Among magnetic resonance imaging MRI and positron emission t

Among magnetic resonance imaging (MRI) and positron emission tomography (PET) studies of functional relationships among Phos-tag Acrylamide regions, CUs demonstrate altered patterns of brain activity when compared to non-using controls, particularly within the prefrontal cortex (), orbitofrontal network (), prefrontal and occipitoparietal cortex (), and frontal-subcortical network (). A potential mechanism driving these differences may be disruption of white matter fiber tracts that support signaling between neurons within and across neural nodes. The direction of alterations in white matter volume in a variety of cortical and subcortical regions has been inconsistently reported in CUs, with one group finding increased density of white matter associated with the left parahippocampal and fusiform gyri and lower density in left parietal lobe white matter (), and a second group noting cerebellar white matter volume reduction in CUs (). However, other studies find no association between cannabis use and white matter extent or volume (), making it difficult to draw general conclusions from the existing studies. It appears that measures of white matter volume or extent derived from T weighted structural MRI scans may not be sufficiently sensitive to subtle alterations in white matter microstructure that impact information processing. DTI has the potential to address this limitation given that white matter organization can be examined at the microstructural level. DTI studies indicate that CUs demonstrate altered white matter organization, although again there are inconsistencies across studies in the direction of MRI-measured changes. Most studies indicate that FA is lower in various white matter regions in CUs. Some DTI reports include findings of increased CU RD and MD, also indicative of reduced white matter organization in CUs. DTI findings for CUs have involved widely scattered brain regions, including the superior longitudinal fasciculus (), arcuate fasciculus (), frontal white matter adjacent to the anterior cingulate cortex () and hippocampus (), internal capsule (), and the rostrum (), genu (), and splenium () of the corpus callosum. Cannabis use may disrupt the developmental trajectory of white matter organization since lower FA levels have been associated with an earlier age of cannabis use onset (). Not all DTI studies have found evidence for lower FA and/or greater RD and MD in CUs. Greater FA and lower RD have been reported in the forceps minor of the corpus callosum, a tract that connects the orbitofrontal cortices (), although years of use within the CU group showed a curvilinear (quadratic) association with declining FA levels and rising RD levels. One early study found increased FA in CUs in white matter associated with medial frontal, cingulate, precentral, and parietal cortex, as well as decreased MD in cingulate and medial frontal white matter (). Though findings are compelling, this literature is comprised of cross-sectional designs, limiting interpretation of group-based differences. Longitudinal research may clarify some interpretative complexities, by assessing neural changes over time in relation to ongoing substance use. Recent longitudinal studies have explored white matter development associated with alcohol initiation (), binge alcohol use with comorbid cannabis use (), and polysubstance use (). No longitudinal study to date has explored white matter microstructure specifically related to sustained cannabis use during young adulthood. This study examines change in measures of axonal fiber organization across time as a function of cannabis use. Young adult, regular CUs and control participants were assessed at two time points, with a two-year time interval between assessments. It was predicted that ongoing development of axonal fiber organization, as measured by increasing FA and decreasing RD, would be relatively diminished among CUs after multiple years of chronic use. Given the broadly distributed DTI findings to date, we expected alterations of fiber organization in frontal white matter as well as fiber tracts connecting frontal and posterior regions; hippocampal white matter; the corpus callosum; and cortical–subcortical projection fibers such as the corticospinal tract. We predicted that these alterations in fiber organization would be correlated with amount of cannabis use in the follow-up interval in the CU group. To facilitate interpretation of the DTI findings in terms of behavioral functioning, we include a correlational analysis of scores on a test of auditory verbal learning and memory. CUs have consistently shown impairments in this domain (e.g., ) and we predicted that test performance would correlate positively with FA changes in task-relevant brain regions.