Molecular identification of aspartate N-acetyltransferase and its mutation in hypoacetylaspartia.

The brain-specific compound NAA (N-acetylaspartate) occurs almost exclusively in neurons, where its concentration reaches approx. 20 mM. Its abundance is determined in patients by MRS (magnetic resonance spectroscopy) to assess neuronal density and health.

The challenge of non-invasive cognitive physiology of the human brain: how to negotiate the irrelevant background noise without spoiling the recorded data through electronic averaging.

Brain mechanisms involved in selective attention in humans can be studied by measures of regional blood flow and metabolism (by positron emission tomography) which help identify the various locations with enhanced activities over a period of time of seconds. The physiological measures provided by scalp-recorded brain electrical potentials have a better resolution (milliseconds) and can reveal the actual sequences of distinct neural events and their precise timing. We studied selective attention to sensory inputs from fingers because the brain somatic representations are deployed over the brain convexity under the scalp thereby making it possible to assess distinct stages of cortical processing and representation through their characteristic scalp topographies.

Failure to recognise objects by active touch (astereognosia) results from lesion of parietal-cortex representation of finger kinaesthesis.

The inability to identify objects by manipulation with eyes closed (astereognosia) results from a focal cortical lesion of the second order parietal area 2, which integrates inputs from finger joints with tactile information.

Human perceptual processing: inhibition of transient prefrontal-parietal 40 Hz binding at P300 onset documented in non-averaged cognitive brain potentials.

Non-averaged scalp-recorded human brain potentials were analyzed during selective attention to somatic (finger) sensory stimuli. Distinct cognitive electrogeneses were identified by numerical assessment of their scalp topographical congruities with appropriate templates. The P300 electrogenesis and the 40 Hz neuronal oscillations disclosed, at different scalp sites, variations in timing from trial to trial.

Non-averaged human brain potentials in somatic attention: the short-latency cognition-related P40 component.

1. Non-averaged scalp-recorded brain potentials were studied in humans during selective attention to randomly intermixed series of stimuli to fingers. Physiological tests were use for validating the presence or absence of the short-latency cognition-related P40 electrogeneses in parietal cortex in the response to a single-target stimulus (P40 signifies a positive polarity of about 40 ms peak latency).

Origin of N18 and P14 far-fields of median nerve somatosensory evoked potentials studied in patients with a brain-stem lesion.

Somatosensory evoked potentials (SEPs) to median nerve stimulation were recorded in 3 patients with a brain-stem or medullary lesion documented by clinical and CT or MRI evidence. The positive P14 and negative N18 scalp far-fields were preserved. The results suggest that P14 reflects the spike volley in caudal medial lemniscus, and that the N18 neural generators are located in the medulla, probably in the dorsal column nuclei and/or the accessory inferior olives.

Consciousness.

Consciousness offers a major challenge to the neurosciences. Even though consciousness is by definition subjective and private to the organism concerned, we consider it to be an intrinsic feature of biological processes in the brain. As such, it should be viewed in the Darwinian perspective of natural selection which implies that the conscious brain function does have survival value and cannot be a mere epiphenomenon.

Transient phase-locking of 40 Hz electrical oscillations in prefrontal and parietal human cortex reflects the process of conscious somatic perception.

Electrical potential oscillations in the range of 35-45 Hz (gamma waves) have recently been shown to occur rather ubiquitously in the brain of awake humans. During selective somatic attention, we demonstrate a transient phase-locking of the gamma waves generated in the contralateral prefrontal and parietal cortical areas that we had previously shown to be involved in such selective attention tasks. In line with other microphysiological evidence obtained on mammalian visual cortex, this selective functional synchronization between critical human brain areas (as far as about 9 cm apart) is proposed to reflect the transient 'binding' of discrete cognitive features that are processed in distributed neuronal assemblies of the brain whereby the conscious perception of an object or event can be achieved.

A method for identifying short-latency human cognitive potentials in single trials by scalp mapping.

Studies of scalp-recorded brain event-related potentials in humans currently depend on the electronic averaging of many responses to the stimulus. In non-averaged single responses, it is sometimes possible to see late components such as the so-called P300, but not the shorter latency components that are much smaller and masked in background noise. We tried to identify short-latency cognitive potentials evoked by finger stimulation by comparing single trial responses that are concomitantly recorded at the contralateral and ipsilateral parietal scalp respectively.

SEPs to finger joint input lack the N20-P20 response that is evoked by tactile inputs: contrast between cortical generators in areas 3b and 2 in humans.

A method using a DC servo motor is described to produce brisk angular movements at finger interphalangeal joints in humans. Small passive flexions of 2 degrees elicited sizable somatosensory evoked potentials (SEPs) starting with a contralateral positive P34 parietal response thought to reflect activation of a radial equivalent dipole generator in area 2 which receives joint inputs. By contrast, electric stimulation of tactile (non-joint) inputs from the distal phalanx evoked the usual contralateral negative N20 reflecting a tangential equivalent dipole generator in area 3b.

Right or left ear reference changes the voltage of frontal and parietal somatosensory evoked potentials.

Short-latency cortical somatosensory evoked potentials (SEPs) to left median nerve stimulation were recorded with either the left or right earlobe as reference. With a right earlobe reference the voltage of the parietal N20 and P27 was reduced while the voltage of the frontal P20 and N30 was enhanced. The effects were consistent, but their size varied with the SEP component considered and also among the subjects.

Nasopharyngeal recordings of somatosensory evoked potentials document the medullary origin of the N18 far-field.

Because the nasopharyngeal electrode provides non-invasive access to the ventral brain-stem at the medullo-pontine level we used it for recording somatosensory evoked potentials (SEPs) to median nerve stimulation (non-cephalic reference). After the P9 and P11 far-fields, the nasopharyngeal SEPs disclosed a negative-going component which was interpreted as the near-field equivalent of the P14 scalp far-field generated in the caudal part of the medial lemniscus. Nasopharyngeal SEPs also revealed a large N18 with voltage and features strikingly similar to those of the scalp-recorded N18 far-field.

Reaction times recording methods: reliability and EMG analysis of patterns of motor commands.

Different methods for estimating reaction times (RTs) from either finger flexion or finger extension responses have been evaluated. The onset of finger movement was recorded with a photoelectric method and the results are compared with RT measures based on microswitch closure or onset of electromyographic (EMG) activity in the prime move muscle. EMG analysis showed the voluntary motor commands to present a characteristic ballistic pattern in RTs.

Focal capsular vascular lesions can selectively deafferent the prerolandic or the parietal cortex: somatosensory evoked potentials evidence.

Four patients with a unilateral focal vascular accident involving the internal capsule (but not the cortex) were studied electrophysiologically. Averaged somatosensory evoked potentials (SEPs) to electrical stimulation of the median nerve on the left or the right side were analyzed. In the 3 patients with hemiparesis and normal somatic sensation, the precentral P22 and N30 SEP components were lost, whereas the parietal components were preserved.

Lymphocyte response is enhanced by supplementation of elderly subjects with selenium-enriched yeast.

The effect of selenium supplementation on plasma selenium concentrations and lymphocyte-proliferation responses to mitogens was investigated in 22 elderly institutionalized subjects. Subjects were assigned to a 6-mo trial with either 100 micrograms Se/d (as selenium-enriched yeast) or a placebo. Plasma selenium concentrations of the selenium-supplemented group increased from 0.

Inadequacy of the average reference for the topographic mapping of focal enhancements of brain potentials.

The main reason for doing topographic mapping of EEG or evoked potentials is to assess regional changes in brain potentials. The use of an average reference is shown to have perverse effects in this relation, namely because it imposes on the recorded data a zero-centering effect which can reduce, eliminate or even reverse the focal changes of bit-mapped brain potentials. Concurrent studies on a true 3-shell head model suggest that such distortions of human EEG data occur because the average reference is computed from a set of (scalp) recording electrodes which do not survey the bottom half of the head volume so that the integral of scalp-recorded potentials frequently differs from zero.

Emulation of somatosensory evoked potential (SEP) components with the 3-shell head model and the problem of 'ghost potential fields' when using an average reference in brain mapping.

In brain topographic mapping, the putative location and orientation in the head space of neural generators are currently inferred from the features of negative and positive scalp potential fields. This procedure requires the use of a fairly neutral reference. The frequently advocated average reference creates problems because its effect is not merely to change a (steady) zero reference level, but to dynamically zero-center all scalp potentials at each latency.

Topographic analysis in brain mapping can be compromised by the average reference.

The average reference introduces ghost potential fields at the latencies for which the integral of scalp-recorded potentials differs from zero. These spurious effects occur because the average reference is computed from a limited number of (scalp) electrodes which do not survey the bottom half of the head. By arbitrarily re-setting the zero at each latency in the maps to be compared, it can also obliterate or even reverse topographical differences in the case of focal brain potentials enhancements thereby defeating the purpose of brain mapping.

Bilateral somatosensory evoked potentials in four patients with long-standing surgical hemispherectomy.

Four patients were studied electrophysiologically 8 to 24 years after surgical removal of one cerebral hemisphere without damage to the striatum or diencephalon. Somatosensory evoked potentials (SEPs) to electrical stimulation of the median nerve on the left or right side were averaged and mapped out over the scalp. Stimulation on the side opposite to the missing hemisphere evoked brief P9 and P14 farfields and a slow N18 negative potential of 15- to 25-msec duration bilaterally.