Synopsis

Patients with Parkinson's disease (PD) are more likely to suffer cognitive decline and experience difficulties in daily living requiring reasoning including medication use, financial management, and nutrition and food preparation even at early stage of the disease.^1,2 The present study aimed to explore L-dopa modulation on the reasoning ability in PD. Twenty non-demented PD underwent reasoning fMRI examinations OFF-medication and ON-medication. It was found that ON-medication PD patients exhibited improved reasoning performance and recruited the striatum compared to OFF-medication. The current findings suggest that L-dopa treatment mediated the neural activity in the striatum and further improved the behavior performance.

INTRODUCTION

Patients with Parkinson's disease (PD) have a higher risk of suffering cognitive decline and impair their daily reasoning ability including medication use, financial management, and nutrition and food preparation compared to healthy controls even at early stage of the disease.^1,2 The present study aimed to explore whether reasoning ability could be modulated by dopaminergic medication in individuals with non-demented PD.

METHODS

Twenty non-demented PD patients (14 males, 60.17±5.21 years old) meeting the UK Bank criteria for the diagnosis of PD,³ were recruited. All PD participants were examined OFF-medication and ON-medication. Disease stage was scored using the H&Y state score and disease severity was captured by the UPDRS III OFF-medication. All participants did not suffer from depression with 17-item Hamilton Depression Rating Scale (HAMD-17). Global cognition of all participants was evaluated by using Montreal Cognitive Assessment (MoCA).

Task-fMRI experiments included two kinds of blocks: numerical inductive reasoning (Rea) block vs. Baseline block with each block last 48 secs and 24 secs respectively and 8 blocks for each condition. As to reasoning block, participants were required to identify the underlying rule (e.g., “+ 3”) and to extrapolate the next number. As to baseline block, a star mark was presented, and participants were required to rest during this period. Distinct reasoning tasks were designed between OFF-medication and ON-medication to control for practice effect.

MRI examinations were performed on a 3.0 Tesla MRI system (Siemens Trio Tim; Erlanger, Germany). High-resolution structural images were acquired using a T1 weighted 3D MPRAGE sequence (TR/TE = 1600/2.25 ms, TI = 800 ms, 192 sagittal slices, FOV = 256 mm, 9° flip angle, voxel size = 1 × 1 × 1 mm³). Functional images were obtained using an T2* gradient-echo EPI sequence (TR/TE = 2000/31 ms, 90° flip angle, 64 × 64 matrix size in 240 × 240 mm² FOV).

Data were analyzed using SPM12 software (http://www.fil.ion.ucl.ac.uk). The fMRI images were preprocessed including slice timing, realign, co-register, normalization to MNI space, and spatially smoothing with a Gaussian kernel of 8 × 8 × 8 mm³ full width at half maximum (FWHM) to decrease spatial noise. Paired t-test was performed between OFF-medication and ON-medication, and results were thresholded at p < 0.05 FEW-corrected. Correlation was further conducted between neural activity in activated region and reasoning performance and p < 0.05 was considered statistically significant.

RESULTS

PD patients exhibited significant improvement in reasoning behavioral performance (i.e., significantly higher accuracy and faster response time) ON-medication compared to OFF-medication. Activations in the bilateral cortico-striatal network were revealed both OFF-medication and ON-medication (see Figure 1); while more activation in the striatum (caudate/putamen) was specifically recruited ON-medication (see Figure 2) and neural activity in this region was significantly correlated with reasoning ability (r = 0.45, p < 0.05).

DISCUSSION

The current study aimed to explore the effect of dopaminergic modulation on reasoning in individuals with non-demented PD. It was found that the specific activation in the striatum was identified in PD patients ON-medication compared to OFF-medication, which further contributes to their better reasoning performance. Previous study has demonstrated that the main biochemical consequence of the progressive loss of nigrostriatal dopamine neurons in PD is a deficiency of dopamine in the striatum, which indirectly affected frontal functions.⁴ In addition, cognitive performance sensitive to cortico-striatal pathway was impaired after withdrawal from levodopa therapy in PD.⁵ Consistent with our previous studies the striatum plays an important role in rule identification and application during reasoning.^6-8

CONCLUSION

The current findings suggested the neural activity in the striatum could be modulated by dopaminergic medication in non-demented PD, which mediate the cognitive performance in this disease.

Acknowledgements

References

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