Striatal Disruption in Attention Deficit-Hyperactivity Disorder (ADHD)

Hypothesis

Hypothesis

Hypothesis:
To determine whether disruption in the normal development of the basal ganglia, as observed in children born prematurely with intraventricular hemorrhage, results in deficits in response inhibition characteristic of the symptomatology observed in ADHD.

Goals:
1. To more directly test, using functional MRI, the hypothesis that the prefrontal cortex and basal ganglia, specifically the caudate nuclei, subserve the processes of response inhibition affected in ADHD.

2. To determine whether disruption in the normal development of the basal ganglia, as observed in children born prematurely with intraventricular hemorrhage (caudate bleeds), results in deficits in response inhibition characteristic of the symptomatology observed in ADHD.

3. To constrain the model of how and when damage to frontostriatal regions leads to ADHD to facilitate the development of early identification and treatment strategies.

Methods:
The researchers collect behavioral measures with a computerized battery of three response inhibition tasks developed in their laboratory and biological measures with both structural and functional magnetic resonance imaging (MRI). Behavioral performance, MRI-based brain volume, and brain activity are then compared across groups of children with and without striatal disruption associated with perinatal insults and in children with and without ADHD.

Follow-on Funding:
John Merck Scholarship PI 04/01/97-03/31/01 Merck Fund

Frontostriatal Development and Cognitive Control PI 05/01/01-04/30/06 NIMH (R01 MH63255)

Functional Neuroanatomical Deficits in ADHD Families PI 05/01/02-04/30/05 NIMH (R01 MH64166)

Findings:
Our behavioral, clinical and neuroimaging data from our children with histories of intraventricular hemorrhage (IVH) are consistent with our hypothesis of disruption in behavioral inhibition at the level of the basal ganglia. First, these children perform poorly on tasks that require them to suppress attention toward a salient stimulus or a compelling response. Second, these children are at greater risk of developing disorders with known inhibitory deficits (e.g., ADHD and Tic Disorders). Third, MRI-based morphometry measures show decreased volume of the basal ganglia, specifically the caudate nucleus, in children with IVH compared to age-matched controls. Fourth, fMRI results showed little to no activity in the caudate nucleus in children with IVH of grade II or higher while activity was reliably observed in prefrontal cortex ( a region assumed to play a role in behavioral inhibition), but was not correlated with behavioral performance. In sum, disruption of the basal ganglia thalamocortical circuits at the level of the basal ganglia appears sufficient to disrupt inhibitory control.