Human voltage-gated Na+ and K+ channel properties underlie sustained fast AP signaling.

Human cortical pyramidal neurons are large, have extensive dendritic trees, and yet have unexpectedly fast input-output properties: Rapid subthreshold synaptic membrane potential changes are reliably encoded in timing of action potentials (APs). Here, we tested whether biophysical properties of voltage-gated sodium (Na+) and potassium (K+) currents in human pyramidal neurons can explain their fast input-output properties. Human Na+ and K+ currents exhibited more depolarized voltage dependence, slower inactivation, and faster recovery from inactivation compared with their mouse counterparts. Computational modeling showed that despite lower Na+ channel densities in human neurons, the biophysical properties of Na+ channels resulted in higher channel availability and contributed to fast AP kinetics stability. Last, human Na+ channel properties also resulted in a larger dynamic range for encoding of subthreshold membrane potential changes. Thus, biophysical adaptations of voltage-gated Na+ and K+ channels enable fast input-output properties of large human pyramidal neurons.

Magnetoencephalographic study of hand and foot sensorimotor organization in 325 consecutive patients evaluated for tumor or epilepsy surgery.

OBJECTIVES: The presence of intracranial lesions or epilepsy may lead to functional reorganization and hemispheric lateralization. We applied a clinical magnetoencephalography (MEG) protocol for the localization of the contralateral and ipsilateral S1 and M1 of the foot and hand in patients with non-lesional epilepsy, stroke, developmental brain injury, traumatic brain injury and brain tumors. We investigated whether differences in activation patterns could be related to underlying pathology. METHODS: Using dipole fitting, we localized the sources underlying sensory and motor evoked magnetic fields (SEFs and MEFs) of both hands and feet following unilateral stimulation of the median nerve (MN) and posterior tibial nerve (PTN) in 325 consecutive patients. The primary motor cortex was localized using beamforming following a self-paced repetitive motor task for each hand and foot. RESULTS: The success rate for motor and sensory localization for the feet was significantly lower than for the hands (motor_hand 94.6% versus motor_feet 81.8%, p < 0.001; sensory_hand 95.3% versus sensory_feet 76.0%, p < 0.001). MN and PTN stimulation activated 86.6% in the contralateral S1, with ipsilateral activation < 0.5%. Motor cortex activation localized contralaterally in 76.1% (5.2% ipsilateral, 7.6% bilateral and 11.1% failures) of all motor MEG recordings. The ipsilateral motor responses were found in 43 (14%) out of 308 patients with motor recordings (range: 8.3-50%, depending on the underlying pathology), and had a higher occurrence in the foot than in the hand (motor_foot 44.8% versus motor_hand 29.6%, p = 0.031). Ipsilateral motor responses tended to be more frequent in patients with a history of stroke, traumatic brain injury (TBI) or developmental brain lesions (p = 0.063). CONCLUSIONS: MEG localization of sensorimotor cortex activation was more successful for the hand compared to the foot. In patients with neural lesions, there were signs of brain reorganization as measured by more frequent ipsilateral motor cortical activation of the foot in addition to the traditional sensory and motor activation patterns in the contralateral hemisphere. The presence of ipsilateral neural reorganization, especially around the foot motor area, suggests that careful mapping of the hand and foot in both contralateral and ipsilateral hemispheres prior to surgery might minimize postoperative deficits.

Slowing of M1 oscillations in brain tumor patients in resting state and during movement.

OBJECTIVE: Brain tumors may severely disrupt the structure and function of the brain. While abnormal low-frequency activity can be found around tumor borders, disrupted structural connectivity may also impinge on neural activity in distant brain regions and other frequency bands. We investigated how glioma in patients with normal motor functioning affects activity in primary motor areas (M1). METHODS: Using magnetoencephalography in 12 patients with unilateral glioma located around the central sulcus, we studied activity in bilateral M1s in resting state and during movement with focus on motor-related mu (8-12Hz) and beta rhythms (15-30Hz). Principal component analysis served to test for differences in spectral content. RESULTS: A shift was found towards lower frequencies for M1 in the tumor hemisphere compared to M1 in the healthy hemisphere, caused by an increase in mu and decrease in beta power. This pattern was observed both in resting state and during movement. CONCLUSIONS: This 'slowing' of brain oscillations in M1 resembles findings in patients with monohemispheric stroke and Parkinson's disease. A loss of intra-cortical connectivity may account for these findings, possibly supplemented by tumor-induced changes in neurotransmitter systems. SIGNIFICANCE: Motor functioning may be unaffected by a spectral shift of mu and beta oscillations.

Localisation of the central sulcus region in glioma patients with three-dimensional fluid-attenuated inversion recovery and volume rendering: comparison with functional and conventional magnetic resonance.

PURPOSE: Volume rendering (VR) of three-dimensional (3D) fluid-attenuated inversion recovery (FLAIR) magnetic resonance (MR) images shows regional intensity differences, reflecting the central sulcus (CS) region and occipital cortex. The purpose of this study was to determine whether 3D FLAIR with VR could be used as an alternative method to localise the CS region in comparison with functional and conventional MR-imaging in patients with perirolandic glioma. METHODS: Eleven patients with intracranial gliomas were studied with single-slab 3D FLAIR including VR and conventional T1-weighted imaging. In all patients, preoperative functional magnetic resonance imaging (fMRI) was performed with a motor paradigm of the hand. The hypo-intense central gyri on 3D FLAIR with VR were interpreted as the CS area. Localisation of the motor hand knob on anatomical images and fMRI results were used for identification of the primary motor cortex. RESULTS: Anatomical localisation of the motor hand knob on T1-weighted images was possible in 91% of both hemispheres. In 73% of the affected hemispheres (AH) and 91% of the unaffected hemispheres (UH) the hand knob and CS region could be identified on 3D FLAIR axial and VR images, respectively. With one exception, fMRI activation confirmed the CS region as observed with 3D FLAIR with VR. CONCLUSIONS: Volume rendering of 3D FLAIR MR images shows central hypo-intensities frequently corresponding with the CS region. Two-dimensional localisation of the CS region on conventional T1-weighted images and fMRI seems favourable compared to 3D FLAIR. However, in selected cases, especially where fMRI is not possible or feasible, volume rendering with 3D FLAIR may enhance the 3D visualisation of gliomas in relation to the CS region which can be used as an alternative method in the presurgical structural and functional evaluation of neurosurgical patients.

Topographical organization of mu and Beta band activity associated with hand and foot movements in patients with perirolandic lesions.

To study the topographical organization of mu and beta band event-related desynchronization (ERD) associated with voluntary hand and foot movements, we used magnetoencephalographic (MEG) recordings from 19 patients with perirolandic lesions. Synthetic aperture magnetometry (SAM) was used to detect and localize changes in the mu (7 - 11 Hz) and beta (13 - 30 Hz) frequency bands associated with repetitive movements of the hand and foot and overlaid on individual coregistered magnetic resonance (MR) images. Hand movements showed homotopic and contralateral ERD at the sensorimotor (S/M) cortex in the majority of cases for mu and to a lesser extent for beta rhythms. Foot movements showed an increased heterotopic distribution with bilateral and ipsilateral ERD compared to hand movements. No systematic topographical segregation between mu and beta ERD could be observed. In patients with perirolandic lesions, the mu and beta band spatial characteristics associated with hand movements retain the expected functional-anatomical boundaries to a large extent. Foot movements have altered patterns of mu and beta band ERD, which may give more insight into the differential functional role of oscillatory activity in different voluntary movements.

Magnetoencephalographic study of posterior tibial nerve stimulation in patients with intracranial lesions around the central sulcus.

OBJECTIVE: To study interhemispheric differences of somatosensory evoked field (SEF) characteristics and the spatial distribution of equivalent current dipole sources in patients with unilateral hemispheric lesions around the central sulcus region. METHODS: In 17 patients with perirolandic lesions, averaged somatosensory responses after posterior tibial nerve stimulation at the ankle were recorded with magnetoencephalography. Dipole source solutions in the affected (AH) and unaffected (UH) hemispheres were analyzed and compared for latency, equivalent current dipole strength, root mean square, and spatial distribution in relation to clinical findings. RESULTS: Three main SEF components, P45m, N60m, and P75m, were identified in the hemisphere contralateral to the stimulated nerve. Dipole strength for the P45m component was significantly higher in the AH compared with the UH. SEF characteristics in the AH and UH showed no significant differences with respect to component latency or dipole strength of the N60m and P75m components. Interdipole location asymmetries exceeded 1.0 cm in 71% of the patients. Comparison of the posterior tibial nerve evoked responses (P45m and N60m) in patients with motor deficits and patients without deficits showed that these responses are enlarged in the AH when perirolandic lesions are present. Patients with motor deficits also showed an increased response for P45m in the UH. CONCLUSION: The results of posterior tibial nerve SEFs suggest spatial and functional changes in the somatosensory network as a result of perirolandic lesions with a possible relationship with clinical symptoms. The results can provide further basis for the evaluation of cortical changes in the presence of perirolandic lesions.