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Purpose In between seizures, the brain of a patient with epilepsy will generate isolated, sporadic discharges (interictal epileptiform discharges [IEDs]). IED identification enables clinicians to diagnose epilepsy, and an understanding of IED waveforms may yield new insights into basic epilepsy mechanisms. I show that intracranial EEGs disclose a previously unreported negative polarity, low-voltage pre-potential at IED onset (i.e., a negative wave [n-wave]). I describe the features of n-waves and propose a plausible mechanism of their generation. Method In intracranial EEGs of the human neocortex, I assessed n-waves’ occurrence, anatomical location, amplitude, kinetics, and association with the subsequent positive pre-potential. I computed a model simulation of IED onset to identify plausible mechanisms behind n-wave generation. Results N-waves manifested in 40% of patients, in zones with and without seizures, and without a statistically significant prevalence in their anatomical location. These waveforms exhibited voltages of 140 + 42 μV and durations of 39.9 + 12.2 msec and were coupled with a positive pre-potential. In simulations of IED onset, n-waves can be generated by sequential recruitment of distinct microfoci over superficial cortical laminae. Conclusions N-waves represent an overlooked component of IED waveforms. They prolong the duration of IED onset and can facilitate synaptic hypersynchrony. They may also be associated with chronic epilepsy.

We seek to understand the relation between invasive high-resolution data and non-invasive measurement in an animal model in an auditory sensory adaptation experimental setting. In a previous study, we estimated the mutual information between the phase of auditory evoked responses (AER) with the phase of local field potentials (LFP) of auditory cortices at different frequency ranges. The results showed a consistently high level of information sharing between the AER activities as well as the responses from the granular layer, which was known as the main thalamo-recipient layer. However, mutual information was fundamentally an undirected measure of information flow. In this study we investigated how well we could characterize direction of information flow, by using Granger causality (GC), between different cortical laminae and functional projections on to the AER activities. We obtained that based on the GC coefficients, we are able to extract the connectivity between different cortical laminae to some extend and also a strong connection between the AER and granular layer. In our future study, we would like to construct a reliable picture of network connectivity, both functionally and anatomically, between different layers at more specified frequencies and much finer temporal resolutions.

The diagenesis of ooids can be a valuable source of paleodepositional information. This study provides an example of ooids dolomitization in the Cambrian Zhangxia Formation, Xiaweidian, China. The ooids were extensively to completely replaced by euhedral dolomite crystals, but the interstitial material of the oolitic limestone was completely free of dolomitization. The selective dolomitization of the oolitic limestone is poorly understood. Stratigraphic, petrographic and X-ray diffraction data suggested that seepage reflux of the high-magnesium brine played a vital role in the early dolomite precipitation in the cortical laminae of the ooids before they were filled with interstitial materials. The sudden increased in the dolomite content of the oolitic limestone in carbonate containing gypsum provided key evidence for seepage-reflux dolomitization of the ooids. The higher porosity and permeability of the high-magnesium fluid in radial ooids demonstrates that the degree of dolomitization was higher than in the concentric ooids. The distribution of the dolomite was strongly influenced by the original cortical structure of the ooids. These data have significant implications for paleoenvironmental studies in this area.

Lower frequency, feedback, activity in the alpha and beta range is thought to predominantly originate from infragranular cortical layers, whereas feedforward signals in the gamma range stem largely from supragranular layers. Distinct anatomical and spectral channels may therefore play specialized roles in communication within hierarchical cortical networks; however, empirical evidence for this organization in humans is limited. We leverage high precision MEG to test this proposal, directly and non-invasively, in human participants during visually guided actions. Visual alpha activity mapped onto deep cortical laminae, whereas visual gamma activity predominantly arose from superficial laminae. This laminar-specificity was echoed in sensorimotor beta and gamma activity. Visual gamma activity scaled with task demands in a way compatible with feedforward signaling. For sensorimotor activity, we observed a more complex relationship with feedback and feedforward processes. Distinct frequency channels thus operate in a laminar-specific manner, but with dissociable functional roles across sensory and motor cortices.

Traumatic brain injury (TBI) initiates a cascade of pathophysiological changes that are both complex and difficult to treat. Progesterone (P4) is a neuroprotective treatment option that has shown excellent preclinical benefits in the treatment of TBI, but these benefits have not translated well in the clinic. We have previously shown that P4 exacerbates the already hypoactive upper cortical responses in the short-term post-TBI and does not reduce upper cortical hyperactivity in the long term, and we concluded that there is no tangible benefit to sensory cortex firing strength. Here we examined the effects of P4 treatment on temporal coding resolution in the rodent sensory cortex in both the short term (4 d) and long term (8 wk) following impact-acceleration–induced TBI. We show that in the short-term postinjury, TBI has no effect on sensory cortex temporal resolution and that P4 also sharpens the response profile in all cortical layers in the uninjured brain and all layers other than layer 2 (L2) in the injured brain. In the long term, TBI broadens the response profile in all cortical layers despite firing rate hyperactivity being localized to upper cortical layers and P4 sharpens the response profile in TBI animals in all layers other than L2 and has no long-term effect in the sham brain. These results indicate that P4 has long-term effects on sensory coding that may translate to beneficial perceptual outcomes. The effects seen here, combined with previous beneficial preclinical data, emphasize that P4 is still a potential treatment option in ameliorating TBI-induced disorders.

Magnetoencephalography (MEG) is a direct measure of neuronal current flow; its anatomical resolution is therefore not constrained by physiology but rather by data quality and the models used to explain these data. Recent simulation work has shown that it is possible to distinguish between signals arising in the deep and superficial cortical laminae given accurate knowledge of these surfaces with respect to the MEG sensors. This previous work has focused around a single inversion scheme (multiple sparse priors) and a single global parametric fit metric (free energy). In this paper we use several different source inversion algorithms and both local and global, as well as parametric and non-parametric fit metrics in order to demonstrate the robustness of the discrimination between layers. We find that only algorithms with some sparsity constraint can successfully be used to make laminar discrimination. Importantly, local t-statistics, global cross-validation and free energy all provide robust and mutually corroborating metrics of fit. We show that discrimination accuracy is affected by patch size estimates, cortical surface features, and lead field strength, which suggests several possible future improvements to this technique. This study demonstrates the possibility of determining the laminar origin of MEG sensor activity, and thus directly testing theories of human cognition that involve laminar- and frequency-specific mechanisms. This possibility can now be achieved using recent developments in high precision MEG, most notably the use of subject-specific head-casts, which allow for significant increases in data quality and therefore anatomically precise MEG recordings. Section Analysis methods. Classifications Source localization: inverse problem; Source localization: other., Highlights • Laminar inferences can be made with MEG using both local and global fit metrics. • Source inversion algorithms with sparsity constraints performed best. • Classification is affected by patch size estimates, anatomy, and lead field strength.

Once referred to as 'short-axon' neurons by Cajal, GABA (gamma-amino butyric acid)-ergic interneurons are essential components of the neocortex. They are distributed throughout the cortical laminae and are responsible for shaping circuit output through a rich array of inhibitory mechanisms. Numerous fate-mapping and transplantation studies have examined the embryonic origins of the diversity of interneurons that are defined along various parameters such as morphology, neurochemical marker expression and physiological properties, and have been extensively reviewed elsewhere. Here, we focus on discussing two recent studies that have, for the first time, examined the production and organization of neocortical interneurons originated from individual progenitors, that is, with clonal resolution, and provided important new insights into the cellular processes underlying the development of inhibitory interneurons in the neocortex.

Egocentric neural coding has been observed in parietal cortex (PC), but its topographical and laminar organization is not well characterized. We used multi-site recording to look for evidence of local clustering and laminar consistency of linear and angular velocity encoding in multi-neuronal spiking activity (MUA) and in the high-frequency (300-900 Hz) component of the local field potential (HF-LFP), believed to reflect local spiking activity. Rats were trained to run many trials on a large circular platform, either to LED-cued goal locations or as a spatial sequence from memory. Tuning to specific self-motion states was observed consistently, and exhibited distinct cortical depth-invariant coding properties. These patterns of collective local and laminar activation during behavior were reactivated in compressed form during post-experience sleep, and temporally coupled to hippocampal sharp wave ripples. Thus, PC neuron motion encoding is consistent across cortical laminae, and this consistency is maintained during memory reactivation.

”Excerpt from den Dunnen et al. No disease in the brain ofa 115-year-old woman. Neurobiol Aging 2008The most widespread degenerative disorder of the humannervous system, Alzheimer’s disease (AD), progressesover decades without spontaneous remission. Two of itsconventional histopathological hallmarks are intraneuronalprotein aggregations in the form of neurofibrillary tangles(NFTs) and neuropil threads (NTs) (Arriagada et al., 1992;Giannakopoulos et al., 2003). Although entangled neuronsare capable of surviving for a long time, they almost cer-tainly become functionally impaired before cell death occurs(Callahan et al., 1994; Coleman et al., 2004; Morris, 2006;Morschetal.,1999).Theneurofibrillarydegenerationiscon-fined to specific nuclei, areas, and cortical laminae (Hymanand Gomez-Isla, 1994´ ) and, based on its topographical dis-tribution pattern in the brain, can be staged (Braak andBraak, 1991; Braak and Del Tredici, 2006; Braak et al.,2006). The pattern of the disease-process is reminiscent ofthe inverse pattern of cortical maturation (myelination) dur-ing both phylogenesis and ontogenesis (Arendt et al., 1998;Braak and Braak, 1996; Miller et al., 2008; Moceri et al.,2000;Rapoport,1988;Rapoport,1990;Reisbergetal.,2003).The initially subtle neurofibrillary lesions can, ulti-mately,induceclinicallydetectablesymptoms(Morris,2006

Neuronal migrations along glial fibers provide a primary pathway for the formation of cortical laminae. To examine the mechanisms underlying glial-guided migration, we analyzed the dynamics of cytoskeletal and signaling components in living neurons. Migration involves the coordinated two-stroke movement of a perinuclear tubulin 'cage' and the centrosome, with the centrosome moving forward before nuclear translocation. Overexpression of mPar6alpha disrupts the perinuclear tubulin cage, retargets PKCzeta and gamma-tubulin away from the centrosome, and inhibits centrosomal motion and neuronal migration. Thus, we propose that during neuronal migration the centrosome acts to coordinate cytoskeletal dynamics in response to mPar6alpha-mediated signaling.

The laminar distribution of the neurofilament inclusions (NI) and swollen achromatic neurons (SN) was studied in gyri of the temporal cortex in four patients with neurofilament inclusion disease (NID). In 84% of gyri analysed, the density of the NI was maximal in the lower cortical laminae. The distribution of the SN was more variable than the NI. Density was maximal in the lower cortex in 46% of gyri, in the upper cortical laminae in 8% of gyri, and a bimodal distribution in 15% of gyri. In the remaining gyri, there was a more even distribution of SN with cortical depth. In 31% of gyri, the vertical density of the NI was positively correlated with that of the SN. The data suggest that cortical degeneration in the temporal lobe of NID initially affects neurons in the lower laminae. Subsequently, the pathology may spread to affect much of the cortical profile, the SN preceding the appearance of the NI.

Inter-areal interactions of neuronal oscillations may be a key mechanism in the coordination of anatomically distributed neuronal processing. In humans, invasive stereo-electroencephalography (SEEG) is emerging as a reference method for electrophysiological recordings because of its excellent spatial and temporal resolution. It could thus be also considered an optimal method for mapping neuronal inter-areal interactions. However, the common bipolar (BP) referencing of SEEG data may both confuse signals from distinct sources and suppress true neuronal interactions whereas the alternative monopolar (MP) reference yields data contaminated by volume conduction. We advance here a novel referencing scheme for SEEG data where electrodes in grey matter are referenced to closest white-matter (CW) electrodes. Using a 22 subject cohort and these three referencing schemes, we observed that both inter-areal phase and amplitude correlations decayed as function of distance and frequency but remained significant and stable across distances up to 10cm. Furthermore, we found that deep and superficial cortical laminae exhibit distinct spectral profiles of oscillation power as well as distinct patterns of inter-areal phase and amplitude interactions. These effects were qualitatively similar in MP and CW but distorted with BP referencing. Importantly CW was not influenced by the apparent large-scale volume conduction inherent to MP. We thus demonstrate here that with CW referencing, the superior anatomical accuracy of SEEG can be leveraged to yield accurate quantification and qualitatively novel insight into phase and amplitude interactions in human brain activity.

Ooids occurring in the middle Jurassic-lower Cretaceous carbonate sediments of Akseki, Antalya (Turkey) are of two distinct kinds. Type 1 ooids are small and of irregular shape. They have 1 to 4 cortical laminae with a fine radial structure and patchy micritization. The nucleus of this type is composed of micrite and in places is not visible. In the radial part of this kind of ooid, microporosity and/or microopenings seem to be micro-borings. Type 2 ooids are large and well rounded with vaguely visible nuclei. They display fine concentric micritic laminae which coincide with endolithic microorganisms and microborings of fossils.

Intrinsic connections are likely to play important roles in cognitive information processing in the prefrontal association cortex. To gain insight into the organization of these circuits, intracortical connections of major laminar and sublaminar divisions were retrogradely labeled in Walker's area 9 and 46 in rhesus monkeys by using cholera toxin (B-subunit) conjugated to colloidal gold. Microinjections placed within particular cortical laminae produced unique patterns of retrograde labeling. Injections in layers II/III yielded labeling which was laterally widespread (2-7 mm) in supragranular layers, and more narrowly focused, i.e., conforming to a column, in layers IV-VI. In contrast, local circuits associated with layers IV and Vb displayed a regular, cylindrical organization, whereas intrinsic connections of layer Va were laterally extensive (3-5 mm) in layers III and Va. Finally, injections in layer VI gave rise to a narrow column of cell labeling traversing all layers, augmented by laterally extensive labeling (approximately 7 mm) in layer VI. The intrinsic connections of the prefrontal cortex were arrayed within mediolaterally elongated stripes which were often distributed asymmetrically in either the medial or lateral direction. In addition, labeled cells within these mediolaterally oriented fields were frequently grouped within discrete clusters or narrow bands. The intrinsic connections identified in this study differ from the local circuits of corresponding layers reported for primary visual cortex; the unique intrinsic wiring diagram of the prefrontal cortex may be related to its specialized cognitive and mnemonic functions.

Recent developments in high field MRI have provided opportunities to detect iron in human brain with much improved sensitivity. The combination of increased magnetic field strength with multi-channel detectors has made it possible to routinely obtain images at about 300 micron resolution. These images can be sensitized to tissue iron by exploiting the improved magnetic susceptibility contrast at high field. Together, these techniques have the potential to map the fine scale distribution of iron in human brain at the level of fiber bundles and cortical laminae, and may aid in the understanding of the role and transport of iron in normal brain and in disease. In this chapter, we will look at these techniques in detail and present some examples of high field MRI data of human brain.

The system of tangential connections was studied in area 17 of normally reared (NR), binocularly deprived (BD) and dark-reared (DR) kittens and adult cats. Connections were labelled antero- and retrogradely by intracortical micro-injections of several fluorescent markers and horseradish peroxidase conjugated with wheat-germ agglutinin (WGA-HRP). In 5-day-old kittens tangential connections consist of homogeneously distributed fibres extending maximally over 2.7 mm. Around postnatal day (pnd) ten these connections start to express the patchy pattern characteristic of the adult. Retrogradely stained somata and anterogradely labelled terminals become organized in individual 300 to 350 microm wide clusters with a centre-to-centre spacing of about 500 microm. During the first three postnatal weeks the horizontal connections increase their span to up to 10.5 mm and the spacing between individual patches increases to about 700 microm. Over the following 4 weeks these projections become reduced in length and number. In adult NR cats, tangential connections span a distance of up to 3 mm and form a lattice of 200 - 500 microm wide clusters, which have an average centre-to-centre spacing of 1050 microm. Tangential connections originate and terminate in all cortical laminae except layer I and they are organized in register. The distances spanned are largest in supragranular, intermediate in infragranular and shortest in granular layers. In BD and DR cats older than 10 weeks, the length of intracortical tangential fibres becomes reduced to the same extent as in NR animals, but individual clusters are less numerous. The authors conclude that the lattice-like structure of lateral connections evolves independently of visual experience, and that the selectivity of interactions results from pruning of initially exuberant connections. It is suggested that this pruning process is dependent on activity and influenced by visual experience.

The pattern of commissural connections of the rat auditory cortex (AC) was investigated with injections of wheat germ agglutinated horseradish peroxidase into the AC. Homotopic and heterotopic patches of neurons were retrogradely labeled in the contralateral hemisphere. Each injection labeled neurons at the corresponding contralateral site, i.e. the homotopic site. In addition, retrogradely labeled neurons were found at non-corresponding locations in contralateral AC, i.e. at heterotopic locations. The pattern of heterotopic labeling changed systematically with the injections. Mapping rules were established that led to the parcellation of areas 41 and 36 into 6 fields. Four fields were defined in Krieg's area 41 (primary AC) and two fields in Krieg's area 36 (secondary AC). In area 41 the heterotopic connection is not reciprocal; in area 36, however, heterotopic projections are organized reciprocally. Contrary to the visual cortex, homotopic and heterotopic projection neurons were equally distributed across the cortical laminae. With double-label experiments it could be shown that a considerable number of the neurons in area 41 bifurcate and project to homotopic as well as to heterotopic sites in the contralateral hemisphere. We conclude that in the AC there are several subtypes of neurons projecting to the contralateral hemisphere; it would be of interest whether these anatomical differences are manifested by physiological differences.

The medial prefrontal cortex (mPFC) projects to the nucleus accumbens shell, core and rostral pole. In this retrograde tract-tracing study of rat mPFC to nucleus accumbens projection neurons, the advantages of Neurobiotin are utilised in order to reveal the detailed morphology of labelled projection cells, and to permit an examination of the laminar projections to shell and core compartments The retrogradely transported Neurobiotin was found in somata, proximal and distal dendrites of neurons that project from the mPFC to the nucleus accumbens. The morphology of these projection neurons was revealed in great detail and confirmed that the projection arises wholly from pyramidal cells. Interestingly, it was also found that retrogradely labelled neurons were exclusively located in prelimbic and infralimbic regions in layers V and VI, after shell injections, but also in layer II following core sites. This observation may reflect possibly different roles for cortical laminae on the nucleus accumbens.

During postnatal development of the visual cortex the thalamocortical afferents serving the two eyes segregate into alternating patches called ocular dominance (OD) columns. Interested in the dynamics of this segregation process we studied the appearance of functional OD columns in the primary visual cortex of normally raised and strabismic kittens aged 2-6 weeks using 2-deoxyglucose labelling in awake animals. In both experimental groups, OD columns covering the entire area 17 and spanning all cortical laminae are first visible at 3 weeks and appear already adult-like at 4 weeks, much earlier than thought on the basis of previous anatomical studies. We hypothesize that a small and anatomically undetectable imbalance between the afferents from the two eyes is amplified by intracortical interactions so that their activity patterns become different and may guide the segregation process of the afferents in cortical layer IV.

Long astroglial processes traversing several cortical laminae appear to be characteristic of primate brains. Whether interlaminar processes develop as a modification of radial glia or are truly postnatal elements stemming from stellate astroglia, could be assessed by analyzing their early developmental stages. A survey of glial fibrillar acidic protein immunoreactive (GFAP-IR) astroglial interlaminar processes in the cerebral cortex of Ceboidea monkeys at various postnatal developmental ages, and in human cortical samples of a ten day and a seven year old child disclosed that such processes develop postnatally. At one month of age GFAP-IR interlaminar processes in monkeys were scarce and short in most frontal, parietal or occipital (striate) cortical areas, except for sulcal (principal and orbital sulci) and temporal cortical areas. Some processes were weakly positive for vimentin, and these were most abundant in ventral temporal cortical areas. At two months of age processes were present in all these areas, albeit in restricted patches and significantly shorter than in adults. The expression of this pattern was increased at seven months of age. At three years of age almost every area showed abundant processes and with lengths comparable to the adult Ceboidea individuals. In humans, at 10 days of age long interlaminar processes were readily apparent in a frontal cortex sample, becoming most apparent at the age of seven years although not reaching yet the adult characteristics as described previously. Conclusions : (1) GFAP-IR interlaminar processes develop postnatally, thus typifying a subtype of the classical stellate forms ; (2) they bear no obvious direct relationship with radial glia ; (3) their development is not contemporary among the various cortical regions. These long cellular processes represent an addition to those already described for other astroglial cell types in the adult mammalian brain (Golgi–Bergmann glia, tanicytes, Muller cells) .

The lateral suprasylvian visual area (LS) is known to have numerous interconnections with visual cortical areas as well as with subcortical structures implicated in visually-guided behaviors. In contrast, little data is available regarding connections within the LS itself. In order to obtain information about intra-areal connections and to re-investigate LS connectivity with various cortical and subcortical areas, the traces (biocytin or WGA-HRP) was injected into various loci along the medial and lateral banks of the LS. The anterograde tracer, biocytin injections into both medial and lateral bank produced label contained within the respective bank that extended rostrally and caudally from the infection site. In addition, following medical bank injections, considerable label was distributed throughout the fundus and, to a lesser extent, in the lateral bank. In contrast, no label could be detected in the medial bank after lateral bank injections, and, although label was observed in the fundus, it was restricted to the most lateral aspects. Moderate labeling could be observed in the medial bank following the tracer injection into the most rostral aspect of the lateral bank. It is likely that input derived from various visual cortical areas which project to the medial bank of the LS has access to this intra-areal circuitry. This may provide a route by which visual cortical information can be relayed to other cortical and subcortical structures involved in visually-guided behaviors such as the anterior ectosylvian visual cortex, striatum, and the deep layers of the superior colliculus, despite the fact that these structures themselves do not receive substantial direct projections from the visual cortical areas that are associated with the medial bank. Examination of the laminar location of the cells-of-origin of striate and extrastriate projections to LS using retrograde trace, WGA-HRP, revealed that the supragranular laminae of areas 17, 18 and 19 were the source of LS afferents whereas afferents from the other cortical areas (e.g., 20a, 20b, 21a, 21b, 7 and anterior ectosylvian visual area) were from both supra- and infragranular laminae. In addition, all LS subregions received intra-areal afferent projections from all LS cortical laminae. Thus, although rather clear hierarchical relationship between LS and visual cortical areas appears to exist, the interconnections among LS subregions provide no clear evidence of simple hierarchical relationships between regions LS or may have feed-forward and feed-back pathways.

The neuropathological staging model proposed by Braak and Braak (1991) implies that the evolution of neurofibrillary pathology follows a predictable sequence and can be ordered in a regular regional hierarchy. A total of 42 cases of an elderly population sample, which had been prospectively clinically assessed, were examined. Clinical diagnosis was made according to the CAMDEX criteria, and the sample reported here did not include cases were vascular dementia according to the criteria proposed by Chui et al. (1991). The neuropathological staging procedure was applied as originally proposed by Braak and Braak (1991). In addition, in all cortical laminae and regions which are essential for the staging model neurofibrillary tangles were quantified. Demented cases had significantly more areas involved and more advanced neuropathological stages. Cases with stages 1–3 tended to be non-demented, and cases with stages 4–6 tended to be demented. However, there was a considerable degree of overlap and no clear-cut threshold could be established. This brings into question the diagnostic value of the staging model.

Early postmitotic cortical neurons are mostly corticofugal projection neurons that take up positions in deep cortical laminae. Later postmitotic neurons are preferentially localized to superficial cortical laminae. In reeler mutant mice it appears that cortical laminar positions with respect to birthdate are reversed (Caviness, 1982). In a reanalysis of reeler lamination we found that early postmitotic cortical neurons labeled by embryonic day (E) 11–13 injections of a birthdate marker, or by early postnatal day (PND) 2 retrograde labeling through their output projections, appear to take up positions both in the superficial and deep cortex. Neurons born on E11 and E12 are more likely to be situated superficially in the reeler cortex and neurons born on E13 are more likely to be situated in the deep reeler cortex. Many corticofugal projection neurons in the deep (but not superficial) reeler cortex either die or retract their axons before PND 21. We hypothesize that the earliest postmitotic (E11-E12) of the early postmitotic reeler cortical neurons are overly adhesive and act as a barrier to later postmitotic migrating neurons. In vitro cortical aggregation cultures confirmed that early postmitotic (E12) reeler neurons are more adhesive than early postmitotic (E12) wild-type neurons or late postmitotic (E16) reeler or wild-type cortical neurons. We suggest that the moderate wild-type preferential adhesion of early postmitotic cortical neurons to each other helps deep and superficially fated lineages to form cortical laminae.

The last 15 years have seen a rapid expansion in studies on human visual evoked potentials (VEP), both a t the fundamental and at the clinical level. A wide variety of stimulus conditions have been explored,’ new types of mathematical tools have been i n t r o d ~ c e d , ~ . ~ and there has been an increasing appreciation of possible VEP correlates with underlying physiological mechanisms! Variability of the folding and size of the human striate cortex’ as well as the remote location of human scalp electrodes, however, limits the accurate localization of human VEP components to particular cortical structures. In this regard it would seem desirable to explore the VEP of a laboratory animal closely related to the human. In this paper I discuss two approaches that may prove both useful and complementary in deciphering visual evoked potentials in monkey, and by extrapolation, in man. The first approach involves the use of fine stimulus control, noting the degree to which the VEP amplitude varies with small changes in stimulus characteristics. The second approach, still in the preliminary stages, involves the use of current source density analysis, a method to localize the generating processes of the VEP to specific cortical laminae and sublaminae.

1. Binocularity and receptive-field type of cortical neurons were assessed relative to the cortical layer in which the neurons were recorded and to receptive-field position in the visual field. 2. Receptive fields were observed up to 2 degrees into the ipsilateral half of the visual field. In the region up to 2 degrees on either side of the vertical meridian, the relative contribution of the ipsilateral eye was reduced. This progression in ocular dominance from ipsilateral to contralateral visual field agrees well with the distribution of X-cells about the nasotemporal division. 3. The region of maximum binocularity in each hemifield was found to be a 12 degree wide vertical strip extending from the vertical meridian to 12 degrees contralateral. In the representation of the central 12 degree strip, most units in all cortical layers were binocular. 4. Low levels of binocularity were observed at a considerable distance before the monocular portion of the visual field was reached. 5. The decrease in binocularity for simple cells occurred closer to the vertical meridian than for complex cells. 6. The proportions of cells classified as simple or complex did not change with position in the visual field. 7. At all locations in the visual field, complex cells showed a higher percentage of binocularity than simple cells. 8. The proportions of two types of simple cells, I and II, and complex cells were variable between cortical layers. Layer IV contained predominantly simple II cells, whereas layer V contained predominantly complex cells. 9. The results are discussed in terms of visual perception and the dynamic pattern of visual stimulation around a moving animal, the optic flow field.

Unit activity of the cingulate cortex and the anteroventral (AV) nucleus of the thalamus in rabbits was recorded during reversal training following differential conditioning of a locomotory (wheel rotation) avoidance response. The positive and negative conditional stimuli (CS+ and CS-) were pure tones (1 kHz and 8 kHz), and the unconditional stimulus was footshock (1.5 mA). During the first session, activity appropriate to the original task (i.e., a greater neuronal response to the CS- than to the CS+) occurred in the deep cortical laminae (V and VI), but the superficial laminae (I-IV) manifested the original discrimination in certain records and the reverse discrimination in others. All discriminative effects diminished during subsequent sessions except the short-latency (25-msec) deep laminar original discrimination, which persisted throughout reversal training. Activity of the AV nucleus underwent gradual transition, in parallel with the behavior, from the original to the reverse discrimination. Arousal-producing footshocks given after behavioral reversal educed the original and reverse discriminations in the deep and superficial laminae, respectively. These data are interpreted to indicate the role of cingulate cortex and anterior thalamus for encoding the associative significance of the conditional stimuli.

Diameters and densities of arterioles and capillaries were measured in thick alkaline phosphatase-stained sections of human visual cortex from normal young adults. Values were compared between laminae. Capillary diameters ranked: IV greater than V-VI greater than II-III greater than I; capillary densities ranked: IV greater than II-III greater than V-VI greater than I. The striking capillary density of lamina IV overlaps the stria Gennarii and, like it, is limited to area 17. The data suggest correlations with similar laminar distributions of some neurotransmitters and of certain common neuropathological lesions.

Methods are described for 3-dimensional visualization and spatial manipulation of complex axonal arborizations. These methods allow 2-dimensional camera lucida drawings of neuron processes passing through serial sections to be redrawn with an altered viewing perspective without need for a computer. Two methods are described: a method for 90° rotation, and a method for approximating smaller angle rotations. The method for small angle rotation was developed to visualize the spatial relationships between cortical laminae (curved as well as planar) and axon branching patterns.

Injections of small quantities of tritiated amino acid were made in the dorsal lateral geniculate nucleus (LGNd) and the adjacent posterior nucleus (PN), and the cortical projections of these nuclei were studied using the autoradiographic tracing method. It was concluded that the laminar division of LGNd projects only to areas 17 and 18 of the ipsilateral hemisphere. That portion of LGNd designated the medial interlaminar nucleus (MIN) projects to areas 18, 19 and the Clare—Bishop are (CB). PN was found to project to areas 19, CB, and a region within the splenial sulcus. No subcortical projections of LGNd or PN were observed. The distribution of transported label within cortical laminae showed that terminations occur largely in layer IV of all cortical areas studied, and that a relatively small number of terminations take place in layers I–III and in layer V. The cortical labeling pattern in areas 17 and 18 indicated that a substantial number of terminations may also exist in layer VI. The initial trajectory of PN and MIN axons was studied. PN fibers coursed laterally and remained closely applied to the dorsal border of LGNd before turning dorsally into the visual radiations. Most MIN fibers, on the other hand, passed laterally through the laminae of LGNd before ascending to the cortex.

The orientations in the tangential plane, i.e., parallel to the pial surface, of dendrites and axons in several functionally different areas of the rat neocortex were investigated. Using a large data base of over 30,000 measurements and the t-test and chi 2 test for significance, we found an overall preference of both dendrites and axons for the anteroposterior and adjacent orientations. The degree of preference varied from area to area and among different cortical laminae. Other variations were correlated with neuron type and dendritic rank (in a tree). The pyramidal cell dendritic fields show little orientation in the tangential plane, whereas a large fraction of the stellate cells are oriented. The overall preferential orientations are apparently related to brain axes and growth lines, whereas the variability is probably due to the influence of the functional topography.

Multiple-unit activity of the cingulate cortex and the anteroventral (AV) nucleus of the thalamus in rabbits was recorded during reversal training, following differential conditioning of a locomotory (wheel rotation) avoidance response. The CS+ and CS− were pure tones (1 or 8 kHz) and the UCS was a footshock delivered through the grid floor of the wheel. One group of the rabbits received original training to a criterion followed immediately by reversal training. A second group received training to criterion followed by additional training sessions (overtraining), prior to reversal training. The results indicated that the overtraining reversal effect (ORE) occurred. That is, the overtrained subjects acquired the reverse discrimination in significantly fewer sessions than the non-overtrained subjects. The overall (non-discriminative) neuronal reactivity in all cingulate cortical laminae was reduced by overtraining, whereas the overall reactivity of the AV thalamus was enhanced. In addition, the non-overtrained subjects manifested a discriminative neuronal response appropriate to the original task (i.e. a greater response to the CS− than to the CS+ for reversal training), throughout the precriterial sessions of reversal training. This persistent ‘original habit effect’ occurred only at brief latencies (20–30 msec) after CS onset, and only in the deep cortical laminae (V–VI). The neuronal activity of the superficial laminae (I–IV) in non-overtrained subjects underwent a transition, in parallel with the behavior, from a discriminative response appropriate to the original task to one appropriate to the reversal task. No significant training-related changes were seen at any cortical depth in the overtrained subjects. Presentation of non-contingent footshocks during two sessions of reversal training following criterion re-enhanced the overall reactivity and the brief-latency discriminative neuronal response appropriate to the original task, which had undergone decline during reversal training, in the deep cortical laminae of the non-overtrained subjects. The enhanced overall reactivity and the discriminative activity in the superficial laminae of non-overtrained subjects had not declined during reversal training and were not altered by the non-contingent footshocks. The implications of these data are discussed in regard to the neural causation of the ORE.

Retrogradely transported horseradish peroxidase (HRP) or HRP conjugated to wheat germ agglutinin was used to demonstrate projections from area 19, the posterior medial lateral suprasylvian area (PMLS) and the lateral posterior-pulvinar complex (LP-PC) of the thalamus to areas 17 and 18 of the visual cortex in young kittens. Areas 17 and 18 in kittens, as in adult cats, receive association fibres from cells lying mainly in deep cortical laminae in area 19 and PMLS, and projections from the LP-PC of the thalamus.

The pattern of intracortical potential distribution during focal interictal epileptiform discharges (FIED) was analysed with respect to the occurrence of descending neuronal activity to the spinal cord recorded as spinal field potentials (SFPs). The experiments were performed in rats. Epileptiform activity was elicited by application of penicillin to the motor cortex. The spread of active penicillin was limited by penicillinase in part of the experiments. (1) When penicillinase was applied 10--20 sec before penicillin to the cortical surface typical FIED appeared in the epicortical lead. During well-established focal activity they were accompanied by negative field potentials at a depth of 300 micrometers and 600 micrometers and by positive field potentials in deeper records. This pattern of intracortical potential distribution was not associated with characteristic SFPs. (2) When penicillinase was applied simultaneously with penicillin, the fully developed epicortical FIED were accompanied by negative intracortical field potentials which in this case reached a depth of 900 micrometers. In the layers below predominantly positive potential fluctuations occurred. This pattern of intracortical potential distribution was associated with characteristic SFPs. (3) Intracortical application of penicillin at a depth of 800--900 micrometers led to negative field potentials of large amplitude in all intracortical records, with the concomitant epicortical potentials being positive in polarity. In this case SFPs occurred throughout the interictal activity. Since seizure activity can be restricted to only a few cortical laminae, descending neuronal activity to the spinal cord need not be correlated with definite epicortical potentials. A prerequisite for cortical output is intracortical activity reflected negative potentials at a depth of approx. 900 micrometers.

The contribution of each cortical lamina to intracortical circuitry was studied in the visual neocortex of the Pakistani hedgehog. Punctate laminar lesions were made electrolytically within the visual cortex, and after five to seven days the brains were processed and stained with the Fink-Heimer technique. The results of this study suggest that both horizontal and vertical connections are important to the organization of visual cortex in the hedgehog. The horizontal projections originate at three distinct cortical depths. Lesions in layer II reveal projections that traverse the inner one-half of layer I; lesions in layers III and IV reveal projections that traverse layer IV and that enter the cortical white matter; lesions in layers V and VI reveal projections that traverse the outer one-half of layer VI and that enter the cortical white matter. The vertical projections are oriented perpendicular to the pial surface. Layers II and III project to underlying layer V. Layers V and VI in turn contribute to a reciprocal projection back to all superficial cortical laminae. This anatomical data about intracortical circuitry is discussed with reference to the functional organization of visual cortex.

The distribution of opiate receptors in the cerebral cortex of the rhesus monkey (Macaca mulatta) was determined by autoradiographic visualization of [3H]naloxone binding to tissue sections. Naloxone was bound in relatively large amounts to the cortical laminae containing the cell bodies of output neurons, to a varying set of additional laminae in different cortical fields, to fields closer to more primitive types of cortex, and to polysensory cortical fields. From these laminar and areal variations in distribution, it appears that opiate receptors play a role in specific aspects of cortical function.

The amount of early cell loss in five neocortical areas was inversely related to adult numbers of neurons in those areas. Differential cell death predicted particularly the thickness of the upper cortical laminae; it was not related to neuron numbers in the lower laminae. Cell loss thus determines some features of local neocortical differentiation.