Publications by authors named "Kelvin O Lim"

209 Publications

Interoception Underlies Therapeutic Effects of Mindfulness Meditation for Post-Traumatic Stress Disorder: A Randomized Clinical Trial.

Biol Psychiatry Cogn Neurosci Neuroimaging 2021 Oct 21. Epub 2021 Oct 21.

Department of Psychiatry, University of Minnesota, Minneapolis, MN, 55455, USA; Veterans Affairs Health Care System, Minneapolis, MN, 55417, USA.

Background: Mindfulness-based interventions have proven efficacy in treating post-traumatic stress disorder (PTSD) but the neurobiological mechanism underlying the therapeutic effects is unknown. As mindfulness meditation cultivates attention to the present-moment and bodily sensations, neural functions related to interoception (i.e., central processes of bodily signals) might be such a mechanism.

Methods: We conducted a clinical trial in which veterans with PTSD were randomly assigned to receive an 8-week mindfulness-based stress reduction (MBSR) intervention (n = 47) or an active control intervention (present-centered group therapy; PCGT; n = 51). We assessed pre- and post-intervention PTSD symptoms and electroencephalography (EEG) measures of neural outcomes, including spontaneous brain activity, cognitive task-related brain responses, and interoceptive brain responses (heartbeat-evoked brain responses [HEBR]). We conducted statistical causal mediation analyses using treatment type as a predictor, and pre- and post-intervention measures of symptom severity as treatment response, and the neural outcomes as mediators.

Results: Compared to controls, the MBSR group had greater improvements in PTSD symptoms and increases in spontaneous alpha (8-13 Hz) power, task-related frontal theta power (4-7 Hz in 140-220 ms post-stimulus), and frontal theta HEBR (3-5 Hz and 265-336 ms post-R-peak). The mediation analysis using latent difference score modeling revealed that only changes in frontal theta HEBR mediated the MBSR treatment effect.

Conclusions: Mindfulness meditation improves brain functions of attentional control and resting brain states reflective of internally oriented relaxation. However, interoceptive neural functions enhanced by MBSR appear to be a primary cerebral mechanism that improves symptoms of PTSD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bpsc.2021.10.005DOI Listing
October 2021

Characterization of Comorbid Posttraumatic Stress Disorder and Major Depressive Disorder Using Ketamine as an Experimental Medicine Probe .

J Psychiatr Brain Sci 2021 29;6. Epub 2021 Jun 29.

Department of Psychiatry & Behavioral Sciences, University of Minnesota Medical School, Minneapolis, MN 55454, USA.

Comorbid posttraumatic stress disorder and major depressive disorder (PTSD + MDD) is the most common pathological response to trauma, yet despite their synergistic detriment to health, knowledge regarding the neurobiological mechanism underlying PTSD + MDD is extremely limited. This study proposes a novel model of PTSD + MDD that is built on biological systems shown to underlay PTSD + MDD and takes advantage of ketamine's unique suitability to probe PTSD + MDD due to its rescue of stress-related neuroplasticity deficits. The central hypothesis is that changes in PTSD + MDD clinical symptoms are associated with functional connectivity changes and cognitive dysfunction and that ketamine infusions improve clinical symptoms by correction of functional connectivity changes and improvement in cognition. Participants with PTSD + MDD ( = 42) will be randomized to receive a series of six ketamine infusions or saline-placebo over three weeks. Pre/post-measures will include: (1) neuroimaging; (2) cognitive functioning task performance; and (3) PTSD, MDD, and rumination self-report measures. These measures will also be collected once in a trauma-exposed group including PTSD-only ( = 10), trauma-exposed-MDD (TE-MDD; = 10), and healthy controls (HC, = 21). Successful completion of the study will strongly support the concept of a biologically-based model of PTSD + MDD. The results will (1) identify functional imaging signatures of the mechanisms underpinning pathological responses to trauma, (2) shift focus from mono-diagnostic silos to unified biological and behavioral disease processes and, thus, (3) inform interventions to correct dysregulation of PTSD + MDD symptom clusters thereby supporting more precise treatments and better outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.20900/jpbs.20210012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500463PMC
June 2021

The psychosis human connectome project: An overview.

Neuroimage 2021 11 30;241:118439. Epub 2021 Jul 30.

Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, United States; Department of Psychology, University of Minnesota, Minneapolis, MN, United State; Minneapolis Veterans Affairs Medical Center, 1 Veterans Drive, Minneapolis, MN 55417, United State. Electronic address:

Investigations within the Human Connectome Project have expanded to include studies focusing on brain disorders. This paper describes one of the investigations focused on psychotic psychopathology: The psychosis Human Connectome Project (P-HCP). The data collected as part of this project were multimodal and derived from clinical assessments of psychopathology, cognitive assessments, instrument-based motor assessments, blood specimens, and magnetic resonance imaging (MRI) data. The dataset will be made publicly available through the NIMH Data Archive. In this report we provide specific information on how the sample of participants was obtained and characterized and describe the experimental tasks and procedures used to probe neural functions involved in psychotic disorders that may also mark genetic liability for psychotic psychopathology. Our goal in this paper is to outline the data acquisition process so that researchers intending to use these publicly available data can plan their analyses. MRI data described in this paper are limited to data acquired at 3 Tesla. A companion paper describes the study's 7 Tesla image acquisition protocol in detail, which is focused on visual perceptual functions in psychotic psychopathology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2021.118439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8542422PMC
November 2021

Emerging ethical issues raised by highly portable MRI research in remote and resource-limited international settings.

Neuroimage 2021 09 29;238:118210. Epub 2021 May 29.

Professor in the Departments of Biomedical Engineering and Radiology, Director of the Columbia Magnetic Resonance Research Center; Principal and Investigator and MR Platform Director of the Zuckerman Institute, Columbia University; Director of the High Field Imaging Lab, Nathan Kline Institute USA.

Smaller, more affordable, and more portable MRI brain scanners offer exciting opportunities to address unmet research needs and long-standing health inequities in remote and resource-limited international settings. Field-based neuroimaging research in low- and middle-income countries (LMICs) can improve local capacity to conduct both structural and functional neuroscience studies, expand knowledge of brain injury and neuropsychiatric and neurodevelopmental disorders, and ultimately improve the timeliness and quality of clinical diagnosis and treatment around the globe. Facilitating MRI research in remote settings can also diversify reference databases in neuroscience, improve understanding of brain development and degeneration across the lifespan in diverse populations, and help to create reliable measurements of infant and child development. These deeper understandings can lead to new strategies for collaborating with communities to mitigate and hopefully overcome challenges that negatively impact brain development and quality of life. Despite the potential importance of research using highly portable MRI in remote and resource-limited settings, there is little analysis of the attendant ethical, legal, and social issues (ELSI). To begin addressing this gap, this paper presents findings from the first phase of an envisioned multi-staged and iterative approach for creating ethical and legal guidance in a complex global landscape. Section 1 provides a brief introduction to the emerging technology for field-based MRI research. Section 2 presents our methodology for generating plausible use cases for MRI research in remote and resource-limited settings and identifying associated ELSI issues. Section 3 analyzes core ELSI issues in designing and conducting field-based MRI research in remote, resource-limited settings and offers recommendations. We argue that a guiding principle for field-based MRI research in these contexts should be including local communities and research participants throughout the research process in order to create sustained local value. Section 4 presents a recommended path for the next phase of work that could further adapt these use cases, address ethical and legal issues, and co-develop guidance in partnership with local communities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2021.118210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382487PMC
September 2021

Corrigendum: Methylation of and in Relation to Treatment Response to Mindfulness Based Stress Reduction for Posttraumatic Stress Disorder.

Front Psychiatry 2021 4;12:642245. Epub 2021 Mar 4.

Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, United States.

[This corrects the article DOI: 10.3389/fpsyt.2018.00418.].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyt.2021.642245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970629PMC
March 2021

Social behaviors and gray matter volumes of brain areas supporting social cognition in children and adolescents with prenatal alcohol exposure.

Brain Res 2021 Feb 20:147388. Epub 2021 Feb 20.

University of Minnesota, Twin Cities, Minneapolis, MN, United States. Electronic address:

The goal of this study was to examine: 1) differences in parent-reported prosocial and antisocial behaviors between children and adolescents with and without prenatal alcohol exposure (PAE); 2) differences in gray matter volumes of brain areas supporting social cognition between children and adolescents with and without PAE; 3) correlations between gray matter volumes of brain areas supporting social cognition and parent-reported prosocial and antisocial behaviors. Parents of children and adolescents ages 8-16 years completed measures on their prosocial and antisocial behaviors (i.e., Behavior Assessment Scale for Children, Vineland Adaptive Behaviors Scales, and Child Behavior Checklist) (n = 84; 41 with PAE, 43 without PAE). Seventy-nine participants (40 with PAE, 39 without PAE) also completed a structural Magnetic Resonance Imaging (MRI) scan with quality data. Gray matter volumes of seven brain areas supporting social cognitive processes were computed using automated procedures (FreeSurfer 6.0): bilateral fusiform gyrus, superior temporal gyrus, medial orbitofrontal cortex, lateral orbitofrontal cortex, posterior cingulate cortex, precuneus, and temporal pole. Children and adolescents with PAE showed decreased prosocial behaviors and increased antisocial behaviors as well as smaller volumes of the precuneus and lateral orbitofrontal cortex, even when controlling for total intracranial volume. Social brain volumes were not significantly correlated with prosocial or antisocial behaviors. These findings suggest that children and adolescents with PAE show worse social functioning and smaller volumes of brain areas supporting self-awareness, perspective-taking and emotion-regulation than their same-age peers without PAE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brainres.2021.147388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377082PMC
February 2021

Alterations in hippocampal subfield and amygdala subregion volumes in posttraumatic subjects with and without posttraumatic stress disorder.

Hum Brain Mapp 2021 05 10;42(7):2147-2158. Epub 2021 Feb 10.

Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province, Department of Radiology, West China Hospital, Sichuan University, Chengdu, China.

The hippocampus and amygdala are important structures in the posttraumatic stress disorder (PTSD); however, the exact relationship between these structures and stress or PTSD remains unclear. Moreover, they consist of several functionally distinct subfields/subregions that may serve different roles in the neuropathophysiology of PTSD. Here we present a subregional profile of the hippocampus and amygdala in 145 survivors of a major earthquake and 56 non-traumatized healthy controls (HCs). We found that the bilateral hippocampus and left amygdala were significantly smaller in survivors than in HCs, and there was no difference between survivors with (n = 69) and without PTSD (trauma-exposed controls [TCs], n = 76). Analyses revealed similar results in most subfields/subregions, except that the right hippocampal body (in a head-body-tail segmentation scheme), right presubiculum, and left amygdala medial nuclei (Me) were significantly larger in PTSD patients than in TCs but smaller than in HCs. Larger hippocampal body were associated with the time since trauma in PTSD patients. The volume of the right cortical nucleus (Co) was negatively correlated with the severity of symptoms in the PTSD group but positively correlated with the same measurement in the TC group. This correlation between symptom severity and Co volume was significantly different between the PTSD and TCs. Together, we demonstrated that generalized smaller volumes in the hippocampus and amygdala were more likely to be trauma-related than PTSD-specific, and their subfields/subregions were distinctively affected. Notably, larger left Me, right hippocampal body and presubiculum were PTSD-specific; these could be preexisting factors for PTSD or reflect rapid posttraumatic reshaping.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hbm.25356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046112PMC
May 2021

Alterations in hippocampal subfield and amygdala subregion volumes in posttraumatic subjects with and without posttraumatic stress disorder.

Hum Brain Mapp 2021 05 10;42(7):2147-2158. Epub 2021 Feb 10.

Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province, Department of Radiology, West China Hospital, Sichuan University, Chengdu, China.

The hippocampus and amygdala are important structures in the posttraumatic stress disorder (PTSD); however, the exact relationship between these structures and stress or PTSD remains unclear. Moreover, they consist of several functionally distinct subfields/subregions that may serve different roles in the neuropathophysiology of PTSD. Here we present a subregional profile of the hippocampus and amygdala in 145 survivors of a major earthquake and 56 non-traumatized healthy controls (HCs). We found that the bilateral hippocampus and left amygdala were significantly smaller in survivors than in HCs, and there was no difference between survivors with (n = 69) and without PTSD (trauma-exposed controls [TCs], n = 76). Analyses revealed similar results in most subfields/subregions, except that the right hippocampal body (in a head-body-tail segmentation scheme), right presubiculum, and left amygdala medial nuclei (Me) were significantly larger in PTSD patients than in TCs but smaller than in HCs. Larger hippocampal body were associated with the time since trauma in PTSD patients. The volume of the right cortical nucleus (Co) was negatively correlated with the severity of symptoms in the PTSD group but positively correlated with the same measurement in the TC group. This correlation between symptom severity and Co volume was significantly different between the PTSD and TCs. Together, we demonstrated that generalized smaller volumes in the hippocampus and amygdala were more likely to be trauma-related than PTSD-specific, and their subfields/subregions were distinctively affected. Notably, larger left Me, right hippocampal body and presubiculum were PTSD-specific; these could be preexisting factors for PTSD or reflect rapid posttraumatic reshaping.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hbm.25356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046112PMC
May 2021

Resting State Hypoconnectivity of Reward Networks in Binge Eating Disorder.

Cereb Cortex 2021 03;31(5):2494-2504

Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, 55454 MN, USA.

The clinical presentation of binge eating disorder (BED) and data emerging from task-based functional neuroimaging research suggests that this disorder may be associated with alterations in reward processing. However, there is a dearth of research investigating the functional organization of brain networks that mediate reward in BED. To address this gap, 27 adults with BED and 21 weight-matched healthy controls (WMC) completed a multimodel assessment consisting of a resting functional magnetic resonance imaging scan, behavioral tasks measuring reward-based decision-making (i.e., delay discounting and reversal learning), and self-report assessing clinical symptoms. A seed-based approach was employed to examine the resting state functional connectivity (rsFC) of the striatum (nucleus accumbens [NAcc] and ventral and dorsal caudate), a collection of regions implicated in reward processing. Compared with WMC, the BED group exhibited lower rsFC of striatal seeds, with frontal regions mediating executive functioning (e.g., superior frontal gyrus [SFG]) and posterior, parietal, and temporal regions implicated in emotional processing. Lower NAcc-SFG rsFC was associated with more difficulties with reversal learning and binge eating frequency in the BED group. Results suggest that hypoconnectivity of striatal networks that integrate self-regulation and reward processing may promote the clinical phenomenology of BED. Interventions for BED may benefit from targeting these circuit-based disturbances.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cercor/bhaa369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248831PMC
March 2021

Association of Optical Coherence Tomography With Longitudinal Neurodegeneration in Veterans With Chronic Mild Traumatic Brain Injury.

JAMA Netw Open 2020 12 1;3(12):e2030824. Epub 2020 Dec 1.

Center for the Prevention and Treatment of Visual Loss, Iowa City VA Healthcare System, Iowa City, Iowa.

Importance: Mild traumatic brain injury (TBI) may predispose individuals to progressive neurodegeneration.

Objective: To identify evidence of neurodegeneration through longitudinal evaluation of changes in retinal layer thickness using optical coherence tomography in veterans with a history of mild TBI.

Design, Setting, And Participants: This longitudinal cohort study evaluated veterans who were receiving services at the Minneapolis Veterans Affairs Health Care System. Symptomatic or mild TBI was diagnosed according to the Mayo TBI Severity Classification System. Participants in the age-matched control group had no history of TBI. Participants with any history or evidence of retinal or optic nerve disease that could affect retinal thickness were excluded. Data analysis was performed from July 2019 to February 2020.

Exposures: The presence and severity of mild TBI were determined through consensus review of self-report responses during the Minnesota Blast Exposure Screening Tool semistructured interview.

Main Outcomes And Measures: Change over time of retinal nerve fiber layer (RNFL) thickness.

Results: A total of 139 veterans (117 men [84%]; mean [SD] age, 49.9 [11.1] years) were included in the study, 69 in the TBI group and 70 in the control group. Veterans with mild TBI showed significantly greater RNFL thinning compared with controls (mean [SE] RNFL slope, -1.47 [0.24] μm/y vs -0.31 [0.32] μm/y; F1,122 = 8.42; P = .004; Cohen d = 0.52). Functionally, veterans with mild TBI showed greater declines in visual field mean deviation (mean [SE] slope, -0.09 [0.14] dB/y vs 0.46 [0.23] dB/y; F1,122 = 4.08; P = .046; Cohen d = 0.36) and pattern standard deviation (mean [SE] slope, 0.09 [0.06] dB/y vs -0.10 [0.07] dB/y; F1,122 = 4.78; P = .03; Cohen d = 0.39) and high spatial frequency (12 cycles/degree) contrast sensitivity compared with controls. Cognitively, there was a significantly greater decrease in the number of errors over time during the Groton Maze Learning Test (GMLT) in controls compared with veterans with mild TBI (mean [SE] slope, -9.30 [1.48] errors/y vs -5.23 [1.24] errors/y; F1,127 = 4.43; P = .04; Cohen d = 0.37). RNFL tissue loss was significantly correlated with both worsening performance on the GMLT over time (Spearman ρ = -0.20; P = .03) and mild TBI severity (Spearman ρ = -0.25; P = .006). The more severe the mild TBI (larger Minnesota Blast Exposure Screening Tool severity score), the faster the reduction in RNFL thickness (ie, the more negative the slope) across time.

Conclusions And Relevance: This cohort study found longitudinal evidence for significant, progressive neural degeneration over time in veterans with mild TBI, as indicated by greater RNFL tissue loss in patients with mild TBI vs controls, as well as measures of function. These results suggest that these longitudinal measures may be useful biomarkers of neurodegeneration. Changes in this biomarker may provide early detection of subsequent cognitive and functional deficits that may impact veterans' independence and need for care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamanetworkopen.2020.30824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756235PMC
December 2020

Hippocampal subfield abnormalities and memory functioning in children with fetal alcohol Spectrum disorders.

Neurotoxicol Teratol 2021 Jan-Feb;83:106944. Epub 2020 Nov 21.

University of Minnesota, Twin Cities, United States of America. Electronic address:

Background: Prenatal alcohol exposure (PAE) affects early brain development and has been associated with hippocampal damage. Animal models of PAE have suggested that some subfields of the hippocampus may be more susceptible to damage than others. Recent advances in structural MRI processing now allow us to examine the morphology of hippocampal subfields in humans with PAE.

Method: Structural MRI scans were collected from 40 children with PAE and 39 typically developing children (ages 8-16). The images were processed using the Human Connectome Project Minimal Preprocessing Pipeline (v4.0.1) and the Hippocampal Subfields package (v21) from FreeSurfer. Using a large dataset of typically developing children enrolled in the Human Connectome Project in Development (HCP-D) for normative standards, we computed age-specific volumetric z-scores for our two samples. Using these norm-adjusted hippocampal subfield volumes, comparisons were performed between children with PAE and typically developing children, controlling for total intracranial volume. Lastly, we investigated whether subfield volumes correlated with episodic memory (i.e., Picture Sequence Memory test of the NIH toolbox).

Results: Five subfields had significantly smaller adjusted volumes in children with PAE than in typically developing controls: CA1, CA4, subiculum, presubiculum, and the hippocampal tail. Subfield volumes were not significantly correlated with episodic memory.

Conclusions: The results suggest that several regions of the hippocampus may be particularly affected by PAE. The finding of smaller CA1 volumes parallels previous reports in rodent models. The novel findings of decreased volume in the subicular cortex, CA4 and the hippocampal tail suggest avenues for future research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ntt.2020.106944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855420PMC
October 2021

Diagnosis of Myotonic Dystrophy Based on Resting State fMRI Using Convolutional Neural Networks.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:1714-1717

Myotonic dystrophies (DM) are neuromuscular conditions that cause widespread effects throughout the body. There are brain white matter changes on MRI in patients with DM that correlate with neuropsychological functional changes. How these brain alterations causally relate to the presence and severity of cognitive symptoms remains largely unknown. Deep neural networks have significantly improved the performance of image classification of huge datasets. However, its application in brain imaging is limited and not well described, due to the scarcity of labeled training data. In this work, we propose an approach for the diagnosis of DM based on a spatio-temporal deep learning paradigm. The obtained accuracy (73.71%) and sensitivities and specificities showed that the implemented approach based on 4-D convolutional neural networks leads to a compact, discriminative, and fast computing DM-based clinical medical decision support system.Clinical relevance- Many adults with DM experience cognitive and neurological effects impacting their quality of life, and ability to maintain employment. A robust and reliable DM-based clinical decision support system may help reduce the long diagnostic delay common to DM. Furthermore, it can help neurologists better understand the pathophysiology of the disease and analyze effects of new drugs that aim to address the neurological symptoms of DM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/EMBC44109.2020.9176455DOI Listing
July 2020

Neural and Behavioral Correlates of Clinical Improvement to Ketamine in Adolescents With Treatment Resistant Depression.

Front Psychiatry 2020 18;11:820. Epub 2020 Aug 18.

Department of Psychiatry and Behavioral Sciences, School of Medicine, University of Minnesota, Twin Cities, MN, United States.

Treatment-resistant depression (TRD) is a serious problem in adolescents. Development and optimization of novel interventions for these youth will require a deeper knowledge of the neurobiology of depression. A well-established phenomenon of depression is an attention bias toward negativity and away from positivity that is evidenced behaviorally and neurally, but it is unclear how symptom reduction is related to changes to this bias. Neurobiological research using a treatment probe has promise to help discover the neural changes that accompany symptom improvement. Ketamine has utility for such research because of its known rapid and strong antidepressant effects in the context of TRD. Our previous study of six open-label ketamine infusions in 11 adolescents with TRD showed variable response, ranging from full remission, partial response, non-response, or clinical worsening. In this study, we examined the performance of these participants on Word Face Stroop (WFS) fMRI task where they indicated the valence of affective words superimposed onto either congruent or incongruent emotional faces before and after the ketamine infusions. Participants also completed a clinical assessment (including measurement of depression symptomology and anhedonia/pleasure) before and after the ketamine infusions. Following ketamine treatment, better WFS performance correlated with self-reported decreased depressive symptoms and increased pleasure. Analyses of corticolimbic, corticostriatal and default mode (DMN) networks showed that across networks, decreased activation during all conditions (congruent negative, congruent positive, incongruent negative, and incongruent positive) correlated with decreases in depressive symptoms and with increases in pleasure. These findings suggest that in adolescents with TRD, clinical improvement may require an attenuation of the negativity bias and re-tuning of these three critical neural networks to attenuate DMN and limbic regions activation and allow more efficient recruitment of the reward network. Lower activation across conditions may facilitate shifting across different salient emotional stimuli rather than getting trapped in downward negative spirals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyt.2020.00820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461781PMC
August 2020

Neurocognitive performance of repeated versus single intravenous subanesthetic ketamine in treatment resistant depression.

J Affect Disord 2020 12 26;277:470-477. Epub 2020 Aug 26.

Drs. T.J. and Ella M. Arneson Land-Grant Chair in Human Behavior, Professor of Psychiatry, Vice Chair for Research Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA.

Background: Ketamine demonstrated rapid antidepressant effects in treatment-resistant depression (TRD). However, evaluation of ketamine's neurocognitive effect in TRD is unclear. We aim to (1) characterize baseline neurocognitive performance as a predictor of the change in severity of depressive symptoms over time, and (2) investigate the association of six versus single intravenous (IV) ketamine and neurocognitive changes from baseline to the end of treatment.

Methods: Subjects with TRD were randomized to receive either five IV midazolam followed by a single IV ketamine or six IV ketamine during a 12-day period. Depression symptom assessments occurred prior and 24 h after infusion days using the Montgomery-Åsberg Depression Rating Scale. Neurocognitive tasks were designed to test attention, memory, speed of processing, and set shifting using the CogState battery at baseline and at the end of treatment.

Results: Better complex working memory at baseline predicted improvement in MADRS scores of ketamine (vs midazolam) after 5 infusions. Most, but not all, neurocognitive functions remained stable or improved after repeated or single ketamine. There was a greater differential effect of treatment on speed of processing, set shifting, and spatial working memory that favors subjects in the six ketamine group. These cognitive improvements from baseline to the end of treatment were robust when controlling for age and changes in depression severity.

Conclusion: The study suggests that six IV ketamine compared to single IV ketamine has a mood independent procognitive effect among TRD patients. Large scale studies are needed to confirm whether ketamine enhances cognitive function in TRD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jad.2020.08.058DOI Listing
December 2020

Brain entropy and neurotrophic molecular markers accompanying clinical improvement after ketamine: Preliminary evidence in adolescents with treatment-resistant depression.

J Psychopharmacol 2021 02 9;35(2):168-177. Epub 2020 Jul 9.

Department of Psychiatry and Behavioral Sciences, Medical School, University of Minnesota, Minneapolis, USA.

Background: Current theory suggests that treatment-resistant depression (TRD) involves impaired neuroplasticity resulting in cognitive and neural rigidity, and that clinical improvement may require increasing brain flexibility and adaptability.

Aims: In this hypothesis-generating study, we sought to identify preliminary evidence of brain flexibility correlates of clinical change within the context of an open-label ketamine trial in adolescents with TRD, focusing on two promising candidate markers of neural flexibility: (a) entropy of resting-state functional magnetic resonance imaging (fMRI) signals; and (b) insulin-stimulated phosphorylation of mammalian target of rapamycin (mTOR) and glycogen synthase-3-beta (GSK3β) in peripheral blood mononuclear cells.

Methods: We collected resting-state functional magnetic resonance imaging data and blood samples from 13 adolescents with TRD before and after a series of six ketamine infusions over 2 weeks. Usable pre/post ketamine data were available from 11 adolescents for imaging and from 10 adolescents for molecular signaling. We examined correlations between treatment response and changes in the central and peripheral flexibility markers.

Results: Depression reduction correlated with increased nucleus accumbens entropy. Follow-up analyses suggested that physiological changes were associated with treatment response. In contrast to treatment non-responders (=6), responders (=5) showed greater increase in nucleus accumbens entropy after ketamine, together with greater post-treatment insulin/mTOR/GSK3β signaling.

Conclusions: These data provide preliminary evidence that changes in neural flexibility may underlie symptom relief in adolescents with TRD following ketamine. Future research with adequately powered samples is needed to confirm resting-state entropy and insulin-stimulated mTOR and GSK3β as brain flexibility markers and candidate targets for future clinical trials.

Clinical Trial Name: Ketamine in adolescents with treatment-resistant depression https://clinicaltrials.gov/ct2/show/NCT02078817 NCT02078817.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0269881120928203DOI Listing
February 2021

A randomized, double-blind, active placebo-controlled study of efficacy, safety, and durability of repeated vs single subanesthetic ketamine for treatment-resistant depression.

Transl Psychiatry 2020 06 26;10(1):206. Epub 2020 Jun 26.

Drs. T.J. and Ella M. Arneson Land-Grant Chair in Human Behavior, Professor of Psychiatry, Vice Chair for Research Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA.

The strategy of repeated ketamine in open-label and saline-control studies of treatment-resistant depression suggested greater antidepressant response beyond a single ketamine. However, consensus guideline stated the lack of evidence to support frequent ketamine administration. We compared the efficacy and safety of single vs. six repeated ketamine using midazolam as active placebo. Subjects received either six ketamine or five midazolam followed by a single ketamine during 12 days followed by up to 6-month post-treatment period. The primary end point was the change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) score at 24 h after the last infusion. Fifty-four subjects completed all six infusions. For the primary outcome measure, there was no significant difference in change of MADRS scores between six ketamine group and single ketamine group at 24 h post-last infusion. Repeated ketamine showed greater antidepressant efficacy compared to midazolam after five infusions before receiving single ketamine infusion. Remission and response favored the six ketamine after infusion 4 and 5, respectively, compared to midazolam before receiving single ketamine infusion. For those who responded, the median time-to-relapse was nominally but not statistically different (2 and 6 weeks for the single and six ketamine group, respectively). Repeated infusions were relatively well-tolerated. Repeated ketamine showed greater antidepressant efficacy to midazolam after five infusions but fell short of significance when compared to add-on single ketamine to midazolam at the end of 2 weeks. Increasing knowledge on the mechanism of ketamine should drive future studies on the optimal balance of dosing ketamine for maximum antidepressant efficacy with minimum exposure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41398-020-00897-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319954PMC
June 2020

Para-limbic Structural Abnormalities Are Associated With Internalizing Symptoms in Children With Prenatal Alcohol Exposure.

Alcohol Clin Exp Res 2020 08 1;44(8):1598-1608. Epub 2020 Jul 1.

University of Minnesota, Twin Cities, Minneapolis, Minnesota.

Background: Prenatal alcohol exposure (PAE) is associated with a variety of structural abnormalities in the brain, including several within the para-limbic system. Children with PAE have higher rates of internalizing disorders, including depression and anxiety, which may be related to underlying limbic system anomalies.

Methods: Children aged 8 to 16 with PAE (n = 41) or without PAE (n = 36) underwent an magnetic resonance imaging of the brain and parents completed behavioral questionnaires about their children. Semi-automated procedures (FreeSurfer) were used to derive para-limbic volumes from T1-weighted anatomical images.

Results: There were significant group differences (PAE vs. nonexposed controls) in the caudate, hippocampus, and the putamen; children with PAE had smaller volumes in these regions even after controlling for total intracranial volume. A trend-level association was seen between caudate volume and internalizing symptoms in children with PAE; smaller caudate volumes (presumably reflecting less optimal neurodevelopment) were associated with higher levels of anxiety and depression symptoms in these children.

Conclusions: Caudate structure may be disproportionately affected by PAE and may be associated with the later development of internalizing symptoms in those affected by PAE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/acer.14390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484415PMC
August 2020

A randomized controlled trial of transcranial direct-current stimulation and cognitive training in children with fetal alcohol spectrum disorder.

Brain Stimul 2020 Jul - Aug;13(4):1059-1068. Epub 2020 Apr 28.

University of Minnesota, Twin Cities, USA. Electronic address:

Background: This study was a randomized double-blind sham-controlled trial examining the effects of transcranial direct current stimulation (tDCS) augmented cognitive training (CT) in children with Fetal Alcohol Spectrum Disorders (FASD). Prenatal alcohol exposure has profound detrimental effects on brain development and individuals with FASD commonly present with deficits in executive functions including attention and working memory. The most commonly studied treatment for executive deficits is CT, which involves repeated drilling of exercises targeting the impaired functions. As currently implemented, CT requires many hours and the observed effect sizes are moderate. Neuromodulation via tDCS can enhance brain plasticity and prior studies demonstrate that combining tDCS with CT improves efficacy and functional outcomes. TDCS-augmented CT has not yet been tested in FASD, a condition in which there are known abnormalities in neuroplasticity and few interventions.

Methods: This study examined the feasibility and efficacy of this approach in 44 children with FASD. Participants were randomized to receive five sessions of CT with either active or sham tDCS targeting the dorsolateral prefrontal cortex, a region of the brain that is heavily involved in executive functioning.

Results: The intervention was feasible and well-tolerated in children with FASD. The tDCS group showed nominally significant improvement in attention on a continuous performance test compared to sham (p = .043). Group differences were observed at the third, fourth and fifth treatment sessions. There was no effect of tDCS on working memory (p = .911). Further, we found no group differences on a trail making task (p = .659) or on the verbal fluency test (p = .826). In the active tDCS group, a significant correlation was observed between improvement in attention scores and decrease in parent-reported attention deficits (p = .010).

Conclusions: These results demonstrate that tDCS-augmented CT is well tolerated in children with FASD and potentially offers benefits over and above CT alone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brs.2020.04.015DOI Listing
December 2020

A randomized controlled trial of transcranial direct-current stimulation and cognitive training in children with fetal alcohol spectrum disorder.

Brain Stimul 2020 Jul - Aug;13(4):1059-1068. Epub 2020 Apr 28.

University of Minnesota, Twin Cities, USA. Electronic address:

Background: This study was a randomized double-blind sham-controlled trial examining the effects of transcranial direct current stimulation (tDCS) augmented cognitive training (CT) in children with Fetal Alcohol Spectrum Disorders (FASD). Prenatal alcohol exposure has profound detrimental effects on brain development and individuals with FASD commonly present with deficits in executive functions including attention and working memory. The most commonly studied treatment for executive deficits is CT, which involves repeated drilling of exercises targeting the impaired functions. As currently implemented, CT requires many hours and the observed effect sizes are moderate. Neuromodulation via tDCS can enhance brain plasticity and prior studies demonstrate that combining tDCS with CT improves efficacy and functional outcomes. TDCS-augmented CT has not yet been tested in FASD, a condition in which there are known abnormalities in neuroplasticity and few interventions.

Methods: This study examined the feasibility and efficacy of this approach in 44 children with FASD. Participants were randomized to receive five sessions of CT with either active or sham tDCS targeting the dorsolateral prefrontal cortex, a region of the brain that is heavily involved in executive functioning.

Results: The intervention was feasible and well-tolerated in children with FASD. The tDCS group showed nominally significant improvement in attention on a continuous performance test compared to sham (p = .043). Group differences were observed at the third, fourth and fifth treatment sessions. There was no effect of tDCS on working memory (p = .911). Further, we found no group differences on a trail making task (p = .659) or on the verbal fluency test (p = .826). In the active tDCS group, a significant correlation was observed between improvement in attention scores and decrease in parent-reported attention deficits (p = .010).

Conclusions: These results demonstrate that tDCS-augmented CT is well tolerated in children with FASD and potentially offers benefits over and above CT alone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brs.2020.04.015DOI Listing
December 2020

The genetic architecture of the human cerebral cortex.

Science 2020 03;367(6484)

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.aay6690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295264PMC
March 2020

The genetic architecture of the human cerebral cortex.

Science 2020 03;367(6484)

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.aay6690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295264PMC
March 2020

Transcranial direct current stimulation (tDCS) elicits stimulus-specific enhancement of cortical plasticity.

Neuroimage 2020 05 4;211:116598. Epub 2020 Feb 4.

Department of Psychiatry, University of Minnesota, Suite 516 717 Delaware Street SE, Minneapolis, MN, 55414, USA. Electronic address:

Background: Deficits in plasticity underlie many severe psychiatric disorders. Transcranial direct current stimulation (tDCS) is a promising method for modulating plasticity. However, given its non-focal nature, there are open questions as to how targeting and outcome specificity can best be achieved.

Objective: Understanding how tDCS interacts with concurrent brain activity is necessary for the rational advancement of tDCS. In the present study, we use an event-related potential (ERP) paradigm to assess the stimulus-specific effects of tDCS on cortical plasticity.

Methods: 22 healthy volunteers underwent a blinded, sham-controlled plasticity paradigm in a crossover design. High frequency presentation of auditory stimuli was used to induce potentiation in specific components of the ERP. We investigated whether anodal tDCS targeting the auditory cortex would modulate plasticity induction across time. Two pure tones were used as stimuli, only one of the tones, the target tone, was used for plasticity induction. Plasticity was quantified as change in the mean amplitude of the N100 component relative to baseline.

Results: TDCS significantly modulated plasticity in the target tone compared to sham (p ​= ​0.02) but had no effect on the control tone (p ​= ​0.73). This effect was time dependent, with tDCS effects no longer apparent 30 ​min after stimulation.

Conclusions: Our results indicate that tDCS can modulate cortical plasticity in the auditory cortex in an activity-dependent manner. These findings bolster the idea that tDCS can be an effective tool to target and modulate plasticity both for research and therapeutic purposes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2020.116598DOI Listing
May 2020

Reproducibility of a ramping protocol to measure cerebral vascular reactivity using functional magnetic resonance imaging.

Clin Physiol Funct Imaging 2020 May 16;40(3):183-189. Epub 2020 Feb 16.

School of Kinesiology, University of Minnesota, Minneapolis, Minnesota.

Though individual differences in arterial carbon dioxide and oxygen levels inherently exist, the degree of their influence on cerebral vascular reactivity (CVR) is less clear. We examined the reproducibility of BOLD signal changes to an iso-oxic ramping P CO protocol. CVR changes were induced by altering P CO while holding P O constant using a computer-controlled sequential gas delivery (SGD) device. Two MRI scans, each including a linear change in P CO , were performed using a 3-Tesla (3T) scanner. This ramp sequence consisted of 1 min at 30 mmHg followed by 4 min period during where P CO was linearly increased from 30 to 50 mmHg, 1 min at 51 mmHg, and concluded with 4 min at baseline. The protocol was repeated at a separate visit with 3 days between visits (minimum). Intraclass correlation coefficients (ICC) and coefficients of variation (CV) were used to verify reproducibility. Eleven subjects (6 females; mean age 26.5 ± 5.7 years) completed the full testing protocol. Good reproducibility was observed for the within-visit ramp sequence (Visit 1: ICC = 0.82, CV = 6.5%; Visit 2: ICC = 0.74, CV = 6.4%). Similarly, ramp sequence were reproducible between visits (Scan 1: ICC = 0.74, CV = 6.5%; Scan 2: ICC = 0.66, CV = 6.1%). Establishing reproducible methodologies for measuring BOLD signal changes in response to P CO alterations using a ramp protocol will allow researchers to study CVR functionality. Finally, adding a ramping protocol to CVR studies could provide information about changes in CVR over a broad range of P CO .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cpf.12621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7131875PMC
May 2020

Reproducibility of a ramping protocol to measure cerebral vascular reactivity using functional magnetic resonance imaging.

Clin Physiol Funct Imaging 2020 May 16;40(3):183-189. Epub 2020 Feb 16.

School of Kinesiology, University of Minnesota, Minneapolis, Minnesota.

Though individual differences in arterial carbon dioxide and oxygen levels inherently exist, the degree of their influence on cerebral vascular reactivity (CVR) is less clear. We examined the reproducibility of BOLD signal changes to an iso-oxic ramping P CO protocol. CVR changes were induced by altering P CO while holding P O constant using a computer-controlled sequential gas delivery (SGD) device. Two MRI scans, each including a linear change in P CO , were performed using a 3-Tesla (3T) scanner. This ramp sequence consisted of 1 min at 30 mmHg followed by 4 min period during where P CO was linearly increased from 30 to 50 mmHg, 1 min at 51 mmHg, and concluded with 4 min at baseline. The protocol was repeated at a separate visit with 3 days between visits (minimum). Intraclass correlation coefficients (ICC) and coefficients of variation (CV) were used to verify reproducibility. Eleven subjects (6 females; mean age 26.5 ± 5.7 years) completed the full testing protocol. Good reproducibility was observed for the within-visit ramp sequence (Visit 1: ICC = 0.82, CV = 6.5%; Visit 2: ICC = 0.74, CV = 6.4%). Similarly, ramp sequence were reproducible between visits (Scan 1: ICC = 0.74, CV = 6.5%; Scan 2: ICC = 0.66, CV = 6.1%). Establishing reproducible methodologies for measuring BOLD signal changes in response to P CO alterations using a ramp protocol will allow researchers to study CVR functionality. Finally, adding a ramping protocol to CVR studies could provide information about changes in CVR over a broad range of P CO .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cpf.12621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7131875PMC
May 2020

Oxytocin Enhances an Amygdala Circuit Associated With Negative Symptoms in Schizophrenia: A Single-Dose, Placebo-Controlled, Crossover, Randomized Control Trial.

Schizophr Bull 2020 04;46(3):661-669

Mental Health Service, San Francisco Veterans Affairs Medical Center, San Francisco, CA.

Negative symptoms are core contributors to vocational and social deficits in schizophrenia (SZ). Available antipsychotic medications typically fail to reduce these symptoms. The neurohormone oxytocin (OT) is a promising treatment for negative symptoms, given its role in complex social behaviors mediated by the amygdala. In sample 1, we used a double-blind, placebo-controlled, crossover design to test the effects of a single dose of intranasal OT on amygdala resting-state functional connectivity (rsFC) in SZ (n = 22) and healthy controls (HC, n = 24) using a whole-brain corrected approach: we identified regions for which OT modulated SZ amygdala rsFC, assessed whether OT-modulated circuits were abnormal in SZ relative to HC on placebo, and evaluated whether connectivity on placebo and OT-induced connectivity changes correlated with baseline negative symptoms in SZ. Given our modest sample size, we used a second SZ (n = 183) and HC (n = 178) sample to replicate any symptom correlations. In sample 1, OT increased rsFC between the amygdala and left middle temporal gyrus, superior temporal sulcus, and angular gyrus (MTG/STS/AngG) in SZ compared to HC. Further, SZ had hypo-connectivity in this circuit compared to HC on placebo. More severe negative symptoms correlated with less amygdala-to-left-MTG/STS/AngG connectivity on placebo and with greater OT-induced connectivity increases. In sample 2, we replicated the correlation between amygdala-left-MTG/STS/AngG hypo-connectivity and negative symptoms, finding a specific association with expressive negative symptoms. These data suggest intranasal OT can normalize functional connectivity in an amygdala-to-left-MTG/STS/AngG circuit that contributes to negative symptoms in SZ.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/schbul/sbz091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147578PMC
April 2020

Transcendental meditation and hypothalamic-pituitary-adrenal axis functioning: a pilot, randomized controlled trial with young adults.

Stress 2020 01 11;23(1):105-115. Epub 2019 Sep 11.

Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA.

Transcendental meditation (TM) is effective in alleviating stress and anxiety and promoting well-being. While the underlying biological mechanisms of TM are not yet fully explored, the hypothalamic-pituitary-adrenal (HPA) axis represents an index providing important clues embodying the stress system cascade. In this pilot study, young adults were randomly assigned to TM training followed by 8 weeks of meditation practice or a wait-list control condition. TM was conducted over 8 weeks. Thirty-four young adult participants were randomized; 27 participants completed the HPA outcome assessments (41% male). To assess HPA axis functioning, salivary samples to assess cortisol awakening response (CAR) that were collected in the morning, both at baseline and at week-4. Salivary cortisol in the context of a social stressor using the Trier Social Stress Test (TSST) was collected at week-8. The results indicate that participants who were randomly assigned to TM had lower awakening salivary cortisol levels and a greater drop in CAR from baseline to week-4 than the control group. There were no significant differences in HPA axis functioning in the context of the TSST. Primary limitations of this randomized controlled trial were the small sample size, the use of a wait-list as opposed to an active control, and the limited scope of HPA axis assessments. The results of this pilot study provide tentative evidence that TM may impact biological stress system functioning and suggests that this may be a worthwhile avenue to continue to examine. It will also be useful to extend these findings to a broader array of meditative and mindful practices, particularly for those who are experiencing more distress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10253890.2019.1656714DOI Listing
January 2020

Longitudinal Alterations in Prefrontal Resting Brain Connectivity in Non-Treatment-Seeking Young Adults With Cannabis Use Disorder.

Front Psychiatry 2019 25;10:514. Epub 2019 Jul 25.

Department of Psychology, University of Minnesota, Minneapolis, MN, United States.

Cannabis is increasingly perceived as a harmless drug by recreational users, yet chronic use may impact brain changes into adulthood. Repeated cannabis exposure has been associated with enduring synaptic changes in executive control and reward networks. It is important to determine whether there are brain functional alterations within these networks in individuals that do not seek treatment for chronic cannabis abuse. This longitudinal study compared resting-state functional connectivity changes in executive control and reward networks between 23 non-treatment-seeking young adults with cannabis use disorder (6 females; baseline age M = 19.3 ± 1.18) and 21 age-matched controls (10 females; baseline age M = 19.4 ± 0.65) to determine group differences in the temporal trajectories of resting-state functional connectivity across a 2-year span. Results showed i) significant increases in resting-state functional connectivity between the caudal anterior cingulate cortex and precentral and parietal regions over time in the control group, but not in the cannabis use disorder group, and ii) sustained lower resting-state functional connectivity of anterior cingulate cortex seeds with frontal and thalamic regions in the cannabis use disorder group vs. the age-matched controls. Resting-state functional connectivity strength was correlated with cannabis use patterns in the cannabis use disorder sample. Longitudinal alterations in intrinsic functional organization of executive control networks found in non-treatment-seeking young adults with cannabis use disorder (when compared to age-matched controls) may impact regulatory control over substance use behavior. Current findings were limited to examining executive control and reward networks seeded in ACC and NAcc, respectively. Future studies with larger sample sizes and enough power are needed to conduct exploratory analyses examining rsFC of other networks beyond those within the scope of the current study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyt.2019.00514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6670783PMC
July 2019

Neurocircuitry associated with symptom dimensions at baseline and with change in borderline personality disorder.

Psychiatry Res Neuroimaging 2019 08 5;290:58-65. Epub 2019 Jul 5.

University of Minnesota Medical School, Department of Psychiatry, 2450 Riverside Avenue, Minneapolis, MN 55454, United States. Electronic address:

Borderline personality disorder (BPD) is a serious illness associated with chronic suffering and self-injurious behavior. Parsing the relationships between specific symptom domains and their underlying biological mechanisms may help us further understand the neural circuits implicated in these symptoms and how they might be amenable to change with treatment. This study examines the association between symptom dimensions (Affective Disturbance, Cognitive Disturbance, Disturbed Relationships, and Impulsivity) and amygdala resting-state functional connectivity (RSFC) in a sample of adults with BPD (n = 18). We also explored the relationships between change in symptom dimensions and change in amygdala RSFC in a subset of this sample (n = 13) following 8 weeks of quetiapine or placebo. At baseline, higher impulsivity was associated with increased positive RSFC between right amygdala and left hippocampus. There were no significant differences in neural change between treatment groups. Improvement in cognitive disturbance was associated with increased positive RSFC between left amygdala and temporal fusiform and parahippocampal gyri. Improvement in disturbed relationships was associated with increased negative RSFC between right amygdala and frontal pole. These results support that specific dimensions of BPD are associated with specific neural connectivity patterns at baseline and with change, which may represent neural treatment targets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pscychresns.2019.07.001DOI Listing
August 2019

Dentate gyrus volume deficit in schizophrenia.

Psychol Med 2020 06 3;50(8):1267-1277. Epub 2019 Jun 3.

Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA92617, USA.

Background: Schizophrenia is associated with robust hippocampal volume deficits but subregion volume deficits, their associations with cognition, and contributing genes remain to be determined.

Methods: Hippocampal formation (HF) subregion volumes were obtained using FreeSurfer 6.0 from individuals with schizophrenia (n = 176, mean age ± s.d. = 39.0 ± 11.5, 132 males) and healthy volunteers (n = 173, mean age ± s.d. = 37.6 ± 11.3, 123 males) with similar mean age, gender, handedness, and race distributions. Relationships between the HF subregion volume with the largest between group difference, neuropsychological performance, and single-nucleotide polymorphisms were assessed.

Results: This study found a significant group by region interaction on hippocampal subregion volumes. Compared to healthy volunteers, individuals with schizophrenia had significantly smaller dentate gyrus (DG) (Cohen's d = -0.57), Cornu Ammonis (CA) 4, molecular layer of the hippocampus, hippocampal tail, and CA 1 volumes, when statistically controlling for intracranial volume; DG (d = -0.43) and CA 4 volumes remained significantly smaller when statistically controlling for mean hippocampal volume. DG volume showed the largest between group difference and significant positive associations with visual memory and speed of processing in the overall sample. Genome-wide association analysis with DG volume as the quantitative phenotype identified rs56055643 (β = 10.8, p < 5 × 10-8, 95% CI 7.0-14.5) on chromosome 3 in high linkage disequilibrium with MOBP. Gene-based analyses identified associations between SLC25A38 and RPSA and DG volume.

Conclusions: This study suggests that DG dysfunction is fundamentally involved in schizophrenia pathophysiology, that it may contribute to cognitive abnormalities in schizophrenia, and that underlying biological mechanisms may involve contributions from MOBP, SLC25A38, and RPSA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S0033291719001144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068799PMC
June 2020

Attention and corpus callosum volumes in individuals with mucopolysaccharidosis type I.

Neurology 2019 05 12;92(20):e2321-e2328. Epub 2019 Apr 12.

From the Departments of Pediatrics (K.K., I.N., V.K., K.A.D., J.B.E., E.G.S.), Psychiatry (J.R.W., B.A.M., K.O.L.), and Genetics and Metabolism (C.B.W.), University of Minnesota Medical Center; Division of Biostatistics (K.D.R.), University of Minnesota School of Public Health, Minneapolis; Department of Psychology (E.G.M., J.R.), Hospital for Sick Children-Toronto, Ontario, Canada; Department of Human Genetics (N.A., S.C.), Emory University, Atlanta, GA; and Division of Gastroenterology and Nutrition (P.H.), UCSF Benioff Children's Hospital Oakland, San Francisco, CA. Dr. Kovac is now at the School of Medicine, Washington University in St. Louis, MO. Dr. Raiman is now at the Department of Inherited Metabolic Diseases, Birmingham Children's Hospital, UK. K.A. Delaney is now at Biomarin Pharmaceuticals, San Rafael, CA.

Objective: Previous research suggests attention and white matter (WM) abnormalities in individuals with mucopolysaccharidosis type I (MPS I); this cross-sectional comparison is one of the first to examine the relationship of WM structural abnormalities as measured by corpus callosum (CC) volumes with attention scores to evaluate this relationship in a larger sample of patients with MPS I.

Methods: Volumetric MRI data and performance on a computerized measure of sustained attention were compared for 18 participants with the severe form of MPS I (MPS IH), 18 participants with the attenuated form of MPS I (MPS I), and 60 typically developing age-matched controls.

Results: The MPS I groups showed below-average mean attention scores ( < 0.001) and smaller CC volumes ( < 0.001) than controls. No significant associations were found between attention performance and CC volume for controls. Attention was associated with posterior CC volumes in the participants with MPS IH ( = 0.053) and total ( = 0.007) and anterior ( < 0.001) CC volumes in participants with MPS I.

Conclusions: We found that attention and CC volumes were reduced in participants with MPS I compared to typically developing controls. Smaller CC volumes in participants with MPS I were associated with decreased attention; such an association was not seen in controls. While hematopoietic cell transplantation used to treat MPS IH may compound these effects, attention difficulties were also seen in the MPS I group, suggesting that disease effects contribute substantially to the clinical attentional difficulties seen in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000007496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598818PMC
May 2019
-->