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Stop-Signal Reaction-Time Task Performance: Role of Prefrontal Cortex and Subthalamic Nucleus: Cereb. Cortex, Vol. 18, No. 1. (1 January 2008), pp. 178-188.The stop-signal reaction-time (SSRT) task measures inhibition of a response that has already been initiated, that is, the ability to stop. Human subjects classified as "impulsive," for example, those with attention deficit and hyperactivity disorder, are slower to respond to the stop signal. Although functional and structural imaging studies in humans have implicated frontal and basal ganglia circuitry in the mediation of this form of response control, the precise roles of the cortex and basal ganglia in SSRT performance are far from understood. We describe effects of excitotoxic fiber-sparing lesions of the orbitofrontal cortex (OF), infralimbic cortex (IL), and subthalamic nucleus (STN) in rats performing a SSRT task. Lesions to the OF slowed SSRT, whereas lesions to the IL or the STN had no effect. On the go-signal trials, neither cortical lesion affected go-trial reaction time (GoRT), but STN lesions speeded such latencies. The STN lesion also significantly reduced accuracy of stopping at all stop-signal delays, indicative of a generalized stopping impairment that was independent of the SSRT itself. 10.1093/cercor /bhm044Dawn Eagle, Christelle Baunez, Daniel Hutcheson, Olivia Lehmann, Aarti Shah, Trevor Robbins

Source: Cereb. Cortex, Vol. 18, No. 1. (1 January 2008), pp. 178-188.
The impact of prescribed psychotropics on youth: Clinical Practice and Epidemiology in Mental Health, Vol. 3 (20 October 2007), 21.Shaheen Lakhan, Gareth Hagger-Johnson

Source: Clinical Practice and Epidemiology in Mental Health, Vol. 3 (20 October 2007), 21.
Cortical Thinning of the Attention and Executive Function Networks in Adults with Attention-Defi cit/Hyperactiv ity Disorder.: Cereb Cortex (18 August 2006)Attention -deficit/hyper activity disorder (ADHD) has been associated with structural alterations in brain networks influencing cognitive and motor behaviors. Volumetric studies in children identify abnormalities in cortical, striatal, callosal, and cerebellar regions. In a prior volumetric study, we found that ADHD adults had significantly smaller overall cortical gray matter, prefrontal, and anterior cingulate volumes than matched controls. Thickness and surface area are additional indicators of integrity of cytoarchitectu re in the cortex. To expand upon our earlier results and further refine the regions of structural abnormality, we carried out a structural magnetic resonance imaging study of cortical thickness in the same sample of adults with ADHD (n = 24) and controls (n = 18), hypothesizing that the cortical networks underlying attention and executive function (EF) would be most affected. Compared with healthy adults, adults with ADHD showed selective thinning of cerebral cortex in the networks that subserve attention and EF. In the present study, we found significant cortical thinning in ADHD in a distinct cortical network supporting attention especially in the right hemisphere involving the inferior parietal lobule, the dorsolateral prefrontal, and the anterior cingulate cortices. This is the first documentation that ADHD in adults is associated with thinner cortex in the cortical networks that modulate attention and EF.Nikos Makris, Joseph Biederman, Eve M Valera, George Bush, Jonathan Kaiser, David N Kennedy, Verne S Caviness, Stephen V Faraone, Larry J Seidman

Source: Cereb Cortex (18 August 2006)
Fatty acid status and behavioural symptoms of Attention Deficit Hyperactivity Disorder in adolescents: A case-control study: Nutrition Journal, Vol. 7 (14 February 2008), 8.Ashley Colter, Caroline Cutler, Kelly Meckling

Source: Nutrition Journal, Vol. 7 (14 February 2008), 8.
Novel Measures of Response Performance and Inhibition in Children with ADHD.: Journal of abnormal child psychology (9 May 2008)Fifteen children with ADHD aged 8 to 12 years and age and gender matched controls performed two different stopping tasks to examine response performance and inhibition and their respective moment-to-mome nt variability. One task was the well-establish ed stop-signal task, while the other was a novel tracking task where the children tracked a spaceship on the screen until an alarm indicated they should stop. Although performance was discrete in the stop signal task and continuous in the tracking task, in both tasks latencies to the stop signal were significantly slowed in children with ADHD. Go performance and variability did not significantly differ between ADHD and control children in either task. Importantly, stopping latency in the novel spaceship tracking task also was more variable in children with ADHD. As stopping variability cannot be measured using the standard stop signal task, the new task offers compelling support for the heretofore untested prediction that stopping is both slowed and more variable in children with ADHD. The results support a response inhibition impairment in ADHD, whilst limiting the extent of an intra-trial variability deficit.Sharon Morein-Zamir, Paul Hommersen, Charlotte Johnston, Alan Kingstone

Source: Journal of abnormal child psychology (9 May 2008)
Validation of attention-defi cit-hyperactiv ity disorder subtypes among Taiwanese children using neuropsycholog ical functioning.: The Australian and New Zealand journal of psychiatry, Vol. 42, No. 6. (June 2008), pp. 526-535.Object ive: The findings regarding the validity of attention-defi cit-hyperactiv ity disorder (ADHD) subtypes using neuropsycholog ical functioning have been inconsistent; and no such study has been conducted in an ethnic Chinese population. The aim of the present paper was therefore to examine the validity of attention tasks in distinguishing the ADHD-combined type (ADHD-C) from the ADHD-inattenti on type (ADHD-I), as compared to children without ADHD in Taiwan. Methods: Participants included 52 children with ADHD-C, 17 with ADHD-I, and 52 controls, aged 7-10years. The clinical diagnosis of DSM-IV ADHD was further confirmed by a standardized psychiatric interview. Four attention components were examined: sensory selection, response selection, capacity/focus , and sustained attention, using the Cancellation Test, Digit Span, Trail-Making Test (TMT), Continuous Performance Test (CPT), and Circle-Tracing Test. Behaviour symptoms were rated by the parents, teachers, and investigators. Results: Compared to children without ADHD, children with ADHD scored significantly higher in parent-reporte d and investigator-r ated behavioural symptoms, and performed worse in the four domains of attention. Multiple comparisons indicated that children with ADHD-C had a worse performance on most tests than children with ADHD-I, except that children with ADHD-I had more off-target errors on the TMT with alphanumeric sequencing than children with ADHD-C. Conclusions: Attention tests can distinguish Taiwanese children with ADHD from those without ADHD, and these tests also demonstrate different profiles between the ADHD-C and ADHD-I groups. Further investigation on this topic should include the ADHD-hyperacti vity-impulsivi ty subtype (ADHD-HI) and increase sample sizes of the children with ADHD-I and ADHD-HI. (ClinicalTrial s.gov number, NCT00494819.). M Chiang, SS Gau

Source: The Australian and New Zealand journal of psychiatry, Vol. 42, No. 6. (June 2008), pp. 526-535.
Functional MRI in ADHD: a systematic literature review.: Expert Rev Neurother, Vol. 7, No. 10. (October 2007), pp. 1337-1356.Func tional MRI (fMRI) research in attention-defi cit/hyperactiv ity disorder (ADHD) is a fast developing and very complex field. Every study appears to show differences in patterns of brain activation between cases and controls, but the interpretation of such differences is not as straightforwar d as it may seem. We present here a systematic review of the fMRI literature in ADHD; areas covered include executive functions, reward processing, the effects of methylphenidat e, comorbidity and spontaneous brain activity in the resting state. To facilitate the interpretation of research in this area, we discuss important conceptual issues, such as the need to take group differences in performance into account or to consider the role of errors. We present common themes that emerge from these studies and we discuss possible reasons for the many discrepancies that were observed. Finally, based on existing literature and current advancements in fMRI research, we discuss the role that fMRI could play in the future as a diagnostic tool or in treatment outcome predictions, and we make predictions for the future directions of research in this field.Y Paloyelis, MA Mehta, J Kuntsi, P Asherson

Source: Expert Rev Neurother, Vol. 7, No. 10. (October 2007), pp. 1337-1356.
Developmental trajectories of brain volume abnormalities in children and adolescents with attention-defi cit/hyperactiv ity disorder.: JAMA, Vol. 288, No. 14. (9 October 2002), pp. 1740-1748.CONT EXT: Various anatomic brain abnormalities have been reported for attention-defi cit/hyperactiv ity disorder (ADHD), with varying methods, small samples, cross-sectiona l designs, and without accounting for stimulant drug exposure. OBJECTIVE: To compare regional brain volumes at initial scan and their change over time in medicated and previously unmedicated male and female patients with ADHD and healthy controls. DESIGN, SETTING, AND PARTICIPANTS: Case-control study conducted from 1991-2001 at the National Institute of Mental Health, Bethesda, Md, of 152 children and adolescents with ADHD (age range, 5-18 years) and 139 age- and sex-matched controls (age range, 4.5-19 years) recruited from the local community, who contributed 544 anatomic magnetic resonance images. MAIN OUTCOME MEASURES: Using completely automated methods, initial volumes and prospective age-related changes of total cerebrum, cerebellum, gray and white matter for the 4 major lobes, and caudate nucleus of the brain were compared in patients and controls. RESULTS: On initial scan, patients with ADHD had significantly smaller brain volumes in all regions, even after adjustment for significant covariates. This global difference was reflected in smaller total cerebral volumes (-3.2%, adjusted F(1,280) = 8.30, P =.004) and in significantly smaller cerebellar volumes (-3.5%, adjusted F(1,280) = 12.29, P =.001). Compared with controls, previously unmedicated children with ADHD demonstrated significantly smaller total cerebral volumes (overall F(2,288) = 6.65; all pairwise comparisons Bonferroni corrected, -5.8%; P =.002) and cerebellar volumes (-6.2%, F( 2,288) = 8.97, P

Source: JAMA, Vol. 288, No. 14. (9 October 2002), pp. 1740-1748.
Age of Methylphenidat e Treatment Initiation in Children With ADHD and Later Substance Abuse: Prospective Follow-Up Into Adulthood.: The American journal of psychiatry (1 April 2008)Objective Animal studies have shown that age at stimulant exposure is positively related to later drug sensitivity. The purpose of this study was to examine whether age at initiation of stimulant treatment in children with attention deficit hyperactivity disorder (ADHD) is related to the subsequent development of substance use disorders. Method The authors conducted a prospective longitudinal study of 176 methylphenidat e-treated Caucasian male children (ages 6 to 12) with ADHD but without conduct disorder. The participants were followed up at late adolescence (mean age=18.4 years; retention rate=94%) and adulthood (mean age=25.3; retention rate=85%). One hundred seventy-eight comparison subjects also were included. All subjects were diagnosed by blinded clinicians. The Cox proportional hazards model included the following childhood predictor variables: age at initiation of methylphenidat e treatment, total cumulative dose of methylphenidat e, treatment duration, IQ, severity of hyperactivity, socioeconomic status, and lifetime parental psychopatholog y. Separate models tested for the following four lifetime outcomes: any substance use disorder, alcohol use disorder, non-alcohol substance use disorder, and stimulant use disorder. Other outcomes included antisocial personality, mood, and anxiety disorders. Results There was a significant positive relationship between age at treatment initiation and non-alcohol substance use disorder. None of the predictor variables accounted for this association. Post hoc analyses showed that the development of antisocial personality disorder explained the relationship between age at first methylphenidat e treatment and later substance use disorder. Even when controlling for substance use disorder, age at stimulant treatment initiation was significantly and positively related to the later development of antisocial personality disorder. Age at first methylphenidat e treatment was unrelated to mood and anxiety disorders. Conclusions Early age at initiation of methylphenidat e treatment in children with ADHD does not increase the risk for negative outcomes and may have beneficial long-term effects.Salvat ore Mannuzza, Rachel G Klein, Nhan L Truong, John L Moulton, Erica R Roizen, Kathryn H Howell, Francisco X Castellanos

Source: The American journal of psychiatry (1 April 2008)
Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI.: Brain Dev (16 August 2006)In children with attention deficit hyperactivity disorder (ADHD), functional neuroimaging studies have revealed abnormalities in various brain regions, including prefrontal-str iatal circuit, cerebellum, and brainstem. In the current study, we used a new marker of functional magnetic resonance imaging (fMRI), amplitude of low-frequency (0.01-0.08Hz) fluctuation (ALFF) to investigate the baseline brain function of this disorder. Thirteen boys with ADHD (13.0+/-1.4 years) were examined by resting-state fMRI and compared with age-matched controls. As a result, we found that patients with ADHD had decreased ALFF in the right inferior frontal cortex, left sensorimotor cortex, and bilateral cerebellum and the vermis as well as increased ALFF in the right anterior cingulated cortex, left sensorimotor cortex, and bilateral brainstem. This resting-state fMRI study suggests that the changed spontaneous neuronal activity of these regions may be implicated in the underlying pathophysiolog y in children with ADHD.Yu-Feng Zang, He Yong, Zhu Chao-Zhe, Cao Qing-Jiu, Sui Man-Qiu, Liang Meng, Tian Li-Xia, Jiang Tian-Zi, Wang Yu-Feng

Source: Brain Dev (16 August 2006)

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