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1.
Brain Topogr. 2018 Jul 21. doi: 10.1007/s10548-018-0664-5. [Epub ahead of print]

Response Hand and Motor Set Differentially Modulate the Connectivity of Brain Pathways During Simple Uni-manual Motor Behavior.

Author information

1
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Suite 5A, Tolan Park Medical Building, 3901 Chrysler Service Drive, Detroit, MI, 48201, USA.
2
Center for Complex Systems and Brain Sciences, Florida Atlantic University, Boca Raton, USA.
3
Department of Psychology, Wayne State University, Detroit, USA.
4
Institute of Gerontology, Wayne State University, Detroit, USA.
5
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Suite 5A, Tolan Park Medical Building, 3901 Chrysler Service Drive, Detroit, MI, 48201, USA. vdiwadka@med.wayne.edu.

Abstract

We investigated the flexible modulation of undirected functional connectivity (uFC) of brain pathways during simple uni-manual responding. Two questions were central to our interests: (1) does response hand (dominant vs. non-dominant) differentially modulate connectivity and (2) are these effects related to responding under varying motor sets. fMRI data were acquired in twenty right-handed volunteers who responded with their right (dominant) or left (non-dominant) hand (blocked across acquisitions). Within acquisitions, the task oscillated between periodic responses (promoting the emergence of motor sets) or randomly induced responses (disrupting the emergence of motor sets). Conjunction analyses revealed eight shared nodes across response hand and condition, time series from which were analyzed. For right hand responses connectivity of the M1 ←→ Thalamus and SMA ←→ Parietal pathways was more significantly modulated during periodic responding. By comparison, for left hand responses, connectivity between five network pairs (including M1 and SMA, insula, basal ganglia, premotor cortex, parietal cortex, thalamus) was more significantly modulated during random responding. uFC analyses were complemented by directed FC based on multivariate autoregressive models of times series from the nodes. These results were complementary and highlighted significant modulation of dFC for SMA → Thalamus, SMA → M1, basal ganglia → Insula and basal ganglia → Thalamus. The results demonstrate complex effects of motor organization and task demand and response hand on different connectivity classes of fMRI data. The brain's sub-networks are flexibly modulated by factors related to motor organization and/or task demand, and our results have implications for assessment of medical conditions associated with motor dysfunction.

KEYWORDS:

Functional connectivity; Granger causality; Motor organization; Right-handers; Uni-manual responses; fMRI

2.
Neuroimage Clin. 2018 Mar 1;18:582-590. doi: 10.1016/j.nicl.2018.02.034. eCollection 2018.

Decreased functional connectivity in the fronto-parietal network in children with mood disorders compared to children with dyslexia during rest: An fMRI study.

Author information

1
Cincinnati Children's Hospital Medical Center, University of Cincinnati, United States.
2
Educational Neuroimaging Center, Faculty of Education in Science and Technology, Technion, Israel.
3
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, United States.
4
The Research Institute at Nationwide Children's Hospital, United States.
5
Department of Psychiatry and Behavioral Health, Wexner Medical Center, Ohio State University, United States.
6
Department of Psychiatry and Behavioral Neuroscience, Wayne State University, United States.
7
University Hospitals Cleveland Medical Center, Case Western Reserve University, United States.
8
Department of Child Psychiatry, New York University School of Medicine, United States.
9
Department of Psychology, University of North Carolina at Chapel Hill, United States.
10
Department of Psychiatry, Johns Hopkins University, United States.

Abstract

Background:

The DSM-5 separates the diagnostic criteria for mood and behavioral disorders. Both types of disorders share neurocognitive deficits of executive function and reading difficulties in childhood. Children with dyslexia also have executive function deficits, revealing a role of executive function circuitry in reading. The aim of the current study is to determine whether there is a significant relationship of functional connectivity within the fronto-parietal and cingulo-opercular cognitive control networks to reading measures for children with mood disorders, behavioral disorders, dyslexia, and healthy controls (HC).

Method:

Behavioral reading measures of phonological awareness, decoding, and orthography were collected. Resting state fMRI data were collected, preprocessed, and then analyzed for functional connectivity. Differences in the reading measures were tested for significance among the groups. Global efficiency (GE) measures were also tested for correlation with reading measures in 40 children with various disorders and 17 HCs.

Results:

Significant differences were found between the four groups on all reading measures. Relative to HCs and children with mood disorders or behavior disorders, children with dyslexia as a primary diagnosis scored significantly lower on all three reading measures. Children with mood disorders scored significantly lower than controls on a test of phonological awareness. Phonological awareness deficits correlated with reduced resting state functional connectivity MRI (rsfcMRI) in the cingulo-opercular network for children with dyslexia. A significant difference was also found in fronto-parietal global efficiency in children with mood disorders relative to the other three groups. We also found a significant difference in cingulo-opercular global efficiency in children with mood disorders relative to the Dyslexia and Control groups. However, none of these differences correlate significantly with reading measures.

Conclusions/significance:

Reading difficulties involve abnormalities in different cognitive control networks in children with dyslexia compared to children with mood disorders. Findings of the current study suggest increased functional connectivity of one cognitive control network may compensate for reduced functional connectivity in the other network in children with mood disorders. These findings provide guidance to clinical professionals for design of interventions tailored for children suffering from reading difficulties originating from different pathologies.

KEYWORDS:

Behavioral disorders; Dyslexia; Executive function networks; Mood disorders; Phonological awareness; Reading; Resting state functional connectivity

3.
Front Psychiatry. 2018 Mar 6;9:66. doi: 10.3389/fpsyt.2018.00066. eCollection 2018.

Working Memory Modulates Glutamate Levels in the Dorsolateral Prefrontal Cortex during 1H fMRS.

Author information

1
Brain Imaging Research Division, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, United States.

Abstract

Glutamate is involved in excitatory neurotransmission and metabolic processes related to brain function. Previous studies using proton functional magnetic resonance spectroscopy (1H fMRS) have demonstrated elevated cortical glutamate levels by 2-4% during visual and motor stimulation, relative to periods of no stimulation. Here, we extended this approach to working memory cognitive task performance, which has been consistently associated with dorsolateral prefrontal cortex (dlPFC) activation. Sixteen healthy adult volunteers completed a continuous visual fixation "rest" task followed by a letter 2-back working memory task during 1H fMRS acquisition of the left dlPFC, which encompassed Brodmann areas 45 and 46 over a 4.5-cm3 volume. Using a 100% automated fitting procedure integrated with LCModel, raw spectra were eddy current-, phase-, and shift-corrected prior to quantification resulting in a 32s temporal resolution or 8 averages per spectra. Task compliance was high (95 ± 11% correct) and the mean Cramer-Rao Lower Bound of glutamate was 6.9 ± 0.9%. Relative to continuous passive visual fixation, left dlPFC glutamate levels were significantly higher by 2.7% (0.32 mmol/kg wet weight) during letter 2-back performance. Elevated dlPFC glutamate levels reflect increased metabolic activity and excitatory neurotransmission driven by working memory-related cognitive demands. These results provide the first in vivo demonstration of elevated dlPFC glutamate levels during working memory.

KEYWORDS:

dorsolateral prefrontal cortex; excitatory neurotransmission; glutamate; magnetic resonance spectroscopy; metabolism; neuroimaging; working memory

4.
Neuroimage. 2018 May 15;172:632-641. doi: 10.1016/j.neuroimage.2018.01.067. Epub 2018 Feb 10.

"Brain over body"-A study on the willful regulation of autonomic function during cold exposure.

Author information

1
Departments of Pediatrics, Wayne State University School of Medicine, Detroit, MI 48201, USA; Departments of Radiology, Wayne State University School of Medicine, Detroit, MI 48201, USA. Electronic address: otto@pet.wayne.edu.
2
TKR Research and Consulting, LLC, Detroit 48201 USA.
3
Departments of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48201, USA.

Abstract

The defense of body temperature against environmental thermal challenges is a core objective of homeostatic regulation governed by the autonomic nervous system. Autonomous mechanisms of thermoregulation are only weakly affected by top-down modulation, allowing only transient tolerance for extreme cold. There is however, anecdotal evidence of a unique set of individuals known for extreme cold tolerance. Here we present a case study of a 57-year old Dutch national, Wim Hof, the so-called "Iceman", with the ability to withstand frequent prolonged periods of extreme cold exposure based on the practice of a self-developed technique involving a combination of forced breathing, cold exposure and meditation (collectively referred to as the Wim Hof Method, henceforth "WHM"). The relative contributions of the brain and the periphery that endow the Iceman with these capabilities is unknown. To investigate this, we conducted multi-modal imaging assessments of the brain and the periphery using a combination of fMRI and PET/CT imaging. Thermoregulatory defense was evoked by subjecting the Iceman (and a cohort of typical controls) to a fMRI paradigm designed to generate periods of mild hypothermia interspersed by periods of return to basal core body temperature. fMRI was acquired in two separate sessions: in a typical (passive) state and following the practice of WHM. In addition, the Iceman also underwent a whole body PET/CT imaging session using the tracers C11-hydroxyephedrine (HED) and 18F-fluorodeoxyglucose (FDG) during both thermoneutral and prolonged mild cold conditions. This acquisition allowed us to determine changes in sympathetic innervation (HED) and glucose consumption (FDG) in muscle and fat tissues in the absence of the WHM. fMRI analyses indicated that the WHM activates primary control centers for descending pain/cold stimuli modulation in the periaqueductal gray (PAG), possibly initiating a stress-induced analgesic response. In addition, the WHM also engages higher-order cortical areas (left anterior and right middle insula) that are uniquely associated with self-reflection, and which facilitate both internal focus and sustained attention in the presence of averse (e.g. cold) external stimuli. However, the activation of brown adipose tissue (BAT) was unremarkable. Finally, forceful respiration results in increased sympathetic innervation and glucose consumption in intercostal muscle, generating heat that dissipates to lung tissue and warms circulating blood in the pulmonary capillaries. Our results provide compelling evidence for the primacy of the brain (CNS) rather than the body (peripheral mechanisms) in mediating the Iceman's responses to cold exposure. They also suggest the compelling possibility that the WHM might allow practitioners to develop higher level of control over key components of the autonomous system, with implications for lifestyle interventions that might ameliorate multiple clinical syndromes.

KEYWORDS:

CNS thermoregulation; Cold exposure; FDG PET; Functional MRI; Hydroxyephedrine PET; Periaqueductal gray; Stress-induced analgesia; Wim Hof method

5.
Front Neurosci. 2017 Nov 16;11:640. doi: 10.3389/fnins.2017.00640. eCollection 2017.

Regulation of Brown Adipose Tissue Activity by Interoceptive CNS Pathways: The interaction between Brain and Periphery.

Author information

1
Departments of Pediatrics, Wayne State University School of Medicine, Detroit, MI, United States.
2
Radiology, Wayne State University School of Medicine, Detroit, MI, United States.
3
Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, United States.

Abstract

To maintain thermal homeostasis, specific thermogenic tissues are under the control of central thermoregulatory networks that regulate the body's response to thermal challenges. One of these mechanisms involves non-shivering thermogenesis in brown adipose tissue (BAT), which is activated in cold environments in order to defend the body against physical damage as a result of hypothermia. The objective of our study was to assess the interaction between CNS thermoregulatory pathways and sympathetic innervation in BAT during a cold exposure paradigm. Our results show that an innocuous whole-body cooling paradigm induces significant differences in fMRI BOLD signal at the location of the right anterior insula and the red nucleus/substantia nigra region, between lean subjects with high levels of sympathetic innervation in supraclavicular BAT (BAT+ group), and subjects with low levels of sympathetic innervation (BAT- group). Specifically, results indicate significantly larger fMRI BOLD signal changes between periods of cooling and warming of the skin in the BAT+ (as compared to BAT-) group at the location of the right anterior insula. In contrast, the BAT+ group showed significantly smaller fMRI BOLD signal changes in the midbrain between periods of skin cooling and warming. Our findings are consistent with a hierarchical thermoregulatory control system that involves the initiation of inhibitory signals from the right anterior insula toward midbrain areas that normally exert tonic inhibition on the medullary raphe, from where BAT is directly innervated. Our data suggests that exposure to cold elicits differential neuronal activity in interoceptive regulatory centers of subjects with high and low level of sympathetic innervation. As a result, the variability of cold-activated BAT mass observed in humans might be, in part, yoked to different sensitivities of interoceptive cortical brain areas to skin temperature changes.

KEYWORDS:

CNS thermoregulation; FDG PET; functional MRI; human brown adipose tissue; variability of BAT mass

6.
PLoS One. 2017 Nov 14;12(11):e0188000. doi: 10.1371/journal.pone.0188000. eCollection 2017.

Common and distinct structural features of schizophrenia and bipolar disorder: The European Network on Psychosis, Affective disorders and Cognitive Trajectory (ENPACT) study.

Author information

1
Department of Neurosciences and Mental Health, IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
2
Department of Psychiatry, University Hospital Marqués de Valdecilla, School of Medicine, University of Cantabria-IDIVAL, Santander, Spain.
3
CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Santander, Spain.
4
Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.
5
Department of Psychiatry and Psychotherapy, Philipps University Marburg / Marburg University Hospital UKGM, Marburg, Germany.
6
Department of Clinical Neurosciences and Centro di Eccellenza Risonanza Magnetica ad Alto Campo, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy.
7
Department of Neurology, Jena University Hospital, Jena, Germany.
8
Department of Experimental and Clinical Medical Sciences (DISM), University of Udine, Udine, Italy.
9
Section of Psychiatry, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy.
10
Department of Neurosciences, Biomedicine and Movement Sciences, Section of Clinical Psychology, University of Verona, Verona, Italy.
11
Department of Neurosciences, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy.
12
Department of Psychiatry & Behavioral Neuroscience, Wayne State University, Detroit, MI, United States of America.
13
IRCCS Scientific Institute "E. Medea", Bosisio Parini, Lecco, Italy.
14
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.

Abstract

INTRODUCTION:

Although schizophrenia (SCZ) and bipolar disorder (BD) share elements of pathology, their neural underpinnings are still under investigation. Here, structural Magnetic Resonance Imaging (MRI) data collected from a large sample of BD and SCZ patients and healthy controls (HC) were analyzed in terms of gray matter volume (GMV) using both voxel based morphometry (VBM) and a region of interest (ROI) approach.

METHODS:

The analysis was conducted on two datasets, Dataset1 (802 subjects: 243 SCZ, 176 BD, 383 HC) and Dataset2, a homogeneous subset of Dataset1 (301 subjects: 107 HC, 85 BD and 109 SCZ). General Linear Model analyses were performed 1) at the voxel-level in the whole brain (VBM study), 2) at the regional level in the anatomical regions emerged from the VBM study (ROI study). The GMV comparison across groups was integrated with the analysis of GMV correlates of different clinical dimensions.

RESULTS:

The VBM results of Dataset1 showed 1) in BD compared to HC, GMV deficits in right cingulate, superior temporal and calcarine cortices, 2) in SCZ compared to HC, GMV deficits in widespread cortical and subcortical areas, 3) in SCZ compared to BD, GMV deficits in insula and thalamus (p<0.05, cluster family wise error corrected). The regions showing GMV deficits in the BD group were mostly included in the SCZ ones. The ROI analyses confirmed the VBM results at the regional level in most of the clusters from the SCZ vs. HC comparison (p<0.05, Bonferroni corrected). The VBM and ROI analyses of Dataset2 provided further evidence for the enhanced GMV deficits characterizing SCZ. Based on the clinical-neuroanatomical analyses, we cannot exclude possible confounding effects due to 1) age of onset and medication in BD patients, 2) symptoms severity in SCZ patients.

CONCLUSION:

Our study reported both shared and specific neuroanatomical characteristics between the two disorders, suggesting more severe and generalized GMV deficits in SCZ, with a specific role for insula and thalamus.

PMID:
29136642
PMCID:
PMC5685634
DOI:
10.1371/journal.pone.0188000
[Indexed for MEDLINE]
Free PMC Article
Icon for Public Library of Science Icon for PubMed Central
7.
Brain Cogn. 2017 Oct 18. pii: S0278-2626(17)30208-7. doi: 10.1016/j.bandc.2017.10.003. [Epub ahead of print]

Cortical-hippocampal functional connectivity during covert consolidation sub-serves associative learning: Evidence for an active "rest" state.

Author information

1
Dept of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, USA.
2
Dept of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, USA. Electronic address: vdiwadka@med.wayne.edu.

Abstract

We studied modulation of undirected functional connectivity (uFC) in cortical-hippocampal sub-networks during associative learning. Nineteen healthy individuals were studied (fMRI acquired on a Siemens Verio 3T), and uFC was studied between nodes in a network of regions identified by standard activation models based on bivariate correlational analyses of time series data. The paradigm alternated between Memory Encoding, Rest and Retrieval. "Rest" intervals promoted covert consolidation. Over the task, performance was broadly separable into linear (Early) and asymptomatic (Late) regimes, with late performance reflecting successful memory consolidation. Significant modulation of uFC was observed during periods of covert consolidation. The sub-networks which were modulated constituted connections between frontal regions such as the dorsal prefrontal cortex (dPFC) and dorsal anterior cingulate cortex (dACC), the medial temporal lobe (hippocampus, HPC), the superior parietal cortex (SPC) and the fusiform gyrus (FG). uFC patterns were dynamic in that sub-networks modulated during Early learning (dACC ↔ SPC, dACC ↔ FG, dPFC ↔ HPC) were not identical to those modulated during Late learning (dACC ↔ HPC, dPFC ↔ FG, FG ↔ SPC). Covert consolidation exerts systematic effects, and these results add to emerging evidence for the constructive role of the brain's "resting state" in potentiating action.

KEYWORDS:

Associative learning; Cortical-hippocampal networks; Functional connectivity; Resting state; fMRI

PMID:
29054542
PMCID:
PMC5927855
[Available on 2019-04-18]
DOI:
10.1016/j.bandc.2017.10.003
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8.
Brain Imaging Behav. 2018 Aug;12(4):1220. doi: 10.1007/s11682-017-9768-x.

Erratum to: Activations in gray and white matter are modulated by uni-manual responses during within and inter-hemispheric transfer: effects of response hand and right-handedness.

Author information

1
Brain Imaging Research Division, Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Suite 5B, 3901 Chrysler Drive, Detroit, MI, 48201, USA. vdiwadka@med.wayne.edu.
2
Department of Public Health and Community Medicine, Section of Psychiatry and Section of Clinical Psychology, University of Verona, 37129, Verona, Italy.
3
Brain Imaging Research Division, Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Suite 5B, 3901 Chrysler Drive, Detroit, MI, 48201, USA.
4
Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
5
National Institute of Neuroscience-Verona, Verona, Italy.
6
Neuroradiology Department, Azienda Ospedaliera Universitaria Integrata di Verona, 37126, Verona, Italy.
7
Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
8
Department of Psychiatry and Behavioral Neurosciences, University of Texas at Houston, Houston, TX, USA.

Abstract

The original version of this article unfortunately contained a mistake. The family name of Paolo Brambilla was incorrectly spelled as Bambilla.

9.
Brain Imaging Behav. 2018 Aug;12(4):942-961. doi: 10.1007/s11682-017-9750-7.

Activations in gray and white matter are modulated by uni-manual responses during within and inter-hemispheric transfer: effects of response hand and right-handedness.

Author information

1
Brain Imaging Research Division, Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Suite 5B, 3901 Chrysler Drive, Detroit, MI, 48201, USA. vdiwadka@med.wayne.edu.
2
Department of Public Health and Community Medicine, Section of Psychiatry and Section of Clinical Psychology, University of Verona, 37129, Verona, Italy.
3
Brain Imaging Research Division, Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Suite 5B, 3901 Chrysler Drive, Detroit, MI, 48201, USA.
4
Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
5
National Institute of Neuroscience-Verona, Verona, Italy.
6
Neuroradiology Department, Azienda Ospedaliera Universitaria Integrata di Verona, 37126, Verona, Italy.
7
Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
8
Department of Psychiatry and Behavioral Neurosciences, University of Texas at Houston, Houston, TX, USA.

Abstract

Because the visual cortices are contra-laterally organized, inter-hemispheric transfer tasks have been used to behaviorally probe how information briefly presented to one hemisphere of the visual cortex is integrated with responses resulting from the ipsi- or contra-lateral motor cortex. By forcing rapid information exchange across diverse regions, these tasks robustly activate not only gray matter regions, but also white matter tracts. It is likely that the response hand itself (dominant or non-dominant) modulates gray and white matter activations during within and inter-hemispheric transfer. Yet the role of uni-manual responses and/or right hand dominance in modulating brain activations during such basic tasks is unclear. Here we investigated how uni-manual responses with either hand modulated activations during a basic visuo-motor task (the established Poffenberger paradigm) alternating between inter- and within-hemispheric transfer conditions. In a large sample of strongly right-handed adults (n = 49), we used a factorial combination of transfer condition [Inter vs. Within] and response hand [Dominant(Right) vs. Non-Dominant (Left)] to discover fMRI-based activations in gray matter, and in narrowly defined white matter tracts. These tracts were identified using a priori probabilistic white matter atlases. Uni-manual responses with the right hand strongly modulated activations in gray matter, and notably in white matter. Furthermore, when responding with the left hand, activations during inter-hemispheric transfer were strongly predicted by the degree of right-hand dominance, with increased right-handedness predicting decreased fMRI activation. Finally, increasing age within the middle-aged sample was associated with a decrease in activations. These results provide novel evidence of complex relationships between uni-manual responses in right-handed subjects, and activations during within- and inter-hemispheric transfer suggest that the organization of the motor system exerts sophisticated functional effects. Moreover, our evidence of activation in white matter tracts is consistent with prior studies, confirming fMRI-detectable white matter activations which are systematically modulated by experimental condition.

KEYWORDS:

Inter-hemispheric transfer; Motor organization; Poffenberger paradigm; Right-handedness; White matter; fMRI

PMID:
28808866
PMCID:
PMC5812841
[Available on 2019-08-01]
DOI:
10.1007/s11682-017-9750-7
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10.
Neuroimage Clin. 2017 Jun 23;15:732-740. doi: 10.1016/j.nicl.2017.06.020. eCollection 2017.

Reading related white matter structures in adolescents are influenced more by dysregulation of emotion than behavior.

Author information

1
Cincinnati Children's Hospital Medical Center, University of Cincinnati, United States.
2
Educational Neuroimaging Center, Faculty of Education in Science and Technology, Technion, Israel.
3
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, United States.
4
University Hospitals Case Medical Center, Case Western Reserve University, United States.
5
Department of Psychiatry and Behavioral Neuroscience, Wayne State University, United States.
6
Department of Child Psychiatry, New York University School of Medicine, United States.
7
Department of Psychiatry and Behavioral Health, Wexner Medical Center, Ohio State University, United States.
8
Department of Psychology, University of North Carolina at Chapel Hill, United States.
9
Department of Psychiatry, Johns Hopkins University, United States.

Abstract

Mood disorders and behavioral are broad psychiatric diagnostic categories that have different symptoms and neurobiological mechanisms, but share some neurocognitive similarities, one of which is an elevated risk for reading deficit. Our aim was to determine the influence of mood versus behavioral dysregulation on reading ability and neural correlates supporting these skills in youth, using diffusion tensor imaging in 11- to 17-year-old children and youths with mood disorders or behavioral disorders and age-matched healthy controls. The three groups differed only in phonological processing and passage comprehension. Youth with mood disorders scored higher on the phonological test but had lower comprehension scores than children with behavioral disorders and controls; control participants scored the highest. Correlations between fractional anisotropy and phonological processing in the left Arcuate Fasciculus showed a significant difference between groups and were strongest in behavioral disorders, intermediate in mood disorders, and lowest in controls. Correlations between these measures in the left Inferior Longitudinal Fasciculus were significantly greater than in controls for mood but not for behavioral disorders. Youth with mood disorders share a deficit in the executive-limbic pathway (Arcuate Fasciculus) with behavioral-disordered youth, suggesting reduced capacity for engaging frontal regions for phonological processing or passage comprehension tasks and increased reliance on the ventral tract (e.g., the Inferior Longitudinal Fasciculus). The low passage comprehension scores in mood disorder may result from engaging the left hemisphere. Neural pathways for reading differ mainly in executive-limbic circuitry. This new insight may aid clinicians in providing appropriate intervention for each disorder.

KEYWORDS:

Behavioral disorders; Mood disorders; Passage comprehension; Phonological processing; Reading; White matter tracts

PMID:
28702350
PMCID:
PMC5491458
DOI:
10.1016/j.nicl.2017.06.020
[Indexed for MEDLINE]
Free PMC Article
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11.
PLoS One. 2017 Jul 6;12(7):e0180221. doi: 10.1371/journal.pone.0180221. eCollection 2017.

Using machine learning and surface reconstruction to accurately differentiate different trajectories of mood and energy dysregulation in youth.

Author information

1
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
2
Department of Statistics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
3
Department of Psychiatry and Behavioral Neuroscience, Wayne State University, Detroit, Michigan, United States of America.
4
University Hospitals Case Medical Center/Case Western Reserve University, Cleveland, Ohio, United States of America.
5
Department of Radiology, University Hospitals Case Medical Center/Case Western Reserve University, Cleveland, Ohio, United States of America.
6
Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States of America.
7
Department of Psychiatry, Ohio State University, Columbus, Ohio, United States of America.
8
Pediatric Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
9
Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
10
Department of Child and Adolescent Psychiatry, New York University School of Medicine, New York City, New York, United States of America.
11
Department of Psychiatry, Johns Hopkins University, Baltimore, Maryland, United States of America.

Abstract

Difficulty regulating positive mood and energy is a feature that cuts across different pediatric psychiatric disorders. Yet, little is known regarding the neural mechanisms underlying different developmental trajectories of positive mood and energy regulation in youth. Recent studies indicate that machine learning techniques can help elucidate the role of neuroimaging measures in classifying individual subjects by specific symptom trajectory. Cortical thickness measures were extracted in sixty-eight anatomical regions covering the entire brain in 115 participants from the Longitudinal Assessment of Manic Symptoms (LAMS) study and 31 healthy comparison youth (12.5 y/o;-Male/Female = 15/16;-IQ = 104;-Right/Left handedness = 24/5). Using a combination of trajectories analyses, surface reconstruction, and machine learning techniques, the present study aims to identify the extent to which measures of cortical thickness can accurately distinguish youth with higher (n = 18) from those with lower (n = 34) trajectories of manic-like behaviors in a large sample of LAMS youth (n = 115; 13.6 y/o; M/F = 68/47, IQ = 100.1, R/L = 108/7). Machine learning analyses revealed that widespread cortical thickening in portions of the left dorsolateral prefrontal cortex, right inferior and middle temporal gyrus, bilateral precuneus, and bilateral paracentral gyri and cortical thinning in portions of the right dorsolateral prefrontal cortex, left ventrolateral prefrontal cortex, and right parahippocampal gyrus accurately differentiate (Area Under Curve = 0.89;p = 0.03) youth with different (higher vs lower) trajectories of positive mood and energy dysregulation over a period up to 5years, as measured by the Parent General Behavior Inventory-10 Item Mania Scale. Our findings suggest that specific patterns of cortical thickness may reflect transdiagnostic neural mechanisms associated with different temporal trajectories of positive mood and energy dysregulation in youth. This approach has potential to identify patterns of neural markers of future clinical course.

PMID:
28683115
PMCID:
PMC5500381
DOI:
10.1371/journal.pone.0180221
[Indexed for MEDLINE]
Free PMC Article
Icon for Public Library of Science Icon for PubMed Central
12.
Eur Psychiatry. 2017 Jul;44:125-133. doi: 10.1016/j.eurpsy.2017.04.004. Epub 2017 Apr 25.

Motor system dysfunction in the schizophrenia diathesis: Neural systems to neurotransmitters.

Author information

1
College of Osteopathic Medicine, Michigan State University Lansing, MI, USA.
2
School of Medicine, University of Michigan, Ann Arbor, MI, USA.
3
Department of Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Suite 5A, Tolan Park Medical Building, 3901 Chrysler Service Drive, 48201 Detroit, MI, USA. Electronic address: vdiwadka@med.wayne.edu.

Abstract

Motor control is a ubiquitous aspect of human function, and from its earliest origins, abnormal motor control has been proposed as being central to schizophrenia. The neurobiological architecture of the motor system is well understood in primates and involves cortical and sub-cortical components including the primary motor cortex, supplementary motor area, dorsal anterior cingulate cortex, the prefrontal cortex, the basal ganglia, and cerebellum. Notably all of these regions are associated in some manner to the pathophysiology of schizophrenia. At the molecular scale, both dopamine and γ-Aminobutyric Acid (GABA) abnormalities have been associated with working memory dysfunction, but particularly relating to the basal ganglia and the prefrontal cortex respectively. As evidence from multiple scales (behavioral, regional and molecular) converges, here we provide a synthesis of the bio-behavioral relevance of motor dysfunction in schizophrenia, and its consistency across scales. We believe that the selective compendium we provide can supplement calls arguing for renewed interest in studying the motor system in schizophrenia. We believe that in addition to being a highly relevant target for the study of schizophrenia related pathways in the brain, such focus provides tractable behavioral probes for in vivo imaging studies in the illness. Our assessment is that the motor system is a highly valuable research domain for the study of schizophrenia.

KEYWORDS:

Dopamine; Motor Cortex; Motor Dysfunction; Schizophrenia

PMID:
28641214
PMCID:
PMC5605775
DOI:
10.1016/j.eurpsy.2017.04.004
[Indexed for MEDLINE]
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13.
Psychiatry Res Neuroimaging. 2017 Aug 30;266:42-52. doi: 10.1016/j.pscychresns.2017.05.010. Epub 2017 May 26.

Attempts at memory control induce dysfunctional brain activation profiles in Generalized Anxiety Disorder: An exploratory fMRI study.

Author information

1
Dept. of Psychiatry & Behavioral Neurosciences, Wayne State University, Tolan Park Medical Building, Suite 5B, 3901 Chrysler Service Drive, Detroit, MI 48301, USA.
2
DISM, University of Udine, Udine 33100, Italy.
3
Scientific Institute IRCCS "Eugenio Medea", San Vito al Tagliamento, Pordenone, Italy.
4
Dept. of Psychiatry, University of Milan, Milan, Italy.

Abstract

Suppression of aversive memories through memory control has historically been proposed as a central psychological defense mechanism. Inability to suppress memories is considered a central psychological trait in several psychiatric disorders, including Generalized Anxiety Disorder (GAD). Yet, few studies have attempted the focused identification of dysfunctional brain activation profiles when patients with Generalized Anxiety Disorders attempt memory control. Using a well-characterized behavioral paradigm we studied brain activation profiles in a group of adult GAD patients and well-matched healthy controls (HC). Participants learned word-association pairs before imaging. During fMRI when presented with one word of the pair, they were instructed to either suppress memory of, or retrieve the paired word. Subsequent behavioral testing indicated both GAD and HC were able to engage in the task, but attempts at memory control (suppression or retrieval) during fMRI revealed vastly different activation profiles. GAD were characterized by substantive hypo-activation signatures during both types of memory control, with effects particularly strong during suppression in brain regions including the dorsal anterior cingulate and the ventral prefrontal cortex. Attempts at memory control in GAD fail to engage brain regions to the same extent HC, providing a putative neuronal signature for a well-established psychological characteristic of the illness.

KEYWORDS:

Dorsal anterior cingulate; Generalized Anxiety Disorder; Memory control; Ventral prefrontal cortex; fMRI

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14.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2017 May;2(4):336-345. doi: 10.1016/j.bpsc.2016.06.009.

Longitudinal relationships among activity in attention redirection neural circuitry and symptom severity in youth.

Author information

1
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh.
2
Department of Psychology, University of Pittsburgh.
3
Alpert Medical School, Brown University.
4
Department of Psychiatry and Behavioral Neuroscience, Wayne State University.
5
University Hospitals Case Medical Center/Case Western Reserve University.
6
Cincinnati Children's Hospital Medical Center, University of Cincinnati.
7
The Research Institute at Nationwide Children's Hospital.
8
Department of Child Psychiatry, New York University School of Medicine.
9
Department of Psychiatry, Ohio State University.
10
Department of Psychiatry and Behavioral Health, Ohio State University.
11
Department of Psychology, University of North Carolina at Chapel Hill.
12
Department of Psychiatry, Johns Hopkins University.

Abstract

BACKGROUND:

Changes in neural circuitry function may be associated with longitudinal changes in psychiatric symptom severity. Identification of these relationships may aid in elucidating the neural basis of psychiatric symptom evolution over time. We aimed to distinguish these relationships using data from the Longitudinal Assessment of Manic Symptoms (LAMS) cohort.

METHODS:

Forty-one youth completed two study visits (mean=21.3 months). Elastic-net regression (Multiple response Gaussian family) identified emotional regulation neural circuitry that changed in association with changes in depression, mania, anxiety, affect lability, and positive mood and energy dysregulation, accounting for clinical and demographic variables.

RESULTS:

Non-zero coefficients between change in the above symptom measures and change in activity over the inter-scan interval were identified in right amygdala and left ventrolateral prefrontal cortex. Differing patterns of neural activity change were associated with changes in each of the above symptoms over time. Specifically, from Scan1 to Scan2, worsening affective lability and depression severity were associated with increased right amygdala and left ventrolateral prefrontal cortical activity. Worsening anxiety and positive mood and energy dysregulation were associated with decreased right amygdala and increased left ventrolateral prefrontal cortical activity. Worsening mania was associated with increased right amygdala and decreased left ventrolateral prefrontal cortical activity. These changes in neural activity between scans accounted for 13.6% of the variance; that is 25% of the total explained variance (39.6%) in these measures.

CONCLUSIONS:

Distinct neural mechanisms underlie changes in different mood and anxiety symptoms overtime.

KEYWORDS:

Elastic-net; behaviorally and emotionally dysregulated youth; emotional regulation; longitudinal; neural mechanism; penalized regression

15.
Neuroimage. 2017 Jun;153:189-197. doi: 10.1016/j.neuroimage.2017.03.051. Epub 2017 Mar 29.

Functional dynamics of hippocampal glutamate during associative learning assessed with in vivo 1H functional magnetic resonance spectroscopy.

Author information

1
Brain Imaging Research Division, Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, United States. Electronic address: jeffrey.stanley@wayne.edu.
2
Brain Imaging Research Division, Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, United States.
3
Translational Neuroscience Program, Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, United States; Institute of Gerontology, Wayne State University, Detroit, MI, United States.
4
Translational Neuroscience Program, Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, United States.

Abstract

fMRI has provided vibrant characterization of regional and network responses associated with associative learning and memory; however, their relationship to functional neurochemistry is unclear. Here, we introduce a novel application of in vivo proton functional magnetic resonance spectroscopy (1H fMRS) to investigate the dynamics of hippocampal glutamate during paired-associated learning and memory in healthy young adults. We show that the temporal dynamics of glutamate differed significantly during processes of memory consolidation and retrieval. Moreover, learning proficiency was predictive of the temporal dynamics of glutamate such that fast learners were characterized by a significant increase in glutamate levels early in learning, whereas this increase was only observed later in slow learners. The observed functional dynamics of glutamate provides a novel in vivo marker of brain function. Previously demonstrated N-methyl-D-aspartate (NMDA) receptor mediated synaptic plasticity during associative memory formation may be expressed in glutamate dynamics, which the novel application of 1H MRS is sensitive to. The novel application of 1H fMRS can provide highly innovative vistas for characterizing brain function in vivo, with significant implications for studying glutamatergic neurotransmission in health and disorders such as schizophrenia.

KEYWORDS:

Associative learning and memory; Functional; Glutamate; In vivo; MRS

PMID:
28363835
PMCID:
PMC5498221
DOI:
10.1016/j.neuroimage.2017.03.051
[Indexed for MEDLINE]
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16.
Trends Cogn Sci. 2017 May;21(5):344-356. doi: 10.1016/j.tics.2017.02.001. Epub 2017 Mar 11.

Oculomotor Prediction: A Window into the Psychotic Mind.

Author information

1
Department of Psychology, Michigan State University, East Lansing, MI, USA. Electronic address: kthakkar@msu.edu.
2
Department of Psychiatry and Behavioral Neurosciences, Brain Imaging Research Division, Wayne State University, Detroit, MI, USA.
3
Bernstein Center for Computational Neuroscience and Department of Psychology, Humboldt Universität, 10099 Berlin, Germany.

Abstract

Psychosis - an impaired contact with reality - is a hallmark of schizophrenia. Many psychotic symptoms are associated with disruptions in agency - the sense that 'I' cause my actions. A failure to predict sensory consequences of one's own actions may underlie agency disturbances. Such predictions rely on corollary discharge (CD) signals, 'copies' of movement commands sent to sensory regions prior to action execution. Here, we make a case that the oculomotor system is a promising model for understanding CD in psychosis, building on advances in our understanding of the behavioral and neurophysiological correlates of CD associated with eye movements. In this opinion article, we provide an overview of recent evidence for disturbed oculomotor CD in schizophrenia, potentially linking bizarre and disturbing psychotic experiences with basic physiological processes.

PMID:
28292639
PMCID:
PMC5401650
DOI:
10.1016/j.tics.2017.02.001
[Indexed for MEDLINE]
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17.
PLoS One. 2017 Mar 9;12(3):e0172531. doi: 10.1371/journal.pone.0172531. eCollection 2017.

Potentiation of motor sub-networks for motor control but not working memory: Interaction of dACC and SMA revealed by resting-state directed functional connectivity.

Author information

1
Dept. of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan, United States of America.
2
Center for Complex Systems and Brain Sciences, Florida Atlantic University, Boca Raton, Florida, United States of America.
3
Department of Psychology, Florida Atlantic University, Boca Raton, Florida, United States of America.

Abstract

The dorsal Anterior Cingulate Cortex (dACC) and the Supplementary Motor Area (SMA) are known to interact during motor coordination behavior. We previously discovered that the directional influences underlying this interaction in a visuo-motor coordination task are asymmetric, with the dACC→SMA influence being significantly greater than that in the reverse direction. To assess the specificity of this effect, here we undertook an analysis of the interaction between dACC and SMA in two distinct contexts. In addition to the motor coordination task, we also assessed these effects during a (n-back) working memory task. We applied directed functional connectivity analysis to these two task paradigms, and also to the rest condition of each paradigm, in which rest blocks were interspersed with task blocks. We report here that the previously known asymmetric interaction between dACC and SMA, with dACC→SMA dominating, was significantly larger in the motor coordination task than the memory task. Moreover the asymmetry between dACC and SMA was reversed during the rest condition of the motor coordination task, but not of the working memory task. In sum, the dACC→SMA influence was significantly greater in the motor task than the memory task condition, and the SMA→dACC influence was significantly greater in the motor rest than the memory rest condition. We interpret these results as suggesting that the potentiation of motor sub-networks during the motor rest condition supports the motor control of SMA by dACC during the active motor task condition.

PMID:
28278267
PMCID:
PMC5344349
DOI:
10.1371/journal.pone.0172531
[Indexed for MEDLINE]
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18.
J Psychiatr Res. 2017 May;88:56-63. doi: 10.1016/j.jpsychires.2016.12.016. Epub 2016 Dec 22.

Hyper-modulation of brain networks by the amygdala among women with Borderline Personality Disorder: Network signatures of affective interference during cognitive processing.

Author information

1
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: soloffph@upmc.edu.
2
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA.

Abstract

Emotion dysregulation is a core characteristic of patients with Borderline Personality Disorder (BPD), and is often attributed to an imbalance in fronto-limbic network function. Hyperarousal of amygdala, especially in response to negative affective stimuli, results in affective interference with cognitive processing of executive functions. Clinical consequences include the impulsive-aggression, suicidal and self-injurious behaviors which characterize BPD. Dysfunctional interactions between amygdala and its network targets have not been well characterized during cognitive task performance. Using psychophysiological interaction analysis (PPI), we mapped network profiles of amygdala interaction with key regulatory regions during a Go No-Go task, modified to use negative, positive and neutral Ekman faces as targets. Fifty-six female subjects, 31 BPD and 25 healthy controls (HC), completed the affectively valenced Go No-Go task during fMRI scanning. In the negative affective condition, the amygdala exerted greater modulation of its targets in BPD compared to HC subjects in Rt. OFC, Rt. dACC, Rt. Parietal cortex, Rt. Basal Ganglia, and Rt. dlPFC. Across the spectrum of affective contrasts, hypermodulation in BPD subjects observed the following ordering: Negative > Neutral > Positive contrast. The amygdala seed exerted modulatory effects on specific target regions important in processing response inhibition and motor impulsiveness. The vulnerability of BPD subjects to affective interference with impulse control may be due to specific network dysfunction related to amygdala hyper-arousal and its effects on prefrontal regulatory regions such as the OFC and dACC.

KEYWORDS:

Amygdala; Borderline Personality Disorder; Cognition; Impulsiveness; Psychophysiological interactions; fMRI

PMID:
28086129
PMCID:
PMC5362299
DOI:
10.1016/j.jpsychires.2016.12.016
[Indexed for MEDLINE]
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19.
Psychiatry Res Neuroimaging. 2017 Feb 28;260:76-85. doi: 10.1016/j.pscychresns.2016.12.009. Epub 2016 Dec 16.

Impulsivity and aggression mediate regional brain responses in Borderline Personality Disorder: An fMRI study.

Author information

1
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: soloffph@upmc.edu.
2
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA.

Abstract

Fronto-limbic brain networks involved in regulation of impulsivity and aggression are abnormal in Borderline Personality Disorder (BPD). However, it is unclear whether, or to what extent, these personality traits actually modulate brain responses during cognitive processing. Using fMRI, we examined the effects of trait impulsivity, aggression, and depressed mood on regional brain responses in 31 female BPD and 25 control subjects during a Go No-Go task using Ekman faces as targets. First-level contrasts modeled effects of negative emotional context. Second-level regression models used trait impulsivity, aggression and depressed mood as predictor variables of regional brain activations. In BPD, trait impulsivity was positively correlated with activation in the dorsal anterior cingulate cortex, orbital frontal cortex (OFC), basal ganglia (BG), and dorsolateral prefrontal cortex, with no areas of negative correlation. In contrast, aggression was negatively correlated with activation in OFC, hippocampus, and BG, with no areas of positive correlation. Depressed mood had a generally dampening effect on activations. Effects of trait impulsivity on healthy controls differed from effects in BPD, suggesting a disorder-specific response. Negative emotional context and trait impulsivity, but not aggression or depression, diminished task performance across both groups. Negative emotional context may interfere with cognitive functioning in BPD through interaction with the neurobiology of personality traits.

KEYWORDS:

Affective interference; Executive cognitive functioning; Inhibition; Neuroimaging; Personality traits

PMID:
28039797
PMCID:
PMC5272782
DOI:
10.1016/j.pscychresns.2016.12.009
[Indexed for MEDLINE]
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20.
Psychol Med. 2017 Jun;47(8):1357-1369. doi: 10.1017/S0033291716003147. Epub 2016 Dec 21.

Reward-related neural activity and structure predict future substance use in dysregulated youth.

Author information

1
Department of Psychiatry,Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh,Pittsburgh, PA,USA.
2
Department of Statistics,University of Pittsburgh,Pittsburgh, PA,USA.
3
Department of Psychiatry and Behavioral Neuroscience,Wayne State University,Detroit, MI,USA.
4
Department of Radiology,University Hospitals Case Medical Center/Case Western Reserve University,Cleveland, OH,USA.
5
Cincinnati Children's Hospital Medical Center, University of Cincinnati,Cincinnati, OH,USA.
6
Department of Psychiatry and Behavioral Health,Ohio State University,Columbus, OH,USA.
7
Pediatric Institute,Cleveland Clinic,Cleveland, OH,USA.
8
Department of Psychology,University of North Carolina at Chapel Hill,Chapel Hill, NC,USA.
9
Department of Child and Adolescent Psychiatry,New York University School of Medicine,New York, NY,USA.
10
Department of Psychiatry,Johns Hopkins University,Baltimore, MD,USA.

Abstract

BACKGROUND:

Identifying youth who may engage in future substance use could facilitate early identification of substance use disorder vulnerability. We aimed to identify biomarkers that predicted future substance use in psychiatrically un-well youth.

METHOD:

LASSO regression for variable selection was used to predict substance use 24.3 months after neuroimaging assessment in 73 behaviorally and emotionally dysregulated youth aged 13.9 (s.d. = 2.0) years, 30 female, from three clinical sites in the Longitudinal Assessment of Manic Symptoms (LAMS) study. Predictor variables included neural activity during a reward task, cortical thickness, and clinical and demographic variables.

RESULTS:

Future substance use was associated with higher left middle prefrontal cortex activity, lower left ventral anterior insula activity, thicker caudal anterior cingulate cortex, higher depression and lower mania scores, not using antipsychotic medication, more parental stress, older age. This combination of variables explained 60.4% of the variance in future substance use, and accurately classified 83.6%.

CONCLUSIONS:

These variables explained a large proportion of the variance, were useful classifiers of future substance use, and showed the value of combining multiple domains to provide a comprehensive understanding of substance use development. This may be a step toward identifying neural measures that can identify future substance use disorder risk, and act as targets for therapeutic interventions.

KEYWORDS:

Functional magnetic resonance imaging; GLMNET; LASSO; substance use; youth

PMID:
27998326
PMCID:
PMC5576722
DOI:
10.1017/S0033291716003147
[Indexed for MEDLINE]
Free PMC Article
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