The sections in this article are:


1
Essence of Prefrontal Function: Regulation of Behavior by Representational Knowledge
11
Subdivisions of Prefrontal Cortex

12
Global Nature of Prefrontal Syndrome in Humans

13
Animal Model for Prefrontal Function in Humans

14
Delayed-Response Tests and Varying Interpretations of Their Functional Significance

15
Distractability and Perseveration: Secondary Consequences of Basic Defect in Representational Memory

16
Representational Memory in Wisconsin Card Sort and Other Diagnostic Tests of Prefrontal Function in Humans

17
Localization of Delayed-Response Function: Principal Sulcus

18
Circuit Basis of Visuospatial Functions




2
Accessing and “On-Line” Processing of Representations in Visuospatial Domain: Parietal-Prefrontal Connections
21
Visuospatial Representational Memory in Humans

22
Spatial-Mnemonic Nature of Delayed-Response Deficit: Domain-Specific Memory Loss

23
Topography of Representational Memory in Prefrontal Cortex

24
Electrophysiological Evidence of Spatial-Mnemonic Processes in Principal Sulcus

25
Parietal-Prefrontal Connectivity

26
Columnar and Laminar Framework for Feedforward and Feedback Mechanisms

27
Functional Significance of Parietal-Prefrontal Collaboration




3
Long-Term Memory and “Off-Line” Processing: Prefrontal-Limbic Connections
31
Role of Hippocampus in Spatial Memory

32
Multiple Connections Between Principal Sulcus and Hippocampal Formation

33
Quadripartite Neural Network: Parietal-Temporal-Cingulate-Prefrontal Circuit

34
Limbic Contribution to Spatial Memory




4
Response Initiation and Inhibition: Projections to Striatum, Tectum, Thalamus, and Premotor Cortex
41
Motor-Control Functions of Prefrontal Cortex

42
Cortical-Striatal Pathway and Related Feedback Loops

43
Cortical-Tectal Pathway

44
Thalamic-Cortical Systems

45
Prefrontal-Premotor Connections: Anterior Supplementary Motor Cortex Relays

46
Functional Speculations




5
Modulatory Mechanisms: Brain Stem Catecholamine Projections
51
Activation of Cognitive Machinery

52
Concentration and Synthesis of Catecholamines in Primate Cortex

53
Brain Stem Innervation of Prefrontal Cortex

54
Delayed-Response Deficits and Recovery Produced by Catecholamine Loss and Replacement in Prefrontal Cortex

55
Circuit Basis for Neuromodulation in Principal Sulcus




6
Multiple Subsystems of Prefrontal Cortex: Unity or Diversity of Function
61
Unity or Diversity of Prefrontal Function

62
Frontal Eye Fields

63
Inferior Convexity

64
Orbital Prefrontal Cortices

65
Problem of Integration




7
Diseases Affecting Prefrontal Cortex
71
Schizophrenia: Loss of Corticocortical Processing and Regulation of Behavior by Representational Knowledge

72
Wernicke-Korsakoff Syndrome: Loss of Thalamocortical and Brain Stem Modulatory Mechanisms

73
Huntington's Chorea and Parkinson's Disease: Loss of Prefrontal-Striatal Mechanisms and Initiation or Inhibition of Motor Response

74
Overview of Neurobiology of Disease




8
Summary

Circuitry of Primate Prefrontal Cortex and Regulation of Behavior by Representational Memory

Staining for the mitochondrial enzyme cytochrome oxidase reveals an array of dense regions (blobs) in the primate primary visual cortex. They are most obvious in the upper layers, 2 and 3, but can also be seen in layers 4B, 5, and 6, in register with the blobs in layers 2 and 3. We compared cells inside and outside blobs in macaque and squirrel monkeys, looking at their physiological responses and anatomical connections. Cells within blobs did not show orientation selectivity, whereas cells between blobs were highly orientation selective. Receptive fields of blob cells had circular symmetry and were of three main types, Broad-Band Center-Surround, Red-Green Double-Opponent, and Yellow-Blue Double-Opponent. Double-Opponent cells responded poorly or not at all to white light in any form, or to diffuse light at any wavelength. In contrast to blob cells, none of the cells recorded in layer 4C beta were Double-Opponent: like the majority of cells in the parvocellular geniculate layers, they were either Broad-Band or Color-Opponent Center-Surround, e.g., red-on-center green-off-surround. To our surprise cells in layer 4C alpha were orientation selective. In tangential penetrations throughout layers 2 and 3, optium orientation, when plotted against electrode position, formed long, regular, usually linear sequences, which were interrupted but not perturbed by the blobs. Staining area 18 for cytochrome oxidase reveals a series of alternating wide and narrow dense stripes, separated by paler interstripes. After small injections of horseradish peroxidase into area 18, we saw a precise set of connections from the blobs in area 17 to thin stripes in area 18, and from the interblob regions in area 17 to interstripes in area 18. Specific reciprocal connections also ran from thin stripes to blobs and from interstripes to interblobs. We have not yet determined the area 17 connections to thick stripes in area 18. In addition, within area 18 there are stripe-to-stripe and interstripe-to-interstripe intrinsic connections. These results suggest that a system involved in the processing of color information, especially color-spatial interactions, runs parallel to and separate from the orientation-specific system. Color, encoded in three coordinates by the major blob cell types, red-green, yellow-blue, and black-white, can be transformed into the three coordinates, red, green, and blue, of the Retinex algorithm of Land.

Anatomy and physiology of a color system in the primate visual cortex.

Sources, Effects and Risks of Ionizing Radiation

Functional anatomy of the basal ganglia. II. The place of subthalamic nucleus and external pallidum in basal ganglia circuitry.

The sections in this article are:


1
Biomechanical and Electromyographical Information
1.1
Single Limb During Locomotion

1.2
Interlimb Coordination

1.3
Treadmill Versus Overground Locomotion

1.4
Trunk Movements During Locomotion

1.5
Pathological Gaits

1.6
Summary




2
Neural Generation of “Basic Locomotor Synergy”
2.1
Central Versus Peripheral

2.2
Parts of CNS of Primary Importance for Neural Control of Basic Locomotor Synergy

2.3
Spinal Centers for Locomotion—Behavioral Results

2.4
Reflex Control of Basic Locomotor Synergy

2.5
Activity in Certain Spinal, Cerebellar, and Brain Stem Neurons and in Certain Reflex Pathways During Locomotion

2.6
Cerebellum and Locomotion

2.7
Initiation of Locomotion—Brain Stem Circuitry

2.8
Central Organization of Spinal Pattern Generation

2.9
Possible Rhythm-Generating Mechanisms and Models—Facts and Fiction

2.10
Developmental Aspects

2.11
Summary




3
Adapting Basic Locomotor Synergy to Animal's Needs
3.1
Changing Speed

3.2
Goal-Directed Locomotion—Turning and Walking Along Curvatures

3.3
Modifications of “Locomotor Posture”

3.4
Positioning of Limb in Each Step

3.5
Reflex Adaptation of Step

3.6
Summary




4
Concluding Remarks

Control of Locomotion in Bipeds, Tetrapods, and Fish

The autoradiographic tracing method has been used to analyze the distribution of ascending tectofugal pathways in the rhesus monkey. Our findings show that axons which arise from deep collicular neurons terminate within several dorsal thalamic nuclei which in turn project upon the frontal eye fields (area 8) and the inferior parietal lobule (area 7). Both of these cortical areas are functionally quite similar to the deep colliculus, and we suggest that ascending channels from the deep tectum must account, at least in part, for these functional similarities. The present autoradiographs reveal projections to several nuclear zones previously not identified as deep collicular targets in the monkey. Such targets include the visceral cell columns of the oculomotor complex, the rostral interstitial nucleus of the medial longitudinal fasciculus, and the magnocellular division of the ventral anterior nucleus. Deep tectal input also has been shown to terminate quite extensively within the paralamellar region of the mediodorsal nucleus and in the parafascicular nucleus; very little input to the central lateral and centromedian nuclei was observed. Radioisotope injections restricted to the superficial layers reveal dense projections to the parabigeminal nucleus, the pretectum, the inferior and lateral pulvinar nuclei, and to the ventral and dorsal lateral geniculate nuclei. Transported protein within the dorsal lateral geniculate nucleus occupied the "S" layers and the interlaminar zones.

Ascending pathways from the monkey superior colliculus: an autoradiographic analysis.

A study was made to determine the efferent projections of the subthalamic nucleus in the monkey. Because of the impossibility of producing lesions in this nucleus, not involving adjacent structures, lesions were produced by different stereotaxic approaches. Comparisons were made with degeneration resulting from localized lesions in substantia nigra and globus pallidus. Degeneration resulting from these lesions was studied in transverse and sagittal sections stained by the Nauta-Gygax method.



Efferent fibers from the subthalamic nucleus pass through the internal capsule into the medial pallidal segment; a few fibers are distributed to the lateral pallidum. Some subthalamic efferent fibers pass to the contralateral globus pallidus via the dorsal supraoptic decussation, but none projection to the thalamus.



Nigral efferent fibers project to parts of the ventral anterior (VAmc) and ventral lateral (VLm) thalamic nuclei. The medial pallidal segment gives fibers to: (1) ventral anterior (VA), ventral lateral (VLo) and centromedian (CM) thalamic nuclei, and (2) the pedunculopontine nucleus. The lateral pallidal segment projects exclusively to the subthalamic nucleus. Thalamic projections of the substania nigra and globus pallidus are distinctive. Subthalamic projections to the globus pallidus are more profuse than those of the substantia nigra.



The following hypothesis is presented: Subthalamic dyskinesia, due to lesions in the subthalamic nucleus, is a consequence of removal of inhibitory influences acting upon the medial segment of the globus pallidus.

Efferent fibers of the subthalamic nucleus in the monkey. A comparison of the efferent projections of the subthalamic nucleus, substantia nigra and globus pallidus.

1. Multiple-barreled microelectrodes were used to record from neurons in the area postrema of anesthetized dogs and to test the responses of the neurons to a variety of substances in this structure, which is known to function as the chemoceptive trigger zone for emesis. 2. The neurons in area postrema were silent at rest but could be "found" by virtue of their response to ionophoretic glutamate. The glutamic response was brief and of short latency with high frequency of discharge. 3. Dog area postrema neurons were also excited by over 20 other substances, including acetylcholine, the biogenic amines, several peptides, and at least two hormones. Not all agents were excitatory, however. 4. The responses to all excitatory agents except glutamate were similar and unusual. All responses showed a relatively long latency (3-20 s), a long duration of excitation (30 s to many minutes), and a low discharge frequency (1-3 Hz). 5. There was a good correlation between substances that were excitatory on area postrema neurons and substances known to cause emesis. Because emesis due to intravenous application of these substances is known to be abolished in animals with ablation of the area postrema, it is very likely that recordings were from the neurons which trigger the response. 6. Because so many substances elicit the same type of response there is a possibility that all utilize a common second messenger. Neurons were not excited by ionophoresis of guanosine 3',5'-cyclic monophosphate (cGMP) but were excited by 8-bromo-adenosine 3',5'-cyclic monophosphate (cAMP) and by forskolin, an activator of adenylate cyclase. 7. Behavioral studies were performed looking for emetic responses in awake dogs following intravenous injection of apomorphine, insulin, angiotensin II, and leucine enkephalin. For each a threshold concentration could be determined, which would consistently evoke emesis. 8. Dogs pretreated with phosphodiesterase inhibitors (theophylline, 3-isobutyl-1-methylxanthine, or RO 1724) showed a shift in the threshold concentration of the above substances that triggered emesis, such that emesis was evoked by lower concentrations than in the control. 9. These results suggest that neurons of the dog area postrema trigger the emetic reflex in response to specific receptors for a great variety of transmitters, peptides, and hormones, and that these receptors act through a common second messenger, cAMP.

Excitation of area postrema neurons by transmitters, peptides, and cyclic nucleotides.

Three types of neuron with differences in Nissl pattern were found in the red nucleus of the rhesus monkey. Neurons with coarse Nissl bodies occurred only in the caudal third of the red nucleus except for a small number which extended rostrally a short distance along the dorsolateral margin. Neurons with fine Nissl bodies occupied the rostral two-thirds of the nucleus. Neurons with slight cytoplasmic basophilia (achromatic) were smaller than the other types and distributed throughout the red nucleus. Perikaryal areas of the coarse and fine neurons, measured with a computer, had widely overlapping distributions.



Electrolytic lesions were made unilaterally in the red nucleus of nine monkeys. Ascending axonal degeneration was studied in sections stained by the Fink-Heimer method. Two separate descending tracts were followed. The rubrobulbo-spinal tract took origin from coarse neurons, crossed completely in the ventral tegmental decussation, and terminated as follows: in parts of the superior sensory trigeminal, motor facial and lateral reticular nuclei; in the gracile and cuneate nuclei; in the nucleus medullae oblongata, subnucleus dorsalis; in Rexed's laminae V, VI, VII at all levels of the spinal cord. In contrast, the rubroreticulo-olivary tract took origin from fine neurons, remained uncrossed, and terminated in some reticular nuclei (pedunculopontine, pontis oralis and caudalis, gigantocellularis) and in parts of the inferior olivary complex. Degeneration was profuse in the dorsal lamina of the main olive, abundant in the ventral lamina, particularly in its lateral side, sparse and inconstant in the medial accessory olive, and invariably absent in the dorsal accessory olive. Thus, nuclei which receive descending projections from the red nucleus may be grouped into those with connections to lower motor neurons, cerebellum, or thalamus.

Efferent connections of the red nucleus in the brainstem and spinal cord of the Rhesus monkey.

1.

The responses of 122 neurons in the area postrema of anesthetized dogs to 17 common transmitters and peptides were determined. Recordings were made from one barrel of a seven-barrel ionophoretic electrode.




2.

All neurons were silent at rest, but most could be detected and excited by the application of glutamate. The glutamate response was a brief, high-frequency response of less than 1-sec duration.




3.

Excitatory responses were also found to histamine, norepinephrine, serotonin, dopamine, apomorphine, angiotensin II, neurotensin, leucine enkephalin, vasoactive intestinal polypeptide, thyrotropin releasing hormone, gastrin, vasopressin, and substance P. While most neurons tested were excited by dopamine and apomorphine, approximately half of those studied were also excited by each of the other substances. Inhibitory responses were found to norepinephrine (6 of 15 cells) and histamine (3 of 45 cells). No responses were found to acetylcholine, somatostatin, or cholecystokinin.




4.

The responses to all 13 excitatory substances other than glutamate were similar. Typically these responses had a latency of 2–20 sec and lasted for 30 sec to 5 min on their first application. The frequency of discharge was usually low (~0.5 Hz). Multiple applications of these agents often induced a maintained spontaneous discharge of low frequency. Each application also induced a transient incremental discharge at a frequency that rarely exceeded 2 Hz.




5.

The area postrema has been proposed to be the “chemoreceptor trigger zone” for emesis (Borison and Wang, 1953). All of the agents which excite area postrema neurons, with the exception of serotonin and norepinephrine, are emetic, while none of the three agents without excitatory effects is known to be emetic. Thus these results provide strong support for the central role of the area postrema in emesis.




6.

The similarity of response to so many substances on small neurons suggests a common ionic and/or metabolic mechanism underlying the response. The prolonged nature of the response to brief administration of these agents would seem to be appropriate for neurons which subserve a sensation and behavior such as nausea and vomiting.

Norman L. Strominger

Papers

Ascending pathways from the monkey superior colliculus: an autoradiographic analysis.

Efferent fibers of the subthalamic nucleus in the monkey. A comparison of the efferent projections of the subthalamic nucleus, substantia nigra and globus pallidus.

Excitation of area postrema neurons by transmitters, peptides, and cyclic nucleotides.

Efferent connections of the red nucleus in the brainstem and spinal cord of the Rhesus monkey.

Responses of neurons of canine area postrema to neurotransmitters and peptides