RESUMEN
Analysis of intracranial electroencephalographic (iEEG) recordings in patients with temporal lobe epilepsy (TLE) has revealed characteristic dynamical features that distinguish the interictal, ictal, and postictal states and inter-state transitions. Experimental investigations into the mechanisms underlying these observations require the use of an animal model. A rat TLE model was used to test for differences in iEEG dynamics between well-defined states and to test specific hypotheses: 1) the short-term maximum Lyapunov exponent (STL(max)), a measure of signal order, is lowest and closest in value among cortical sites during the ictal state, and highest and most divergent during the postictal state; 2) STL(max) values estimated from the stimulated hippocampus are the lowest among all cortical sites; and 3) the transition from the interictal to ictal state is associated with a convergence in STL(max) values among cortical sites. iEEGs were recorded from bilateral frontal cortices and hippocampi. STL(max) and T-index (a measure of convergence/divergence of STL(max) between recorded brain areas) were compared among the four different periods. Statistical tests (ANOVA and multiple comparisons) revealed that ictal STL(max) was lower (p<0.05) than other periods, STL(max) values corresponding to the stimulated hippocampus were lower than those estimated from other cortical regions, and T-index values were highest during the postictal period and lowest during the ictal period. Also, the T-index values corresponding to the preictal period were lower than those during the interictal period (p<0.05). These results indicate that a rat TLE model demonstrates several important dynamical signal characteristics similar to those found in human TLE and support future use of the model to study epileptic state transitions.
Asunto(s)
Electroencefalografía/métodos , Epilepsia del Lóbulo Temporal/diagnóstico , Epilepsia del Lóbulo Temporal/fisiopatología , Potenciales Evocados/fisiología , Lóbulo Temporal/fisiopatología , Potenciales de Acción/fisiología , Algoritmos , Animales , Interpretación Estadística de Datos , Modelos Animales de Enfermedad , Estimulación Eléctrica , Hipocampo/fisiopatología , Excitación Neurológica/fisiología , Masculino , Modelos Neurológicos , Neuronas/fisiología , Dinámicas no Lineales , Ratas , Ratas Sprague-Dawley , Procesamiento de Señales Asistido por Computador , Estado Epiléptico/fisiopatologíaRESUMEN
PURPOSE: Phenylketonuria (PKU) is a disorder of phenylalanine (Phe) metabolism that frequently results in epilepsy if a low Phe diet was not implemented at birth. The mechanisms by which Phe affects the brain are poorly understood. METHODS: Audiogenic seizures (AGS) were studied in female homozygous Pah(enu2) BTBR (PKU) mice. RESULTS: Adult PKU mice, 18-20 weeks of age, in contrast to wild-type and heterozygous counterparts, exhibited a full range of AGS. Younger PKU mice, 5-7 weeks of age, had higher serum Phe levels (2.22 +/- 0.20 mM) in comparison with the adult animals (1.72 +/- 0.05 mM) and were not susceptible to AGS. Among adult mice, animals susceptible to AGS had significantly lower serum Phe levels (1.62 +/- 0.06 mM) in comparison with those resistant to AGS (1.86 +/- 0.07 mM). Susceptibility to AGS tended to increase in the afternoon when serum Phe concentration decreased in comparison to evening and morning. Normalization of serum Phe level by instituting a low Phe diet generally prevented susceptibility to AGS within 12 h. Although return to a standard diet raised Phe levels to hyperphenylalaninemic within 12 h in animals treated with a low Phe diet for 2 weeks, more than 7 weeks were needed for a complete resumption of AGS. CONCLUSIONS: Transient decrease in Phe levels within hyperphenylalaninemic range may be a necessary condition for PKU-related seizures to occur. A low Phe diet prevents susceptibility to seizures, which can resume with the significant delay after termination of dietary treatment.
Asunto(s)
Epilepsia Refleja/sangre , Epilepsia/sangre , Fenilalanina/sangre , Fenilcetonurias/sangre , Estimulación Acústica , Factores de Edad , Animales , Ritmo Circadiano , Modelos Animales de Enfermedad , Epilepsia/diagnóstico , Epilepsia/genética , Epilepsia Refleja/diagnóstico , Epilepsia Refleja/genética , Femenino , Alimentos Formulados , Predisposición Genética a la Enfermedad , Ratones , Ratones Mutantes , Fenilalanina/administración & dosificación , Fenilalanina/metabolismo , Fenilcetonurias/dietoterapia , Fenilcetonurias/genéticaRESUMEN
Epilepsy research for the design of seizure detection/prediction neuroprosthetics has been faced with the search for electrophysiologic control parameters that can be used to infer the epileptic state of the animal and be leveraged at a later time to deliver neurotherapeutic feedback. The analysis presented here uses multi-microelectrode array technology to provide an electrophysiologic quantification of a hippocampal neural ensemble during the latent period of epileptogenesis. Through the use of signal processing system identification methodologies, we were able to assess the spatial and temporal interrelations of ensembles of hippocampal neurons and relate them to the evolution of the epileptic condition. High-field magnetic resonance (MR) imaging was used to determine the location of electrode placement and to evaluate hippocampal pyramidal cell structural damage. Long-term single unit activity analysis suggests that hippocampal neurons in both CA1-2 and dentate regions increase the number of occurrences and duration of their bursting activity after injury to the contra-lateral hippocampus. The trends inferred from both single neuron and ensemble analysis suggests that the evolution into epilepsy is not abrupt but modulates gradually from the time of injury.
Asunto(s)
Modelos Animales de Enfermedad , Galvanoplastia , Imagen por Resonancia Magnética/métodos , Estado Epiléptico/patología , Estado Epiléptico/fisiopatología , Potenciales de Acción/fisiología , Potenciales de Acción/efectos de la radiación , Animales , Azidas , Mapeo Encefálico , Estimulación Eléctrica/métodos , Hipocampo/patología , Hipocampo/fisiopatología , Hipocampo/efectos de la radiación , Masculino , Modelos Neurológicos , Neuronas/patología , Neuronas/fisiología , Octreótido/análogos & derivados , Ratas , Ratas Sprague-Dawley , Análisis Espectral , Factores de TiempoRESUMEN
A total of 32 microwire electrodes were implanted bilaterally into the hippocampus of Sprague-Dawley rats, which were then stimulated in the manner prescribed for the chronic limbic epilepsy model. After the initial seizure brought on by the stimulation, the animals were recorded at a high sampling rate (approximately 12 kHz) for the entire duration of the latent period. Coherence was calculated across channels in both stimulated (and later seizing) animals and non-stimulated (and thus non-seizing control) animals. Average coherence over time was greatest in intrahemispherical electrode pairs in both stimulated and non-stimulated animals. However, the 200-800 Hz band displays increased coherence interhemispherically and up to 200 Hz band displays decreased coherence interhemispherically: this occurs only in stimulated animals.
Asunto(s)
Algoritmos , Mapeo Encefálico/métodos , Cerebro/fisiopatología , Epilepsia/fisiopatología , Sistema Límbico/fisiopatología , Modelos Neurológicos , Tiempo de Reacción , Animales , Modelos Animales de Enfermedad , Ratas , Ratas Sprague-DawleyRESUMEN
Epilepsy is a common neurological disorder that can have damaging effects in the brain including over 50% loss of neuronal activity in the hippocampal regions of the CA1 and CA3. The pre-ictal period was studied in an animal model of limbic epilepsy using Shannon entropy and correlation analysis. The primary aim was to uncover underlying relative changes in signals between the Dentate Gyrus and CA1 areas of the bilateral hippocampus. Preliminary entropy analysis results included dynamical changes between channels in the Dentate Gyrus and channels in the CA1 region at and around the time of the seizure.
Asunto(s)
Algoritmos , Diagnóstico por Computador/métodos , Modelos Animales de Enfermedad , Electroencefalografía/métodos , Epilepsia/diagnóstico , Epilepsia/fisiopatología , Hipocampo/fisiopatología , Animales , Electrodos Implantados , Electroencefalografía/instrumentación , Entropía , Sistema Límbico/fisiopatología , RatasRESUMEN
High frequency oscillations (HFO) in limbic epilepsy represent a marked difference between abnormal and normal brain activity. Faced with the difficult of visually detecting HFOs in large amounts of intracranial EEG data, it is necessary to develop an automated process. This paper presents Teager Energy as a method of finding HFOs. Teager energy is an ideal measure because unlike conventional energy it takes into account the frequency component of the signal as well as signal amplitude. This greatly aids in the dissection of HFOs out of the noise and other signals contained in the EEG. Therein, Teager energy analysis is able to detect high-frequency, low-amplitude components that conventional energy measurements would miss.
Asunto(s)
Mapeo Encefálico/métodos , Diagnóstico por Computador/métodos , Electrocardiografía/métodos , Epilepsia/diagnóstico , Epilepsia/fisiopatología , Sistema Límbico/fisiopatología , Oscilometría/métodos , Algoritmos , Animales , Modelos Animales de Enfermedad , RatasRESUMEN
Progressive preictal dynamical convergence and postictal divergence of dynamical EEG descriptors among brain regions has been reported in human temporal lobe epilepsy (TLE) and in a rodent model of TLE. There are also reports of anticonvulsant effects of high frequency stimulation of the hippocampus in humans. We postulate that this anticonvulsant effect is due to dynamical resetting by the electrical stimulation. The following study investigated the effects of acute hippocampal electrical stimulation on dynamical transitions in the brain of a spontaneously seizing animal model of TLE to test the hypothesis of divergence in dynamical values by electrical stimulation of the hippocampus.