Currently, neuroimaging remains a research tool and the diagnosis of ADHD remains a clinical skill. There are many steps before neuroimaging becomes clinically useful: the scans need to be reliable (replicable across different scanners), valid (ideally reflecting a process central to ADHD or one of its underlying, often transdiagnostic dimensions), and feasible (affordable and acceptable).
Many groups are, however, trying to make imaging more clinically useful. Several researchers are applying newer methods to analyze imaging data such as pattern recognition/machine learning in order to predict a diagnosis. In pattern recognition analyses, neural features are provided to an algorithm (such as a support vector machine) that “learns” a rule to predict diagnosis; the rule is then tested on independent cohorts.
The hope is that we can translate the modest, but significant neural differences between groups—those with and without ADHD—to the individual level. To date, there has been modest success in these approaches, which have used mainly neuroanatomic data, attaining diagnostic accuracy in diagnosis of 60% to 80%.18 Further advances may rely on the integration of multimodal imaging with genomic and cognitive data.
Parents sometimes ask if decisions about treatment can be informed by objective markers, such as those obtained in neuroimaging (as seen in the Case Vignette). Currently, treatment choices for ADHD remain based on an impressive body of clinical trials rather than neuroimaging, or indeed any biological assay or psychological test. Nonetheless, neuroimaging studies have elucidated the mode of action of treatments, particularly psychostimulants, which are the most widely used medications. Findings suggest that psychostimulant-induced improvement of core symptoms is underpinned by a shift in the activation of key brain networks toward a more typical range.19,20
There is also either no clear association between anatomy and psychostimulant treatment or that the medication is associated with dimensions seen in unaffected controls.21 It is important to note that most studies have been observational and thus other factors, such as access to care, demographic features, or comorbidities, may be driving associations between psychostimulants and brain structure/function. Randomized trials allow us to come closer to causal inference and one interesting trial found that methylphenidate—a psychostimulant—increased cerebral blood flow in the thalamus in children, but not in adults with ADHD.22
There is a long history in ADHD of providing individuals feedback on their neural activity, usually via a visual representation, so that they can shift brain activity into more typical patterns. EEG has mostly been used to try to correct ADHD associated patterns (that is, excessive slow [theta] wave and suboptimal fast [beta] wave activity) and to augment slow cortical potentials that might improve the allocation of cognitive resources.
Meta-analyses suggest such EEG neurofeedback has trend level efficacy, with estimates varying widely between clinician, parent, and teacher ratings.23 A new wave of studies use fMRI to provide feedback on spatially well-defined brain activation, and such spatial precision is generally absent on EEG. For example, a recent RCT provided children with ADHD visual feedback on the activation of their right inferior frontal gyrus during a task requiring sustained attention.24 Over time, children learned to boost neural activation and showed symptomatic improvement.
We are moving into the era of large, collaborative studies that will provide more robust measures of the anomalies of brain structure and function seen in ADHD. Such collaborations face challenges, such as integrating data acquired using different scanners and sequences, but nonetheless promise to provide the sample sizes that will be needed for future gene discovery and understanding.
Dr Shaw is an Earl Stadtman Investigator, Neurobehavioral Research Section, Social and Behavioral Research Branch, National Human Genome Research Institute, NIH; Adjunct Faculty National Institute of Mental Health, Bethesda, MD. Dr Shaw reports no conflicts of interest concerning the subject matter of this article.
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