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. 2012 Jul 4:6:52.
doi: 10.3389/fnsys.2012.00052. eCollection 2012.

L-DOPA changes spontaneous low-frequency BOLD signal oscillations in Parkinson's disease: a resting state fMRI study

Y Kwak  1 , S J Peltier, N I Bohnen, M L T M Müller, P Dayalu, R D Seidler
Affiliations

L-DOPA changes spontaneous low-frequency BOLD signal oscillations in Parkinson's disease: a resting state fMRI study

Y Kwak et al. Front Syst Neurosci. .

Abstract

Analysis of the amplitude of low frequency BOLD signal fluctuations (ALFF) in the resting state has recently been used to study the dynamics of intrinsic neural activity. Several studies have also suggested its potential as a biomarker for neuropsychiatric disease. In the current study, we quantified ALFF to determine changes in intrinsic neural oscillations in patients with Parkinson's disease (PD) on and off L-DOPA. Twenty-four PD patients and 24 healthy age-matched controls participated in the study. PD patients underwent two resting state fMRI sessions, either ON a controlled dose of L-DOPA or following a placebo pill (OFF). Control participants underwent one test session. We found that there was increased amplitude of low frequency BOLD signal oscillations for PD patients OFF L-DOPA in the primary and secondary motor areas, and in the middle and medial prefrontal cortices. L-DOPA significantly reduced the amplitude of low frequency oscillations within these regions. The degree of ALFF in the premotor cortex predicted patients' motor performance as measured by the Grooved Pegboard task, such that greater ALFF was associated with poorer performance. These results are in line with the pathophysiology of PD, which shows changes in neural oscillations. Thus, frequency domain analyses of resting state BOLD fMRI signals may provide a useful means to study the pathophysiology of PD and the physiology of the brain's dopaminergic pathways.

Keywords: BOLD signal; Parkinson's disease; dopamine; neural oscillation; resting-state fMRI.

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Figures

Figure 1
Figure 1
Comparison of ALFF between groups within the predefined ROIs of the cortico-striatal network. No significant results were found for controls > PD OFF or PD ON > PD OFF contrasts. P < 0.0017 based on correction.
Figure 2
Figure 2
ALFF power comparison of PD ON to PD OFF and PD ON to controls for brain regions identified in PD OFF > controls contrast. L-DOPA significantly down-regulates the abnormally increased ALFF power in PD as shown by the PD ON vs. PD OFF comparison. A difference in ALFF power still existed after L-DOPA administration as shown by PD ON vs. controls comparison. The negative y axis values (ALFF power z score) indicate ALFF power lower than the mean of the whole brain. ACC, anterior cingulate cortex; Mid_F_G, middle frontal gyrus; M1, precentral gyrus.
Figure 3
Figure 3
Correlation between ALFF of the premotor cortex in the less affected hemisphere (LA) and performance on the grooved pegboard task of the more affected body side (MA) in PD OFF. Greater ALFF is associated with worse performance (i.e., slower movement).
Figure 4
Figure 4
Whole brain ALFF comparisons between groups. PD OFF > controls, red, PD OFF < controls, green (A), PD OFF > PD ON, red, PD OFF < PD ON, green (B), PD ON > controls, red, PD ON < controls, green (C).
Figure 5
Figure 5
ALFF power of the three groups (i.e., PD ON, PD OFF, and controls) for brain regions identified in PD OFF > controls contrast (A) and in PD OFF < controls contrast (B) in the whole brain analysis.
Figure A1
Figure A1
Comparison of fALFF between groups within the predefined ROIs of the cortico-striatal network. No significant results were found for controls > PD OFF or Controls > PD ON contrasts. P < 0.0017 based on correction.
Figure A2
Figure A2
fALFF power comparison of PD ON to PD OFF and PD ON to controls for brain regions identified in PD OFF > controls contrast. L-DOPA down-regulates the abnormally increased fALFF power in PD as shown by the marginal difference in PD ON vs. PD OFF comparison. Difference in fALFF power was no more present after L-DOPA administration as shown by PD ON vs. controls comparison. M1, precentral gyrus.
Figure A3
Figure A3
Whole brain fALFF comparisons between groups. PD OFF > controls, red, PD OFF < controls, green (A), PD OFF > PD ON, red, PD OFF < PD ON, green (B), PD ON > controls, red, PD ON < controls, green (C).
See this image and copyright information in PMC

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