RESUMEN
Reinforcement-based adaptive decision-making is believed to recruit fronto-striatal circuits. A critical node of the fronto-striatal circuit is the thalamus. However, direct evidence of its involvement in human reinforcement learning is lacking. We address this gap by analyzing intra-thalamic electrophysiological recordings from eight participants while they performed a reinforcement learning task. We found that in both the anterior thalamus (ATN) and dorsomedial thalamus (DMTN), low frequency oscillations (LFO, 4-12 Hz) correlated positively with expected value estimated from computational modeling during reward-based learning (after outcome delivery) or punishment-based learning (during the choice process). Furthermore, LFO recorded from ATN/DMTN were also negatively correlated with outcomes so that both components of reward prediction errors were signaled in the human thalamus. The observed differences in the prediction signals between rewarding and punishing conditions shed light on the neural mechanisms underlying action inhibition in punishment avoidance learning. Our results provide insight into the role of thalamus in reinforcement-based decision-making in humans.
Asunto(s)
Refuerzo en Psicología , Recompensa , Humanos , Reacción de Prevención/fisiología , Castigo , TálamoRESUMEN
BACKGROUND: The exact architecture of the human auditory cortex remains a subject of debate, with discrepancies between functional and microstructural studies. In a hierarchical framework for sensory perception, simple sound perception is expected to take place in the primary auditory cortex, while the processing of complex, or more integrated perceptions is proposed to rely on associative and higher-order cortices. OBJECTIVES: We hypothesize that auditory symptoms induced by direct electrical stimulation (DES) offer a window into the architecture of the brain networks involved in auditory hallucinations and illusions. The intracranial recordings of these evoked perceptions of varying levels of integration provide the evidence to discuss the theoretical model. METHODS: We analyzed SEEG recordings from 50 epileptic patients presenting auditory symptoms induced by DES. First, using the Juelich cytoarchitectonic parcellation, we quantified which regions induced auditory symptoms when stimulated (ROI approach). Then, for each evoked auditory symptom type (illusion or hallucination), we mapped the cortical networks showing concurrent high-frequency activity modulation (HFA approach). RESULTS: Although on average, illusions were found more laterally and hallucinations more posteromedially in the temporal lobe, both perceptions were elicited in all levels of the sensory hierarchy, with mixed responses found in the overlap. The spatial range was larger for illusions, both in the ROI and HFA approaches. The limbic system was specific to the hallucinations network, and the inferior parietal lobule was specific to the illusions network. DISCUSSION: Our results confirm a network-based organization underlying conscious sound perception, for both simple and complex components. While symptom localization is interesting from an epilepsy semiology perspective, the hallucination-specific modulation of the limbic system is particularly relevant to tinnitus and schizophrenia.
Asunto(s)
Corteza Auditiva , Epilepsia , Ilusiones , Estimulación Acústica , Corteza Auditiva/fisiología , Mapeo Encefálico , Estimulación Eléctrica , Electroencefalografía , Alucinaciones/etiología , Humanos , Ilusiones/fisiologíaRESUMEN
As you might experience it while reading this sentence, silent reading often involves an imagery speech component: we can hear our own "inner voice" pronouncing words mentally. Recent functional magnetic resonance imaging studies have associated that component with increased metabolic activity in the auditory cortex, including voice-selective areas. It remains to be determined, however, whether this activation arises automatically from early bottom-up visual inputs or whether it depends on late top-down control processes modulated by task demands. To answer this question, we collaborated with four epileptic human patients recorded with intracranial electrodes in the auditory cortex for therapeutic purposes, and measured high-frequency (50-150 Hz) "gamma" activity as a proxy of population level spiking activity. Temporal voice-selective areas (TVAs) were identified with an auditory localizer task and monitored as participants viewed words flashed on screen. We compared neural responses depending on whether words were attended or ignored and found a significant increase of neural activity in response to words, strongly enhanced by attention. In one of the patients, we could record that response at 800 ms in TVAs, but also at 700 ms in the primary auditory cortex and at 300 ms in the ventral occipital temporal cortex. Furthermore, single-trial analysis revealed a considerable jitter between activation peaks in visual and auditory cortices. Altogether, our results demonstrate that the multimodal mental experience of reading is in fact a heterogeneous complex of asynchronous neural responses, and that auditory and visual modalities often process distinct temporal frames of our environment at the same time.
Asunto(s)
Atención/fisiología , Corteza Auditiva/fisiología , Mapeo Encefálico/psicología , Lectura , Corteza Visual/fisiología , Percepción Visual/fisiología , Estimulación Acústica/métodos , Estimulación Acústica/psicología , Adulto , Mapeo Encefálico/métodos , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/psicología , Masculino , Estimulación Luminosa/métodos , Habla/fisiología , Percepción del Habla/fisiologíaRESUMEN
Several brain regions involved in visual perception have been shown to also participate in non-sensory cognitive processes of visual representations. Here we studied the role of ventral visual pathway areas in visual imagery and working memory. We analyzed intracerebral EEG recordings from the left inferior temporal lobe of an epileptic patient during working memory tasks and mental imagery. We found that high frequency gamma-band activity (50-150 Hz) in the inferior temporal gyrus (ITG) increased with memory load only during visuo-spatial, but not verbal, working memory. Using a real-time set-up to measure and visualize gamma-band activity online--BrainTV--we found a systematic activity increase in ITG when the patient was visualizing a letter (visual imagery), but not during perception of letters. In contrast, only 7 mm more medially, neurons located in the fusiform gyrus exhibited a complete opposite pattern, responding during verbal working memory retention and letter presentation, but not during imagery or visuo-spatial working memory maintenance. Talairach coordinates indicate that the fusiform contact site corresponds to the word form area, suggesting that this region has a role not only in processing letter-strings, but also in working memory retention of verbal information. We conclude that neural networks supporting imagination of a visual element are not necessarily the same as those underlying perception of that element. Additionally, we present evidence that gamma-band activity in the inferior temporal lobe, can be used as a direct measure of the efficiency of top-down attentional control over visual areas with implications for the development of novel brain-computer interfaces. Finally, by just reading gamma-band activity in these two recording sites, it is possible to determine, accurately and in real-time, whether a given memory content is verbal or visuo-spatial.
Asunto(s)
Imaginación/fisiología , Memoria a Corto Plazo/fisiología , Lóbulo Temporal/fisiología , Percepción Visual/fisiología , Adolescente , Mapeo Encefálico , Electroencefalografía , Femenino , HumanosRESUMEN
A large body of evidence from animal studies indicates that motor intention can be decoded via multiple single-unit recordings or from local field potentials (LFPs) recorded not only in primary motor cortex, but also in premotor or parietal areas. In humans, reports of invasive data acquisition for the purpose of BCI developments are less numerous and signal selection for optimal control still remains poorly investigated. Here we report on our recent implementation of a real-time analysis platform for the investigation of ongoing oscillations in human intracerebral recordings and review various results illustrating its utility for the development of novel brain-computer and brain-robot interfaces. Our findings show that the insight gained both from off-line experiments and from online functional exploration can be used to guide future selection of the sites and frequency bands to be used in a translation algorithm such as the one needed for a BCI-driven cursor control. Overall, the findings reported with our online spectral analysis platforms (Brain TV and Brain Ball) indicate the feasibility of online functional exploration via intracranial recordings in humans and outline the direct benefits of this approach for the improvement of invasive BCI strategies in humans. In particular, our findings suggest that current BCI performance may be improved by using signals recorded from various systems previously unexplored in the context of BCI research such as the oscillatory activity recorded in the oculomotor networks as well as higher cognitive processes including working memory, attention, and mental calculation networks. Finally, we discuss current limitations of the methodology and outline future paths for innovative BCI research.
Asunto(s)
Atención/fisiología , Encéfalo/fisiología , Electroencefalografía , Sistemas Hombre-Máquina , Televisión , Interfaz Usuario-Computador , Biorretroalimentación Psicológica , Mapeo Encefálico , Cognición/fisiología , Humanos , Desempeño Psicomotor/fisiología , Procesamiento de Señales Asistido por ComputadorRESUMEN
Neurostimulation represents an interesting alternative therapy for patients resistant to drug treatment or who cannot benefit from resective surgery. Theoretically, neurostimulation allows the control of seizures to be tailored to the individual patient and specific form of epilepsy. Here, we review both experimental and clinical studies that have reported the possible control of epileptic seizures by means of different approaches using electrical stimulation (vagus nerve stimulation, deep brain stimulation and repetitive transcranial magnetic stimulation). The rationale for targeting specific areas that have thus far been considered (i.e., vagus nerve, cerebellum, anterior or centromedial thalamus, basal ganglia, cortex and temporal lobe) is addressed in the light of experimental data and clinical effectiveness in different models and forms of epilepsy. The type of seizures that can be considered for neurostimulation, as well as the optimal parameters such as stimulation frequency and modes of stimulation (chronic, continuous or adaptative), are discussed to determine the best candidates for such a therapeutic strategy. This review points out the need for improved knowledge of neural circuits that generate seizures and/or allow their propagation, as well as a better understanding of the mechanisms of action of neurostimulation.
Asunto(s)
Encéfalo/fisiopatología , Encéfalo/cirugía , Estimulación Encefálica Profunda/métodos , Epilepsia/terapia , Estimulación Magnética Transcraneal/métodos , Estimulación del Nervio Vago/métodos , Animales , Ganglios Basales/fisiopatología , Ganglios Basales/cirugía , Cerebelo/fisiopatología , Cerebelo/cirugía , Epilepsia/fisiopatología , Humanos , Tálamo/fisiopatología , Tálamo/cirugía , Resultado del TratamientoRESUMEN
Our understanding of the brain's functional organisation has greatly benefited from occasional exploratory sessions during electrophysiological studies, trying various manipulations of an animal's environment to trigger responses in particular neurons. Famous examples of such exploration have unveiled various unexpected response properties, such as those of mirror neurons. This approach, which relies on the possibility to test online the reactivity of precise neural populations has no equivalent so far in humans. The present study proposes and applies a radically novel framework for mapping human brain functions in ecological situations based on a combination of a) exploratory sessions, using real-time electrophysiology to formulate hypotheses about the functional role of precise cortical regions and b) controlled experimental protocols specifically adapted to test these hypotheses. Using this two-stage approach with an epileptic patient candidate for surgery and implanted with intracerebral electrodes, we were able to precisely map high-level auditory functions in the patients' superior temporal lobe. We propose that this procedure constitutes at the least a useful complement of electrical cortical stimulations to map eloquent brain areas in epileptic patients before their surgery, but also a path of discovery for human functional brain mapping.
Asunto(s)
Biorretroalimentación Psicológica , Mapeo Encefálico/métodos , Encéfalo/fisiopatología , Epilepsia/fisiopatología , Red Nerviosa/fisiopatología , Estimulación Eléctrica , Electrodos Implantados , Electroencefalografía , Electrofisiología , HumanosRESUMEN
Our understanding of the brain's functional organisation has greatly benefited from occasional exploratory sessions during electrophysiological studies, trying various manipulations of an animal's environment to trigger responses in particular neurons. Famous examples of such exploration have unveiled various unexpected response properties, such as those of mirror neurons. This approach, which relies on the possibility to test online the reactivity of precise neural populations has no equivalent so far in humans. The present study proposes and applies a radically novel framework for mapping human brain functions in ecological situations based on a combination of a) exploratory sessions, using real-time electrophysiology to formulate hypotheses about the functional role of precise cortical regions and b) controlled experimental protocols specifically adapted to test these hypotheses. Using this two-stage approach with an epileptic patient candidate for surgery and implanted with intracerebral electrodes, we were able to precisely map high-level auditory functions in the patients' superior temporal lobe. We propose that this procedure constitutes at the least a useful complement of electrical cortical stimulations to map eloquent brain areas in epileptic patients before their surgery, but also a path of discovery for human functional brain mapping.
Asunto(s)
Humanos , Biorretroalimentación Psicológica , Mapeo Encefálico/métodos , Encéfalo/fisiopatología , Epilepsia/fisiopatología , Red Nerviosa/fisiopatología , Estimulación Eléctrica , Electrodos Implantados , Electroencefalografía , ElectrofisiologíaAsunto(s)
Terapia por Estimulación Eléctrica/tendencias , Enfermedad de Parkinson/terapia , Técnicas Estereotáxicas/tendencias , Animales , Encéfalo/patología , Encéfalo/fisiopatología , Encéfalo/cirugía , Terapia por Estimulación Eléctrica/normas , Terapia por Estimulación Eléctrica/estadística & datos numéricos , Electrodos/normas , Epilepsia/fisiopatología , Epilepsia/terapia , Trastornos de Alimentación y de la Ingestión de Alimentos/fisiopatología , Trastornos de Alimentación y de la Ingestión de Alimentos/terapia , Humanos , Fármacos Neuroprotectores/uso terapéutico , Enfermedad de Parkinson/fisiopatología , Técnicas Estereotáxicas/normas , Técnicas Estereotáxicas/estadística & datos numéricosRESUMEN
Patients having a hypothalamic hamartoma (HH) frequently present gelastic or dacrystic seizures, and they often later experience multiple additional seizure types which lead to a severe epileptic encephalopathy. There is now increasing evidence that the HH itself plays a crucial role in this syndrome, but the relationships between the lesion and the different types of seizures remain a questionable issue. Stereotactic intracerebral EEG recordings were performed in 5 patients suffering from a medically intractable epilepsy associated with a HH. The hamartoma was investigated in all cases, and various cortical areas were also evaluated in 4 of the 5 patients. The epileptic discharges arose and remained confined within the hamartoma in 3 of the 4 patients in whom laughing and crying episodes were recorded. In addition, interictal spikes were recorded from the hamartoma in 4 of the 5 patients, whereas the stimulation of the HH could reproduce gelastic or dacrystic episodes in 3. The three patients in whom other types of seizure were recorded showed that the latter were associated with cortical ictal discharges not affecting the HH. Ictal onset appeared either bifrontal, right fronto-central and lateral temporal, or bifrontal with a right side predominance. The cingulate gyrus was involved in all these 3 cases, and the lateralization of the ictal discharges was always ipsilateral to the predominating side of the hamartoma. Interestingly, these seizure types were sometimes immediately preceded by the laughing or crying attacks, as if ictal discharges within the hamartoma triggered those which seemed to originate in the cortex. Therefore, if these findings confirm the intrinsic epileptogenicity of HH, they also demonstrate that epileptic seizures associated with HH can exhibit different types of electroclinical patterns. We propose a speculative pathophysiology in which the mamillo-thalamo-cingulate tract would serve as a relay of HH discharges towards the cortex, the excitability of which would then progressively increase, first leading to cortical interictal epileptiform abnormalities and then to seizures of cortical origin. Whether this proposal of secondary epileptogenesis is valid or not remains a major issue, since it could provide arguments on the moment to discuss surgery.
Asunto(s)
Corteza Cerebral/fisiopatología , Llanto/fisiología , Electroencefalografía , Epilepsias Parciales/fisiopatología , Hamartoma/fisiopatología , Enfermedades Hipotalámicas/fisiopatología , Hipotálamo/fisiopatología , Adolescente , Adulto , Daño Encefálico Crónico/diagnóstico , Daño Encefálico Crónico/fisiopatología , Mapeo Encefálico , Niño , Diagnóstico Diferencial , Dominancia Cerebral/fisiología , Estimulación Eléctrica , Electrodos Implantados , Epilepsias Parciales/diagnóstico , Epilepsia Generalizada/diagnóstico , Epilepsia Generalizada/fisiopatología , Femenino , Hamartoma/diagnóstico , Humanos , Enfermedades Hipotalámicas/diagnóstico , Imagen por Resonancia Magnética , Masculino , SíndromeRESUMEN
Alternative methods, for the treatment of medically refractory epileptic patients, who cannot be treated by resective surgery, such as chronic deep brain neurostimulation, are under development. Such methods have been used in the cerebellum, various thalamic nuclei, and in the caudate nucleus. In Grenoble, encouraged by the suppressive effects of pharmacological or electrical inhibition of the STN on different types of seizure in animal models of epilepsy, and by our experience with STN high frequency stimulation (HFS) in patients with movement disorders, we have evaluated the high frequency stimulation of the subthalamic nucleus (STN HFS). STN HFS was performed in five patients suffering from medically intractable seizures and considered unsuitable for resective surgery. A 67% to 80% reduction in seizure frequency was observed in three patients, with a partial symptomatic epilepsy of the central region. An additional patient suffering from severe myoclonic epilepsy (Dravet syndrome) also responded to STN HFS, with a weaker reduction of seizure frequency. The fifth patient who suffered from an autosomal dominant frontal lobe epilepsy with insulo-frontal seizures did not show any improvement. These results suggest that stimulation of STN could be a promising treatment for patients with drug-resistant epilepsy who would not benefit from conventional surgery.
Asunto(s)
Terapia por Estimulación Eléctrica , Epilepsia/terapia , Núcleo Subtalámico/fisiología , Adolescente , Adulto , Ganglios Basales/fisiología , Cerebelo/fisiología , Niño , Preescolar , Electrodos Implantados , Electroencefalografía , Epilepsia/cirugía , Femenino , Humanos , Masculino , Vías Nerviosas/fisiología , Procedimientos NeuroquirúrgicosRESUMEN
The temporopolar region is not clearly defined from an anatomical point of view. A line going through the rostral area of the inferior temporal, occipito temporal and superior temporal sulci is considered to represent its posterior limit on the lateral and inferior sides. On the internal side, this posterior limit corresponds to the rhinal sulcus, an anterior and internal extention of the collateral sulcus. From a cyto-architectonic point of view, the temporopolar region is caracterized by a dysgranular paralimbic cortex which ensures the transition between allo- and isocortical areas. The temporal pole is mainly connected with the amygadala, the hippocampus, the superior temporal gyrus, and the occipitobasal cortex, but also with the orbitary gyrus and the insula with which it forms the insulo-orbito-polar-temporo-complex. The temporal pole occupies the most rostral part of the temporal lobe and can only be accurately defined once the anatomy of the temporal lobe as a whole has been outlined. The architectonic configuration of this region as well as its connections with the limbic system, and the superior, orbital and insular temporal cortices make it a discrete temporal structure. Understanding the anatomical and functional organization of the temporal pole enables us to hypothesize about the role played by this structure in the pathogenesis of the forms of epilepsy originating in mesial temporal lobe structures.
Asunto(s)
Lóbulo Temporal/anatomía & histología , Ganglios Basales/anatomía & histología , Ganglios Basales/fisiología , Humanos , Hipotálamo/anatomía & histología , Hipotálamo/fisiología , Sistema Límbico/anatomía & histología , Sistema Límbico/fisiología , Fibras Nerviosas/fisiología , Red Nerviosa/anatomía & histología , Red Nerviosa/fisiología , Lóbulo Temporal/fisiología , Tálamo/anatomía & histología , Tálamo/fisiologíaRESUMEN
OBJECTIVE AND IMPORTANCE: Currently, some forms of epilepsy are resistant to both pharmacological and surgical interventions. As a result, there is a need for new therapeutic strategies. Because the nigral system modulates neuronal excitability in animal models of epilepsy, we considered therapeutic high-frequency stimulation of the subthalamic nucleus (STN). We were encouraged by the known relationship between the STN and the nigral system, as well as by our experience with high-frequency stimulation of the STN in Parkinsonian patients. CLINICAL PRESENTATION: A 5-year-old girl with pharmacologically resistant, inoperable epilepsy caused by focal centroparietal dysplasia underwent implantation with a permanent electrode in the left STN and was chronically stimulated. To date, we have followed up this patient for 30 months postoperatively. TECHNIQUE: High-frequency stimulation of the STN induced a significant voltage-dependent reduction (by 80%) in the number and severity of seizures. In addition, consistent improvement in both motor and cognitive functions was noted as a result of reduced postictal states. The effect was more prominent for seizures occurring in clusters (89% reduction) and during the day (88% reduction) than for those that occurred during sleep (53% reduction). CONCLUSION: This is the first report of epilepsy control using chronic high-frequency stimulation of the STN. Preliminary observations in three other operated patients (at 2, 12, and 18 mo) confirm these data. We think that high-frequency stimulation of the STN may hold significant future potential as a treatment for epilepsy, similar to its established role in the treatment of Parkinson's disease. This finding opens completely new experimental and therapeutic avenues for the treatment of surgically and medically intractable epilepsy.