Drive problems in ADHD - Neurophysiological correlates

Drive and motivation problems are neurologically linked primarily to the striatum, the brain’s reinforcement center.

• 1. Anhedonia consequence of dopamine (effect) deficiency
• 2. Reward discounting by dopamine (effect) deficiency and hypoactivity in the striatum
• 3. GABA deficiency reduces drive for long-term goals

1. Anhedonia consequence of dopamine (effect) deficiency¶

Decreased dopamine levels in the mesocorticolimbic system and nucleus accumbens correlate with anhedonia.¹

In many mental health problems, where the drive to obtain pleasurable things is reduced, the PFC is overexcited. In the overexcited state (characterized by elevated levels of dopamine and norepinephrine), it signals to the nucleus accumbens in the striatum that further effort is not worthwhile. In response, the nucleus accumbens shuts down its dopaminergic activity - with the result that rewards no longer seem as appealing. When the overexcitation of the PFC is stopped, the nucleus accumbens is again open to stimulation and can reactivate the motivation to strive for things that promise pleasure. In summary, much dopamine in the (m)PFC reduces dopamine levels in the striatum.²³⁴⁵

An article at Heise, written in a wonderfully understandable way even for laymen, explains this interaction of an overexcited PFC and an underactivated nucleus accumbens (part of the striatum) in relation to anhedonia and motivational problems.⁶

Conversely, decreased activity of dopamine transporters (which is the result of downregulation due to increased dopamine levels, but may also result from other causes) causes increased motivation, as is known to occur in bipolar disorder during manic phases.⁷
Results on the number of DAT in ADHD are inconsistent (see above).

2. Reward discounting by dopamine (effect) deficiency and hypoactivity in the striatum¶

Adults with ADHD showed reduced activation in a number of brain regions (including the dorsolateral PFC, anterior frontal gyrus, ACC, caudate nucleus, and cerebellum) during a delay discounting task under fMRI. At the same time, the extent to which affected individuals discounted (devalued) delayed rewards was associated with reduced cerebellar activation. As a result, the striatum was thus underactivated with respect to reward anticipation and the dorsolateral PFC and orbitofrontal cortex overactivated with respect to reward receipt.⁸

The brain’s reinforcement center is located in the nucleus accumbens, a part of the striatum that is part of the basal ganglia. A reduced number of dopamine D2 and D3 receptors in the brain’s reward center in ADHD sufferers results in fewer things being found (be)rewarding, i.e. sufficiently exciting, than in non-affected individuals.⁹ Children with ADHD show flattened dopaminergic mesolimbic reactivity to stimuli / in anticipation of reward in the ventral striatum.¹⁰¹¹ The severity of ADHD symptomatology correlated with hypoactivation of the right nucleus accumbens during expectation of reward.¹²

The measure of motivational problems (as well as the measure of inattention) in ADHD correlated with decreased numbers of D2 and D3 dopamine receptors in the striatum. In contrast, other altered personality parameters in ADHD did not correlate with the number of D2 and D3 receptors.¹³⁹

3. GABA deficiency reduces drive for long-term goals¶

GABA deficiency in the PFC and hippocampus appears to correlate with drive problems related to long-term rewards, although GABA deficiency is not associated with anhedonia or behavioral depression in this context. Mice with reduced GABA levels in the hippocampus and cortex (esp. mPFC) showed a range of effort-related behavioral deficits that could not be explained by anhedonia or behavioral despair. Dopamine in the anterior cingulate cortex (ACC) has been implicated in evaluating the cost of effort to perform actions. Cortical GABA reduction, through a deficit in ACC dopamine release, appears to affect primarily effort-based behaviors that require much effort with little benefit and are not triggered by reward-based behavior.¹⁴
GAD67 is an enzyme that converts glutamate to GABA and is controlled by the GAD1 and GAD2 genes. A cortical GAD67 reduction with a simultaneous decrease in GABA levels is often observed in schizophrenia and depression.