Search

Objective The dual hit hypothesis about the pathogenesis of Parkinson disease (PD) suggests that the brainstem is a convergent area for the propagation of pathological α-synuclein from the periphery to the brain. Although brainstem structures are likely to be affected early in the course of the disease, detailed information regarding specific brainstem regions is lacking. The aim of our study was to investigate the function of the superior colliculus, a sensorimotor brainstem structure, in de novo PD patients compared to controls using brain functional magnetic imaging and visual stimulation paradigms. Methods De novo PD patients and controls were recruited. PD subjects were imaged before and after starting PD medications. A recently developed functional magnetic resonance imaging protocol was used to stimulate and visualize the superior colliculus and 2 other visual structures: the lateral geniculate nucleus and the primary visual cortex. Results In the 22 PD patients, there was no modulation of the superior colliculus responses to the luminance contrasts compared to controls. This implies a hypersensitivity to low luminance contrast and abnormal rapid blood oxygenation level-dependent signal saturation to high luminance contrasts. The lateral geniculate nucleus was only modulated by 3 to 9% luminance contrasts compared to controls. No major differences were found in the primary visual cortex between both groups. Interpretation Our findings suggest that pathological superior colliculus visual responses in de novo PD patients are present early in the course of the disease. Changes in imaging the superior colliculus could play an important role as a preclinical biomarker of the disease. ANN NEUROL 2020;87:533-546.

BackgroundPD is associated with non-motor symptoms appearing before the motor symptoms onset. Recent studies report dysfunctions of visual structures at early stages of PD.ObjectiveThis study addresses effective connectivity in the visual network of PD patients.MethodsUsing brain functional MRI and Dynamic Causal Modeling analysis, we investigated the connectivity between the superior colliculus, the lateral geniculate nucleus and the primary visual area V1 in 22 de novo untreated PD patients and six months after starting dopaminergic treatment compared to age-matched healthy controls.ResultsOur findings indicate that the superior colliculus drives cerebral activity for luminance contrast processing both in healthy controls and untreated PD patients. The same effective connectivity was observed with neuromodulatory differences in terms of neuronal dynamic interactions. The modulation induced by luminance contrast changes of the superior colliculus connectivity (self-connectivity and connectivity to the lateral geniculate nucleus) was inhibited in PD patients (effect of contrast: p = 0.79 and p = 0.77 respectively). The introduction of dopaminergic medication failed to restore the effective connectivity modulation observed in the healthy controls.InterpretationThe deficits in luminance contrast processing in PD seem due to a deficiency in connectivity adjustment from the superior colliculus to the lateral geniculate nucleus and to V1. Administration of a dopaminergic treatment over six months was not able to normalize the observed alterations in inter-regional coupling. These findings highlight the presence of early dysfunctions in primary visual areas, which might be used as early markers of the disease.

Representing multiple agents and their mutual relations is a prerequisite to understand social events. Using functional MRI on human adults, we show that visual areas dedicated to body-form and body-motion perception contribute to processing social events, by holding the representation of multiple moving bodies and encoding the spatial relations between them. In particular, seeing animations of human bodies facing and moving toward (vs. away from) each other, increased neural activity in the body-selective cortex (extrastriate body area -EBA) and posterior superior temporal sulcus for biological-motion perception (bm-pSTS). In those areas, representation of body postures and movements, as well as of the overall scene, was more accurate for facing-body (vs. non-facing body) stimuli. Effective connectivity analysis with Dynamic Causal Modeling revealed increased coupling between EBA and bm-pSTS during perception of facing-body stimuli. The attunement of human vision to multiple-body scenes involving perceptual cues of interaction such as face-to-face positioning and approaching behaviour, was further supported by the participants’ better performance in a match-to-sample task with facing-body vs. non-facing body stimuli. Thus, visuo-spatial cues of interaction in multiple-person scenarios affect the perceptual representation of body and body motion and, by promoting functional integration, streamline the process from body perception to action representation.

Some of the behavioral disorders observed in Parkinson’s disease (PD) may be related to an altered processing of social messages, including emotional expressions. Emotions conveyed by whole body movements may be difficult to generate and be detected by PD patients. The aim of the present study was to compare valence judgments of emotional whole body expressions in individuals with PD and in healthy controls matched for age, gender and education. Twenty-eight participants (13 PD patients and 15 healthy matched control participants) were asked to rate the emotional valence of short movies depicting emotional interactions between two human characters presented with the “Point Light Displays” technique. To ensure understanding of the perceived scene, participants were asked to briefly describe each of the evaluated movies. Patients’ emotional valence evaluations were less intense than those of controls for both positive (p

Background: The dual hit hypothesis about the pathogenesis of Parkinson's disease (PD) suggests that the brainstem can convey pathological entries to the brain. However, information about the involvement of different brainstem structures are difficult to collect in living PD patients. We have filled this gap by studying with functional brain MRI the superior colliculus (SC), a brainstem sensorimotor structure. Starting with the discovery that the SC shows abnormal visual responses in PD rat models, we aimed at studying the SC also in de novo PD patients. Methods: De novo PD patients and controls were studied using a recently developed fMRI protocol to stimulate and visualize the SC, the lateral geniculate nucleus (LGN) and the primary visual cortex (V1). The visual responses modulation of these structures was studied using luminance contrasts from 1% to 9%. We compared SC, LGN, and V1 BOLD responses of de novo PD patients with matching controls. The effects of dopaminergic treatment in PD patients were further evaluated. Findings: In the 22 enrolled PD patients, there was no modulation of the SC responses to the luminance contrasts, and the LGN was only modulated by 3%-9% luminance contrasts compared to the 22 controls. No major differences were found in V1 between both groups. Moreover, SC lack of modulation was more frequent in less affected de novo PD patients (Hoehn & Yahr stage 1). Dopaminergic treatment had no effect on SC and LGN modulation. Interpretation: De novo PD patients showed pathological responses to the luminance contrasts in the SC, suggesting that SC dysfunction could be diagnostic of PD. Since the SC seems to be more affected at stage 1 of PD, its dysfunction might be detected even earlier, supporting its potential role as a prodromal biomarker of PD. Clinical Trial Number: ClinicalTrial.gov (NCT02488395). Funding Statement: The work was funded by the University Grenoble Alpes, “La Fondation de l’Avenir” and “France Parkinson”. The Grenoble MRI facility IRMaGe was partly funded by the French program ‘Investissement d’Avenir” run by the Agence Nationale pour la Recherche (ANR-11-INBS-0006). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: All participants provided written informed consent to the study. The study was approved by the local ethical committee (ID RCB- 2014-A01835-42).

International audience; Luminance contrast is a fundamental visual cue. Using a dedicated neuroimaging framework, we sought to characterize typical Blood Oxygen Level Dependent (BOLD) responses in two subcortical regions, the superior colliculus (SC) and the lateral geniculate nucleus (LGN), and V1, the primary visual cortex area, and how they change over the lifespan. For imaging subcortical activity related to luminance contrast modulation, specific measurements were introduced to rule out possible signal contamination by cardiovascular activity and vascular alterations with age that could hamper the BOLD signal interpretation. Clearly, BOLD responses increased in these three regions with luminance contrast, with a statistically significant diminution in LGN and V1 for older compared to younger participants, while basal perfusion remained unchanged. Additionally, perceptual responses, as assessed with psychophysical experiments, were highly correlated to BOLD measures in the three studied regions. Taken together, fMRI and psychophysics results indicate an alteration of luminance contrast processing with normal aging. Based on this knowledge we can better recognize when age-related brain changes vary from these expectations especially during neurodegenerative diseases progression where the functioning of subcortical structures is altered. The proposed fMRI-physchophysics methodology allows performing such investigation.