Drive problems in ADHD - neurophysiological correlates

Drive is the ability and will to engage in goal-oriented activity. Drive disorders can manifest themselves in the form of inhibition (e.g. depression) or restless impulsiveness (e.g. ADHD).
Motivation, on the other hand, is a current process that is triggered by the stimulation of a motive. A motive is a persistent characteristic of a person. Motivation is therefore a state of a person at a certain point in time, i.e. in a certain situation.

Neurologically, drive problems are primarily associated with the striatum, the reinforcement center of the brain.

• 1. Anhedonia as a result of dopamine deficiency, among other things
• 2. Reward discounting due to dopamine deficiency and hypoactivity in the striatum
• 3. GABA deficiency reduces drive for long-term goals

1. Anhedonia as a result of dopamine deficiency, among other things¶

Anhedonia is an impaired ability to experience positive emotions, the loss of the ability to feel joy in situations that used to bring joy.

Anhedonia correlates with:

• reduced dopamine levels¹
  • in the mesocorticolimbic system (mPFC, VTA, NAc)
  • in the nucleus accumbens
• Deficits in the processing of reward information²
• reduced activity in the nucleus accumbens³⁴
• Changes in neurotransmitter levels in the nucleus accumbens of DA, 5-HT and noradrenaline⁴
• increased expression of Glu1 receptors in the nucleus accumbens⁵
• reduced expression of Glu2 receptors in the nucleus accumbens⁵
• reduced NMDA-2B receptor expression in the nucleus accumbens⁶
• reduced functional connectivity
  • of the posterior vmPFC (seed region) and NAc, VTA/Substantia nigra, OFC (left) and insula (right)⁷
  • of the right NAc nucleus with the left middle anterior OFC and the right inferior parietal lobe in MDD⁸

In many psychological problems where the drive to obtain pleasurable things is reduced, the PFC is overexcited. In an overexcited state (characterized by increased dopamine and noradrenaline levels), it signals to the nucleus accumbens in the striatum that further effort is not worthwhile. The nucleus accumbens then reduces its dopaminergic activity - with the result that rewards no longer seem so appealing. If the overexcitation of the PFC is stopped, the nucleus accumbens is once again open to stimulation and can reactivate the motivation to strive for things that promise pleasure. In summary, a lot of dopamine in the (m)PFC reduces the dopamine level in the striatum.^9101112

An article in Heise, written in a way that is wonderfully understandable even for laypeople, explains this interaction of an overexcited PFC and an underactivated nucleus accumbens (part of the striatum) in relation to anhedonia and motivation problems.¹³

Conversely, reduced activity of dopamine transporters (which is the result of downregulation due to increased dopamine levels, but can also occur for other reasons) causes increased motivation, as is known in bipolar disorders in manic phases.¹⁴
The results on the number of DAT in ADHD are inconsistent (see above).

2. Reward discounting due to dopamine 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 those affected discounted (devalued) delayed rewards was associated with reduced activation of the cerebellum. As a result, the striatum was underactivated in relation to reward anticipation and the dorsolateral PFC and the orbitofrontal cortex were overactivated in relation to reward acceptance.¹⁵

The brain’s reinforcement center is located in the nucleus accumbens, a part of the striatum, which is part of the basal ganglia. A reduced number of dopamine D2 and D3 receptors in the reward center of the brain in ADHD sufferers means that fewer things are found rewarding, i.e. sufficiently exciting, than in non-affected people.¹⁶ Children with ADHD show a flattened dopaminergic mesolimbic reactivity to stimuli/expectation of reward in the ventral striatum.¹⁷¹⁸ The severity of ADHD symptoms correlated with hypoactivation of the right nucleus accumbens during reward anticipation.¹⁹

The level of motivational problems (as well as the level of inattention) in ADHD correlated with a reduced number 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.²⁰¹⁶

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. 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) is involved in evaluating the effort cost of performing actions. Cortical GABA reduction, through a deficit in ACC dopamine release, appears to primarily affect effort-based behaviors that require a lot of effort with little benefit and are not triggered by reward-oriented behavior.²¹
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 frequently observed in schizophrenia and depression.