Christine C. Cloak

Bio: Christine C. Cloak is an academic researcher from University of Maryland, Baltimore. The author has contributed to research in topics: Methamphetamine & Cognition. The author has an hindex of 17, co-authored 33 publications receiving 1514 citations. Previous affiliations of Christine C. Cloak include University of Hawaii at Manoa & Cedars-Sinai Medical Center.

Image processing and analysis methods for the Adolescent Brain Cognitive Development Study

Abstract: The Adolescent Brain Cognitive Development (ABCD) Study is an ongoing, nationwide study of the effects of environmental influences on behavioral and brain development in adolescents. The ABCD Study is a collaborative effort, including a Coordinating Center, 21 data acquisition sites across the United States, and a Data Analysis and Informatics Center (DAIC). The main objective of the study is to recruit and assess over eleven thousand 9-10-year-olds and follow them over the course of 10 years to characterize normative brain and cognitive development, the many factors that influence brain development, and the effects of those factors on mental health and other outcomes. The study employs state-of-the-art multimodal brain imaging, cognitive and clinical assessments, bioassays, and careful assessment of substance use, environment, psychopathological symptoms, and social functioning. The data will provide a resource of unprecedented scale and depth for studying typical and atypical development. Here, we describe the baseline neuroimaging processing and subject-level analysis methods used by the ABCD DAIC in the centralized processing and extraction of neuroanatomical and functional imaging phenotypes. Neuroimaging processing and analyses include modality-specific corrections for distortions and motion, brain segmentation and cortical surface reconstruction derived from structural magnetic resonance imaging (sMRI), analysis of brain microstructure using diffusion MRI (dMRI), task-related analysis of functional MRI (fMRI), and functional connectivity analysis of resting-state fMRI.

Marijuana use is associated with a reorganized visual-attention network and cerebellar hypoactivation

Abstract: Attention and memory deficits have been reported in heavy marijuana users, but these effects may be reversible after prolonged abstinence. It remains unclear whether the reversibility of these cognitive deficits indicates that chronic marijuana use does not alter cortical networks, or that such changes occur but the brain adapts to the drug-induced changes. Blood oxygenation-level dependent (BOLD) functional MRI (fMRI) was performed in 24 chronic marijuana users (12 abstinent and 12 active) and 19 age-, sex- and education-matched control subjects during a set of visual-attention tasks with graded levels of difficulty. Neuropsychological tests were also administered on each subject. The two marijuana user groups showed no significant difference in usage pattern (frequency or duration of use, age of first use, cumulative joints used, averaged >2000 joints) or estimated cumulative lifetime exposure of Δ-9-tetrahydrocannabinol (THC) (mean 168 ± 45 versus 244 ± 135 g). Despite similar task and cognitive test performance compared with control subjects, active and abstinent marijuana users showed decreased activation in the right prefrontal, medial and dorsal parietal, and medial cerebellar regions, but greater activation in various frontal, parietal and occipital brain regions during the visual-attention tasks (all with P ≤ 0.001, corrected, cluster level). However, the BOLD signals in the right frontal and medial cerebellar regions normalized with duration of abstinence in the abstinent users. Active marijuana users, with positive urine tests for THC, showed greater activation in the frontal and medial cerebellar regions than abstinent marijuana users and greater usage of the reserve network (regions with load effect), suggesting a neuroadaptive state. Both earlier age of first use and greater estimated cumulative dose of THC exposure were related to lower BOLD signals in the right prefrontal region and medial cerebellum. The altered BOLD activation pattern in the attention network and hypoactivation of the cerebellum suggest neuroadaptive processes or alteration of brain development in chronic marijuana users. These changes also may be related to marijuana-induced alteration in resting cerebral blood volume/flow or downregulation of cannabinoid (CB1) receptors. The greater activation in the active compared with abstinent marijuana users demonstrates a neuroadaptive state in the setting of active marijuana use, while the long-term chronic effect of marijuana on the altered brain network may be reversible with prolonged abstinence.

Greater than age-related changes in brain diffusion of HIV patients after 1 year.

Abstract: Chronic infection with HIV is associated with neuroinflammation. Prior diffusion tensor imaging (DTI) studies demonstrated increased mean diffusion (MD) and decreased fractional anisotropy (FA) in the white matter (WM) and subcortical brain regions of HIV patients. The current study aims to detect whether there are greater than age-related brain changes in HIV patients after a 1-year follow-up period using DTI. Thirty-nine antiretroviral-stable HIV subjects and 32 HIV-seronegative (SN) controls were evaluated, with neuropsychological tests and DTI, at baseline and after 1 year. MD and FA in the genu and splenium of the corpus callosum and in six other subcortical and white matter regions were evaluated bilaterally. Compared to SN controls, HIV subjects had significantly higher MD in the frontal WM (p = 0.0104) and lower FA in the parietal WM (p = 0.006). After 1 year, HIV subjects showed increase in MD in frontal and parietal WM, putamen, and genu; HIV subjects also showed greater increased genu diffusion than SN controls (p = 0.005). Changes in global cognitive deficit score correlated with changes in MD in the genu and FA in the parietal and frontal WM and putamen (multiple regression, p = 0.0008). Lastly, normal age-dependent changes in frontal WM diffusion and FA in genu and putamen were not observed in HIV subjects. Since increased MD may reflect increased neuroinflammation, our findings suggest greater than normal age-related inflammatory changes in the genu of these HIV patients, which may contribute to the cognitive deficits. Measurements of MD in the genu may be useful for monitoring disease progression in HIV brain infection.

Metabolism and Disposition Kinetics of Nicotine

Abstract: Nicotine is of importance as the addictive chemical in tobacco, pharmacotherapy for smoking cessation, a potential medication for several diseases, and a useful probe drug for phenotyping cytochrome P450 2A6 (CYP2A6). We review current knowledge about the metabolism and disposition kinetics of nicotine, some other naturally occurring tobacco alkaloids, and nicotine analogs that are under development as potential therapeutic agents. The focus is on studies in humans, but animal data are mentioned when relevant to the interpretation of human data. The pathways of nicotine metabolism are described in detail. Absorption, distribution, metabolism, and excretion of nicotine and related compounds are reviewed. Enzymes involved in nicotine metabolism including cytochrome P450 enzymes, aldehyde oxidase, flavin-containing monooxygenase 3, amine N-methyltransferase, and UDP-glucuronosyltransferases are represented, as well as factors affecting metabolism, such as genetic variations in metabolic enzymes, effects of diet, age, gender, pregnancy, liver and kidney diseases, and racial and ethnic differences. Also effects of smoking and various inhibitors and inducers, including oral contraceptives, on nicotine metabolism are discussed. Due to the significance of the CYP2A6 enzyme in nicotine clearance, special emphasis is given to the effects and population distributions of CYP2A6 alleles and the regulation of CYP2A6 enzyme.

HIV-associated neurocognitive disorder — pathogenesis and prospects for treatment

Abstract: In the past two decades, several advancements have improved the care of HIV-infected individuals. Most importantly, the development and deployment of combination antiretroviral therapy (CART) has resulted in a dramatic decline in the rate of deaths from AIDS, so that people living with HIV today have nearly normal life expectancies if treated with CART. The term HIV-associated neurocognitive disorder (HAND) has been used to describe the spectrum of neurocognitive dysfunction associated with HIV infection. HIV can enter the CNS during early stages of infection, and persistent CNS HIV infection and inflammation probably contribute to the development of HAND. The brain can subsequently serve as a sanctuary for ongoing HIV replication, even when systemic viral suppression has been achieved. HAND can remain in patients treated with CART, and its effects on survival, quality of life and everyday functioning make it an important unresolved issue. In this Review, we describe the epidemiology of HAND, the evolving concepts of its neuropathogenesis, novel insights from animal models, and new approaches to treatment. We also discuss how inflammation is sustained in chronic HIV infection. Moreover, we suggest that adjunctive therapies--treatments targeting CNS inflammation and other metabolic processes, including glutamate homeostasis, lipid and energy metabolism--are needed to reverse or improve HAND-related neurological dysfunction.

Reproducible brain-wide association studies require thousands of individuals

Abstract: Magnetic resonance imaging (MRI) has transformed our understanding of the human brain through well-replicated mapping of abilities to specific structures (for example, lesion studies) and functions1-3 (for example, task functional MRI (fMRI)). Mental health research and care have yet to realize similar advances from MRI. A primary challenge has been replicating associations between inter-individual differences in brain structure or function and complex cognitive or mental health phenotypes (brain-wide association studies (BWAS)). Such BWAS have typically relied on sample sizes appropriate for classical brain mapping4 (the median neuroimaging study sample size is about 25), but potentially too small for capturing reproducible brain-behavioural phenotype associations5,6. Here we used three of the largest neuroimaging datasets currently available-with a total sample size of around 50,000 individuals-to quantify BWAS effect sizes and reproducibility as a function of sample size. BWAS associations were smaller than previously thought, resulting in statistically underpowered studies, inflated effect sizes and replication failures at typical sample sizes. As sample sizes grew into the thousands, replication rates began to improve and effect size inflation decreased. More robust BWAS effects were detected for functional MRI (versus structural), cognitive tests (versus mental health questionnaires) and multivariate methods (versus univariate). Smaller than expected brain-phenotype associations and variability across population subsamples can explain widespread BWAS replication failures. In contrast to non-BWAS approaches with larger effects (for example, lesions, interventions and within-person), BWAS reproducibility requires samples with thousands of individuals.

Neurocognitive Effects of Methamphetamine: A Critical Review and Meta-analysis

Abstract: This review provides a critical analysis of the central nervous system effects of acute and chronic methamphetamine (MA) use, which is linked to numerous adverse psychosocial, neuropsychiatric, and medical problems. A meta-analysis of the neuropsychological effects of MA abuse/dependence revealed broadly medium effect sizes, showing deficits in episodic memory, executive functions, information processing speed, motor skills, language, and visuoconstructional abilities. The neuropsychological deficits associated with MA abuse/dependence are interpreted with regard to their possible neural mechanisms, most notably MA-associated frontostriatal neurotoxicity. In addition, potential explanatory factors are considered, including demographics (e.g., gender), MA use characteristics (e.g., duration of abstinence), and the influence of common psychiatric (e.g., other substance-related disorders) and neuromedical (e.g., HIV infection) comorbidities. Finally, these findings are discussed with respect to their potential contribution to the clinical management of persons with MA abuse/dependence.

Major physical and psychological harms of methamphetamine use

Abstract: Issues. The major physical and psychological health effects of methamphetamine use, and the factors associated with such harms. Approach. Comprehensive review. Key Findings. Physical harms reviewed...