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Dopaminergic Modulation of Medial Prefrontal Cortex Deactivation in Parkinson Depression.

Andersen AH, Smith CD, Slevin JT, Kryscio RJ, Martin CA, Schmitt FA, Blonder LX - Parkinsons Dis (2015)

Bottom Line: Results indicate that dopaminergic medications have opposite effects in the prefrontal cortex depending upon depression status.DPD patients show greater deactivation in the ventromedial prefrontal cortex (VMPFC) on dopaminergic medications than off, while ndPD patients show greater deactivation in this region off drugs.Thus dopaminergic medications may promote increased attention to external visual stimuli among dPD patients but impede normal suppression of DMN activity during external stimulation among ndPD patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY 40536, USA; Magnetic Resonance Imaging and Spectroscopy Center, University of Kentucky, Lexington, KY 40536, USA.

ABSTRACT
Parkinson's disease (PD) is associated with emotional abnormalities. Dopaminergic medications ameliorate Parkinsonian motor symptoms, but less is known regarding the impact of dopaminergic agents on affective processing, particularly in depressed PD (dPD) patients. The aim of this study was to examine the effects of dopaminergic pharmacotherapy on brain activation to emotional stimuli in depressed versus nondepressed Parkinson disease (ndPD) patients. Participants included 18 ndPD patients (11 men, 7 women) and 10 dPD patients (7 men, 3 women). Patients viewed photographs of emotional faces during functional MRI. Scans were performed while the patient was taking anti-Parkinson medication and the day after medication had been temporarily discontinued. Results indicate that dopaminergic medications have opposite effects in the prefrontal cortex depending upon depression status. DPD patients show greater deactivation in the ventromedial prefrontal cortex (VMPFC) on dopaminergic medications than off, while ndPD patients show greater deactivation in this region off drugs. The VMPFC is in the default-mode network (DMN). DMN activity is negatively correlated with activity in brain systems used for external visual attention. Thus dopaminergic medications may promote increased attention to external visual stimuli among dPD patients but impede normal suppression of DMN activity during external stimulation among ndPD patients.

No MeSH data available.


Related in: MedlinePlus

(a) Illustrating a hypothetical inverted-U dependence of frontal lobe function on dopaminergic medication associated with individual variation in baseline dopamine level. (b) Nondepressed PD patients (red) are positioned at the upstroke lower end of the curve: they reduce their level of VMPFC deactivation and increase VLPFC activation with levodopa medication. Depressed PD patients (blue) are positioned at the downstroke upper end of the curve: they increase their level of VMPFC deactivation and decrease VLPFC activation with levodopa medication. Labels a, b, c, and d indicate representative ndPD and dPD patients; open symbols denote the VMPFC and closed symbols the VLPFC brain regions; dashed lines represent the activity gap off dopaminergic medication, while solid lines represent that on levodopa.
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fig5: (a) Illustrating a hypothetical inverted-U dependence of frontal lobe function on dopaminergic medication associated with individual variation in baseline dopamine level. (b) Nondepressed PD patients (red) are positioned at the upstroke lower end of the curve: they reduce their level of VMPFC deactivation and increase VLPFC activation with levodopa medication. Depressed PD patients (blue) are positioned at the downstroke upper end of the curve: they increase their level of VMPFC deactivation and decrease VLPFC activation with levodopa medication. Labels a, b, c, and d indicate representative ndPD and dPD patients; open symbols denote the VMPFC and closed symbols the VLPFC brain regions; dashed lines represent the activity gap off dopaminergic medication, while solid lines represent that on levodopa.

Mentions: In the present study, dPD patients off dopaminergic drugs exhibited a failure to suppress the default-mode activity manifested as a reduced level of deactivation in VMPFC during external stimulation with photographs of emotional faces. Suppression of the default-mode activity during task performance was restored by dopaminergic medication. The inverse effect involving activation of the VLPFC supports the view of reciprocal limbic-cortical function and negative mood state [51]. We posit that brain activity in the prefrontal cortex may follow an inverted-U shape with the effects of dopaminergic medication dependent upon individual variation in COMT polymorphisms that influence baseline dopamine levels (see Figure 5). If true, and in keeping with the findings of Argyelan et al. [9], we would expect an association between the met-allele genotype and Parkinson's depression to explain increased suppression of the VMPFC and reduced activation of the VLPFC following administration of dopaminergic medications. Future research will assess this hypothesis.


Dopaminergic Modulation of Medial Prefrontal Cortex Deactivation in Parkinson Depression.

Andersen AH, Smith CD, Slevin JT, Kryscio RJ, Martin CA, Schmitt FA, Blonder LX - Parkinsons Dis (2015)

(a) Illustrating a hypothetical inverted-U dependence of frontal lobe function on dopaminergic medication associated with individual variation in baseline dopamine level. (b) Nondepressed PD patients (red) are positioned at the upstroke lower end of the curve: they reduce their level of VMPFC deactivation and increase VLPFC activation with levodopa medication. Depressed PD patients (blue) are positioned at the downstroke upper end of the curve: they increase their level of VMPFC deactivation and decrease VLPFC activation with levodopa medication. Labels a, b, c, and d indicate representative ndPD and dPD patients; open symbols denote the VMPFC and closed symbols the VLPFC brain regions; dashed lines represent the activity gap off dopaminergic medication, while solid lines represent that on levodopa.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4697088&req=5

fig5: (a) Illustrating a hypothetical inverted-U dependence of frontal lobe function on dopaminergic medication associated with individual variation in baseline dopamine level. (b) Nondepressed PD patients (red) are positioned at the upstroke lower end of the curve: they reduce their level of VMPFC deactivation and increase VLPFC activation with levodopa medication. Depressed PD patients (blue) are positioned at the downstroke upper end of the curve: they increase their level of VMPFC deactivation and decrease VLPFC activation with levodopa medication. Labels a, b, c, and d indicate representative ndPD and dPD patients; open symbols denote the VMPFC and closed symbols the VLPFC brain regions; dashed lines represent the activity gap off dopaminergic medication, while solid lines represent that on levodopa.
Mentions: In the present study, dPD patients off dopaminergic drugs exhibited a failure to suppress the default-mode activity manifested as a reduced level of deactivation in VMPFC during external stimulation with photographs of emotional faces. Suppression of the default-mode activity during task performance was restored by dopaminergic medication. The inverse effect involving activation of the VLPFC supports the view of reciprocal limbic-cortical function and negative mood state [51]. We posit that brain activity in the prefrontal cortex may follow an inverted-U shape with the effects of dopaminergic medication dependent upon individual variation in COMT polymorphisms that influence baseline dopamine levels (see Figure 5). If true, and in keeping with the findings of Argyelan et al. [9], we would expect an association between the met-allele genotype and Parkinson's depression to explain increased suppression of the VMPFC and reduced activation of the VLPFC following administration of dopaminergic medications. Future research will assess this hypothesis.

Bottom Line: Results indicate that dopaminergic medications have opposite effects in the prefrontal cortex depending upon depression status.DPD patients show greater deactivation in the ventromedial prefrontal cortex (VMPFC) on dopaminergic medications than off, while ndPD patients show greater deactivation in this region off drugs.Thus dopaminergic medications may promote increased attention to external visual stimuli among dPD patients but impede normal suppression of DMN activity during external stimulation among ndPD patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY 40536, USA; Magnetic Resonance Imaging and Spectroscopy Center, University of Kentucky, Lexington, KY 40536, USA.

ABSTRACT
Parkinson's disease (PD) is associated with emotional abnormalities. Dopaminergic medications ameliorate Parkinsonian motor symptoms, but less is known regarding the impact of dopaminergic agents on affective processing, particularly in depressed PD (dPD) patients. The aim of this study was to examine the effects of dopaminergic pharmacotherapy on brain activation to emotional stimuli in depressed versus nondepressed Parkinson disease (ndPD) patients. Participants included 18 ndPD patients (11 men, 7 women) and 10 dPD patients (7 men, 3 women). Patients viewed photographs of emotional faces during functional MRI. Scans were performed while the patient was taking anti-Parkinson medication and the day after medication had been temporarily discontinued. Results indicate that dopaminergic medications have opposite effects in the prefrontal cortex depending upon depression status. DPD patients show greater deactivation in the ventromedial prefrontal cortex (VMPFC) on dopaminergic medications than off, while ndPD patients show greater deactivation in this region off drugs. The VMPFC is in the default-mode network (DMN). DMN activity is negatively correlated with activity in brain systems used for external visual attention. Thus dopaminergic medications may promote increased attention to external visual stimuli among dPD patients but impede normal suppression of DMN activity during external stimulation among ndPD patients.

No MeSH data available.


Related in: MedlinePlus