Maria-Jose Marti

Neuroanatomical correlates of impaired decision-making and facial emotion recognition in early Parkinson’s disease

Decision‐making and recognition of emotions are often impaired in patients with Parkinson’s disease (PD). The orbitofrontal cortex (OFC) and the amygdala are critical structures subserving these functions. This study was designed to test whether there are any structural changes in these areas that might explain the impairment of decision‐making and recognition of facial emotions in early PD. We used the Iowa Gambling Task (IGT) and the Ekman 60 faces test which are sensitive to the integrity of OFC and amygdala dysfunctions in 24 early PD patients and 24 controls. High‐resolution structural magnetic resonance images (MRI) were also obtained. Group analysis using voxel‐based morphometry (VBM) showed significant and corrected (P < 0.05 FEW‐small volume correction) gray matter (GM) loss in the right amygdala and bilaterally in the OFC in PD patients. Volumetric analyses were also performed but did not yield significant differences between groups. Left lateral GM volume in OFC showed a slight correlation with the IGT, and bilateral OFC GM was strongly correlated with Ekman test performance in PD patients. We conclude that: (i) impairment in decision‐making and recognition of facial emotions occurs at the early stages of PD, (ii) these neuropsychological deficits are accompanied by degeneration of OFC and amygdala, and (iii) bilateral OFC reductions are associated with impaired recognition of emotions, and GM volume loss in left lateral OFC is related to decision‐making impairment in PD.

Assessment of cortical degeneration in patients with Parkinson's disease by voxel-based morphometry, cortical folding, and cortical thickness.

Noninvasive brain imaging methods provide useful information on cerebral involution and degenerative processes. Here we assessed cortical degeneration in 20 nondemented patients with Parkinsons disease (PD) and 20 healthy controls using three quantitative neuroanatomical approaches: voxel‐based morphometry (VBM), cortical folding (BrainVisa), and cortical thickness (FreeSurfer). We examined the relationship between global and regional gray matter (GM) volumes, sulcal indices, and thickness measures derived from the previous methods as well as their association with cognitive performance, age, severity of motor symptoms, and disease stage. VBM analyses showed GM volume reductions in the left temporal gyrus in patients compared with controls. Cortical folding measures revealed significant decreases in the left frontal and right collateral sulci in patients. Finally, analysis of cortical thickness showed widespread cortical thinning in right lateral occipital, parietal and left temporal, frontal, and premotor regions. We found that, in patients, all global anatomical measures correlated with age, while GM volume and cortical thickness significantly correlated with disease stage. In controls, a significant association was found between global GM volume and cortical folding with age. Overall these results suggest that the three different methods provide complementary and related information on neurodegenerative changes occurring in PD, however, surface‐based measures of cortical folding and especially cortical thickness seem to be more sensitive than VBM to identify regional GM changes associated to PD. Hum Brain Mapp, 2012.

Amygdalar and hippocampal MRI volumetric reductions in Parkinson's disease with dementia

Parkinsons disease (PD) involves neuropathological changes in the limbic system that lead to neuronal loss and volumetric reductions of several nuclei. We investigated possible volumetric reductions of the amygdala and hippocampus associated to PD. We carried out magnetic resonance imaging (MRI) volumetric studies in 16 patients with PD and dementia (PDD), 16 patients with PD without dementia (PD), and 16 healthy subjects. The general analysis of variance (ANOVA) showed a significant group effect (for the amygdala, P = 0.01; for the hippocampus, P = 0.005). A post‐hoc test demonstrated that the differences were due to PDD and control group comparisons for the amygdala (P = 0.008) and for the hippocampus (P = 0.004). In nondemented PD subjects, we observed an 11% reduction in the amygdala and a 10% reduction in the hippocampus compared with that in controls. In summary, demented PD patients have clear amygdalar and hippocampal atrophy that remains statistically significant after controlling for global cerebral atrophy. Nondemented PD patients also showed a degree of volumetric reduction in these structures although the differences were not statistically significant.

Cerebral atrophy in Parkinson's disease patients with visual hallucinations

Although visual hallucinations (VH) are relatively frequent in Parkinsons disease (PD) patients, their neural substrates are only known from neuropathological and functional magnetic resonance studies. The aim of this study was to investigate possible structural brain changes on MRI in non‐demented PD patients with VH using voxel‐based morphometry. Eighteen PD patients with VH were compared to 20 patients with PD without VH and 21 healthy controls. Compared with both controls and the non‐hallucinating PD group, PD patients with VH had grey matter volume reductions in the lingual gyrus and superior parietal lobe. Structural changes in these areas involved in higher visual processing may be important in understanding the VH and visual deficits in PD patients.

Hippocampal head atrophy predominance in Parkinson's disease with hallucinations and with dementia.

We studied regional gray matter density in the hippocampus in Parkinson’s disease (PD) patients. We obtained magnetic resonance scans in 44 PD patients (PD patients with dementia (PDD) = 9, non-demented PD patients with visual hallucinations (PD + VH) = 16, and PD patients without dementia and without visual hallucinations (PD - VH) = 19) and 56 controls matched for age and years of education. A region of interest (ROI) of the hippocampus following voxel-based morphometry (VBM) procedures was used to perform group comparisons, single-case individual analysis and correlations with learning scores. Group comparisons showed that PDD patients and PD+VH patients had significant hippocampal gray matter loss compared to controls. In PDD patients, hippocampal gray matter loss involved the entire hippocampus and in PD+VH this reduction was mainly confined to the hippocampal head. 78 % of PDD patients, 31 % of PD+VH patients and 26 % of PD-VH patients had hippocampal head gray matter loss when compared to controls. These results suggest that in PD the neurodegenerative process in the hippocampus starts in the head of this structure and later spreads to the tail and that, in addition, memory impairment assessed by Rey’s Auditory Verbal Learning Test (RAVLT) correlates with hippocampal head gray matter loss.

Cognitive impairment and resting‐state network connectivity in Parkinson's disease

The purpose of this work was to evaluate changes in the connectivity patterns of a set of cognitively relevant, dynamically interrelated brain networks in association with cognitive deficits in Parkinsons disease (PD) using resting‐state functional MRI. Sixty‐five nondemented PD patients and 36 matched healthy controls were included. Thirty‐four percent of PD patients were classified as having mild cognitive impairment (MCI) based on performance in attention/executive, visuospatial/visuoperceptual (VS/VP) and memory functions. A data‐driven approach using independent component analysis (ICA) was used to identify the default‐mode network (DMN), the dorsal attention network (DAN) and the bilateral frontoparietal networks (FPN), which were compared between groups using a dual‐regression approach controlling for gray matter atrophy. Additional seed‐based analyses using a priori defined regions of interest were used to characterize local changes in intranetwork and internetwork connectivity. Structural group comparisons through voxel‐based morphometry and cortical thickness were additionally performed to assess associated gray matter atrophy. ICA results revealed reduced connectivity between the DAN and right frontoinsular regions in MCI patients, associated with worse performance in attention/executive functions. The DMN displayed increased connectivity with medial and lateral occipito‐parietal regions in MCI patients, associated with worse VS/VP performance, and with occipital reductions in cortical thickness. In line with data‐driven results, seed‐based analyses mainly revealed reduced within‐DAN, within‐DMN and DAN‐FPN connectivity, as well as loss of normal DAN‐DMN anticorrelation in MCI patients. Our findings demonstrate differential connectivity changes affecting the networks evaluated, which we hypothesize to be related to the pathophysiological bases of different types of cognitive impairment in PD. Hum Brain Mapp, 36:199–212, 2015.

Functional brain networks and cognitive deficits in Parkinson's disease

Graph‐theoretical analyses of functional networks obtained with resting‐state functional magnetic resonance imaging (fMRI) have recently proven to be a useful approach for the study of the substrates underlying cognitive deficits in different diseases. We used this technique to investigate whether cognitive deficits in Parkinsons disease (PD) are associated with changes in global and local network measures. Thirty‐six healthy controls (HC) and 66 PD patients matched for age, sex, and education were classified as having mild cognitive impairment (MCI) or not based on performance in the three mainly affected cognitive domains in PD: attention/executive, visuospatial/visuoperceptual (VS/VP), and declarative memory. Resting‐state fMRI and graph theory analyses were used to evaluate network measures. We have found that patients with MCI had connectivity reductions predominantly affecting long‐range connections as well as increased local interconnectedness manifested as higher measures of clustering, small‐worldness, and modularity. The latter measures also tended to correlate negatively with cognitive performance in VS/VP and memory functions. Hub structure was also reorganized: normal hubs displayed reduced centrality and degree in MCI PD patients. Our study indicates that the topological properties of brain networks are changed in PD patients with cognitive deficits. Our findings provide novel data regarding the functional substrate of cognitive impairment in PD, which may prove to have value as a prognostic marker. Hum Brain Mapp 35:4620–4634, 2014.

Neuropsychological deficits in Parkinson's disease patients with visual hallucinations.

Recent neuropathological and neuroimaging studies suggest the involvement of several temporal regions in Parkinsons disease (PD) patients with visual hallucinations (VH). We examined 24 nondemented PD patients with VH, 21 PD patients without VH, and 21 healthy controls using a battery of tests assessing different aspects of temporal lobe function. PD patients with VH showed poorer performance in language, verbal learning, semantic fluency, and visuoperceptive functions compared to controls and PD patients without VH. Differences in verbal learning and visuoperceptive functions were independent of general cognitive status, disease severity, and depression. We suggest that a wide range of neuropsychological deficits can contribute to the emergence of VH in PD.

Cognitive Changes in Parkinson’s Disease Patients with Visual Hallucinations

Objective: To evaluate the decline in specific neuropsychological functions in nondemented Parkinson’s disease (PD) patients with a history of visual hallucinations (VH). Methods: Twenty PD patients with VH, 20 PD patients without VH and 18 normal controls were followed up over a 1-year period and assessed for cognitive decline. Results: Forty-five percent of nondemented hallucinating PD patients developed dementia during the 1-year period between baseline and follow-up evaluations. Of the nondemented hallucinating PD patients nearly 70% showed impairment in multiple cognitive domains. The progressive decline in hallucinating PD patients affected mainly visual memory for faces and visuoperceptive-visuospatial functions. Conclusion: Our results support a fast impairment of complex visual functions in hallucinating PD patients, but also a progressive decline in multiple cognitive domains, which have been identified as a risk of developing dementia in PD.

Olfactory impairment in Parkinson's disease and white matter abnormalities in central olfactory areas: A voxel-based diffusion tensor imaging study†

Olfactory dysfunction is known to occur before the appearance of the classical motor signs in Parkinsons disease (PD) and diffusion tensor imaging (DTI) studies in PD have reported fractional anisotropy (FA) reductions in the early disease stages. We aimed to investigate the relationship between olfactory dysfunction and white matter (WM) FA of central olfactory areas in early PD. Twenty‐four patients at Hoehn and Yahr stages I and II and 24 healthy controls matched by age, gender and years of education participated in this study. DTI was acquired at a 3 Tesla scanner and odor identification was assessed using the University of Pennsylvania Smell Identification Test (UPSIT). We performed FA voxelwise group comparisons in the central olfactory structures using tract‐based spatial statistics (TBSS) and correlation analyses between FA values in these central olfactory areas and UPSIT scores. Patients with severe microsmia (UPSIT between 19 and 25) and anosmia (UPSIT lower or equal to 18) had lower FA values than PD patients with mild/moderate or no olfactory dysfunction (UPSIT between 26 and 40) and healthy controls in the WM adjacent to gyrus rectus. In addition, patients with anosmia had reduced FA in the WM surrounding primary olfactory areas in comparison with healthy controls. FA values in the WM adjacent to primary olfactory cortex and right gyrus rectus correlated with UPSIT scores in the PD group. This study demonstrates, for the first time, that microstructural WM reductions are present in the central olfactory system of early stage PD patients and that these reductions are associated with reduced ability to smell.