Calbindin immunoreactivity in the geniculo-extrastriate system of the macaque: implications for heterogeneity in the koniocellular pathway and recovery from cortical damage.

Although most projection neurons in the primate dorsal lateral geniculate nucleus (dLGN) target striate cortex (V1), a small number project instead to extrastriate visual areas and have been suggested to play a role in the preserved vision ("blindsight") that survives damage to V1. Moreover, the distribution of dLGN cells projecting to extrastriate bears a striking similarity to that of neurons that stain for calbindin D-28K (Cal), a calcium-binding protein involved in regulating neuronal excitability and considered a marker for the koniocellular or "K" pathway of geniculocortical processing. In these studies, we used double-labeling techniques to examine whether Cal content characterizes all or a subset of neurons making up the geniculo-extrastriate pathway in normal macaque monkeys. After injections of cholera toxin B-subunit into the prelunate gyrus, the proportion of retrogradely labeled neurons in the dLGN that were also immunoreactive for Cal varied from less than 40% to over 80%, indicating that only a subset of the geniculo-extrastriate projection falls within the K pathway as defined by Cal content. Analysis of the injected territories indicated that identity of the extrastriate cortical target may be systematically related to Cal content in the geniculo-extrastriate projection. To see whether the Cal-immunoreactive dLGN population might potentially play a role in preserved vision after V1 damage, we also examined the dLGN of a macaque that had sustained a lesion of V1 in infancy and survived until 4 years. In this animal, large, intensely Cal-immunoreactive neurons were found scattered throughout the otherwise degenerated dLGN zones and made up over 95% of the identifiable remaining neurons. The results support an emerging view that the macaque koniocellular system is highly heterogeneous in nature and also suggest that Cal content may be a critical feature of the pathway by which visual information reaches extrastriate cortex in the absence of V1.

Direction of motion discrimination after early lesions of striate cortex (V1) of the macaque monkey.

Previous studies have established that humans and monkeys with damage to striate cortex are able to detect and localize bright targets within the resultant scotoma. Electrophysiological evidence in monkeys suggests that residual vision also might include sensitivity to direction of visual motion. We tested whether macaque monkeys with longstanding lesions of striate cortex (V1), sustained in infancy, could discriminate visual stimuli on the basis of direction of motion. Three monkeys with unilateral striate cortex lesions sustained in infancy were tested 2-5 years postlesion on a direction of motion discrimination task. Each monkey was trained to make saccadic eye movements to a field of moving dots or to withhold such eye movements, depending on the direction of motion in a coherent random dot display. With smaller motion displays, monkeys were unable to detect or discriminate motion within the scotoma, although they could discriminate moving from static stimuli. Yet, each monkey was able to discriminate direction of motion when the motion stimulus was larger, but still confined to the scotoma. The results demonstrate that the recovery after infant damage to striate cortex includes some sensitivity to direction of visual motion.

A transient geniculo-extrastriate pathway in macaques? Implications for 'blindsight'.

Both monkeys and cats receiving primary visual cortex lesions in infancy show better residual vision than animals sustaining similar damage in adulthood. In cats, the better recovery has been explained in part by stabilization of a transient pathway from the dorsal lateral geniculate nucleus (dLGN) to cortical visual area PMLS. To test the hypothesis that a similar transient pathway from the dLGN to dorsal extrastriate areas exists in primates and thus serves as a candidate for recruitment after early V1 damage, retrograde tracers were injected into areas MT, MST, and/or 7a of infant macaques. No evidence of a transient pathway from the dLGN to these areas was obtained, despite projections from the pulvinar and other extrastriate areas in all cases.

The effects of combined superior temporal polysensory area and frontal eye field lesions on eye movements in the macaque monkey.

We previously found [42] that lesions of the superior temporal polysensory area (STP) cause temporary deficits in the production of eye movements. In order to both define regions participating in the ensuing recovery and to further explore the cortical control of eye movements, we examined the effects of addition of frontal eye field (FEF) lesions to STP lesions, on visual fixation, saccadic eye movements, and smooth pursuit eye movements. Three monkeys received bilateral STP lesions followed by a FEF lesion and as a control, an additional monkey received a bilateral inferior temporal cortex (IT) lesion followed by a FEF lesion. All animals had a profound impairment in foveating the central fixation point. This impairment was completely eliminated by turning on a dim light in the testing chamber. Large neglect-like impairments in making saccades were only seen after combined STP and FEF lesions. Impairments in making smooth pursuit eye movements after combined lesions of STP and FEF were larger than those seen after STP lesions but within the range of deficits that have been reported after FEF lesions alone. The impairment of visual fixation in darkness and the lack of impairment under conditions of dim illumination appear to reflect a specific role for the FEF in spatial orientation in the absence of visual landmarks. The FEF also appears to play a more critical role than STP in smooth pursuit. By contrast, STP and the FEF appear to work cooperatively with respect to the production of saccades. We suggest that cortical oculomotor control can flow either through the midbrain or through the FEF and that the FEF pathway is specifically involved in tasks with a discontiguity between the stimuli and the behavioral response while the midbrain pathways are preferentially involved in more stimulus-driven eye movements.

Greater residual vision in monkeys after striate cortex damage in infancy.

1. Monkeys with large unilateral surgical ablations of striate cortex, sustained either in adulthood or at 5-6 wk of age, were trained on an oculomotor detection and localization task and tested with visual stimuli in the hemifields ipsilateral and contralateral to the lesion 2-5 yr after surgery. 2. Monkeys with lesions sustained in adulthood were largely unable to detect stimuli in the hemifield contralateral to the lesion, with only one monkey showing recovery toward the end of testing. Monkeys with lesions of striate cortex made in infancy, however, each showed residual detection capacity at the beginning of testing and improved to near normal by the end of testing. 3. Each of the monkeys showing a residual ability to detect within the contralateral hemifield was also able to localize visual targets with eye movements. 4. These findings demonstrate that the vision surviving striate cortex damage in primates is more robust after early damage as has been shown to be the case for primary somatosensory, motor, and association cortex.

The lateral geniculate nucleus does not project to area TE in infant or adult macaques.

We sought to determine if there are any direct projections from the dorsal lateral geniculate nucleus (dLGN) to visual cortical area TE in either adult or infant primates. To do so, we examined labelling in the thalamus of eight macaque monkeys which received injections of the retrograde tracer cholera toxin-B subunit within TE. Four of these cases were infants in which the injections revealed transient patterns of inputs to TE from various other brain regions. Although each monkey showed extensive label in the pulvinar nucleus and other subcortical structures, none showed unambiguous labelling in the dLGN. The absence of direct connections between the dLGN and area TE indicates that rudimentary color and form processing capacities in the absence of striate cortex must utilize other pathways even when damage to striate cortex takes place early in life.

The effects of superior temporal cortex lesions on the processing and retention of auditory information in monkeys (Cebus apella).

Three monkeys with extensive preoperative training on visual and auditory memory tasks (delayed matching-to-sample), an auditory pattern-discrimination task, and a visual serial-order task, received bilateral lesions of the superior temporal (ST) cortex in two stages, with testing after each lesion. Unilateral ST cortex lesions resulted in only moderate auditory memory impairments, whereas bilateral ST cortex lesions resulted in severe auditory memory impairments. The bilateral ST cortex lesions also resulted in severe impairments in the ability to relearn the auditory pattern-discrimination task. In contrast to the auditory impairments, neither unilateral nor bilateral ST cortex lesions had any effect whatsoever on either visual memory or visual serial-order behavior. These findings indicate that the ST cortex plays a role in auditory processing and retention similar to that played by the inferior temporal cortex for visual processing and retention.

Localization of visual stimuli after striate cortex damage in monkeys: parallels with human blindsight.

Blindsight is a phenomenon in which human patients with damage to striate cortex deny any visual sensation in the resultant visual field defect but can nonetheless detect and localize stimuli when persuaded to guess. Although monkeys with striate lesions have also been shown to exhibit some residual vision, it is not yet clear to what extent the residual capacities in monkeys parallel the phenomenon of human blindsight. To clarify this issue, we trained two monkeys with unilateral lesions of striate cortex to make saccadic eye movements to visual targets in both hemifields under two conditions. In the condition analogous to clinical perimetry, they failed to initiate saccades to targets presented in the contralateral hemifield and thus appeared "blind." Only in the condition where the fixation point was turned off simultaneously with the onset of the target--signaling the animal to respond at the appropriate time--were monkeys able to localize targets contralateral to the striate lesion. These results indicate that the conditions under which residual vision is demonstrable are similar for monkeys with striate cortex damage and humans with blindsight.

Laminar distribution and sources of catecholaminergic input to the optic tectum of the pigeon (Columbia livia).

A combined immunohistochemical and retrograde tracing approach was used to characterize the catecholaminergic innervation of the optic tectum (TeO), the major target of retinal projections in many avian species. Giemsa counterstaining was employed to determine precisely the laminar localization of immunoreactive fibers and presumptive terminals. The TeO of the pigeon is densely innervated by fibers immunoreactive for tyrosine hydroxylase (TH), which are most heavily distributed to the superficial layers of its dorsal and anterior portions. Within the dorsal-anterior tectum, TH-immunoreactive processes are particularly dense in retinorecipient layers 4 and 7 and in layer 5a. As in the mammalian superior colliculus, the bulk of the catecholaminergic innervation of the pigeon TeO reflects inputs, presumably noradrenergic, originating in the locus coeruleus and nucleus subcoeruleus. However, the catecholaminergic innervation of the pigeon TeO shows several features distinct from those reported for the mammalian superior colliculus. These include an input from a pretectal TH-positive cell group unknown in mammals and the presence of residual TH immunoreactivity after administration of the noradrenergic neurotoxin DSP-4. Moreover, the pattern of TH-immunoreactive fibers in pigeon TeO indicates more laminar and regional specialization within this structure than has been reported for the catecholaminergic innervation of the superior colliculus in mammals.

Effects of superior temporal polysensory area lesions on eye movements in the macaque monkey.

1. On the basis of its anatomic connections and single-unit properties, the superior temporal polysensory area (STP) would seem to be primarily involved in visuospatial functions. We have examined the effects of lesions of STP on saccadic eye movements, visual fixation, and smooth pursuit eye movements to directly test the hypothesis that STP is involved in visuospatial and visuomotor behavior. 2. Seven monkeys were trained to make saccades to targets 8, 15, and 22 degrees from a central fixation point along the horizontal meridian and 8 degrees from the central fixation point along the vertical meridian. One monkey was also trained to make saccades to auditory targets. The same monkeys were trained to foveate a stationary central fixation point and to follow it with a smooth pursuit eye movement when it began moving 5, 13, or 20 degrees/s. Four monkeys received unilateral STP lesions, one received a bilateral STP lesion, and as a control, two received unilateral inferior temporal cortex (IT) lesions. After testing, three of the animals with unilateral STP lesions received an additional STP lesion in the hemisphere contralateral to the first lesion. Similarly, one animal with a unilateral IT lesion received an additional IT lesion in the hemisphere contralateral to the first lesion. 3. All monkeys with complete removal of STP showed a significant increase in saccade latency to the most peripheral contralateral target, and most also had increased saccade latencies to the other contralateral targets. Saccades directed to targets along the vertical meridian or toward targets in the hemifield ipsilateral to the lesion were not impaired by removal of STP. By contrast, IT lesions did not impair the monkeys' ability to make saccadic eye movements to visual stimuli at any location, showing that saccades to visually guided targets are not impaired nonspecifically by damage to visual cortex. 4. The deficit in making eye movements after STP lesions was specific to saccade latency, with little effect on the accuracy of saccades to visual targets. 5. In the one monkey trained to make saccades to auditory targets, removal of STP did not impair saccades to auditory targets contralateral to its lesion, despite this monkey showing the largest increase in saccades latencies to visual targets. 6. There was complete recovery of saccade latency to the baseline level of performance on the saccade task after all STP lesions.(ABSTRACT TRUNCATED AT 400 WORDS)

Development of inferior temporal cortex in the monkey.

Inferior temporal (IT) cortex is critical for visual pattern recognition in adult primates. However, the functional development of IT cortex appears to be incomplete until late in the first year of life in monkeys and probably beyond. Responses of neurons in IT are substantially weaker, of longer latency, and more susceptible to anesthesia within at least the first half year of life. In addition, refinement of connections of IT, particularly those with regions in the opposite hemisphere and with regions related to memory and attention, continues for at least several months after birth. Moreover, many of the pattern recognition functions that IT supports in adulthood themselves show a very protracted period of development, and damage to IT cortex in infancy appears to have relatively little effect on pattern recognition abilities, despite the pronounced effects of comparable damage in adulthood. These findings all suggest that IT undergoes an extended period of postnatal development, during which both visual experience and the maturation of other brain structures may contribute to the emergence of mechanisms of pattern recognition within IT. In other respects, fundamental characteristics of IT emerge quite early. For example, despite their weaker responses, IT neurons have adult-like patterns of responsiveness--including pronounced form selectivity and large bilateral receptive fields--as early as we were able to test (approximately 6 weeks). Thus, IT cortex appears to be prewired with (or predisposed to develop rapidly) neural circuitry sufficient to produce basic properties remarkably similar to those found in the adult animal. Future studies of IT cortex will need to address the development of signals related to perceptual constancies and to formation and retrieval of visual object memories, the development of interactions with other regions involved in visual recognition (particularly frontal cortex), and the specific mechanisms underlying various types of plasticity present in IT cortex in both developing and mature primates.

Cortical projections to anterior inferior temporal cortex in infant macaque monkeys.

Inferior temporal (IT) cortex is a "high-order" region of extrastriate visual cortex important for visual form perception and recognition in adult primates. The pattern of cortical afferents from both ipsilateral and contralateral hemispheres to anterior IT cortex was determined in infant macaque monkeys 7-18 weeks of age following injections of wheat-germ agglutinin-HRP. Within the ipsilateral hemisphere, the locations and laminar distribution of labeled cells were similar to those observed after comparable injections in adult monkeys. Specifically, ipsilateral afferents derived from visual areas V4, TEO, anterior and posterior IT, and STP, from parahippocampal, perirhinal, and parietal zones, and from several anterior zones including lateral and ventral frontal cortex, the insula, and cingulate cortex. Within the contralateral hemisphere, we observed labeled cells in homotopic regions of IT and in parahippocampal and perirhinal areas, as has been reported for adult monkeys. However, we also identified additional contralateral regions not previously known to provide input to anterior IT, including lateral and ventral frontal cortex, cingulate cortex, and STP. Overall, the strongest and most widespread projections from outside the temporal lobe were found in the youngest monkey, suggesting that some of these projections may represent transient circuitry necessary for the development of complex visual response properties in anterior IT.

Response properties of neurons in temporal cortical visual areas of infant monkeys.

1. Inferior temporal cortex (IT) is a "high-order" region of primate temporal visual cortex implicated in visual pattern perception and recognition. To gain some insight into the development of this area, we compared the properties of single neurons in IT in infant monkeys ranging from 5 wk to 7 mo of age with those of neurons in IT in adult animals. Both anesthetized and awake behaving paradigms were used. 2. In immobilized infant monkeys under nitrous oxide anesthesia, the incidence of visually responsive cells was markedly less than in adult monkeys studied under similar conditions. In infants 4-7 mo of age, only half of IT neurons studied were visually responsive, compared with > 80% in adult monkeys. In monkeys < 4 mo old, even fewer (< 10%) could be visually driven. "Habituation" of IT cells to repeated stimulus presentation appeared more pronounced in infant monkeys under nitrous oxide anesthesia than in adult animals. 3. IT cells in the anesthetized infant monkeys that did respond showed receptive field properties similar to those of responsive adult IT neurons studied under similar conditions. Two thirds of the receptive fields plotted in the anesthetized 4 to 7-mo-old group were bilateral, and median field size did not differ between the infants and comparable adult groups, being approximately 20 degrees on a side in each case. 4. In contrast to the results obtained under anesthesia, most IT cells in alert infant monkeys 5 wk-7 mo of age (80%) were responsive to visual stimuli, and this incidence of visually responsive IT neurons did not differ from that obtained in awake adult macaques. However, response magnitude, measured as spikes per second above baseline rate, was significantly lower in the infant alert sample than in the adult control (5.2 vs. 12.6 spikes/s, mean +/- SE, deviation from spontaneous rate, respectively). 5. In addition to having lower magnitudes of visual response, IT cells in the awake infants also tended to have longer and more variable latencies. The overall mean for the infant cells was 196 ms, compared with an overall mean of 140 ms for IT neurons in the alert control adult. 6. Although the magnitude of response of neurons in alert infant IT cortex was lower overall, the incidence and features of stimulus selectivity shown by alert infant IT neurons were strikingly similar to those of IT cells of both anesthetized and unanesthetized adult monkeys.(ABSTRACT TRUNCATED AT 400 WORDS)

Stimulus selectivity and state dependence of activity in inferior temporal cortex of infant monkeys.

Inferior temporal cortex is necessary for visual object recognition in adult primates but is less critical in infants. Nonetheless, in macaques as young as 6 weeks old, inferior temporal neurons showed adult-like visual response properties, including form selectivity and bilateral receptive fields, indicating that extended maturation and visual experience may not be necessary for adult-like encoding of complex objects. However, before the animals were 4 months old, visual responsiveness was found in inferior temporal cortex only in awake monkeys performing a behavioral task and not in anesthetized ones, suggesting that extraretinal factors profoundly influence function in "association" cortex in developing as well as mature animals.

Methods for repeated recording in visual cortex of anesthetized and awake behaving infant monkeys.

This report describes methods for making repeated recordings from visual cortex in infant macaque monkeys (age range 5 weeks to 7 months) both under nitrous oxide anesthesia and in an alert behaving state. These methods permitted successful collection of single-unit data from inferior temporal cortex and other areas in a longitudinal fashion from individual infants. For the anesthetized experiments, modifications of our standard techniques for surgical preparation and maintenance of the animal in an anesthetized, artificially ventilated state permitted repeated recording sessions while assuring the animal's continued health and normal growth. Following implantation with an eye coil, monkeys as young as 5 weeks could be trained to perform a fixation task during alert recording sessions which were likewise performed on a repeated basis with maintained health and development. Further, comparison of results from anesthetized and awake recording sessions indicates that alert recording is preferable for collecting certain types of data from visual cortex in infant monkeys.

Afferent basis of visual response properties in area MT of the macaque. II. Effects of superior colliculus removal.

In a previous study (Rodman et al., 1989), we found that many neurons in the middle temporal area (MT) of the macaque monkey remain visually responsive and directionally selective after striate cortex lesions or cooling. In the present study, we examined the effects of superior colliculus (SC) lesions and combined lesions of striate cortex and the SC on the visual properties of MT neurons. Removal of the SC alone had no effect on the proportion of visually responsive cells, strength of direction selectivity and direction tuning, orientation tuning, receptive field size, or binocularity in MT. There was, however, a slight increase in response strength to both stationary and moving slit stimuli. In contrast to the minor effects of SC lesions alone, addition of an SC lesion to striate cortex damage abolished all visual responsiveness in area MT. The results indicate that pathways damaged by the SC lesion are not necessary for most of the properties of MT neurons found in the intact animal, although these pathways are capable of sustaining considerable visual responsiveness and direction selectivity when striate input is removed.

Auditory association cortex lesions impair auditory short-term memory in monkeys.

Monkeys that were trained to perform auditory and visual short-term memory tasks (delayed matching-to-sample) received lesions of the auditory association cortex in the superior temporal gyrus. Although visual memory was completely unaffected by the lesions, auditory memory was severely impaired. Despite this impairment, all monkeys could discriminate sounds closer in frequency than those used in the auditory memory task. This result suggests that the superior temporal cortex plays a role in auditory processing and retention similar to the role the inferior temporal cortex plays in visual processing and retention.

Afferent basis of visual response properties in area MT of the macaque. I. Effects of striate cortex removal.

The middle temporal area (MT) of the macaque monkey is a region of extrastriate cortex involved in the analysis of visual motion. MT receives strong projections from striate cortex and from area V2, which is dependent on striate for visual responsiveness. Accordingly, the visual properties of MT neurons have been thought to reflect the further processing of its input from striate cortex. We examined the dependence of MT activity on pathways deriving from striate cortex by recording from MT neurons following removal of their striate input. Repeated recordings in area MT were made in 4 hemispheres of anesthetized macaques following either partial or total ablations of striate cortex. Cells in MT were tested for responsiveness, selectivity for direction of motion and direction tuning, and ocular dominance. Receptive fields were also plotted. In an additional animal, we recorded from MT neurons during reversible cooling of the central representation in striate cortex. We found that striate cortex removal or inactivation did not abolish the visual responsiveness of the majority of MT cells. Although the residual responses were generally much weaker than in the intact animal, direction selectivity and binocularity were still present. Moreover, receptive field size and overall topography appeared unaltered.

Single-unit analysis of pattern-motion selective properties in the middle temporal visual area (MT).

The middle temporal visual area (MT) in macaque extrastriate cortex is characterized by a high proportion of neurons selective for the direction of stimulus motion, and is thus thought to play an important role in motion perception. Previous studies identified a population of cells in MT that appeared capable of coding the motion of whole visual patterns independent of the motions of contours within them (Gizzi et al. 1983; Movshon et al. 1985). These "pattern-motion selective" neurons are unlike motion sensitive cells that have been observed at earlier stages of the visual system. Using very different criteria, we have also previously identified an apparently functionally distinct group of MT neurons (Albright 1984). We predicted that these "Type II" neurons correspond to the pattern-motion neurons. In the present study, we have applied both sets of criteria to individual neurons in MT and found that these two differently defined sets of cells actually form the same population. These results support the idea that MT contributes to a specialized type of motion processing which reflects the integrity of normal perception.