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Objective. To determine whether ranolazine, a newanti-angina medication, could be an effective anal-gesic agent in complete Freund’s adjuvant-inducedinflammatory pain.Background. Plantar injection of complete Freund’sadjuvant (CFA) produces an extended period ofhyperalgesia that is associated with a dramaticup-regulation of Na v 1.7 sodium channels in popula-tions of large and small dorsal root ganglionneurons related to the injection site. Ranolazineappears to produce its anti-angina effect throughblocking the late sodium current associated with thevoltage-gated sodium channel, Na v 1.5. Becauseranolazine also inhibits Na v 1.7, and 1.8, we soughtto determine whether it could be an effective anal-gesic agent in CFA-induced inflammatory pain.Methods. Baseline determinations of withdrawalfrom thermal and mechanical stimulation were madein Sprague-Dawley rats ( ~ 300–350 ¥ g ). Followingdetermination of baseline, one hindpaw in eachgroup was injected with 0.1 mL of CFA. The con-tralateral paw received saline. Thermal andmechanical stimulation was repeated on the thirdday post-injection. Vehicle (0.9% isotonic saline;pH 3.0) or ranolazine was then administered in ran-domized and blinded doses either by intraperitoneal(ip) injection (0, 10, 20, and 50 mg/kg) or by oralgavage (po; 0, 20, 50, 100, and 200 mg/kg). Animalswere again tested 30 minutes (ip) and 1 hour (po)after drug administration.Results. Ranolazine produced dose-dependantanalgesia on mechanical allodynia induced by CFAinjection, but had no effect on thermal hyperalgesia.Conclusions. Ranolazine’s potential as a newoption for managing both angina and chronicinflammatory pain warrants further study.Key Words. Ranolazine; CFA; Pain; AllodyniaIntroduction

Connections between the primary motor cortex (MI) and the corpus striatum were studied in the owl monkey. Representations of specific body movements were elicited in MI by microstimulation techniques, and the efferent projections from these stimulation sites were labeled with wheat germ agglutinin-horseradish peroxidase conjugate (WGA-HRP). Dense projections were found in the putamen ipsilateral to the injection site and sparser projections occupied comparable areas in the contralateral putamen. Representations of hindpaw regions projected to the dorsomedial portion of the putamen with only slight extensions across cell bridges into the caudate nucleus. Representations of the forepaw and head projected to progressively more ventrolateral zones of the dorsal two-thirds of the putamen. Projections from injections of cortex representing discrete body movements terminated in an irregular or patchy distribution over a relatively large portion of the putamen. Extensive projections from relatively discrete injections in MI are indicative of a large degree of divergence and provide evidence for possible overlap from representations of relatively disparate body parts. The results are consistent with observations reported in other species of primates, but different from those seen in carnivores. This difference is discussed with regard to possible general features of corticostriate organization. Many regions of the cerebral cortex provide afferent connections to the corpus striatum and have been shown to terminate in a topographic fashion (Kemp and Powell, '70; Yeterian and VanHoesen, '78; Selemon and GoldmanRakic, '85). In primates, the frontal, parietal, and temporal association cortices project predominantly to the caudate nucleus (Goldman and Nauta, '77; Kunzle, '78; Yeterian and VanHoesen, '78; VanHoesen et al., '81; Selemon and Goldman-Rakic, '85; Alexander et al., '86; Arikuni and Kubota, '86; Jayaraman, '87) whereas motor, premotor, supplementary motor, and somatosensory cortices project predominantnly to the putamen (Kunzle, '75, '77, '78; Jones et al., '77; Jurgens, '84; Liles and Updyke, '85; Alexander et al., '86). In general, corticostriate projections that originate in primary motor cortex are broadly distributed in the putamen and are organized in a basically topographic fashion; projections from those portions of motor cortex related to the representation of the head terminate primarily in the ventral putamen whereas the representations of the upper limb, trunk, lower limb, and tail project to successively more dorsal portions of the putamen (Kiinzle, '75, '77; Jones et al., '77). The general topographic organization of projections from primary motor cortex to the corpus striatum provides the basis for much of our understanding of functional localization in the neostriatum. This framework, however, was determined in early studies in which the sites for injection were anatomically defined according to the physiological map of Woolsey ('58). Conclusions are based on the assumption that large injections in precentral cortex involve specific body representations identical to those depicted in the same relative position of precentral cortex in previously generated summary stimulation maps (Woolsey, '58). While providing a general framework, however, it is difficult to assign a specific role to corticostriate projections in particular isolated movements when large injections, possibly involving several body representations, are utilized. Summary maps of the primate primary motor cortex have been generated in several laboratories by using contemporary

PURPOSE OF REVIEW: Chronic pain leads to a reduction in the quality of life for those who suffer it. Due also to high medical costs and lost productivity, chronic pain is a significant burden on society. One contributor to the burden of pain is the fear that medications used in pain management produce dependency, leading to diversion and addiction. Certain medications used in practice, although not abused by the patient, seem to be favored and these are frequently reported to be used recreationally by the nonpatient population. This report identifies medications that most frequently present a problem in pain practices, why they are a problem, and possible alternatives to their use. RECENT FINDINGS: Problem medications used in analgesic regimens tend to be those that have rapid onset due to their lipophilic nature or route of administration, short duration, and a sedating or energizing effect. These medications are generally more affordable than alternatives with less abuse potential. These medications are more often covered by insurance and more frequently prescribed. Changes in prescribing habits have resulted in predictable shifts in abuse. SUMMARY: Addiction and diversion of prescription medications is a multidimensional problem. Its multifactorial solution will require efforts at many regulatory levels.

Although nerve growth factor plays a role in augmenting sodium channel expression in small dorsal root ganglion (DRG) cells, the cytochemical mediators responsible for enhanced expression in large DRG neurons are unknown. To narrow the search for mediators involved in the increased production of sodium channels in large DRG neurons, we examined the effect of cyclooxygenase inhibition on sodium channel production during inflammation. Thirty minutes before the subcutaneous injection of complete Freund's adjuvant (CFA), rats received ibuprofen (nonselective, cyclooxygenase inhibitor), NS-398 (selective, cyclooxygenase inhibitor), or vehicle. Withdrawal thresholds from thermal and mechanical stimulation were measured before and immediately after CFA injection and at selected hourly intervals after injection for the next 24 hours. Sodium channel up-regulation was then examined in DRG by using site-specific, anti–sodium channel antibodies, Na v 1.7 and 1.8. Both ibuprofen and NS-398 provided analgesia during the second phase of inflammatory hyperalgesia that begins 3 hours after CFA injection. The up-regulation, predominantly of Na v 1.7 and minimally of Na v 1.8 channels, seen in vehicle-treated rats was suppressed by both drugs at 24 hours after injection. By 72 hours after injection, no difference in labeling between the drug- and vehicle-treated animals was observed. Sodium channel labeling in large DRG neurons returned to baseline between 1 and 2 weeks after CFA injection, whereas small cell labeling persisted. The cytochemical signal for sodium channel up-regulation in the large DRG cells that most closely correlates with inflammatory hyperalgesia is mediated at least in part through products of the cyclooxygenase pathway. Perspective Expression of sodium channels in dorsal root ganglia increases dramatically during inflammation. The increase in sodium channels is thought to enhance neuronal excitability and to play a role in hyperalgesia and wound vigilance during healing. We provide evidence that prostaglandins play a role in signaling channel augmentation.

Much of our current understanding about chronic pain and the mechanisms of nociception has been derived from animal models (Bennett GJ. Animal models of neuropathic pain. In: Gebhart, GF, Hammond DL, Jensen TS, editors. Progress in pain research and management, vol. 2, Proceedings of the 7th World Congress of Pain. Seattle, WA: IASP Press, 1994. pp. 495-510; Dubner R, Methods of assessing pain in animals. In: Wall PD, Melzack R, editors. Textbook of pain, vol. 3. Edinburgh: Churchill Livingstone, 1994. pp. 293-302). It has been argued in some cases that animals do not perceive 'pain' as humans do, and thus extrapolation of the results of studies in animals is invalid. Clearly, the animal models used in the laboratory do not approach the complexity of chronic pain encountered in the clinical setting. Human pain perception is more complex since it encompasses lesion variability, as well as psychosocial, cultural, developmental, and environmental variables. Where parallels exist, it is possible to gain insight into certain aspects of human pain syndromes that are likely to lead to improved therapeutic opportunities for individual patients. One such model that is frequently used in animals to study pain associated with inflammation is the subcutaneous injection of complete Freund's adjuvant (CFA). For ethical reasons, however, little information is available from humans concerning pain associated with this form of inflammation. Due to an inadvertent subcutaneous injection of CFA into the terminal phalanx of this investigator, a study with an N of 1, was conducted to compare the subjective effects of CFA-induced inflammation with objective measurements.

Gabapentin is an effective option for the treatment of neuropathic pain syndromes because of its efficacy and favorable side-effect profile. A case is presented of a 58 year old man who developed a painful polyneuropathy while being treated with gabapentin.

BACKGROUND Implantable pumps for the delivery of intrathecal morphine have become a common option for administering opiate medication for the management of pain in patients with terminal cancer. Options for treating chronic pain of non-malignant origin are more controversial. This study describes responses to intrathecal morphine administration for managing chronic pain in patients without an underlying malignancy. METHODS Eleven patients between the ages of 29 and 81 years, nine with failed back syndrome (FBS) and two with neuropathic pain (NP) from other causes, were chosen from 15 consecutive individuals referred to neurosurgery clinic. The presenting levels of pain and a functional-economic outcome level were determined for each patient. Patients were admitted to the hospital for therapeutic trials and were assessed for the appropriateness of their analgesic response and for adverse responses to the medication. A morphine pump was implanted in five males and six females who were followed for up to 3 years. RESULTS A good to excellent analgesic response was seen in 8 (73%) patients (6 FBS; 2 NP). In the remaining three patients (27%), the analgesic response was judged poor (3 FBS). In patients with FBS, the total effective response was 67%. Two patients experienced bladder dysfunction requiring pump removal. Other adverse effects of pump placement were rare. CONCLUSIONS The morphine pump was found to be a viable alternative in the management of failed back syndrome. Its use in long-term therapy, however, is not without limitations and should be a last choice option.

Ranolazine modulates the cardiac voltage-gated sodium channel (NaV 1.5) and is approved by the FDA in the treatment of ischemic heart disease. Ranolazine also targets neuronal (NaV 1.7, 1.8) isoforms that are implicated in neuropathic pain. Therefore, we determined the analgesic efficacy of ranolazine in a preclinical animal model of neuropathic pain. Both intraperitoneal and oral administration of ranolazine dose-dependently inhibited the mechanical and cold allodynia associated with spared nerve injury, without producing ataxia or other behavioral side effects. These data warrant clinical investigation of the potential use of ranolazine in the treatment of neuropathic pain.

Interhemispheric connections of visual cortex were studied in owl monkeys, marmosets, and galagos after multiple injections of horseradish peroxidase into one cerebral hemisphere. Areal patterns of connections were revealed in sections of cortex that was flattened and cut parallel to the surface. Results were related to the locations of known visual areas, especially in owl monkeys, in which more visual areas have been established. The connection patterns in owl monkeys and marmosets are very similar, suggesting that the organization of visual cortex differs little in these two New World simians. Galagos have a basically similar pattern, but the connections are more widespread. In all three primates, connections are not restricted to cortex representing the line of decussation of the retina, and even striate cortex has connections displaced from the border. These connections extend up to 2 mm into area 17 in owl monkeys, and they are most extensive in galagos, where they form foci that are coextensive with regions of high cytochrome oxidase activity. Connections are concentrated in the caudal half of area 18, but protrusions of connections cross of the width of the field. The middle temporal visual area (MT) has unevenly distributed connections throughout, with some increase in density along the border. The dorsomedial visual area (DM) of owl monkeys has connections restricted to the rostral border, and a similar region of sparse connections identifies the probable location of DM in marmosets and galagos. Caudal parts of the dorsolateral visual area (DL) of owl monkeys have dense interhemispheric connections. Other visual areas are characterized by unevenly distributed clumps of connections, suggesting that functions are not uniformly distributed, and that semiregular processing modules exist. The results indicate that most extrastriate visual neurons are subject to interhemispheric influences and support the conclusion that callosal connections are functionally heterogeneous.

The results of this study demonstrate the existence of single neocortical neurons that send axon collaterals into the corpus callosum, to terminate within the contralateral hemisphere, and subcortically, to terminate within the ipsilateral superior colliculus.

The callosal connections within the posterior parietal and occipital cortices were studied in the squirrel monkey with horseradish peroxidase tracing techniques. The data were evaluated with particular emphasis on the relationship of major callosal connections along the 17-18 border. The overall pattern of callosal connections in the squirrel monkey also was compared with callosal patterns in other New World simians. Our results show that the dense band of callosal connections along the 17-18 border in the squirrel monkey differs from the connections observed in other New World monkeys in that it is virtually confined to area 18 and avoids area 17. In addition to a continuous band of callosal connections in area 18 that parallels the 17-18 border, rostral extensions of the band are oriented perpendicular to the 17-18 border and present an obvious periodicity. The remaining parieto-occipital cortex contains a complex pattern of callosal connections that is strikingly similar to patterns reported for other New World monkeys. Thus, it is likely that the dorsolateral extrastriate visual cortex in the squirrel monkey is organized in a manner similar to that found within other New World monkeys.

The connections of the cortical dysgranular "unresponsive zone" (UZ) (Sur et al.: J. Comp. Neurol. 179:425-450, '78) in the grey squirrel were studied with horseradish peroxidase and autoradiographic techniques. The results of these experiments show that the major subcortical connections of the unresponsive zone are in large part reciprocal. Connections are distributed within the thalamus in a poorly defined region including restricted portions of several nuclei that lie along the rostral, dorsal, and caudal borders of the ventral posterior nucleus. Additional thalamic connections of the UZ terminate in the reticular nucleus and are reciprocally related to the paralaminar and central median nuclei. Extrathalamic terminations were observed in the zona incerta, the intermediate and deep layers of the superior colliculus, the red nucleus, and several subdivisions of the pontine nuclei. The similarity between the pattern of subcortical connections of the UZ in the grey squirrel and patterns reported for the parietal septal region in rats (Chapin and Lin: J. Comp. Neurol. 229:199-213, '84) and for area 3a in primates (Friedman and Jones: J. Neurophysiol. 45:59-85, '81), suggests that the UZ in the grey squirrel may represent a counterpart of at least part of area 3a as described in primates. The results are further discussed with respect to a possible role of the thalamus in control or modulation of interhemispheric circuits and of the UZ in the modulation of nociceptive and kinesthetic pathways through the thalamus. Finally, the term parietal dysgranular cortex (PDC) is proposed as an alternative to denote the region currently called the unresponsive zone.

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 topographic distribution of somesthetic interhemispheric projections was studied in grey squirrels using the Fink-Heimer technique follow- ing large aspiration lesions of' the corpus callosum. On the day of perfusion, receptive fields were determined for microelectrode recording sites in the first, S I, and second, S 11, somatosensory areas of cortex, and small electrolytic lesions were made in order to identify some of these sites in prepared brain sections. The cortex was then separated from the rest of the brain, flattened, and cut parallel, so that with the aid of the reference lesions, the total pattern of degeneration could be related to a surface view of the brain and to previous electrophysiological maps of S I (Sur et al., '78) and S I1 (Nelson et al., '79). The results show that callosal terminations are unevenly distributed in S I and S 11, and suggest that there are several categories of callosal inputs to S I. A major region of terminations is in the architectonically distinct "unresponsive zone" within SI, and perhaps in other similar, but narrower, specialized zones within and bordering S I, as previously described in rats (Ryugo and Killackey, '75; Wise and Jones, '76, '78 Akers and Killackey, '78). Other callosal projections terminate within the responsive regions of S I. These regions include at least some of the representation of the body midline, most clearly the midline of the representations of the upper and lower face, as well as regions unrelated to the midline of the body. Most or all of the SI cortex responsive to stimuli away from the midline on the upper and lower lips, the mystacial vibrissae, and the glabrous forepaw was almost free of direct callosal terminations. Except for a central core region, most of S I1 appears to receive a moderate distribution of callosal inputs. Patterns of callosal connections in parietal cortex have been studied in a range of mamma- lian species with the consistent observation that terminations are unevenly distributed within the first (S I) and second (S 11) somato- sensory representations (for review see Akers and Killackey, '78). Many of these studies have attempted to relate the observed distribution of terminations to prevailing concepts of how the body is represented in these two fields, with the result that several different, although not nec- essarily incompatible, concepts of the func- tional roles of callosal connections have evolved. Two different explanations were used to account for the conclusion that the represen- tations of the distal limbs have few or no callosal connections in S I and S 11. The earlier view was that the separate maps of the contra- lateral body surface in each hemisphere are connected along the representations of the dor- sal midline of the body through the corpus callosum so as to form continuous or joined rep- resentations (Ebner and Myers, '62, '65; Ebner, '69; Jones, '67; Jones and Powell, '68, '69a, '73; Pandya and Vignolo, '69; Karol and Pandya, '71; Jones et al., '75; Shanks et al., '75) in a manner analogous to the joining of the visual hemifield representations along the vertical meridian. An alternative explanation for this conclusion is that commissural terminations are devoted to those parts of the two hemirepre- sentations that have integrated or coordinated sensory-motor functions, while callosal connec- tions are lacking in parts of S I and S I1 with highly independent or "lateralized functional roles (Jacobson, '70; Yorke and Caviness, '75).

Corpus callosum connections of parietal and motor cortex were studied in New World owl monkeys (Aotus trivirgatus) and Old World macaque monkeys (Macaca fascicularis) after multiple injections of 3H-proline and horseradish peroxidase, HRP, into one cerebral hemisphere, and extensive microelectrode mapping of architectonic Areas 3b, 1, and 2 of the other hemisphere. Results were obtained both from parasagittal brain sections cut orthogonal to the brain surface and from sections from flattened brains cut parallel to the brain surface. Cortical fields varied in density of callosal connections, and the density of connections varied according to body part within sensory representations. Thus, Area 3b had few, Area 1 had more, and Area 2 had relatively dense callosal connections. Within each of these fields, connections were much less dense for the representations of the glabrous hand and foot and much more dense for the representations of the face and trunk. For the representation of the hand, retrogradely labeled cells were extremely sparse in Area 3b, moderately sparse in Area 1, and moderate in Area 2. There were less dense callosal connections in the hand representations of Areas 3b, 1, and 2 in macaque as compared to owl monkeys. Label in posterior parietal cortex was uneven with zones of extremely dense connections. A large region of very dense callosal connections was noted in motor cortex just medial to the probable location of the hand representation. In all regions, callosally projecting cells appeared to be more broadly distributed than callosal terminations. In no region was the discontinuous arrangement of callosal connections obviously organized into an extensive pattern of mediolateral or rostrocaudal bands or strips.

A new technique is described that minimizes the damage to neural tissues caused by the cortical incisions that must be made when operating on intracerebral or intraventricular lesions. Symmetric cortical incisions were made bilaterally in the same region of the middle suprasylvian gyrus in six dogs. Blunt dissection was performed on the right side. A new technique, which utilizes a balloon catheter, was employed on the left side. A greater hemiparesis was observed on the left side in all dogs. There was a mild but definite hemiparesis on the right side in four dogs, which improved within 2–3 days postoperatively. The dogs were killed on the sixth postoperative day. The Fink-Heimer technique for selective staining of degenerating axons and their terminal boutons was used to determine the extent of neuronal damage. Histologic studies support clinical observations in the experimental animal that the neural damage resulting from cortical incision is significantly decreased when the balloon catheter technique is applied.

Cortical subdivisions based on cytoarchitectural and myeloarchitectural observations of normal tissue were correlated with the topography of corticocortical connections in the visual system of the Pakistani hedgehog. Large subpial aspiration lesions were made in both visual and non-visual cortical regions to determine the areal limits of the corticocortical connections of the visual cortex. Subsequently, discrete electrolytic lesions were placed within the visual cortex. After appropriate survival periods, the brains were processed and stained with the Fink-Heimer technique. The results of these studies show that the visual cortex may be subdivided into four distinct regions from lateral to medial; the lateral parastriate cortex, the lateral and medial part of striate cortex, and the medial parastriate cortex. Within these regions, interhemispheric connections between visual cortices arise mainly in the lateral striate and lateral parastriate regions and terminate in a single band within the lateral portion of the cytoarchitecturally defined striate cortex. These corticocortical projections, therefore, substantially overlap with the geniculostriate projections. Lateral striate cortex and lateral parastriate cortex project in a reciprocal fashion that correlates well with the physiologically defined mirror image representation of two retinotopic maps of the binocular visual field on cortex. These connections are reflected about a line that is closely correlated with the medial edge of the band of commissural axon terminals that is located within the lateral striate cortex, instead of corresponding exactly with the striate-parastriate border as they do in other mammals. Medial striate cortex projects to medial parastriate cortex, indicating that the monocular portion of V I is related to a separate secondary area of cortex on the medial wall of the hemisphere.

The total pattern of visual callosal connections was studied in the grey squirrel by using the Fink-Heimer technique for axonal and terminal degeneration and the autoradiographic and horseradish peroxidase techniques for axonal transport. The pattern of terminations was correlated with architectonic landmarks. The results show that callosal terminations are distributed in a complex fashion within the visual cortical areas. The major terminations form a band in area 17 along its border with area 18. This band is contiguous rostrally with the callosal terminations in area L that extend caudomedially onto the medial wall of the hemisphere. Caudally the band in area 17 wraps around the ventral aspect of the occipital pole and ends medially at the level of the hippocampus. This band exhibits a distinct periodicity in the density of terminations. The callosal terminations in area 18 are usually found along the lateral and medial borders and are concentrated in discrete patches. The pattern in area 19 exhibits two or three primary patches and only loosely corresponds to the borders of the area. Few callosal terminations are found in area 19p and the posterior temporal area, Tp, while the intermediate temporal area, Ti, receives an extensive input. The laminar distribution of callosal terminations is different in each area studied. Characteristically, area 18 has dense terminations in layers III, II, and the inner one-half of layer I, with less dense terminations in layers V and VI, and sparse terminations in layer IV. Area 17 has a similar pattern in the supragranular and infragranular layers but also has dense terminations in layer IV. The patterns in area 19 are intermediate between these extremes but are more similar to those in area 17. The cells that give rise to the callosal projections were found primarily in layers III and V and occasionally in layers II, IV, and VI. The distribution of the callosal efferent neurons is more extensive than the areas of terminations. The distribution of callosal terminations suggests that the organization of visual cortical areas in the grey squirrel is more complex than had been previously recognized. This finding is discussed with reference to the general organization of the mammalian visual cortical areas, and a need for more extensive analyses of visual cortical areas in the grey squirrel, particularly with respect to extrastriate visual areas, is indicated.

The organization of somatosensory maps was examined in rabbits with the aid of microelectrode multi-unit recording techniques. Two complete maps of the contralateral body surface are identified in the parietal cortex. The first map, S I, is found entirely on the lateral convexity of the hemisphere and closely resembles S I described in the rat (Welker, '71, '76). It is organized in a complex, though systematic, fashion with the representations of the hindlimb and tail located caudomedially. These representations are followed laterally in sequence by those of the trunk and forelimb and then the representation of the head. Within the head representation the lips are found rostrally, the vibrissae caudomedially, and the displaced representation of the pinna of the ear is located caudolaterally. Unlike the disposition in most other mammals, the dorsal midline of the trunk is represented along the caudal border of S I. Within S I, the representations of the circumoral surfaces, including the lips, philtrum, nose, and vibrissae, are emphasized, occupying approximately 86.4% of the map. It is suggested that S I is contained within a single major koniocortical region, here called the medial parietal area, or Pm. The several previously described parietal regions (Rose, '31; Fleischhauer et al., '80) are interpreted as subregions that are related to particular representations of portions of the body surface. The second map, S II, is located lateral to S I in a region here called the lateral parietal area or Pl. S II shares a common border with S I along the representations of the philtrum, bridge of the nose, and top of the head. The body is oriented in an erect conformation with the head located rostrally and medially and the hindlimb and tail located caudally and laterally.

Corpus callosal connections of somatosensory cortex were studied in rabbits by combining anatomical tracing and electrophysiological mapping in the same animals. The results show that callosal connections are unevenly distributed in SI and SII. In SI, the representations of all body surfaces caudal to the neck and midline structures of the head have dense callosal connections. Conversely, connections are sparse to absent within representations of laterally positioned surfaces of the head, such as the sinus hairs, vibrissae, and nonmidline portions of the lips. Almost all of SII has dense callosal connections; only the representations of the vibrissae and sinus hairs have moderate callosal connections. The laminar distribution of callosal connections in rabbit SI and SII is similar to that observed in other mammals. Callosal terminations extend from the inner portion of layer I to the outer portion of layer VI, are moderately denser in the supragranular layers, and are sparse in layer IV. Callosally projecting cells are found predominantly in layers II, III, and V and are sparse in layers IV and VI. These data further emphasize the direct correspondence between the pattern of callosal connections in SI and the functional importance of particular body surfaces. Hence, representations of body surfaces important in the exploration of the environment are relatively free of callosal connections, whereas representations of midline and more lateral surfaces, less significant in tactile exploration, receive dense callosal connections. Callosal connections in rabbits are distributed extensively throughout responsive koniocortical regions rather than being relegated to distinct, specialized regions of “unresponsive” dysgranular cortex as in rodents.

Microstimulation and anatomical techniques were combined to reveal the organization and interhemispheric connections of motor cortex in owl monkeys. Movements of body parts were elicited with low levels of electrical stimulation delivered with microelectrodes over a large region of precentral cortex. Movements were produced from three physiologically defined cortical regions. The largest region, the primary motor field, M-I, occupied a 4-6-mm strip of cortex immediately rostral to area 3a. M-I represented body movements from tail to mouth in a grossly somatotopic mediolateral cortical sequence. Specific movements were usually represented at more than one location, and often at as many as six or seven separate locations within M-I. Although movements related to adjoining joints typically were elicited from adjacent cortical sites, movements of nonadjacent joints also were produced by stimulation of adjacent sites. Thus, both sites producing wrist movements and sites producing shoulder movements were found next to sites producing digit movements. Movements of digits of the forepaw were evoked at several locations including a location rostral to or within cortex representing the face. Overall, the somatotopic organization did not completely correspond to previous concepts of M-I in that it was neither a single topographic representation, nor two serial or mirror symmetric representations, nor a "nesting about joints" representation. Instead, M-I is more adequately described as a mosaic of regions, each representing movements of a restricted part of the body, with multiple representations of movements that tend to be somatotopically related. A second pattern of representation of body movements, the supplementary motor area (SMA), adjoined the rostromedial border of M-I. SMA represented the body from tail to face in a caudorostral cortical sequence, with the most rostral portion related to eye movements. Movements elicited by near-threshold levels of current were often restricted to a single muscle or joint, as in M-I, and the same movement was sometimes multiply represented. Typically, more intense stimulating currents were required for evoking movements in SMA than in M-I. A third motor region, the frontal eye field (FEF), bordered the representation of eyelids and face in M-I. Eye movements elicited from this cortex consisted of rapid horizontal and downward deviation of gaze into the contralateral visual hemifield.