Music and movement therapy improves quality of life and attention and associated electroencephalogram changes in patients with attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder. Treatments for ADHD include pharmacological and nonpharmacological therapy. However, pharmacological treatments have side effects such as poor appetite, sleep disturbance, and headache. Moreover, nonpharmacological treatments are not effective in ameliorating core symptoms and are time-consuming. Hence, developing an alternative and effective treatment without (or with fewer) side effects is crucial. Music therapy has long been used to treat numerous neurological diseases. Although listening to music is beneficial for mood and cognitive functions in patients with ADHD, research on the effects of music and movement therapy in children with ADHD is lacking. METHODS: The present study investigated the effects of an 8-week music and movement intervention in 13 children with ADHD. The Pediatric Quality of Life Inventory (PedsQL) was used to evaluate changes in participants' quality of life. Conners' Kiddie Continuous Performance Test (K-CPT 2) and the Swanson, Nolan, and Pelham rating scale (SNAP-IV) were used to assess core symptoms. Electroencephalogram (EEG) recordings were analyzed to determine neurophysiological changes. RESULTS: The results revealed that the participants' quality of life increased significantly after the 8-week intervention. Furthermore, the participants' hit reaction times in the block 1 and block 2 tests of K-CPT 2 decreased significantly after the intervention. EEG analysis demonstrated an increase in alpha power and Higuchi's fractal dimension and a decrease in delta power in certain EEG channels. CONCLUSION: Our music and movement intervention is a potential alternative and effective tool for ADHD treatment and it can significantly improve patients' quality of life and attention.

Increased sensitivity in detection of deficits following two commonly used animal models of stroke.

Stroke is a leading cause of death and disability in the United States. Most strokes are ischemic, resulting in both cognitive and motor impairments. Animal models of ischemic stroke such as the distal middle cerebral artery occlusion (dMCAO) and photothrombotic stroke (PTS) procedures have become invaluable tools, with their own advantages and disadvantages. The dMCAO model is clinically relevant as it occludes the artery most affected in humans, but yields variability in the infarct location as well as the behavioral and cognitive phenotypes disrupted. The PTS model has the advantage of allowing for targeted location of infarct, but is less clinically relevant. The present study evaluates phenotype disruption over time in mice subjected to either dMCAO, PTS, or a sham surgery. Post-surgery, animals were tested over 28 days on standard motor tasks (grid walk, cylinder, tapered beam, and rotating beam), as well as a novel odor-based operant task; the 5:1 Odor Discrimination Task (ODT). Results demonstrate a significantly greater disturbance of motor control with PTS as compared with Sham and dMCAO. Disruption of the PTS group was detected up to 28 days post-stroke on the grid walk, and up to 7 days on the rotating and tapered beam tasks. PTS also led to significant short-term disruption of ODT performance (1-day post-surgery), exclusively in males, which appeared to be driven by motoric disruption of the lick response. Together, this data provides critical insights into the selection and optimization of animal models for ischemic stroke research. Notably, the PTS procedure was best suited for producing disruptions of motor behavior that can be detected with common behavioral assays and are relatively enduring, as is observed in human stroke.

Sex-Dependent Attentional Impairments in a Subchronic Ketamine Mouse Model for Schizophrenia.

Background: The development of more effective treatments for schizophrenia targeting cognitive and negative symptoms has been limited, partly due to a disconnect between rodent models and human illness. Ketamine administration is widely used to model symptoms of schizophrenia in both humans and rodents. In mice, subchronic ketamine treatment reproduces key dopamine and glutamate dysfunction; however, it is unclear how this translates into behavioral changes reflecting positive, negative, and cognitive symptoms. Methods: In male and female mice treated with either subchronic ketamine or saline, we assessed spontaneous and amphetamine-induced locomotor activity to measure behaviors relevant to positive symptoms, and used a touchscreen-based progressive ratio task of motivation and the rodent continuous performance test of attention to capture specific negative and cognitive symptoms, respectively. To explore neuronal changes underlying the behavioral effects of subchronic ketamine treatment, we quantified expression of the immediate early gene product, c-Fos, in key corticostriatal regions using immunofluorescence. Results: We showed that spontaneous locomotor activity was unchanged in male and female subchronic ketamine-treated animals, and amphetamine-induced locomotor response was reduced. Subchronic ketamine treatment did not alter motivation in either male or female mice. In contrast, we identified a sex-specific effect of subchronic ketamine on attentional processing wherein female mice performed worse than control mice due to increased nonselective responding. Finally, we showed that subchronic ketamine treatment increased c-Fos expression in prefrontal cortical and striatal regions, consistent with a mechanism of widespread disinhibition of neuronal activity. Conclusions: Our results highlight that the subchronic ketamine mouse model reproduces a subset of behavioral symptoms that are relevant for schizophrenia.

A systematic review of the utility of continuous performance tests among adults with ADHD.

OBJECTIVE: The clinical utility of continuous performance tests (CPTs) among adults with attention-deficit/hyperactivity disorder (ADHD) has increasingly been brought under question. Therefore, the objective of this study was to systematically review the literature to investigate the clinical utility of various commercially available CPTs, including the Conner's Continuous Performance Test (CCPT), Test of Variables of Attention (TOVA), Gordon Diagnostic System (GDS), and Integrated Visual and Auditory Continuous Performance Test (IVA) in the adult ADHD population. METHODS: This systematic review followed the a priori PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Articles were gathered from PsycINFO, PsycARTICLES, Academic Search Complete, and Google Scholar on 11 April 2022. Sixty-nine articles were included in the final review. Risk of bias was assessed using the National Institute of Health Quality Assessment Took for Observational Cohort and Cross-Sectional Studies. RESULTS: Most articles demonstrated high risk of bias, and there was substantial heterogeneity across studies. Overall, the reviewed CPTs appeared to have limited diagnostic utility and classification accuracy. Although many studies showed differing scores between adults with ADHD and comparison groups, findings were not consistent. Characteristics of CPT performances among adults with ADHD were mixed, with little consistency and no evidence of a clear profile of performances; however, CCPT commission errors appeared to have the most utility when used a treatment or experimental outcome measure, compared to other CCPT scores. CONCLUSION: Overall, CPTs should not be used in isolation as a diagnostic test but may be beneficial when used as a component of a comprehensive assessment.

Effect of biofeedback intervention on neurological characteristics of children with attention deficit hyperactivity disorder.

OBJECTIVE: To evaluate the effects of biofeedback intervention on the neurological characteristics of children with attention deficit hyperactivity disorder (ADHD). METHODS: 150 children aged 6-12 years with ADHD were divided into two groups according to the treatment method. The atomoxetine group received atomoxetine drug treatment, and the combined treatment group received EEG biofeedback therapy. Continuous performance test (CPT), SNAP-IV and WFIRS-P were used to assess attention and behavior, and functional magnetic resonance imaging (fMRI) was used to observe changes in brain activity. RESULTS: The response time, error times, error response rate and attention fluctuation index of CPT in the combined treatment group were significantly lower than those in the atomoxetine group (p < 0.05), and the correct response rate was higher than that in the atomoxetine group (p < 0.05). After intervention, SNAP-IV and WFIRS-P scores in the combined treatment group were significantly lower than those in the atomoxetine group (p < 0.001). fMRI results showed that the activity of the prefrontal, parietal, amygdala and hippocampus in the combined treatment group was significantly higher than that in the atomoxetine group (p < 0.001). CONCLUSION: Biofeedback intervention can significantly improve the attention and behavior of ADHD children and positively regulate the neural activity in related brain areas on the basis of drug treatment, suggesting that biofeedback therapy can be considered as a potential effective nondrug treatment option for ADHD children.

ADHD and Anxiety Symptoms: Does Construct or Assessment Type Matter More?

OBJECTIVE: This study examined the relationships between self-reported ADHD symptoms, self-reported anxiety, and continuous performance test (CPT) performance. METHOD: 128 postsecondary students referred for clinical evaluation for possible ADHD and related conditions completed the Conners Adult ADHD Rating Scale, the Behavior Assessment Scale for Children, Third Edition, and either of two CPTs. RESULTS: Multiple regression models found that when self-reported anxiety and CPT performance were used to simultaneously predict self-reported ADHD symptoms, CPT performance was not a significant predictor, whereas self-reported anxiety was. This finding was replicated across two different subsamples that took different CPTs. CONCLUSION: Self-reported anxiety and ADHD symptoms are strongly related, but neither of these variables is significantly related to CPT performance. Implications for clinical practice and future research are discussed.

Diagnostic Utility of Conners Continuous Performance Test-3 for Attention Deficit/Hyperactivity Disorder: A Systematic Review.

OBJECTIVE: To review the literature on the utility of the Conners CPT-3 in persons with ADHD. METHODS: A systematic review was conducted. Six databases were searched using inclusion criteria: research studies, year 2000+, English, and ages 8+. Two raters independently screened 1,480 title/abstracts and subsequently reviewed 399 full texts. Data extraction and critical appraisal were conducted. Reflective thematic analysis through inductive coding identified qualitative themes. RESULTS: Thirteen studies met inclusion criteria with five themes identified. Five studies found CPT-3 was a weak or poor predictor of ADHD diagnosis while two found it was an adequate predictor. Two studies found CPT-3 could differentiate clients with comorbid ADHD/anxiety from ADHD or ADHD from obsessive-compulsive disorder. One found CPT-3 could not differentiate ADHD from ASD or comorbid ADHD/ASD. CONCLUSIONS: Results revealed CPT-3 as a standalone measure is a weak or poor predictor of ADHD. Multiple measures for evaluating persons with ADHD are recommended.

Driving impairment due to psychoactive substances and attention deficit disorder: A pilot study.

Objective: Attention disorder and substance use disorder are linked to driving impairment and increased road crash involvement. This study explores attention deficits in a population of drivers found driving under the influence (DUI) of psychoactive substances. Methods: A case-control study was conducted comparing subjects with a previous DUI episode (cases) to subjects who were negative for DUI offenses (controls). Personal, socio-demographic, and DUI data were collected for both groups. All subjects were administered the Continuous Performance Test-third edition (CPT-3), which measures dimensions of attention, including inattentiveness, impulsivity, sustained attention, and vigilance. Possible associations with a previous DUI episode, the use of illicit substances or excessive alcohol use, and road crash involvement were analyzed statistically. Results: Overall, the study included 147 subjects (100 cases, 47 controls). The parameter distributions of detectability, probability of ADHD, and inattentiveness indicated statistical differences between the two groups. No attention deficits predicted substance use disorder or excessive alcohol consumption. Inattentiveness was an independent risk factor for previous road collision involvement. Conclusions: The results suggest that alterations exist in some attention dimensions in a population of DUI subjects who were users of alcohol or other psychoactive substances and involved in road traffic crashes. The CPT-3 had successfully distinguished between the two study groups, and after validation, it could be useful in the process of reinstating a driver's license. Future research should expand the study sample to better understand the relevance of the proposed methodological approach in terms of prevention, rehabilitation, and the monitoring of subjects evaluated for driving eligibility requirements.

Development of a novel rodent rapid serial visual presentation task reveals dissociable effects of stimulant versus nonstimulant treatments on attentional processes.

The rapid serial visual presentation (RSVP) task and continuous performance tasks (CPT) are used to assess attentional impairments in patients with psychiatric and neurological conditions. This study developed a novel touchscreen task for rats based on the structure of a human RSVP task and used pharmacological manipulations to investigate their effects on different performance measures. Normal animals were trained to respond to a target image and withhold responding to distractor images presented within a continuous sequence. In a second version of the task, a false-alarm image was included, so performance could be assessed relative to two types of nontarget distractors. The effects of acute administration of stimulant and nonstimulant treatments for ADHD (amphetamine and atomoxetine) were tested in both tasks. Methylphenidate, ketamine, and nicotine were tested in the first task only. Amphetamine made animals more impulsive and decreased overall accuracy but increased accuracy when the target was presented early in the image sequence. Atomoxetine improved accuracy overall with a specific reduction in false-alarm responses and a shift in the attentional curve reflecting improved accuracy for targets later in the image sequence. However, atomoxetine also slowed responding and increased omissions. Ketamine, nicotine, and methylphenidate had no specific effects at the doses tested. These results suggest that stimulant versus nonstimulant treatments have different effects on attention and impulsive behaviour in this rat version of an RSVP task. These results also suggest that RSVP-like tasks have the potential to be used to study attention in rodents.

Differentiating Performance on the Connors Continuous Performance Test (CPT-3) as a Function of Comorbid Internalizing Psychopathology.

OBJECTIVE: Internalizing psychopathology commonly co-occurs with attention-deficit/hyperactivity disorder (ADHD). Attention concerns are present in both ADHD and internalizing disorders, yet the neuropsychological functioning of those with comorbid ADHD and internalizing psychopathology is underexamined. METHOD: This study compared Conners' Continuous Performance Test-Third Edition (CPT-3) profiles across ADHD (n = 141), internalizing psychopathology (n = 78), and comorbid (ADHD/internalizing psychopathology; n = 240) groups. RESULTS: Compared to the internalizing psychopathology group, the comorbid group had higher mean T-scores on CPT-3 indices indicative of inattentiveness and impulsivity and more clinically elevated T-scores (T>60) on indices measuring inattentiveness and impaired sustained attention. Patients in the comorbid group were also more likely to have abnormal overall CPT-3 profiles (>2 elevated T-scores) than the ADHD and psychopathology only groups. CONCLUSION: Patients with comorbid ADHD/internalizing psychopathology may evidence a more impaired attentional performance on the CPT-3, which could aid in more tailored treatment planning.

Is the Conners' continuous performance test helpful for assessing attention deficit hyperactivity disorder in a clinical setting?

BACKGROUND: Despite lacking validation for Norwegian populations, the Conners Continuous Performance Test II (CCPT-II) is applied to almost one-third of children receiving an ADHD diagnosis. However, evidence of the CCPT-II's ability to differentiate between children with and without ADHD is contradictory. Thus, this study examines how CCPT-II results correlate with ADHD symptoms reported by mothers and teachers in a sample representing ordinary child and adolescent mental health services and explores the extent to which the CCPT-II influences the diagnostic result. METHODS: Correlations between CCPT-II results and ADHD Rating Scale scores and a clinical diagnosis of ADHD were analysed in children aged 6-15 years (N = 69) referred to a child and adolescent psychiatric outpatient clinic. RESULTS: Total ADHD symptom scores rated by mothers correlated with hit reaction time (HRT) block change (.260), HRT inter-stimulus interval (ISI) change (.264) and CCPT-II overall index (.263), while hyperactivity subscale scores correlated with omissions (.285), HRT (.414) and variability (.400). In teachers' ratings, total ADHD and both subscale scores correlated with commissions (.280-.382), while hyperactivity scores correlated with variability (.265). A higher number of commissions was the only significant difference in CCPT-II performance between children diagnosed with and children without ADHD. CONCLUSIONS: Correlations between CCPT-II results and ADHD symptoms were all small to moderate. As such, CCPT-II results should be interpreted with caution, because they correspond to a limited degree with other sources of information.

Review of Studies on Incremental Validity of Assessment Measures Used in Psychological Assessment of Attention-Deficit Hyperactivity Disorder.

Few studies have summarized the literature relevant to the incremental validity of tools and procedures for the assessment of attention-deficit hyperactivity disorder (ADHD). The current project reviewed such studies published in the prior 18 years. Results from studies on the incremental validity of measures used in the assessment of ADHD were reviewed. Measures included symptom reports, clinical interviews, behavioral observation, continuous performance and other psychomotor tasks, intelligence tests, and measures of executive function. Twenty-nine published studies and two reviews were identified from 2004 to 2022. Incremental validity was determined using various statistics including R2, classification metrics, odds ratios, and post-test probabilities. Findings suggest that symptom reports from a collateral source and continuous performance test measures have incremental validity over self-reports and clinical interviews. Measures of intellectual and executive functioning did not show incremental validity in the diagnosis of ADHD. Findings are relevant to the practitioner, as they bear on the optimization of both the cost-effectiveness and the diagnostic accuracy of combined procedures in the assessment of ADHD.

Vigilance to Painful Laser Stimuli is Associated with Increased State Anxiety and Tense Arousal.

Introduction: Pain is frequently accompanied by enhanced arousal and hypervigilance to painful sensations. Here, we describe our findings in an experimental vigilance task requiring healthy participants to indicate when randomly timed moderately painful stimuli occur in a long train of mildly painful stimuli. Methods: During a continuous performance task with painful laser stimuli (CPTpain), 18 participants rated pain intensity, unpleasantness, and salience. We tested for a vigilance decrement over time using classical metrics including correct targets (hits), incorrectly identified non-targets (false alarms), hit reaction time, and false alarm reaction time. We measured state anxiety and tense arousal before and after the task. Results: We found a vigilance decrement across four 12.5-minute blocks of painful laser stimuli in hits [F3,51=2.91; p=0.043; time block 1>block 4 (t=2.77; p=0.035)]. Both self-report state anxiety (tpaired,17=3.34; p=0.0039) and tense arousal (tpaired,17=3.20; p=0.0053) increased after the task. We found a vigilance decrement during our laser pain vigilance task consistent with vigilance decrements found in other stimulus modalities. Furthermore, state anxiety positively correlated with tense arousal. Discussion: CPTpain acutely increased tense arousal and state anxiety, consistent with previous results implicating the reciprocal interaction of state anxiety and acute painful sensations and the role of pain in augmenting tense arousal. These results may indicate a psychological process which predisposes the hypervigilant to developing greater acute pain, resulting in positive feedback, greater pain and anxiety.

Quantifying attention span across the lifespan.

Introduction: Studies examining sustained attention abilities typically utilize metrics that quantify performance on vigilance tasks, such as response time and response time variability. However, approaches that assess the duration that an individual can maintain their attention over time are lacking. Methods: Here we developed an objective attention span metric that quantified the maximum amount of time that a participant continuously maintained an optimal "in the zone" sustained attention state while performing a continuous performance task. Results: In a population of 262 individuals aged 7-85, we showed that attention span was longer in young adults than in children and older adults. Furthermore, declines in attention span over time during task engagement were related to clinical symptoms of inattention in children. Discussion: These results suggest that quantifying attention span is a unique and meaningful method of assessing sustained attention across the lifespan and in populations with inattention symptoms.

Effects of one single-dose methylphenidate compared to one single-dose placebo on QbTest performance in adults with untreated ADHD: a randomized controlled trial.

BACKGROUND: Treatment of adults with attention-deficit/hyperactivity disorder (ADHD) primary involves methylphenidate (MPH). Earlier studies have identified placebo responders to increase toward the end of the treatment periods. However, little is known about the immediate effects of placebo on the core symptoms of ADHD in adults. The present study aimed to examine the effects of one single-dose MPH compared to one single-dose placebo during clinical assessments with continuous performance tests (CPT). METHODS: In a randomized study with cross-over design, 40 adults between 19 and 64 years (72.5% women) with untreated ADHD were consecutively enrolled. The study comprised two trial days with four days in between. The QbTest was performed twice on the same day, before and 80 min after intake of one single-dose 20 mg immediate release methylphenidate (IR-MPH) and with one single-dose placebo, in randomized order. RESULTS: Performance improved in QbInattention, F (3, 117) = 38.25, p < 0.001, after given IR-MPH (mean diff = 1.14) and after placebo (mean diff = 0.60) with the effect sizes 1.17 and 0.63 respectively. IR-MPH improved performance in QbActivity (mean diff = 0.81, p < 0.001) and QbImpulsivity (mean diff = 0.46, p < 0.04). The proportion of improvements (a decrease by ≥ 0.5 Qb-score) in the parameters QbInattention, QbActivity and QbImpulsivity were 90%, 60% and 52.5%, respectively. After given placebo, corresponding proportions were 60%, 30% and 35%, respectively. CONCLUSIONS: There seems to be an immediate placebo response in the core symptom inattention. The effect of placebo cannot be ruled out and must be taken in consideration during drug trials with continuous performance tests (CPTs). TRIAL REGISTRATION: ClinicalTrials.gov; Identifier: NCT02473185.

Effects of psilocybin, the 5-HT2A receptor agonist TCB-2, and the 5-HT2A receptor antagonist M100907 on visual attention in male mice in the continuous performance test.

RATIONALE: Neuropsychiatric disorders such as depression are characterized in part by attention deficits. Attention is modulated by the serotonin (5-HT) neurotransmitter system. The 5-HT2A agonist and hallucinogen psilocybin (PSI) is a promising treatment for disorders characterized by attention changes. However, few studies have investigated PSI's direct effect on attention. OBJECTIVE: Using the rodent continuous performance task (CPT), we assessed PSI's effect on attention. We also evaluated the impact of 5-HT2A receptor agonist TCB-2 and antagonist M100907 for comparative purposes. METHODS: In the CPT, mice learned to distinguish visual targets from non-targets for milkshake reward. Performance was then tested following injections of PSI (0.3, 1, and 3 mg/kg), TCB-2 (0.3, 1, and 3 mg/kg), or M100907 (0.1, 0.3, and 1 mg/kg). Subsequently, drug effects were then evaluated using a more difficult CPT with variable stimulus durations. Mice were then tested on the CPT following repeated PSI injections. Drug effects on locomotor activity were also measured. RESULTS: In the CPT, all three drugs reduced hit and false alarm rate and induced conservative responding. PSI also reduced target discrimination. These effects were seen primarily at doses that also significantly reduced locomotor activity. No drug effects were seen on the more difficult CPT or following repeated PSI injections. CONCLUSIONS: Psilocybin, TCB-2, and M100907 impaired performance of the CPT. However, this may be in part due to drug-induced locomotor changes. The results provide little support for the idea that psilocybin alters visual attention, or that 5-HT2A receptors modulate this process.

Beyond Attention-Deficit Hyperactivity Disorder: Exploring Psychiatric Comorbidities and Their Neuropsychological Consequences in Adults.

Objectives: This study aimed to identify the psychiatric comorbidity status of adult patients diagnosed with attention-deficit hyperactivity disorder (ADHD) and determine the impact of comorbidities on neuropsychological outcomes in ADHD. Methods: The study participants were 124 adult patients with ADHD. Clinical psychiatric assessments were performed by two boardcertified psychiatrists in accordance with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. All participants were assessed using the Mini-International Neuropsychiatric Interview Plus version 5.0.0 to evaluate comorbidities. After screening, neuropsychological outcomes were assessed using the Comprehensive Attention Test (CAT) and the Korean version of the Wechsler Adult Intelligence Scale, Fourth Edition (K-WAIS-IV). Results: Mood disorders (38.7%) were the most common comorbidity of ADHD, followed by anxiety (18.5%) and substance use disorders (13.7%). The ADHD with comorbidities group showed worse results on the Perceptual Organization Index and Working Memory Index sections of the K-WAIS than the ADHD-alone group (p=0.015 and p=0.024, respectively). In addition, the presence of comorbidities was associated with worse performance on simple visual commission errors in the CAT tests (p=0.024). Conclusion: These findings suggest that psychiatric comorbidities are associated with poor neuropsychological outcomes in adult patients with ADHD, highlighting the need to identify comorbidities in these patients.

Attention, attention! Posttraumatic stress disorder is associated with altered attention-related brain function.

Posttraumatic stress disorder (PTSD) is a debilitating condition characterized by altered arousal, mood, and cognition. Studies report attentional alterations such as threat bias in individuals with PTSD, though this work has largely been conducted within emotionally-charged contexts (e.g., threatening stimuli). Emerging behavioral evidence suggests that PTSD-related attention deficits exist even in the absence of threatening cues or anxiety triggers. However, the role and functioning of attention brain circuits as they relate to PTSD remains underexplored. In this mini review, we highlight recent work using non-emotional stimuli to investigate the neurobiology of attention and disruptions to attention-related brain function among individuals with PTSD. We then discuss gaps in the current literature, including questions pertaining to the neural circuitry of attentional alterations in PTSD, as well as the contributions that trauma exposure, PTSD symptoms, comorbidities, and pre-existing vulnerabilities may have in this relationship. Finally, we suggest future directions for this emerging area of research, which may further inform knowledge surrounding the neurobiological underpinnings of PTSD and potential treatments.

Relationship between two forms of impulsivity in mice at baseline and under acute and sub-chronic atomoxetine treatment.

RATIONALE: Impulsivity is a symptom of various mental disorders, including attention deficit hyperactivity disorder (ADHD), bipolar disorder, and addiction. Impulsivity is not a unitary construct, but is present in different forms, yet only a few rodent studies have explored the relationship between these forms within individual subjects. OBJECTIVES: In this study, we compared behaviors representing two impulsivity forms, delay discounting (choice impulsivity) and premature responding (waiting impulsivity), within the same mice. METHODS: C57BL/6J male mice were concurrently trained and tested in the delay discounting task and the rodent continuous performance test in a counterbalanced design. The effects of the ADHD medication atomoxetine were tested in both tasks, after both acute (0.3-5.0 mg/kg) and sub-chronic (0.3 mg/kg twice daily for seven days) administration. RESULTS: There was no correlation between the two impulsivity forms at baseline. Acute atomoxetine treatment (1, 3, and 5 mg/kg) significantly reduced premature responding. Furthermore, sub-chronic treatment with 0.3 mg/kg of atomoxetine caused a stable decrease in premature responding. Atomoxetine had no significant effect on delay discounting after acute or sub-chronic administration, although the acute administration of 1 mg/kg showed a trend towards increasing delay discounting. CONCLUSIONS: The present results support that delay discounting and premature responding represent two different forms of impulsivity that show dissimilar responses to atomoxetine treatment. The consistency with findings in humans lends support to the translatability of the results in mice.

Prefrontal GABA and glutamate-glutamine levels affect sustained attention.

Attention levels fluctuate during the course of daily activities. However, factors underlying sustained attention are still unknown. We investigated mechanisms of sustained attention using psychological, neuroimaging, and neurochemical approaches. Participants were scanned with functional magnetic resonance imaging (fMRI) while performing gradual-onset, continuous performance tasks (gradCPTs). In gradCPTs, narrations or visual scenes gradually changed from one to the next. Participants pressed a button for frequent Go trials as quickly as possible and withheld responses to infrequent No-go trials. Performance was better for the visual gradCPT than for the auditory gradCPT, but the 2 were correlated. The dorsal attention network was activated during intermittent responses, regardless of sensory modality. Reaction-time variability of gradCPTs was correlated with signal changes (SCs) in the left fronto-parietal regions. We also used magnetic resonance spectroscopy (MRS) to measure levels of glutamate-glutamine (Glx) and γ-aminobutyric acid (GABA) in the left prefrontal cortex (PFC). Glx levels were associated with performance under undemanding situations, whereas GABA levels were related to performance under demanding situations. Combined fMRI-MRS results demonstrated that SCs of the left PFC were positively correlated with neurometabolite levels. These findings suggest that a neural balance between excitation and inhibition is involved in attentional fluctuations and brain dynamics.