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
8 resultados
Resultados de Busca
Agora exibindo 1 - 8 de 8
- 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.
- Case report: 5 Years follow-up on posterior hypothalamus deep brain stimulation for intractable aggressive behaviour associated with drug-resistant epilepsy(2021) GOUVEIA, Flavia Venetucci; GERMANN, Jurgen; ELIAS, Gavin JB.; HAMANI, Clement; FONOFF, Erich Talamoni; MARTINEZ, Raquel Chacon Ruiz
- 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.
- Longitudinal Changes After Amygdala Surgery for Intractable Aggressive Behavior: Clinical, Imaging Genetics, and Deformation-Based Morphometry Study-A Case Series(2021) GOUVEIA, Flavia Venetucci; GERMANN, Jurgen; MORAIS, Rosa de; FONOFF, Erich Talamoni; HAMANI, Clement; ALHO, Eduardo Joaquim; BRENTANI, Helena; MARTINS, Ana Paula; DEVENYI, Gabriel; PATEL, Raihaan; STEELE, Christopher; GRAMER, Robert; CHAKRAVARTY, Mallar; MARTINEZ, Raquel Chacon Ruiz
- Intraoperative Dopamine Release During Globus Pallidus Internus Stimulation in Parkinson's Disease(2013) MARTINEZ, Raquel C. R.; HAMANI, Clement; CARVALHO, Milene Cristina de; OLIVEIRA, Amanda Ribeiro de; ALHO, Eduardo; NAVARRO, Jessie; GHILARDI, Maria Gabriela dos Santos; BOR-SENG-SHU, Edson; HEINSEN, Helmut; OTOCH, Jose Pinhata; BRANDAO, Marcus Lira; BARBOSA, Egberto Reis; TEIXEIRA, Manoel Jacobsen; FONOFF, Erich TalamoniBackgroundIt is still unclear whether dopamine (DA) levels correlate with Parkinson's disease (PD) severity or play a role in the mechanisms of high-frequency stimulation (HFS). MethodsWe have used microdialysis to record pallidal DA in 5 patients with PD undergoing microelectrode-guided pallidotomy. ResultsWe found that patients with more severe disease and, consequently, lower pallidal DA did poorly after pallidal lesions. In the operating room, 4 of 5 patients had a significant increase in DA levels during HFS (600%, on average). To test the hypothesis that DA was important for the effects of stimulation, we correlated the amelioration in rigidity observed in the operating room with pallidal DA release. Though rigidity was 56% better during stimulation, no correlation was found between such an improvement and DA release. ConclusionsThese findings suggest that additional mechanisms not directly dependent on pallidal DA release may be involved in the clinical effects of HFS of the globus pallidus internus. (c) 2013 International Parkinson and Movement Disorder Society
- 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.
- Reduction of aggressive behaviour following hypothalamic deep brain stimulation: Involvement of 5-HT1A and testosterone(2023) GOUVEIA, Flavia Venetucci; DIWAN, Mustansir; MARTINEZ, Raquel C. R.; GIACOBBE, Peter; LIPSMAN, Nir; HAMANI, ClementBackground: Aggressive behaviour (AB) may occur in patients with different neuropsychiatric disorders. Although most patients respond to conventional treatments, a small percentage continue to experience AB despite optimized pharmacological management and are considered to be treatment-refractory. For these pa-tients, hypothalamic deep brain stimulation (pHyp-DBS) has been investigated. The hypothalamus is a key structure in the neurocircuitry of AB. An imbalance between serotonin (5-HT) and steroid hormones seems to exacerbate AB.Objectives: To test whether pHyp-DBS reduces aggressive behaviour in mice through mechanisms involving testosterone and 5-HT.Methods: Male mice were housed with females for two weeks. These resident animals become territorial and aggressive towards intruder mice placed in their cages. Residents had electrodes implanted in the pHyp. DBS was administered for 5 h/day for 8 consecutive encounters prior to the interaction with the intruder. After testing, blood and brains were recovered for measuring testosterone and 5-HT receptor density, respectively. In a second experiment, residents received WAY-100635 (5-HT1A antagonist) or saline injections prior to pHyp-DBS. After the first 4 encounters, the injection allocation was crossed, and animals received the alternative treatment during the next 4 encounters.Results: DBS-treated mice showed reduced AB that was correlated with testosterone levels and an increase in 5-HT1A receptor density in the orbitofrontal cortex and amygdala. Pre-treatment with WAY-100635 blocked the anti-aggressive effect of pHyp-DBS.Conclusions: This study shows that pHyp-DBS reduces AB in mice via changes in testosterone and 5-HT1A mechanisms.
- Refractoriness of aggressive behaviour to pharmacological treatment: cortical thickness analysis in autism spectrum disorder(2020) GOUVEIA, Flavia Venetucci; GERMANN, Juergen; DEVENYI, Gabriel A.; MORAIS, Rosa M. C. B.; SANTOS, Ana Paula M.; FONOFF, Erich T.; HAMANI, Clement; BRENTANI, Helena; CHAKRAVARTY, M. Mallar; MARTINEZ, Raquel C. R.Aggressive behaviour is a highly prevalent and devastating condition in autism spectrum disorder resulting in impoverished quality of life. Gold-standard therapies are ineffective in about 30% of patients leading to greater suffering. We investigated cortical thickness in individuals with autism spectrum disorder with pharmacological-treatment-refractory aggressive behaviour compared with those with non-refractory aggressive behaviour and observed a brain-wide pattern of local increased thickness in key areas related to emotional control and overall decreased cortical thickness in those with refractory aggressive behaviour, suggesting refractoriness could be related to specific morphological patterns. Elucidating the neurobiology of refractory aggressive behaviour is crucial to provide insights and potential avenues for new interventions.