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Layout of a multiplexed electrode VLSI circuit for monitoring evoked responses in cerebral cortex.

This paper summarizes the details of the design of an integrated circuit layout usable as a multiple-electrode implantable cerebral cortex sensor. The purpose of implanting multiplexed electrode circuits in a cerebral cortex is to monitor the electroencephalograph (EEG) and visual evoked response (VER) generated while the subject performs normal visual functions. A summary of the human image processing system is given as a background for the circuit design work. A typical subject for the research would be a laboratory animal. External power, clocking, and analogue data lines required for its operation posed problems for the original electrode chip. The second generation brain chip includes self contained-power with on-board multiplexing and clocking circuits. The most significant improvement is the incorporation of analogue to digital (A/D) converters. Through the use of A/D converters, brain signal data can be converted at the site of implant, eliminating induced noise from analogue wires used on the original chip. Conversion at the implant site, the primary visual cortex, yields a more accurate indication of the actual brain data.

Cerebral Cortex↗

A model of the ventral visual system based on temporal stability and local memory.

The cerebral cortex is a remarkably homogeneous structure suggesting a rather generic computational machinery. Indeed, under a variety of conditions, functions attributed to specialized areas can be supported by other regions. However, a host of studies have laid out an ever more detailed map of functional cortical areas. This leaves us with the puzzle of whether different cortical areas are intrinsically specialized, or whether they differ mostly by their position in the processing hierarchy and their inputs but apply the same computational principles. Here we show that the computational principle of optimal stability of sensory representations combined with local memory gives rise to a hierarchy of processing stages resembling the ventral visual pathway when it is exposed to continuous natural stimuli. Early processing stages show receptive fields similar to those observed in the primary visual cortex. Subsequent stages are selective for increasingly complex configurations of local features, as observed in higher visual areas. The last stage of the model displays place fields as observed in entorhinal cortex and hippocampus. The results suggest that functionally heterogeneous cortical areas can be generated by only a few computational principles and highlight the importance of the variability of the input signals in forming functional specialization.

Cerebral Cortex↗

Auditory evoked visual awareness following sudden ocular blindness: an EEG and TMS investigation.

Neurophysiological and neuroanatomical studies have provoked controversy about whether the visual cortex may be more modifiable than previously believed. Auditory processing is enhanced in blind compared to sighted people, and the enhancement might reflect encroachment of auditory transmission onto visual cortex. To address this issue, we recorded the auditory event-related potentials (ERPs) correlated with auditory related paradoxical visual awareness in a subject with traumatic total late-onset blindness. We found that (1) there was auditory related brain activity over the occipital visual scalp regions starting from a very early stage (< 80 ms) and (2) this occipital activity was significantly different between "visually aware" and "visually unaware" responses in the P1 (40-80 ms) component following meaningful stimuli. There was also a significant difference between responses with and without visual awareness in the N1 (100-120 ms) component following either tones or meaningful stimuli. The phosphenes accompanying auditory stimuli in the ERP experiment were always perceived to be directly in front of the subject and this was reproduced by transcranial magnetic stimulation over the blind primary visual cortex and by sudden sounds delivered to the side or behind the subject. The TMS induced phosphenes were restricted to the central part of the space and were, at least qualitatively, the same as those induced by sounds. The results are clear evidence that human perceptual functions can be reorganized after sudden, late-onset, total ocular blindness.

Acoustic Stimulation↗

Dynamics of neuronal processing in rat somatosensory cortex.

Recently, the study of sensory cortex has focused on the context-dependent evolution of receptive fields and cortical maps over millisecond to second time-scales. This article reviews advances in our understanding of these processes in the rat primary somatosensory cortex (SI). Subthreshold input to individual rat SI neurons is extensive, spanning several vibrissae from the center of the receptive field, and arrives within 25 ms of vibrissa deflection. These large subthreshold receptive fields provide a broad substrate for rapid excitatory and inhibitory multi-vibrissa interactions. The 'whisking' behavior, an approximately 8 Hz ellipsoid movement of the vibrissae, introduces a context-dependent change in the pattern of vibrissa movement during tactile exploration. Stimulation of vibrissae over this frequency range modulates the pattern of activity in thalamic and cortical neurons, and, at the level of the cortical map, focuses the extent of the vibrissa representation relative to lower frequency stimulation (1 Hz). These findings suggest that one function of whisking is to reset cortical organization to improve tactile discrimination. Recent discoveries in primary visual cortex (VI) demonstrate parallel non-linearities in center-surround interactions in rat SI and VI, and provide a model for the rapid integration of multi-vibrissa input. The studies discussed in this article suggest that, despite its original conception as a uniquely segregated cortex, rat SI has a wide array of dynamic interactions, and that the study of this region will provide insight into the general mechanisms of cortical dynamics engaged by sensory systems.

Animals↗

Preserved visual-vestibular interaction in patients with bilateral vestibular failure.

BACKGROUND: During caloric vestibular stimulation, subjects showed bilateral activation of the vestibular cortex in the posterior insula and retroinsular region as well as concurrent deactivation of visual cortex areas bilaterally. This finding was the basis for the concept of a reciprocal inhibitory interaction between the vestibular and the visual systems. OBJECTIVE: To analyze the modulations of this activation and deactivation pattern in patients with loss of vestibular input, that is, in patients with bilateral vestibular failure (BVF). METHODS: Modulations of regional cerebral blood flow (rCBF) in PET were measured in nine patients with BVF and compared with those in healthy volunteers using statistical group as well as single-subject analyses (Statistical Parametric Mapping 96b). RESULTS: The group analysis of the BVF patients showed only one small region of activation in the posterior insula contralateral to the stimulated ear, whereas the other areas correlating with vestibular, autonomic, and ocular motor function were not activated. Furthermore, the concurrent rCBF decreases of the primary visual cortex seen in healthy volunteers were not found in the patients. These decreases seem to be dependent on an intact vestibular input with concurrent vestibular nystagmus. CONCLUSIONS: The results are compatible with the concept of a reciprocal inhibitory sensorisensory interaction between the vestibular and visual systems that normally act together for orientation in space and perception of motion. This interaction appears to be preserved in the patients at a significantly lower level, that is, with less activation and less deactivation.

Adult↗

Immunoreactivity for Taurine Characterizes Subsets of Glia, GABAergic and non-GABAergic Neurons in the Neo- and Archicortex of the Rat, Cat and Rhesus Monkey: Comparison with Immunoreactivity for Homocysteic Acid.

The cerebral cortex is an area rich in taurine (2-aminoethanesulphonic acid), but only limited information exists regarding its cellular distribution. We therefore examined taurine-like immunoreactivity in the cerebral cortex of the rat, cat and macaque monkey using antiserum directed against glutaraldehyde-conjugated taurine. Immunostaining was assessed at the light and electron microscopic level, and patterns obtained in light microscopic studies were compared to those produced with antiserum to gamma-aminobutyric acid (GABA) and homocysteic acid (HCA). In all three species, strong taurine-like immunoreactive perivascular endothelial cells, pericytes and oligodendrocytes were found. These cells were located throughout the neuropil, which itself showed a low level of immunoreactivity. In rats and cats, a small number of weakly taurine-enriched neurons were observed, particularly in superficial layers. In all cortical areas of the macaque, however, glial staining was matched by strong, selective staining of subpopulations of cortical neurons which were distributed in a bilaminar pattern involving layers II/III and VI. In addition, in primary visual cortex, area 17, immunopositive neurons were also present in sublayer IVCbeta, while in the hippocampus strongly taurine-positive neurons were most conspicuous in the granule cell layer of the dentate gyrus. In all regions, strongly taurine-positive neurons constituted only a subpopulation of the neurons occupying a given layer. Examination of adjacent sections for GABA immunoreactivity showed that the most strongly taurine-positive neurons in layers II/III were immunoreactive for GABA. The cells located in layers IVCbeta and VI, and the granule cells of the dentate gyrus, however, were GABA-negative. The morphological features of these latter groups suggested that the antiserum to taurine identifies subsets of spiny stellate, small pyramidal and dentate granule cells. None of these neurons showed immunoreactivity with antiserum to HCA in the primate; HCA-positive glia were found along the pial and white matter boundaries of the cortex, and showed no overlap with strongly taurine-positive glial elements. Although a transmitter role for taurine may be unlikely, particularly in view of its enrichment in subpopulations of both inhibitory and excitatory cells, the capacity of taurine to influence membrane-associated functions in excitable tissues, and its selective distribution demonstrated here, provides the potential for a contribution to communication between cortical cells.

Journal Article↗

Is there a role of visual cortex in spatial hearing?

The integration of auditory and visual spatial information is an important prerequisite for accurate orientation in the environment. However, while visual spatial information is based on retinal coordinates, the auditory system receives information on sound location in relation to the head. Thus, any deviation of the eyes from a central position results in a divergence between the retinal visual and the head-centred auditory coordinates. It has been suggested that this divergence is compensated for by a neural coordinate transformation, using a signal of eye-in-head position. Using functional magnetic resonance imaging, we investigated which cortical areas of the human brain participate in such auditory-visual coordinate transformations. Sounds were produced with different interaural level differences, leading to left, right or central intracranial percepts, while subjects directed their gaze to visual targets presented to the left, to the right or straight ahead. When gaze was to the left or right, we found the primary visual cortex (V1/V2) activated in both hemispheres. The occipital activation did not occur with sound lateralization per se, but was found exclusively in combination with eccentric eye positions. This result suggests a relation of neural processing in the visual cortex and the transformation of auditory spatial coordinates responsible for maintaining the perceptual alignment of audition and vision with changes in gaze direction.

Acoustic Stimulation↗

Neuronal number and volume alterations in the neocortex of HIV infected individuals.

Substantial neuronal loss in the superior frontal gyrus in patients who have died of AIDS have been reported previously. This investigation examined the distribution of neuronal loss in three other neocortical areas and, alteration in neuronal volume in four neocortical areas. This was carried out using two stereological probes, the "disector" and the "nucleator". These recently developed methods provide estimations, regardless of size and shape, in real three-dimensional space, and are more efficient than conventional quantitation. The study was performed on 12 HIV infected individuals and nine controls. The HIV group had no neuropathological evidence of opportunistic infections or neoplasms, five had HIV encephalitis and the remaining seven had only minimal pathology. There was significant neuronal loss of 30% (p = 0.018) in the calcarine cortex (primary visual area), and loss of 18% in the superior parietal lobule which just failed to reach significance. This loss was not related to the presence of HIV encephalitis. The mean neuronal volume was increased in the occipital area by 29% (p = 0.028) and the frequency of large neurons (over 2000 microns 3) doubled in the frontal (p < 0.05) and parietal (p < 0.02) areas. The results confirm the hypothesis that HIV infection is associated with neuronal injury and death, and suggest that increase in neuronal size may be a feature of the cytopathology of this condition.

Acquired Immunodeficiency Syndrome↗

High spatial resolution functional magnetic resonance imaging at very-high-magnetic field.

Although neuroimaging methods have been used successfully to map large-scale neurocognitive networks distributed across the human cortex, functional mapping and differentiation of localized brain organization within a small structure has been limited by inadequate sensitivity for high spatial resolution imaging. Functional magnetic resonance imaging (fMRI) technique based on blood oxygenation level-dependent (BOLD) contrast has become one of the most useful neuroimaging techniques. It has been used extensively to study human brain function from sensory perception to cognitive performance. However, the majority of these studies used a relatively low spatial resolution (typically with a voxel size of 3.1 x 3.1 x 5.0 mm3), which is incapable of mapping on the millimeter and submillimeter spatial scale. In this article, we review the technical aspects of the high-resolution fMRI technique and the sensitivity and spatial specificity of BOLD-based fMRI. We demonstrate applications of high-resolution fMRI in studying the human visual pathway from the lateral geniculate nucleus in the thalamus to the ocular dominance columns in the primary visual cortex. Most results were obtained at very-high-magnetic fields (3.0 and 4.0 Tesla). They reveal that high-resolution fMRI at very-high-magnetic field is promising for functional mapping of brain organization from large cortical networks, small nuclei, and even to cellular layer structures.

Brain↗

Model of blood-brain transfer of oxygen explains nonlinear flow-metabolism coupling during stimulation of visual cortex.

The coupling between cerebral metabolic rate of oxygen (CMRO2) and blood flow (CBF) in response to visual stimulation was evaluated by means of a model of oxygen delivery. The model predicted a nonlinear relationship between stimulus-evoked changes of oxygen consumption and blood flow. The magnitude of the CMRO2/CBF ratio index (IO2) was used to indicate the degree of flow-metabolism coupling prevailing in specific areas of the brain during physiological stimulation. Therefore, the index provided a measure of the blood oxygenation level dependent (BOLD) magnetic resonance contrast. To evaluate the changes of IO2 in response to visual stimulation, the model was applied to the effect of a changing flicker rate of a visual stimulus on the magnitudes of CBF, CMRO2, and oxygen diffusion capacity, in the human brain. Positron emission tomography (PET) was used to measure the CBF and the CMRO2 in 12 healthy volunteers who viewed a cross-hair (baseline) or a yellow-blue annular checkerboard reversing at frequencies of 1, 4, or 8 Hz. The magnitude of CBF in the primary visual cortex increased as a function of the checkerboard reversal rate and reached a maximum at the frequency of 8 Hz (z=16.0), while the magnitude of CMRO2 reached a maximum at 4 Hz (z=4.0). Therefore, the calculated IO2 was lower at 8 Hz than at 1 and 4 Hz, in contrast to the oxidative metabolic rate that reached its maximum at 4 Hz. The model explained the increase of oxygen consumption as the combined effect of increased blood flow and increased oxygen diffusion capacity in the region of visual activation.

Adult↗

Visual cortex reactivity in sedated children examined with perfusion MRI (FAIR).

Sleeping and sedated children can respond to visual stimulation with a decrease in blood oxygenation level dependent (BOLD) functional MRI signal response. The contribution of metabolic and hemodynamic parameters to this inverse signal response is incompletely understood. It has been hypothesized that it is caused by a relatively greater increase of oxygen consumption compared to rCBF (regional cerebral blood flow) increase. We studied the rCBF changes during visual stimulation in four sedated children, aged 4-71 months, and four alert adults, with an arterial water spin labeling technique (FAIR) and BOLD fMRI in a 1.5T MR scanner. In the children, FAIR signal decreased by a mean of 0.96% (range 0.77-1.05) of the baseline periods of the non-selective images, while BOLD signal decreased by 2.03% (range 1.99-2.93). In the adults, FAIR and BOLD signal increased by 0.88% (range 0.8-0.99) and 2.63% (range 1.99-2.93), respectively. Thus, in the children, an rCBF increase could not be detected by perfusion MRI, but indications of a FAIR signal decrease were found. An rCBF decrease in the primary visual cortex during stimulation has not been reported previously, but it is a possible explanation for the negative BOLD response. Future studies will have to address if this response pattern is a consequence of age or sleep/sedation.

Adult↗

Tachykinins preferentially excite certain complex cells in the infragranular layers of feline striate cortex.

Microiontophoretically administered substance P (SP) affected the visually evoked responses (VER) and the spontaneous firing of 22 (14%) of the 152 neurons recorded from the striate cortex of anaesthetised cats. Enhancing effects were seen in 14 neurons and suppressant actions in 8 neurons. Most of the cells excited by SP were located in infragranular layers and had complex receptive fields; a few belonged to the movement-sensitive class or responded only weakly to visual stimulation. Of the neurons recorded in layer V, about 70% were excited by SP; the respective proportions were 8% in layer VI, and 2% in layer IV. Cells suppressed by SP had either simple or unimodal receptive fields including hypercomplex varieties; most of them were located in layer IVc. The effects of other tachykinins (neurokinin A, neurokinin B) and of the NK-3 receptor agonist Senktide tested in 36 cells were identical to those of SP with respect to types, and intracortical locations, of cells affected. During the enhancement induced by the tachykinins functional parameters of the neurons such as orientation and direction sensitivity were not substantially affected. It seems likely therefore that the effect of tachykinins in the primary visual cortex is not a shaping of receptive field properties, but rather a modulation of the general excitability of neurons projecting to subcortical centers, in particular to the midbrain and pons.

Animals↗

Dynamics of striate cortical activity in the alert macaque: I. Incidence and stimulus-dependence of gamma-band neuronal oscillations.

Using single and multiunit recordings in the striate cortex of alert macaque monkeys, we find that gamma-band (20-70 Hz) oscillations in neuronal firing are a prominent feature of V1 neuronal activity. The properties of this rhythmic activity are very similar to those previously observed in the cat. Gamma-band activity is strongly dependent on visual stimulation, largely absent during spontaneous activity and, under the conditions of our experiment, not time-locked to the vertical refresh of the computer monitor (80 Hz) used to present the stimuli. In our sample, 61% of multiunit activity (MUA) and 46% of single-unit activity (SUA) was significantly oscillatory, with mean frequencies of 48+/-9 and 42+/-13 Hz, respectively. Gamma-band activity was most likely to occur when cells were activated by their optimal stimuli, but still occurred, although less often and with lower amplitude, in response to nonoptimal stimuli. The frequency of gamma-band activity also reflected stimulus properties, with drifting gratings evoking higher-frequency oscillations than stationary gratings. As in the cat, the spike trains of single cells showing gamma-band oscillations often displayed a pattern of repetitive burst firing, with intraburst firing rates of 300-800 Hz. The overall similarity of rhythmic neuronal activity in the primary visual cortex of cats and monkeys suggests that the phenomenon is not species-specific. The stimulus-dependence of the rhythmic activity is consistent with a functional role in visual perception.

Action Potentials↗

Parcellation of the frontal cortex of the New World monkey Callithrix jacchus by eight neurotransmitter-binding sites.

The most extensive development during primate brain evolution involves the cortex of the frontal lobe, especially its prefrontal region. The distribution of neurotransmitter receptors is unknown in this part of the cortex of New World monkeys. The respective distributions of eight different receptors for the transmitters L-glutamate (L-glu and NMDA), gamma-amino-butyric acid (GABAA), noradrenaline (alpha 1), acetylcholine (M1 and M2) and serotonin (5-HT1 and 5-HT2) were therefore studied in cortical areas of the frontal lobe of the lissencephalic New World monkey, Callithrix jacchus. The results are compared to earlier data on Old World monkeys in order to obtain insight into evolutionary trends at the level of chemical neuroanatomy. Our results indicate that the density and laminar pattern of some receptors change precisely at the cytoarchitectonic boundaries between different cortical areas, while some other receptors do not exhibit measurable changes. For example, the premotor area 6 can be distinguished from prefrontal areas by its high concentration of adrenergic alpha 1 receptors as labelled with [3H] prazosin, with only the cingulate area 24 showing higher values. In other cases, the receptor distribution changes within a cytoarchitectonically homogeneous area. Thus, area 8 can be subdivided into dorsal and ventral regions on the basis of the distribution of GABAA, muscarinic and serotonin receptors. Comparison of these results in a New World monkey with receptor distributions in other primate species reveals much larger interspecies differences in the areas of the frontal lobe than e.g. in the primary visual cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Transplantation of fetal lateral geniculate nucleus to the occipital cortex: connectivity with host's area 17.

The developing lateral geniculate complex was excised from fetal albino rats at 18 days of gestation and implanted into the occipital cortex of host animals at 5 days of postnatal age. Groups of host animals were sacrificed at 10, 20 and 30 days following this procedure. The transplant tissue of selected animals was stereotaxically lesioned 2 days prior to scheduled sacrifice and their brains subjected to either Fink-Heimer or electron microscopic analysis of the distribution and density of degenerating efferents from the transplant. The remaining animals were analysed by means of Bodian, Golgi-Cox or electron microscopic techniques. Transplanted neurons displayed typical dendritic branching patterns of geniculate relay neurons by 20 days following implantation. Intrinsic neurons, characterized by a small ovoid soma and two main stem dendrites, only became evident in transplant tissue by 30 days and were much reduced in number. Synapses developed by 10 days and rapidly increased in number by 20 and 30 days. Most complexes were simple axo-dendritic, asymmetric junctions. Multiple serial and reciprocal complexes, as well as the characteristic glomerular complex, failed to appear. Analysis of Bodian stained material revealed a dense network of fibers coursing about the transplant. Distinct bundles of these fibers were observed extending from the medial edge of the transplant into area 17 by 20 days following implantation. A Fink-Heimer analysis of animals whose transplants were stereotaxically lesioned revealed degeneration in Layers II-VI of the primary visual cortex but the majority of these fibers terminated within the lateral two-thirds of Layer IV. Few degenerated fibers could be found in the underlying white matter indicating that efferents from the transplant found their way to their "correct" target zone by growing through a complex neuropil which provided minimal physical substrates to guide such growth. Most of the contacts formed by these fibers were simple junctions along the shafts of dendrites with a wide range in diameter. It is concluded that the nearby host visual neurons, which are the correct target cells for the afferents arising in the transplant, induced a directed growth of these fibers.

Animals↗

Motion discrimination in cortically blind patients.

Some patients with brain damage affecting the striate cortex, though clinically blind in their field defects, can still discriminate visual stimuli when forced choice procedures are used. Such patients seem particularly sensitive to moving stimuli in their scotomata, though there are conflicting reports as to whether they can discriminate the direction of motion. We tested three patients with areas of cortical blindness for their ability to detect and discriminate the direction of motion of a variety of first-order motion stimuli, namely bars, gratings, plaids and random dot kinematograms depicting translation and motion in depth, during forced choice tasks. The patients could detect the presence of movement in any kind of stimulus, and could discriminate the direction of single bars, but none could discriminate the direction of motion of the more complex stimuli (gratings, plaids and random dot kinematograms) or discriminate between 0 and 100% coherent random dot kinematograms at any speed tested (from 4 to 64 degrees /s). Similar results were obtained from one of the patients who was additionally tested with second-order versions of the translated bar and random dot kinematograms, eliminating light scatter as an explanation. Overall, the results suggest that motion processing in the scotoma is severely impaired, and that the puzzling discrepancies between previous studies can be accounted for by the type of stimulus used. The motion discrimination impairment caused by brain damage affecting the primary visual cortex is inconsistent with the proposed existence of a subcortical pathway to extrastriate cortical motion areas (such as areas MT and MST) which bypasses the striate cortex and is specialized for analysing 'fast' motion.

Adult↗

Early and late mechanisms of surround suppression in striate cortex of macaque.

The response of a neuron in striate cortex to an optimally configured visual stimulus is generally reduced when the stimulus is enlarged to encroach on a suppressive region that surrounds its classical receptive field (CRF). To characterize the mechanism that gives rise to this suppression, we measured its spatiotemporal tuning, its susceptibility to contrast adaptation, and its capacity for interocular transfer. Responses to an optimally configured grating confined to the CRF were strongly suppressed by annular surrounding gratings drifting at a wide range of temporal and spatial frequencies (including spatially uniform fields) that extended from well below to well above the range that drives most cortical neurons. Suppression from gratings capable of driving cortical CRFs was profoundly reduced by contrast adaptation and showed substantial interocular transfer. Suppression from stimuli that lay outside the spatiotemporal passband of most cortical CRFs was relatively stronger when the stimulus on the CRF was of low contrast, was generally insusceptible to contrast adaptation, and showed little interocular transfer. Our findings point to the existence of two mechanisms of surround suppression: one that is prominent when high-contrast stimuli drive the CRF, is orientation selective, has relatively sharp spatiotemporal tuning, is binocularly driven, and can be substantially desensitized by adaptation; the other is relatively more prominent when low-contrast stimuli drive the CRF, has very broad spatiotemporal tuning, is monocularly driven, and is insusceptible to adaptation. Its character suggests an origin in the input layers of primary visual cortex, or earlier.

Animals↗

Aging and the myelinated fibers in prefrontal cortex and corpus callosum of the monkey.

In the rhesus monkey, the myelin sheaths of nerve fibers in area 46 of prefrontal cortex and in splenium of the corpus callosum show age-related alterations in their structure. The alterations are of four basic types. Most common is splitting of the dense line of myelin sheaths to accommodate electron dense cytoplasm derived from the oligodendroglia. Less common are splits of the intraperiod line to form balloons or blisters that appear to contain fluid, the occurrence of sheaths with redundant myelin, and thick sheaths that are almost completely split so that one set of compact lamellae is surrounded by another set. But despite these alterations in the sheaths, few nerve fibers show axonal degeneration. To quantify the frequency of the age-related alterations in myelin, transversely sectioned nerve fibers from the splenium of the corpus callosum and from the vertical bundles of nerve fibers within area 46 were examined in electron photomicrographs. The material was taken from 19 monkeys, ranging between 5 and 35 years of age. It was found that the frequency of alterations in myelin sheaths from both locations correlates significantly with age. In area 46, the age-related alterations also significantly correlate (P < 0.001) with an overall assessment of impairment in cognition, i.e., the cognitive impairment index, displayed by individual monkeys. The correlation is also significant when only the old monkeys are considered as a group. A similar result was obtained previously in our examination of the effects of age on the myelin sheaths of nerve fibers in primary visual cortex (Peters et al. [2000] J Comp Neurol. 419:364-376). However, in the corpus callosum the myelin alterations correlate significantly with only one component of the cognitive impairment index, namely the delayed nonmatching to sample task with a 2-minute delay. It is proposed that age-related myelin alterations are ubiquitous and that the correlations between their frequency and impairments in cognition occur because the conduction velocity along the affected nerve fibers is reduced, so that the normal timing sequences within neuronal circuits break down.

Aging↗