Reduced activation and inter-regional functional connectivity of fronto-striatal networks in adults with childhood Attention-Deficit Hyperactivity Disorder (ADHD) and persisting symptoms during tasks of motor inhibition and cognitive switching

https://doi.org/10.1016/j.jpsychires.2009.11.016Get rights and content

Abstract

Attention-Deficit Hyperactivity Disorder (ADHD) in children has been associated with fronto-striatal functional abnormalities during tasks of inhibitory control. In adults with ADHD, however, hardly any functional magnetic resonance imaging (fMRI) studies have investigated the neurofunctional correlates of the most compromised cognitive functions of motor response inhibition and no study has investigated cognitive flexibility. In this study we used fMRI to compare brain function and task-relevant inter-regional functional connectivity between 11 medication-naïve adults with persistent inattentive/hyperactive behaviours, followed up from childhood when they had been diagnosed with ADHD, and 14 age-matched healthy controls during a Stop and a cognitive Switch tasks. Whole-brain regression MR analyses were conducted within patients to correlate symptoms with brain activation. Despite comparable task performance, adults with childhood ADHD showed reduced activation compared to controls in bilateral inferior prefrontal cortex, caudate and thalamus during both tasks, as well as in left parietal lobe during the Switch task. Within patients, the severity of the behavioural symptoms was negatively correlated with more extensive activation of similar regions in fronto-striatal, parietal and cerebellar brain areas. In the Stop task, patients showed reduced inter-regional functional connectivity between right inferior fronto-frontal, fronto-striatal and fronto-parietal neural networks. The findings demonstrate that adults with childhood ADHD and persisting behavioural symptoms show strikingly similar patterns of fronto-striatal and parietal dysfunction to those observed in childhood ADHD during the same tasks of inhibitory control. This suggests that neuro-functional abnormalities in ADHD patients are likely to continue between childhood and early adulthood.

Section snippets

Background

Attention-Deficit Hyperactivity Disorder (ADHD) is a developmental disorder of 1–5% prevalence, beginning in childhood (Faraone and Biederman, 2005), comprising age-inappropriate levels of hyperactivity, impulsivity and inattention (DSM-IV) (American Psychiatric Association, 1994).

The most consistent neuropsychological findings in children and adults with ADHD are deficits in motor response inhibition and cognitive switching (Boonstra et al., 2005, Rubia et al., 2001a, Rubia et al., 2007a,

Participants

Patients were 11 male right-handed adults aged 26–30 years (mean age (yrs) = 29, SD = 1), recruited from a 20-year prospective longitudinal epidemiological study (Taylor et al., 1991). Only male subjects were included to increase homogeneity. This is driven by the fact that ADHD is more prevalent in males in children (Costello et al., 2003, Gaub and Carlson, 1997) and adults (Biederman et al., 2004, Simon et al., 2009) and that gender differences exist in clinical manifestation (Biederman et al., 2002

Task performance

As expected no group differences were observed in probability of inhibition, suggesting that the tracking algorithm worked. For the Stop task, multivariate ANCOVA (with IQ as covariate) showed no group effect for the inhibitory variables of SSRT and the probability of inhibition (F = 2, df = 2, 20, p = 2.2). For the Switch task, repeated measures ANCOVA with group as factor and trial type as within-subject variable showed no significant effect of trial type on either reaction times (F = 2, df = 1, 21, p = 

Discussion

Despite comparable task performance, adults with childhood ADHD and persistent inattentive/hyperactive behaviours showed reduced activation compared to healthy adults during both inhibition tasks in bilateral fronto-striatal brain regions as well as in the parietal lobe during the Switch task. Furthermore, they also showed reduced functional inter-regional connectivity in the Stop task in right inferior fronto-frontal, fronto-striatal, fronto-cingulate and fronto-parietal networks. The

Conclusions

Despite comparable task performance, adults with childhood ADHD and persistent inattentive/hyperactive behaviours showed reduced activation compared to healthy adults in bilateral fronto-striatal brain regions during the Stop and Switch tasks, and additionally in the parietal lobe during the Switch task. Within patients, the severity of symptoms was negatively associated with activation in these fronto-striatal, parietal and cerebellar regions. Furthermore, during the Stop task, the adults with

Authors’ contributions

AC and KR drafted the manuscript. RH performed the imaging and clinical data acquisition, and pre-processed the imaging data. AC and KR analysed the clinical, behavioural and imaging data. VG assisted the analyses of the imaging data. CE performed the functional connectivity analyses. KR and ET conceived and designed the MRI study, and obtained funding for imaging controls and patients. ET was responsible for the psychometric assessment of patients and methods description regarding patients. KR

Role of funding source

The Wellcome Trust, MRC or Koplowitz foundation had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

Conflict of interest

None of the authors has any conflict of interest to declare.

Acknowledgement

The research was supported by grants from the Medical Research Council (G9900839) and The Wellcome Trust (053272/Z/98/Z/JRS/JP/JAT). AC was supported by a fellowship from the Alicia Koplowitz Foundation.

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