Publications by authors named "Josiane Bourque"

25 Publications

  • Page 1 of 1

Cannabis and Cognitive Functioning: From Acute to Residual Effects, From Randomized Controlled Trials to Prospective Designs.

Front Psychiatry 2021 10;12:596601. Epub 2021 Jun 10.

Department of Psychiatry and Addiction, Faculty of Medicine, University of Montreal, Montreal, QC, Canada.

In recent years, several jurisdictions have revised their regulation policy toward both medical and recreational use of cannabis. These changes have elicited concerns regarding how legalization impacts academic achievement and work performance. This review evaluates the acute and long-term (residual) association between cannabis use and cognitive functioning that underlies poor academic and work performance. Relative to other reviews, this article focuses on cross-over randomized controlled trials and prospective designs given that they allow to test the impairing effects of cannabis exposure at the within-subject level. Acute cannabis cognitive effects are discussed separately for known confounding factors such as levels of delta-9-tetrahydrocannabinol (Δ-THC), Δ-THC:cannabidiol ratio, previous cannabis use and, comorbidity with psychosis-spectrum disorders. The cognitive residual effects of cannabis are detailed in relation to duration of abstinence, frequency of use, comorbidity with psychosis-spectrum disorders, types of cognitive domains assessed, and age of cannabis use initiation. Moreover, considering the fact that adequate longitudinal studies can make inferences about causality between cannabis use and impaired cognitive functioning when disentangling between-subject from within-subject variation, proofs for the three main non-mutually exclusive hypotheses about this relationship will be presented: i) the cognitive vulnerability hypothesis as part of the more general common antecedent hypothesis, ii) the concurrent cannabis impairing hypothesis, and iii) the neurotoxic hypothesis of cannabis. Current research provides evidence for mild to moderate acute cannabis effects on episodic and working memory, processing speed, and executive functions. Mild residual impairing effects were also observed in these exact same cognitive domains, suggesting that adverse effects following cannabis intoxication persist at least days or weeks following cannabis abstinence. Relative to adult-onset, adolescent-onset cannabis use seems to explain the dose-response relationship and is associated with longer lasting residual effects even in mild users (
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http://dx.doi.org/10.3389/fpsyt.2021.596601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222623PMC
June 2021

QSIPrep: an integrative platform for preprocessing and reconstructing diffusion MRI data.

Nat Methods 2021 07 21;18(7):775-778. Epub 2021 Jun 21.

University of Pennsylvania, Philadelphia, PA, USA.

Diffusion-weighted magnetic resonance imaging (dMRI) is the primary method for noninvasively studying the organization of white matter in the human brain. Here we introduce QSIPrep, an integrative software platform for the processing of diffusion images that is compatible with nearly all dMRI sampling schemes. Drawing on a diverse set of software suites to capitalize on their complementary strengths, QSIPrep facilitates the implementation of best practices for processing of diffusion images.
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http://dx.doi.org/10.1038/s41592-021-01185-5DOI Listing
July 2021

Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3-90 years.

Hum Brain Mapp 2021 Feb 17. Epub 2021 Feb 17.

Laboratory of Psychiatric Neuroimaging, Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
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http://dx.doi.org/10.1002/hbm.25364DOI Listing
February 2021

Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years.

Hum Brain Mapp 2021 Feb 11. Epub 2021 Feb 11.

Department of Psychology, Center for Brain Science, Harvard University, Cambridge, Massachusetts, USA.

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
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http://dx.doi.org/10.1002/hbm.25320DOI Listing
February 2021

Adolescent Resting-State Brain Networks and Unique Variability of Conduct Problems Within the Externalizing Dimension.

J Pers Disord 2020 Oct;34(5):609-627

Department of Psychiatry, University of Montreal, Montréal, Quebec, Canada.

The externalizing psychopathological dimension is associated with alterations in adolescents' functional brain connectivity. The current study aims to identify the functional correlates of the unique variability in conduct problems within the context of the broad externalizing dimension. The broad externalizing dimension and unique variability in conduct problems were estimated using a bifactor model. Resting-state data were available for a sample of 125 adolescents. Based on multiresolution parcellation of functional brain networks atlas, major resting-state functional brain networks and the connectivity correlates of unique conduct problems and the broad externalizing dimension were established. The broad externalizing dimension was related to connectivity alterations in the ventral attention/salience network, while unique variability in conduct problems dimension was related to connectivity alterations in the cerebellum crusi as well as the mesolimbic network. The current study is a first step toward the identification of functional resting-state network correlates of broad and specific variability in the externalizing dimension.
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http://dx.doi.org/10.1521/pedi.2020.34.5.609DOI Listing
October 2020

Greater male than female variability in regional brain structure across the lifespan.

Hum Brain Mapp 2020 Oct 12. Epub 2020 Oct 12.

FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain.

For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
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http://dx.doi.org/10.1002/hbm.25204DOI Listing
October 2020

Longitudinal Development of Brain Iron Is Linked to Cognition in Youth.

J Neurosci 2020 02 27;40(9):1810-1818. Epub 2020 Jan 27.

Department of Psychiatry, Perelman School of Medicine.

Brain iron is vital to multiple aspects of brain function, including oxidative metabolism, myelination, and neurotransmitter synthesis. Atypical iron concentration in the basal ganglia is associated with neurodegenerative disorders in aging and cognitive deficits. However, the normative development of brain iron concentration in adolescence and its relationship to cognition are less well understood. Here, we address this gap in a longitudinal sample of 922 humans aged 8-26 years at the first visit (M = 15.1, SD = 3.72; 336 males, 486 females) with up to four multiecho T2* scans each. Using this sample of 1236 imaging sessions, we assessed the longitudinal developmental trajectories of tissue iron in the basal ganglia. We quantified tissue iron concentration using R2* relaxometry within four basal ganglia regions, including the caudate, putamen, nucleus accumbens, and globus pallidus. The longitudinal development of R2* was modeled using generalized additive mixed models (GAMMs) with splines to capture linear and nonlinear developmental processes. We observed significant increases in R2* across all regions, with the greatest and most prolonged increases occurring in the globus pallidus and putamen. Further, we found that the developmental trajectory of R2* in the putamen is significantly related to individual differences in cognitive ability, such that greater cognitive ability is increasingly associated with greater iron concentration through late adolescence and young-adulthood. Together, our results suggest a prolonged period of basal ganglia iron enrichment that extends into the mid-twenties, with diminished iron concentration associated with poorer cognitive ability during late adolescence. Brain tissue iron is essential to healthy brain function. Atypical basal ganglia tissue iron levels have been linked to impaired cognition in iron deficient children and adults with neurodegenerative disorders. However, the normative developmental trajectory of basal ganglia iron concentration during adolescence and its association with cognition are less well understood. In the largest study of tissue iron development yet reported, we characterize the developmental trajectory of tissue iron concentration across the basal ganglia during adolescence and provide evidence that diminished iron content is associated with poorer cognitive performance even in healthy youth. These results highlight the transition from adolescence to adulthood as a period of dynamic maturation of tissue iron concentration in the basal ganglia.
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http://dx.doi.org/10.1523/JNEUROSCI.2434-19.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046454PMC
February 2020

Accelerated cortical thinning within structural brain networks is associated with irritability in youth.

Neuropsychopharmacology 2019 12 2;44(13):2254-2262. Epub 2019 Sep 2.

Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Irritability is an important dimension of psychopathology that spans multiple clinical diagnostic categories, yet its relationship to patterns of brain development remains sparsely explored. Here, we examined how transdiagnostic symptoms of irritability relate to the development of structural brain networks. All participants (n = 137, 83 females) completed structural brain imaging with 3 Tesla MRI at two timepoints (mean age at follow-up: 21.1 years, mean inter-scan interval: 5.2 years). Irritability at follow-up was assessed using the Affective Reactivity Index, and cortical thickness was quantified using Advanced Normalization Tools software. Structural covariance networks were delineated using non-negative matrix factorization, a multivariate analysis technique. Both cross-sectional and longitudinal associations with irritability at follow-up were evaluated using generalized additive models with penalized splines. The False Discovery Rate (q < 0.05) was used to correct for multiple comparisons. Cross-sectional analysis of follow-up data revealed that 11 of the 24 covariance networks were associated with irritability, with higher levels of irritability being associated with thinner cortex. Longitudinal analyses further revealed that accelerated cortical thinning within nine networks was related to irritability at follow-up. Effects were particularly prominent in brain regions implicated in emotion regulation, including the orbitofrontal, lateral temporal, and medial temporal cortex. Collectively, these findings suggest that irritability is associated with widespread reductions in cortical thickness and accelerated cortical thinning, particularly within the frontal and temporal cortex. Aberrant structural maturation of regions important for emotional regulation may in part underlie symptoms of irritability.
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http://dx.doi.org/10.1038/s41386-019-0508-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6897907PMC
December 2019

A Population-Based Analysis of the Relationship Between Substance Use and Adolescent Cognitive Development.

Am J Psychiatry 2019 02 3;176(2):98-106. Epub 2018 Oct 3.

From the Departments of Psychology and Psychiatry, University of Montreal, Montreal; Centre Hospitalier Universitaire Sainte-Justine, Montreal; and the Departments of Psychiatry, Psychology, and Community Health and Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada.

Objective: Alcohol and cannabis misuse are related to impaired cognition. When inferring causality, four nonexclusive theoretical models can account for this association: 1) a common underlying vulnerability model; 2) a neuroplasticity model in which impairment is concurrent with changes in substance use but temporary because of neuroplastic brain processes that restore function; 3) a neurotoxicity model of long-term impairment consequential to substance use; and 4) a developmental sensitivity hypothesis of age-specific effects. Using a developmentally sensitive design, the authors investigated relationships between year-to-year changes in substance use and cognitive development.

Method: A population-based sample of 3,826 seventh-grade students from 31 schools consisting of 5% of all students entering high school in 2012 and 2013 in the Greater Montreal region were assessed annually for 4 years on alcohol and cannabis use, recall memory, perceptual reasoning, inhibition, and working memory, using school-based computerized assessments. Multilevel regression models, performed separately for each substance, were used to simultaneously test vulnerability (between-subject) and concurrent and lagged within-subject effects on each cognitive domain.

Results: Common vulnerability effects were detected for cannabis and alcohol on all domains. Cannabis use, but not alcohol consumption, showed lagged (neurotoxic) effects on inhibitory control and working memory and concurrent effects on delayed memory recall and perceptual reasoning (with some evidence of developmental sensitivity). Cannabis effects were independent of any alcohol effects.

Conclusions: Beyond the role of cognition in vulnerability to substance use, the concurrent and lasting effects of adolescent cannabis use can be observed on important cognitive functions and appear to be more pronounced than those observed for alcohol.
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http://dx.doi.org/10.1176/appi.ajp.2018.18020202DOI Listing
February 2019

Mesolimbic connectivity signatures of impulsivity and BMI in early adolescence.

Appetite 2019 01 29;132:25-36. Epub 2018 Sep 29.

Montreal Neurological Institute, McGill University, Montreal, QC, Canada.

Across age groups, differences in connectivity of the mesolimbic and the prefrontal cortex co-vary with trait impulsivity and sensation-seeking. Impulsivity and sensation-seeking are also known to increase during early adolescence as maturation of subcortical structures outpaces that of the prefrontal cortex. While an imbalance between the striatum and prefrontal cortex is considered a normal developmental process, higher levels of adolescent impulsivity and sensation-seeking are associated with an increased risk for diverse problems, including obesity. To determine how the relationship between sensation-seeking, impulsivity and body mass index (BMI) is related to shared neural correlates we measured their relationships with the connectivity of nuclei in the striatum and dopaminergic midbrain in young adolescents. Data were collected from 116 children between the ages of 12 and 14, and included resting state functional magnetic resonance imaging, personality measures from the Substance Use Risk Profile Scale, and BMI Z-score for age. The shared variance for the connectivity of regions of interest in the substantia nigra, ventral tegmental area, ventral striatum and sub-thalamic nucleus, personality measures and BMI Z-score for age, were analyzed using partial least squares correlation. This analysis identified a single significant striato-limbic network that was connected with the substantia nigra, ventral tegmental area and sub-thalamic nuclei (p = 0.002). Connectivity within this network which included the hippocampi, amygdalae, parahippocampal gyri and the regions of interest, correlated positively with impulsivity and BMI Z-score for age and negatively with sensation-seeking. Together, these findings emphasize that, in addition to the well-established role that frontostriatal circuits play in the development of adolescent personality traits, connectivity of limbic regions with the striatum and midbrain also impact impulsivity, sensation-seeking and BMI Z-score in adolescents.
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http://dx.doi.org/10.1016/j.appet.2018.09.019DOI Listing
January 2019

Association of Cannabis Use With Adolescent Psychotic Symptoms.

JAMA Psychiatry 2018 08;75(8):864-866

Department of Psychiatry, University of Montreal, CHU Sainte-Justine Research Center, Montreal, Quebec, Canada.

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http://dx.doi.org/10.1001/jamapsychiatry.2018.1330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584279PMC
August 2018

Cannabis use and psychotic-like experiences trajectories during early adolescence: the coevolution and potential mediators.

J Child Psychol Psychiatry 2017 Dec 5;58(12):1360-1369. Epub 2017 Jul 5.

Centre de recherche CHU Sainte-Justine, Montreal, QC, Canada.

Background: The authors sought to model the different trajectories of psychotic-like experiences (PLE) during adolescence and to examine whether the longitudinal relationship between cannabis use and PLE is mediated by changes in cognitive development and/or change in anxiety or depression symptoms.

Methods: A total of 2,566 youths were assessed every year for 4-years (from 13- to 16-years of age) on clinical, substance use and cognitive development outcomes. Latent class growth models identified three trajectories of PLE: low decreasing (83.9%), high decreasing (7.9%), and moderate increasing class (8.2%). We conducted logistic regressions to investigate whether baseline levels and growth in cannabis use were associated with PLE trajectory membership. Then, we examined the effects of potential mediators (growth in cognition and anxiety/depression) on the relationship between growth in cannabis use and PLE trajectory.

Results: A steeper growth in cannabis use from 13- to 16-years was associated with a higher likelihood of being assigned to the moderate increasing trajectory of PLE [odds ratio, 2.59; 95% confidence interval (CI), 1.11-6.03], when controlling for cumulative cigarette use. Growth in depression symptoms, not anxiety or change in cognitive functioning, mediated the relationship between growth in cannabis use and the PLE moderate increasing group (indirect effect: 0.07; 95% CI, 0.03-0.11).

Conclusions: Depression symptoms partially mediated the longitudinal link between cannabis use and PLE in adolescents, suggesting that there may be a preventative effect to be gained from targeting depression symptoms, in addition to attempting to prevent cannabis use in youth presenting increasing psychotic experiences.
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http://dx.doi.org/10.1111/jcpp.12765DOI Listing
December 2017

Functional Neuroimaging Predictors of Self-Reported Psychotic Symptoms in Adolescents.

Am J Psychiatry 2017 06 21;174(6):566-575. Epub 2017 Mar 21.

From the Department of Psychiatry, Université de Montréal, CHU Ste.-Justine Hospital and IUSMM Research Center, Montreal; the Departments of Psychiatry and Psychology, University of Vermont, Burlington; the Department of Psychology, University College Dublin, Dublin; the Department of Child and Adolescent Psychiatry and Psychotherapy and the Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; the Department of Psychology, School of Social Sciences, University of Mannheim, Mannheim, Germany; the Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin; the University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; the Medical Research Council-Social, Genetic and Developmental Psychiatry Centre and the Department of Psychological Medicine and Psychiatry, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, U.K.; Neurospin, Commissariat à l'Energie Atomique, CEA-Saclay Center, Paris; the Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, Nottingham, U.K.; the Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin; the Physikalisch-Technische Bundesanstalt, Braunschweig and Berlin, Germany; the Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging and Psychiatry," University Paris Sud, University Paris Descartes-Sorbonne Paris Cité, Paris; the Maison de Solenn, Paris; the Department of Adolescent Psychopathology and Medicine, Maison de Solenn, Cochin Hospital, Paris; the Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles; the Rotman Research Institute, Baycrest, and the Departments of Psychology and Psychiatry, University of Toronto, Toronto; the Department of Child and Adolescent Psychiatry and Psychotherapy, Medical University of Vienna, Vienna; the Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.

Objective: This study investigated the neural correlates of psychotic-like experiences in youths during tasks involving inhibitory control, reward anticipation, and emotion processing. A secondary aim was to test whether these neurofunctional correlates of risk were predictive of psychotic symptoms 2 years later.

Method: Functional imaging responses to three paradigms-the stop-signal, monetary incentive delay, and faces tasks-were collected in youths at age 14, as part of the IMAGEN study. At baseline, youths from London and Dublin sites were assessed on psychotic-like experiences, and those reporting significant experiences were compared with matched control subjects. Significant brain activity differences between the groups were used to predict, with cross-validation, the presence of psychotic symptoms in the context of mood fluctuation at age 16, assessed in the full sample. These prediction analyses were conducted with the London-Dublin subsample (N=246) and the full sample (N=1,196).

Results: Relative to control subjects, youths reporting psychotic-like experiences showed increased hippocampus/amygdala activity during processing of neutral faces and reduced dorsolateral prefrontal activity during failed inhibition. The most prominent regional difference for classifying 16-year-olds with mood fluctuation and psychotic symptoms relative to the control groups (those with mood fluctuations but no psychotic symptoms and those with no mood symptoms) was hyperactivation of the hippocampus/amygdala, when controlling for baseline psychotic-like experiences and cannabis use.

Conclusions: The results stress the importance of the limbic network's increased response to neutral facial stimuli as a marker of the extended psychosis phenotype. These findings might help to guide early intervention strategies for at-risk youths.
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http://dx.doi.org/10.1176/appi.ajp.2017.16080897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5951182PMC
June 2017

Effects of delaying binge drinking on adolescent brain development: a longitudinal neuroimaging study.

BMC Psychiatry 2016 Dec 13;16(1):445. Epub 2016 Dec 13.

Centre de recherche CHU Sainte-Justine, 3175 Côte Ste-Catherine, Montreal, Québec, H3T 1C5, Canada.

Background: Onset of alcohol use by 14 relative to 21 years of age strongly predicts elevated risk for severe alcohol use problems, with 27% versus 4% of individuals exhibiting alcohol dependence within 10 years of onset. What remains unclear is whether this early alcohol use (i) is a marker for later problems, reflected as a pre-existing developmental predisposition, (ii) causes global neural atrophy or (iii) specifically disturbs neuro-maturational processes implicated in addiction, such as executive functions or reward processing. Since our group has demonstrated that a novel intervention program targeting personality traits associated with adolescent alcohol use can prevent the uptake of drinking and binge drinking by 40 to 60%, a crucial question is whether prevention of early onset alcohol misuse will protect adolescent neurodevelopment and which domains of neurodevelopment can be protected.

Methods: A subsample of 120 youth at high risk for substance misuse and 30 low-risk youth will be recruited from the Co-Venture trial (Montreal, Canada) to take part in this 5-year follow-up neuroimaging study. The Co-Venture trial is a community-based cluster-randomised trial evaluating the effectiveness of school-based personality-targeted interventions on substance use and cognitive outcomes involving approximately 3800 Grade 7 youths. Half of the 120 high-risk participants will have received the preventative intervention program. Cognitive tasks and structural and functional neuroimaging scans will be conducted at baseline, and at 24- and 48-month follow-up. Two functional paradigms will be used: the Stop-Signal Task to measure motor inhibitory control and a modified version of the Monetary Incentive Delay Task to evaluate reward processing.

Discussion: The expected results should help identify biological vulnerability factors, and quantify the consequences of early alcohol abuse as well as the benefits of early intervention using brain metrics.
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http://dx.doi.org/10.1186/s12888-016-1148-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5153672PMC
December 2016

Altered brain connectivity in patients with schizophrenia is consistent across cognitive contexts.

J Psychiatry Neurosci 2017 01;42(1):17-26

From the Department of Psychiatry, Université de Montréal, Montreal, Que., Canada (Orban); the Department of Psychology, Faculty of Medicine, University of Namur, Belgium (Desseilles); the Department of Psychology, Bishop's University, Sherbrooke, Que., Canada (Mendrek); the Department of Psychiatry, Université de Montréal, Montreal, Que., Canada (Bourque); the Department of Computer Sciences and Operational Research, Université de Montréal, Montreal, Que., Canada (Bellec); and the Department of Psychiatry, Université de Montréal, Montreal, Que., Canada (Stip).

Background: Schizophrenia has been defined as a dysconnection syndrome characterized by aberrant functional brain connectivity. Using task-based fMRI, we assessed to what extent the nature of the cognitive context may further modulate abnormal functional brain connectivity.

Methods: We analyzed data matched for motion in patients with schizophrenia and healthy controls who performed 3 different tasks. Tasks 1 and 2 both involved emotional processing and only slighlty differed (incidental encoding v. memory recognition), whereas task 3 was a much different mental rotation task. We conducted a connectome-wide general linear model analysis aimed at identifying context-dependent and independent functional brain connectivity alterations in patients with schizophrenia.

Results: After matching for motion, we included 30 patients with schizophrenia and 30 healthy controls in our study. Abnormal connectivity in patients with schizophrenia followed similar patterns regardless of the degree of similarity between cognitive tasks. Decreased connectivity was most notable in the medial prefrontal cortex, the anterior and posterior cingulate, the temporal lobe, the lobule IX of the cerebellum and the premotor cortex.

Limitations: A more circumscribed yet significant context-dependent effect might be detected with larger sample sizes or cognitive domains other than emotional and visuomotor processing.

Conclusion: The context-independence of functional brain dysconnectivity in patients with schizophrenia provides a good justification for pooling data from multiple experiments in order to identify connectivity biomarkers of this mental illness.
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http://dx.doi.org/10.1503/jpn.150247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5373708PMC
January 2017

Cigarette Cravings, Impulsivity, and the Brain.

Front Psychiatry 2015 8;6:125. Epub 2015 Sep 8.

Centre de Recherche de l'Institut Universitaire en Santé Mentale de Montréal , Montreal, QC , Canada ; Department of Psychology, Bishop's University , Lennoxville, QC , Canada.

Craving is a core feature of tobacco use disorder as well as a significant predictor of smoking relapse. Studies have shown that appetitive smoking-related stimuli (e.g., someone smoking) trigger significant cravings in smokers impede their self-control capacities and promote drug seeking behavior. In this review, we begin by an overview of functional magnetic resonance imaging (fMRI) studies investigating the neural correlates of smokers to appetitive smoking cues. The literature reveals a complex and vastly distributed neuronal network underlying smokers' craving response that recruits regions involved in self-referential processing, planning/regulatory processes, emotional responding, attentional biases, and automatic conducts. We then selectively review important factors contributing to the heterogeneity of results that significantly limit the implications of these findings, namely between- (abstinence, smoking expectancies, and self-regulation) and within-studies factors (severity of smoking dependence, sex-differences, motivation to quit, and genetic factors). Remarkably, we found that little to no attention has been devoted to examine the influence of personality traits on the neural correlates of cigarette cravings in fMRI studies. Impulsivity has been linked with craving and relapse in substance and tobacco use, which prompted our research team to examine the influence of impulsivity on cigarette cravings in an fMRI study. We found that the influence of impulsivity on cigarette cravings was mediated by fronto-cingulate mechanisms. Given the high prevalence of cigarette smoking in several psychiatric disorders that are characterized by significant levels of impulsivity, we conclude by identifying psychiatric patients as a target population whose tobacco-smoking habits deserve further behavioral and neuro-imaging investigation.
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http://dx.doi.org/10.3389/fpsyt.2015.00125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4562259PMC
October 2015

Sex differences and menstrual cycle phase-dependent modulation of craving for cigarette: an FMRI pilot study.

Psychiatry J 2014 13;2014:723632. Epub 2014 Nov 13.

Centre de Recherche de l'Institut Universitaire en Santé Mentale de Montréal, 7331 rue Hochelaga, Montreal, QC, Canada H1N 3V2 ; Department of Psychiatry, Faculty of Medicine, University of Montreal, CP 6128, Succursale Centre-Ville, Montréal, QC, Canada H3C 3J7.

While overall more men than women smoke cigarettes, women and girls take less time to become dependent after initial use and have more difficulties quitting the habit. One of the factors contributing to these differences may be that women crave cigarettes more than men and that their desire to smoke is influenced by hormonal fluctuations across the menstrual cycle. Therefore, the purpose of the present study was twofold: (a) to examine potential sex/gender differences in functional neuroanatomy of craving and to (b) delineate neural correlates of cigarette cravings in women across their menstrual cycle. Fifteen tobacco-smoking men and 19 women underwent a functional MRI during presentation of neutral and smoking-related images, known to elicit craving. Women were tested twice: once during early follicular phase and once during midluteal phase of their menstrual cycle. The analysis did not reveal any significant sex differences in the cerebral activations associated with craving. Nevertheless, the pattern of activations in women varied across their menstrual cycle with significant activations in parts of the frontal, temporal, and parietal lobe, during follicular phase, and only limited activations in the right hippocampus during the luteal phase.
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http://dx.doi.org/10.1155/2014/723632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248329PMC
December 2014

Executive-affective connectivity in smokers viewing anti-smoking images: an fMRI study.

Psychiatry Res 2014 Dec 1;224(3):262-8. Epub 2014 Nov 1.

Centre de recherche de l׳Institut Universitaire en Santé Mentale de Montréal and Department of Psychiatry, University of Montreal, Montreal, Canada. Electronic address:

Despite knowledge of the harmful consequences of smoking on health, tobacco users continue to smoke. Neuroimaging studies have begun to provide insight into the mechanisms underlying this response. Regions involved in executive control and affective processing/persuasion are activated when viewing the negative value of smoking, but these systems can interact in ways that promote or hinder its impact on behavior. The goal of this functional magnetic resonance imaging (fMRI) study was to examine the dynamics between these systems during the processing of images designed to elicit a negative emotional response regarding tobacco smoking in a group of current smokers. Thirty chronic smokers passively viewed aversive smoking-related, aversive nonsmoking-related and neutral images presented in a block design while being scanned. Functional connectivity analyses showed that the left inferior frontal gyrus (IFG) is negatively associated to activity in medial frontal, cingulate, limbic, subcortical and parietal regions in chronic smokers during the processing of aversive smoking-related material, a pattern that was significantly greater when stimuli were drug-related compared with when they were nondrug-related. Our results suggest that individuals with tobacco dependence present different patterns of functional connectivity depending on whether the aversive stimuli are smoking- or nonsmoking-related. Activity in the left inferior frontal gyrus may act to down-regulate corresponding activity in regions key to an affective and persuasive response during the processing of anti-smoking material. This mechanism may reduce the extent to which "feeling bad" brings about a change in behavior.
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http://dx.doi.org/10.1016/j.pscychresns.2014.10.018DOI Listing
December 2014

Where there's smoke, there's fire: the brain reactivity of chronic smokers when exposed to the negative value of smoking.

Prog Neuropsychopharmacol Biol Psychiatry 2014 Apr 18;50:66-73. Epub 2013 Dec 18.

Centre de recherche Fernand-Seguin, Institut Universitaire de Santé Mentale de Montréal, Montreal, Canada; Department of Psychiatry, Faculty of Medicine, University of Montreal, Montreal, Canada. Electronic address:

Rational: The addictive nature of smoking is characterized by responses to cigarette stimuli that significantly impede smoking cessation efforts. Studies have shown that smokers are roused by appetitive smoking-related stimuli, and their consumption tends to be unaffected by the negative value of smoking.

Purpose: Using functional magnetic resonance imaging, the goal of this study was two-fold: to examine the brain reactivity of chronic smokers when processing the negative value of smoking using aversive smoking-related cues; to further characterize this response by comparing the latter to the processing of aversive nonsmoking-related and appetitive smoking-related cues.

Method: Thirty chronic smokers passively viewed aversive smoking-related, aversive nonsmoking-related, appetitive smoking-related and neutral images presented in a block design while being scanned.

Results: Aversive smoking-related stimuli elicited significantly greater activation in the medial prefrontal cortex, amygdala, inferior frontal gyrus and lateral orbitofrontal cortex than neutral stimuli. Aversive smoking-related stimuli elicited lower activation in the parahippocampal gyrus, insula and inferior frontal gyrus compared to the aversive nonsmoking-related condition, as well as lower activation in the posterior cingulate, precuneus and medial prefrontal cortices compared to appetitive smoking-related cues.

Conclusion: The brain activation pattern observed suggests that chronic smokers experience an aversive response when processing aversive smoking-related stimuli, however we argue that the latter triggers a weaker negative emotional and driving response than the aversive non-smoking-related and appetitive smoking-related cues respectively. These fMRI results highlight potentially important processes underlying the insensitivity to the negative value of smoking, an important characteristic of addiction.
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http://dx.doi.org/10.1016/j.pnpbp.2013.12.009DOI Listing
April 2014

The neural correlates of mental rotation abilities in cannabis-abusing patients with schizophrenia: an FMRI study.

Schizophr Res Treatment 2013 17;2013:543842. Epub 2013 Jul 17.

Centre de Recherche de l'Institut Universitaire de Santé Mentale de Montréal, 7331 Hochelaga, Montreal, QC, Canada H1N 3V2 ; Department of Psychiatry, Faculty of Medicine, University of Montreal, 2900 Edouard-Montpetit, Montreal, QC, Canada H3C 3J7.

Growing evidence suggests that cannabis abuse/dependence is paradoxically associated with better cognition in schizophrenia. Accordingly, we performed a functional magnetic resonance imaging (fMRI) study of visuospatial abilities in 14 schizophrenia patients with cannabis abuse (DD), 14 nonabusing schizophrenia patients (SCZ), and 21 healthy controls (HCs). Participants performed a mental rotation task while being scanned. There were no significant differences in the number of mistakes between schizophrenia groups, and both made more mistakes on the mental rotation task than HC. Relative to HC, SCZ had increased activations in the left thalamus, while DD patients had increased activations in the right supramarginal gyrus. In both cases, hyper-activations are likely to reflect compensatory efforts. In addition, SCZ patients had decreased activations in the left superior parietal gyrus compared to both HC and DD patients. This latter result tentatively suggests that the neurophysiologic processes underlying visuospatial abilities are partially preserved in DD, relative to SCZ patients, consistently with the findings showing that cannabis abuse in schizophrenia is associated with better cognitive functioning. Further fMRI studies are required to examine the neural correlates of other cognitive dysfunctions in schizophrenia patients with and without comorbid cannabis use disorder.
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http://dx.doi.org/10.1155/2013/543842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730190PMC
August 2013

Cannabis abuse is associated with better emotional memory in schizophrenia: a functional magnetic resonance imaging study.

Psychiatry Res 2013 Oct 30;214(1):24-32. Epub 2013 Jul 30.

Centre de recherche Fernand-Seguin, Montreal, QC, Canada.

In schizophrenia cannabis abuse/dependence is associated with poor compliance and psychotic relapse. Despite this, the reasons for cannabis abuse remain elusive, but emotions may play a critical role in this comorbidity. Accordingly, we performed a functional magnetic resonance imaging study of emotional memory in schizophrenia patients with cannabis abuse (dual-diagnosis, DD). Participants comprised 14 DD patients, 14 non-abusing schizophrenia patients (SCZ), and 21 healthy controls (HC) who had to recognize positive and negative pictures while being scanned. Recognition of positive and negative emotions was prominently impaired in SCZ patients, relative to HC, while differences between DD and HC were smaller. For positive and negative stimuli, we observed significant activations in frontal, limbic, temporal and occipital regions in HC; in frontal, limbic and temporal regions in DD; and in temporal, parietal, limbic and occipital regions in the SCZ group. Our results suggest that emotional memory and prefrontal lobe functioning are preserved in DD relative to SCZ patients. These results are consistent with previous findings showing that cannabis abuse is associated with fewer negative symptoms and better cognitive functioning in schizophrenia. Longitudinal studies will need to determine whether the relative preservation of emotional memory is primary or secondary to cannabis abuse in schizophrenia.
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http://dx.doi.org/10.1016/j.pscychresns.2013.05.012DOI Listing
October 2013

Neural circuitry of impulsivity in a cigarette craving paradigm.

Front Psychiatry 2013 16;4:67. Epub 2013 Jul 16.

Centre de Recherche de l'Institut Universitaire de Santé Mentale de Montréal , Montréal, QC , Canada ; Department of Psychiatry, Faculty of Medicine, University of Montreal , Montreal, QC , Canada.

Impulsivity has been shown to play a pivotal role in the onset, pattern of consumption, relapse and, most notably, craving of illicit and licit drugs such as cigarette smoking. The goal of this study was to examine the neurobiological influence of trait impulsivity during cue-induced cigarette craving. Thirty-one chronic smokers passively viewed appetitive smoking-related and neutral images while being scanned and reported their feelings of craving. They completed the Barratt Impulsiveness Scale, a measure of trait impulsivity. We conducted functional connectivity analyses using the psycho-physiological interaction method. During the processing of smoking stimuli, participants presented increased activations in the cingulate and prefrontal cortices. We observed a significant positive relationship between impulsivity scores and reported craving. A negative correlation was observed between the impulsivity score and activity in the posterior cingulate cortex (PCC). The insula, dorsal anterior cingulate cortex (dACC) as well as the dorsolateral prefrontal cortex (DLPFC) presented a negative connectivity with the PCC. Consistent with the view that the PCC is related to the ability to resist cigarette craving, our results suggest that high impulsive smokers have greater difficulty in controlling their cravings, and that this weakness may be mediated by lower PCC activity. Moreover, we argue that the less PCC activity, the greater the probability of a stronger emotional, physiological, and biased attentional response to smoking cues mediated by insula, dACC, and DLPFC activity. This is the first study on this topic, and so, results will need to be replicated in both licit and illicit drug abusers. Our findings also highlight a need for more emphasis on the PCC in drug addiction research, as it is one of the most consistently activated regions in functional magnetic resonance imaging studies examining the neural correlates of cue-induced alcohol, drug, and tobacco cravings.
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http://dx.doi.org/10.3389/fpsyt.2013.00067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712893PMC
July 2013

Clozapine and visuospatial processing in treatment-resistant schizophrenia.

Cogn Neuropsychiatry 2013 23;18(6):615-30. Epub 2013 Jan 23.

a Fernand-Seguin Research Centre of Louis-H. Lafontaine Hospital , Montreal , Quebec , Canada.

Introduction: Clozapine, the most widely used option in treatment-resistant schizophrenia, has been shown to be superior to other antipsychotic medications in improving cognitive function in patients. However, the results have not been consistent and the mechanisms underlying this effect have not been elucidated. Thus, the purpose of the present study was to evaluate verbal and nonverbal cognition (using visuospatial processing tests) in patients treated with clozapine (initially treatment resistant) and those treated with other second-generation antipsychotics, relative healthy control subjects. Furthermore, we examined neural correlates of visuospatial processing in the three groups.

Methods: Twenty schizophrenia patients treated with clozapine (TR-C group), 23 patients stabilised with atypical antipsychotics other than clozapine (NTR group), and 21 healthy control participants completed a battery of verbal and visuospatial cognitive tests. In addition, participants underwent functional magnetic resonance imaging (fMRI) while performing one of the visuospatial tests (the mental rotation task). The fMRI data were analysed separately in each group using Statistical Parametric Mapping software (SPM5).

Results: Overall, schizophrenia patients exhibited deficit on verbal and nonverbal processing relative to the healthy controls, but we observed some interesting differences between the two groups of patients. Specifically, the NTR group performed better than the TR-C group on the Block Design and the Raven's Progressive Matrices. With respect to brain function during mental rotation, the NTR group showed significant activations in regions of the temporal and occipital cortex, whereas the TR-C patients did not. The relative deactivations associated with the task were also more robust in NTR compared to the other group of patients, despite a similar performance.

Conclusion: Present results suggest better visuospatial processing in the NTR relative to the TR-C group. This difference could be attributed to the treatment resistance itself or a lack of beneficial effect of clozapine relative to other atypical antipsychotics in ameliorating nonverbal abilities. Future studies of the relationship between clozapine and cognition, as well as between treatment resistance and cognition, are warranted.
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http://dx.doi.org/10.1080/13546805.2012.760917DOI Listing
May 2014

Progesterone and Cerebral Function during Emotion Processing in Men and Women with Schizophrenia.

Schizophr Res Treatment 2012 15;2012:917901. Epub 2012 Feb 15.

Centre de Recherche Fernand-Séguin, Hôpital Louis-Hippolyte Lafontaine, 7331 Rue Hochelaga, Montréal, QC, Canada H1N 3V2.

Schizophrenia has been associated with disturbed levels of sex-steroid hormones, including estrogen and testosterone. In the present study we have examined the implication of a less studied hormone progesterone. Forty-three patients with schizophrenia (21 women) and 43 control participants (21 women) underwent functional MRI while viewing emotionally positive, negative, and neutral images. Blood samples were taken prior to the scanning session to evaluate progesterone levels. Simple regression analyses between levels of progesterone and brain activations associated with emotion processing were performed using SPM5. A positive correlation was found between progesterone levels and brain activations during processing of emotionally charged images in both healthy and schizophrenia men, but no significant relationship was revealed in women. These preliminary results indicate that progesterone is significantly associated with brain activations during processing of positive and negative affect in healthy and schizophrenia men, but not in women. Further investigation is warranted.
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http://dx.doi.org/10.1155/2012/917901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3420639PMC
September 2012

Emotion processing in women with schizophrenia is menstrual cycle phase and affective valence dependent: an FMRI study.

ISRN Psychiatry 2012 1;2012:656274. Epub 2012 Mar 1.

Centre de Recherche Fernand-Seguin, Department of Psychiatry, Université de Montréal, 7331 Hochelaga, Montreal, QC, Canada H1N 3V2.

Despite a large number of functional neuroimaging investigations of emotion processing in schizophrenia, very few have included women. In the present study 21 schizophrenia and 23 healthy women underwent functional MRI (3T) on two occasions (during the follicular and luteal phase of their menstrual cycle) while viewing blocks of emotionally negative, positive and neutral images. During exposure to negatively charged images patients showed relatively less activations than controls during the luteal phase, but no between-group differences were observed during the follicular phase. In contrast, the exposure to positively valenced material produced no significant interaction, but the main effect of group; schizophrenia patients exhibited less activation than healthy controls during both phases of the menstrual cycle. This is the first study demonstrating that atypical neural activations associated with emotion processing in women diagnosed with schizophrenia depend on the menstrual cycle phase and on the affective valence of presented stimuli.
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http://dx.doi.org/10.5402/2012/656274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3658698PMC
June 2013
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