Primate Cerebral Cortex Research Articles

Ontogeny of cholecystokinin-8 and glutamic acid decarboxylase in cerebral neocortex of macaque monkey.

Concentration of cholecystokinin-8 and the activity of glutamic acid decarboxylase were determined in the various cerebral cortical subdivisions of Japanese monkey (Macaca fuscata fuscata) at three different ages (embryonic 4 months, full-term and adult). The CCK-8 immunoreactive material extracted with 90% methanol from the cerebral cortex of the adult and foetal monkey were shown to be identical with synthetic cholecystokinin-8 by the criterion of co-elution on gel filtration chromatography (Sephadex G-50). The peptide concentration increased dramatically by about 30-80 fold (in terms of protein) and 17-28 fold (in terms of wet weight) between embryonic 4-month-old and full-term monkeys, while the level decreased 1/6-1/16 (protein) and 1/4-1/10 (wet weight) between full-term and adult monkeys. In adults, the highest levels of the peptide was observed in the association cortex, orbital prefrontal cortex and posterior parietal cortex. Glutamic acid decarboxylase activity, on the other hand, gradually increased about 4-10 fold (protein) between embryonic 4-month-old and adult animals and there was little variation in the increase rate among the cerebral subdivisions. In contrast to cholecystokinin-8, no reduction in the enzyme activity occurred between full-term and adult animals. The high level of cholecystokinin-8 in the embryonic period suggests that the peptide may participate in the regulation of the development of primate cerebral cortex.

Distribution of muscarinic receptor subtypes within architectonic subregions of the primate cerebral cortex.

The regional distributions of muscarinic receptor subtypes (M1 and M2) in the macaque brain were investigated by in vitro receptor autoradiography. Putative muscarinic receptor subtypes were distinguished by their differential affinities for pirenzepine and carbachol in competition with [3H]-quinuclidinyl benzilate. Autoradiographic visualization of muscarinic receptor subtypes demonstrated marked regional and laminar variations that respected architectonic boundaries. The M1 receptor subtype was widely distributed throughout most cortical areas and was most intense over the superficial layers. Almost all limbic and paralimbic regions including the amygdala, hippocampus, orbitofrontal, temporopolar, parahippocampal, cingulate, and parolfactory areas displayed peak densities of the M1 receptor subtype. The M2 receptor subtype was selectively elevated in the primary sensory areas of all five sensory modalities, including the visual (area 17, V1), auditory (A1), and somatosensory (3b, S1) koniocortices, the anterior olfactory nucleus, and the gustatory area. The primary motor area also displayed a relative peak of M2 receptor subtype labeling. In the hippocampal formation, M1, M2, and nicotine receptors were distributed differentially, with each subdivision having a specific complement of cholinergic receptor subtype. The M1 receptor subtype was prevalent in the dentate gyrus, the CA4-CA3 region, and the CA1 ammonic sector. The M2 receptor subtype was concentrated in the CA2 sector, the subiculum, the rhinal cortices, and the parasubiculum. Putative neural nicotinic receptors, tagged with L-[3H]-nicotine, were most concentrated within the presubiculum.

PH, K+, and PO2 of the extracellular space during ischaemia of primate cerebral cortex.

pH and K+ from the extracellular space, PO2, and CBF have been measured in the same region during progressive ischaemia of primate cerebral cortex. As blood flow was reduced, the other changes had the following sequence. PO2 fell rapidly to 30% of control levels at regional CBF (rCBF) of 30 ml 100 g-1 min-1. As CBF was further reduced, PO2 continued to fall. pH remained stable until around 20 ml 100 g-1 min-1, below which pH fell rapidly, with an exponential increase in H+ concentration. K+ showed the well-known relationship to CBF, remaining normal until around 10 ml 100 g-1 min-1, below which K+ rose rapidly. pHe and log K+ were lin-early related and confirmed that pH fell by 0.3 U before K+ rose significantly, and fell by 0.6 U before the massive rise in K+. The mechanisms involved in this sequence of events and the role of pH changes in the development of the so-called "ischaemic penumbra" are discussed.

Regional distribution of cholecystokinin receptors in primate cerebral cortex determined by in vitro receptor autoradiography.

Cholecystokinin (CCK) is a putative peptide neurotransmitter present in high concentration in the cerebral cortex. By using techniques of in vitro receptor autoradiography, CCK binding sites in primate cortex were labeled with 125I-Bolton-Hunter-labeled CCK-33 (the 33-amino-acid C-terminal peptide) and 3H-CCK-8 (the C-terminal octapeptide). Biochemical studies performed on homogenized and slide-mounted tissue sections showed that the two ligands labeled a high-affinity, apparently single, saturable site. Autoradiography revealed that binding sites labeled by both ligands were anatomically indistinguishable and were distributed in two basic patterns. A faint and diffuse label characterized portions of medial prefrontal cortex, premotor and motor cortices, the superior parietal lobule, and the temporal pole. In other cortical areas the pattern of binding was layer-specific; i.e., binding sites were concentrated within particular cortical layers and were superimposed upon the background of diffuse label. Layer-specific label was found in the prefrontal cortex, anterior and posterior cingulate gyrus, somatosensory cortex, inferior parietal lobule, retrosplenial cortex, insula, temporal lobe cortices, and in the primary visual and adjacent visual association cortices. The areal and laminar localization of layer-specific CCK binding sites consistently coincided with the cortical projections of thalamic nuclei. In prefrontal cortex, CCK binding sites were present in layers III and IV, precisely paralleling the terminal fields of thalamocortical projections from the mediodorsal and medial pulvinar nucleus of the thalamus. In somatosensory cortex, the pattern of CCK binding in layer IV coincided with thalamic inputs arising from the ventrobasal complex, while in the posterior cingulate gyrus, insular cortex, and retrosplenial cortex, layer IV and lower III binding mirrored the laminar distribution of cortical afferents of the medial pulvinar. CCK binding in layers IVa, IVc alpha, IVc beta, and VI of primary visual cortex corresponded to the terminal field disposition of lateral geniculate neurons, whereas in adjacent visual association cortex, binding in layers III, IV, and VI faithfully followed the cortical distribution of projections from the inferior and lateral divisions of the pulvinar nucleus of the thalamus. We interpret the diffusely labeled binding sites in primate cortex as being associated with the intrinsic system of CCK-containing interneurons that are distributed throughout all layers and areas of the cortex. The stratified binding sites, however, appear to be associated with specific extrinsic peptidergic projections.(ABSTRACT TRUNCATED AT 400 WORDS)

Relation of neurons in the nonprimary motor cortex to bilateral hand movement.

In the primate cerebral cortex there are at least two somatotopically organized, nonprimary motor fields rostral to the primary motor area. To understand the functions of these multiple motor representations we have compared the neuronal activity in each of these fields while monkeys performed a trained motor task, using right, left or both hands. In the nonprimary motor cortex, activity in a number of neurons was related to the movement the animal chose and performed, whereas in the primary motor cortex, changes in the firing of most neurons were simply related to activity in the contralateral muscles. This result indicates that the nonprimary motor cortex is involved in higher-order coding of the laterality of the motor response, implying that it exerts its motor control function at a higher hierarchical level than its counterpart in the primary motor cortex.

Both striate cortex and superior colliculus contribute to visual properties of neurons in superior temporal polysensory area of macaque monkey.

Although the tectofugal system projects to the primate cerebral cortex by way of the pulvinar, previous studies have failed to find any physiological evidence that the superior colliculus influences visual activity in the cortex. We studied the relative contributions of the tectofugal and geniculostriate systems to the visual properties of neurons in the superior temporal polysensory area (STP) by comparing the effects of unilateral removal of striate cortex, the superior colliculus, or of both structures. In the intact monkey, STP neurons have large, bilateral receptive fields. Complete unilateral removal of striate cortex did not eliminate visual responses of STP neurons in the contralateral visual hemifield; rather, nearly half the cells still responded to visual stimuli in the hemifield contralateral to the lesion. Thus the visual properties of STP neurons are not completely dependent on the geniculostriate system. Unilateral striate lesions did affect the response properties of STP neurons in three ways. Whereas most STP neurons in the intact monkey respond similarly to stimuli in the two visual hemifields, responses to stimuli in the hemifield contralateral to the striate lesion were usually weaker than responses in the ipsilateral hemifield. Whereas the responses of many STP neurons in the intact monkey were selective for the direction of stimulus motion or for stimulus form, responses in the hemifield contralateral to the striate lesion were not selective for either motion or form. Whereas the median receptive field in the intact monkey extended 80 degrees into the contralateral visual field, the receptive fields of cells with responses in the contralateral field that survived the striate lesions had a median border that extended only 50 degrees into the contralateral visual field. Removal of both striate cortex and the superior colliculus in the same hemisphere abolished the responses of STP neurons to visual stimuli in the hemifield contralateral to the combined lesion. Nearly 80% of the cells still responded to visual stimuli in the hemifield ipsilateral to the lesion. Unilateral removal of the superior colliculus alone had only small effects on visual responses in STP. Receptive-field size and visual response strength were slightly reduced in the hemifield contralateral to the collicular lesion. As in the intact monkey, selectivity for stimulus motion or form were similar in the two visual hemifields. We conclude that both striate cortex and the superior colliculus contribute to the visual responses of STP neurons. Striate cortex is crucial for the movement and stimulus specificity of neurons in STP.(ABSTRACT TRUNCATED AT 400 WORDS)

Concurrent overproduction of synapses in diverse regions of the primate cerebral cortex.

Synapses develop concurrently and at identical rates in different layers of the visual, somatosensory, motor, and prefrontal areas of the primate cerebral cortex. This isochronic course of synaptogenesis in anatomically and functionally diverse regions indicates that the entire cerebral cortex develops as a whole and that the establishment of cell-to-cell communication in this structure may be orchestrated by a single genetic or humoral signal. This is in contrast to the traditional view of hierarchical development of the cortical regions and provides new insight into the maturation of cortical functions.

Systematic regional differences in the cholinergic innervation of the primate cerebral cortex: distribution of enzyme activities and some behavioral implications.

Choline acetyltransferase and acetylcholinesterase enzymatic activities were measured in 33 cytoarchitectonic subregions of the cerebral cortex in two rhesus monkeys. As expected, the hippocampus and amygdala were rich in these enzymes. In addition, the paralimbic (mesocortical) regions of the brain (e.g., parahippocampal, insular, caudal orbitofrontal, and temporopolar areas) also contained high levels of both enzymes. In contrast, the concentration of these cholinergic markers was the lowest within all frontal and temporoparietal association areas. As a group, the primary sensory and motor regions contained an intermediate level of choline acetyltransferase activity. Both cholinergic markers also showed a gradual increase from the isocortical toward the more primitive periallocortical subsectors of paralimbic areas. These anatomical patterns have potential implications for the role of cholinergic pathways in the memory process and in the pathogenesis of Alzheimer's disease.

Region‐specific distribution of catecholamine afferents in primate cerebral cortex: A fluorescence histochemical analysis

The density, laminar distribution, spatial orientation, and intrahemispheric pathways of norepinephrine (NE)- and dopamine (DA)- containing axons were analyzed in a wide range of cytoarchitectonically distinct areas of cerebral cortex in the adult rhesus monkey by fluorescence histochemistry. Although the boundaries between most areas were rarely sharp, there were marked regional differences in density and distribution of monoamine afferents in different cortical regions. Fibers exhibiting typical DA-like morphology were found only in the temporal and frontal lobes including motor and premotor areas as well as anterior cingulate and prefrontal cortices. In contrast, NE-containing axons were present in all cerebral lobes, with notably high density in the somatosensory area and low numbers in primary visual cortex. Intracerebral distribution was characterized by a network of large preterminal axons coursing both anteroposteriorly and mediolaterally in layer VI and in the subjacent white matter. In most cytoarchitectonic regions examined, catecholamine (CA)-containing axons exhibited a bilaminar distribution into one superficial and one deep fiber band. The location and width of the two dense bands, as well as the orientation and relative density of fibers within them, was region specific. Although fluorescent axons were found at all cortical depths, layers I, and IV usually contained relatively few fluorescent axons while layers II-III and IV-V were often densely innervated. An observation that may reflect a specialization in gyrencephalic brains is the particularly dense CA innervation around sulcal invaginations in all cerebral lobes. The present results confirm previous biochemical evidence of regional heterogeneity in the concentration of DA and NE in the primate neocortex (Brown and Goldman, '77:Brain Res. 124:576-550) an provide the first anatomical demonstration of corresponding differences in the pattern and density of CA innervation in diverse cytoarchitectonic areas in rhesus monkey. These findings raise the possibility of selective targets and functions for CA fibers in different layers and regions of the primate cortex.

Kinetics of resolution of transient increases in extracellular potassium activity: relationships to regional blood flow in primate cerebral cortex.

Previous studies have established that in cerebral cortex subjected to progressive reduction in blood flow, two distinct thresholds of flow may be identified below which cellular function is impaired: the cortical evoked response loses amplitude when local flow falls below 18ml/100gm/min, and below 11ml/100gm/min a major increase in extracellular K+ activity (Ke) occurs. However, further evidence suggests that even at higher flows the capacity of the tissue to handle induced ionic changes may be impaired. To investigate this point, we studied the kinetics of resolution of Ke following a transient increase produced by local electrical stimulation, in relation to the local pre-stimulus flow (reduced by acute middle cerebral artery occlusion) in baboons. Flow was measured by the hydrogen clearance method and Ke by ion-exchanger micro-electrodes, in the same cortical regions. In primary induced transients (those increases in Ke elicited by cortical stimulation, and reported previously,) Ke attained a maximum value of 8-10 mM and then decayed towards the 4-mM baseline. The half-time of this decay was significantly increased from normal in the flow range 20-40 ml/100 gm/min, and increased further at lower flows until, below 11ml/100gm/min, Ke clearance was undetectable. Thus, cortical ion homeostasis appeared impaired at flows substantially closer to normal than those thresholds mentioned above, a result discussed in terms of impairment of active Ke clearance mechanisms. Secondary induced transients arose during a primary induced transient, reaching considerably higher peak values (8-30 mM) of Ke (indicating temporary clearance loss) and with slower decay rate than the primary. Spontaneous transients, not associated with any stimulus, were also observed; like secondary transients, they occurred only at flows below 20ml/100gm/min and showed a reduction in clearance rate with progressive ischemia. They resemble spreading depression and their generation is discussed in terms of the ionic and metabolic conditions at their time of origin.

Opiate receptor gradients in monkey cerebral cortex: correspondence with sensory processing hierarchies.

In order to obtain information on the possible functions of endogenous opiates in the primate cerebral cortex, we assessed the distribution of mu-like opiate receptors (which selectively bind 3H-labeled naloxone) and delta-like opiate receptors (which selectively bind 3H-labeled D-Ala2, D-Leu5-enkephalin) throughout the cerebral cortex of the rhesus monkey. Stereospecific [3H]naloxone binding sites increased in a gradient along hierarchically organized cortical systems that sequentially process modality-specific sensory information of a progressively more complex nature. Specific [3H]enkephalin binding sites, in contrast, were relatively evenly distributed throughout the cerebral cortex. These results, in combination with electrophysiological studies of monkeys and humans, suggest that mu-like opiate receptors may play a role in the affective filtering of sensory stimuli at the cortical level, that is, in emotion-induced selective attention.

Regional changes of monoamines in cerebral cortex and subcortical structures of aging rhesus monkeys

The concentration and rates of synthesis of monoaminergic neurotransmitters were determined in selected cortical and subcortical brain regions of rhesus monkeys ranging in age from 2 to over 18 y of age. Major changes that occur with advancing age include: (1) a decrease in endogenous concentrations of dopamine in restricted regions of the cerebral cortex; the reduction is most drastic in the prefrontal association cortex where the loss is over 50%; (2) cortical levels of norepinephrine and serotonin remain essentially unaltered in prefrontal association cortex and exhibit only slight or modest reductions in other cortical areas over the same time scale; (3) catecholamine biosynthesis is reduced by at least 60% in all sensory and association cortical areas between 2 and 18 y of age but is surprisingly steady in the premotor and motor cortex over the same period of time; (4) serotonergic activity does not change with age in any cortical or subcortical structure examined; (5) age-related losses in subcortical structures occur only in dopamine concentrations and/or catecholamine biosynthesis: dopamine levels fall in the caudate nucleus and hypothalamus and catecholamine synthesis declines to varying degrees in all subcortical structures studied. These findings collectively emphasize the distinctive regional patterns and selective biochemical changes that take place in various neurotransmitter systems of the primate cerebral cortex during the process of aging.

An anatomical investigation of the corticopontine projection in the primate ( Macaca fascicularis and Saimiri sciureus)—II. The projection from frontal and parietal association areas

In continuation of a previous study on the corticopontine projection from sensorimotor areas of the cerebral cortex in primates, the projection from frontal and parietal association areas has been investigated with degeneration and autoradiographic tracing techniques. Since the connexions are ipsilateral the projection from peri-Rolandic areas was also studied on the contralateral side of the same animals as a control. It was found that association areas have only a modest contribution to the corticopontine system as compared to the massive projection from sensorimotor areas. Of those association areas studied in the present experiments, area 5 of the parietal cortex and the premotor cortex contributed most corticopontine fibres. The prefrontal cortex and area 7 were found to have only very weak connexions. It is evident, especially from autoradiographic studies, that the corticopontine system has an intricate organization, with one particular cortical area projecting to multiple small target zones in the pontine nuclei interdigitating with target zones or ‘patches’ receiving fibres from other cortical areas. The distribution of these zones may be rather widespread, especially those receiving afferents from the motor cortex, thus providing ample opportunities for integration of motor command signals with sensory, mainly somatosensory, signals. The fact that the pontine nuclei receive chiefly signals from primary cortical areas, rather than from high-order association areas, may be taken to indicate that the cortico-ponto-cerebellar system subserves rapid corrections of movements and ‘triggered actions’, a proposition which is also supported by behavioural studies in monkeys subjected to reversible cooling of the dentate nucleus.

The functional significance of certain duplicate motor patterns on the cerebral cortex in primates including man

Rotation elicitable from direct irritation or implantation of the cortical irritant, penicillin, in both rostral and posterior parts of the temporal operculum and on the island cortex in the monkey (Macaca mulatta) has been described and illustrated in photographs. The pathways to and from these temporal and island areas have been considered and the results obtained have been compared with related reports in the literature on rotation in monkeys and man. The probable role of the precentral and postcentral insular areas and their related paths to the contraction of the muscles (sometimes called the agonists) on the side of an extremity in the direction of movement of that extremity and the commensurate relaxation of the muscles (sometimes called the antagonists) cooperating with them on the other side of the extremity is discussed.

Further studies on the K + -dependent swelling of primate cerebral cortex in vivo: the enzymatic basis of the K + -dependent transport of chloride.

Abstract— The swelling of intact, exposed primate cerebral cortex perfused in vioo under, isosmotic conditions was a linear function of the concentration of K+ in perfusate over the range 25–117 mM. The K+‐dependent swelling was manifested throughout the depth of the cerebral cortex studied and was associated with an increased content of chloride in the swollen tissue, despite the constancy of the concentration of external chloride. The swelling of the cerebral cortex was a linear function of the temperature of the perfusate over the range 15–38°C, despite the constancy of the concentration of external K+. Moreover, the content of chloride in the swollen cerebral cortex was a linear function of the temperature of the overlying perfusate, despite the constancy of the external concentration of chloride. The changes in the contents of Na+ and K+ in the swollen cerebral cortex perfused with solutions containing constant concentrations of external Na+ and K+ but differing in temperature suggested that the fluid of swelling in the tissue was rich in both K+ and CI‐, as had been shown previously in vitro. Perfusion of the exposed, intact cerebral cortex in uiuo with K+‐rich fluids usually involved the reciprocal reduction of the concentrations of Na+ in the perfusate to maintain isotonicity. When comparable reductions in the concentration of external Na+ were achieved by replacement with choline (instead of K+), swelling of the perfused, exposed cortex was significantly less than that attributed to isotonic, K+‐rich but Na+‐poor fluids. These observations suggested that it was the elevated levels of K+ rather than lowered concentrations of Na+ that promoted the swelling of the perfused cerebral cortex.The apparent rate of influx of 36Cl from the perfusate into the underlying exposed and intact monkey cerebral cortex in vivo was a linear function of the concentration of K+ in perfusate over the range 25–117 mM and conformed to Michaelis‐Menten kinetics when plotted according to Lineweaver and Burk. Moreover, the apparent influx of chloride from perfusate into swollen cerebral cortex was a linear function of the percentage swelling of cerebral cortex over the range 6–30 per cent. However, the apparent rate of influx of chloride from perfusate into unswollen cortex was not consistent with the linear correlation already described for swollen cerebral cortex. One reason for this discrepancy was the reduction in the size of the true (inulin) extracellular space associated with the K+‐dependent swelling of cerebral cortex in vivo. The anatomical locus for this K+‐dependent swelling of cerebral cortex was an expanded glial compartment, as demonstrated by electron‐microscopy. The parenteral administration (50 mg/kg) or local perfusion (5 mM) of acetazolamide inhibited the K+‐dependent swelling of cerebral cortex in vivo. Moreover, administration of acetazolamide inhibited the K+‐dependent increase in content of C1‐ and the K+‐dependent rate of influx of 36Cl into swollen cerebral cortex. We have discussed the possible enzymatic basis of these K+‐dependent alterations in content of fluid and chloride and transport of chloride in mammalian cerebral cortex in viuo.

The Brain: Towards an Understanding

An extensive and delightfully written introduction entreats the public to become intrigued with the burgeoning brain science of our time. The author takes up a host of questions: the problem of memory, the neurophysiologic correlates of consciousness; the emergence of the questioning intellect of mankind as derived from primate cerebral cortex; the neurologic mechanisms of behavior; the numerous facets of perception and consciousness; the simile of computers and living brains; the feasibility of neurologically controlled prostheses for special sensory and locomotor deficits; the cure of a variety of degenerative diseases affecting the brain; the attempt to solve the riddle of mind and brain. Illustrative material is in the form of line drawings. The approach of the text is fundamentally through the eyes of a biophysicist dominated by extensive experience in molecular biology. Interdisciplinary boundaries are crossed with some decrement to the initial promises of the book. For the educated reader

Studies of the production and subsequent reduction swelling in primate. Cerebral cortex under isosmotic conditions in vivo.

1. The swelling of intact primate cerebral cortex perfused under isosmotic conditionsin vivo, like swelling of slices of mammalian cerebral cortex incubatedin vitro, is a linear function of the concentration of K+ in the extracellular fluid over the range 20–120 mM. 2. The simultaneous presence of the Cl− ion is required for the development of K+-dependent swelling of cerebral cortex under various experimental conditionsin vivo andin vitro. 3. The maintenance of previously established K+-dependent swelling of cerebral cortex bothin vitro andin vivo requires the relative concentrations of both K+ and Cl− in the extracellular fluid to remain constant. A reduction in the concentration of either ion is associated with an absolute loss of fluid of swelling of cerebral cortex. 4. The content of Cl− in cerebral cortex is a function of the magnitude of K+-dependent swelling even though the concentration of Cl− in the extracellular fluid is maintained constant. 5. The mechanism of swelling in primate cerebral cortex following cerebral circulatory arrest is discussed in the light of the experimental findings, as a model of the type of brain injury encountered in massive clinical stroke.

Oculomotor function following cerebral hemidecortication in the monkey. A study with special reference to optokinetic and vestibular nystagmus.

The role of the primate cerebral cortex in oculomotor function has been extensively investigated with electrical stimulation techniques. Recent experiments have demonstrated that deviational (horizontal and vertical), and centering eye movements may be elicited upon stimulations from almost every point on the cortex or subcortex. In the alert preparation, such as monkeys with cervical transection or chronically implanted electrodes,12,22the evoked ocular movements are usually of the deviational type. As a rule the binocular movement is horizontal and contralateral in direction. In the occipital lobe, vertical or oblique movements are more frequently obtained than from other areas of the brain.20Electrical stimulation in the anesthetized preparation, in contrast, induces more of eye centering; horizontal movements are less frequent, and vertical are rare.11These observations suggest that the entire cerebrum influences oculomotor function. In man, there seems to be some cortical specificity for ocular responses. Electrical stimulations elicit

Cell counts in the primate cerebral cortex.

Cell counts in the primate cerebral cortex.

The Main Afferent Fiber Systems of the Cerebral Cortex in Primates: An Investigation of the Central Portions of the Somato-Sensory, Auditory and Visual Paths of the Cerebral Cortex, with Consideration of Their Normal and Pathological Function, Based on Experiments with Monkeys. By Stephen Poliak, M.D., Associate Professor of Neurology, University of Chicago. University of California Publications in Anatomy, Volume 2.

This fine monograph is really a preliminary, and a necessary, one to a study of the comparatively little known association connections of various cortical areas as determined by cyto-architectural and myelo-architectural investigations. Obviously an accurate knowledge of the afferent projection systems is a necessary basis for an anatomic study of the association systems by which impulses received by the cortex are, so to speak, spread to other cortical regions or mechanisms. As the author points out, such knowledge has not been attained as yet. The two principal problems in attaining such knowledge are, first: disclosing the anatomic identity of functionally distinct afferent paths from their peripheral receptor organs to their cortical terminations and, second, establishing the internal organization of the afferent paths. Only after these problems have found a satisfactory solution can an attack be made on the following question: By what paths and mechanisms are the impulses streaming into