Repetitive Transcranial Magnetic Stimulation (rTMS): New Tool, New Therapy and New Hope for ADHD

Maria T. Acosta, Fidias E. Leon-Sarmiento

Disclosures

Curr Med Res Opin. 2003;19(2) 

In This Article

Neurobiological Considerations

Anatomical studies have shown significant prefrontal asymmetry in ADHD, with smaller right-sided prefrontal brain regions.[13] A decrease in grey matter in the right frontal gyrus, the right posterior cingulate gyrus and the left central white matter have been reported.[3,11] Left-to-right asymmetry of the caudate nucleus,[14,15] or volume abnormalities of it,[13] as well as a significant decrease in the right globus pallidus size16 or smaller posterior-inferior cerebellar vermis, are also common features of this disease.[3,17,18] The significance of these findings is still under debate;[13] however, they do support the involvement of a circuit in the above-mentioned areas that are certainly hypofunctional in ADHD.[3]

The pathophysiology of ADHD has been based on the catecholamine hypothesis[19,20] since the 1970s. Unfortunately, after a quarter-century of research, its role still remains unclear. Dopaminergic dysfunction has been suspected in ADHD, among other neuro-transmitters, because symptoms respond favourably, albeit temporarily, to stimulant medications such as dextroamphetamine and methylphenidate (MPH).[21] These medications increase the release and inhibit the re-uptake of catecholamines, especially dopamine, whose modulatory influence is pervasive in frontalstriatal regions. This evidence suggests that the dysfunction in dopaminergic transmission is located in the frontal lobe and in striatal structures.[21,22] Genetic studies have also reported an association between ADHD and dopaminergic gene dysfunction, including associations between ADHD and variability of the dopamine transporter as well as D4 and D2 receptor gene abnormalities.[23,24,25] Such receptors have an inhibitory effect on GABAergic synapsis and are found in the relevant cortical, basal ganglia, thalamus and cerebellar vermis interneurons related to ADHD pathophysiology.[26]

From a neuropsychological perspective, ADHD has commonly been defined by sustained attention deficits, impulsiveness and a high level of activity.[27] More recently, the nature of the disorder has been examined and is undergoing further redefinition, being considered a disorder of executive functions. Although an extensive review of the correlation between executive function and its anatomical substrates is beyond the scope of this article, it can be said that the location of executive functions implies activation of pre-frontal lobes, basal ganglia structures and other cortical and subcortical areas, including cortico-striatal-thalamo-cortical circuits,[28] which select, initiate and execute complex motor and cognitive responses.[29] The cerebellum provides an on-line guidance of these functions.[13,14,15]

Using functional magnetic resonance imaging, Vaidya et al. found differences between children with ADHD and healthy controls in their fronto-striatal functioning during response inhibition tasks.[30] However, changes in caudate and putamen, as well as prefrontal and striatal activation, varied according to the task itself only in patients. Interestingly, MPH enhanced activation in prefrontal and striatal areas in both patients and normals and decreased the latter in normals.[31] These findings suggest an atypical functioning of the fronto-striatal circuit in ADHD probably making a significant contribution to striatal dysfunction. In fact, functional studies showed decreased blood flow in the striatum of ADHD subjects,[32] mostly in prefrontal regions, with a frontal-cerebral decreased metabolism in adults with ADHD demonstrated by positron-emission tomography with [18F]-fluoro-2-deoxy-D-glucose, 133xenon inhalation and single-photon emission tomography.[33]

While neurophysiological studies have been difficult to integrate into the physiopathology of ADHD, P300 studies have shown smaller amplitude and longer latencies which correlated with attentional dysfunction.[34] Steady-state visually evoked potentials[35] were also strongly supportive of right prefrontal dysfunction in ADHD.[13,36] The main findings with magnetic stimulation are discussed below.

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