Functional MRI in ADHD: a systematic literature review

MRC Social Genetic Developmental Psychiatry Centre (P080), Institute of Psychiatry, De Crespigny Park, London, SE5 8AF, UK.
Expert Review of Neurotherapeutics (Impact Factor: 2.78). 11/2007; 7(10):1337-56. DOI: 10.1586/14737175.7.10.1337
Source: PubMed


Functional MRI (fMRI) research in attention-deficit/hyperactivity 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 straightforward 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 methylphenidate, 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.

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    • "Long-standing cognitive theories of ADHD postulate a deficiency in top–down cognitive control processes underpinning attention and executive function deficits (Barkley, 1997; Nigg, 2000; Bush et al., 2005; Kuntsi et al., 2006; Paloyelis et al., 2007 for review see Del Campo et al., 2012). Providing support to these theories, one of the best replicated findings in ADHD is that of reduced grey matter volume in the catecholamine-rich frontostriato-cerebellar circuits known to subserve these cognitive functions (Seidman et al., 2005; Nakao et al., 2011). "
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    ABSTRACT: Through the combined use of (18)F-fallypride positron emission tomography and magnetic resonance imaging this study examined the neural mechanisms underlying the attentional deficits associated with attention deficit/hyperactivity disorder and their potential reversal with a single therapeutic dose of methylphenidate. Sixteen adult patients with attention deficit/hyperactivity disorder and 16 matched healthy control subjects were positron emission tomography and magnetic resonance imaging scanned and tested on a computerized sustained attention task after oral methylphenidate (0.5 mg/kg) and placebo administration in a within-subject, double-blind, cross-over design. Although patients with attention deficit/hyperactivity disorder as a group showed significant attentional deficits and reduced grey matter volume in fronto-striato-cerebellar and limbic networks, they had equivalent D2/D3 receptor availability and equivalent increases in endogenous dopamine after methylphenidate treatment to that observed in healthy control subjects. However, poor attentional performers drawn from both the attention deficit/hyperactivity disorder and the control groups had significantly reduced left caudate dopamine activity. Methylphenidate significantly increased dopamine levels in all nigro-striatal regions, thereby normalizing dopamine levels in the left caudate in low performers. Behaviourally, methylphenidate improved sustained attention in a baseline performance-dependent manner, irrespective of diagnosis. This finding was accompanied by an equally performance-dependent effect of the drug on dopamine release in the midbrain, whereby low performers showed reduced dopamine release in this region. Collectively, these findings support a dimensional model of attentional deficits and underlying nigro-striatal dopaminergic mechanisms of attention deficit/hyperactivity disorder that extends into the healthy population. Moreover, they confer midbrain dopamine autoreceptors a hitherto neglected role in the therapeutic effects of oral methylphenidate in attention deficit/hyperactivity disorder. The absence of significant case-control differences in D2/D3 receptor availability (despite the observed relationships between dopamine activity and attention) suggests that dopamine dysregulation per se is unlikely to be the primary cause underlying attention deficit/hyperactivity disorder pathology in adults. This conclusion is reinforced by evidence of neuroanatomical changes in the same set of patients with attention deficit/hyperactivity disorder.
    Brain 11/2013; 136(Pt 11):3252-70. DOI:10.1093/brain/awt263 · 9.20 Impact Factor
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    • "The decrease of alpha desynchronization in ADHD patients in all task conditions could reflect the reduction of cortical activation at early post-stimulus time points. In line with this observation, functional imaging studies revealed significant default activation within right parietal, occipital and anterior cingulate cortex, as well as cortico-striato-thalamic networks in young adults with ADHD performing attention and WM tasks (Paloyelis et al., 2007; Shaw et al., 2007; Greene et al., 2008; Schecklmann et al., 2010, 2012). "
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    ABSTRACT: Functional imaging studies have revealed differential brain activation patterns in Attention Deficit Hyperactivity Disorder (ADHD) adult patients performing working memory (WM) tasks. The existence of alterations in WM-related cortical circuits during childhood may precede executive dysfunctions in this disorder in adults. To date, there is no study exploring the electrophysiological activation of WM-related neural networks in ADHD. To address this issue, we carried out an electroencephalographic (EEG) activation study associated with time-frequency (TF) analysis in 15 adults with ADHD and 15 controls performing two visual N-back WM tasks, as well as oddball detection and passive fixation tasks. Frontal transient (phasic) theta event-related synchronization (ERS, 0-500msec) was significantly reduced in ADHD as compared to control subjects. Such reduction was equally present in a task-independent manner. In contrast, the power of the later sustained (∼500-1200 msec) theta ERS for all tasks was comparable in ADHD and control groups. In active WM tasks, ADHD patients displayed lower alpha event-related desynchronization (ERD, ∼200-900msec) and higher subsequent alpha ERS (∼900-2400msec) compared to controls. The time course of alpha ERD/ERS cycle was modified in ADHD patients compared to controls, suggesting that they are able to use late compensatory mechanisms in order to perform this WM task. These findings support the idea of an ADHD-related dysfunction of neural generators sub-serving attention directed to the incoming visual information. ADHD cases may successfully face WM needs depending on the preservation of sustained theta ERS and prolonged increase of alpha ERS at later post-stimulus time points.
    Neuroscience 03/2013; 241. DOI:10.1016/j.neuroscience.2013.03.011 · 3.36 Impact Factor
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    • "Consistent with this result, acute oral MPH treatment (0.3 mg/kg) of ADHD adolescents increases dopamine concentrations in the ventral striatum, which is associated with reduced symptom severity (Rosa-Neto et al., 2005). Functionally, many studies revealed improvements in neural responses during reward, attention, response inhibition, and resting state processing following MPH treatment in ADHD patients (for see review, Cortese et al., 2012; Paloyelis et al., 2007). With respect to reward tasks, reduced activation of the striatum in ADHD children and adolescents during reward processing was improved by acute MPH treatment (Rubia et al., 2009). "
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    ABSTRACT: Attention-deficit/hyperactivity disorder (ADHD) is neurobehavioral disorder characterized by inattention, hyperactivity/impulsivity and impaired reward system function, such as delay aversion and low reward sensitivity. The pharmacological treatment for ADHD includes methylphenidate (MPH), or osmotic release oral system-MPH (OROS-MPH), which increases extrasynaptic dopamine and noradrenaline levels by blocking their reuptake. Although previous functional magnetic resonance imaging (fMRI) studies revealed that acute treatment with MPH alters activation of the nucleus accumbens during delay aversion in children and adolescents with ADHD, the effects a relatively long period of OROS-MPH treatment on delay aversion as well as reward sensitivity remain unclear. Thus, we evaluated brain activation with fMRI during a reward sensitivity paradigm that consists of high monetary reward and low monetary reward conditions before and after a 3-month treatment with OROS-MPH in 17 children and adolescents with ADHD (mean age, 13.3 ± 2.2) and 17 age- and sex-matched healthy controls (mean age, 13.0 ± 1.9). We found that before treatment there was decreased activation of the nucleus accumbens and thalamus in patients with ADHD during only the low monetary reward condition, which was improved to same level as those of the healthy controls after the treatment. The observed change in brain activity was associated with improved ADHD symptom scores, which were derived from Japanese versions of the ADHD rating scale-IV. These results suggest that treatment with OROS-MPH for a relatively long period is effective in controlling reward sensitivity in children and adolescents with ADHD.
    Clinical neuroimaging 03/2013; 2(1):366-76. DOI:10.1016/j.nicl.2013.03.004 · 2.53 Impact Factor
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