Fernanda Martins Maia

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.

Effects of repetitive transcranial magnetic stimulation on voice and speech in Parkinson's disease

Objective –  To investigate the effects of repetitive transcranial magnetic stimulation (rTMS) on vocal function in Parkinsons disease (PD).

Immediate Placebo Effect in Parkinson’s Disease – Is the Subjective Relief Accompanied by Objective Improvement?

Background: A recent well-conducted meta-analysis showed that placebo effect is associated with a possible small benefit for subjective outcomes, but has no significant effects on objective outcomes. Objective: Herein, we aimed to investigate the immediate effects of two different types of placebo [placebo pill and sham transcranial magnetic stimulation (TMS)] in Parkinson’s disease (PD) patients and compared them to the standard treatment (levodopa) in a proper randomized, double-blind, crossover clinical trial. Methods: PD patients received three different interventions on different days: levodopa, placebo pill, and sham TMS. The motor function was assessed using simple and choice reaction time, Unified Parkinson’s Disease Rating Scale (UPDRS), finger tapping, Purdue Pegboard test, time to button up, walking time and supination-pronation. The subjective motor function was measured by a visual analogue scale (VAS). Results: The results showed that there was a significant motor function in the motor function only after the treatment with levodopa, but not after treatment with placebo pills or sham TMS. However, patients reported a similar subjective improvement in motor function indexed by VAS following these three treatments. Conclusion: These results suggest that placebo interventions in PD may have an immediate subjective sensation of improvement but result in no significant objective motor changes compared with levodopa treatment. Although physiological changes are possible after a placebo intervention, our findings suggest that the acute placebo effect in PD may be the result of the subjective change in the motor rating only.

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.

Clinical changes of cervical dystonia pattern in long-term botulinum toxin treated patients.

Cervical dystonia (CD) is a complex disorder but the response to long-term botulinum toxin (BTX) therapy is satisfactory in most cases. Bad results are attributed by some authors to changes in muscle activation. Our purpose is to verify if the change in head deviation affects negatively the response to BTX therapy in a long-term follow-up, and if there are any differences in clinical parameters of these patients in comparison to those with stable pattern. From a total of 88 patients evaluated at the Movement Disorders Clinics of Hospital das Clinicas - University of São Paulo School of Medicine between January 1993 and December 2005, 67 were included. In 24 (35.8%) change in pattern of CD was observed, in a medium follow-up period of 80 months. The time between onset of dystonia and the diagnosis of pattern change was 9.7 years. Comparing with patients with no changes in CD pattern, there were no significant statistical differences. Improvement of symptoms around 60% was reported in both groups. In conclusion, the change in head deviation observed in CD was not responsible for bad response to therapy with BTX and there were no significant differences between both groups.

Pseudoathetosis: Report of three patients

We report on 3 patients with pseudoathetosis, which are involuntary, slow, writhing movements due to loss of proprioception.

Correlation of impaired subjective visual vertical and postural instability in Parkinson's disease.

Perception of verticality is essential for postural control. On the other hand, postural instability is one of the cardinal features in Parkinsons disease (PD). Thus, the objective of this study was to evaluate the vertical perception using the subjective visual vertical test in PD patients with different degrees of postural instability and in different stages of disease. Forty five idiopathic PD patients were evaluated using the Unified Parkinsons Disease Rating Scale (UPDRS), the Hoehn and Yahr Scale, the clinical test for postural instability, and the subjective visual vertical test. Forty-five healthy individuals were evaluated in the control group. PD patients had a compromised perception of verticality and a disturbed processing of graviceptive pathways. Good correlation was also found between subjective visual vertical and postural instability. Patients with the worst postural instability had greater deviations of subjective visual vertical. There was also a positive correlation between subjective visual vertical and scores on the UPDRS and Hoehn and Yahr Scale, with good and reasonable degree of intensity, respectively. These findings suggest that the perception of verticality is affected in PD patients and this abnormal vertical perception and disturbed processing of graviceptive pathways are associated with postural instability and to a lesser degree with disease severity.

Avaliação da vertical visual subjetiva em indivíduos brasileiros normais

A funcao otolitica pode ser avaliada pela Vertical Visual Subjetiva (VVS) que determina a capacidade de um individuo julgar se objetos estao na posicao vertical na ausencia de outras referencias visuais. O objetivo deste estudo foi avaliar a VVS em individuos brasileiros normais usando um aparelho portatil. As medidas da VVS foram realizadas em 160 individuos (16 a 85 anos). O valor medio da VVS foi obtido apos dez ajustes. A VVS teve valores medios entre -2,0o e +2,4o (media=0,18o, e DP=0,77o). Nao houve diferenca entre as medias da VVS em relacao a idade (teste de Kruskal-Wallis; p=0,40), mas as faixas etarias maiores tiveram variância maior (teste de Levene; p=0,016). Os valores da VVS encontrados neste estudo foram semelhantes aos registrados na literatura. Nao houve diferenca nas medias das inclinacoes da VVS de acordo com a idade, mas foi encontrada maior variância entre individuos mais idosos.