RAQUEL CHACON RUIZ MARTINEZ
Projetos de Pesquisa
Unidades Organizacionais
Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
LIM/23 - Laboratório de Psicopatologia e Terapêutica Psiquiátrica, Hospital das Clínicas, Faculdade de Medicina
LIM/23 - Laboratório de Psicopatologia e Terapêutica Psiquiátrica, Hospital das Clínicas, Faculdade de Medicina
5 resultados
Resultados de Busca
Agora exibindo 1 - 5 de 5
- Long-Term Follow-Up on Bilateral Posterior Hypothalamic Deep Brain Stimulation for Treating Refractory Aggressive Behavior in a Patient with Cri du Chat Syndrome: Analysis of Clinical Data, Intraoperative Microdialysis, and Imaging Connectomics(2023) RIOS, Adriana Lucia Lopez; GERMANN, Jurgen; HUTCHISON, William D.; POSADA, Luis Fernando Botero; VELASQUEZ, Luisa Fernanda Ahunca; JIMENEZ, Francisco Aureliano Garcia; ESCOBAR, Jose Miguel Gloria; MARTINEZ, Raquel Chacon Ruiz; HAMANI, Clement; LEBRUN, Ivo; AUADA, Aline V. V.; BRAVO, Carlos Anibal Restrepo; GOUVEIA, Flavia VenetucciPosterior hypothalamic-deep brain stimulation (pHyp-DBS) has been reported as a successful treatment for reducing refractory aggressive behaviors in patients with distinct primary diagnoses. Here, we report on a patient with cri du chat syndrome presenting severe self-injury and aggressive behaviors toward others, who was treated with pHyp-DBS. Positive results were observed at long-term follow-up in aggressive behavior and quality of life. Intraoperative microdialysis and imaging connectomics analysis were performed to investigate possible mechanisms of action. Our results suggest the involvement of limbic and motor areas and alterations in main neurotransmitter levels in the targeted area that are associated with positive results following treatment.
- Fully Automated Habenula Segmentation Provides Robust and Reliable Volume Estimation Across Large Magnetic Resonance Imaging Datasets, Suggesting Intriguing Developmental Trajectories in Psychiatric Disease(2020) GERMANN, Juergen; GOUVEIA, Flavia Venetucci; MARTINEZ, Raquel C. R.; ZANETTI, Marcus Vinicius; DURAN, Fabio Luis de Souza; CHAIM-AVANCINI, Tiffany M.; SERPA, Mauricio H.; CHAKRAVARTY, M. Mallar; DEVENYI, Gabriel A.Studies of habenula (Hb) function and structure provided evidence of its involvement in psychiatric disorders, including schizophrenia and bipolar disorder. Previous studies using magnetic resonance imaging (manual/semi-automated segmentation) have reported conflicting results. Aiming to improve Hb segmentation reliability and the study of large datasets, we describe a fully automated protocol that was validated against manual segmentations and applied to 3 datasets (childhood/adolescence and adult bipolar disorder and schizophrenia). It achieved reliable Hb segmentation, providing robust volume estimations across a large age range and varying image acquisition parameters. Applying it to clinically relevant datasets, we found smaller Hb volumes in the adult bipolar disorder dataset and larger volumes in the adult schizophrenia dataset compared with healthy control subjects. There are indications that Hb volume in both groups shows deviating developmental trajectories early in life. This technique sets a precedent for future studies, as it allows for fast and reliable Hb segmentation and will be publicly available.
- Effect of Subthalamic Stimulation and Electrode Implantation in the Striatal Microenvironment in a Parkinson's Disease Rat Model(2022) CAMPOS, Ana Carolina Pinheiro; MARTINEZ, Raquel Chacon Ruiz; AUADA, Aline Vivian Vatti; LEBRUN, Ivo; FONOFF, Erich Talamoni; HAMANI, Clement; PAGANO, Rosana LimaDeep brain stimulation (DBS) of the subthalamic nucleus (STN) is considered the gold-standard treatment for PD; however, underlying therapeutic mechanisms need to be comprehensively elucidated, especially in relation to glial cells. We aimed to understand the effects of STN-microlesions and STN-DBS on striatal glial cells, inflammation, and extracellular glutamate/GABAergic concentration in a 6-hydroxydopamine (6-OHDA)-induced PD rat model. Rats with unilateral striatal 6-OHDA and electrodes implanted in the STN were divided into two groups: DBS OFF and DBS ON (5 days/2 h/day). Saline and 6-OHDA animals were used as control. Akinesia, striatal reactivity for astrocytes, microglia, and inflammasome, and expression of cytokines, cell signaling, and excitatory amino acid transporter (EAAT)-2 were examined. Moreover, striatal microdialysis was performed to evaluate glutamate and GABA concentrations. The PD rat model exhibited akinesia, increased inflammation, glutamate release, and decreased glutamatergic clearance in the striatum. STN-DBS (DBS ON) completely abolished akinesia. Both STN-microlesion and STN-DBS decreased striatal cytokine expression and the relative concentration of extracellular glutamate. However, STN-DBS inhibited morphological changes in astrocytes, decreased inflammasome reactivity, and increased EAAT2 expression in the striatum. Collectively, these findings suggest that the beneficial effects of DBS are mediated by a combination of stimulation and local microlesions, both involving the inhibition of glial cell activation, neuroinflammation, and glutamate excitotoxicity.
- Directional Deep Brain Stimulation of the Posteromedial Hypothalamus for Refractory Intermittent Explosive Disorder: A Case Series Using a Novel Neurostimulation Device and Intraoperative Microdialysis(2021) LOPEZ, William Omar Contreras; NAVARRO, Paula Alejandra; GOUVEIA, Flavia Venetucci; FONOFF, Erich Talamoni; LEBRUN, Ivo; AUADA, Aline V. V.; ALHO, Eduardo Joaquim Lopes; MARTINEZ, Raquel C. R.BACKGROUND: Intermittent explosive disorder (IED) is a psychiatric disorder characterized by recurrent outbursts of aggressive behavior. Deep brain stimulation (DBS) in the posteromedial nucleus of the hypothalamus (pHyp) is an alternative therapy for extreme cases and shows promising results. Intraoperative microdialysis can help elucidate the neurobiological mechanism of pHyp-DBS. We sought to evaluate efficacy and safety of pHyp-DBS using 8-contact directional leads in patients with refractory IED (rIED) and the accompanying changes in neurotransmitters. METHODS: This was a prospective study in which patients with a diagnosis of rIED were treated with pHyp-DBS for symptom alleviation. Bilateral pHyp-DBS was performed with 8-contact directional electrodes. Follow-up was performed at 3, 6, and 12 months after surgery. RESULTS: Four patients (3 men, mean age 27 +/- 2.8 years) were included. All patients were diagnosed with rIED and severe intellectual disability. Two patients had congenital rubella, one had a co-diagnosis of infantile autism, and the fourth presented with drug-resistant epilepsy. There was a marked increase in the levels of gamma-aminobutyric acid and glycine during intraoperative stimulation. The average improvement in aggressive behavior in the last follow-up was 6 points (D: 50%, P [ 0.003) while also documenting an important improvement of the Short Form Health Survey in all domains except bodily pain. No adverse events associated with pHyp-DBS were observed. CONCLUSIONS: This is the first study to show the safety and beneficial effect of directional lead pHyp-DBS in patients with rIED and to demonstrate the corresponding mechanism of action through increases in gamma-aminobutyric acid and glycine concentration in the pHyp.
- Multi-centre analysis of networks and genes modulated by hypothalamic stimulation in patients with aggressive behaviours(2023) GOUVEIA, Flavia Venetucci; GERMANN, Jurgen; ELIAS, Gavin J. B.; BOUTET, Alexandre; LOH, Aaron; RIOS, Adriana Lucia Lopez; DIAZ, Cristina Torres; LOPEZ, William Omar Contreras; MARTINEZ, Raquel Chacon Ruiz; FONOFF, Erich Talamoni; BENEDETTI-ISAAC, Juan Carlos; GIACOBBE, Peter; PAVA, Pablo M. Arango; YAN, Han; IBRAHIM, George M.; LIPSMAN, Nir; LOZANO, Andres; HAMANI, ClementDeep brain stimulation targeting the posterior hypothalamus (pHyp-DBS) is being investigated as a treatment for refractory aggressive behavior, but its mechanisms of action remain elusive. We conducted an integrated imaging analysis of a large multi-centre dataset, incorporating volume of activated tissue modeling, probabilistic mapping, normative connectomics, and atlas-derived transcriptomics. Ninety-one percent of the patients responded positively to treatment, with a more striking improvement recorded in the pediatric population. Probabilistic mapping revealed an optimized surgical target within the posterior-inferior-lateral region of the posterior hypothalamic area. Normative connectomic analyses identified fiber tracts and functionally connected with brain areas associated with sensorimotor function, emotional regulation, and monoamine production. Functional connectivity between the target, periaqueductal gray and key limbic areas - together with patient age - were highly predictive of treatment outcome. Transcriptomic analysis showed that genes involved in mechanisms of aggressive behavior, neuronal communication, plasticity and neuroinflammation might underlie this functional network.