Neurocognitive, Autonomic, and Mood Effects of Adderall: A Pilot Study of Healthy College Students

Prescription stimulant medications are considered a safe and long-term effective treatment for Attention Deficit Hyperactivity Disorder (ADHD). Studies support that stimulants enhance attention, memory, self-regulation and executive function in individuals with ADHD. Recent research, however, has found that many college students without ADHD report misusing prescription stimulants, primarily to enhance their cognitive abilities. This practice raises the question whether stimulants actually enhance cognitive functioning in college students without ADHD. We investigated the effects of mixed-salts amphetamine (i.e., Adderall, 30 mg) on cognitive, autonomic and emotional functioning in a pilot sample of healthy college students without ADHD (n = 13), using a double-blind, placebo-controlled, within-subjects design. The present study was the first to explore cognitive effects in conjunction with mood, autonomic effects, and self-perceptions of cognitive enhancement. Results revealed that Adderall had minimal, but mixed, effects on cognitive processes relevant to neurocognitive enhancement (small effects), and substantial effects on autonomic responses, subjective drug experiences, and positive states of activated emotion (large effects). Overall, the present findings indicate dissociation between the effects of Adderall on activation and neurocognition, and more importantly, contrary to common belief, Adderall had little impact on neurocognitive performance in healthy college students. Given the pilot design of the study and small sample size these findings should be interpreted cautiously. The results have implications for future studies and the education of healthy college students and adults who commonly use Adderall to enhance neurocognition

Anger, agency, risk and action: A neurobehavioral model with proof-of-concept in healthy young adults

Anger can engender action by individuals and groups. It is thus important to understand anger’s behavioral phenotypes and their underlying neural substrates. Here we introduce a construct we term agentic anger, a state that motivates action to achieve risky goals. We test predictions of our neurobehavioral model in two proof-of-concept studies. Study 1 used the Incentive Balloon Analogue Risk Task (iBART) in a within-subjects, repeated measures design in 39 healthy volunteers to evaluate: a) impact of frustrative non-reward on agentic anger, assessed by self-reports of negative activation (NA), b) impact of achieved reward on exuberance, assessed by self-reports of positive activation (PA), c) their interrelationship, and d) their relationship with traits of positive emotion, negative emotion, immersive emotion and impulsivity. Task-induced NA was positively correlated with task-induced PA (r=0.56, p<.001), risk-taking on the task (r=0.27 to 0.36, p≤.05, .01) and trait Social Potency (SP, r=0.34 to 0.35, p<.05), a measure of reward sensitivity on the Multidimensional Personality Questionnaire Brief-Form (MPQ-BF). Study 2 assessed functional MRI response to stakes for risk-taking in healthy volunteers receiving 20 mg d-amphetamine (AMP) in a double-blinded, placebo-controlled crossover design (N = 10 males; 20 MRI scans), providing preliminary information on ventral striatal response to risky rewards during catecholamine (CA) activation. Trait SP and task-induced PA were strongly positively related to AMP-facilitated BOLD response in the right nucleus accumbens, a brain region in which DA prediction error signal shapes action value and selection (SP r=+.60, p=.03; PA r=+.72, p=.02, respectively). Participants’ task-induced NA was also strongly positively related with trait SP (r=0.51; d=1.2) and task-induced PA (r=0.68; d=1.9), replicating the findings of Study 1. Together these results inform the phenomenology and neurobiology of agentic anger, which recruits incentive motivational circuitry and motivates personal action in response to goals that entail risk (defined as exposure to uncertainty, obstacles, potential harm, loss and/or financial, emotional, bodily or moral peril). Neural mechanisms of agency, anger, exuberance and risk-taking are discussed, with implications for personal and group action, decision-making, social justice, and behavior change

The neurobiology of wellness: 1H-MRS correlates of agency, flexibility and neuroaffective reserves in healthy young adults

Proton magnetic resonance spectroscopy (1H-MRS) is a noninvasive imaging technique that measures the concentration of metabolites in defined areas of the human brain in vivo. The underlying structure of natural metabolism-emotion relationships is unknown. Further, there is a wide range of between-person differences in metabolite concentration in healthy individuals, but the significance of this variation for understanding emotion in healthy humans is unclear. Here we investigated the relationship of two emotional constructs, agency and flexibility, with the metabolites glutamate and glutamine (Glx), N-acetylaspartate (tNAA), choline (Cho), creatine (tCr), and myo-inositol (Ins) in the right dorsal anterior cingulate cortex (dACC) in medically and psychiatrically healthy volunteers (N = 20, 9 female; mean age = 22.8 years, SD = 3.40). The dACC was selected because this region is an integrative hub involved in multiple brain networks of emotion, cognition and behavior. Emotional traits were assessed using the Multidimensional Personality Questionnaire Brief Form (MPQ-BF), an empirically derived self-report instrument with an orthogonal factor structure. Phenotypes evaluated were positive and negative agency (MPQ-BF Social Potency, Aggression), emotional and behavioral flexibility (MPQ-BF Absorption, Control-reversed), and positive and negative affect (MPQ-BF Social Closeness; Stress Reaction, Alienation). The resting concentration of tNAA in the dACC was robustly positively correlated with Absorption (r = +0.56, unadjusted p = .005), moderately positively correlated with Social Potency (r = +0.42, unadjusted p = .03), and robustly negatively correlated with Aggression (r = -0.59, unadjusted p = .003). Absorption and Aggression accounted for substantial variance in tNAA (R2 = 0.31, 0.35; combined R2 = 0.50), and survived correction for multiple comparisons (Holm-Bonferroni adjusted p = .032, 0.021, respectively). dACC Glx and Cho had modest relationships with behavioral flexibility and social affiliation that did not survive this multiple correction, providing effect sizes for future work. Principal Component Analysis (PCA) revealed a three-factor orthogonal solution indicating specific relationships between: 1) Glx and behavioral engagement; 2) Cho and affiliative bonding; and 3) tNAA and a novel dimension that we term neuroaffective reserves. Our results inform the neurobiology of agency and flexibility and lay the groundwork for understanding mechanisms of natural emotion using 1H-MRS.Othe

Characteristics of study participants.

<p>Statistical tests were performed using ANOVA or chi-square as appropriate, with alpha (2-tailed) = 0.05. Abbreviations: fMRI, functional magnetic resonance imaging; PANSS, positive and negative syndrome scale; CPZ, chlorpromazine.</p><p>*n/s, no significant main effects of genotype or diagnosis, or significant genotype×diagnosis interaction.</p><p>**Post-error slowing was calculated as the difference in saccadic latency between correct trials following an error and correct trials immediately prior to errors.</p

Dopamine D1 signaling organizes network dynamics underlying working memory

Local prefrontal dopamine signaling supports working memory by tuning pyramidal neurons to task-relevant stimuli. Enabled by simultaneous positron emission tomography–magnetic resonance imaging (PET-MRI), we determined whether neuromodulatory effects of dopamine scale to the level of cortical networks and coordinate their interplay during working memory. Among network territories, mean cortical D1 receptor densities differed substantially but were strongly interrelated, suggesting cross-network regulation. Indeed, mean cortical D1 density predicted working memory–emergent decoupling of the frontoparietal and default networks, which respectively manage task-related and internal stimuli. In contrast, striatal D1 predicted opposing effects within these two networks but no between-network effects. These findings specifically link cortical dopamine signaling to network crosstalk that redirects cognitive resources to working memory, echoing neuromodulatory effects of D1 signaling on the level of cortical microcircuits

Effects of <i>MTHFR</i> 677C>T genotype on error-related dACC activation.

<p>Both schizophrenia patients (a) and healthy participants (b) exhibited significant condition×genotype interactions (patients: F = 4.51, p = .042; healthy participants: F = 10.32, p = .004) indicating that C/C participants, but not T allele carriers, showed significant error-related dACC activation. (c) Pseudocolor statistical maps of the relationship between 677C allele load (0, 1, or 2 copies) and error-related activation (error minus correct) in the combined group, displayed on the inflated medial cortical surface. The dACC is outlined in green. Graphs illustrate the effects of allele load on error-related activation, averaged across vertices in the anatomically defined dACC, for patients and healthy participants. Error bars indicate the standard error of the mean.</p

Relation of error-related dACC activation with antisaccade error rate in C/C (a) and T carrier (b) participants.

<p>Gray triangles indicate data points from schizophrenia patients; black circles indicate healthy participants.</p

Regions with significant (p<.05) effects of genotype on antisaccade error-related activation following whole-brain correction.

<p>Abbreviation: ACC, anterior cingulate cortex.</p

Schematic and timeline of the three trial types: Easy, Hard, and Fake Hard.

<p>For fMRI analyses comparing error and correct responses, we did not distinguish between trial types. All trials begin with an instructional cue (300 ms) of a color (blue or yellow) indicating either a Hard or Easy trial, followed by fixation. At 1800 ms, the central fixation ring disappears (200 ms gap), and at 2000 ms, it re-appears on either the right or left side as the imperative stimulus to which participants must respond. Hard trials are distinguished by an increase in luminance of both the peripheral squares that mark the potential locations of stimulus appearance during the gap and of the imperative stimulus. Except for the Hard cue, Fake Hard trials are identical to Easy trials. In the trials depicted, the correct response is a saccade <i>away</i> from the stimulus on the left side of the display. An error would involve a saccade towards the stimulus. After one second, the fixation ring returns to the center, where participants return their gaze to await the next trial.</p