Social Cognition Processes Are Impaired And Brain Functional Connectivity Alteration In Parkinson’s Disease

Objective Parkinson’s disease(PD) is a progressive neurodegenerative disorder pathologically characterized by the selective loss of dopaminergic neurons in the substantia nigra. Clinical manifestations include resting tremors, rigidity, bradykinesia, and postural instability. Qulitity of daily life and social function in patients with PD symptoms were affected not only by the motor symptoms, but also by many no motor symptoms. Cognitive impairment is one of the most common and important non-motor aspects of PD. Recent studies suggest that most patients with PD will eventually develop impairment not only of cognitive domains such as attention, executive function, memory and visuospatial functions, but also social cognition. Moreover, the relationship between subcomponents of social cognitive with PD patients impairment and basic cognition is currently under debate, and the neural mechanism of social cognitive impairment in PD patients is unclear. We investigated that social cognition impairment in the early/ moderate PD patients, and the relationship between social cognition impairment and the basic cognition. In addition, we investigated the relationship between social cognition impairment and brain network function connectivity alteration by resting state magnetic resonance functional.Method Fifteen early to moderately affected patients with PD(7 male, 8 female; 15 right-handed) and fifteen HC(6 male, 9 female; 15 right-handed) participated. All patients with PD were diagnosed by a movement disorders specialist and were recruited from the Department of Neurology in the First Hospital of Anhui Medical University and the Department of Neurology in the Third Hospital of Anhui Medical University. All patients received typical dopaminergic medication(levodopa, dopamine-agonists). We excluded patients and controls with other significant neurological problems by history of substance abuse,current or previous psychiatric diagnoses, and history of head trauma and stroke or severe head injury. Disease severity was graded according to the Hoehn and Yahr(H-Y) rating scale and the motor score on Section III of the Unified Parkinson’s disease Rating Scale(UPDRS). The following neuropsychological tests were administered to all participants and(1) the Mini-Mental State Examination(MMSE)(2) the Hamilton Depression Scale(3) verbal fluency(4) the Stroop test(5) the Digit Span test(6) the Rey Auditory Verbal Learning Test(AVLT)(7) the Hooper Visual Organization Task(HVOT)(7) Symbol digit modalities test. The aim of this study was also to investigate social cognition in patients with PD and healthy controls(HC) on a task assessing affective To M(Reading the Mind in the Eyes, RME) and two decision-making tasks(Iowa Gambling Task, IGT; Game of Dice Task, GDT). All participants were scanned using a 3.0 T Trio Siemens scanner(Germany) with a 8-channel head coil. Head motion was restricted with foam padding around the head, and the importance of head immobility was explained to each subject. Resting-state functional images were acquired using echo-planar imaging(EPI) sequence with the following parameters: TR/TE = 2,000/30 ms, flip angle = 90°, matrix = 64×64, thickness= 4.5mm, gap =0 mm, 33 slices, field of view(FOV) = 256 mm×256 mm, Structural images were acquired using Magnetization-prepared rapid gradient echo(MPRAGE) sequence with the following parameters: TR/TE/ Flip = 1700/2.93/15°, matrix =256×256, thickness = 1.0 mm, no gap, 176 slices, voxel size = 1×1×1 mm3.Result The results indicated that the PD group performed significantly worse compared with the HC group as revealed on measures of verbal fluency, Stroop test, AVLT delayed recognition, and the HVOT Task(all P < 0.05). The RME task revealed the presence of a significant difference between the two groups; the PD group performed worse than the HC group in emotion recognition(Mind Reading)(P < 0.001). However, there was no significant difference between the two groups in gender recognition(P >0.05). We found that the PD group chose significantly fewer advantageous cards than the HC group(P= 0.02) in IGT task. Independent t-tests were used to investigate whether the PD and HC groups differed in final capital and GDT choices. The results showed that the final capital of the PD patients was significantly lower than that of HC(PD: M =-4346.67, SD = 2707.36; HC: M =-520, SD = 2905.46; t(28) = 3.73, P = 0.001). Furthermore, there was a significant difference between the two groups in the selection of risky options during the GDT. PD patients showed a greater preference for risky and less safe options than the HC group(P = 0.02). Pearson correlations were computed between performance in the RME, the IGT or GDT, and the demographic data and neuropsychological tests. The score of emotion recognition(Mind Reading) in the RME task showed significant negative correlations with the(H-Y) Stages(r =-0.58, P = 0.02) and the score of UPDRS III(r =-0.81, P < 0.01), and a significant positive correlation with the total number of advantageous cards in the IGT(r = 0.58, P = 0.02). The scores of the IGT were not correlated with other demographic data and neuropsychological tests(all p > 0.05). We found that the final capital in GDT was correlated significantly with the AVLT delayed recall(r=0.57, P=0.03) but was not correlated with any other neuropsychological tests(all P > 0.05). Here we utilized resting state functional magnetic resonance imaging to measure the functional connectivity of prefrontal cortex and amygdala in patients with PD and HC. Functional connectivity analysis was carried out by applying seed-region approach using the left and right ROIs(dorsolateral prefrontal cortex, orbitofrontal cortex, amygdala) as defined in the automated anatomical labeling atlas(AAL). Compared to controls, patients with PD exhibited significantly decreased functional connectivity within right dorsolateral prefrontal cortex and right amygdala, left dorsolateral prefrontal cortex and left amygdala, the right orbitofrontal cortex and right amygdala. However, compared to controls, patients with PD exhibited enhanced functional connectivity with right dorsolateral prefrontal cortex and right orbitofrontal cortex. The degree of functional connectivity within right dorsolateral prefrontal cortex and right amygdale was related to the final capital of GDT(P<0.001), the functional connectivity left dorsolateral prefrontal cortex and left amygdale was related to the total number of disadvantage cards( P=0.05), the enhanced degree of functional connectivity with the right dorsolateral prefrontal cortex and right orbitofrontal cortex was related to the final capital of GDT(P=0.059. The functional connectivity within the right orbitofrontal cortex and right amygdale was related to the RME(P=0.01).Conclusion1. The results showed that the PD were impaired not only on basic cognitive domains such as executive function, attention,memory and visuospatial function, but also affective theory of mind and decision making.2. The present study implied that affective To M aggravated gradually with progression of disease severity in PD;The ability of affective To M may affect decision making under ambiguity, while memory impairment in PD could further affect selection strategy during GDT.3. Social cognitive impairment with PD may be attributed to the abnormal functional connectivity between the prefrontal cortex and amygdala. Decision making under ambiguity and decision making under risk may involve processing of different neural networks.