Molecular signatures of cortical expansion in the human fetal brain.

The third trimester of human gestation is characterised by rapid increases in brain volume and cortical surface area. A growing catalogue of cells in the prenatal brain has revealed remarkable molecular diversity across cortical areas.1,2 Despite this, little is known about how this translates into the patterns of differential cortical expansion observed in humans during the latter stages of gestation. Here we present a new resource, µBrain, to facilitate knowledge translation between molecular and anatomical descriptions of the prenatal developing brain. Built using generative artificial intelligence, µBrain is a three-dimensional cellular-resolution digital atlas combining publicly-available serial sections of the postmortem human brain at 21 weeks gestation3 with bulk tissue microarray data, sampled across 29 cortical regions and 5 transient tissue zones.4 Using µBrain, we evaluate the molecular signatures of preferentially-expanded cortical regions during human gestation, quantified in utero using magnetic resonance imaging (MRI). We find that differences in the rates of expansion across cortical areas during gestation respect anatomical and evolutionary boundaries between cortical types5 and are founded upon extended periods of upper-layer cortical neuron migration that continue beyond mid-gestation. We identify a set of genes that are upregulated from mid-gestation and highly expressed in rapidly expanding neocortex, which are implicated in genetic disorders with cognitive sequelae. Our findings demonstrate a spatial coupling between areal differences in the timing of neurogenesis and rates of expansion across the neocortical sheet during the prenatal epoch. The µBrain atlas is available from: https://garedaba.github.io/micro-brain/ and provides a new tool to comprehensively map early brain development across domains, model systems and resolution scales.

"There should be one spot that you can go:" BRCA mutation carriers' perspectives on cancer risk management and a hereditary cancer registry.

Individuals who carry BRCA1 or BRCA2 pathogenic variants are recommended to have extensive cancer prevention screening and risk-reducing surgeries. Uptake of these recommendations is variable, and there remains room for improvement in the risk management of BRCA carriers. This paper explores female BRCA carriers' experiences with the current model of care and their perspectives on (and interest in) an inherited cancer registry. Findings can inform the development of a dedicated high-risk screening and management program for these patients. Quantitative and qualitative data were gathered through a provincial descriptive survey and semi-structured qualitative interviews to assess BRCA carriers' opinions toward risk management services in the province of Newfoundland and Labrador (NL), Canada. Survey (n = 69) and interview data (n = 15) revealed continuity and coordination challenges with the current system of care of high-risk individuals. Respondents suggested an inherited cancer registry would help identify high-risk individuals and provide a centralized system of risk management for identified carriers. Respondents identified concerns about the privacy of their registry data, including who could access it. Findings suggest BRCA carriers see great value in an inherited cancer registry. Specifically, participants noted it could provide a centralized system to help improve the coordination of burdensome, life-long risk management. Important patient concerns about protecting their privacy and their health data confidentiality must be addressed in patient and public information and informed consent documents about a registry.

Characterizing White Matter Tract Organization in Polymicrogyria and Lissencephaly: A Multifiber Diffusion MRI Modeling and Tractography Study.

BACKGROUND AND PURPOSE: Polymicrogyria and lissencephaly may be associated with abnormal organization of the undelying white matter tracts that have been rarely investigated so far. Our aim was to characterize white matter tract organization in polymicrogyria and lissencephaly using constrained spherical deconvolution, a multifiber diffusion MR imaging modeling technique for white matter tractography reconstruction. MATERIALS AND METHODS: We retrospectively reviewed 50 patients (mean age, 8.3 ± 5.4 years; range, 1.4-21.2 years; 27 males) with different polymicrogyria (n = 42) and lissencephaly (n = 8) subtypes. The fiber direction-encoded color maps and 6 different white matter tracts reconstructed from each patient were visually compared with corresponding images reconstructed from 7 age-matched, healthy control WM templates. Each white matter tract was assessed by 2 experienced pediatric neuroradiologists and scored in consensus on the basis of the severity of the structural abnormality, ranging from the white matter tracts being absent to thickened. The results were summarized by different polymicrogyria and lissencephaly subgroups. RESULTS: More abnormal-appearing white matter tracts were identified in patients with lissencephaly compared with those with polymicrogyria (79.2% versus 37.3%). In lissencephaly, structural abnormalities were identified in all studied white matter tracts. In polymicrogyria, the more frequently affected white matter tracts were the cingulum, superior longitudinal fasciculus, inferior longitudinal fasciculus, and optic radiation-posterior corona radiata. The severity of superior longitudinal fasciculus and cingulum abnormalities was associated with the polymicrogyria distribution and extent. A thickened superior fronto-occipital fasciculus was demonstrated in 3 patients. CONCLUSIONS: We demonstrated a range of white matter tract structural abnormalities in patients with polymicrogyria and lissencephaly. The patterns of white matter tract involvement are related to polymicrogyria and lissencephaly subgroups, distribution, and, possibly, their underlying etiologies.

Cortical remodelling in childhood is associated with genes enriched for neurodevelopmental disorders.

Cortical development during childhood and adolescence has been characterised in recent years using metrics derived from Magnetic Resonance Imaging (MRI). Changes in cortical thickness are greatest in the first two decades of life and recapitulate the genetic organisation of the cortex, highlighting the potential early impact of gene expression on differences in cortical architecture over the lifespan. It is important to further our understanding of the possible neurobiological mechanisms that underlie these changes as cortical thickness may be altered in several common neurodevelopmental and psychiatric disorders. In this study, we combine MRI acquired from a large typically-developing childhood population (n â€‹= â€‹768) with comprehensive human gene expression databases to test the hypothesis that disrupted mechanisms common to neurodevelopmental disorders are encoded by genes expressed early in development and nested within those associated with typical cortical remodelling in childhood. We find that differential rates of thinning across the developing cortex are associated with spatially-varying gradients of gene expression. Genes that are expressed highly in regions of accelerated thinning are expressed predominantly in cortical neurons, involved in synaptic remodelling, and associated with common cognitive and neurodevelopmental disorders. Further, we identify subsets of genes that are highly expressed in the prenatal period and jointly associated with both developmental cortical morphology and neurodevelopmental disorders.

Individual variation in longitudinal postnatal development of the primate brain.

Quantifying individual variation in postnatal brain development can provide insight into cognitive diversity within a population and the aetiology of common neuropsychiatric and neurodevelopmental disorders. Non-invasive studies of the non-human primate can aid understanding of human brain development, facilitating longitudinal analysis during early postnatal development when comparative human populations are difficult to sample. In this study, we perform analysis of a longitudinal MRI dataset of 32 macaques, each with up to five magnetic resonance imaging (MRI) scans acquired between 3 and 36 months of age. Using nonlinear mixed effects model we derive growth trajectories for whole brain, cortical and subcortical grey matter, cerebral white matter and cerebellar volume. We then test the association between individual variation in postnatal tissue volumes and birth weight. We report nonlinear growth models for all tissue compartments, as well as significant variation in total intracranial volume between individuals. We also demonstrate that regional subcortical grey matter varies both in total volume and rate of change between individuals and is associated with differences in birth weight. This supports evidence that birth weight may act as a marker of subsequent brain development and highlights the importance of longitudinal MRI analysis in developmental studies.

Eastern Canadian Colorectal Cancer Consensus Conference 2017.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2017 was held in St. John's, Newfoundland and Labrador, 28-30 September. Experts in radiation oncology, medical oncology, surgical oncology, and cancer genetics who are involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics in the management of gastric, rectal, and colon cancer, including ■ identification and management of hereditary gastric and colorectal cancer (crc);■ palliative systemic therapy for metastatic gastric cancer;■ optimum duration of preoperative radiation in rectal cancer-that is, short- compared with long-course radiation;■ management options for peritoneal carcinomatosis in crc;■ implications of tumour location for treatment and prognosis in crc; and■ new molecular markers in crc.

Advances in the systemic treatment of triple-negative breast cancer.

Triple-negative breast cancer constitutes a heterogeneous group of malignancies that are often aggressive and associated with a poor prognosis. Molecular characterization, while not a standard of care, can further subtype triple-negative breast cancer and provide insight into prognostication and behaviour. Optimal chemotherapy regimens have yet to be established; however, there have been advances in the systemic treatment of triple-negative breast cancer in the neoadjuvant, adjuvant, and metastatic settings. In this review, we discuss evidence for the potential benefit of neoadjuvant platinum-based chemotherapy, adjuvant combination chemotherapy with weekly paclitaxel, and BRCA mutation-directed therapy in the metastatic setting. The role for adjuvant capecitabine in patients who do not achieve a pathologic complete response with neoadjuvant chemotherapy is reviewed. Future directions and data concerning novel targeted agents are reviewed, including the most recent data on parp [poly (adp-ribose) polymerase] inhibitors, antiandrogen agents, and immunotherapy.

Study protocol: families and childhood transitions study (FACTS) - a longitudinal investigation of the role of the family environment in brain development and risk for mental health disorders in community based children.

BACKGROUND: Extant research has demonstrated that parenting behaviour can be a significant contributor to the development of brain structure and mental health during adolescence. Nonetheless, there is limited research examining these relationships during late childhood, and particularly in the critical period of brain development occurring between 8 and 10 years of age. The effects of the family environment on the brain during late childhood may have significant implications for later functioning, and particularly mental health. The Families and Childhood Transitions Study (FACTS) is a multidisciplinary longitudinal cohort study of brain development and mental health, with two waves of data collection currently funded, occurring 18-months apart, when child participants are aged approximately 8- and 10-years old. METHODS/DESIGN: Participants are 163 children (M age [SD] = 8.44 [0.34] years, 76 males) and their mothers (M age [SD] = 40.34 [5.43] years). Of the 163 families who consented to participate, 156 completed a video-recorded and observer-coded dyadic interaction task and 153 completed a child magnetic resonance imaging brain scan at baseline. Families were recruited from lower socioeconomic status (SES) areas to maximise rates of social disadvantage and variation in parenting behaviours. All experimental measures and tasks completed at baseline are repeated at an 18-month follow-up, excluding the observer coded family interaction tasks. The baseline assessment was completed in October 2015, and the 18-month follow up will be completed May 2017. DISCUSSION: This study, by examining the neurobiological and mental health consequences of variations in parenting, has the potential to significantly advance our understanding of child development and risk processes. Recruitment of lower SES families will also allow assessment of resilience factors given the poorer outcomes often associated with this population.

Treatment and outcomes for glioblastoma in elderly compared with non-elderly patients: a population-based study.

PURPOSE: Elderly patients make up a large percentage of the individuals newly diagnosed with glioblastoma (gbm), but they face particular challenges in tolerating standard therapy, and compared with younger patients, they experience significantly shorter survival. We set out to compare clinical characteristics, treatment patterns, and outcomes in a non-elderly group (<65 years) and an elderly group (≥65 years) of patients diagnosed with gbm. METHODS: This retrospective population-based study used a province-wide cancer registry to identify patients with a new diagnosis of gbm within a 6-year period (2006-2012). Of the 138 patients identified, 56 (40.6%) were 65 years of age or older. Demographic characteristics, treatment patterns, and overall survival (os) in the elderly and non-elderly groups were compared. Predictors of os were determined using multivariate analysis. RESULTS: Elderly patients were more likely to present with a poor performance status (Eastern Cooperative Oncology Group ≥ 2), to undergo biopsy without resection, and to receive whole-brain or hypofractionated radiotherapy. Compared with non-elderly patients, the elderly patients were less likely to receive adjuvant temozolomide. Survival time was significantly shorter in the elderly than in the non-elderly patients (7.2 months vs. 11.2 months). In multivariate analysis, surgical resection, hypofractionated radiotherapy (compared with whole-brain or conventional radiotherapy), and chemotherapy were predictive of os in older patients. Among elderly patients receiving radiation, survival was improved with the use of combined therapy compared with the use of radiation only (11.3 months vs. 4.6 months). CONCLUSIONS: Overall survival was shorter for elderly patients with gbm than for non-elderly patients; the elderly patients were also less likely to receive intensive surgical or adjuvant therapy. Our population-based analysis demonstrated improved os with surgical resection, hypofractionated radiotherapy, and temozolomide, and supports the results of recent clinical trials demonstrating a benefit for combination chemoradiotherapy in older patients.

Eastern Canadian Colorectal Cancer Consensus Conference 2013: emerging therapies in the treatment of pancreatic, rectal, and colorectal cancers.

The annual Eastern Canadian Colorectal Cancer Consensus Conference held in Montreal, Quebec, 17-19 October 2013, marked the 10-year anniversary of this meeting that is attended by leaders in medical, radiation, and surgical oncology. The goal of the attendees is to improve the care of patients affected by gastrointestinal malignancies. Topics discussed during the conference included pancreatic cancer, rectal cancer, and metastatic colorectal cancer.

Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016 was held in Montreal, Quebec, 5-7 February. Experts in radiation oncology, medical oncology, surgical oncology, and infectious diseases involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics: ■ Follow-up and survivorship of patients with resected colorectal cancer■ Indications for liver metastasectomy■ Treatment of oligometastases by stereotactic body radiation therapy■ Treatment of borderline resectable and unresectable pancreatic cancer■ Transarterial chemoembolization in hepatocellular carcinoma■ Infectious complications of antineoplastic agents.

Using tablet-based technology in patient education about systemic therapy options for early-stage breast cancer: a pilot study.

BACKGROUND: Patient education in early-stage breast cancer has been shown to improve patient well-being and quality of life, but it poses a challenge given the increasingly complex regimens and time constraints in clinical practice. Technology-aided teaching in the clinic could help to improve the understanding of adjuvant systemic therapy for patients. In this prospective pilot study, we used a clinician-administered, tablet-based teaching aid to teach patients with early-stage breast cancer about adjuvant systemic therapy. METHODS: Participation was offered to newly diagnosed patients with early-stage breast cancer presenting for their first medical oncology visit at a provincial cancer centre. Participants were shown a tablet-based presentation describing procedures, rationales, risks, and benefits of adjuvant systemic therapy as an adjunct to a discussion with the medical oncologist. After the clinic visit, participants completed a questionnaire measuring satisfaction with the visit and knowledge of the treatment plan discussed. RESULTS: The 25 patients recruited for the study had a mean age of 57 years. An offer of upfront chemotherapy alone was made to 12 participants (48%), chemotherapy with trastuzumab to 4 (16%), and hormonal therapy to 9 (36%). Correct answers to all questions related to treatment knowledge were given by 22 patients (88%). Satisfaction with the clinic visit was high (mean satisfaction score: 4.53 ± 0.1 of a possible 5). CONCLUSIONS: We found that a tablet-based presentation about adjuvant systemic therapy was satisfactory to patients with early-stage breast cancer and that knowledge retention after the clinic visit was high. Tablet-based teaching could be a feasible and effective way of educating patients in the breast oncology clinic and warrants further investigation in randomized studies.

Evidence of a dimensional relationship between schizotypy and schizophrenia: a systematic review.

The personality dimension of schizotypy is well established, and schizotypal traits can be taken to represent a proneness toward developing psychosis. Yet, there are competing theories about the latent structure of schizotypy. More specifically, there is controversy over the extent to which this propensity toward psychosis is present only in a small proportion of the population, or whether it is spread dimensionally throughout the general community. On the basis of accumulating research findings the present article argues for a fully dimensional model of schizotypy. It describes recent neurobiological, neuropsychological, social and environmental evidence supporting the idea that schizotypy in healthy populations, and disorders on the schizophrenia spectrum are fundamentally linked. Directions for further research are also considered.

Cannabis affects people differently: inter-subject variation in the psychotogenic effects of Δ9-tetrahydrocannabinol: a functional magnetic resonance imaging study with healthy volunteers.

BACKGROUND: Cannabis can induce transient psychotic symptoms, but not all users experience these adverse effects. We compared the neural response to Δ9-tetrahydrocannabinol (THC) in healthy volunteers in whom the drug did or did not induce acute psychotic symptoms. Method In a double-blind, placebo-controlled, pseudorandomized design, 21 healthy men with minimal experience of cannabis were given either 10 mg THC or placebo, orally. Behavioural and functional magnetic resonance imaging measures were then recorded whilst they performed a go/no-go task. RESULTS: The sample was subdivided on the basis of the Positive and Negative Syndrome Scale positive score following administration of THC into transiently psychotic (TP; n = 11) and non-psychotic (NP; n = 10) groups. During the THC condition, TP subjects made more frequent inhibition errors than the NP group and showed differential activation relative to the NP group in the left parahippocampal gyrus, the left and right middle temporal gyri and in the right cerebellum. In these regions, THC had opposite effects on activation relative to placebo in the two groups. The TP group also showed less activation than the NP group in the right middle temporal gyrus and cerebellum, independent of the effects of THC. CONCLUSIONS: In this first demonstration of inter-subject variability in sensitivity to the psychotogenic effects of THC, we found that the presence of acute psychotic symptoms was associated with a differential effect of THC on activation in the ventral and medial temporal cortex and cerebellum, suggesting that these regions mediate the effects of the drug on psychotic symptoms.

Outcomes of women with early-stage breast cancer receiving adjuvant trastuzumab.

INTRODUCTION: Large randomized trials assessing the benefit of adjuvant trastuzumab in early-stage breast cancer positive for the human epidermal growth factor receptor 2 (her2) have demonstrated a significant improvement in survival. The objective of the present study was to describe the outcomes of women who received adjuvant trastuzumab for her2-positive breast cancer in British Columbia since publicly funded population-based use was initiated in July 2005. METHODS: Women from British Columbia, newly diagnosed with stage i-iii breast cancer between July 2004 and December 2006, who were positive for her2 overexpression by immunohistochemistry (3+) or amplification by fluorescence in situ hybridization (ratio ≥ 2.0) were included in the study. Data were collected from the prospectively assembled BC Cancer Agency Outcomes Unit, with cases linked to the provincial pharmacy data repository to determine the proportion of women who received adjuvant trastuzumab. RESULTS: Our retrospective study identified 703 her2-positive patients, of whom 480 (68%) received trastuzumab. In patients receiving trastuzumab, the 2-year relapse-free survival was 96.1% [95% confidence interval (CI): 93.6% to 97.7%] and the overall survival was 99.3% (95% CI: 97.9% to 99.8%). Among node-negative and -positive patients, the 2-year relapse-free survival was 97.8% and 94.8% respectively (p = 0.09) for the trastuzumab-treated group and 90.9% and 77.3% (p = 0.01) for the group not receiving trastuzumab (n = 223). Site of first distant metastasis was the central nervous system in 19.5% of the entire cohort and in 37.5% of patients treated with trastuzumab. DISCUSSION: This population-based analysis of adjuvant trastuzumab use among Canadian women demonstrates highly favorable outcomes at the 2-year follow-up.

Acute effects of a single, oral dose of d9-tetrahydrocannabinol (THC) and cannabidiol (CBD) administration in healthy volunteers.

RATIONALE: Animal and humans studies suggest that the two main constituents of cannabis sativa, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have quite different acute effects. However, to date the two compounds have largely been studied separately. OBJECTIVE: To evaluate and compare the acute pharmacological effects of both THC and CBD in the same human volunteers. METHODS: A randomised, double-blind, cross-over, placebo controlled trial was conducted in 16 healthy male subjects. Oral THC 10 mg or CBD 600 mg or placebo was administered in three consecutive sessions, at one-month interval. Physiological measures and symptom ratings were assessed before, and at 1, 2 and 3 hours post drug administration. The area under the curve (AUC) between baseline and 3 hours, and the maximum absolute change from baseline at 2 hours were analysed by one-way repeated measures analysis of variance, with drug condition (THC or CBD or placebo) as the factor. RESULTS: Relative to both placebo and CBD, administration of THC was associated with anxiety, dysphoria, positive psychotic symptoms, physical and mental sedation, subjective intoxication (AUC and effect at 2 hours: p < 0.01), an increase in heart rate (p < 0.05). There were no differences between CBD and placebo on any symptomatic, physiological variable. CONCLUSIONS: In healthy volunteers, THC has marked acute behavioural and physiological effects, whereas CBD has proven to be safe and well tolerated.

White and gray matter alterations in adults with Niemann-Pick disease type C: a cross-sectional study.

OBJECTIVE: Niemann-Pick disease type C (NPC) is a progressive neurovisceral disorder with disrupted intracellular cholesterol metabolism that results in significant alterations to neuronal and axonal structure. Adult patients present with ataxia, gaze palsy, impaired cognition, and neuropsychiatric illness, but the neural substrate has not been well-characterized in vivo. Our aim was to investigate a well-characterized sample of adults with confirmed NPC for gray and white matter abnormalities. METHODS: We utilized a combination of optimized voxel-based morphometry of T1-weighted images and tract-based spatial statistics of diffusion tensor images to examine gray matter volume and white matter structural differences in 6 adult patients with NPC and 18 gender- and age-matched controls. RESULTS: Patients with NPC demonstrated bilateral gray matter reductions in large clusters in bilateral hippocampus, thalamus, superior cerebellum, and insula, in addition to smaller regions of inferoposterior cortex. Patients demonstrated widespread reductions in fractional anisotropy in major white matter tracts. Subsequent analysis of measures of axial and radial diffusivity suggest that these changes are contributed to by both impaired myelination and altered axonal structure. CONCLUSIONS: Findings in gray matter areas are broadly consistent with human and animal studies of selective vulnerability of neuronal populations to the neuropathology of NPC, whereas more widespread white matter changes are consistent with the hypothesis that disrupted myelination and axonal structure predate changes to the neuronal cell body. These findings suggest that volumetric analysis of gray matter and diffusion tensor imaging may be useful modalities for indexing illness stage and monitoring response to emerging treatment.

Effect of image analysis software on neurofunctional activation during processing of emotional human faces.

Functional brain imaging techniques such as functional MRI (fMRI) that allow the in vivo investigation of the human brain have been exponentially employed to address the neurophysiological substrates of emotional processing. Despite the growing number of fMRI studies in the field, when taken separately these individual imaging studies demonstrate contrasting findings and variable pictures, and are unable to definitively characterize the neural networks underlying each specific emotional condition. Different imaging packages, as well as the statistical approaches for image processing and analysis, probably have a detrimental role by increasing the heterogeneity of findings. In particular, it is unclear to what extent the observed neurofunctional response of the brain cortex during emotional processing depends on the fMRI package used in the analysis. In this pilot study, we performed a double analysis of an fMRI dataset using emotional faces. The Statistical Parametric Mapping (SPM) version 2.6 (Wellcome Department of Cognitive Neurology, London, UK) and the XBAM 3.4 (Brain Imaging Analysis Unit, Institute of Psychiatry, Kings College London, UK) programs, which use parametric and non-parametric analysis, respectively, were used to assess our results. Both packages revealed that processing of emotional faces was associated with an increased activation in the brain's visual areas (occipital, fusiform and lingual gyri), in the cerebellum, in the parietal cortex, in the cingulate cortex (anterior and posterior cingulate), and in the dorsolateral and ventrolateral prefrontal cortex. However, blood oxygenation level-dependent (BOLD) response in the temporal regions, insula and putamen was evident in the XBAM analysis but not in the SPM analysis. Overall, SPM and XBAM analyses revealed comparable whole-group brain responses. Further studies are needed to explore the between-group compatibility of the different imaging packages in other cognitive and emotional processing domains.

Neuroimaging in cannabis use: a systematic review of the literature.

BACKGROUND: We conducted a systematic review to assess the evidence for specific effects of cannabis on brain structure and function. The review focuses on the cognitive changes associated with acute and chronic use of the drug. METHOD: We reviewed literature reporting neuroimaging studies of chronic or acute cannabis use published up until January 2009. The search was conducted using Medline, EMBASE, LILACS and PsycLIT indexing services using the following key words: cannabis, marijuana, delta-9-tetrahydrocannabinol, THC, cannabidiol, CBD, neuroimaging, brain imaging, computerized tomography, CT, magnetic resonance, MRI, single photon emission tomography, SPECT, functional magnetic resonance, fMRI, positron emission tomography, PET, diffusion tensor MRI, DTI-MRI, MRS and spectroscopy. RESULTS: Sixty-six studies were identified, of which 41 met the inclusion criteria. Thirty-three were functional (SPECT/PET/fMRI) and eight structural (volumetric/DTI) imaging studies. The high degree of heterogeneity across studies precluded a meta-analysis. The functional studies suggest that resting global and prefrontal blood flow are lower in cannabis users than in controls. The results from the activation studies using a cognitive task are inconsistent because of the heterogeneity of the methods used. Studies of acute administration of THC or marijuana report increased resting activity and activation of the frontal and anterior cingulate cortex during cognitive tasks. Only three of the structural imaging studies found differences between users and controls. CONCLUSIONS: Functional neuroimaging studies suggest a modulation of global and prefrontal metabolism both during the resting state and after the administration of THC/marijuana cigarettes. Minimal evidence of major effects of cannabis on brain structure has been reported.

Characterizing anterior cingulate activation in chronic schizophrenia: a group and single-subject fMRI study.

OBJECTIVE: Functional abnormalities of the dorsal anterior cingulate (dAC) region have been emphasized in schizophrenia, particularly in relation to cognitive deficits. In this study, we sought to further evaluate the notion of dAC hypofunction in chronic schizophrenia patients using a cognitive task specifically designed to activate this region, enabling both group and single-subject level analyses. METHOD: Twelve male schizophrenia patients and 14 male healthy subjects were studied with functional magnetic resonance imaging (fMRI) and the multi-source interference task (MSIT). Patients and healthy subjects were matched for age, gender, education, task performance and gross surface morphology of the AC region. fMRI analyses were conducted at the group and single-subject levels using stringent whole-brain activation thresholds. RESULTS: Multi-source interference task performance was associated with large and significant activation of the dAC and supplementary motor area (SMA) in patients and healthy subjects. Standard comparison of the two groups indicated that the patients were comparable with healthy subjects in their dAC activation, but had a small cluster of greater SMA activation, while single-subject analyses identified minimal differences in the magnitude or spatial dispersion of dAC activation between the groups. CONCLUSION: These findings challenge existing notions of impaired dAC activation in chronic schizophrenia and suggest that the functional pathophysiology of this medial-wall region should be considered beyond straightforward models of hypoactivation.