The present study compared three commonly used cognitive screeners: the Test of Cognitive Skills – Second Edition (TCS-2), the Kaufman Brief Intelligence Test (K-BIT), the Wide Range Achievement Test – Third editions (WRAT3) and the impact of marijuana use on these screeners in a population of juvenile delinquents. One hundred records (67 males and 33 females) were selected from archival data at the Allen County Juvenile Center. Results from this study found, that as predicted, individuals who tested positive for marijuana performed significantly worse on all subtests of the TCS-2, on the Verbal and Composite Score of the K-BIT, and the Spelling subtest of the WRAT3 than individuals who tested negative for marijuana use. The results of this study support the notion that marijuana can impair cognitive abilities in a group of adolescents. / Department of Psychological Science

Prior caffeine research has examined the effects of caffeine on performance using simple, lower-level cognitive tasks. The present study extended this work to investigate the effects of caffeine on performance and self-report mood measures during execution of a complex cognitive task. In a between-subjects design, 116 participants were administered either caffeinated or non-caffeinated chewing gum. Results showed higher fatigue and negative affect (NA) levels and lower positive affect (PA) and task performance levels in the placebo condition. These findings replicate prior findings on mood effects of caffeine; also, they extend the limited results on performance effects of caffeine by demonstrating moderate support for improved complex cognitive task performance after caffeine intake. Furthermore, these results show the efficacy of gum for caffeine administration in research.

Background. Various studies show that cannabis use alters attention and cognitive functioning in healthy humans and may contribute to development of schizophrenia or worsening of pre-existing psychosis. However, the impact of cannabis use on brain function in humans is not well understood. Schizophrenia is associated with a deficit in prepulse inhibition (PPI), the normal inhibition of the startle reflex by a non-startling stimulus (prepulse), presented before the startle stimulus at short time intervals (lead-time intervals). Such PPI deficit is thought to reflect a sensorimotor gating dysfunction in schizophrenia. PPI is also modulated by attention and PPI reduction in schizophrenia is observed when patients are asked to attend to, not ignore, the stimuli producing PPI. The aim of the current study was to investigate the association between self-reported chronic cannabis use and attentional modulation of PPI in healthy controls and in patients with schizophrenia. Furthermore, the association between cannabis use and other startle reflex modulators, including prepulse facilitation (PPF) of the startle reflex magnitude at long lead-time intervals, prepulse facilitation of the startle reflex onset latency and habituation of the startle reflex magnitude, were examined. Method. Auditory-evoked electromyographic signals were recorded from orbicularis oculi muscles in chronic cannabis users (29 healthy controls and 5 schizophrenia patients) and non-users (22 controls and 14 patients). The data for 36 participants (12 non-user controls, 16 healthy cannabis users, and eight non-user patients) were used in the final analyses and the patient data were used as a pilot study, because relatively few participants met the rigorous exclusionary criteria. Participants were instructed to attend to or to ignore either the startle stimuli alone (70 100 dB) or prepulse (70 dB) and startle stimuli (100 dB) separated by short lead-time intervals (20 200 ms) and long lead-time intervals (1600 ms). In order to ignore the auditory stimuli the participants played a visually guided hand-held computer game. A pilot study showed that the response component of playing the game had no effects on attentional modulation of the startle reflex magnitude and onset latency. Results. Relative to controls, cannabis use in healthy humans was associated with a reduction in PPI similar to that observed in schizophrenia while attending to stimuli, and with an attention-dependent dysfunction in the startle reflex magnitude habituation. While ignoring the stimuli there were no statistical differences in PPI between cannabis users and controls, although PPI in cannabis users tended to differ from that of the patients. The reduction in PPI in cannabis users was correlated with the increased duration of cannabis use, in years, but not with the concentration of cannabinoid metabolites in urine or with the recency of cannabis use in the preceding 24 hours. Furthermore, cannabis use was not associated with any differences in PPF, onset latency facilitation, and startle reflex magnitude in the absence of prepulses. The accuracy of self-reports of substance use was also investigated in this study and was found to be excellent. In addition, the study examined the validity of the substance use module of the diagnostic interview, CIDI-Auto 2.1, which was found to be acceptable for cannabis misuse diagnoses (abuse and/or dependence). Finally, cannabis dependence was found to be associated with more diagnoses of mental illness other than schizophrenia (mainly depression). Conclusions. The results of the current study suggest that chronic cannabis use is associated with schizophrenia-like deficit in PPI in otherwise healthy humans. This PPI reduction is associated with attentional impairment rather than a global sensorimotor gating deficit in healthy cannabis users.

Despite extensive research into the effects of alcohol consumption, there is no clear understanding into the mechanisms underlying human information processing impairment. The acute consumption of alcohol was investigated to determine the implications for human information processing capabilities, and to identify the extent to which these implications were stage-specific. Further aims included the investigation and quantification of caffeine-induced antagonism of alcohol impairment. Moreover, the aforementioned relationships were investigated in morning versus evening conditions. A test battery of six resource-specific tasks was utilised to measure visual perceptual, cognitive and sensory-motor performance, fashioned to return both simple and complex measures of each task. The tasks implemented were: visual perceptual performance (accommodation, visual detection, visual pattern recognition); cognition (memory recall- digit span); and motor output (modified Fitts‟ and a driving simulated line-tracking). Performance measures were recorded by the respective computer based tasks. Physiological variables measured included heart rate frequency, heart rate variability (RMSSD, High and Low Frequency Power) and body temperature. Saccade speed, saccade amplitude, pupil size and fixation duration were the oculomotor parameters measured. Three groups of participants (alcohol, caffeine+alcohol and control) n=36 were studied, split evenly between sexes in a mixed repeated/non-repeated measures design. The control group performed all test batteries under no influence. The alcohol group performed test batteries one and two sober, and three and four under the influence of a 0.4 g/kg dose of alcohol. Group caffeine+alcohol conducted test battery one sober, two under the effect of caffeine only (4 mg/kg), and three and four under the influence of both caffeine and alcohol (0.4 g/kg). The third test battery demonstrated the effects of alcohol during the inclining phase of the blood alcohol curve, and the fourth represented the declining phase. Morning experimentation occurred between 10:00 - 12: 45 and 10:30 -13:15 with evening experimentation between 19:00 - 21:30 and 19:30 - 22:00. Acute alcohol consumption at a dose of approximately 0.4 g/kg body weight effected an average peak breath alcohol concentration of 0.062 % and 0.059 % for the alcohol and caffeine+alcohol groups respectively. Task-related visual perceptual performance demonstrated significant decrements for simple reaction time, choice reaction time and error rate. Cognitive performance demonstrated no significant performance decrements, while motor performance indicated significant decrements in target accuracy only. Physiological parameters in response to alcohol consumption showed significantly decreased heart rate variability (RMSSD) in the modified Fitts‟ task only. A significant decrease in saccade amplitude in the memory task was the only change in oculomotor parameters. Prior caffeine consumption demonstrated limited antagonism to task-related alcohol impairment, significantly improving performance only in reduced error rate while reading. Caffeine consumption showed stimulating effects on physiological parameters, significantly increasing heart rate and heart rate variability when compared to alcohol alone. The design of the tasks allows for comparison between complex and simple task performance, indicating resource utilisation and depletion. Complex tasks demonstrated higher resource utilisation, however with no statistical performance differences to simple tasks. Physiological parameters showed greater change in response to alcohol consumption, than did the performance measures. Alcohol consumption imposed significant changes in physiological and oculomotor parameters for cognitive tasks only, significantly increasing heart rate frequency and decreasing heart rate variability, skin temperature and saccade amplitude. Caffeine consumption showed no antagonism of alcohol-induced performance measures. Physiological measures showed that caffeine consumption imposed stimulating effects in only the neural reflex and memory tasks, significantly increasing heart rate frequency and heart rate variability. Prior caffeine consumption significantly decreased fixation duration in the memory task only. The time of day at which alcohol was consumed demonstrated significant performance and physiological implications. Results indicated that morning consumption of alcohol imposes greater decrements in performance and larger fluctuations in physiological parameters than the decrements in evening experimental sessions. It can be concluded that alcohol consumption at a dose of 0.4 g/kg affects all stages in the information processing chain. Task performance indicates that alcohol has a greater severity on the early stages of information processing. Conversely, under the influence of alcohol an increased task complexity induces greater effects on central stage information processing. In addition, caffeine consumption at a dose of 4 mg/kg prior to alcohol does not antagonise the alcohol-induced performance decrements.

Indiana University-Purdue University Indianapolis (IUPUI) / The time course and biological mechanisms by which breast cancer (BC) and/or alterations in estrogen status lead to cognitive and brain changes remain unclear. The studies presented here use neuroimaging, cognitive testing, genetics, and biomarkers to investigate how post-chemotherapy interval (PCI), chemotherapy-induced amenorrhea (CIA), and genetic variation in the estrogen pathway affect the brain. Chapter 1 examines the association of post-chemotherapy interval (PCI) with gray matter density (GMD) and working memory-related brain activation in BC survivors (mean PCI 6.4, range 3-10 years). PCI was positively associated with GMD and activation in the right frontal lobe, and GMD in this region was correlated with global neuropsychological function. In regions where BC survivors showed decreased GMD compared to controls, this was inversely related to oxidative DNA damage and learning and memory scores. This is the first study to show neural effects of PCI and relate DNA damage to brain alterations in BC survivors. Chapter 2 demonstrates prospectively, in an independent cohort, decreased combined magnitudes of brain activation and deactivation from pre-to post-chemotherapy in patients undergoing CIA compared to both postmenopausal BC patients undergoing chemotherapy and healthy controls. CIA’s change in activity magnitude was strongly correlated with change in processing speed, suggesting this activity increase reflects effective cognitive compensation. These results demonstrate that the pattern of change in brain activity from pre- to post-chemotherapy varies according to pre-treatment menopausal status. Chapter 3 presents the effects of variation in ESR1, the gene that codes for estrogen receptor-α, on brain structure in healthy older adults. ESR1 variation was associated with hippocampus and amygdala volumes, particularly in females. Single nucleotide polymorphism (SNP) rs9340799 influenced cortical GMD and thickness differentially by gender. Apolipoprotein E (APOE)-ε4 carrier status modulated the effect of SNP rs2234693 on amygdala volumes in women. This study showed that genetic variation in estrogen relates to brain morphology in ways that differ by sex, brain region and APOE-ε4 carrier status. The three studies presented here explore the interplay of BC, estrogen, and cognition, showing that PCI, CIA, and ESR1 genotype influence brain phenotypes. Cognitive correlates of neuroimaging findings indicate potential clinical significance of these results.

The role of executive functioning in substance dependence and addiction has received increased attention in recent years; however, the findings of empirical studies are at times contradictory and difficult to compare at face value. To address the current state of fragmentation and to delineate the current body of knowledge a systematic review of existing studies was conducted. The synthesis of the findings from these studies confirmed that lower neuropsychological performance scores of executive functioning are observed in substance dependent populations. Furthermore, the synthesis of the components of these studies provided a comprehensive overview and revealed a number of critical gaps in the current body of knowledge. The gaps include limitations concerning specific demographics of the samples studied (under-representation of females, adolescents, the elderly, individuals with limited education, and individuals from Africa, Oceania, Asia, Latin America and the Caribbean), as well as the scarce number of studies investigating specific substances; insufficient longitudinal studies; and the fragmentation of executive functioning as a theoretical construct. / Psychology / M.A. (Psychology)

Indiana University-Purdue University Indianapolis (IUPUI) / Down syndrome (DS) is caused by three copies of human chromosome 21 (Hsa21) and results in an array of phenotypes including intellectual disability. Ts65Dn mice, the most extensively studied DS model, have three copies of ~50% of the genes on Hsa21 and display many phenotypes associated with DS, including cognitive deficits. DYRK1A is found in three copies in humans with Trisomy 21 and in Ts65Dn mice, and is involved in a number of critical pathways including CNS development and osteoclastogenesis. Epigallocatechin-3-gallate (EGCG), the main polyphenol in green tea, inhibits Dyrk1a activity. We have shown that a three-week EGCG treatment (~10mg/kg/day) during adolescence normalizes skeletal abnormalities in Ts65Dn mice, yet the same dose did not rescue deficits in the Morris water maze spatial learning task (MWM) or novel object recognition (NOR). Others have reported that An EGCG dose of 2-3 mg per day (90mg/ml) improved hippocampal-dependent task deficits in Ts65Dn mice. The current study investigated deficits in a radial arm maze pattern separation task in Ts65Dn mice. Pattern separation requires differentiation between similar memories acquired during learning episodes; distinguishing between these similar memories is thought to depend on distinctive encoding in the hippocampus. Pattern separation has been linked to functional activity of newly generated granule cells in the dentate gyrus. Recent studies in Ts65Dn mice have reported significant reductions in adult hippocampal neurogenesis, and after EGCG treatment, enhanced hippocampal neurogenesis. Thus, it was hypothesized that Ts65Dn mice would be impaired in the pattern separation task, and that EGCG would alleviate the pattern separation deficits seen in trisomic mice, in association with increased adult hippocampal neurogenesis. At weaning, Ts65Dn mice and euploid littermates were randomly assigned to the water control, or EGCG [0.4 mg/mL], with both treatments yielding average daily intakes of ~50 mg/kg/day. Beginning on postnatal day 75, all mice were trained on a radial arm maze-delayed non-matching-to-place pattern separation task. Euploid mice performed significantly better over training than Ts65Dn mice, including better performance at each of the three separations. EGCG did not significantly alleviate the pattern separation deficits in Ts65Dn mice. After the behavioral testing commenced, animals were given ad libitum food access for five days, received a 100mg/kg injection of BrdU, and were perfused two hours later. Coronal sections through the dorsal hippocampus were processed for BrdU labeling, and cells were manually counted throughout the subgranular zone of the dentate gyrus. The euploid controls had significantly more BrdU labeled cells than Ts65Dn mice, however, EGCG does not appear to increase proliferation of the hippocampal neuroprogenitor cells. This is the first report of deficits in Ts65Dn mice on a pattern separation task. To the extent that pattern separation depends on the functional involvement of newly generated neurons in an adult dentate gyrus, this approach in Ts65Dn mice may help identify more targeted pharmacotherapies for cognitive deficits in individuals with DS.