RESUMEN
Simulation theories predict that the observation of other's expressions modulates neural activity in the same centres controlling their production. This hypothesis has been developed by two models, postulating that the visual input is directly projected either to the motor system for action recognition (motor resonance) or to emotional/interoceptive regions for emotional contagion and social synchronization (emotional resonance). Here we investigated the role of frontal/insular regions in the processing of observed emotional expressions by combining intracranial recording, electrical stimulation and effective connectivity. First, we intracranially recorded from prefrontal, premotor or anterior insular regions of 44 patients during the passive observation of emotional expressions, finding widespread modulations in prefrontal/insular regions (anterior cingulate cortex, anterior insula, orbitofrontal cortex and inferior frontal gyrus) and motor territories (Rolandic operculum and inferior frontal junction). Subsequently, we electrically stimulated the activated sites, finding that (i) in the anterior cingulate cortex and anterior insula, the stimulation elicited emotional/interoceptive responses, as predicted by the 'emotional resonance model'; (ii) in the Rolandic operculum it evoked face/mouth sensorimotor responses, in line with the 'motor resonance' model; and (iii) all other regions were unresponsive or revealed functions unrelated to the processing of facial expressions. Finally, we traced the effective connectivity to sketch a network-level description of these regions, finding that the anterior cingulate cortex and the anterior insula are reciprocally interconnected while the Rolandic operculum is part of the parieto-frontal circuits and poorly connected with the former. These results support the hypothesis that the pathways hypothesized by the 'emotional resonance' and the 'motor resonance' models work in parallel, differing in terms of spatio-temporal fingerprints, reactivity to electrical stimulation and connectivity patterns.
Asunto(s)
Emociones , Expresión Facial , Humanos , Emociones/fisiología , Masculino , Femenino , Adulto , Adulto Joven , Persona de Mediana Edad , Mapeo Encefálico/métodos , Estimulación Eléctrica , Corteza Insular/diagnóstico por imagen , Corteza Insular/fisiología , Imagen por Resonancia Magnética/métodosRESUMEN
Although clinical neuroscience and the neuroscience of consciousness have long sought mechanistic explanations of tactile-awareness disorders, mechanistic insights are rare, mainly because of the difficulty of depicting the fine-grained neural dynamics underlying somatosensory processes. Here, we combined the stereo-EEG responses to somatosensory stimulation with the lesion mapping of patients with a tactile-awareness disorder, namely tactile extinction. Whereas stereo-EEG responses present different temporal patterns, including early/phasic and long-lasting/tonic activities, tactile-extinction lesion mapping co-localizes only with the latter. Overlaps are limited to the posterior part of the perisylvian regions, suggesting that tonic activities may play a role in sustaining tactile awareness. To assess this hypothesis further, we correlated the prevalence of tonic responses with the tactile-extinction lesion mapping, showing that they follow the same topographical gradient. Finally, in parallel with the notion that visuotactile stimulation improves detection in tactile-extinction patients, we demonstrated an enhancement of tonic responses to visuotactile stimuli, with a strong voxel-wise correlation with the lesion mapping. The combination of these results establishes tonic responses in the parietal operculum as the ideal neural correlate of tactile awareness.
Asunto(s)
Hipoestesia/fisiopatología , Lóbulo Parietal/fisiopatología , Percepción del Tacto/fisiología , Adulto , Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The neural correlates of perceptual awareness are usually investigated by comparing experimental conditions in which subjects are aware or not aware of the delivered stimulus. This, however, implies that subjects report their experience, possibly biasing the neural responses with the postperceptual processes involved. This Neuro Forum article reviews evidence from an electroencephalography (EEG) study by Cohen and colleagues (Cohen M, Ortego K, Kyroudis A, Pitts M. J Neurosci 40: 4925-4935, 2020) addressing the importance of no-report paradigms in the neuroscience of consciousness. In particular, authors show that P3b, one of the proposed canonical "signatures" of the conscious processing, is strongly elicited only when subjects have to report their experience, proposing a reconsideration in the approach to the neuroscience of consciousness.
Asunto(s)
Estado de Conciencia , Neurociencias , Concienciación , Electroencefalografía , HumanosRESUMEN
BACKGROUND & AIMS: Potential celiac disease is characterized by positive results from serologic tests for tissue transglutaminase antibodies (anti-TG2) but normal duodenal architecture (Marsh stages 0-1). There is controversy over the best way to manage these patients. We investigated risk factors associated with the development of villous atrophy in children with potential celiac disease. METHODS: We performed a prospective study of 280 children (ages 2-18 years) in Italy with suspected celiac disease, followed for up to 12 years (range, 18-150 months; median 60 months). The subjects had 2 consecutive positive results from tests for anti-TG2, tested positive for the endomysial antibody (anti-EMA), had total serum levels of immunoglobulin A in the normal range, normal duodenal architecture (Marsh stages 0-1) in 5 biopsies, and HLA DQ2- or DQ8-positive haplotypes. The children underwent serologic tests and clinical analyses every 6 months and a small bowel biopsy was taken every 2 years. A total of 210 patients of the original cohort were assessed at the 9-year follow-up evaluation. We performed multivariate analyses of clinical, genetic, and histologic data to identify factors associated with progression to villous atrophy. RESULTS: During the follow-up period, 42 (15%) of 280 children developed villous atrophy, whereas 89 (32%) children no longer tested positive for anti-TG2 or anti-EMA. The cumulative incidence of progression to villous atrophy was 43% at 12 years. In multivariate analysis, the baseline factors most strongly associated with development of villous atrophy were numbers of γδ intraepithelial lymphocyte cells followed by age and homozygosity for the HLA DQB1*02. In discriminant analysis, these baseline factors identified 80% of the children who developed baseline atrophy. CONCLUSIONS: In a long-term study of 280 children with suspected celiac disease (based on anti-TG2 and anti-EMA) on gluten-containing diets, the cumulative incidence of progression to villous atrophy was 43% over a 12-year period. We identified factors that can be used to identify children at highest risk for villous atrophy. This approach might be used to determine whether children with suspected celiac disease should immediately start a gluten-free diet or be monitored on their regular diet.
Asunto(s)
Atrofia/patología , Autoanticuerpos/sangre , Enfermedad Celíaca/patología , Proteínas de Unión al GTP/inmunología , Mucosa Intestinal/patología , Transglutaminasas/inmunología , Adolescente , Atrofia/sangre , Atrofia/epidemiología , Atrofia/inmunología , Autoanticuerpos/inmunología , Biopsia , Enfermedad Celíaca/sangre , Enfermedad Celíaca/dietoterapia , Enfermedad Celíaca/inmunología , Niño , Preescolar , Dieta Sin Gluten , Progresión de la Enfermedad , Duodeno , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Italia , Masculino , Estudios Prospectivos , Proteína Glutamina Gamma Glutamiltransferasa 2RESUMEN
In this prospective study, we evaluated the effect of gluten-free diet (GFD) in a cohort of 65 children with potential celiac disease. Patients received GFD for signs/symptoms (Nâ=â47) or parents' choice (Nâ=â18). Most frequent signs/symptoms were low body mass index (36%), recurrent abdominal pain (34%), and diarrhea (19%). Of the 35/47 patients followed-up on GFD, only 54% (19/35) showed a complete clinical response. In 9 of 65 patients an intestinal biopsy was also performed after at least 1 year of GFD. No significant differences were observed in terms of Marsh grade (Pâ=â0.33), lamina propria CD25+ cells (Pâ=â0.80), CD3+ (Pâ=â0.9), and γδ+ (Pâ=â0.59) intraepithelial lymphocytes density and intestinal anti-TG2 deposits (Pâ=â0.60). In conclusion, caution is necessary before attributing all symptoms to gluten in this condition.
Asunto(s)
Enfermedad Celíaca/dietoterapia , Dieta Sin Gluten/métodos , Mucosa Intestinal/patología , Adolescente , Enfermedad Celíaca/patología , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Intracranial EEG data offer a unique spatio-temporal precision to investigate human brain functions. Large datasets have become recently accessible thanks to new iEEG data-sharing practices and tighter collaboration with clinicians. Yet, the complexity of such datasets poses new challenges, especially regarding the visualization and anatomical display of iEEG. NEW METHOD: We introduce HiBoP, a multi-modal visualization software specifically designed for large groups of patients and multiple experiments. Its main features include the dynamic display of iEEG responses induced by tasks/stimulations, the definition of Regions and electrodes Of Interest, and the shift between group-level and individual-level 3D anatomo-functional data. RESULTS: We provide a use-case with data from 36 patients to reveal the global cortical dynamics following tactile stimulation. We used HiBoP to visualize high-gamma responses [50-150â¯Hz], and define three major response components in primary somatosensory and premotor cortices and parietal operculum. COMPARISON WITH EXISTING METHODS(S): Several iEEG softwares are now publicly available with outstanding analysis features. Yet, most were developed in languages (Python/Matlab) chosen to facilitate the inclusion of new analysis by users, rather than the quality of the visualization. HiBoP represents a visualization tool developed with videogame standards (Unity/C#), and performs detailed anatomical analysis rapidly, across multiple conditions, patients, and modalities with an easy export toward third-party softwares. CONCLUSION: HiBoP provides a user-friendly environment that greatly facilitates the exploration of large iEEG datasets, and helps users decipher subtle structure/function relationships.
Asunto(s)
Programas Informáticos , Humanos , Masculino , Femenino , Adulto , Electrocorticografía/métodos , Encéfalo/fisiología , Encéfalo/diagnóstico por imagen , Conjuntos de Datos como Asunto , Mapeo Encefálico/métodosRESUMEN
BACKGROUND: Scalp EEG is one of the main tools in the clinical evaluation of epilepsy. In some cases intracranial Interictal Epileptiform Discharges (IEDs) are not visible from the scalp. Recent studies have shown the feasibility of revealing them in the EEG if their timings are extracted from simultaneous intracranial recordings, but their potential for the localization of the epileptogenic zone is not yet well defined. NEW METHOD: We recorded simultaneous high-density EEG (HD-EEG) and stereo-electroencephalography (SEEG) during interictal periods in 8 patients affected by drug-resistant focal epilepsy. We identified IEDs in the SEEG and systematically analyzed the time-locked signals on the EEG by means of evoked potentials, topographical analysis and Electrical Source Imaging (ESI). The dataset has been standardized and is being publicly shared. RESULTS: Our results showed that IEDs that were not clearly visible at single-trials could be uncovered by averaging, in line with previous reports. They also showed that their topographical voltage distributions matched the position of the SEEG electrode where IEDs had been identified, and that ESI techniques can reconstruct it with an accuracy of â¼2â¯cm. Finally, the present dataset provides a reference to test the accuracy of different methods and parameters. COMPARISON WITH EXISTING METHODS: Our study is the first to systematically compare ESI methods on simultaneously recorded IEDs, and to share a public resource with in-vivo data for their evaluation. CONCLUSIONS: Simultaneous HD-EEG and SEEG recordings can unveil hidden IEDs whose origins can be reconstructed using topographical and ESI analyses, but results depend on the selected methods and parameters.
Asunto(s)
Epilepsia Refractaria , Electroencefalografía , Cuero Cabelludo , Humanos , Electroencefalografía/métodos , Masculino , Cuero Cabelludo/fisiopatología , Femenino , Adulto , Epilepsia Refractaria/fisiopatología , Epilepsia Refractaria/diagnóstico , Adulto Joven , Encéfalo/fisiopatología , Epilepsias Parciales/fisiopatología , Epilepsias Parciales/diagnóstico , Persona de Mediana Edad , Procesamiento de Señales Asistido por Computador , Técnicas Estereotáxicas , Mapeo Encefálico/métodos , Potenciales Evocados/fisiología , AdolescenteRESUMEN
Prostate cancer (PC) is still the second cause of cancer-related death among men. Although patients with metastatic presentation have an ominous outcome, the vast majority of PCs are diagnosed at an early stage. Nonetheless, even among patients with clinically localized disease the outcome may vary considerably. Other than androgen sensitivity, little is known about which other signaling pathways are deranged in aggressive, localized cancers. The elucidation of such pathways may help to develop innovative therapies aimed at specific molecular targets. We report that in a hormone-sensitive PC cell line, LNCaP, Notch3 was activated by hypoxia and sustained cell proliferation and colony formation in soft agar. Hypoxia also modulated cellular cholesterol content and the number and size of lipid rafts, causing a coalescence of small rafts into bigger clusters; under this experimental condition, Notch3 migrated from the non-raft into the raft compartment where it colocalized with the γ-secretase complex. We also looked at human PC biopsies and found that expression of Notch3 positively correlated with Gleason score and with expression of carbonic anhydrase IX, a marker of hypoxia. In conclusion, hypoxia triggers the activation of Notch3, which, in turn, sustains proliferation of PC cells. Notch3 pathway represents a promising target for adjuvant therapy in patients with PC.
Asunto(s)
Neoplasias Hormono-Dependientes/metabolismo , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Receptores Notch/genética , Antígenos de Neoplasias/metabolismo , Biopsia , Anhidrasa Carbónica IX , Anhidrasas Carbónicas/metabolismo , Línea Celular Tumoral , Proliferación Celular , Colesterol/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Hipoxia/metabolismo , Hipoxia/patología , Masculino , Microdominios de Membrana/metabolismo , Terapia Molecular Dirigida , Estadificación de Neoplasias , Neoplasias Hormono-Dependientes/genética , Neoplasias Hormono-Dependientes/patología , Neoplasias de la Próstata/genética , Receptor Notch3 , Receptores Notch/biosíntesisRESUMEN
SUMMARY: In this review, we retrace the results of 70 years of human cingulate cortex (CC) intracerebral electrical stimulation and discuss its contribution to our understanding of the anatomofunctional and clinical aspects of this wide cortical region. The review is divided into three main sections. In the first section, we report the results obtained by the stimulation of the anterior, middle, and posterior CC, in 30 studies conducted on approximately 1,000 patients from the 1950s to the present day. These studies show that specific manifestations can be reliably associated with specific cingulate subfields, with autonomic, interoceptive, and emotional manifestations clustered in the anterior cingulate, goal-oriented motor behaviors elicited from the anterior midcingulate and a variety of sensory symptoms characterizing the posterior cingulate regions. In the second section, we compare the effect of CC intracerebral electrical stimulation with signs and manifestations characterizing cingulate epilepsy, showing that the stimulation mapping of CC subfields provides precious information for understanding cingulate epileptic manifestations. The last section tackles the issue of the discrepancy emerging when comparing the results of clinical (electrical stimulation, epilepsy) studies-revealing the quintessential affective and motor nature of the CC-with that reported by neuroimaging studies-which focus on high-level cognitive functions. Particular attention will be paid to the hypothesis that CC hosts a "Pain Matrix" specifically involved in pain perception, which we will discuss in the light of the fact that the stimulation of CC (as well as cingulate epileptic seizures) does not induce nociceptive effects.
Asunto(s)
Epilepsia , Giro del Cíngulo , Humanos , Giro del Cíngulo/fisiología , Dolor , Percepción del Dolor , Emociones , Epilepsia/terapia , Estimulación Eléctrica , Mapeo Encefálico/métodosRESUMEN
Language lateralization in patients with focal epilepsy frequently diverges from the left-lateralized pattern that prevails in healthy right-handed people, but the mechanistic explanations are still a matter of debate. Here, we debate the complex interaction between focal epilepsy, language lateralization, and functional neuroimaging techniques by introducing the case of a right-handed patient with unaware focal seizures preceded by aphasia, in whom video-EEG and PET examination suggested the presence of focal cortical dysplasia in the right superior temporal gyrus, despite a normal structural MRI. The functional MRI for language was inconclusive, and the neuropsychological evaluation showed mild deficits in language functions. A bilateral stereo-EEG was proposed confirming the right superior temporal gyrus origin of seizures, revealing how ictal aphasia emerged only once seizures propagated to the left superior temporal gyrus and confirming, by cortical mapping, the left lateralization of the posterior language region. Stereo-EEG-guided radiofrequency thermocoagulations of the (right) focal cortical dysplasia not only reduced seizure frequency but led to the normalization of the neuropsychological assessment and the "restoring" of a classical left-lateralized functional MRI pattern of language. This representative case demonstrates that epileptiform activity in the superior temporal gyrus can interfere with the functioning of the contralateral homologous cortex and its associated network. In the case of presurgical evaluation in patients with epilepsy, this interference effect must be carefully taken into consideration. The multimodal language lateralization assessment reported for this patient further suggests the sensitivity of different explorations to this interference effect. Finally, the neuropsychological and functional MRI changes after thermocoagulations provide unique cues on the network pathophysiology of focal cortical dysplasia and the role of diverse techniques in indexing language lateralization in complex scenarios.
RESUMEN
The interaction between different sensory modalities represents a crucial issue in the neuroscience of consciousness: when the processing of one modality is deficient, the concomitant presentation of stimuli of other spared modalities may sustain the restoration of the damaged sensory functions. In this regard, visual enhancement of touch may represent a viable tool in rehabilitating tactile disorders, yet the specific visual features mostly modulating the somatosensory experience remain unsettled. In this study, healthy subjects underwent a tactile detection task during the observation of videos displaying different contents, including static gratings, meaningless motions and natural or point-lights reach-to-grasp-and-manipulate actions. Concurrently, near-threshold stimuli were delivered to the median nerve at different time-points. The subjective report was collected after each trial; the sensory detection rate was computed and compared across video conditions. Our results indicate that the specific presence of haptic contents (i.e., the vision of manipulation), either fully displayed or implied by point-lights, magnifies tactile sensitivity. The notion that such stimuli prompt a conscious tactile experience opens to novel rehabilitation approaches for tactile consciousness disorders.
Asunto(s)
Tecnología Háptica , Percepción del Tacto , Estado de Conciencia , Fuerza de la Mano , Humanos , Corteza Somatosensorial/fisiología , Tacto/fisiología , Percepción del Tacto/fisiologíaRESUMEN
Understanding mental processes in complex human behavior is a key issue in driving, representing a milestone for developing user-centered assistive driving devices. Here, we propose a hybrid method based on electroencephalographic (EEG) and electromyographic (EMG) signatures to distinguish left and right steering in driving scenarios. Twenty-four participants took part in the experiment consisting of recordings of 128-channel EEG and EMG activity from deltoids and forearm extensors in non-ecological and ecological steering tasks. Specifically, we identified the EEG mu rhythm modulation correlates with motor preparation of self-paced steering actions in the non-ecological task, while the concurrent EMG activity of the left (right) deltoids correlates with right (left) steering. Consequently, we exploited the mu rhythm de-synchronization resulting from the non-ecological task to detect the steering side using cross-correlation analysis with the ecological EMG signals. Results returned significant cross-correlation values showing the coupling between the non-ecological EEG feature and the muscular activity collected in ecological driving conditions. Moreover, such cross-correlation patterns discriminate the steering side earlier relative to the single EMG signal. This hybrid system overcomes the limitation of the EEG signals collected in ecological settings such as low reliability, accuracy, and adaptability, thus adding to the EMG the characteristic predictive power of the cerebral data. These results prove how it is possible to complement different physiological signals to control the level of assistance needed by the driver. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-021-09776-w.
RESUMEN
The perspective from which body-related stimuli are observed plays a fundamental role in modulating cerebral activity during the processing of others' bodies and actions. Previous research has shown perspective-dependent cerebral responses during the observation of both ongoing actions and static images of an acting body with implied motion information, with an advantage for the egocentric viewpoint. The present high-density EEG study assessed event-related potentials triggered by the presentation of a forearm at rest before reach-to-grasp actions, shown from four different viewpoints. Through a spatiotemporal analysis of the scalp electric field and the localization of cortical generators, our study revealed overall different processing for the third-person perspective relative to other viewpoints, mainly due to a later activation of motor-premotor regions. Since observing a static body effector often precedes action observation, our results integrate previous evidence of perspective-dependent encoding, with cascade implications on the design of neurorehabilitative or motor learning interventions based on action observation.
Asunto(s)
Lóbulo Frontal/fisiología , Red Nerviosa/fisiología , Observación , Lóbulo Parietal/fisiología , Adulto , Mapeo Encefálico , Electroencefalografía , Potenciales Evocados , Femenino , Humanos , Masculino , Estimulación Luminosa , Percepción Visual/fisiología , Adulto JovenRESUMEN
Driving a car requires high cognitive demands, from sustained attention to perception and action planning. Recent research investigated the neural processes reflecting the planning of driving actions, aiming to better understand the factors leading to driving errors and to devise methodologies to anticipate and prevent such errors by monitoring the driver's cognitive state and intention. While such anticipation was shown for discrete driving actions, such as emergency braking, there is no evidence for robust neural signatures of continuous action planning. This study aims to fill this gap by investigating continuous steering actions during a driving task in a car simulator with multimodal recordings of behavioural and electroencephalography (EEG) signals. System identification is used to assess whether robust neurophysiological signatures emerge before steering actions. Linear decoding models are then used to determine whether such cortical signals can predict continuous steering actions with progressively longer anticipation. Results point to significant EEG signatures of continuous action planning. Such neural signals show consistent dynamics across participants for anticipations up to 1 s, while individual-subject neural activity could reliably decode steering actions and predict future actions for anticipations up to 1.8 s. Finally, we use canonical correlation analysis to attempt disentangling brain and non-brain contributors to the EEG-based decoding. Our results suggest that low-frequency cortical dynamics are involved in the planning of steering actions and that EEG is sensitive to that neural activity. As a result, we propose a framework to investigate anticipatory neural activity in realistic continuous motor tasks.
Asunto(s)
Anticipación Psicológica/fisiología , Conducción de Automóvil/psicología , Corteza Cerebral/fisiología , Análisis de Correlación Canónica , Simulación por Computador , Electroencefalografía , Humanos , Modelos Lineales , Redes Neurales de la Computación , Desempeño Psicomotor/fisiologíaRESUMEN
Simulation theories predict that the observation of other's laughter modulates activity in the same centers controlling its production. Investigating this issue is particularly challenging, given the technical difficulties of studying laughter production. Previous observations from surgical patients reported laughter production following the electrical stimulation (ES) of the pregenual anterior cingulate (pACC), the frontal operculum (FO) and the temporal pole (TP), deemed to control emotional, communicative and cognitive aspects of laughter, respectively. Here we investigated which region is recruited during laughter observation and production, by adopting a twofold strategy which combines ES and intracranial recording in the same patients. We identified nine sites equally distributed in the pACC, FO and TP, where ES elicited laughter. Subsequently, we presented the patients with visual stimuli depicting dynamic (video) and static (pictures) expressions of laughter, along with emotional and neutral controls, while intracranially recording high-frequency gamma activity (50-150 Hz) from the same sites. pACC sites showed a selective activation during laughter observation, but only if laughter is presented in a dynamical fashion. FO and TP failed to respond during both dynamic and static expressions. We conclude that pACC host a mirror mechanism directly mapping other's laughter onto the neural substrate responsible for the production of emotional laughter.
Asunto(s)
Risa , Corteza Cerebral , Lóbulo Frontal , Giro del Cíngulo , Humanos , Lóbulo TemporalRESUMEN
The properties of the secondary somatosensory area (SII) have been described by many studies in monkeys and humans. Recent studies on monkeys, however, showed that beyond somatosensory stimuli, SII responds to a wider number of stimuli, a finding requiring a revision that human SII is purely sensorimotor. By recording cortical activity with stereotactic electroencephalography (stereo-EEG), we examined the properties of SI and SII in response to a motor task requiring reaching, grasping and manipulation, as well as the observation of the same actions. Furthermore, we functionally characterized this area with a set of clinical tests, including tactile, acoustical, and visual stimuli. The results showed that only SII activates both during execution and observation with a common temporal profile, whereas SI response were limited to execution. Together with their peculiar response to tactile stimuli, we conclude that the role of SII is pivotal also in the observation of actions involving haptic control.
Asunto(s)
Función Ejecutiva/fisiología , Observación , Corteza Somatosensorial/fisiología , Tacto/fisiología , Adulto , Mapeo Encefálico/métodos , Epilepsia Refractaria/diagnóstico por imagen , Epilepsia Refractaria/fisiopatología , Epilepsia Refractaria/psicología , Electrodos Implantados , Electroencefalografía , Fenómenos Electrofisiológicos , Femenino , Mano/fisiología , Humanos , Masculino , Examen Neurológico , Neuronas/fisiología , Monitorización Neurofisiológica , Corteza Somatosensorial/anatomía & histología , Corteza Somatosensorial/citología , Percepción Visual/fisiologíaRESUMEN
PURPOSE: GOLFIG chemoimmunotherapy regimen proved to be a safe and very active chemoimmunotherapy regimen in advanced colon cancer patients. We have thus investigated the immunobiological feedback to the treatment and its possible correlation with the clinical outcome of these patients. EXPERIMENTAL DESIGN: This clinical and immunologic study involved 46 patients, 27 males and 19 females, enrolled in the GOLFIG-1 phase II trial who received gemcitabine (1,000 mg/m(2) on days 1 and 15), oxaliplatin (85 mg/m(2) on days 2 and 16), levofolinic acid (100 mg/m(2) on days 1, 2, 15, and 16), and 5-fluorouracil (400 mg/m(2) as a bolus, and 800 mg/m(2) as a 24-hour infusion on days 1, 2, 15, and 16) followed by s.c. granulocyte macrophage colony-stimulating factor (100 mug, on days 3-7) and interleukin 2 (0.5 x 10(6) IU twice a day on days 8-14 and 17-29). RESULTS: The regimen was confirmed to be safe and very active in pretreated patients with metastatic colorectal cancer. A subgroup analysis of these patients revealed a prolonged time to progression and survival in six patients who developed late signs of autoimmunity. A multivariate analysis validated the occurrence of autoimmunity signs as an independent predictor of favorable outcome. A parallel immunologic study detected in the peripheral blood mononuclear cells of these patients a progressive increase in lymphocyte and eosinophil counts, amplification in central memory, a marked depletion of immunosuppressive regulatory T cells, and activation of colon cancer-specific cytotoxic T cells. CONCLUSIONS: Our results suggest that immunity feedback to GOLFIG regimen and its antitumor activity are tightly correlated.
Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Desoxicitidina/análogos & derivados , Factor Estimulante de Colonias de Granulocitos y Macrófagos/administración & dosificación , Inmunoterapia/métodos , Interleucina-2/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Colon/inmunología , Terapia Combinada/métodos , Desoxicitidina/administración & dosificación , Femenino , Fluorouracilo/uso terapéutico , Humanos , Inyecciones Subcutáneas , Interleucina-2/administración & dosificación , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/uso terapéutico , Proteínas Recombinantes/administración & dosificación , Resultado del Tratamiento , GemcitabinaRESUMEN
In the present study, we mapped the spatio-temporal dynamics of cortical responses to ipsilateral median nerve stimulation using intracerebral recordings (stereo-EEG) in 38 drug-resistant epileptic patients. Furthermore, we compared the pattern of responsiveness obtained in the same leads across ipsilateral and contralateral stimulations. Ipsilateral responses were found mostly confined to SII and posterior insula, while no activity was found in ipsilateral SI. By examining the temporal profiles of activation, ipsilateral SII showed a prominent tonic pattern, while contralateral SII exhibited both phasic and tonic responses. Beyond the localization of the active cortical nodes, these data contributed to identify the cortico-cortical connections carrying the somatosensory information to the ipsilateral hemisphere, with a major role of transcallosal projections from contralateral SII. In light of previous literature and of its localization, the functional role possibly covered by long lasting discharge in SII and insular cortex is also discussed. Overall, the presence of tonic activities was neglected so far due to the impossibility to identify deep sources along with a resolved description of their time course. The use of stereo-EEG, instead, allows one to achieve a four-dimensional characterization, complementing the classical view about the somatosensory system organization.
Asunto(s)
Epilepsias Parciales/fisiopatología , Potenciales Evocados Somatosensoriales , Nervio Mediano/fisiopatología , Corteza Somatosensorial/fisiopatología , Adulto , Anticonvulsivantes/uso terapéutico , Mapeo Encefálico/métodos , Resistencia a Medicamentos , Estimulación Eléctrica , Electroencefalografía , Epilepsias Parciales/diagnóstico , Epilepsias Parciales/tratamiento farmacológico , Epilepsias Parciales/psicología , Femenino , Humanos , Masculino , Factores de Tiempo , Tacto , Percepción del Tacto , Adulto JovenRESUMEN
BACKGROUND: C-IRIV/PTR-4 is a novel anticancer vaccine construct composed of immune-reconstituted influenza virosomes (IRIV) assembled with the PTH-rP derived peptide (PTR)-4, a synthetic CTL epitope with HLA-A(*)02.01 amino acid binding motifs. This peptide is able to generate a human PTH-rP specific CTL response with anti-tumor activity in vitro and in mice. MATERIALS AND METHODS: We have investigated the immunological and preventive anti-tumor activity of C-IRIV/PTR-4 compared with the soluble PTR-4 peptide, in HHD mice inoculated with autologous PTH-rP+ tumor cells. RESULTS: Peptide vaccination with either a soluble and an IRIV formulation showed similar immunological activity and the ability to purge the tumor tissue of tumor cell clones able to produce the target antigen (PTR-rP). The most efficient protection from tumor growth was however observed in animals vaccinated with C-IRIV/PTR-4 in which an additional IRIV related anti-angiogenetic effect was detected in the tumor tissue. CONCLUSIONS: These results confirm the immunological activity of PTR-4 vaccination and suggest a more efficacious therapeutic potential of C-IRIV/PTR-4 against bone metastases and malignancies like breast, prostate and lung which very often over-express PTH-rP.
Asunto(s)
Vacunas contra el Cáncer/farmacología , Virus de la Influenza A/inmunología , Neovascularización Patológica/tratamiento farmacológico , Proteína Relacionada con la Hormona Paratiroidea/administración & dosificación , Vacunas de Virosoma/farmacología , Animales , Vacunas contra el Cáncer/uso terapéutico , Línea Celular Tumoral , Citotoxicidad Inmunológica , Humanos , Ratones , Ratones Transgénicos , Vacunas de Subunidad/uso terapéutico , Vacunas de Virosoma/uso terapéuticoRESUMEN
Urachus' carcinoma represents a rare oncologic disease with an unfavourable prognosis due to the usual delay of correct diagnosis for its anatomical localization. Its surgical treatment varies from radical cystectomy to segmentary resection of the bladder with pelvic lymphadenectomy. We report a case occurred in a ninety years old female, in which the diagnosis was achieved only at laparotomy. The patient was submitted to surgery with the only generic diagnosis of "lower abdominal mass", and treated with segmentary resection.