Abnormal brain gamma oscillations in response to auditory stimulation in Dravet syndrome.

OBJECTIVE: To evaluate the capability of children with Dravet syndrome to generate brain γ-oscillatory activity in response to auditory steady-state stimulation. METHODS: Fifty-one subjects were included: 13 with Dravet syndrome with SCN1A gene alterations, 26 with non-Dravet epilepsies and 12 healthy controls. Responses to auditory steady-state stimulation elicited with a chirp-modulated tone between 1 and 120 Hz were collected in subjects and compared across groups. RESULTS: Subjects with Dravet syndrome showed weak or no responses in the 1-120 Hz frequency range. Healthy controls showed oscillatory responses following the frequency of the modulation that were maximal in the low (30-70 Hz) and high (80-120) γ-ranges both, in the power and inter-trial coherence estimates. Non-Dravet epileptic children showed differences in the auditory responses when compared with the healthy controls but were able to generate oscillatory evoked activities following the frequency-varying stimulation. CONCLUSIONS: The ability to generate brain γ-oscillatory activity of children with Dravet in response to a chirp-modulated auditory stimulus is highly impaired, is not due to epilepsy and is consistent with the Nav1.1 channel dysfunction affecting interneuron activity seen in Dravet mouse models. SIGNIFICANCE: The reported deficits in the brain oscillatory activity evoked by chirp modulated tones in children with Dravet is compatible with Dravet syndrome disease mechanisms and constitutes a potential biomarker for future disease-modifying interventions.

Atypical antipsychotics normalize low-gamma evoked oscillations in patients with schizophrenia.

The symptoms of schizophrenia might be mediated by a cortical network disconnection which may disrupt the cortical oscillatory activity. Steady-state responses are an easy and consistent way to explore cortical oscillatory activity. A chirp-modulated tone (increasing the frequency of the modulation in a linear manner) allows a fast measure of the steady-state response to different modulation rates. With this approach, we studied the auditory steady-state responses in two groups of patients with schizophrenia (drug-naive and treated with atypical antipsychotic drugs), in order to assess the differences in their responses with respect to healthy subjects, and study any potential effect of medication. Drug-naive patients had reduced amplitude and inter-trial phase coherence of the response in the 30-50Hz range, and reduced amplitude of the response in the 90-100Hz range, when compared to controls. In the treated patients group, the response in the 30-50Hz range was normalized to values similar to the control group, but the reduction in amplitude in the 90-100Hz range remained as in the drug-naive group. These results suggest that gamma activity impairment in schizophrenia is a complex phenomenon that affects a wide band of frequencies and may be influenced by antipsychotic treatment.

Cortical oscillations scan using chirp-evoked potentials in 6-hydroxydopamine rat model of Parkinson's disease.

There has been a growing interest during the last years on the relationship between Parkinson's disease and changes in the oscillatory activity, mostly in the cortico-basal motor loop. As Parkinson's disease (PD) is not limited to motor symptoms, it is logical to assume that the changes in oscillatory activity are not limited to this loop. Steady-state responses (SSR) are the result of averaging individual responses to trains of rhythmic stimuli delivered at a constant frequency. The amplitude of the response varies depending on the stimulus modality and stimulation rate, with a frequency of maximal response that is probably associated to the working frequency of the pathway involved. The study of SSR may be of interest in PD as a non-invasive test of cortical oscillatory activity. Our aim was to study the changes in auditory steady-state responses (ASSR) in the 6-hydroxydopamine (6-OHDA) model of Parkinson's disease in rats. We recorded the ASSR over the auditory cortex in a group of 10 control and 17 6-OHDA lesioned rats (the latter before and after the administration of the dopaminergic agonist apomorphine) both awake and under anesthesia with ketamine/xylazine, using chirp-modulated stimuli. The three conditions (control, lesion, lesion plus apomorphine) were compared with special emphasis on the amplitude, inter-trial phase coherence, and frequency of maximal response. A reduction in the frequency of maximal response (between 40 and 60 Hz) was observed in the 6-OHDA lesioned rats that was normalized after apomorphine injection. The administration of this dopaminergic agonist also reduced the inter-trial phase coherence of the response in frequencies above 170 Hz. These findings suggest that the nigrostriatal dopaminergic system may be involved in the regulation of oscillatory activity not only in motor circuits, but also in sensory responses.

Effect of reduced attention on auditory amplitude-modulation following responses: a study with chirp-evoked potentials.

The amplitude of the auditory amplitude-modulation following responses (AMFR) is variable, depending on the modulation rate. Although 40-Hz responses have higher amplitudes in adults, the AMFR in the 80- to 120-Hz range are less influenced by sleep and more consistent in children. The effect of attention on 40-Hz responses has been addressed in some studies; however, no study to our knowledge has investigated the effect of attention on other stimulation rates. Our aim was to test the effect of attention on the AMFR to different frequencies of stimulation, using a chirp-modulated tone as stimulus. We recorded chirp-evoked responses in 12 subjects while attending to the sound (first condition) and reading a novel (second condition), in a randomly determined sequence. The energy of the response and the intertrial coherence (ITC) were measured by means of time-frequency transforms. The frequency range of response was similar in both conditions. No significant differences were found in the ITC values in the 40-Hz and the 80- to 120-Hz ranges, nor in the energy of the 40-Hz response. The only statistically significant difference found was the lower energy of the response in the 80- to 120-Hz range in the reading condition. Our results suggest that attention may affect auditory steady-state clinical testing using amplitude values. Phase measures may be preferable in this context.

Evaluación de la actividad reepitelizante del Triticum vulgare en la cervicitis crónica erosiva / Evaluation of reepithelizing activity of Triticum vulgare in chronic cervicitis

Las fitoestimulinas o bioestimulinas de origen vegetal, obtenidas por un proceso de extracción en gramíneas (principalmente en Triticum vulgare o trigo), estimulan la síntesis de RNAm y DNA en fibroblastos y activan la reepitelización de los tejidos. La cervicitis crónica se caracteriza por colecciones difusas de células inflamatorias en el estroma subepitelial y ocurre una proliferación del tejido conectivo fibroso en el estroma cervical. Ello resulta en una hipertrofia del cuello uterino.Se realizó un estudio clínico doble ciego en 40 pacientes con cervicitis crónica erosiva. Veinte pacientes recibieron crema vaginal del extracto acuoso de Triticum vulgare, dos veces al día durante 14 días consecutivos y las restantes placebo. Una vez iniciado el tratamiento con el Triticum vulgare, la leucorrea disminuyó tanto en cantidad como en porcentaje de pacientes que la presentaban (16.7por ciento vs 42.1por ciento en los grupos Triticum vulgare y placebo respectivamente). El tamaño de la lesión se redujo significativamente y la reepitelización completa de la misma empezó a manifestarse desde el día 16 en el grupo con Triticum vulgare. Al día 48, el 77.8por ciento de las pacientes con Triticum vulgare presentaban reepitelización total, comparado con 47.4por ciento del grupo con placebo. Observamos un caso de hipersensibilidad probablemente relacionada al medicamento; asimismo, también se presentó una inflamación intensa en una paciente del grupo placebo. Podemos concluir que el extracto acuoso de Triticum vulgare es un medicamento útil en la cervicitis crónica erosiva, ya que acelera significativamente la reepitelización del cuello uterino.