Data_Sheet_1_Directed functional connectivity of the sensorimotor system in young and older individuals.docx

IntroductionStudies in the sensorimotor system of older versus young individuals have shown alterations in functional connectivity and organization. Our objective was to explore the implications of these differences in terms of local organizations, and to identify processes that correlate with neuropsychological parameters.MethodsUsing a novel multivariate analysis method on resting-state functional MRI data obtained from 50 young and 31 older healthy individuals, we identified directed 4-node functional pathways within the sensorimotor system and examined their correlations with neuropsychological assessments.ResultsIn young individuals, the functional pathways were unidirectional, flowing from the primary motor and sensory cortices to higher motor and visual regions. In older individuals, the functional pathways were more complex. They originated either from the calcarine sulcus or the insula and passed through mutually coupled high-order motor areas before reaching the primary sensory and motor cortices. Additionally, the pathways in older individuals that resembled those found in young individuals exhibited a positive correlation with years of education.DiscussionThe flow pattern of young individuals suggests efficient and fast information transfer. In contrast, the mutual coupling of high-order motor regions in older individuals suggests an inefficient and slow transfer, a less segregated and a more integrated organization. The differences in the number of sensorimotor pathways and of their directionality suggests reduced efferent degenerated pathways and increased afferent compensated pathways. Furthermore, the positive effect of years of education may be associated with the Cognitive Reserve Hypothesis, implying that cognitive reserve could be maintained through specific information transfer pathways.</p

Bilateral STN-DBS active contact positions of 20 patients with Parkinson's disease plotted in the coronal plane with respect to weight gain.

<p>Patients (N = 11) with at least one active contact (a) placed within 9.3-mm of the wall of the third ventricle gained significantly more weight than patients (N = 9) with both contacts (b) located more laterally (p<0.001).</p

Mean changes in weight after implantation in 20 patients with Parkinson's disease.

<p>Body weight gradually increased during the study period. Weight gain represents the difference in weight (±SD) compared to the preoperative state.</p

Weight gain in 20 patients with Parkinson's disease in relation to the mediolateral position of the active contact with bilateral STN-DBS (r = −0.55, p<0.01).

<p>Only one active contact (more medial contact from both hemispheres) was used in each patient. The x-coordinate represents the distance of the active contact from the wall of the third ventricle. Each millimeter in the medial direction was associated on average with a 1.6-kg increase in body weight. Dotted lines denote the 95% confidence interval of the regression line.</p

Hemi-body UPDRS-III subscores in the sON condition after overnight withdrawal of dopaminergic therapy in relation to the mediolateral position of the contralateral active contact.

<p>After initiation of STN-DBS, the hemi-body side with the lowest motor score (best motor condition) had the contralateral contacts located more laterally from the wall of the third ventricle (r = −0.42, p<0.01). Dotted lines denote the 95% confidence interval of the regression line.</p

Accounting for Movement Increases Sensitivity in Detecting Brain Activity in Parkinson's Disease

<div><p>Parkinson's disease (PD) is manifested by motor impairment, which may impede the ability to accurately perform motor tasks during functional magnetic resonance imaging (fMRI). Both temporal and amplitude deviations of movement performance affect the blood oxygenation level-dependent (BOLD) response. We present a general approach for assessing PD patients' movement control employing simultaneously recorded fMRI time series and behavioral data of the patients' kinematics using MR-compatible gloves. Twelve male patients with advanced PD were examined with fMRI at 1.5T during epoch-based visually paced finger tapping. MR-compatible gloves were utilized online to quantify motor outcome in two conditions with or without dopaminergic medication. Modeling of individual-level brain activity included <em>(i)</em> a predictor consisting of a condition-specific, constant-amplitude boxcar function convolved with the canonical hemodynamic response function (HRF) as commonly used in fMRI statistics (standard model), or <em>(ii)</em> a custom-made predictor computed from glove time series convolved with the HRF (kinematic model). Factorial statistics yielded a parametric map for each modeling technique, showing the medication effect on the group level. Patients showed bilateral response to levodopa in putamen and globus pallidus during the motor experiment. Interestingly, kinematic modeling produced significantly higher activation in terms of both the extent and amplitude of activity. Our results appear to account for movement performance in fMRI motor experiments with PD and increase sensitivity in detecting brain response to levodopa. We strongly advocate quantitatively controlling for motor performance to reach more reliable and robust analyses in fMRI with PD patients.</p> </div

Group-level response (ON-OFF) of PD patients to levodopa treatment.

<p>Uncorrected threshold of <i>p</i><0.001 was adopted and maps were overlaid on coronal and axial slices (left, blue: group maps obtained by standard first-level modeling without further assumptions on motor performance; right, orange: improvement of group-level maps obtained using various kinematic modeling techniques taking movement performance into account). AI^‡ - amplitude invariant.</p

Main effect of ‘Modeling approach’: percent signal change in anatomical ROI (left, right precentral gyrus) as <i>F</i>-statistics obtained by comparing particular modeling approaches in levodopa OFF and levodopa ON conditions.

<p>AI^‡ - amplitude invariant.</p

Demographic and clinical summary of studied patients (N = 12).

<p>UPDRS* - Unified Parkinson's Disease Rating Scale. MMSE^† - Mini Mental State Examination.</p

Comparison of modeling approaches as average effect size in anatomical ROI (contralateral precentral gyrus).

<p>Each bar represents the average value from ROI for the ‘group-level mean’ PSC image, and each error bar the average of the ‘group-level standard error’ PSC image. A: Percent signal change for the Levodopa OFF condition and all modeling approaches. B: Percent signal change for the Levodopa ON condition and all modeling approaches. AI^‡ - amplitude invariant.</p