Short- and long-latency somatosensory neuronal responses reveal selective brain injury and effect of hypothermia in global hypoxic ischemia

Evoked potentials recorded from the somatosensory cortex have been shown to be an electrophysiological marker of brain injury in global hypoxic ischemia (HI). The evoked responses in somatosensory neurons carry information pertaining to signal from the ascending pathway in both the subcortical and cortical areas. In this study, origins of the subcortical and cortical signals are explored by decomposing the evoked neuronal activities into short- and long-latency responses (SLR and LLR), respectively. We evaluated the effect of therapeutic hypothermia on SLR and LLR during early recovery from cardiac arrest (CA)-induced HI in a rodent model. Twelve rats were subjected to CA, after which half of them were treated with hypothermia (32-34°C) and the rest were kept at normal temperature (36-37°C). Evoked neuronal activities from the primary somatosensory cortex, including multiunit activity (MUA) and local field potential (LFP), were continuously recorded during injury and early recovery. Results showed that upon initiation of injury, LLR disappeared first, followed by the disappearance of SLR, and after a period of isoelectric silence SLR reappeared prior to LLR. This suggests that cortical activity, which primarily underlies the LLR, may be more vulnerable to ischemic injury than SLR, which relates to subcortical activity. Hypothermia potentiated the SLR but suppressed the LLR by delaying its recovery after CA (hypothermia: 38.83 ± 5.86 min, normothermia: 23.33 ± 1.15 min; P < 0.05) and attenuating its amplitude, suggesting that hypothermia may selectively downregulate cortical activity as an approach to preserve the cerebral cortex. In summary, our study reveals the vulnerability of the somatosensory neural structures to global HI and the differential effects of hypothermia on these structures.     

Spatiotemporal variation of multiple neurophysiological signals in the primary motor cortex during dexterous reach-to-grasp movements

To examine the spatiotemporal distribution of discriminable information about reach-to-grasp movements in the primary motor cortex upper extremity representation, we implanted four microelectrode arrays in the anterior bank and lip of the central sulcus in each of two monkeys. We used linear discriminant analysis to compare information, quantified as decoding accuracy, contained in various neurophysiological signals. For all signal types, decoding accuracy increased immediately after the movement cue, peaked around movement onset, and declined during the static hold. Spike recordings and local field potential (LFP) time domain amplitude provided more discriminable information than LFP frequency domain power. Discriminable information on movement type was distributed evenly across recording sites by LFP amplitude and 1-4 Hz power but unevenly by 100-170 Hz power and spike recordings. These latter two signal types provided higher decoding accuracies closer to the hemispheric surface than deep in the anterior bank and also provided accuracies that varied along the central sulcus. This variation in the distribution of movement-type information may be related to differences in the rostral versus caudal regions of the primary motor cortex and to its underlying somatotopic organization. The even distribution of information by LFP amplitude and 1-4 Hz power compared with the more localized distribution by 100-170 Hz power and spikes suggest that these different neurophysiological signals reflect different underlying processes that distribute information through the motor cortex during reach-to-grasp movements.     

Efficient Generation of Schwann Cells from Human Embryonic Stem Cell-Derived Neurospheres

Schwann cells (SC), the glial cells of peripheral nerves, are involved in many diseases including Charcot Marie Tooth and neurofibromatosis, and play a pivotal role in peripheral nerve regeneration. Although it is possible to obtain human SC from nerve biopsies, they are difficult to maintain and expand in culture. Here we describe an efficient system for directing the differentiation of human embryonic stem cells (hESC) into cells with the morphological and molecular characteristics of SC. Neurospheres were generated from hESC using stromal cell induction and grown under conditions supportive of SC differentiation. After 8 weeks, hESC-derived SC expressed characteristic markers GFAP, S100, HNK1, P75, MBP and PMP-22, and were observed in close association with hESC-derived neurites. ~60% of the cells were double-immunostained for the SC markers GFAP/S100. RT-PCR analysis confirmed the expression of GFAP, S100, P75, PMP-22 and MBP and demonstrated expression of the SC markers P0, KROX20 and PLP in the cultures. Expression of CAD19 was observed in 2 and 4 week cultures and then was down-regulated, consistent with its expression in SC precursor, but not mature stages. Co-culture of hESC-derived SC with rat, chick or hESC-derived axons in compartmentalized microfluidic chambers resulted in tight association of the SC with axons. Apparent wrapping of the axons by SC was occasionally observed, suggestive of myelination. Our method for generating SC from hESC makes available a virtually unlimited source of human SC for studies of their role in nerve regeneration and modeling of disease.     

Detection of non-linearity in the EEG of schizophrenic patients.

OBJECTIVE: The aim of this study is to detect non-linearity in the EEG of schizophrenia with a modified method of surrogate data. We also want to identify if dimension complexity (correlation dimension using spatial embedding) could be used as a discriminating statistic to demonstrate non-linearity in the EEG. The difference between the attractor dimension of healthy subjects and schizophrenic subjects is expected to be interpreted as reflecting some mechanisms underlying brain wave by views of non-linear dynamics analysis may reflect mechanistic differences. METHODS: EEGs were recorded with 14 electrodes in 18 healthy male subjects (average age: 26.3; range: 20--35) and 18 male schizophrenic patients (average age: 30.6; range: 24--40) during a resting eye-closed state. Neither of two groups was taking medicines. All artificial epochs in the EEG records were rejected by an experienced doctor's visual inspection. RESULTS: Testing non-linearity with modified surrogate data, we showed that correlation dimension of EEG data of schizophrenia does refuse the null hypothesis that the data were resulted from a linear dynamic system. A decrease of dimension complexity was found in the EEG of schizophrenia compared with controls. We interpreted it as the result of the psychopath's dysfunction overall brain. The surrogating procedure results in a significant increase in D(s). CONCLUSIONS: Non-linearity of the EEG in schizophrenia was proven in our study. We think the correlation dimension with spatial embedding as a good discriminating statistic for testing such non-linearity. Moreover, schizophrenic patients' EEGs were compared with controls and a lower dimension complexity was found. The results of our study indicate the possibility of using the methods of non-linear time series analysis to identify the EEGs of schizophrenic patients.