Publications by authors named "Guldamla Kalender"

5 Publications

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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

Combining neuroimaging and behavior to discriminate children with attention deficit-hyperactivity disorder with and without prenatal alcohol exposure.

Brain Imaging Behav 2021 Jun 5. Epub 2021 Jun 5.

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

In many patients, ostensible idiopathic attention deficit-hyperactivity disorder (ADHD) may actually stem from covert prenatal alcohol exposure (PAE), a treatment-relevant distinction. This study attempted a receiver-operator characteristic (ROC) classification of children with ADHD into those with PAE (ADHD+PAE) and those without (ADHD-PAE) using neurobehavioral instruments alongside magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) of supraventricular brain white matter. Neurobehavioral, MRS, and DTI endpoints had been suggested by prior findings. Participants included children aged 8-13 years, 23 with ADHD+PAE, 19 with familial ADHD-PAE, and 28 typically developing (TD) controls. With area-under-the-curve (AUC) >0.90, the Conners 3 Parent Rating Scale Inattention (CIn) and Hyperactivity/Impulsivity (CHp) scores and the Behavioral Regulation Index (BRI) of the Behavior Rating Inventory of Executive Function (BRIEF2) excellently distinguished the clinical groups from TD, but not from each other (AUC < 0.70). Combinations of MRS glutamate (Glu) and N-acetyl-compounds (NAA) and DTI mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) yielded "good" (AUC > 0.80) discrimination. Neuroimaging combined with CIn and BRI achieved AUC 0.72 and AUC 0.84, respectively. But neuroimaging combined with CHp yielded 14 excellent combinations with AUC ≥ 0.90 (all p < 0.0005), the best being Glu·AD·RD·CHp/(NAA·FA) (AUC 0.92, sensitivity 1.00, specificity 0.82, p < 0.0005). Using Cho in lieu of Glu yielded AUC 0.83. White-matter microstructure and metabolism may assist efforts to discriminate ADHD etiologies and to detect PAE, beyond the ability of commonly used neurobehavioral measures alone.
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http://dx.doi.org/10.1007/s11682-021-00477-wDOI Listing
June 2021

Neuroimaging of Supraventricular Frontal White Matter in Children with Familial Attention-Deficit Hyperactivity Disorder and Attention-Deficit Hyperactivity Disorder Due to Prenatal Alcohol Exposure.

Neurotox Res 2021 Aug 22;39(4):1054-1075. Epub 2021 Mar 22.

Division of Child & Adolescent Psychiatry, Jane & Terry Semel Instutute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.

Attention-deficit hyperactivity disorder (ADHD) is common in patients with (ADHD+PAE) and without (ADHD-PAE) prenatal alcohol exposure (PAE). Many patients diagnosed with idiopathic ADHD actually have covert PAE, a treatment-relevant distinction. To improve differential diagnosis, we sought to identify brain differences between ADHD+PAE and ADHD-PAE using neurobehavioral, magnetic resonance spectroscopy, and diffusion tensor imaging metrics that had shown promise in past research. Children 8-13 were recruited in three groups: 23 ADHD+PAE, 19 familial ADHD-PAE, and 28 typically developing controls (TD). Neurobehavioral instruments included the Conners 3 Parent Behavior Rating Scale and the Delis-Kaplan Executive Function System (D-KEFS). Two dimensional magnetic resonance spectroscopic imaging was acquired from supraventricular white matter to measure N-acetylaspartate compounds, glutamate, creatine + phosphocreatine (creatine), and choline-compounds (choline). Whole brain diffusion tensor imaging was acquired and used to to calculate fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity from the same superventricular white matter regions that produced magnetic resonance spectroscopy data. The Conners 3 Parent Hyperactivity/Impulsivity Score, glutamate, mean diffusivity, axial diffusivity, and radial diffusivity were all higher in ADHD+PAE than ADHD-PAE. Glutamate was lower in ADHD-PAE than TD. Within ADHD+PAE, inferior performance on the D-KEFS Tower Test correlated with higher neurometabolite levels. These findings suggest white matter differences between the PAE and familial etiologies of ADHD. Abnormalities detected by magnetic resonance spectroscopy and diffusion tensor imaging co-localize in supraventricular white matter and are relevant to executive function symptoms of ADHD.
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http://dx.doi.org/10.1007/s12640-021-00342-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442735PMC
August 2021

Stimulation of the right entorhinal white matter enhances visual memory encoding in humans.

Brain Stimul 2021 Jan-Feb;14(1):131-140. Epub 2020 Dec 3.

Department of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, 300 Stein Plaza, Los Angeles, CA, 90095, USA; Department of Psychiatry and Biobehavioral Sciences, Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA, University of California, Los Angeles, 760 Westwood Plaza, Los Angeles, CA, 90095, USA; Department of Psychology, University of California, Los Angeles, 502 Portola Plaza, Los Angeles, CA, 90095, USA; Department of Bioengineering, University of California, Los Angeles, 410 Westwood Plaza, Los Angeles, CA, 90095, USA. Electronic address:

Background: While deep brain stimulation has been successful in treating movement disorders, such as in Parkinson's disease, its potential application in alleviating memory disorders is inconclusive.

Objective/hypothesis: We investigated the role of the location of the stimulating electrode on memory improvement and hypothesized that entorhinal white versus gray matter stimulation would have differential effects on memory.

Methods: Intracranial electrical stimulation was applied to the entorhinal area of twenty-two participants with already implanted electrodes as they completed visual memory tasks.

Results: We found that stimulation of right entorhinal white matter during learning had a beneficial effect on subsequent memory, while stimulation of adjacent gray matter or left-sided stimulation was ineffective. This finding was consistent across three different visually guided memory tasks.

Conclusions: Our results highlight the importance of precise stimulation site on modulation of human hippocampal-dependent memory and suggest that stimulation of afferent input into the right hippocampus may be an especially promising target for enhancement of visual memory.
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http://dx.doi.org/10.1016/j.brs.2020.11.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855810PMC
December 2020

Dorsolateral prefrontal γ-aminobutyric acid in patients with treatment-resistant depression after transcranial magnetic stimulation measured with magnetic resonance spectroscopy

J Psychiatry Neurosci 2019 Nov;44(6):386-394

From the Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles (Levitt, Diaz, Cook, Ginder, Krantz, Minzenberg, Vince-Cruz, Nguyen, Leuchter); the Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles (Levitt, Kalender, O’Neill, Cook, Krantz, Minzenberg, Leuchter); the Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles (Kalender); the Division of Child and Adolescent Psychiatry, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles (Levitt, O’Neill); the Department of Bioengineering, Henry Samueli School of Engineering at Applied Science at UCLA, Los Angeles (Cook); the Department of Neurology, UCLA David Geffen School of Medicine at UCLA, Los Angeles (Alger); the Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas (Alger); and the NeuroSpectroScopics, LCC, Sherman Oaks, California (Alger).

Background: The therapeutic mechanism of repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD) may involve modulation of γ-aminobutyric acid (GABA) levels. We used proton magnetic resonance spectroscopy (MRS) to assess changes in GABA levels at the site of rTMS in the left dorsolateral prefrontal cortex (DLPFC).

Methods: In 26 adults with TRD, we used Mescher–Garwood point-resolved spectroscopy (MEGA-PRESS) spectral-editing MRS to measure GABA in the left DLPFC before and after standard clinical treatment with rTMS. All participants but 1 were medicated, including 12 patients on GABA agonist agents.

Results: Mean GABA in the DLPFC increased 10.0% (p = 0.017) post-rTMS in the overall sample. As well, GABA increased significantly in rTMS responders (n = 12; 23.6%, p = 0.015) but not in nonresponders (n = 14; 4.1%, p = not significant). Changes in GABA were not significantly affected by GABAergic agonists, but clinical response was less frequent (p = 0.005) and weaker (p = 0.035) in the 12 participants who were receiving GABA agonists concomitant with rTMS treatment.

Limitations: This study had an open-label design in a population receiving naturalistic treatment.

Conclusion: Treatment using rTMS was associated with increases in GABA levels at the stimulation site in the left DLPFC, and the degree of GABA change was related to clinical improvement. Participants receiving concomitant treatment with a GABA agonist were less likely to respond to rTMS. These findings were consistent with earlier studies showing the effects of rTMS on GABA levels and support a GABAergic model of depression.
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http://dx.doi.org/10.1503/jpn.180230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821508PMC
November 2019
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