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Biomedical subjects

J M Sprague

Publications and source records attributed to J M Sprague.

13 recordsLinked to original sources

Longterm impairment of cat optokinetic nystagmus following visual cortical lesions.

Binocular and monocular gain of optokinetic nystagmus (OKN), OKN dynamics, vestibulo-ocular reflex (VOR) and VOR adaptation were measured in 5 normal cats and in 5 cats which underwent bilateral visual cortical lesions involving the 17-18 complex at least 4 months before testing. We observed longterm deficits after bilateral lesions involving area 17 and variable parts of area 18 but failed to observe deficits after 18-19 lesions. These deficits were limited to the OKN gain and the build-up time constant of OKN; the VOR and the optokinetic after-nystagmus (OKAN) time constant were within normal limits. Our results suggest that areas 17-18 operate in parallel to control the encoding of retinal slip velocity at the level of the nucleus of the optic tract (NOT) and the accessory optic system (AOS), which are known to represent the initial stage of the optokinetic pathways.

Animals

Striate cortex and visual acuity functions in the cat.

Using a two-choice visual discrimination paradigm, thresholds for size (gratings), parallelness (parallel vs. non-parallel lines), contour alignment (vernier offset), and angularity (polygon figures) were behaviorally determined in cats before and after ablations of portions of the geniculo-cortical system. Animals with a total loss of cortical area 17, and with a loss, in some cases, of up to 90% of areas 18 (with and without infringement into area 19), showed about a 30% reduction in grating acuity, a three-fold increase in parallelness and angularity thresholds, and a total loss of contour alignment ability. Control animals with ablations sparing area 17 showed no significant threshold changes. All animals were able to learn classic form discriminations postoperatively, but those with area 17-18 lesions at a somewhat slower than normal rate. Control procedures indicated that all tested discrimination capabilities did not depend on luminance differences between targets, local flux cues within the targets, or on the animals' use of residual portions of area 17 representing the peripheral visual field. Since the cat has multiple thalamo-cortical visual pathways, the results of the present study are consistent with the hypothesis that pathways parallel to the geniculo-striate system are capable of processing spatial information of considerable detail. The results also suggest, however, that the geniculo-striate system is uniquely necessary for the processing of the finest attributes of spatial contours.

Animals

Behavioral and electrophysiological effects of unilateral optic tract section in ordinary and Siamese cats.

In ordinary cats, section of one optic tract produced a complete contralateral hemianopsia in both eyes. Single-unit recordings showed a normal representation of the contralateral nasal retina and ipsilateral temporal retina in the SC on the side of the intact optic tract. In addition, in the rostral portion of this SC there was a representation of a small portion of the contralateral temporal retina. This portion was apposed to the vertical meridian and its width was at most 6 degrees. In the anterior half of the SC on the side of the optic tract section, despite the interruption of any direct optic input, there was an extensive representation of the ipsilateral nasal retina and the contralateral temporal retina. This indirect visual input to the SC ipsilateral to the optic tract section was absent in a cat with a section of the forebrain commissures. In Boston Siamese cats, section of one optic tract led to a virtually complete blindness in the eye contralateral to the section, whereas the other eye retained a full visual field, although the responsiveness of the temporal retina beyond 20 degrees from the vertical meridian was reduced. Similarly, the nasal hemiretina and most of the temporal hemiretina on the side of the section were represented in the opposite SC, whereas stimulation of the eye contralateral to the section could not drive SC units. There was some evidence that the visual field of the eye on the side of the section could at least in part be represented in the SC on the same side. The findings indicate that the crossed projections from temporal hemiretina in the ordinary cat, and the uncrossed projections from temporal hemiretina in the Siamese cat are insufficient by themselves to sustain visual orientation and to drive SC neurons. Each half of the visual field in the ordinary cat, and the field of each eye in the Siamese cat, can be represented in the ipsilateral SC via across-the-midline, indirect connections.

Animals

Learning and interhemispheric transfer of visual pattern discriminations following unilateral suprasylvian lesions in split-chiasm cats.

A suprasylvian lesion removing cortical areas 7 and 21 and portions of area 19 and of the lateral suprasylvian area was placed in one hemisphere of split-chiasm cats. By comparison with the normal side and with cortically intact split-chiasm and split-brain cats, form discrimination learning with the eye on the injured side was severely retarded. This deficit could not be attributed to an unintentional undercutting of areas 17 and 18, since in three cases the laminae of the lateral geniculate nucleus showed little retrograde atrophy; marked degeneration was found in the medial interlaminar nucleus and the pulvinar complex. In addition, interocular transfer of form discriminations to the eye on the injured side was absent or poor, while transfer in the opposite direction was normal. A cat with a suprasylvian lesion undercutting areas 17 and 18 was unable to learn pattern discriminations with the eye on the injured side, in spite of prolonged training with that eye and normal learning with the other eye. Another cat with a suprasylvian lesion selectively removing the anteromedial and posteromedial portions of the lateral suprasylvian area showed no learning deficit on the injured side, but poor transfer to that side. A learning deficit on the side of the lesion emerged in this cat after forebrain commissurotomy. The results support the hypothesis of a major involvement of cortical areas outside of 17 and 18 in the processes of abstraction and generalization of visual information necessary for learning and interhemispheric transfer of form discrimination in the cat.

Animals

Importance of corpus callosum for visual receptive fields of single neurons in cat superior colliculus.

1. Section of the posterior two-thirds of the corpus callosum eliminates almost completely the response of superior colliculus (SC) neurons to stimulation of the contralateral eye in split-chiasm cats. On the contrary, the responsiveness of SC neurons to stimulation of the contralateral eye is not abolished by a transection of the posterior and tectal commissures leaving the corpus callosum intact. The callosal section also reduces the number of SC receptive fields abutting the vertical meridian in the ipsilateral eye of split-chiasm cats. 2. In cats with intact optic pathways, a similar callosal section abolishes the SC representation of the ipsilateral visual field in the ipsilateral eye and also reduces the number of receptive fields adjoining the vertical meridian in the same eye. In the contralateral eye, the SC representation of the ipsilateral visual field is reduced in extension to about one-fifth of that seen in cats with intact commissures. 3. The results suggest that the corpus callosum is the main pathway for cross-midline communication of visual information at not only the cortical, but also the midbrain level. The corpus callosum may subserve this function because it contains uninterrupted crossed corticotectal projections or because it transmits visual information from one hemisphere to contralateral cortical areas projecting ipsilaterally to SC. The latter hypothesis is more likely but, in any case, the findings imply that the lack of interhemispheric transfer of visual learning in cats with a chiasmatic and callosal section may depend on a midline disconnection of both subcortical and cortical visual centers. 4. The corpus callosum is also responsible for the representation of the ipsilateral visual field of the ipsilateral eye in the cat SC. The SC representation of the ipsilateral visual field in the contralateral eye is due, in minimal part, to direct retinotectal connections from temporal retina and, for the largest part, to the corpus callosum. 5. Finally, the corpus callosum contributes to the representation of the contralateral visual field near the vertical meridian of the temporal retina in both split-chiasm and normal cats. This is probably due to the scarcity of direct retinotectal projections from this part of the retina and to their supplementation by corticotectal neurons influenced by the callosal afferents.

Animals

Visual acuity functions and pattern discrimination in the destriate cat.

The study provides evidence that the cat is capable of processing visual information of some detail after removal of area 17 and most of area 18. This postoperative discrimination of complex spatial stimuli is not based on the use of such cues as luminance differences or local flux cues. From the deficits which follow extensive lesions of areas 17-18, it appears as though these cortices participate in the detection of fine details. We found a modest increase in the threshold of grating acuity, moderate loss in orientation acuity and extensive deficit in a task requiring topographic alignment of contours (vernier offset). Further evidence for the substantial preservation of spatial vision in the destriate cat is provided by experiments which show that perceptual grouping of rectilinear arrays of figural elements (dots or line segments) into obliquely oriented rows is largely unaffected by the lesion, even when the grouping is initiated by near-threshold proximity cues. Since grouping effects are felt to be involved in the organization of the visual field into the figure-ground dichotomy, these results indicate that the neural mechanisms subserving the initial stage of form perception lie outside of areas 17 and 18. Consistent with the increased acuity thresholds of destriate cats, these animals have deficits in several pattern discriminations that require fine-grained spatial analysis The results suggest that areas 17-18 serve as a high-spatial frequency analyzer, but are not essential to pattern and form recognition.

Animals

Effects of lesions of areas 17, 18 and 19 on interocular transfer of pattern discriminations in split-chiasm cats.

Split-chiasm cats with unilateral or bilateral lesions largely removing the commissurally connected portions of visual cortical areas 17, 18 and 19 showed good interocular transfer of monocularly learned pattern discriminations. The capacity for interocular transfer in these cats was in fact little or not different from that of split-chiasm cats with an intact cortex. Split-chiasm cats with an additional section of the forebrain commissures, as well as two split-chiasm cats with 17-18 lesions also submitted to forebrain commissurotomy after having shown good interocular transfer, were generally incapable of transferring pattern discriminations between the eyes. It is concluded that interocular transfer of pattern discriminations, in split-chiasm cats does not require areas 17, 18 and 19 and must therefore depend on other cortical areas.

Animals

Indirect, across-the-midline retinotectal projections and representation of ipsilateral visual field in superior colliculus of the cat.

1. In agreement with previous work, we have found that the ipsilateral visual field is represented in an extensive rostral portion--from one-third to one-half--of the superior colliculus (SC) of the cat. This representation is binocular. The SC representation of the ipsilateral visual field can be mediated both directly, by crossed retinotectal connections originating from temporal hemiretina, and indirectly, by across-the-midline connections relaying visual information from one-half of the brain to contralateral SC. 2. In order to study the indirect, across-the-midline visual input to the SC, we have recorded responses of SC neurons to visual stimuli presented to either the ipsilateral or the contralateral eye of cats with a midsagittal splitting of the optic chiasm. Units driven by the ipsilateral eye, presumably through the direct retinotectal input and/or corticotectal connections from ipsilateral visual cortex, were found throughout the SC, except at its caudal pole, which normally receives fibers from the extreme periphery of the contralateral nasal hemiretina. Units driven by the contralateral eye, undoubtedly through an indirect across-the-midline connection, were found only in the anterior portion of the SC, in which is normally represented the ipsilateral visual field. Receptive fields in both ipsilateral and contralateral eye had properties typical of SC receptive fields in cats with intact optic pathways. 3. All units having a receptive field in the contralateral eye had also a receptive field in the ipsilateral eye; for each of these units, the receptive fields in both eyes invariably abutted the vertical meridian of the visual field. The receptive field in one eye had about the same elevation relative to the horizontal meridian and the same vertical extension as the receptive field in the other eye; the two receptive fields of each binocular unit matched each other at the vertical meridian and formed a combined receptive field straddling the vertical midline of the horopter...

Animals

Visual cortical areas mediating form discrimination in the cat.

Cats were trained pre- and/or postoperatively on flux and pattern discriminations, and were examined in a series of visuomotor tests which measured attention and orientation to, and following and localization of stationary and moving stimuli, in a free situation and in a perimetry test. Cortical lesions were placed in areas 17 and 18, or in the middle and posterior suprasylvian gyri and sulci--areas 19, 20, 21, 7 and lateral suprasylvian cortex (LSA), as delineated by cyto- and myeloarchitecture, and by electrophysiological mapping. After removal of all of area 17 and up to 90-95% of 18, postoperative learning of flux and pattern discriminations is at a high level, although in some cases slowed. Visuomotor behavior is normal. Such lesions result in severe atrophy only of laminae A, A1 and C in the lateral geniculate nuclear complex (LGNd). The neuronal systems for perceiving and discriminating simple, large planimetric patterns and forms, and for mediating visually guided behavior characteristic of this species lie outside of areas 17-18. The cortices primarily responsible for form discrimination in the cat include those in the suprasylvian gyri and sulci. After lesions which removed areas 19, 20, 21 and LSA, sparing most of 17-18, form discriminations based on orientation or shape were prolonged or absent. Although these animals showed slow tracking and poor depth judgment, the visual fields were full and they had good sensory and perceptive capacity as seen in normal flux and near normal pattern (gratings) discrimination. Such lesions result in severe atrophy in lateral and inferior pulvinar complex. Although these nuclei receive visual input primarily from the superficial laminae of the superior colliculus and certain nuclei of the pretectum, both areas 19 and LSA receive a dual input from pulvinar and parts of LGNd. Whether these marked deficits in form discrimination after suprasylvian lesions are due to involvement of certain crucial areas of this extensive cortex, or whether all are involved in some integrated fashion, is not yet completely clear. Removal of 19, 21 and parts of LSA are followed by similar (but somewhat less marked) deficits of both retention and learning. Lesion in area 20 alone (cortical target of the lateral pulvinar) leaves retention of preoperatively learned discriminations intact but results in prolonged initial learning. Previous work by the present authors has shown similar deficits in form discrimination in the cat after lesions in the pretectum-superior colliculus. These data, together with the present findings appear to support the hypothesis that the midbrain-pulvinar-cortical pathways provide the first stage in simple, coarse form perception and discrimination in this species.

Animals

2-pyridylimidazoles as inhibitors of xanthine oxidase.

A series of 28 4-substituted and 4,5-disubstituted 2-pyridylimidazoles was synthesized and evaluated in vitro for inhibition of xanthine oxidase. Included within this group are examples of 2-pyridylimidazopyridines and halo-substituted 2-pyridylbenzimidazoles. Five compounds exhibited inhibitory activity in the same range as the standards, 4-hydroxypyrazolo[3,4-d]pyrimidine and 2-(4-pyridyl)-4-trifluoromethylimidazole (22). Two examples, 2-(4-pyridyl)-4,5-dicyanoimidazole (16) and 2-(4-pyridyl)-4-nitroimidazole (3), were at least an order of magnitude more active than the standards and therefore rank among the most potent known inhibitors of the enzyme.

Chemical Phenomena

4-Trifluoromethylimidazoles and 5-(4-pyridyl)-1,2,4-triazoles, new classes of xanthine oxidase inhibitors.

The syntheses of a number of 2-substituted 4-trifluoromethylimidazoles and 3-substituted 5-(4-pyridyl)-1,2,4-triazoles are described. The trifluoromethylimidazoles were prepared from 3,3-dibromo-1,1,1-trifluoroacetone after hydrolysis with aqueous sodium acetate solution and condensation with an aldehyde in the presence of ammonia. Basic hydrolysis of the trifluoromethyl group was found to provide a facile method for the synthesis of imidazole-4-carboxylic acids. In the imidazole series a 2-aryl substituent and a free imino group were required for xanthine oxidase inhibitory activity. The triazoles were obtained through the reaction of an aroylhydrazine and an imino ether followed by thermal ring closure of the intermediate acylamidrazone. As in the imidazole series, a free imino group is an absolute requirement for in vitro activity. Additional structure-activity relationships of these compounds are presented.

Animals