A. Gonenc

Worth the wait: effects of age of onset of marijuana use on white matter and impulsivity

RationaleMarijuana (MJ) use continues to rise, and as the perceived risk of using MJ approaches an all-time historic low, initiation of MJ use is occurring at even younger ages. As adolescence is a critical period of neuromaturation, teens and emerging adults are at greater risk for experiencing the negative effects of MJ on the brain. In particular, MJ use has been shown to be associated with alterations in frontal white matter microstructure, which may be related to reports of increased levels of impulsivity in this population.ObjectivesThe aim of this study was to examine the relationship between age of onset of MJ use, white matter microstructure, and reported impulsivity in chronic, heavy MJ smokers.MethodsTwenty-five MJ smokers and 18 healthy controls underwent diffusion tensor imaging and completed the Barratt Impulsiveness Scale. MJ smokers were also divided into early onset (regular use prior to age 16) and late onset (age 16 or later) groups in order to clarify the impact of age of onset of MJ use on these variables.ResultsMJ smokers exhibited significantly reduced fractional anisotropy (FA) relative to controls, as well as higher levels of impulsivity. Earlier MJ onset was also associated with lower levels of FA. Interestingly, within the early onset group, higher impulsivity scores were correlated with lower FA, a relationship that was not observed in the late onset smokers.ConclusionsMJ use is associated with white matter development and reported impulsivity, particularly in early onset smokers.

Age of onset of marijuana use impacts inhibitory processing.

Difficulties in the ability to successfully inhibit impulsive behaviors have been reported in marijuana (MJ) smokers, yet few studies have made direct comparisons between early (prior to age 16) and late (age 16 or later) onset MJ smokers, specifically during behavioral inhibition tasks. The current study utilized the Multi-Source Interference Task (MSIT) during functional magnetic resonance imaging (fMRI) in chronic, heavy MJ smokers and healthy non-MJ smoking controls which revealed a more focal pattern of anterior cingulate activity in controls relative to smokers. Early onset smokers had more focal activation but tended to make more errors of commission relative to late onset smokers, suggesting a possible neural adaptation despite difficulty with behavioral inhibition. Further investigation is warranted, as early exposure to MJ may result in reorganization of critical brain regions.

The impact of initiation: Early onset marijuana smokers demonstrate altered Stroop performance and brain activation ☆

Highlights • MJ smokers exhibited poorer performance and altered activation on the Stroop.• MJ smokers reported significantly higher impulsivity than control subjects.• Poorer performance and neural alterations were primarily related to early MJ onset.• Early onset smokers reported higher levels of MJ use than late onset smokers.• Earlier MJ onset and increased MJ use predicted poorer Stroop performance.

Combined diffusion tensor imaging and transverse relaxometry in early-onset bipolar disorder.

OBJECTIVE Transverse relaxation time (T2) imaging provides the opportunity to examine membrane fluidity, which can affect a number of cellular functions. The objective of the present work was to examine T2 abnormalities in children with unmodified DSM-IV-TR bipolar disorder (BD) in bilateral cingulate-paracingulate (CPC) white matter. METHOD A total of 21 children and adolescents with BD and 16 healthy control subjects underwent magnetic resonance imaging at 1.5 Tesla and were compared using a region-of-interest analysis. A post hoc diffusion tensor imaging (DTI) analysis was also performed on selected subjects. RESULTS The T2 values were significantly decreased on the right-side of the subjects with BD compared with that of the control subjects. Hemispheric difference was also observed in the BD group, with decreased T2 on the right side compared with the left side. No significant difference was observed between left and right CPC T2 in control subjects. For participants who had both T2 and DTI measurements, significant DTI differences were observed: On the left side, fractional anisotropy was reduced and trace and radial diffusivity were increased, whereas on the right side, trace was increased and T2 was decreased in subjects with BD compared with control subjects. CONCLUSIONS Our findings suggest that the observed T2 difference is a reflection of cerebral blood flow rather than an alteration of the fluidity of cell membranes. It is possible that myelin damage occurs on the left side in early-onset BD, in addition to changes in the blood flow. Prospective studies with larger numbers of subjects are warranted to further explore the relevance of the presented results.

Comparison of Spectral Fitting Methods for Overlapping J- Coupled Metabolite Resonances

There is increasing interest in the use of two‐dimensional J‐resolved spectroscopic acquisition (multiecho) methods for in vivo proton magnetic resonance spectroscopy due to the improved discrimination of overlapping J‐coupled multiplet resonances that is provided. Of particular interest is the potential for discrimination of the overlapping resonances of glutamate and glutamine. In this study, a new time‐domain parametric spectral model that makes use of all available data is described for fitting the complete two‐dimensional multiecho data, and the performance of this method was compared with fitting of one‐dimensional spectra obtained following averaging multiecho data (echo time‐averaged) and single‐echo time PRESS (Point Resolved Spectroscopy) acquired spectra. These methods were compared using data obtained from a phantom containing typical brain metabolites and a human brain. Results indicate that improved performance and accuracy is obtained for the two‐dimensional acquisition and spectral fitting model. Magn Reson Med, 2010.

Altered affective processing in bipolar disorder: an fMRI study.

BACKGROUND Previous studies have reported that patients with bipolar disorder (BPD) exhibit altered emotional processing and regulation. However, results remain largely inconsistent across studies. The aim of the current study was to further examine affective processing in patients with bipolar disorder. METHODS Twenty-three patients diagnosed with BPD (Type I) and 18 healthy matched controls completed a backward-masked affect paradigm while undergoing functional magnetic resonance imaging. Participants also completed a computerized, overt task of facial emotional discrimination after scanning. RESULTS Results demonstrated altered affective processing of happy and fearful stimuli in bipolar participants in the amygdala, anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC) relative to controls. BPD participants also displayed significant deficits in identifying fearful facial affect. LIMITATIONS This study has a moderate sample size, and the patients with BPD were significantly older than the healthy control participants; this did not appear to impact results, and although statistically significant, it is not likely biologically significant. CONCLUSIONS These findings may have implications for patients with BPD, as altered affective processing could result in deficits in reading social cues.

The Grass Might Be Greener: Medical Marijuana Patients Exhibit Altered Brain Activity and Improved Executive Function after 3 Months of Treatment

The vast majority of states have enacted full or partial medical marijuana (MMJ) programs, causing the number of patients seeking certification for MMJ use to increase dramatically in recent years. Despite increased use of MMJ across the nation, no studies thus far have examined the specific impact of MMJ on cognitive function and related brain activation. In the present study, MMJ patients seeking treatment for a variety of documented medical conditions were assessed prior to initiating MMJ treatment and after 3 months of treatment as part of a larger longitudinal study. In order to examine the effect of MMJ treatment on task-related brain activation, MMJ patients completed the Multi-Source Interference Test (MSIT) while undergoing functional magnetic resonance imaging (fMRI). We also collected data regarding conventional medication use, clinical state, and health-related measures at each visit. Following 3 months of treatment, MMJ patients demonstrated improved task performance accompanied by changes in brain activation patterns within the cingulate cortex and frontal regions. Interestingly, after MMJ treatment, brain activation patterns appeared more similar to those exhibited by healthy controls from previous studies than at pre-treatment, suggestive of a potential normalization of brain function relative to baseline. These findings suggest that MMJ use may result in different effects relative to recreational marijuana (MJ) use, as recreational consumers have been shown to exhibit decrements in task performance accompanied by altered brain activation. Moreover, patients in the current study also reported improvements in clinical state and health-related measures as well as notable decreases in prescription medication use, particularly opioids and benzodiapezines after 3 months of treatment. Further research is needed to clarify the specific neurobiologic impact, clinical efficacy, and unique effects of MMJ for a range of indications and how it compares to recreational MJ use.

Citicoline Treatment Improves Measures of Impulsivity and Task Performance in Chronic Marijuana Smokers: A Pilot BOLD fMRI Study

Objective Citicoline is an endogenous nucleotide that has historically been used to treat stroke, traumatic brain injury, and cognitive dysfunction. Research has also shown that citicoline treatment is associated with improved cognitive performance in substance-abusing populations. We hypothesized that marijuana (MJ) smokers who received citicoline would demonstrate improvement in cognitive performance as well as increased neural efficiency during tasks of cognitive control relative to those who received placebo. Method The current study tested this hypothesis by examining the effects of citicoline in treatment-seeking chronic MJ smokers. In an 8-week double-blind, placebo-controlled study, 19 MJ smokers were randomly assigned via a double-blind procedure to the citicoline (8 Males, 2 Females) or placebo group (9 Males, 0 Females). All participants completed fMRI scanning at baseline and after 8 weeks of treatment during two cognitive measures of inhibitory processing, the Multi Source Interference Test (MSIT) and Stroop Color Word Test, and also completed the Barratt Impulsiveness Scale (BIS-11), a self-report measure of impulsivity. Results Following the 8 week trial, MJ smokers treated with citicoline demonstrated significantly lower levels of behavioral impulsivity, improved task accuracy on both the MSIT and Stroop tasks, and exhibited significantly different patterns of brain activation relative to baseline levels and relative to those who received placebo. Conclusions Findings suggest that citicoline may facilitate the treatment of MJ use disorders by improving the cognitive skills necessary to fully engage in comprehensive treatment programs.

Elevated Preattentive Affective Processing in Individuals with Borderline Personality Disorder: A Preliminary fMRI Study

Background: Emotion dysregulation is central to the clinical conceptualization of borderline personality disorder (BPD), with individuals often displaying instability in mood and intense feelings of negative affect. Although existing data suggest important neural and behavioral differences in the emotion processing of individuals with BPD, studies thus far have only explored reactions to overt emotional information. Therefore, it is unclear if BPD-related emotional hypersensitivity extends to stimuli presented below the level of conscious awareness (preattentively). Methods: Functional magnetic resonance imaging (fMRI) was used to measure neural responses to happy, angry, fearful, and neutral faces presented preattentively, using a backward masked affect paradigm. Given their tendency toward emotional hyperreactivity and altered amygdala and frontal activation, we hypothesized that individuals with BPD would demonstrate a distinct pattern of fMRI responses relative to those without BPD during the viewing of masked affective versus neutral faces in specific regions of interests (ROIs). Results: Results indicated that individuals with BPD demonstrated increases in frontal, cingulate, and amygdalar activation represented by number of voxels activated and demonstrated a different pattern of activity within the ROIs relative to those without BPD while viewing masked affective versus neutral faces. Conclusion: These findings suggest that in addition to the previously documented heightened responses to overt displays of emotion, individuals with BPD also demonstrate differential responses to positive and negative emotions, early in the processing stream, even before conscious awareness.

Depression is associated with dimensional and categorical effects on white matter pathways

Diffusion tensor imaging (DTI) studies report reduced fractional anisotropy (FA) in major depressive disorder (MDD). However, whether FA covaries with key depressive symptoms, such as anhedonia, is unclear.