Ellison Fernando Cardoso

Depression in Parkinson's disease: Convergence from voxel-based morphometry and functional magnetic resonance imaging in the limbic thalamus

Depression is the most frequent psychiatric disorder in Parkinsons disease (PD). Although evidence suggests that depression in PD is related to the degenerative process that underlies the disease, further studies are necessary to better understand the neural basis of depression in this population of patients. In order to investigate neuronal alterations underlying the depression in PD, we studied thirty-six patients with idiopathic PD. Twenty of these patients had the diagnosis of major depression disorder and sixteen did not. The two groups were matched for PD motor severity according to Unified Parkinson Disease Rating Scale (UPDRS). First we conducted a functional magnetic resonance imaging (fMRI) using an event-related parametric emotional perception paradigm with test retest design. Our results showed decreased activation in the left mediodorsal (MD) thalamus and in medial prefrontal cortex in PD patients with depression compared to those without depression. Based upon these results and the increased neuron count in MD thalamus found in previous studies, we conducted a region of interest (ROI) guided voxel-based morphometry (VBM) study comparing the thalamic volume. Our results showed an increased volume in mediodorsal thalamic nuclei bilaterally. Converging morphological changes and functional emotional processing in mediodorsal thalamus highlight the importance of limbic thalamus in PD depression. In addition this data supports the link between neurodegenerative alterations and mood regulation.

rTMS treatment for depression in Parkinson`s disease increases BOLD responses in the left prefrontal cortex

The mechanisms underlying the effects of antidepressant treatment in patients with Parkinsons disease (PD) are unclear. The neural changes after successful therapy investigated by neuroimaging methods can give insights into the mechanisms of action related to a specific treatment choice. To study the mechanisms of neural modulation of repetitive transcranial magnetic stimulation (rTMS) and fluoxetine, 21 PD depressed patients were randomized into only two active treatment groups for 4 wk: active rTMS over left dorsolateral prefrontal cortex (DLPFC) (5 Hz rTMS; 120% motor threshold) with placebo pill and sham rTMS with fluoxetine 20 mg/d. Event-related functional magnetic resonance imaging (fMRI) with emotional stimuli was performed before and after treatment - in two sessions (test and re-test) at each time-point. The two groups of treatment had a significant, similar mood improvement. After rTMS treatment, there were brain activity decreases in left fusiform gyrus, cerebellum and right DLPFC and brain activity increases in left DLPFC and anterior cingulate gyrus compared to baseline. In contrast, after fluoxetine treatment, there were brain activity increases in right premotor and right medial prefrontal cortex. There was a significant interaction effect between groups vs. time in the left medial prefrontal cortex, suggesting that the activity in this area changed differently in the two treatment groups. Our findings show that antidepressant effects of rTMS and fluoxetine in PD are associated with changes in different areas of the depression-related neural network.

Performing functional magnetic resonance imaging in patients with Parkinson's disease treated with deep brain stimulation

Deep brain stimulation (DBS) is a relatively novel treatment in advanced Parkinsons disease (PD). Functional magnetic resonance imaging (fMRI) is a useful technique for examining the effects of DBS both within the basal ganglia and its cortical connectivity. There are technical difficulties in imaging patients with PD, and the DBS itself can generate image artifacts. We describe aspects related to optimizing the fMRI acquisition parameters in patients with DBS and the results of sensorimotor activation tasks performed by four PD patients during hand, foot, and tongue movements, both before and after DBS implant. Provided that all safety conditions are followed, it is possible to perform fMRI in patients with PD and DBS. The standard DBS surgical procedure has to be slightly modified in order to reduce image artifacts. The event‐related design provided increased power to detect sensorimotor cortex and basal ganglia activation.

Abnormal visual activation in Parkinson's disease patients.

Among nonmotor symptoms observed in Parkinsons disease (PD) dysfunction in the visual system, including hallucinations, has a significant impact in their quality of life. To further explore the visual system in PD patients we designed two fMRI experiments comparing 18 healthy volunteers with 16 PD patients without visual complaints in two visual fMRI paradigms: the flickering checkerboard task and a facial perception paradigm. PD patients displayed a decreased activity in the primary visual cortex (Broadmann area 17) bilaterally as compared to healthy volunteers during flickering checkerboard task and increased activity in fusiform gyrus (Broadmann area 37) during facial perception paradigm. Our findings confirm the notion that PD patients show significant changes in the visual cortex system even before the visual symptoms are clinically evident. Further studies are necessary to evaluate the contribution of these abnormalities to the development visual symptoms in PD.

Intervention Models in Functional Connectivity Identification Applied to fMRI

Recent advances in neuroimaging techniques have provided precise spatial localization of brain activation applied in several neuroscience subareas. The development of functional magnetic resonance imaging (fMRI), based on the BOLD signal, is one of the most popular techniques related to the detection of neuronal activation. However, understanding the interactions between several neuronal modules is also an important task, providing a better comprehension about brain dynamics. Nevertheless, most connectivity studies in fMRI are based on a simple correlation analysis, which is only an association measure and does not provide the direction of information flow between brain areas. Other proposed methods like structural equation modeling (SEM) seem to be attractive alternatives. However, this approach assumes prior information about the causality direction and stationarity conditions, which may not be satisfied in fMRI experiments. Generally, the fMRI experiments are related to an activation task; hence, the stimulus conditions should also be included in the model. In this paper, we suggest an intervention analysis, which includes stimulus condition, allowing a nonstationary modeling. Furthermore, an illustrative application to real fMRI dataset from a simple motor task is presented.

An fMRI-compatible force measurement system for the evaluation of the neural correlates of step initiation

Knowledge of brain correlates of postural control is limited by the technical difficulties in performing controlled experiments with currently available neuroimaging methods. Here we present a system that allows the measurement of anticipatory postural adjustment of human legs to be synchronized with the acquisition of functional magnetic resonance imaging data. The device is composed of Magnetic Resonance Imaging (MRI) compatible force sensors able to measure the level of force applied by both feet. We tested the device in a group of healthy young subjects and a group of elderly subjects with Parkinson’s disease using an event-related functional MRI (fMRI) experiment design. In both groups the postural behavior inside the magnetic resonance was correlated to the behavior during gait initiation outside the scanner. The system did not produce noticeable imaging artifacts in the data. Healthy young people showed brain activation patterns coherent with movement planning. Parkinson’s disease patients demonstrated an altered pattern of activation within the motor circuitry. We concluded that this force measurement system is able to index both normal and abnormal preparation for gait initiation within an fMRI experiment.

Altered Functional Connectivity Between Precuneus and Motor Systems in Parkinson's Disease Patients

Parkinsons disease (PD) is a neurodegenerative disorder that affects motor skills and cognition. As brain structure and function are compromised, functional magnetic resonance imaging (fMRI) can be a helpful tool to further investigate how intrinsic connectivity is impaired on the disease. The precuneus and medial prefrontal cortex (mPFC) are hub regions involved on the default mode network (DMN), a system that is active during rest and related to cognitive processes. We hypothesized that PD patients would present a decrease in functional connectivity among these two regions and the rest of the brain. Our goal was to identify regions in which functional connectivity to precuneus and mPFC was altered in PD. This study was based on resting-state fMRI data from 37 healthy subjects and 55 PD patients. Precuneus and mPFC were selected as seed regions in a whole brain functional connectivity mapping. As expected, we found abnormal connectivity from precuneus to motor system regions in PD patients, pointing toward a decreased connectivity in the disease. No significant group effects were found for the mPFC. Our findings suggest that internetwork connectivity from DMN to motor system is impaired in PD.

Nonlinear estimation of neural processing time from BOLD signal with application to decision-making

The extraction of information about neural activity timing from BOLD signal is a challenging task as the shape of the BOLD curve does not directly reflect the temporal characteristics of electrical activity of neurons. In this work, we introduce the concept of neural processing time (NPT) as a parameter of the biophysical model of the hemodynamic response function (HRF). Through this new concept we aim to infer more accurately the duration of neuronal response from the highly nonlinear BOLD effect. The face validity and applicability of the concept of NPT are evaluated through simulations and analysis of experimental time series. The results of both simulation and application were compared with summary measures of HRF shape. The experiment that was analyzed consisted of a decision‐making paradigm with simultaneous emotional distracters. We hypothesize that the NPT in primary sensory areas, like the fusiform gyrus, is approximately the stimulus presentation duration. On the other hand, in areas related to processing of an emotional distracter, the NPT should depend on the experimental condition. As predicted, the NPT in fusiform gyrus is close to the stimulus duration and the NPT in dorsal anterior cingulate gyrus depends on the presence of an emotional distracter. Interestingly, the NPT in right but not left dorsal lateral prefrontal cortex depends on the stimulus emotional content. The summary measures of HRF obtained by a standard approach did not detect the variations observed in the NPT. Hum Brain Mapp, 2012.

Emotional Face Perception in Healthy Subjects and Parkinson’s Disease: An Effective Connectivity Study

We investigated the neural connectivity induced by face presentation with different emotional valences in Parkinson’s disease (PD) patients and a control group of healthy, drug-free volunteers, using event-related fMRI in a parametric design. The focus of this work was applying Dynamic Causal Modelling (DCM), an approach that allows the assessment of effective connectivity within cortical networks [1], to the study of effective connectivity between maximally activated brain regions in response to passive viewing of facial stimuli. A connectivity model was built based on the literature and in our fMRI analyses, which included the fusiform gyrus (FG), the anterior cingulate cortex (ACG), the dorsolateral prefrontal cortex (DLPFC) and the dorso-medial pre-frontal cortex (DMPFC) areas. The results showed differences in connectivity between the PD group and the control group. We found that the intrinsic connectivities among DLPFC/DMPFC and FG, DLPFC/DMPFC and ACG, were higher in PD patients than in healthy subjects, while the effective connectivity among FG and ACG was lower in PD patients.

Individual latent state scoring based on Hyperplane Navigation

Joao Ricardo Sato1,4, Carlos Eduardo Thomaz2, Ellison Fernando Cardoso1, Andre Fujita3, Maria da Graca Morais Martin1, Edson Amaro Jr1 1 NIF/LIM44 – Institute of Radiology, Hospital das Clinicas, University of Sao Paulo – Brazil. 2 Centro Universitario da FEI, Sao Paulo – Brazil. 3 Institute of Medical Sciences, University of Tokyo – Japan 4 Mathematics, Computation and Cognition Center –Universidade Federal do ABC Brazil email : joao.sato@ufabc.edu.br