Publications by authors named "Shantanu H Joshi"

85 Publications

Accounting for symptom heterogeneity can improve neuroimaging models of antidepressant response after electroconvulsive therapy.

Hum Brain Mapp 2021 Aug 13. Epub 2021 Aug 13.

Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, UCLA, Los Angeles, California, USA.

Depression symptom heterogeneity limits the identifiability of treatment-response biomarkers. Whether improvement along dimensions of depressive symptoms relates to separable neural networks remains poorly understood. We build on work describing three latent symptom dimensions within the 17-item Hamilton Depression Rating Scale (HDRS) and use data-driven methods to relate multivariate patterns of patient clinical, demographic, and brain structural changes over electroconvulsive therapy (ECT) to dimensional changes in depressive symptoms. We included 110 ECT patients from Global ECT-MRI Research Collaboration (GEMRIC) sites who underwent structural MRI and HDRS assessments before and after treatment. Cross validated random forest regression models predicted change along symptom dimensions. HDRS symptoms clustered into dimensions of somatic disturbances (SoD), core mood and anhedonia (CMA), and insomnia. The coefficient of determination between predicted and actual changes were 22%, 39%, and 39% (all p < .01) for SoD, CMA, and insomnia, respectively. CMA and insomnia change were predicted more accurately than HDRS-6 and HDRS-17 changes (p < .05). Pretreatment symptoms, body-mass index, and age were important predictors. Important imaging predictors included the right transverse temporal gyrus and left frontal pole for the SoD dimension; right transverse temporal gyrus and right rostral middle frontal gyrus for the CMA dimension; and right superior parietal lobule and left accumbens for the insomnia dimension. Our findings support that recovery along depressive symptom dimensions is predicted more accurately than HDRS total scores and are related to unique and overlapping patterns of clinical and demographic data and volumetric changes in brain regions related to depression and near ECT electrodes.
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http://dx.doi.org/10.1002/hbm.25620DOI Listing
August 2021

Central white matter integrity alterations in 2-3-year-old children following prenatal alcohol exposure.

Drug Alcohol Depend 2021 08 24;225:108826. Epub 2021 Jun 24.

Department of Pediatrics and Child Health, University of Cape Town, South Africa; Neuroscience Institute, University of Cape Town, South Africa.

Background: Prenatal alcohol exposure (PAE) remains a potentially preventable, but pervasive risk factor to neurodevelopment. Yet, evidence is lacking on the impact of alcohol on brain development in toddlers. This study aimed to investigate the impact of PAE on brain white matter integrity in 2-3-year-old children.

Methods: Children (n = 83, 30-37 months old) of the Drakenstein Child Health Study birth cohort, underwent diffusion MRI on a 3 T Siemens scanner during natural sleep. Parameters were extracted in children with PAE (n = 25, 56 % boys) and unexposed controls (n = 58, 62 % boys) using Tract-based Spatial Statistics, and compared by group. The contribution of maternal tobacco smoking to white matter differences was also explored.

Results: Children with PAE had altered fractional anisotropy, radial diffusivity and axial diffusivity in brain stem, limbic and association tracts compared to unexposed controls. Notably lower fractional anisotropy was found in the uncinate fasciculus, and lower mean and radial diffusivity were found in the fornix stria terminalis and corticospinal tract (FDR corrected p < 0.05). There was a significant interaction effect of PAE and prenatal tobacco exposure which lowered mean, radial and axial diffusivity in the corticospinal tract significantly in the PAE group but not controls.

Conclusion: Widespread altered white matter microstructural integrity at 2-3 years of age is consistent with findings in neonates in the same and other cohorts, indicating persistence of effects of PAE through early life. Findings also highlight that prenatal tobacco exposure impacts the association of PAE on white matter alterations, amplifying effects in tracts underlying motor function.
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http://dx.doi.org/10.1016/j.drugalcdep.2021.108826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299546PMC
August 2021

Cortical gyrification in children with attention deficit-hyperactivity disorder and prenatal alcohol exposure.

Drug Alcohol Depend 2021 08 18;225:108817. Epub 2021 Jun 18.

Division of Child & Adolescent Psychiatry, Jane & Terry Semel Institute for Neuroscience, University of California, Los Angeles, CA, USA.

Background: An improved understanding of the neurodevelopmental differences between attention deficit hyperactivity disorder with and without prenatal alcohol exposure (ADHD + PAE and ADHD-PAE, respectively) is needed. Herein, we evaluated gyrification (cortical folding) in children with ADHD + PAE compared to that in children with familial ADHD-PAE and typically developing (TD) children.

Methods: ADHD + PAE (n = 37), ADHD-PAE (n = 25), and TD children (n = 27), aged 8-13 years, were compared on facial morphological, neurobehavioral, and neuroimaging assessments. Local gyrification index (LGI) maps were compared between groups using general linear modelling. Relationships between LGI and clincobehavioral parameters in children with ADHD ± PAE were evaluated using multivariate partial least squares.

Results: ADHD + PAE and ADHD-PAE groups showed significantly lower LGI (relative to TD) in numerous regions, overlapping in medial prefrontal, parietal, and temporo-occipital cortices (p < 0.001). However, LGI in left mid-dorsolateral prefrontal cortex was uniquely lower in the ADHD + PAE group (p < 0.001). Partial least squares analysis identified one significant latent variable (accounting for 59.3 % of the crossblock correlation, p < 0.001), reflecting a significant relationship between a profile of lower LGI in prefrontal (including left mid-dorsolateral), insular, cingulate, temporal, and parietal cortices and a clinicobehavioral profile of PAE, including a flat philtrum and upper vermillion border, lower IQ, poorer behavioral regulation scores, and greater hyperactivity/impulsivity.

Conclusions: Children with ADHD + PAE uniquely demonstrate lower mid-dorsolateral LGI, with widespread lower LGI related to more severe facial dysmorphia and neurobehavioral impairments. These findings add insight into the brain bases of PAE symptoms, potentially informing more targeted ADHD treatments based on an objective differential diagnosis of ADHD + PAE vs. ADHD-PAE.
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http://dx.doi.org/10.1016/j.drugalcdep.2021.108817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445068PMC
August 2021

BRAIN NETWORK CONNECTIVITY FROM MATCHING CORTICAL FEATURE DENSITIES.

Proc IEEE Int Symp Biomed Imaging 2020 Apr 22;2020:995-998. Epub 2020 May 22.

Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, UCLA, USA.

We present a new method for constructing structural inference brain networks from functional measures of cortical features. Instead of averaging vertex-wise cortical features, we propose the use of full functions of spatial densities of measures such as thickness and use two dimensional pairwise correlations between regions to construct population networks. We show increased within group correlations for both healthy controls and toddlers with prenatal alcohol exposure compared to the existing mean-based correlation approach. Further, we also show significant differences in brain connectivity between the healthy controls and the exposed group.
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http://dx.doi.org/10.1109/isbi45749.2020.9098689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722986PMC
April 2020

Modulation of the functional connectome in major depressive disorder by ketamine therapy.

Psychol Med 2020 Dec 3:1-10. Epub 2020 Dec 3.

Department of Neurology, Ahmanson-Lovelace Brain Mapping Center, University of California Los Angeles, Los Angeles, CA, USA.

Background: Subanesthetic ketamine infusion therapy can produce fast-acting antidepressant effects in patients with major depression. How single and repeated ketamine treatment modulates the whole-brain functional connectome to affect clinical outcomes remains uncharacterized.

Methods: Data-driven whole brain functional connectivity (FC) analysis was used to identify the functional connections modified by ketamine treatment in patients with major depressive disorder (MDD). MDD patients (N = 61, mean age = 38, 19 women) completed baseline resting-state (RS) functional magnetic resonance imaging and depression symptom scales. Of these patients, n = 48 and n = 51, completed the same assessments 24 h after receiving one and four 0.5 mg/kg intravenous ketamine infusions. Healthy controls (HC) (n = 40, 24 women) completed baseline assessments with no intervention. Analysis of RS FC addressed effects of diagnosis, time, and remitter status.

Results: Significant differences (p < 0.05, corrected) in RS FC were observed between HC and MDD at baseline in the somatomotor network and between association and default mode networks. These disruptions in FC in MDD patients trended toward control patterns with ketamine treatment. Furthermore, following serial ketamine infusions, significant decreases in FC were observed between the cerebellum and salience network (SN) (p < 0.05, corrected). Patient remitters showed increased FC between the cerebellum and the striatum prior to treatment that decreased following treatment, whereas non-remitters showed the opposite pattern.

Conclusion: Results support that ketamine treatment leads to neurofunctional plasticity between distinct neural networks that are shown as disrupted in MDD patients. Cortico-striatal-cerebellar loops that encompass the SN could be a potential biomarker for ketamine treatment.
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http://dx.doi.org/10.1017/S0033291720004560DOI Listing
December 2020

Deep Learning of Warping Functions for Shape Analysis.

Conf Comput Vis Pattern Recognit Workshops 2020 Jun 28;2020:3782-3790. Epub 2020 Jul 28.

Ahmanson Lovelace Brain Mapping Center, Department of Neurology, UCLA.

Rate-invariant or reparameterization-invariant matching between functions and shapes of curves, respectively, is an important problem in computer vision and medical imaging. Often, the computational cost of matching using approaches such as dynamic time warping or dynamic programming is prohibitive for large datasets. Here, we propose a deep neural-network-based approach for learning the warping functions from training data consisting of a large number of optimal matches, and use it to predict optimal diffeomorphic warping functions. Results show prediction performance on a synthetic dataset of bump functions and two-dimensional curves from the ETH-80 dataset as well as a significant reduction in computational cost.
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http://dx.doi.org/10.1109/cvprw50498.2020.00441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520101PMC
June 2020

Measurement accuracy of 3-Dimensional mapping technologies versus standard goniometry for angle assessment.

J Pediatr Urol 2020 Oct 26;16(5):547-554. Epub 2020 Aug 26.

Department of Urology, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue Box 951738, Los Angeles, CA, 90095-1738, USA. Electronic address:

Background: A specific aspect of the hypospadias phenotype that may contribute to long-term outcomes is the presence of ventral penile curvature and the adequacy of its surgical correction. The current gold standard to assess this angle is intraoperative goniometry of an erect penis. 3-dimensional (3D) mapping technologies may overcome the limitations of these traditional methods through their combination of digital image and geometric replication to produce consistent 3D digital forms of a physical structure. The aim of this study is to evaluate the measurement accuracy and reliability of handheld 3D mapping technologies versus standard goniometry for angle assessment in a laboratory setting.

Methods: Blocks with specified angles (10-45°) were printed using a Zortrax M200 3D printer (±0.2% accuracy). Following the completion of standardized training, blinded participants measured each block angle using a baseline digit goniometer. Additionally, complete digital models of the blocks were created using 3D mapping technologies. Structured light scanning was completed using an Artec Space Spider and Artec Studio 13. Traditional photogrammetry was completed using a Canon Eos Rebel T5i DSLR camera and Agisoft Metashape Pro. Photogrammetry with a 3D camera was completed using the VECTRA H1 and VECTRA Analysis Module. All 3D models were imported into the software Autodesk Inventor in which automated angle measurements through the central plane were obtained. Statistical analysis was performed to determine the accuracy, precision and reliability of each modality using SAS 9.4 software. The reliability of goniometry and each mapping technology was evaluated using two-way random effect models with absolute agreement.

Results: Six 3D printed blocks were evaluated. 5 digital models per block were created using each of the 3 mapping technologies. Inter-rater reliability of goniometry was moderate (ICC 0.76, 95% CI 0.46, 0.92), whereas all mapping technologies demonstrated excellent test-retest reliability: structured light scanning (ICC 0.99; 95% CI 0.999, 0.999); traditional photogrammetry (0.99; 0.99, 0.99); 3D camera (0.99; 0.99, 0.99). Mean angle measurements and standard error for each angle and modality are provided in the table.

Conclusions: This study demonstrated excellent accuracy, precision and reliability of off-the-shelf, handheld 3D mapping technologies and moderate reliability for goniometry when applied to measurements of angulation in a laboratory setting. The described methods developed in the laboratory for optimization of angle analysis from 3D models are an important step toward reliable, reproducible phenotypic analysis of congenital genitourinary conditions in future intraoperative and database development applications.
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http://dx.doi.org/10.1016/j.jpurol.2020.08.021DOI Listing
October 2020

Modulation of inhibitory control networks relate to clinical response following ketamine therapy in major depression.

Transl Psychiatry 2020 07 30;10(1):260. Epub 2020 Jul 30.

Department of Neurology, Ahmanson-Lovelace Brain Mapping Center, Los Angeles, CA, USA.

Subanesthetic ketamine is found to induce fast-acting and pronounced antidepressant effects, even in treatment resistant depression (TRD). However, it remains unclear how ketamine modulates neural function at the brain systems-level to regulate emotion and behavior. Here, we examined treatment-related changes in the inhibitory control network after single and repeated ketamine therapy in TRD. Forty-seven TRD patients (mean age = 38, 19 women) and 32 healthy controls (mean age = 35, 18 women) performed a functional magnetic resonance imaging (fMRI) response inhibition task at baseline, and 37 patients completed the fMRI task and symptom scales again 24 h after receiving both one and four 0.5 mg/kg intravenous ketamine infusions. Analyses of fMRI data addressed effects of diagnosis, time, and differences between treatment remitters and non-remitters. Significant decreases in brain activation were observed in the inhibitory control network, including in prefrontal and parietal regions, and visual cortex following serial ketamine treatment, p < 0.05 corrected. Remitters were distinguished from non-remitters by having lower functional activation in the supplementary motor area (SMA) prior to treatment, which normalized towards controls following serial ketamine treatment. Results suggest that ketamine treatment leads to neurofunctional plasticity in executive control networks including the SMA during a response-inhibitory task. SMA changes relate to reductions in depressive symptoms, suggesting modulation of this network play an important role in therapeutic response. In addition, early changes in the SMA network during response inhibition appear predictive of overall treatment outcome, and may serve as a biomarker of treatment response.
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http://dx.doi.org/10.1038/s41398-020-00947-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393172PMC
July 2020

Modularity and heterochrony in the evolution of the ceratopsian dinosaur frill.

Ecol Evol 2020 Jul 22;10(13):6288-6309. Epub 2020 May 22.

Integrative Research Center Field Museum of Natural History Chicago IL USA.

The fossil record provides compelling examples of heterochrony at macroevolutionary scales such as the peramorphic giant antlers of the Irish elk. Heterochrony has also been invoked in the evolution of the distinctive cranial frill of ceratopsian dinosaurs such as . Although ceratopsian frills vary in size, shape, and ornamentation, quantitative analyses that would allow for testing hypotheses of heterochrony are lacking. Here, we use geometric morphometrics to examine frill shape variation across ceratopsian diversity and within four species preserving growth series. We then test whether the frill constitutes an evolvable module both across and within species, and compare growth trajectories of taxa with ontogenetic growth series to identify heterochronic processes. Evolution of the ceratopsian frill consisted primarily of progressive expansion of its caudal and caudolateral margins, with morphospace occupation following taxonomic groups. Although taphonomic distortion represents a complicating factor, our data support modularity both across and within species. Peramorphosis played an important role in frill evolution, with acceleration operating early in neoceratopsian evolution followed by progenesis in later diverging cornosaurian ceratopsians. Peramorphic evolution of the ceratopsian frill may have been facilitated by the decoupling of this structure from the jaw musculature, an inference that predicts an expansion of morphospace occupation and higher evolutionary rates among ceratopsids as indeed borne out by our data. However, denser sampling of the meager record of early-diverging taxa is required to test this further.
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http://dx.doi.org/10.1002/ece3.6361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381594PMC
July 2020

Brain Metabolism During A Lower Extremity Voluntary Movement Task in Children With Spastic Cerebral Palsy.

Front Hum Neurosci 2020 25;14:159. Epub 2020 May 25.

Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, United States.

Reduced selective voluntary motor control (SVMC) is a primary impairment due to corticospinal tract (CST) injury in spastic cerebral palsy (CP). There are few studies of brain metabolism in CP and none have examined brain metabolism during a motor task. Nine children with bilateral spastic CP [Age: 6-11 years, Gross Motor Function Classification System (GMFCS) Levels II-V] completed this study. SVMC was evaluated using Selective Control Assessment of the Lower Extremity (SCALE) ranging from 0 (absent) to 10 (normal). Brain metabolism was measured using positron emission tomography (PET) scanning in association with a selective ankle motor task. Whole brain activation maps as well as ROI averaged metabolic activity were correlated with SCALE scores. The contralateral sensorimotor and superior parietal cortex were positively correlated with SCALE scores ( < 0.0005). In contrast, a negative correlation of metabolic activity with SCALE was found in the cerebellum ( < 0.0005). Subsequent ROI analysis showed that both ipsilateral and contralateral cerebellar metabolism correlated with SCALE but the relationship for the ipsilateral cerebellum was stronger ( = 0.80, < 0.001 vs. = 0.46, = 0.045). Decreased cortical and increased cerebellar activation in children with less SVMC may be related to task difficulty, activation of new motor learning paradigms in the cerebellum and potential engagement of alternative motor systems when CSTs are focally damaged. These results support SCALE as a clinical correlate of neurological impairment.
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http://dx.doi.org/10.3389/fnhum.2020.00159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263017PMC
May 2020

Neuroimaging young children and associations with neurocognitive development in a South African birth cohort study.

Neuroimage 2020 10 15;219:116846. Epub 2020 Apr 15.

Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, South Africa; Neuroscience Institute, University of Cape Town, South Africa.

Magnetic resonance imaging (MRI) is an indispensable tool for investigating brain development in young children and the neurobiological mechanisms underlying developmental risk and resilience. Sub-Saharan Africa has the highest proportion of children at risk of developmental delay worldwide, yet in this region there is very limited neuroimaging research focusing on the neurobiology of such impairment. Furthermore, paediatric MRI imaging is challenging in any setting due to motion sensitivity. Although sedation and anesthesia are routinely used in clinical practice to minimise movement in young children, this may not be ethical in the context of research. Our study aimed to investigate the feasibility of paediatric multimodal MRI at age 2-3 years without sedation, and to explore the relationship between cortical structure and neurocognitive development at this understudied age in a sub-Saharan African setting. A total of 239 children from the Drakenstein Child Health Study, a large observational South African birth cohort, were recruited for neuroimaging at 2-3 years of age. Scans were conducted during natural sleep utilising locally developed techniques. T1-MEMPRAGE and T2-weighted structural imaging, resting state functional MRI, diffusion tensor imaging and magnetic resonance spectroscopy sequences were included. Child neurodevelopment was assessed using the Bayley-III Scales of Infant and Toddler Development. Following 23 pilot scans, 216 children underwent scanning and T1-weighted images were obtained from 167/216 (77%) of children (median age 34.8 months). Furthermore, we found cortical surface area and thickness within frontal regions were associated with cognitive development, and in temporal and frontal regions with language development (beta coefficient ≥0.20). Overall, we demonstrate the feasibility of carrying out a neuroimaging study of young children during natural sleep in sub-Saharan Africa. Our findings indicate that dynamic morphological changes in heteromodal association regions are associated with cognitive and language development at this young age. These proof-of-concept analyses suggest similar links between the brain and cognition as prior literature from high income countries, enhancing understanding of the interplay between cortical structure and function during brain maturation.
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http://dx.doi.org/10.1016/j.neuroimage.2020.116846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443699PMC
October 2020

Single and repeated ketamine treatment induces perfusion changes in sensory and limbic networks in major depressive disorder.

Eur Neuropsychopharmacol 2020 04 12;33:89-100. Epub 2020 Feb 12.

Department of Neurology, Ahamason-Lovelace Brain Mapping Center, United States; Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, 635 Charles E Young Drive South Suite, Los Angeles, CA 90095-7334, United States. Electronic address:

Ketamine infusion therapy can produce fast-acting antidepressant effects in patients with major depressive disorder (MDD). Yet, how single and repeated ketamine treatment induces brain systems-level neuroplasticity underlying symptom improvement is unknown. Advanced multiband imaging (MB) pseudo-continuous arterial spin labeling (pCASL) perfusion MRI data was acquired from patients with treatment resistant depression (TRD) (N = 22, mean age=35.2 ± 9.95 SD, 27% female) at baseline, and 24 h after receiving single, and four subanesthetic (0.5 mg/kg) intravenous ketamine infusions. Changes in global and regional CBF were compared across time points, and relationships with overall mood, anhedonia and apathy were examined. Comparisons between patients at baseline and controls (N = 18, mean age=36.11 ± 14.5 SD, 57% female) established normalization of treatment effects. Results showed increased regional CBF in the cingulate and primary and higher-order visual association regions after first ketamine treatment. Baseline CBF in the fusiform, and acute changes in CBF in visual areas were related to symptom improvement after single and repeated ketamine treatment, respectively. In contrast, after serial infusion therapy, decreases in regional CBF were observed in the bilateral hippocampus and right insula with ketamine treatment. Findings demonstrate that neurophysiological changes occurring with single and repeated ketamine treatment follow both a regional and temporal pattern including sensory and limbic regions. Initial changes are observed in the posterior cingulate and precuneus and primary and higher-order visual areas, which relate to clinical responses. However, repeated exposure to ketamine, though not relating to clinical outcome, appears to engage deeper limbic structures and insula. ClinicalTrials.gov: Biomarkers of Fast Acting Therapies in Major Depression, https://clinicaltrials.gov/ct2/show/NCT02165449, NCT02165449.
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http://dx.doi.org/10.1016/j.euroneuro.2020.01.017DOI Listing
April 2020

Hippocampal subregions and networks linked with antidepressant response to electroconvulsive therapy.

Mol Psychiatry 2020 Feb 6. Epub 2020 Feb 6.

Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California Los Angeles, Los Angeles, CA, 90095, USA.

Electroconvulsive therapy (ECT) has been repeatedly linked to hippocampal plasticity. However, it remains unclear what role hippocampal plasticity plays in the antidepressant response to ECT. This magnetic resonance imaging (MRI) study tracks changes in separate hippocampal subregions and hippocampal networks in patients with depression (n = 44, 23 female) to determine their relationship, if any, with improvement after ECT. Voxelwise analyses were restricted to the hippocampus, amygdala, and parahippocampal cortex, and applied separately for responders and nonresponders to ECT. In analyses of arterial spin-labeled (ASL) MRI, nonresponders exhibited increased cerebral blood flow (CBF) in bilateral anterior hippocampus, while responders showed CBF increases in right middle and left posterior hippocampus. In analyses of gray matter volume (GMV) using T1-weighted MRI, GMV increased throughout bilateral hippocampus and surrounding tissue in nonresponders, while responders showed increased GMV in right anterior hippocampus only. Using CBF loci as seed regions, BOLD-fMRI data from healthy controls (n = 36, 19 female) identified spatially separable neurofunctional networks comprised of different brain regions. In graph theory analyses of these networks, functional connectivity within a hippocampus-thalamus-striatum network decreased only in responders after two treatments and after index. In sum, our results suggest that the location of ECT-related plasticity within the hippocampus may differ according to antidepressant outcome, and that larger amounts of hippocampal plasticity may not be conducive to positive antidepressant response. More focused targeting of hippocampal subregions and/or circuits may be a way to improve ECT outcome.
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http://dx.doi.org/10.1038/s41380-020-0666-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415508PMC
February 2020

Cognitive Correlates of Hippocampal Atrophy and Ventricular Enlargement in Adults with or without Mild Cognitive Impairment.

Dement Geriatr Cogn Dis Extra 2019 May-Aug;9(2):281-293. Epub 2019 Aug 13.

Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA.

We analyzed structural magnetic resonance imaging data from 58 cognitively normal and 101 mild cognitive impairment subjects. We used a general linear regression model to study the association between cognitive performance with hippocampal atrophy and ventricular enlargement using the radial distance method. Bilateral hippocampal atrophy was associated with baseline and longitudinal memory performance. Left hippocampal atrophy predicted longitudinal decline in visuospatial function. The multidomain ventricular analysis did not reveal any significant predictors.
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http://dx.doi.org/10.1159/000490044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751474PMC
August 2019

Multimodal Data Registration for Brain Structural Association Networks.

Med Image Comput Comput Assist Interv 2019 Oct 10;11765:373-381. Epub 2019 Oct 10.

Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California Los Angeles, Los Angeles, CA, USA.

We present a method for multimodal brain data registration that aligns shapes of nodal network configurations in an invertible manner. We use ideas from shape analysis to represent an individual subject data configuration as an element on a hypersphere, where geodesics have closed form solutions. The method not only performs inter-subject data registration, but also allows for the construction of a population data template to which all subject data configurations can be registered. Results show compression of data measures and significant reduction in variance after registration. We also observe increased predictive power of regions of interest (ROI) node identification, significant increases in pairwise network connectivity measures, as well as significant increases in canonical correlations with age after registration.
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http://dx.doi.org/10.1007/978-3-030-32245-8_42DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744134PMC
October 2019

Depressive Symptom Dimensions in Treatment-Resistant Major Depression and Their Modulation With Electroconvulsive Therapy.

J ECT 2020 Jun;36(2):123-129

Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX.

Objective: Symptom heterogeneity in major depressive disorder obscures diagnostic and treatment-responsive biomarker identification. Whether symptom constellations are differentially changed by electroconvulsive therapy (ECT) remains unknown. We investigate the clustering of depressive symptoms over the ECT index and whether ECT differentially influences symptom clusters.

Methods: The 17-item Hamilton Depression Rating Scale (HDRS-17) was collected from 111 patients with current depressive episode before and after ECT from 4 independent participating sites of the Global ECT-MRI Research Collaboration. Exploratory factor analysis of HDRS-17 items pre- and post-ECT treatment identified depressive symptom dimensions before and after ECT. A 2-way analysis of covariance was used to determine whether baseline symptom clusters were differentially changed by ECT between treatment remitters (defined as patients with posttreatment HDRS-17 total score ≤8) and nonremitters while controlling for pulse width, titration method, concurrent antidepressant treatment, use of benzodiazepine, and demographic variables.

Results: A 3-factor solution grouped pretreatment HDRS-17 items into core mood/anhedonia, somatic, and insomnia dimensions. A 2-factor solution best described the symptoms at posttreatment despite poorer separation of items. Among remitters, core mood/anhedonia symptoms were significantly more reduced than somatic and insomnia dimensions. No differences in symptom dimension trajectories were observed among nonremitting patients.

Conclusions: Electroconvulsive therapy targets the underlying source of depressive symptomatology and may confer differential degrees of improvement in certain core depressive symptoms. Our findings of differential trajectories of symptom clusters over the ECT index might help related predictive biomarker studies to refine their approaches by identifying predictors of change along each latent symptom dimension.
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http://dx.doi.org/10.1097/YCT.0000000000000623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044066PMC
June 2020

Elastic Registration of Single Subject Task Based fMRI Signals.

Med Image Comput Comput Assist Interv 2018 Sep 13;11072:154-162. Epub 2018 Sep 13.

Ahmanson-Lovelace Brain Mapping Center, Department of Neurology University of California Los Angeles, CA.

Single subject task-based fMRI analyses generally suffer from low detection sensitivity with parameter estimates from the general linear model (GLM) lying below the significance threshold especially for similar contrasts or conditions. In this paper, we present a shape-based approach for alignment of condition-specific time course activity for single subject task-based fMRI. Our approach extracts signals for each condition from the entire time course, constructs an unbiased average of those signals, and warps each signal to the mean. As the warping is diffeomorphic, non-linear and allows large deformations of time series if required, we term this approach as elastic functional registration. On a single subject level, our method significantly detects more clusters and more activated voxels in relevant subcortical regions in healthy controls.
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http://dx.doi.org/10.1007/978-3-030-00931-1_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521968PMC
September 2018

Variations in Hippocampal White Matter Diffusivity Differentiate Response to Electroconvulsive Therapy in Major Depression.

Biol Psychiatry Cogn Neurosci Neuroimaging 2019 03 14;4(3):300-309. Epub 2018 Nov 14.

Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California, Los Angeles, Los Angeles, California; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California. Electronic address:

Background: Electroconvulsive therapy (ECT) is an effective treatment for severe depression and is shown to increase hippocampal volume and modulate hippocampal functional connectivity. Whether variations in hippocampal structural connectivity occur with ECT and relate to clinical response is unknown.

Methods: Patients with major depression (n = 36, 20 women, age 41.49 ± 13.57 years) underwent diffusion magnetic resonance imaging at baseline and after ECT. Control subjects (n = 32, 17 women, age 39.34 ± 12.27 years) underwent scanning twice. Functionally defined seeds in the left and right anterior hippocampus and probabilistic tractography were used to extract tract volume and diffusion metrics (fractional anisotropy and axial, radial, and mean diffusivity). Statistical analyses determined effects of ECT and time-by-response group interactions (>50% change in symptoms before and after ECT defined response). Differences between baseline measures across diagnostic groups and in association with treatment outcome were also examined.

Results: Significant effects of ECT (all p < .01) and time-by-response group interactions (all p < .04) were observed for axial, radial, and mean diffusivity for right, but not left, hippocampal pathways. Follow-up analyses showed that ECT-related changes occurred in responders only (all p < .01) as well as in relation to change in mood examined continuously (all p < .004). Baseline measures did not relate to symptom change or differ between patients and control subjects. All measures remained stable across time in control subjects. No significant effects were observed for fractional anisotropy and volume.

Conclusions: Structural connectivity of hippocampal neural circuits changed with ECT and distinguished treatment responders. The findings suggested neurotrophic, glial, or inflammatory response mechanisms affecting axonal integrity.
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http://dx.doi.org/10.1016/j.bpsc.2018.11.003DOI Listing
March 2019

Mechanisms of Antidepressant Response to Electroconvulsive Therapy Studied With Perfusion Magnetic Resonance Imaging.

Biol Psychiatry 2019 03 5;85(6):466-476. Epub 2018 Oct 5.

Ahmanson-Lovelace Brain Mapping Center, University of California Los Angeles, Los Angeles, California; Department of Neurology, and Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California.

Background: Converging evidence suggests that electroconvulsive therapy (ECT) induces neuroplasticity in patients with severe depression, though how this relates to antidepressant response is less clear. Arterial spin-labeled functional magnetic resonance imaging tracks absolute changes in cerebral blood flow (CBF) linked with brain function and offers a potentially powerful tool when observing neurofunctional plasticity with functional magnetic resonance imaging.

Methods: Using arterial spin-labeled functional magnetic resonance imaging, we measured global and regional CBF associated with clinically prescribed ECT and therapeutic response in patients (n = 57, 30 female) before ECT, after two treatments, after completing an ECT treatment "index" (∼4 weeks), and after long-term follow-up (6 months). Age- and sex-matched control subjects were also scanned twice (n = 36, 19 female), ∼4 weeks apart.

Results: Patients with lower baseline global CBF were more likely to respond to ECT. Regional CBF increased in the right anterior hippocampus in all patients irrespective of clinical outcome, both after 2 treatments and after ECT index. However, hippocampal CBF increases postindex were more pronounced in nonresponders. ECT responders exhibited CBF increases in the dorsomedial thalamus and motor cortex near the vertex ECT electrode, as well as decreased CBF within lateral frontoparietal regions.

Conclusions: ECT induces functional neuroplasticity in the hippocampus, which could represent functional precursors of ECT-induced increases in hippocampal volume reported previously. However, excessive functional neuroplasticity within the hippocampus may not be conducive to positive clinical outcome. Instead, our results suggest that although hippocampal plasticity may contribute to antidepressant response in ECT, balanced plasticity in regions relevant to seizure physiology including thalamocortical networks may also play a critical role.
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http://dx.doi.org/10.1016/j.biopsych.2018.09.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380917PMC
March 2019

Measuring Brain Connectivity via Shape Analysis of fMRI Time Courses and Spectra.

Connectomics Neuroimaging (2017) 2017 09 2;10511:125-133. Epub 2017 Sep 2.

Ahmanson-Lovelace Brain Mapping Center, Department of Neurology University of California Los Angeles, CA.

We present a shape matching approach for functional magnetic resonance imaging (fMRI) time course and spectral alignment. We use ideas from differential geometry and functional data analysis to define a functional representation for fMRI signals. The space of fMRI functions is then equipped with a reparameterization invariant Riemannian metric that enables elastic alignment of both amplitude and phase of the fMRI time courses as well as their power spectral densities. Experimental results show significant increases in pairwise node to node correlations and coherences following alignment. We apply this method for finding group differences in connectivity between patients with major depression and healthy controls.
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http://dx.doi.org/10.1007/978-3-319-67159-8_15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018059PMC
September 2017

Fronto-Temporal Connectivity Predicts ECT Outcome in Major Depression.

Front Psychiatry 2018 21;9:92. Epub 2018 Mar 21.

Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California Los Angeles, Los Angeles, CA, United States.

Background: Electroconvulsive therapy (ECT) is arguably the most effective available treatment for severe depression. Recent studies have used MRI data to predict clinical outcome to ECT and other antidepressant therapies. One challenge facing such studies is selecting from among the many available metrics, which characterize complementary and sometimes non-overlapping aspects of brain function and connectomics. Here, we assessed the ability of aggregated, functional MRI metrics of basal brain activity and connectivity to predict antidepressant response to ECT using machine learning.

Methods: A radial support vector machine was trained using arterial spin labeling (ASL) and blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) metrics from n = 46 (26 female, mean age 42) depressed patients prior to ECT (majority right-unilateral stimulation). Image preprocessing was applied using standard procedures, and metrics included cerebral blood flow in ASL, and regional homogeneity, fractional amplitude of low-frequency modulations, and graph theory metrics (strength, local efficiency, and clustering) in BOLD data. A 5-repeated 5-fold cross-validation procedure with nested feature-selection validated model performance. Linear regressions were applied post hoc to aid interpretation of discriminative features.

Results: The range of balanced accuracy in models performing statistically above chance was 58-68%. Here, prediction of non-responders was slightly higher than for responders (maximum performance 74 and 64%, respectively). Several features were consistently selected across cross-validation folds, mostly within frontal and temporal regions. Among these were connectivity strength among: a fronto-parietal network [including left dorsolateral prefrontal cortex (DLPFC)], motor and temporal networks (near ECT electrodes), and/or subgenual anterior cingulate cortex (sgACC).

Conclusion: Our data indicate that pattern classification of multimodal fMRI metrics can successfully predict ECT outcome, particularly for individuals who will not respond to treatment. Notably, connectivity with networks highly relevant to ECT and depression were consistently selected as important predictive features. These included the left DLPFC and the sgACC, which are both targets of other neurostimulation therapies for depression, as well as connectivity between motor and right temporal cortices near electrode sites. Future studies that probe additional functional and structural MRI metrics and other patient characteristics may further improve the predictive power of these and similar models.
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http://dx.doi.org/10.3389/fpsyt.2018.00092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871748PMC
March 2018

Inter and intra-hemispheric structural imaging markers predict depression relapse after electroconvulsive therapy: a multisite study.

Transl Psychiatry 2017 12 8;7(12):1270. Epub 2017 Dec 8.

Department of Neurology, UCLA, Ahmanson-Lovelace Brain Mapping Center, Los Angeles, USA.

Relapse of depression following treatment is high. Biomarkers predictive of an individual's relapse risk could provide earlier opportunities for prevention. Since electroconvulsive therapy (ECT) elicits robust and rapidly acting antidepressant effects, but has a >50% relapse rate, ECT presents a valuable model for determining predictors of relapse-risk. Although previous studies have associated ECT-induced changes in brain morphometry with clinical response, longer-term outcomes have not been addressed. Using structural imaging data from 42 ECT-responsive patients obtained prior to and directly following an ECT treatment index series at two independent sites (UCLA: n = 17, age = 45.41±12.34 years; UNM: n = 25; age = 65.00±8.44), here we test relapse prediction within 6-months post-ECT. Random forests were used to predict subsequent relapse using singular and ratios of intra and inter-hemispheric structural imaging measures and clinical variables from pre-, post-, and pre-to-post ECT. Relapse risk was determined as a function of feature variation. Relapse was well-predicted both within site and when cohorts were pooled where top-performing models yielded balanced accuracies of 71-78%. Top predictors included cingulate isthmus asymmetry, pallidal asymmetry, the ratio of the paracentral to precentral cortical thickness and the ratio of lateral occipital to pericalcarine cortical thickness. Pooling cohorts and predicting relapse from post-treatment measures provided the best classification performances. However, classifiers trained on each age-disparate cohort were less informative for prediction in the held-out cohort. Post-treatment structural neuroimaging measures and the ratios of connected regions commonly implicated in depression pathophysiology are informative of relapse risk. Structural imaging measures may have utility for devising more personalized preventative medicine approaches.
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http://dx.doi.org/10.1038/s41398-017-0020-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802464PMC
December 2017

A Riemannian Framework for Linear and Quadratic Discriminant Analysis on the Tangent Space of Shapes.

Conf Comput Vis Pattern Recognit Workshops 2017 24;2017:726-734. Epub 2017 Aug 24.

UCLA Brain Mapping Center, University of California, Los Angeles, Los Angeles, CA, USA.

We present a Riemannian framework for linear and quadratic discriminant classification on the tangent plane of the shape space of curves. The shape space is infinite dimensional and is constructed out of square root velocity functions of curves. We introduce the notion of mean and covariance of shape-valued random variables and samples from a tangent space to the pre-shapes (invariant to translation and scaling) and then extend it to the full shape space (rotational invariance). The shape observations from the population are approximated by coefficients of a Fourier basis of the tangent space. The algorithms for linear and quadratic discriminant analysis are then defined using reduced dimensional features obtained by projecting the original shape observations on to the truncated Fourier basis. We show classification results on synthetic data and shapes of cortical sulci, corpus callosum curves, as well as facial midline curve profiles from patients with fetal alcohol syndrome (FAS).
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http://dx.doi.org/10.1109/CVPRW.2017.102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710852PMC
August 2017

Superficial white matter damage in anti-NMDA receptor encephalitis.

J Neurol Neurosurg Psychiatry 2018 05 3;89(5):518-525. Epub 2017 Nov 3.

Department of Neurology, Charité University Medicine Berlin, Berlin, Germany.

Background: Clinical brain MRI is normal in the majority of patients with anti--methyl-D-aspartate receptor (NMDAR) encephalitis. However, extensive deep white matter damage wasrecently identifiedin these patients using diffusion weighted imaging. Here, our aim was to study a particularly vulnerable brain compartment, the late myelinating superficial white matter.

Methods: Forty-six patients with anti-NMDAR encephalitis were included. Ten out of these were considered neurologically recovered (modified Rankin scale of zero), while 36 patients were non-recovered. In addition, 30 healthy controls were studied. MRI data were collected from all subjects and superficial white matter mean diffusivity derived from diffusion tensor imaging was compared between groups in whole brain, lobar and vertex-based analyses. Patients underwent comprehensive cognitive testing, and correlation analyses were performed between cognitive performance and superficial white matter integrity.

Results: Non-recovered patients showed widespread superficial white matter damage in comparison to recovered patients and healthy controls. Vertex-based analyses revealed that damage predominated in frontal and temporal lobes. In contrast, the superficial white matter was intact in recovered patients. Importantly, persistent cognitive impairments in working memory, verbal memory, visuospatial memory and attention significantly correlated with damage of the superficial white matter in patients.

Conclusions: Anti-NMDAR encephalitis is associated with extensive superficial white matter damage in patients with incomplete recovery. The strong association with impairment in several cognitive domains highlights the clinical relevance of white matter damage in this disorder and warrants investigations of the underlying pathophysiological mechanisms.
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http://dx.doi.org/10.1136/jnnp-2017-316822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899027PMC
May 2018

Short- and Long-term Cognitive Outcomes in Patients With Major Depression Treated With Electroconvulsive Therapy.

J ECT 2017 Dec;33(4):278-285

Objectives: The risk of cognitive impairment is a concern for patients with major depressive disorder receiving electroconvulsive therapy (ECT). Here, we evaluate the acute, short-term and long-term effects of ECT on tests of processing speed, executive function, memory, and attention.

Methods: Forty-four patients with major depressive disorder receiving ECT (61% right unilateral, 39% mixed right unilateral-bitemporal, left unilateral, and/or bitemporal lead placement) underwent a cognitive battery prior to ECT (T1), after 2 sessions (T2), and at the end of the index (T3). Thirty-two patients returned for a 6-month follow-up (T4). Thirty-three control subjects were assessed at 2 times approximately 4 weeks apart (C1 and C2).

Results: At baseline, patients showed deficits in processing speed, executive function, and memory compared with control subjects. Including depression severity and lead placement covariates, linear mixed-model analysis showed significant improvement in only processing speed between T1 and T3 and between T1 and T4 in patients. An acute decline in attention and verbal memory was observed at T2, but performance returned to baseline levels at T3. Longitudinal cognitive outcomes did not differ in patients defined as ECT responders/nonresponders.

Limitations: Episodic memory was not measured, and medications were not controlled between T3 and T4. Control subjects also showed improvements in processing speed, suggesting practice effects for some measures.

Conclusions: In this naturalistic ECT treatment study, results show that the initiation of ECT may transiently affect memory and executive function, but cognition is largely unaffected during and after ECT. Whereas some functions might improve, others will at least remain stable up to 6 months following the ECT index.
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http://dx.doi.org/10.1097/YCT.0000000000000426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705261PMC
December 2017

DATA-DRIVEN CLUSTER SELECTION FOR SUBCORTICAL SHAPE AND CORTICAL THICKNESS PREDICTS RECOVERY FROM DEPRESSIVE SYMPTOMS.

Proc IEEE Int Symp Biomed Imaging 2017 Apr 19;2017:502-506. Epub 2017 Jun 19.

Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, UCLA.

Patients with major depressive disorder (MDD) who do not achieve full symptomatic recovery after antidepressant treatment have a higher risk of relapse. Compared to pharmacotherapies, electroconvulsive therapy (ECT) more rapidly produces a greater extent of response in severely depressed patients. However, prediction of which candidates are most likely to improve after ECT remains challenging. Using structural MRI data from 42 ECT patients scanned prior to ECT treatment, we developed a random forest classifier based on data-driven shape cluster selection and cortical thickness features to predict remission. Right hemisphere hippocampal shape and right inferior temporal cortical thickness was most predictive of remission, with the predicted probability of recovery decreasing when these regions were thicker prior to treatment. Remission was predicted with an average 73% balanced accuracy. Classification of MRI data may help identify treatment-responsive patients and aid in clinical decision-making. Our results show promise for the development of personalized treatment strategies.
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http://dx.doi.org/10.1109/ISBI.2017.7950570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354762PMC
April 2017

Relationships Between Altered Functional Magnetic Resonance Imaging Activation and Cortical Thickness in Patients With Euthymic Bipolar I Disorder.

Biol Psychiatry Cogn Neurosci Neuroimaging 2016 Nov;1(6):507-517

Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA.

Background: Performance during cognitive control functional magnetic resonance imaging (fMRI) tasks are associated with frontal lobe hypoactivation in patients with bipolar disorder, even while euthymic. Here, we study the structural underpinnings for this functional abnormality simultaneously with brain activation data.

Methods: In a sample of ninety adults (45 with inter-episode Bipolar I disorder and 45 healthy controls), we explored whether abnormal functional activation patterns in bipolar euthymic subjects during a Go-NoGo fMRI task are associated with regional deficits in cortical gray matter thickness in the same regions. Cross-sectional differences in fMRI activation were used to form hypotheses for region-of-interest cortical gray matter thickness analyses. fMRI BOLD to structural magnetic resonance imaging (sMRI) thickness correlations were conducted across the sample and within patients and controls separately.

Results: During response inhibition (NoGo minus Go), bipolar subjects showed significant hypoactivation and reduced thickness in the inferior frontal cortex (IFC), superior frontal gyrus and cingulate compared to controls. Cingulate hypoactivation corresponded with reduced regional thickness. A significant activation by disease state interaction was observed with thickness in left prefrontal areas.

Conclusions: Reduced cingulate fMRI activation is associated with reduced cortical thickness. In the left frontal lobe, a thinner cortex was associated with increased fMRI activation in patients, but showed a reverse trend in controls. These findings suggest that reduced activation in the IFC and cingulate during a response inhibition task may have an underlying structural etiology, which may explain task-related functional hypoactivation that persists even when patients are euthymic.
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http://dx.doi.org/10.1016/j.bpsc.2016.06.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5157843PMC
November 2016

Neural correlates of proactive and reactive aggression in adolescent twins.

Aggress Behav 2017 May 21;43(3):230-240. Epub 2016 Oct 21.

Department of Psychology, University of Southern California, Los Angeles, California.

Verbal and physical aggression begin early in life and steadily decline thereafter in normal development. As a result, elevated aggressive behavior in adolescence may signal atypical development and greater vulnerability for negative mental and health outcomes. Converging evidence suggests that brain disturbances in regions involved in impulse control, emotional regulation, and sensation seeking may contribute to heightened aggression. However, little is known regarding the neural mechanisms underlying subtypes of aggression (i.e., proactive and reactive aggression) and whether they differ between males and females. Using a sample of 106 14-year-old adolescent twins, this study found that striatal enlargement was associated with both proactive and reactive aggression. We also found that volumetric alterations in several frontal regions including smaller middle frontal and larger orbitofrontal cortex were correlated with higher levels of aggression in adolescent twins. In addition, cortical thickness analysis showed that thickness alterations in many overlapping regions including middle frontal, superior frontal, and anterior cingulate cortex and temporal regions were associated with aggression in adolescent twins. Results support the involvement of fronto-limbic-striatal circuit in the etiology of aggression during adolescence. Aggr. Behav. 43:230-240, 2017. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ab.21683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192547PMC
May 2017

Neurochemical correlates of rapid treatment response to electroconvulsive therapy in patients with major depression.

J Psychiatry Neurosci 2017 01;42(1):6-16

From the Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California, Los Angeles, Calif., USA (Njau, Joshi, Leaver, Vasavada, Woods, Narr); the Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Calif., USA (Espinoza, Woods, Narr); and the Department of Mathematics, University of Valencia, Valencia, Spain (Marquina).

Background: Electroconvulsive therapy (ECT) is a highly effective brain stimulation treatment for severe depression. Identifying neurochemical changes linked with ECT may point to biomarkers and predictors of successful treatment response.

Methods: We used proton magnetic resonance spectroscopy (1H-MRS) to measure longitudinal changes in glutamate/glutamine (Glx), creatine (Cre), choline (Cho) and -acetylaspartate (NAA) in the dorsal (dACC) and subgenual anterior cingulate cortex (sgACC) and bilateral hippocampus in patients receiving ECT scanned at baseline, after the second ECT session and after the ECT treatment series. Patients were compared with demographically similar controls at baseline. Controls were assessed twice to establish normative values and variance.

Results: We included 50 patients (mean age 43.78 ± 14 yr) and 33 controls (mean age 39.33 ± 12 yr) in our study. Patients underwent a mean of 9 ± 4.1 sessions of ECT. At baseline, patients showed reduced Glx in the sgACC, reduced NAA in the left hippocampus and increased Glx in the left hippocampus relative to controls. ECT was associated with significant increases in Cre in the dACC and sgACC and decreases in NAA in the dACC and right hippocampus. Lower NAA levels in the dACC at baseline predicted reductions in depressive symptoms. Both ECT and symptom improvement were associated with decreased Glx in the left hippocampus and increased Glx in the sgACC.

Limitations: Attrition and clinical heterogeneity may have masked more subtle findings.

Conclusion: ECT elicits robust effects on brain chemistry, impacting Cre, NAA and Glx, which suggests restorative and neurotrophic processes. Differential effects of Glx in the sgACC and hippocampus, which approach control values with treatment, may reflect previously implicated underactive cortical and overactive subcortical limbic circuitry in patients with major depression. NAA levels at baseline are predictive of therapeutic outcome and could inform future treatment strategies.
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http://dx.doi.org/10.1503/jpn.150177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5373714PMC
January 2017

Variations in myo-inositol in fronto-limbic regions and clinical response to electroconvulsive therapy in major depression.

J Psychiatr Res 2016 09 28;80:45-51. Epub 2016 May 28.

Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California Los Angeles, 635 Charles E Young Drive S #225, Los Angeles, CA, 90095, USA; Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, 200 UCLA Medical Plaza #265, Los Angeles, CA, 90095, USA. Electronic address:

Though electroconvulsive therapy (ECT) is an established treatment for severe depression, the neurobiological factors accounting for the clinical effects of ECT are largely unknown. Myo-inositol, a neurometabolite linked with glial activity, is reported as reduced in fronto-limbic regions in patients with depression. Whether changes in myo-inositol relate to the antidepressant effects of ECT is unknown. Using magnetic resonance spectroscopy ((1)H-MRS), we measured dorsomedial anterior cingulate cortex (dmACC) and left and right hippocampal myo-inositol in 50 ECT patients (mean age: 43.78, 14 SD) and 33 controls (mean age: 39.33, 12 SD) to determine cross sectional effects of diagnosis and longitudinal effects of ECT. Patients were scanned prior to treatment, after the second ECT and at completion of the ECT index series. Controls were scanned twice at intervals corresponding to patients' baseline and end of treatment scans. Myo-inositol increased over the course of ECT in the dmACC (p = 0.042). A significant hemisphere by clinical response effect was observed for the hippocampus (p = 0.003) where decreased myo-inositol related to symptom improvement in the left hippocampus. Cross-sectional differences between patients and controls at baseline were not detected. Changes in myo-inositol observed in the dmACC in association with ECT and in the hippocampus in association with ECT-related clinical response suggest the mechanisms of ECT could include gliogenesis or a reversal of gliosis that differentially affect dorsal and ventral limbic regions. Change in dmACC myo-inositol diverged from control values with ECT suggesting compensation, while hippocampal change suggested normalization.
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http://dx.doi.org/10.1016/j.jpsychires.2016.05.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4980182PMC
September 2016
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