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
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conferenceObject Lateral Insertion of Leads and Treatment Outcomes in Ventral Capsule/Ventral Striatum Deep Brain Stimulation for Obsessive-Compulsive Disorder(2020) LOPES, Antonio; GODINHO, Fabio; MURAKAMI, Mario; IGLESIO, Ricardo; LEEMANS, Alexander; FONOFF, Erich; MIGUEL, Euripedes; TEIXEIRA, Manoel; ARANTES, Paula- Motor cortex stimulation inhibits thalamic sensory neurons and enhances activity of PAG neurons: Possible pathways for antinociception(2012) PAGANO, Rosana L.; FONOFF, Erich T.; DALE, Camila S.; BALLESTER, Gerson; TEIXEIRA, Manoel J.; BRITTO, Luiz R. G.Motor cortex stimulation is generally suggested as a therapy for patients with chronic and refractory neuropathic pain. However, the mechanisms underlying its analgesic effects are still unknown. In a previous study, we demonstrated that cortical stimulation increases the nociceptive threshold of naive conscious rats with opioid participation. In the present study, we investigated the neurocircuitry involved during the antinociception induced by transdural stimulation of motor cortex in naive rats considering that little is known about the relation between motor cortex and analgesia. The neuronal activation patterns were evaluated in the thalamic nuclei and midbrain periaqueductal gray. Neuronal inactivation in response to motor cortex stimulation was detected in thalamic sites both in terms of immunolabeling (Zif268/Fos) and in the neuronal firing rates in ventral posterolateral nuclei and centromedian-parafascicular thalamic complex. This effect was particularly visible for neurons responsive to nociceptive peripheral stimulation. Furthermore, motor cortex stimulation enhanced neuronal firing rate and Fos immunoreactivity in the ipsilateral periaqueductal gray. We have also observed a decreased Zif268, delta-aminobutyric acid (GABA), and glutamic acid decarboxylase expression within the same region, suggesting an inhibition of GABAergic interneurons of the midbrain periaqueductal gray, consequently activating neurons responsible for the descending pain inhibitory control system. Taken together, the present findings suggest that inhibition of thalamic sensory neurons and disinhibition of the neurons in periaqueductal gray are at least in part responsible for the motor cortex stimulation-induced antinociception.
- Magnetic resonance diffusion tensor imaging for the pedunculopontine nucleus: proof of concept and histological correlation(2017) ALHO, A. T. D. L.; HAMANI, C.; ALHO, E. J. L.; SILVA, R. E. da; SANTOS, G. A. B.; NEVES, R. C.; CARREIRA, L. L.; ARAUJO, C. M. M.; MAGALHAES, G.; COELHO, D. B.; ALEGRO, M. C.; MARTIN, M. G. M.; GRINBERG, L. T.; PASQUALUCCI, C. A.; HEINSEN, H.; FONOFF, E. T.; AMARO JR., E.The pedunculopontine nucleus (PPN) has been proposed as target for deep brain stimulation (DBS) in patients with postural instability and gait disorders due to its involvement in muscle tonus adjustments and control of locomotion. However, it is a deep-seated brainstem nucleus without clear imaging or electrophysiological markers. Some studies suggested that diffusion tensor imaging (DTI) may help guiding electrode placement in the PPN by showing the surrounding fiber bundles, but none have provided a direct histological correlation. We investigated DTI fractional anisotropy (FA) maps from in vivo and in situ postmortem magnetic resonance images (MRI) compared to histological evaluations for improving PPN targeting in humans. A post-mortem brain was scanned in a clinical 3T MR system in situ. Thereafter, the brain was processed with a special method ideally suited for cytoarchitectonic analyses. Also, nine volunteers had in vivo brain scanning using the same MRI protocol. Images from volunteers were compared to those obtained in the post-mortem study. FA values of the volunteers were obtained from PPN, inferior colliculus, cerebellar crossing fibers and medial lemniscus using histological data and atlas information. FA values in the PPN were significantly lower than in the surrounding white matter region and higher than in areas with predominantly gray matter. In Nissl-stained histologic sections, the PPN extended for more than 10 mm in the rostro-caudal axis being closely attached to the lateral parabrachial nucleus. Our DTI analyses and the spatial correlation with histological findings proposed a location for PPN that matched the position assigned to this nucleus in the literature. Coregistration of neuroimaging and cytoarchitectonic features can add value to help establishing functional architectonics of the PPN and facilitate neurosurgical targeting of this extended nucleus.
conferenceObject The Effect Of Epidural Ozone Therapy In Patients With Chronic Pain Related To Failed Back Surgery Syndrome.(2013) FONOFF, Erich T.; MAGALHAES, Francisco N.; TEIXEIRA, Manoel J.- Use of computational fluid dynamics for 3D fiber tract visualization on human high-thickness histological slices: histological mesh tractography(2021) ALHO, Eduardo Joaquim Lopes; FONOFF, Erich T.; ALHO, Ana Tereza Di Lorenzo; NAGY, Jozsef; HEINSEN, HelmutUnderstanding the intricate three-dimensional relationship between fiber bundles and subcortical nuclei is not a simple task. It is of paramount importance in neurosciences, especially in the field of functional neurosurgery. The current methods for in vivo and post mortem fiber tract visualization have shortcomings and contributions to the field are welcome. Several tracts were chosen to implement a new technique to help visualization of white matter tracts, using high-thickness histology and dark field images. Our study describes the use of computational fluid dynamic simulations for visualization of 3D fiber tracts segmented from dark field microscopy in high-thickness histological slices (histological mesh tractography). A post mortem human brain was MRI scanned prior to skull extraction, histologically processed and serially cut at 430 mu m thickness as previously described by our group. High-resolution dark field images were used to segment the outlines of the structures. These outlines served as basis for the construction of a 3D structured mesh, were a Finite Volume Method (FVM) simulation of water flow was performed to generate streamlines representing the geometry. The simulations were accomplished by an open source computer fluid dynamics software. The resulting simulation rendered a realistic 3D impression of the segmented anterior commissure, the left anterior limb of the internal capsule, the left uncinate fascicle, and the dentato-rubral tracts. The results are in line with clinical findings, diffusion MR imaging and anatomical dissection methods.
- Lateral hypothalamic activity indicates hunger and satiety states in humans(2017) TALAKOUB, Omid; PAIVA, Raquel R.; MILOSEVIC, Matija; HOEXTER, Marcelo Q.; FRANCO, Ruth; ALHO, Eduardo; NAVARRO, Jessie; PEREIRA JR., Jose F.; POPOVIC, Milos R.; SAVAGE, Cary; LOPES, Antonio C.; ALVARENGA, Pedro; DAMIANI, Durval; TEIXEIRA, Manoel J.; MIGUEL, Euripides C.; FONOFF, Erich T.; BATISTUZZO, Marcelo C.; HAMANI, ClementLateral hypothalamic area (LHA) local field potentials (LFPs) were recorded in a Prader-Willi patient undergoing deep brain stimulation (DBS) for obesity. During hunger, exposure to food-related cues induced an increase in beta/low-gamma activity. In contrast, recordings during satiety were marked by prominent alpha rhythms. Based on these findings, we have delivered alpha-frequency DBS prior to and during food intake. Despite reporting an early sensation of fullness, the patient continued to crave food. This suggests that the pattern of activity in LHA may indicate hunger/satiety states in humans but attest to the complexity of conducting neuromodulation studies in obesity.
- Peduncolopontine DBS improves balance in progressive supranuclear palsy: Instrumental analysis(2016) SOUZA, Carolina de Oliveira; LIMA-PARDINI, Andrea Cristina de; COELHO, Daniel Boari; MACHADO, Rachael Brant; ALHO, Eduardo Joaquim Lopes; ALHO, Ana Tereza Di Lorenzo; TEIXEIRA, Luis Augusto; TEIXEIRA, Manoel Jacobsen; BARBOSA, Egberto Reis; FONOFF, Erich Talamoni
- High thickness histological sections as alternative to study the three-dimensional microscopic human sub-cortical neuroanatomy(2018) ALHO, Eduardo Joaquim Lopes; ALHO, Ana Tereza Di Lorenzo; GRINBERG, Lea; AMARO JR., Edson; SANTOS, Glaucia Aparecida Bento dos; SILVA, Rafael Emidio da; NEVES, Ricardo Caires; ALEGRO, Maryana; COELHO, Daniel Boari; TEIXEIRA, Manoel Jacobsen; FONOFF, Erich Talamoni; HEINSEN, HelmutStereotaxy is based on the precise image-guided spatial localization of targets within the human brain. Even with the recent advances in MRI technology, histological examination renders different (and complementary) information of the nervous tissue. Although several maps have been selected as a basis for correlating imaging results with the anatomical locations of sub-cortical structures, technical limitations interfere in a point-to-point correlation between imaging and anatomy due to the lack of precise correction for post-mortem tissue deformations caused by tissue fixation and processing. We present an alternative method to parcellate human brain cytoarchitectural regions, minimizing deformations caused by post-mortem and tissue-processing artifacts and enhancing segmentation by means of modified high thickness histological techniques and registration with MRI of the same specimen and into MNI space (ICBM152). A three-dimensional (3D) histological atlas of the human thalamus, basal ganglia, and basal forebrain cholinergic system is displayed. Structure's segmentations were performed in high-resolution dark-field and light-field microscopy. Bidimensional non-linear registration of the histological slices was followed by 3D registration with in situ MRI of the same subject. Manual and automated registration procedures were adopted and compared. To evaluate the quality of the registration procedures, Dice similarity coefficient and normalized weighted spectral distance were calculated and the results indicate good overlap between registered volumes and a small shape difference between them in both manual and automated registration methods. High thickness high-resolution histological slices in combination with registration to in situ MRI of the same subject provide an effective alternative method to study nuclear boundaries in the human brain, enhancing segmentation and demanding less resources and time for tissue processing than traditional methods.
- Parkinson's disease and pain: Modulation of nociceptive circuitry in a rat model of nigrostriatal lesion(2019) DOMENICI, Roberta A.; CAMPOS, Aria Carolina P.; MACIEL, Soraya T.; BERZUINO, Miria B.; HERNANDES, Marina S.; FONOFF, Erich T.; PAGANO, Rosana L.Parkinson's disease (PD) is a neurodegenerative disorder that causes progressive dysfunction of dopaminergic and non-dopaminergic neurons, generating motor and nonmotor signs and symptoms. Pain is reported as the most bothersome nonmotor symptom in PD; however, pain remains overlooked and poorly understood. In this study, we evaluated the nociceptive behavior and the descending analgesia circuitry in a rat model of PD. Three independent experiments were performed to investigate: i) thermal nociceptive behavior; ii) mechanical nociceptive behavior and dopaminergic repositioning; and iii) modulation of the pain control circuitry. The rat model of PD, induced by unilateral striatal 6-hydroxydopamine (6-OHDA), did not interfere with thermal nociceptive responses; however, the mechanical nociceptive threshold was decreased bilaterally compared to that of naive or striatal saline-injected rats. This response was reversed by apomorphine or levodopa treatment. Striatal 6-OHDA induced motor impairments and reduced dopaminergic neuron immunolabeling as well as the pattern of neuronal activation (c-Fos) in the substantia nigra ipsilateral (IPL) to the lesion. In the midbrain periaqueductal gray (PAG), 6-OHDA-induced lesion increased IPL and decreased contralateral PAG GABAergic labeling compared to control. In the dorsal horn of the spinal cord, lesioned rats showed bilateral inhibition of enkephalin and p-opioid receptor labeling. Taken together, we demonstrated that the unilateral 6-OHDA-induced PD model induces bilateral mechanical hypernociception, which is reversed by dopamine restoration, changes in the PAG circuitry, and inhibition of spinal opioidergic regulation, probably due to impaired descending analgesic control. A better understanding of pain mechanisms in PD patients is critical for developing better therapeutic strategies to improve their quality of life.
- Relationship Between Posturography, Clinical Balance and Executive Function in Parkinson ' s Disease(2019) SOUZA, Carolina de Oliveira; VOOS, Mariana Callil; BARBOSA, Alessandra Ferreira; CHEN, Janini; FRANCATO, Debora Cristina Valente; MILOSEVIC, Matija; POPOVIC, Milos; FONOFF, Erich Talamoni; CHIEN, Hsin Fen; BARBOSA, Egberto ReisThis study aimed to evaluate the relationship between posturography, clinical balance, and executive function tests in Parkinson ' s disease (PD). Seventy-one people participated in the study. Static posturography evaluated the center of pressure fluctuations in quiet standing and dynamic posturography assessed sit-to-stand, tandem walk, and step over an obstacle. Functional balance was evaluated by Berg Balance Scale, MiniBESTest, and Timed Up and Go test. Executive function was assessed by Trail Making Test (TMT) and semantic verbal fluency test. Step over obstacle measures (percentage of body weight transfer and movement time) were moderately correlated to Timed Up and Go, part B of TMT and semantic verbal fluency (r > 0.40; p < 0.05 in all relationships). Stepping over an obstacle assesses the responses to internal perturbations. Participants with shorter movement times and higher percentage of body weight transfer (higher lift up index) on this task were also faster in Timed Up and Go, part B of TMT, and semantic verbal fluency. All these tasks require executive function (problem solving, sequencing, shifting attention), which is affected by PD and contribute to postural assessment.