ERICH TALAMONI FONOFF
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Neurologia, Faculdade de Medicina - Docente
LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica, Hospital das Clínicas, Faculdade de Medicina
LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica, Hospital das Clínicas, Faculdade de Medicina
19 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 19
conferenceObject Non-motor symptoms in PD candidates for DBS treatment(2016) GHILARDI, M. G. dos Santos; MARTINEZ, R. C. R.; CURY, R. G.; ARANHA, J. R.; TEIXEIRA, M. J.; BARBOSA, E. R.; FONOFF, E. T.conferenceObject Pallidal versus subthalamic stimulation for PD: Beyond the motor effects(2016) GHILARDI, M. G. dos Santos; CURY, R. G.; MARTINEZ, R. C. R.; TEIXEIRA, M. J.; BARBOSA, E. R.; FONOFF, E. T.- Bilateral Amygdala Radio-Frequency Ablation for Refractory Aggressive Behavior Alters Local Cortical Thickness to a Pattern Found in Non-refractory Patients(2021) GOUVEIA, Flavia Venetucci; GERMANN, Jurgen; DEVENYI, Gabriel A.; FONOFF, Erich T.; MORAIS, Rosa M. C. B.; BRENTANI, Helena; CHAKRAVARTY, M. Mallar; MARTINEZ, Raquel C. R.Aggressive behaviors comprise verbal and/or physical aggression directed toward oneself, others, or objects and are highly prevalent among psychiatric patients, especially patients diagnosed with autism spectrum disorder and severe intellectual disabilities. Some of these patients are considered refractory to treatment, and functional neurosurgery targeting the amygdala can result in widespread plastic brain changes that might reflect ceasing of some abnormal brain function, offering symptom alleviation. This study investigated cortical thickness changes in refractory aggressive behavior patients that were treated with bilateral amygdala ablation and compared to control patients presenting non-refractory aggressive behavior [three refractory and seven non-refractory patients, all males diagnosed with autism spectrum disorder (ASD) and intellectual disabilities]. The Overt Aggression Scale (OAS) was used to quantify behavior and magnetic resonance imaging was performed to investigate cortical thickness. Before surgery, both groups presented similar total OAS score, however refractory patients presented higher physical aggression against others. After surgery the refractory group showed 88% average reduction of aggressive behavior. Imaging analysis showed that while refractory patients present an overall reduction in cortical thickness compared to non-refractory patients across both timepoints, the local pattern of thickness difference found in areas of the neurocircuitry of aggressive behavior present before surgery is diminished and no longer detected after surgery. These results corroborate the hypotheses on induction of widespread neuronal plasticity following functional neurosurgical procedures resulting in modifications in brain morphology and improvement in behavior. Further studies are necessary to determine the underlying cause of these morphological changes and to better understand and improve treatment options.
- Does TRODAT-1 SPECT Uptake Correlate with Cerebrospinal Fluid alpha-Synuclein Levels in Mid-Stage Parkinson's Disease?(2023) COUTINHO, Artur M.; GHILARDI, Maria Gabriela; CAMPOS, Ana Carolina P.; ETCHEBEHERE, Elba; FONOFF, Fernanda C.; CURY, Rubens G.; PAGANO, Rosana L.; MARTINEZ, Raquel C. R.; FONOFF, Erich T.Background: Parkinson's disease (PD) is characterized by a progressive loss of nigrostriatal dopaminergic neurons with impaired motor and non-motor symptoms. It has been suggested that motor asymmetry could be caused due to an imbalance in dopamine levels, as visualized by dopamine transporter single emission computed tomography test (DAT-SPECT), which might be related to indirect measures of neurodegeneration, evaluated by the Montreal Cognitive Assessment (MOCA) and alpha-synuclein levels in the cerebrospinal fluid (CSF). Therefore, this study aimed to understand the correlation between disease laterality, DAT-SPECT, cognition, and alpha-synuclein levels in PD. Methods: A total of 28 patients in the moderate-advanced stage of PD were subjected to neurological evaluation, TRODAT-1-SPECT/CT imaging, MOCA, and quantification of the levels of alpha-synuclein. Results: We found that alpha-synuclein in the CSF was correlated with global cognition (positive correlation, r(2) = 0.3, p = 0.05) and DAT-SPECT concentration in the putamen (positive correlation, r(2) = 0.4, p = 0.005), and striatum (positive correlation, r(2) = 0.2, p = 0.03), thus working as a neurodegenerative biomarker. No other correlations were found between DAT-SPECT, CSF alpha-synuclein, and cognition, thus suggesting that they may be lost with disease progression. Conclusions: Our data highlight the importance of understanding the dysfunction of the dopaminergic system in the basal ganglia and its complex interactions in modulating cognition.
- 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
conferenceObject Rat brain basal ganglia imaged with optical coherence tomography: Feasibility and future perspectives(2015) ANGELOS, J. S. dos; LOPEZ, W. O. C.; MARTINEZ, R. C. R.; REIS, P. R.; TAKIMURA, C. K.; TEIXEIRA, M. J.; LEMOS NETO, P. A.; FONOFF, E. T.- Increased Anxiety-Like Behavior in the Acute Phase of a Preclinical Model of Periodontal Disease(2020) VAROTTO, Bruna Luiza Roim; MARTINEZ, Raquel Chacon Ruiz; GOUVEIA, Flavia Venetucci; ANTUNES, Geiza Fernanda; FABRI, Gisele Maria de Campos; BALLESTER, Gerson; ANTEQUERA, Reynaldo; SIQUEIRA, Silvia Regina Dowgan Tesseroli de; FONOFF, Erich Talamoni; TEIXEIRA, Manoel Jacobsen; SIQUEIRA, Jose Tadeu Tesseroli dePeriodontal disease (PD) is an infectious-inflammatory oral disease that is highly prevalent among adolescence and adulthood and can lead to chronic orofacial pain and be associated with anxiety, stress and depression. This study aimed to identify anxiety-like behaviors in the ligature-induced murine preclinical model of PD in different phases of the disease (i.e., acute vs. chronic). Also, we investigated orofacial mechanical allodynia thresholds and superficial cortical plasticity along the orofacial motor cortex in both disease phases. To this aim, 25 male Wistar rats were randomly allocated in acute (14 days) or chronic (28 days) ligature-induced-PD groups and further divided into active-PD or sham-PD. Anxiety-like behavior was evaluated using the elevated plus maze, mechanical allodynia assessed using the von Frey filaments test and superficial motor cortex mapping was performed with electrical transdural stimulation. We observed increased anxiety-like behavior in active-PD animals in the acute phase, characterized by decreased number of entries into the open arm extremities [t((1,7)) = 2.42, p = 0.04], and reduced time spent in the open arms [t((1,7)) = 3.56, p = 0.01] and in the open arm extremities [t((1,7)) = 2.75, p = 0.03]. There was also a reduction in the mechanical allodynia threshold in all active-PD animals [Acute: t((1,7)) = 8.81, p < 0.001; Chronic: t((1,6)) = 60.0, p < 0.001], that was positively correlated with anxiety-like behaviors in the acute group. No differences were observed in motor cortex mapping. Thus, our findings show the presence of anxiety-like behaviors in the acute phase of PD making this a suitable model to study the impact of anxiety in treatment response and treatment efficacy.
- 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.
- Dopamine modulates individual differences in avoidance behavior: A pharmacological, immunohistochemical, neurochemical and volumetric investigation(2020) ANTUNES, Geiza Fernanda; GOUVEIA, Flavia Venetucci; REZENDE, Fabiana Strambio; SENO, Midia Dias de Jesus; CARVALHO, Milene Cristina de; OLIVEIRA, Caroline Cruz de; SANTOS, Lennon Cardoso Tosati dos; CASTRO, Marina Correia de; KUROKI, Mayra Akemi; TEIXEIRA, Manoel Jacobsen; OTOCH, Jose Pinhata; BRANDAO, Marcus Lira; FONOFF, Erich Talamoni; MARTINEZ, Raquel Chacon RuizAvoidance behavior is a hallmark in pathological anxiety disorders and results in impairment of daily activities. Individual differences in avoidance responses are critical in determining vulnerability or resistance to anxiety disorders. Dopaminergic activation is implicated in the processing of avoidance responses; however, the mechanisms underlying these responses are unknown. In this sense, we used a preclinical model of avoidance behavior to investigate the possibility of an intrinsic differential dopaminergic pattern between good and poor performers. The specific goal was to assess the participation of dopamine (DA) through pharmacological manipulation, and we further evaluated the effects of systemic injections of the dopaminergic receptor type 1 (D1 antagonist - SCH23390) and dopaminergic receptor type 2 (D2 antagonist - sulpiride) antagonists in the good performers. Additionally, we evaluated the effects of intra-amygdala microinjection of a D1 antagonist (SCH23390) and a D2 antagonist (sulpiride) in good performers as well as intra-amygdala microinjection of a D1 agonist (SKF38393) and D2 agonist (quinpirole) in poor performers. Furthermore, we quantified the contents of dopamine and metabolites (3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)) in the amygdala, evaluated the basal levels of tyrosine hydroxylase expression (catecholamine synthesis enzyme) and measured the volume of the substantia nigra, ventral tegmental area and locus coeruleus. Our results showed that it could be possible to convert animals from good to poor performers, and vice versa, by intra-amygdala (basolateral and central nucleus) injections of D1 receptor antagonists in good performers or D2 receptor agonists in poor performers. Additionally, the good performers had lower levels of DOPAC and HVA in the amygdala, an increase in the total volume of the amygdala (AMG), substantia nigra (SN), ventral tegmental area (VTA) and locus coeruleus (LC), and an increase in the number of tyrosine hydroxylase-positive cells in SN, VTA and LC, which positively correlates with the avoidance behavior. Taken together, our data show evidence for a dopaminergic signature of avoidance performers, emphasizing the role of distinct dopaminergic receptors in individual differences in avoidance behavior based on pharmacological, immunohistochemical, neurochemical and volumetric analyses. Our findings provide a better understanding of the role of the dopaminergic system in the execution of avoidance behavior.
- 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.