Notable strengths of the study include acquisition

Notable strengths of the study include acquisition of spectral data through the use of 2D-JPRESS at 4.0T, which permits improved spatial and spectral resolution, high SNR afforded by high field MRS, and optimal detection of Glu separately from Gln. However, it should be noted that the MRS technique employed in the present study is only capable of a milimolar level of measurement, and that the observed Glu and Gln levels and ratios only reflect turnover of the general glutamatergic metabolic pool (Öngür et al., 2008; Yüksel and Öngür, 2010) While the current study included a large number of subjects for an MRS study, the current study is limited by the smaller samples sizes of FH+ individuals compared to those that were FH−. Due to the small sample sizes for FH+, findings in these groups should be considered preliminary. Accidental findings may have occurred given the multiple measures examined, however multiple comparison corrections were applied when possible. The major Z-IETD-FMK and behavior findings reported in this study are correlational in nature, and thus, follow-up investigations are necessary to better characterize neurochemical profiles and associations measures of impulsivity observed in FH− and FH+ individuals.
Conclusions
Conflict of interest statement
Acknowledgements This research was supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA K01 AA022392, PI Cohen-Gilbert; NIAAA R01 AA018153, PI Silveri; NIAAA K01 AA014651, PI Silveri). The authors would like to thank Michael J. Covell and Deepa Acharya for assistance with data collection, and Elena Stein for editorial comments.
Introduction
Methods 51 subjects between the ages of 14 to 16 years were drawn from a prospective, longitudinal study on the effects of prenatal cocaine to participate in the current study. A complete, detailed description of the longitudinal study has been published previously (Eyler et al., 1998). Institutional Review Board approval of the study was obtained at University of Florida. After an explanation of procedures, the parents/legal guardians provided written informed consent and the adolescent participants provided written assent to participate in the study. All youth participants were consented the following way: Subjects who lived within 2h of the study site were invited to participate using a letter that was accompanied by a study-designed brochure explaining magnetic resonance imaging (MRI). Follow-up phone calls to participants were made as part of the recruiting process. For subjects who showed interest, the purpose of the study and study procedures were explained to both the parent/legal guardian and the adolescent subject. A screening questionnaire was also completed by telephone to ensure that subjects met inclusion criteria (e.g., right-handed, no metal in the body, etc.) On the day of study participation, the informed consent form was read and reviewed. Youth were provided a $50 Walmart gift card for participation. Subjects underwent a brief neurocognitive battery administered by TDW, a licensed neuropsychologist who was blinded to the PCE exposure status of each subject followed by a structural scan. Of these 51 subjects, 4 subjects were excluded due to the following reasons: obvious cognitive impairment (1), metal artifacts in body (1), developed claustrophobia (1), history of head injury with loss of consciousness for >5min (1) and structural data was lost for 5 subjects. The final sample size was 42 with 27 prenatally exposed and 15 non-PCE exposed age-matched controls. Maternal cocaine use in the longitudinal study was determined using self-report as well as through unanticipated urine tests, and drug usage were quantified for the same time period. The amount and frequency of maternal drug use was obtained during private, structured interviews conducted at the end of each trimester or after birth if the woman had no prenatal care. The frequency of cocaine exposure was quantified by calculating the total number of weeks during gestation and 3 months prior to pregnancy then dividing by the total number of 12 weeks plus the number of weeks of the entire pregnancy. The decision to use gestational week ratio for cocaine use stemmed from the fact that the primary mode of ingestion of cocaine was “rocks” which varied widely by size, shape and quality. Hence, quantity and dosage could vary widely and could not be pinpointed with accuracy. Thus, the proportion of actual use of cocaine was obtained. In contrast, prenatal alcohol and tobacco use could be measured with better accuracy in regards to dosage. Alcohol use was measured as the average number of absolute ounces of alcohol consumed per day during pregnancy (same time period as cocaine). Women who consumed greater than 1.5 ounces of alcohol per day were excluded to minimize the number of children with fetal alcohol effects. Tobacco exposure and marijuana exposure were, respectively, defined as the average number of cigarettes per day and the average number joints per day that were smoked during pregnancy (same time period as cocaine). Only 10 mothers in the PCE group and 1 control reported marijuana exposure, and of these, 6 reported consumption of less than 0.03 joints/per week. Hence, marijuana exposure was not further explored in the study due to small sample size and very low levels of use.