor severity in patients with functional tremor.
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http://dx.doi.org/10.1212/WNL.0000000000008442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946484PMC
November 2019

Sex, Age, and Handedness Modulate the Neural Correlates of Active Learning.

Front Neurosci 2019 11;13:961. Epub 2019 Sep 11.

Department of Neurology, The University of Alabama at Birmingham, Birmingham, AL, United States.

Background: Self-generation of material compared to passive learning results in mproved memory performance; this may be related to recruitment of a fronto-temporal encoding network. Using a verbal paired-associate learning fMRI task, we examined the effects of sex, age, and handedness on the neural correlates of self-generation.

Methods: Data from 174 healthy English-speaking participants (78M, 56 atypically handed; ages 19-76) were preprocessed using AFNI and FSL. Independent component analysis was conducted using GIFT (Group ICA fMRI Toolbox). Forty-one independent components were temporally sorted by task time series. Retaining correlations ( > 0.25) resulted in three task-positive ("generate") and three task-negative ("read") components. Using participants' back-projected components, we evaluated the effects of sex, handedness, and aging on activation lateralization and localization in task-relevant networks with two-sample -tests. Further, we examined the linear relationship between sex and neuroimaging data with multiple regression, covarying for scanner, age, and handedness.

Results: Task-positive components identified using ICA revealed a fronto-parietal network involved with self-generation, while task-negative components reflecting passive reading showed temporo-occipital involvement. Compared to older adults, younger adults exhibited greater task-positive involvement of the left inferior frontal gyrus and insula, whereas older adults exhibited reduced prefrontal lateralization. Greater involvement of the left angular gyrus in task-positive encoding networks among right-handed individuals suggests the reliance on left dominant semantic processing areas may be modulated by handedness. Sex effects on task-related encoding networks while controlling for age and handedness suggest increased right hemisphere recruitment among males compared to females, specifically in the paracentral lobe during self-generation and the suparmarginal gyrus during passive reading.

Implications: Identified neuroimaging differences suggest that sex, age, and handedness are factors in the differential recruitment of encoding network regions for both passive and active learning.
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http://dx.doi.org/10.3389/fnins.2019.00961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6749092PMC
September 2019

Electrical stimulation mapping of language with stereo-EEG.

Epilepsy Behav 2019 10 15;99:106395. Epub 2019 Aug 15.

Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Objective: We prospectively validated stereo-electroencephalography (EEG) electrical stimulation mapping (ESM) of language against a reference standard of meta-analytic functional magnetic resonance imaging (fMRI) framework (Neurosynth).

Methods: Language ESM was performed using 50 Hz, biphasic, bipolar, stimulation at 1-8 mA, with a picture naming task. Electrode contacts (ECs) were scored as ESM+ if ESM interfered with speech/language function. For each patient, presurgical MRI was transformed to a standard space and coregistered with computed tomographic (CT) scan to obtain EC locations. After whole-brain parcellation, this fused image data were intersected with three-dimensional language fMRI (Neurosynth), and each EC was classified as lying within/outside the fMRI language parcel. Diagnostic odds ratio (DOR) and other indices were estimated. Current thresholds for language inhibition and after-discharges (ADs) were analyzed using multivariable linear mixed models.

Results: In 10 patients (5 females), aged 5.4-21.2 years, speech/language inhibition was noted with ESM on 87/304 (29%) ECs. Stereo-EEG language ESM was a valid classifier of fMRI (Neurosynth) language sites (DOR: 9.02, p < 0.0001), with high specificity (0.87) but poor sensitivity (0.57). Similar diagnostic indices were seen for ECs in frontal or posterior regions, and gray or white matter. Language threshold (3.1 ± 1.5 mA) was lower than AD threshold (4.0 ± 2.0 mA, p = 0.0001). Language and AD thresholds decreased with age and intelligence quotient. Electrical stimulation mapping triggered seizures/auras represented patients' habitual semiology with 1 Hz stimulation.

Conclusions: Stereo-EEG ESM can reliably identify cerebral parcels with/without language function but may under detect all language sites. We suggest a 50-Hz stimulation protocol for language ESM with stereo-EEG.
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http://dx.doi.org/10.1016/j.yebeh.2019.06.038DOI Listing
October 2019

A model for visual naming based on spatiotemporal dynamics of ECoG high-gamma modulation.

Epilepsy Behav 2019 10 13;99:106455. Epub 2019 Aug 13.

Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States of America; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States of America.

Objective: We studied spatiotemporal dynamics of electrocorticographic (ECoG) high-gamma modulation (HGM) during visual naming.

Methods: In 8 patients, aged 4-19 years, with left hemisphere subdural electrodes, propagation of ECoG HGM during overt visual naming was mapped with trial-averaged time-frequency analysis. Group-level synthesis was performed by transforming all electrodes to a standard space and assigning cortical parcels based on a reference atlas.

Results: After image display following cortical parcels were activated: inferior occipital, caudal angular, fusiform, and middle temporal gyri, and superior temporal sulcus [0-400 ms]; rostral pars triangularis (A45r), inferior frontal sulcus, caudal dorsolateral premotor cortex (A6cdl) [300-600 ms]; caudal ventrolateral premotor cortex (A6cvl), caudal pars triangularis (A45c), pars opercularis (A44) [400-800 ms]; primary sensorimotor cortex [600-1400 ms], with most prominent HGM in glossolaryngeal region (A4tl). Lastly, auditory cortex (A41/A42) and superior temporal gyrus (A22) were activated [900 ms-1.4 s]. After 1.5 s, HGM decreased globally, except in ventrolateral premotor cortex.

Conclusions: During visual naming, ECoG HGM shows a sequential but overlapping spatiotemporal course through cortical regions. We provide neurophysiologic validation for a model of visual naming incorporating both modular and distributed cortical processing. This may explain cognitive deficits seen in some patients after surgery involving HGM naming sites outside perisylvian language cortex.
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http://dx.doi.org/10.1016/j.yebeh.2019.106455DOI Listing
October 2019

Neuropsychological outcomes after resection of cortical sites with visual naming associated electrocorticographic high-gamma modulation.

Epilepsy Res 2019 03 29;151:17-23. Epub 2019 Jan 29.

Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Background: Language mapping with high-gamma modulation (HGM) has compared well with electrical cortical stimulation mapping (ESM). However, there is limited prospective data about its functional validity. We compared changes in neuropsychological evaluation (NPE) performed before and 1-year after epilepsy surgery, between patients with/without resection of cortical sites showing HGM during a visual naming task.

Methods: Pediatric drug-resistant epilepsy (DRE) patients underwent pre-surgical language localization with ESM and HGM using a visual naming task. Surgical decisions were based solely on ESM results. NPE difference scores were compared between patients with/without resection of HGM naming sites using principal component (PC) analysis. Follow-up NPE scores were modeled with resection group as main effect and respective pre-surgical score as a covariate, using analysis of covariance.

Results: Seventeen native English speakers (12 females), aged 6.5-20.2 years, were included. One year after epilepsy surgery, first PC score increased by (mean ± standard deviation) 14.4 ± 16.5 points in patients without resection, whereas it decreased by 7.6 ± 24.6 points in those with resection of HGM naming sites (p = 0.040). This PC score represented verbal comprehension, working memory, perceptual reasoning (Wechsler subscales); Woodcock-Johnson Tests of Achievement; and Peabody Picture Vocabulary Test. Subsequent analysis showed significant difference in working memory score between patients with/without resection of HGM naming sites (-15.2 points, 95% confidence limits -29.7 to -0.7, p = 0.041).

Conclusion: We highlight the functional consequences of resecting HGM language sites, and suggest that NPE of DRE patients should include comprehensive assessment of multiple linguistic and cognitive domains besides naming ability.
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http://dx.doi.org/10.1016/j.eplepsyres.2019.01.011DOI Listing
March 2019

Youth-Onset Type 2 Diabetes and the Developing Brain.

Curr Diab Rep 2019 01 21;19(1). Epub 2019 Jan 21.

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Purpose Of Review: This review describes the literature evaluating the potential adverse effects of youth-onset type 2 diabetes on the developing brain. A summary of recently published articles and the current state of knowledge are covered succinctly in this manuscript.

Recent Findings: Current literature suggests both cognitive and brain structural differences are found in youth with type 2 diabetes. Studies have shown poorer scores in a number of neurocognitive domains, particularly in areas of executive functioning and memory. Additionally, imaging studies have found differences in brain gray matter volume, white matter volume, and microstructural integrity. These findings are largely consistent with the adult literature. Youth with type 2 diabetes demonstrate lower cognitive scores and structural brain differences. Although causality has not yet been established, these findings are important because these individuals are still undergoing neurodevelopmental maturation.
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http://dx.doi.org/10.1007/s11892-019-1120-yDOI Listing
January 2019

Resting-state functional connectivity of subcortical locomotor centers explains variance in walking capacity.

Hum Brain Mapp 2018 12 27;39(12):4831-4843. Epub 2018 Jul 27.

Pediatric Neuroimaging Research Consortium, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

Walking capacity influences the quality of life and disability in normal aging and neurological disease, but the neural correlates remain unclear and subcortical locomotor regions identified in animals have been more challenging to assess in humans. Here we test whether resting-state functional MRI connectivity (rsFC) of midbrain and cerebellar locomotor regions (MLR and CLR) is associated with walking capacity among healthy adults. Using phenotypic and MRI data from the Nathan Kline Institute Rockland Sample (n =119, age 18-85), the association between walking capacity (6-min walk test distance) and rsFC was calculated from subcortical locomotor regions to 81 other gait-related regions of interest across the brain. Additional analyses assessed the independence and specificity of the results. Walking capacity was associated with higher rsFC between the MLR and superior frontal gyrus adjacent to the anterior cingulate cortex, higher rsFC between the MLR and paravermal cerebellum, and lower rsFC between the CLR and primary motor cortex foot area. These rsFC correlates were more strongly associated with walking capacity than phenotypic variables such as age, and together explained 25% of the variance in walking capacity. Results were specific to locomotor regions compared with the other brain regions. The rsFC of locomotor centers correlates with walking capacity among healthy adults. These locomotion-related biomarkers may prove useful in future work aimed at helping patients with reduced walking capacity.
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http://dx.doi.org/10.1002/hbm.24326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218296PMC
December 2018

Cortical morphology, epileptiform discharges, and neuropsychological performance in BECTS.

Acta Neurol Scand 2018 Nov 10;138(5):432-440. Epub 2018 Jul 10.

Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

Objectives: The aim of this study was to understand the relationship between cortical morphology, centrotemporal spike (CTS), and neuropsychological functioning in children with BECTS compared to their typically developing peers.

Materials And Methods: To examine whole-brain differences in cortical thickness between groups, a general linear model approach was applied to T1-weighted structural magnetic resonance imaging (MRI) in children with BECTS and typically developing children. Further region-of-interest (ROI) analyses were performed to examine the effects of frequency and lateralization of CTS. In addition, the relationship between Processing Speed Index (PSI) and cortical thickness was investigated.

Results: Twenty-three patients with BECTS and thirty-two controls were included. There was no statistically significant difference in global cortical thickness between groups. With ROI analyses, we found significantly thinner cortex within right pars opercularis when comparing children with right predominant CTS, and with very frequent right CTS (>10/min) to the control group (P = 0.028 and P = 0.026, respectively). A statistically significant interaction of group (controls vs BECTS) and PSI was seen in bilateral frontal and right superior parietal cortices, indicating a positive relationship between cortical thickness and PSI in healthy controls but not BECTS.

Conclusion: A region of cortex where right CTS may originate was thinner in BECTS compared to children without BECTS. Typically developing children with faster processing speed had thicker cortices in regions supporting visuomotor integration, motor, and executive function, but this relationship was not observed in BECTS. These results suggest that BECTS is associated with atypical cortical morphology that may underlie poorer neuropsychological performance.
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http://dx.doi.org/10.1111/ane.12997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175642PMC
November 2018

A feasibility study of combined intermittent theta burst stimulation and modified constraint-induced aphasia therapy in chronic post-stroke aphasia.

Restor Neurol Neurosci 2018 ;36(4):503-518

Department of Physical Medicine and Rehabilitation, University of Alabama at Birmingham, Birmingham, AL, USA.

Purpose: The purpose of this feasibility study was to assess whether combined intermittent theta burst suppression (iTBS) applied to the ipsilesional hemisphere and modified constraint-induced aphasia therapy (mCIAT) are safe and logistically feasible within the time interval associated with iTBS induced long-term potentiation in patients with post-stroke aphasia. We also wanted to determine whether combining priming with iTBS and CIAT improves language functions after treatment.

Methods: Twelve participants received fMRI (semantic decision/tone decision task) and neuropsychological testing of language skills at three time points - before starting the iTBS/mCIAT intervention (T1), immediately after completing 2-week long course of intervention (T2), and at 3-months follow-up (T3). ITBS was applied to the individually determined fMRI language "hot spot" located in the left fronto-temporal regions.

Results: There were no serious adverse events, and all mCIAT group therapy sessions (3-4 subjects each) were initiated within 30 minutes of the first group subject receiving iTBS. Neuropsychological assessments of language showed a significant effect of session on Western Aphasia Battery aphasia quotient (WAB-AQ; p = 0.04) and spontaneously correct responses on Boston Naming Test (BNT; p = 0.002), with improvement noted at T2 (p = 0.002) and T3 (p = 0.05) versus T1. FMRI showed significant changes between all timepoints. Post-hoc correlations showed associations between improvements in WAB-AQ from T2 to T3 and decreased BOLD signal in left inferior parietal lobe, and improvements in BNT from T1 to T3 with decreased signal in right inferior frontal gyrus.

Conclusion: This study shows feasibility and safety for combining behavioral and neurostimulation interventions for chronic post-stroke aphasia. Observed changes in linguistic measures were relatively small. However, they were statistically significant and associated with parallel changes observed in the neuroimaging. Our findings support further development and testing of the combined mCIAT and iTBS protocol and comparisons to either CIAT/mCIAT or iTBS applied alone for the treatment of post-stroke aphasia.
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http://dx.doi.org/10.3233/RNN-180812DOI Listing
October 2018

Longitudinal fMRI study of language recovery after a left hemispheric ischemic stroke.

Restor Neurol Neurosci 2018 ;36(3):359-385

Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA.

Background: Recovery from stroke-induced aphasia is typically protracted and involves complex functional reorganization. The relative contributions of the lesioned and non-lesioned hemispheres to this process have been examined in several cross-sectional studies but longitudinal studies involving several time-points and large numbers of subjects are scarce.

Objective: The aim of this study was to address the gaps in the literature by longitudinally studying the evolution of post-stroke lateralization and localization of language-related fMRI activation in the first year after single left hemispheric ischemic stroke.

Method: Seventeen patients with stroke-induced aphasia were enrolled to undergo detailed behavioral testing and fMRI at 2, 6, 12, 26, and 52 weeks post-stroke. Matched for age, handedness and sex participants were also enrolled to visualize canonical language regions.

Results: Behavioral results showed improvements over time for all but one of the behavioral scores (Semantic Fluency Test). FMRI results showed that the left temporal area participates in compensation for language deficits in the first year after stroke, that there is a correlation between behavioral improvement and the left cerebellar activation over time, and that there is a shift towards stronger frontal left-lateralization of the fMRI activation over the first year post-stroke. Temporary compensation observed in the initial phases of post-stroke recovery that involves the non-lesioned hemisphere may not be as important as previously postulated, since in this study the recovery was driven by activations in the left fronto-temporal regions.

Conclusion: Language recovery after left hemispheric ischemic stroke is likely driven by the previously involved in language and attention left hemispheric networks.
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http://dx.doi.org/10.3233/RNN-170767DOI Listing
October 2018

fMRI connectivity of expressive language in young children and adolescents.

Hum Brain Mapp 2018 09 2;39(9):3586-3596. Epub 2018 May 2.

Pediatric Neuroimaging Research Consortium (PNRC), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

Studies of language representation in development have shown a bilateral distributed pattern of activation that becomes increasingly left-lateralized and focal from young childhood to adulthood. However, the level by which canonical and extra-canonical regions, including subcortical and cerebellar regions, contribute to language during development has not been well-characterized. In this study, we employed fMRI connectivity analyses (fcMRI) to characterize the distributed network supporting expressive language in a group of young children (age 4-6) and adolescents (age 16-18). We conducted an fcMRI analysis using seed-to-voxel and seed-to-ROI (region of interest) strategies to investigate interactions of left pars triangularis with other brain areas. The analyses showed significant interhemispheric connectivity in young children, with a minimal connectivity of the left pars triangularis to subcortical and cerebellar regions. In contrast, adolescents showed significant connectivity between the left IFG seed and left perisylvian cortex, left caudate and putamen, and regions of the right cerebellum. Importantly, fcMRI analyses indicated significant differences between groups at 3 anatomical clusters, including left IFG, left supramarginal gyrus, and right cerebellar crura, suggesting a role in the functional development of language.
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http://dx.doi.org/10.1002/hbm.24196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6866395PMC
September 2018

Ictal connectivity in childhood absence epilepsy: Associations with outcome.

Epilepsia 2018 05 6;59(5):971-981. Epub 2018 Apr 6.

Division of Neurology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Objective: The understanding of childhood absence epilepsy (CAE) has been revolutionized over the past decade, but the biological mechanisms responsible for variable treatment outcomes are unknown. Our purpose in this prospective observational study was to determine how pretreatment ictal network pathways, defined using a combined electroencephalography (EEG)-functional magnetic resonance imaging (EEG-fMRI) and magnetoencephalography (MEG) effective connectivity analysis, were related to treatment response.

Methods: Sixteen children with newly diagnosed and drug-naive CAE had 31 typical absence seizures during EEG-fMRI and 74 during MEG. The spatial extent of the pretreatment ictal network was defined using fMRI hemodynamic response with an event-related independent component analysis (eICA). This spatially defined pretreatment ictal network supplied prior information for MEG-effective connectivity analysis calculated using phase slope index (PSI). Treatment outcome was assessed 2 years following diagnosis and dichotomized to ethosuximide (ETX)-treatment responders (N = 11) or nonresponders (N = 5). Effective connectivity of the pretreatment ictal network was compared to the treatment response.

Results: Patterns of pretreatment connectivity demonstrated strongest connections in the thalamus and posterior brain regions (parietal, posterior cingulate, angular gyrus, precuneus, and occipital) at delta frequencies and the frontal cortices at gamma frequencies (P < .05). ETX treatment nonresponders had pretreatment connectivity, which was decreased in the precuneus region and increased in the frontal cortex compared to ETX responders (P < .05).

Significance: Pretreatment ictal connectivity differences in children with CAE were associated with response to antiepileptic treatment. This is a possible mechanism for the variable treatment response seen in patients sharing the same epilepsy syndrome.
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http://dx.doi.org/10.1111/epi.14067DOI Listing
May 2018

Electrocorticographic high-gamma modulation with passive listening paradigm for pediatric extraoperative language mapping.

Epilepsia 2018 04 20;59(4):792-801. Epub 2018 Feb 20.

Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Objective: This prospective study compared the topography of high-gamma modulation (HGM) during a story-listening task requiring negligible patient cooperation, with the conventional electrical stimulation mapping (ESM) using a picture-naming task, for presurgical language localization in pediatric drug-resistant epilepsy.

Methods: Patients undergoing extraoperative monitoring with subdural electrodes were included. Electrocorticographic signals were recorded during quiet baseline and a story-listening task. The likelihood of 70- to 150-Hz power modulation during the listening task relative to the baseline was estimated for each electrode and plotted on a cortical surface model. Sensitivity, specificity, accuracy, and diagnostic odds ratio (DOR) were estimated compared to ESM, using a meta-analytic framework.

Results: Nineteen patients (10 with left hemisphere electrodes) aged 4-19 years were analyzed. HGM during story listening was observed in bilateral posterior superior temporal, angular, supramarginal, and inferior frontal gyri, along with anatomically defined language association areas. Compared to either cognitive or both cognitive and orofacial sensorimotor interference with naming during ESM, left hemisphere HGM showed high specificity (0.82-0.84), good accuracy (0.66-0.70), and DOR of 2.23 and 3.24, respectively. HGM was a better classifier of ESM language sites in the left temporoparietal cortex compared to the frontal lobe. Incorporating visual naming with the story-listening task substantially improved the accuracy (0.80) and DOR (13.61) of HGM mapping, while the high specificity (0.85) was retained. In the right hemisphere, no ESM sites for aphasia were seen, and the results of HGM and ESM comparisons were not significant.

Significance: HGM associated with story listening is a specific determinant of left hemisphere ESM language sites. It can be used for presurgical language mapping in children who cannot cooperate with conventional language tasks requiring active engagement. Incorporation of additional language tasks, if feasible, can further improve the diagnostic accuracy of language localization with HGM.
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http://dx.doi.org/10.1111/epi.14029DOI Listing
April 2018

Pattern of executive functioning in adolescents with epilepsy: A multimethod measurement approach.

Epilepsy Behav 2018 03 3;80:5-10. Epub 2018 Feb 3.

Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.

Youth with epilepsy demonstrate deficits in executive functioning (EF), the skills necessary for goal-directed behavior (e.g., problem-solving, initiating, monitoring, organization, planning, and working memory). Despite 30-50% of youth with epilepsy demonstrating EF deficits, no extant studies have utilized both performance and questionnaire-based measures to examine the pattern of EF deficits in adolescents with epilepsy. Study aims were to 1) identify the pattern of EF deficits in adolescents with epilepsy and 2) identify which assessment tools are most sensitive to EF deficits in this population (adolescents, ages 13-17, with epilepsy). An exploratory aim was to examine group differences on measures of EF by epilepsy type. Standard performance-based neuropsychological measures (Wechsler Intelligence Scale for Children - Version V or Wechsler Adult Intelligence Scale Working Memory Index-Version IV, Delis Kaplan Executive Functioning System, NIH Toolbox, Test of Everyday Attention for Children) and the Behavior Rating Inventory of Executive Functioning (BRIEF) comprised the multimethod assessment battery. Depending on the measure, 30% of adolescents with epilepsy had deficits in working memory, 17% in cognitive flexibility/problem solving, 6% in inhibition, and 18% in planning/organization. Attention was a significant problem for 15% of adolescents with epilepsy. Correlations among the various EF measures were quite poor. Across various EF domains, results indicated that adolescents with localization-related epilepsy demonstrated better EF skills compared to adolescents with unclassified epilepsy. Overall, our findings suggest that executive functioning deficits are selective and different from those observed in other neurological populations (e.g., attention deficit hyperactivity disorder (ADHD), traumatic brain injury) where problems with self-regulation (i.e., inhibition, planning/organization) are more pronounced. These findings support utilizing multiple measures, including both performance-based neuropsychological tests and parent- and self-reports, to assess executive functioning difficulties in adolescents with epilepsy as they are uniquely sensitive to executive functioning domains. Adolescents with unclassified epilepsy also appear to be at higher risk for EF deficits and thus represent an important group to target for intervention.
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http://dx.doi.org/10.1016/j.yebeh.2017.12.021DOI Listing
March 2018

Brain gray matter volume differences in obese youth with type 2 diabetes: a pilot study.

J Pediatr Endocrinol Metab 2018 Mar;31(3):261-268

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Background: Adults with type 2 diabetes (T2D) have significantly lower gray matter volume (GMV) compared to healthy peers. Whether GMV differences exist in youth with T2D remains unclear. Thus, we compared global and regional GMV between obese youth with T2D with age, race and sex similar healthy controls.

Methods: In a cross-sectional study, 20 obese youth with T2D underwent T1-weighted brain magnetic resonance imaging (MRI). Comparisons were made to 20 age, race and sex similar controls. Differences in global and regional GMV between groups were identified using voxel-based morphometry (VBM).

Results: Youth with T2D had a significantly lower global GMV-to-intracranial volume ratio (0.51±0.02 in T2D vs. 0.53±0.02 in controls, p=0.02, Cohen's d=0.85). There were 14 regions where GMV was significantly lower in the T2D group, and nine of these were found in either the temporal or occipital lobes. There were six regions with increased GMV in T2D. All regional differences were significant at p<0.05 after adjusting for multiple comparisons.

Conclusions: Results from this pilot study show obese youth with T2D have significantly lower global GMV and regional GMV differences, when compared to their age, race and sex similar peers. Future work is needed to determine whether these brain findings are a direct result of adolescent-onset T2D.
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http://dx.doi.org/10.1515/jpem-2017-0349DOI Listing
March 2018

The feasibility of improving discourse in people with aphasia through AAC: Clinical and functional MRI correlates.

Aphasiology 2018 9;32(6):693-719. Epub 2018 Mar 9.

University of Alabama at Birmingham.

Aims: The purpose of this study is twofold: (1) to examine the feasibility of providing high-tech augmentative and alternative communication (AAC) treatment to people with chronic aphasia, with the goal of evoking changes in spoken language; and (2) to identify evidence of AAC-induced changes in brain activation.

Method & Procedures: We employed a pre- post-treatment design with a control (usual care) group to observe the impact of an AAC treatment on aphasia severity and spoken discourse. Further, we used functional magnetic resonance imaging (fMRI) to examine associated neural reorganization.

Outcomes & Results: Compared to the usual care group, the AAC intervention trended toward larger treatment effects and resulted in a higher number of responders on behavioral outcomes. Both groups demonstrated a trend toward greater leftward lateralization of language functions via fMRI. Secondary analyses of responders to treatment revealed increased activation in visual processing regions, primarily for the AAC group.

Conclusions: This study provides preliminary guidance regarding how to implement AAC treatment in a manner that simultaneously facilitates language recovery across a variety of aphasia types and severity levels while compensating for residual deficits in people with chronic aphasia. Further, this work motivates continued efforts to unveil the role of AAC-based interventions in the aphasia recovery process and provides insight regarding the neurobiological mechanisms supporting AAC-induced language changes.
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http://dx.doi.org/10.1080/02687038.2018.1447641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523709PMC
March 2018

Dysfunction in emotion processing underlies functional (psychogenic) dystonia.

Mov Disord 2018 01 10;33(1):136-145. Epub 2017 Nov 10.

UC Neuroscience Institute, Department of Neurology, University of Cincinnati, Cincinnati, Ohio, USA.

Objective: We sought to determine whether abnormalities in emotion processing underlie functional (psychogenic) dystonia, one of the most common functional movement disorders.

Methods: Motor and emotion circuits were examined in 12 participants with functional dystonia, 12 with primary organic dystonia, and 25 healthy controls using functional magnetic resonance imaging at 4T and a finger-tapping task (motor task), a basic emotion-recognition task (emotional faces task), and an intense-emotion stimuli task.

Results: There were no differences in motor task activation between groups. In the faces task, when compared with the other groups, functional dystonia patients showed areas of decreased activation in the right middle temporal gyrus and bilateral precuneus and increased activation in the right inferior frontal gyrus, bilateral occipital cortex and fusiform gyrus, and bilateral cerebellum. In the intense-emotion task, when compared with the other groups, functional dystonia patients showed decreased activation in the left insular and left motor cortices (compared to organic dystonia, they showed an additional decrease in activation in the right opercular cortex and right motor cortex) and increased activation in the left fusiform gyrus.

Conclusions: Functional dystonia patients exhibited stimulus-dependent altered activation in networks involved in motor preparation and execution, spatial cognition, and attentional control. These results support the presence of network dysfunction in functional dystonia. © 2017 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.27217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5767134PMC
January 2018

Impaired emotion processing in functional (psychogenic) tremor: A functional magnetic resonance imaging study.

Neuroimage Clin 2018 18;17:179-187. Epub 2017 Oct 18.

Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA.

Background: Despite its high prevalence and associated disability, the neural correlates of emotion processing in patients with functional (psychogenic) tremor (FT), the most common functional movement disorder, remain poorly understood.

Methods: In this cross sectional functional magnetic resonance imaging (fMRI) study at 4T, 27 subjects with FT, 16 with essential tremor (ET), and 25 healthy controls (HCs) underwent a finger-tapping motor task, a basic-emotion task, and an intense-emotion task to probe motor and emotion circuitries. Anatomical and functional MRI data were processed with FSL (FMRIB Software Library) and AFNI (Analysis of Functional Neuroimages), followed by seed-to-seed connectivity analyses using anatomical regions defined from the Harvard-Oxford subcortical atlas; all analyses were corrected for multiple comparisons.

Results: After controlling for depression scores and correcting for multiple comparisons, the FT group showed increased activation in the right cerebellum compared to ET during the motor task; and increased activation in the paracingulate gyrus and left Heschl's gyrus compared with HC with decreased activation in the right precentral gyrus compared with ET during the basic-emotion task. No significant differences were found after adjusting for multiple comparisons during the intense-emotion task but increase in connectivity between the left amygdala and left middle frontal gyrus survived corrections in the FT subjects during this task, compared to HC.

Conclusions: In response to emotional stimuli, functional tremor is associated with alterations in activation and functional connectivity in networks involved in emotion processing and theory of mind. These findings may be relevant to the pathophysiology of functional movement disorders.
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http://dx.doi.org/10.1016/j.nicl.2017.10.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655406PMC
June 2018