Background The brain undergoes major remodeling during adolescence, resulting in improved cognitive control and decision-making, and reduced impulsivity, components of behavior mediated in part by the maturing frontal lobe. Gamma-amino butyric acid (GABA), the main inhibitory neurotransmitter system, also matures during adolescence, with frontal lobe GABA receptors reaching adult levels late in adolescence. Thus, the objective of this study was to characterize in vivo developmental differences in brain GABA levels. Methods Proton magnetic resonance spectroscopy (MRS) was employed at 4 Tesla to acquire metabolite data from the anterior cingulate cortex (ACC) and the parieto-occipital (POC) cortex in adolescents (n=30) and emerging adults (n=20). Results ACC GABA/Cr levels were significantly lower in adolescents relative to emerging adults, whereas no age differences were observed in the POC. Lower ACC GABA/Cr levels were significantly associated with greater impulsivity and worse response inhibition, with relationships being most pronounced for ACC GABA/Cr and No-Go response inhibition in adolescent males. Conclusions These data provide the first human developmental in vivo evidence confirming frontal lobe GABA maturation, which was linked to impulsiveness and cognitive control. These findings suggest that reduced GABA may be an important neurobiological mechanism in the immature adolescent brain, contributing to the reduced, yet rapidly developing, ability to inhibit risky behaviors and to make decisions, which could compromise adolescent health and safety.

Background The brain undergoes dynamic and requisite changes into the early twenties that are associated with improved cognitive efficiency, particularly in prefrontal regions that are still undergoing neuromaturation. As alcohol consumption is typically initiated and progresses to binge drinking during this time, the objective of the present study was to investigate the impact of binge alcohol consumption on frontal lobe cortical thickness in emerging adults. Methods Twenty-three binge drinking (BD; 11 females, mean age 21.5 ± 1.4) and thirty-one light drinking (LD; 15 females, mean age 21.9 ± 1.6) emerging adults underwent high-resolution magnetic resonance imaging at 3 Tesla. Cortical surface reconstruction and thickness estimation were performed using Freesurfer for three a priori brain regions of interest: bilateral anterior cingulate cortex (ACC), posterior cingulate cortex (PCC) and parieto-occipital sulcus (POS). Cortical thickness measurements were then compared between BD and LD groups. Results Cortical thickness was significantly lower in BD than LD in the right middle ACC (mid-ACC; p≤0.05) and in the left dorsal PCC (dPCC; p≤0.01). No significant differences in cortical thickness were observed in the POS. Cortical thickness in the mid-ACC correlated negatively with higher quantity and frequency of drinks consumed (p<0.01), and positively with the number of days elapsed since most recent use (p<0.05). Furthermore, less cortical thickness in the mid-ACC in the BD group alone correlated with reported patterns of high quantity and frequency of alcohol consumption (p≤0.05). Conclusions Findings suggest that past and recent patterns of intermittent heavy alcohol consumption are associated with less frontal cortical thickness (i.e. ‘thinness’) of the right mid-ACC and left dPCC in emerging adults, but not the POS. While cortical thinness could have predated binge drinking, this pattern of maladaptive consumption may have acute neurotoxic effects that interfere with the finalization of neuromaturational processes in the vulnerable frontal cortex, resulting in increased microarchitectural pruning.

Magnetic resonance (MR) techniques provide opportunities to non-invasively characterize neurobiological milestones of adolescent brain development. Juxtaposed to the critical finalization of brain development is initiation of alcohol and substance use, and increased frequency and quantity of use, patterns that can lead to abuse and addiction. This review provides a comprehensive overview of existing MR studies of adolescent alcohol and drug users. The most common alteration reported across substance used and MR modalities is in the frontal lobe (63% of published studies). This is not surprising, given that this is the last region to reach neurobiological adulthood. Comparatively, evidence is less consistent regarding alterations in regions that mature earlier (e.g., amygdala, hippocampus), however newer techniques now permit investigations beyond regional approaches that are uncovering network-level vulnerabilities. Regardless of whether neurobiological signatures exist prior to the initiation of use, this body of work provides important direction for ongoing prospective investigations of adolescent brain development, and the significant impact of alcohol and substance use on the brain during the second decade of life.

Chronic marijuana (MRJ) use is associated with altered cognition and mood state, altered brain metabolites, functional and structural brain changes. The objective of this study was to apply proton magnetic resonance spectroscopic imaging (MRSI) to compare proton metabolite levels in 15 young men with MRJ-dependence and 11 healthy non-using (NU) young men. Spectra were acquired at 4.0 Tesla using 2D J-resolved MRSI to resolve coupled resonances in J-space and to quantify the entire J-coupled spectral surface of metabolites from voxels containing basal ganglia and thalamus, temporal and parietal lobe, and occipital white and gray matter. This method permitted investigation of high-quality spectra for regression analyses to examine metabolites relative to tissue type. Distribution of myo-inositol (mI)/creatine (Cr) was altered in the MRJ group whereas the NU group exhibited higher mI/Cr in WM than GM, this pattern was not observed in MRJ subjects. Significant relationships observed between global mI/Cr and distribution in WM, and self-reported impulsivity and mood symptoms were also unique between MRJ and NU groups. These preliminary findings suggest that mI, and distribution of this glial metabolite in WM, is altered by MRJ use and is associated with behavioral and affective features reported by young MRJ-dependent men.

Background Binge alcohol consumption is associated with multiple neurobiological consequences, including altered neurophysiology, brain structure and functional activation. Magnetic resonance spectroscopy (MRS) studies have demonstrated neurochemical alterations in the frontal lobe of alcohol users, although most studies focused on older, alcohol dependent subjects. Methods In this study, neurochemical data were acquired using MRS at 4T from emerging adults (18–24 years old) who were binge alcohol drinkers (BD, n=23) or light drinkers (LD, n=31). Since binge drinking is also associated with increased prevalence of experiencing an alcohol-induced blackout, BD were stratified into alcohol-induced blackout (BDBO) and non-blackout groups (BDN). Results Overall, BD had significantly lower gamma amino-butyric acid (GABA) and N-acetyl-aspartate (NAA) in the anterior cingulate cortex (ACC) than LD. When stratified by blackout history, BDBO also had lower ACC glutamate (Glu) than LD. No group differences in MRS metabolites were observed in the parietal-occipital cortex. Lower ACC GABA and glutamate remained significant after accounting for lower grey matter content in BD, however NAA differences were no longer evident. In addition, low ACC GABA levels were associated with greater alcohol use consequences, and worse response inhibition and attention/mental flexibility in BD. Conclusions These data indicate that binge drinking affects frontal lobe neurochemistry, more so in those who had experienced an alcohol-induced blackout. Characterization of the neurochemical profiles associated with binge alcohol consumption and blackout history may help identify unique risk factors for the later manifestation of alcohol abuse and dependence, in young individuals who are heavy, frequent drinkers, but who do not meet the criteria for alcohol use disorders.

Numerous studies have reported neurocognitive impairments associated with chronic marijuana use. Given that the hippocampus contains a high density of cannabinoid receptors, hippocampal-mediated cognitive functions, including visuospatial memory, may have increased vulnerability to chronic marijuana use. Thus, the current study examined brain activation during the performance of a virtual analogue of the classic Morris water maze task in 10 chronic marijuana (MJ) users compared to 18 nonusing (NU) comparison subjects. Imaging data were acquired using blood oxygen level-dependent (BOLD) functional MRI at 3.0 Tesla during retrieval (hidden platform) and motor control (visible platform) conditions. While task performance on learning trials was similar between groups, MJ users demonstrated a deficit in memory retrieval. For BOLD fMRI data, NU subjects exhibited greater activation in the right parahippocampal gyrus and cingulate gyrus compared to the MJ group for the Retrieval-Motor Control contrast (NU > MJ). These findings suggest that hypoactivation in MJ users may be due to differences in the efficient utilization of neuronal resources during the retrieval of memory. Given the paucity of data on visuospatial memory function in MJ users, these findings may help elucidate the neurobiological effects of marijuana on brain activation during memory retrieval.

Cerebral blood volume (CBV) studies have provided important insight into the effects of illicit substances such as cannabis. The present study examined changes in regional blood volume in the frontal and temporal lobe, and the cerebellum during 28 days of supervised abstinence from cannabis. Dynamic susceptibility contrast MRI (DSCMRI) data were collected on 15 current, long-term cannabis users between 6 and 36 hours after the subjects' last reported cannabis use (Day 0), and again after 7 and 28 days of abstinence. Resting state CBV images were also acquired on 17 healthy comparison subjects. The present findings demonstrate that at Day 7, cannabis users continued to display increased blood volumes in the right frontal region, the left and right temporal regions, and the cerebellum. However, after 28 days of abstinence, only the left temporal area and cerebellum showed significantly increased CBV values in cannabis users. These findings suggest that while CBV levels begin to normalize with continued abstinence from cannabis, specifically in frontal areas, other temporal and cerebellar brain regions show slower CBV decreases.

Males typically outperform females on spatial tasks, beginning early in life and continuing into adulthood. This study aimed to characterize age and sex differences in human spatial ability using a virtual Water Maze Task (vWMT), which is based on the classic Morris water maze spatial navigation task used in rodents. Performance on the vWMT and on a task assessing visuospatial perception, Mental Rotations Test (MRT), was examined in 33 adolescents and 39 emerging adults. For the vWMT, significant effects of age and sex were observed for path length in the target region (narrower spatial sampling), and heading error, with emerging adults performing better than adolescents, and an overall male advantage. For the MRT, males scored higher than females, but only in emerging adulthood. Overall, sex differences in visuospatial perception (MRT) emerge differently from those observed on a classic navigation task, with age and sex-specific superior vWMT performance likely related to the use of more efficient strategies. Importantly, these results extend the developmental timeline of spatial ability characterization to include adolescent males and females performing a virtual version of the classic vWMT.