António Freire

Motion integration deficits are independent of magnocellular impairment in Parkinson’s disease

Motion processing involves multiple hierarchical steps, from the magnocellular pathway, sensitive to high temporal frequency modulations, to subsequent motion integration within the visual cortical dorsal stream. We have tested whether motion integration deficits in mild Parkinson disease (PD) can be explained by visual deficits in earlier processing nodes. Contrast sensitivity deficits in the magnocellular pathway, were compared with speed discrimination of local dots moving in random directions, speed and direction discrimination of moving surfaces and motion integration as measured by 2D coherence thresholds (n=27). We have found that low-level magnocellular impairment in PD does not explain deficits in subsequent steps in motion processing. High-level performance was abnormal in particular for tasks requiring perception of coherently moving surfaces. Motion coherence deficits were predictive of visuomotor impairment, corroborating a previous magnetic stimulation study in normal subjects. We conclude that dorsal stream deficits in PD have a high-level visual cortical basis independent of low-level magnocellular damage.

Specific retinotopically based magnocellular impairment in a patient with medial visual dorsal stream damage.

We report here retinotopically based magnocellular deficits in a patient with a unilateral parieto-occipital lesion. We applied convergent methodologies to study his dorsal stream processing, using psychophysics as well as structural and functional imaging. Using standard perimetry we found deficits involving the periphery of the left inferior quadrant abutting the horizontal meridian, suggesting damage of dorsal retinotopic representations beyond V1. Retinotopic damage was much more extensive when probed with frequency-doubling based contrast sensitivity measurements, which isolate processing within the magnocellular pathway: sensitivity losses now encroached on the visual central representation and did not respect the horizontal meridian, suggesting further damage to dorsal stream retinotopic areas that contain full hemi-field representations, such as human V3A or V6. Functional imaging revealed normal responses of human MT+ to motion contrast. Taken together, these findings are consistent with a recent proposal of two distinct magnocellular dorsal stream pathways: a latero-dorsal pathway passing to MT+ and concerned with the processing of coherent motion, and a medio-dorsal pathway that routes information from V3A to the human homologue of V6. Anatomical evidence was consistent with sparing of the latero-dorsal pathway in our patient, and was corroborated by his normal performance in speed, direction discrimination and motion coherence tasks with 2D and 3D objects. His pattern of dysfunction suggests damage only to the medio-dorsal pathway, an inference that is consistent with structural imaging data, which revealed a lesion encompassing the right parieto-occipital sulcus.

Specific impairment of visual spatial covert attention mechanisms in Parkinson's disease

Visual deficits in early and high level processing nodes have been documented in Parkinsons disease (PD). Non-motor high level visual integration deficits in PD seem to have a cortical basis independently of a low level retinal contribution. It is however an open question whether sensory and visual attention deficits can be separated in PD. Here, we have explicitly separated visual and attentional disease related patterns of performance, by using bias free staircase procedures measuring psychophysical contrast sensitivity across visual space under covert attention conditions with distinct types of cues (valid, neutral and invalid). This further enabled the analysis of patterns of dorsal-ventral (up-down) and physiological inter-hemispheric asymmetries. We have found that under these carefully controlled covert attention conditions PD subjects show impaired psychophysical performance enhancement by valid attentional cues. Interestingly, PD patients also show paradoxically increased visual homogeneity of spatial performance profiles, suggesting flattening of high level modulation of spatial attention. Finally we have found impaired higher level attentional modulation of contrast sensitivity in the visual periphery, where mechanisms of covert attention are at higher demands. These findings demonstrate a specific loss of attentional mechanisms in PD and a pathological redistribution of spatial mechanisms of covert attention.

Distinct functional properties of the vertical and horizontal saccadic network in Health and Parkinson's disease: An eye-tracking and fMRI study.

Saccadic behaviour ranges from reflexive (e.g., prosaccade) to goal oriented voluntary movements (e.g., antisaccade). Behavioural asymmetries between vertical and horizontal saccades have been described both in normal individuals (greater delay of vertical prosaccades) and in disease states such as Parkinsons disease (PD) (prosaccades are short and antisaccades are delayed, especially in the vertical plane, possibly due to a frontostriatal deficit). Importantly, the cortical mechanisms for the generation of vertical saccades are largely unknown, both in health and disease, when compared with their horizontal counterpart. Moreover, studies exploring saccadic neural correlates and putative compensatory mechanisms at a functional level in PD are scarce. We investigated horizontal and vertical prosaccades and antisaccades in an eye tracking paradigm in 19 PD patients off medication and 22 healthy controls, followed by a block-design functional Magnetic Resonance Imaging (fMRI) study, consisting of two runs (prosaccade, antisaccade) of 6 blocks each (3 vertical, 3 horizontal). While saccade metrics were not significantly different between groups, PD showed left frontal underactivation during horizontal prosaccades and right parietal overactivation during horizontal and vertical prosaccades and horizontal antisaccades. Moreover, controls showed greater deactivation of the default-mode network (DMN) during antisaccades. Vertical prosaccades were associated with greater right frontal and cerebellar activity in controls, and cuneus hypoactivity in PD. Vertical antisaccades were associated with greater DMN deactivation in both groups and left frontal hypoactivity in PD. Putative functional compensatory changes in the right parietal cortex in PD patients may help to keep saccadic behaviour at the same level as the healthy controls. We provide first time evidence showing that functional cortical asymmetries between vertical and horizontal saccades occur distinctively in PD patients and healthy controls.

Substantia nigra hyperechogenicity does not correlate with motor features in Parkinson's disease

INTRODUCTION The evaluation of hyperechogenicity of the substantia nigra (SN) by transcranial sonography (TCS) is validated for the diagnosis of Parkinsons disease (PD). However, its correlation with the severity of motor involvement is still uncertain. METHODS We included patients with clinical diagnosis of idiopathic PD in a cross-sectional study. All patients were evaluated with Unified Parkinsons Disease Rating Scale-motor score (UPDRS-III) and TCS at the same day with measurement of the area of SN hyperechogenicity for each side. We analysed the association between the area of SN hyperechogenicity and the contralateral motor scores of UPDRS-III, adjusting for age and dominance of the patient (statistical significance set to p<0.05). RESULTS 35 patients were analysed, 3 (8.6%) were excluded due to poor temporal acoustic bone window. From a total of 32 patients, the mean age was 58.4 (±11.2)years. The mean area of SN hyperechogenicity was: right 0.26 (±0.12)cm(2) and left 0.27 (±0.07)cm(2). The mean score of UPDRS-III was 18.9 (±6.1). There were no statistically significant association between the scores of the UPDRS-III (rigidity, tremor and bradykinesia) and the contralateral area of SN hyperechogenicity. CONCLUSION The area of SN hyperechogenicity did not correlate with motor deterioration in Parkinsons disease.

Transcranial Sonography and DaTSCAN in Early Stage Parkinson's Disease and Essential Tremor

Background: The diagnosis of Parkinsons disease (PD) can sometimes be a challenge in the early stages of the disease. Both transcranial sonography (TCS) and DaTSCAN are recommended as auxiliary examinations for the differential diagnosis of PD; however, only few data exist regarding their diagnostic accuracy in the early stage of PD and essential tremor (ET). Methods: We evaluated patients with clinically suspected diagnosis of PD at early stages (Hoehn and Yahr ≤2) or ET. All patients underwent DaTSCAN and TCS with a maximum interval of 6 months. Final diagnosis was established after 1-year follow-up. Results: From the 63 patients recruited, 3 were excluded due to transcranial insonability and 2 for uncertain clinical diagnosis. The final clinical diagnosis was ET in 44.8% and PD in 55.2%. Compared to clinical diagnosis of PD, TCS had a sensitivity of 87.5% and specificity of 96.2%; DaTSCAN sensitivity was 84.4% and specificity was 96.2%. Both diagnostic tests demonstrated a substantial level of agreement (Cohens kappa coefficient: 0.83, 95% CI 0.68-0.97, p < 0.001). Conclusion: TCS and DaTSCAN have similar diagnostic accuracy for the diagnosis of early stage PD versus ET.

Tremor modulations across periods with and without voluntary motion and limb load task demands using movement quantification

Understanding the neurobiological mechanisms underlying different types of tremor and the altered functional connectivity of the involved areas is a timely goal in clinical neuroscience. If successful, this quest may open new perspectives on how to achieve tremor modulation, which is notably relevant, in Parkinsons disease (PD). Tremor can be characterized by simple parameters such as frequency and amplitude. It is therefore prone to be objectively targeted by neuromodulation and quantitatively investigated using multimodal techniques, such as, accelerometry, EMG and functional Magnetic Resonance Imaging (fMRI). Embarking on the latter challenge requires an a priori knowledge of how effective functional connectivity is altered in PD tremor. This works aims to ascertain which postural and voluntary movement tasks with distinct types of physical load are suitable for designing efficient fMRI protocols, by performing an accelerometry analysis to measure spontaneous and imposed tremor modulation on cohorts of PD patients, essential tremor patients and a group of voluntary healthy controls.

Cortical control of vertical and horizontal saccades in progressive supranuclear palsy: An exploratory fMRI study

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder showing predominant brainstem involvement, characterized by marked slowing of rapid eye movements (saccades), particularly along the vertical plane. While the contribution of the brainstem damage for the saccadic disturbance in PSP has been extensively studied, much less is known about its cortical and subcortical pathomechanisms. We measured reflexive (prosaccades) and voluntary (antisaccades) saccades in the vertical and horizontal plane in PSP patients (n=8) and controls (n=10) in an eye tracking study, followed by the measurement of blood oxygenation-level dependent (BOLD) activation (PSP, n=6; controls, n=10) during similar saccade paradigms. Behaviorally, PSP patients evidenced slower and lower amplitude prosaccades (horizontal and vertical) and lower amplitude antisaccades (vertical) than controls. Functionally, patients showed decreased frontostriatal BOLD activation during prosaccades (horizontal and vertical) and antisaccades (vertical), relative to controls. Additionally, PSP patients showed less default mode network (DMN) deactivation than controls for all types of saccades. Within groups, controls showed no BOLD differences between horizontal and vertical prosaccades while PSP patients demonstrated greater DMN deactivation during vertical prosaccades. Both groups evidenced greater DMN deactivation during vertical antisaccades when compared to their horizontal counterpart and patients further showed relative frontostriatal BOLD hypoactivity during vertical antisaccades. We found fMRI evidence of frontostriatal hypoactivity in PSP patients relative to controls, especially during vertical saccades. These new findings highlight the impact of cortical impairment in saccadic disturbance of PSP.

Apathy Profile in Parkinson’s and Huntington’s Disease: A Comparative Cross-Sectional Study

Background/Aims: Apathy is one of the most frequent, disabling and difficult-to-treat symptoms that show up in many neurodegenerative disorders. The aim of this study was to assess and compare apathy profile in Parkinson’s and Huntington’s patients using the same comprehensive instruments to measure apathy, cognition and depressive symptoms. Materials and Methods: We consecutively assessed Parkinson’s disease (PD) and Huntington’s disease (HD) patients recruited from a Movement Disorders Unit. In all patients, information related to demographics, clinical data, motor score (Movement Disorders Society-Unified Parkinson Disease Rating Scale; Unified Huntington Disease Rating Scale), cognition (Montreal Cognitive Assessment scale), depressive symptoms (Beck Depression Inventory II) and apathy (Apathy Evaluation Scale – clinical version) was collected. Patients with dementia or major depression according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revised criteria were excluded from the study. Results: Seventy-five patients were enrolled, 45 with PD and 30 with HD. Apathy was present in 42.5% of PD patients and 51.7% of HD patients. In PD patients, apathy was associated with motor score, shorter duration of disease, lower dose of levodopa equivalent daily dose and depressive symptomatology, whereas in HD patients, apathy was related to disease duration, motor score and cognitive impairment. Conclusions: We found a similar prevalence of apathy in PD and HD patients but with different clinical correlations and different apathy domains involved, and this may warrant the development of different therapeutic approaches.

Contents Vol. 76, 2016

Basel • Freiburg • Paris • London • New York • Chennai • New Delhi • Bangkok • Beijing • Shanghai • Tokyo • Kuala Lumpur • Singapore • Sydney Founded 1897 as ‘Monatsschrift für Psychiatrie und Neurologie’, continued 1957–1967 as ‘Psychiatria et Neurologia’ Founders: C. Wernicke and Th. Ziehen. Successors: K. Bonhoeffer (1912–1938), J. Klaesi (1939–1967), E. Grünthal (1953–1967), H.E. Kaeser (1968–1993)