Split-brain Monkeys Research Articles

Representation of the Ipsilateral Visual Field by Neurons in the Macaque Lateral Intraparietal Cortex Depends on the Forebrain Commissures

Our eyes are constantly moving, allowing us to attend to different visual objects in the environment. With each eye movement, a given object activates an entirely new set of visual neurons, yet we perceive a stable scene. One neural mechanism that may contribute to visual stability is remapping. Neurons in several brain regions respond to visual stimuli presented outside the receptive field when an eye movement brings the stimulated location into the receptive field. The stored representation of a visual stimulus is remapped, or updated, in conjunction with the saccade. Remapping depends on neurons being able to receive visual information from outside the classic receptive field. In previous studies, we asked whether remapping across hemifields depends on the forebrain commissures. We found that, when the forebrain commissures are transected, behavior dependent on accurate spatial updating is initially impaired but recovers over time. Moreover, neurons in lateral intraparietal cortex (LIP) continue to remap information across hemifields in the absence of the forebrain commissures. One possible explanation for the preserved across-hemifield remapping in split-brain animals is that neurons in a single hemisphere could represent visual information from both visual fields. In the present study, we measured receptive fields of LIP neurons in split-brain monkeys and compared them with receptive fields in intact monkeys. We found a small number of neurons with bilateral receptive fields in the intact monkeys. In contrast, we found no such neurons in the split-brain animals. We conclude that bilateral representations in area LIP following forebrain commissures transection cannot account for remapping across hemifields.

Spatial Updating in Monkey Superior Colliculus in the Absence of the Forebrain Commissures: Dissociation Between Superficial and Intermediate Layers

In previous studies, we demonstrated that the forebrain commissures are the primary pathway for remapping from one hemifield to the other. Nonetheless, remapping in lateral intraparietal cortex (LIP) across hemifield is still present in split brain monkeys. This finding indicates that a subcortical structure must contribute to remapping. The primary goal of the current study was to characterize remapping activity in the superior colliculus in intact and split brain monkeys. We recorded neurons in both the superficial and intermediate layers of the SC. We found that across-hemifield remapping was reduced in magnitude and delayed compared with within-hemifield remapping in the intermediate layers of the SC in split brain monkeys. These results mirror our previous findings in area LIP. In contrast, we found no difference in the magnitude or latency for within- compared with across-hemifield remapping in the superficial layers. At the behavioral level, we compared the performance of the monkeys on two conditions of a double-step task. When the second target remained within a single hemifield, performance remained accurate. When the second target had to be updated across hemifields, the split brain monkeys' performance was impaired. Remapping activity in the intermediate layers was correlated with the accuracy and latency of the second saccade during the across-hemifield trials. Remapping in the superficial layers was correlated with latency of the second saccade during the within- and across-hemifield trials. The differences between the layers suggest that different circuits underlie remapping in the superficial and intermediate layers of the superior colliculus.

Resection of the Medial Temporal Lobe Disconnects the Rostral Superior Temporal Gyrus from Some of its Projection Targets in the Frontal Lobe and Thalamus

Auditory memory in the monkey does not appear to extend beyond the limits of working memory. It is therefore surprising that this ability is impaired by medial temporal lobe (MTL) resections, because such lesions spare working memory in other sensory modalities. To determine whether MTL ablations might have caused the auditory deficit through inadvertent transection of superior temporal gyrus (STG) projections to its downstream targets, and, if so, which targets might have been compromised, we injected anterograde tracer (biotinylated dextran amine) in the STG of both the normal and MTL-lesioned hemispheres of split-brain monkeys. Interhemispheric comparison of label failed to show any effect of the MTL ablation on efferents from caudal STG, which projects to the inferior prefrontal convexity. However, the ablation did consistently interrupt the normally dense projections from rostral STG to both the ventral medial prefrontal cortex and medial thalamic nuclei. The findings support the possibility that the auditory working memory deficit after MTL ablation is due to transection of downstream auditory projections, and indicate that the candidate structures for mediating auditory working memory are the ventral medial prefrontal cortical areas, the medial thalamus, or both.

Dynamic Circuitry for Updating Spatial Representations. III. From Neurons to Behavior

Each time the eyes move, the visual system must adjust internal representations to account for the accompanying shift in the retinal image. In the lateral intraparietal cortex (LIP), neurons update the spatial representations of salient stimuli when the eyes move. In previous experiments, we found that split-brain monkeys were impaired on double-step saccade sequences that required updating across visual hemifields, as compared to within hemifield. Here we describe a subsequent experiment to characterize the relationship between behavioral performance and neural activity in LIP in the split-brain monkey. We recorded from single LIP neurons while split-brain and intact monkeys performed two conditions of the double-step saccade task: one required across-hemifield updating and the other required within-hemifield updating. We found that, despite extensive experience with the task, the split-brain monkeys were significantly more accurate for within-hemifield than for across-hemifield sequences. In parallel, we found that population activity in LIP of the split-brain monkeys was significantly stronger for the within-hemifield than for the across-hemifield condition of the double-step task. In contrast, in the normal monkey, both the average behavioral performance and population activity showed no bias toward the within-hemifield condition. Finally, we found that the difference between within-hemifield and across-hemifield performance in the split-brain monkeys was reflected at the level of single-neuron activity in LIP. These findings indicate that remapping activity in area LIP is present in the split-brain monkey for the double-step task and covaries with spatial behavior on within-hemifield compared to across-hemifield sequences.

Exploring the extent and function of higher-order auditory cortex in rhesus monkeys

Just as cortical visual processing continues far beyond the boundaries of early visual areas, so too does cortical auditory processing continue far beyond the limits of early auditory areas. In passively listening rhesus monkeys examined with metabolic mapping techniques, cortical areas reactive to auditory stimulation were found to include the entire length of the superior temporal gyrus (STG) as well as several other regions within the temporal, parietal, and frontal lobes. Comparison of these widespread activations with those from an analogous study in vision supports the notion that audition, like vision, is served by several cortical processing streams, each specialized for analyzing a different aspect of sensory input, such as stimulus quality, location, or motion. Exploration with different classes of acoustic stimuli demonstrated that most portions of STG show greater activation on the right than on the left regardless of stimulus class. However, there is a striking shift to left-hemisphere “dominance” during passive listening to species-specific vocalizations, though this reverse asymmetry is observed only in the region of temporal pole. The mechanism for this left temporal pole “dominance” appears to be suppression of the right temporal pole by the left hemisphere, as demonstrated by a comparison of the results in normal monkeys with those in split-brain monkeys.

Dynamic Circuitry for Updating Spatial Representations. II. Physiological Evidence for Interhemispheric Transfer in Area LIP of the Split-Brain Macaque

With each eye movement, a new image impinges on the retina, yet we do not notice any shift in visual perception. This perceptual stability indicates that the brain must be able to update visual representations to take our eye movements into account. Neurons in the lateral intraparietal area (LIP) update visual representations when the eyes move. The circuitry that supports these updated representations remains unknown, however. In this experiment, we asked whether the forebrain commissures are necessary for updating in area LIP when stimulus representations must be updated from one visual hemifield to the other. We addressed this question by recording from LIP neurons in split-brain monkeys during two conditions: stimulus traces were updated either across or within hemifields. Our expectation was that across-hemifield updating activity in LIP would be reduced or abolished after transection of the forebrain commissures. Our principal finding is that LIP neurons can update stimulus traces from one hemifield to the other even in the absence of the forebrain commissures. This finding provides the first evidence that representations in parietal cortex can be updated without the use of direct cortico-cortical links. The second main finding is that updating activity in LIP is modified in the split-brain monkey: across-hemifield signals are reduced in magnitude and delayed in onset compared with within-hemifield signals, which indicates that the pathways for across-hemifield updating are less effective in the absence of the forebrain commissures. Together these findings reveal a dynamic circuit that contributes to updating spatial representations.

Dynamic Circuitry for Updating Spatial Representations. I. Behavioral Evidence for Interhemispheric Transfer in the Split-Brain Macaque

Internal representations of the sensory world must be constantly adjusted to take movements into account. In the visual system, spatial updating provides a mechanism for maintaining a coherent map of salient locations as the eyes move. Little is known, however, about the pathways that produce updated spatial representations. In the present study, we asked whether direct cortico-cortical links are required for spatial updating. We addressed this question by investigating whether the forebrain commissures-the direct path between the two cortical hemispheres-are necessary for updating visual representations from one hemifield to the other. We assessed spatial updating in two split-brain monkeys using the double-step task, which involves saccades to two sequentially appearing targets. Accurate performance requires that the representation of the second target be updated to take the first saccade into account. We made two central discoveries regarding the pathways that underlie spatial updating. First, we found that split-brain monkeys exhibited a selective initial impairment on double-step sequences that required updating across visual hemifields. Second, and most surprisingly, these impairments were neither universal nor permanent: the monkeys were ultimately able to perform the across-hemifield sequences and, in some cases, this ability emerged rapidly. These findings indicate that direct cortical links provide the main substrate for updating visual representations, but they are not the sole substrate. Rather, a unified and stable representation of visual space is supported by a redundant cortico-subcortical network with a striking capacity for reorganization.

Selective zif268 mRNA induction in the perirhinal cortex of macaque monkeys during formation of visual pair-association memory.

To elucidate the molecular basis of cognitive memory formation in the primate, transcriptional activation during learning of a visual pair-association (PA) task was evaluated systematically along the occipito-temporo-hippocampal pathway in the macaque monkey brain. Split-brain monkeys were used for intra-animal comparison, which enables elimination of animal-to-animal variation in gene expression. We found that the expression of the mRNA of an immediate-early gene (IEG), zif268, was up-regulated selectively in the perirhinal cortex (area 36) during the formation of PA memory compared to that during learning of a visual control task. The mRNA expression levels of another IEG, c-jun, were not up-regulated during the PA learning in any cortical areas examined. We also showed that cells strongly expressing zif268 mRNA accumulated in patches in area 36 during learning of the PA task. As the zif268 gene encodes a transcription factor, these results suggest that the activation of zif268 mRNA in area 36 may function as a trigger of the cascade of gene activation that leads to cellular events underlying neuronal reorganization for visual long-term memory formation.

BDNF upregulation during declarative memory formation in monkey inferior temporal cortex.

In primates, visual long-term memory of objects is presumably stored in the inferior temporal (IT) cortex. Because brain-derived neurotrophic factor (BDNF) is involved in activity-dependent neural reorganization, we tested the hypothesis that BDNF would be upregulated in IT cortex during formation of visual pair-association memory. To eliminate genetic and cognitive variations between individual animals, we used split-brain monkeys for intra-animal comparison in PCR-based mRNA quantitation. The monkeys learned a pair-association (PA) task using one hemisphere and a control visual task using the other, to balance the amount of visual input. We found that BDNF was upregulated selectively in area 36 of IT cortex during PA learning, but not in areas involved in earlier stages of visual processing. In situ hybridization showed that BDNF-expressing cells were localized in a patchlike cluster. The results suggest that BDNF contributes to reorganization of neural circuits for visual long-term memory formation in the primate.

Induction of BDNF mRNA during visual paired associate learning: Quantitative analysis using split-brain monkeys

Induction of BDNF mRNA during visual paired associate learning: Quantitative analysis using split-brain monkeys

Inversion effect for faces in split-brain monkeys

Inverting facial stimuli disrupts recognition in human subjects more severely than does inversion of other objects normally seen upright. Furthermore, this disruption affects mechanisms in the right hemisphere, which is the hemisphere preeminent for face processing, more than mechanisms in the left. To determine the extent of these effects in monkeys we retrained each hemisphere of 20 split-brain rhesus monkeys on eight upright facial discriminations they had previously learned. As a group, the monkeys again performed better with the right hemisphere than with the left in remembering these problems, confirming the right hemispheric advantage previously found. As soon as a particular discrimination was relearned to criterion with one hemisphere, the same discrimination was presented inverted. The monkeys learned the inverted facial discriminations with each hemisphere but as a group no longer showed a right hemispheric advantage. Thus, the monkeys, like people, show a greater inversion effect for faces with the right hemisphere than with the left. This result indicates that monkeys normally process faces configurally using holistic mechanisms in the right hemisphere but, when required by the nature of the stimuli, can utilize piecemeal processing of specific features with either hemisphere.

Right-hemispheric superiority in split-brain monkeys for learning and remembering facial discriminations.

Twenty-six split-brain rhesus monkeys learned and remembered 8 go/no-go discriminations of monkey faces significantly better with the right hemisphere than with the left. Four discriminations required differentiating individual identity with expression held constant, and 4 required discriminating facial expression with identity held constant. There was no significant difference in the degree of laterality shown for these 2 types of problems. Female monkeys were more lateralized for learning to discriminate faces than were males. This sex difference in laterality was significant for learning but not for memory. Laterality for the facial discriminations was not significantly related to handedness of the monkeys. Overall, rhesus monkeys, like humans, show a right-hemispheric superiority for facial processing.

Right-hemispheric superiority in split-brain monkeys for learning and remembering facial discriminations.

Right-hemispheric superiority in split-brain monkeys for learning and remembering facial discriminations.

Lateral Asymmetries in Infancy: Implications for the Development of the Hemispheres

TREVARTHEN, C., Lateral asymmetries in infancy: implications for the development of the hemispheres. NEUROSCI BIOBEHAV REV 20 (4)571–586, 1996.—Cerebral asymmetry of cognitive processing of stimulus information is commonly viewed as a neocortical phenomenon. However, a number of lines of evidence give innate asymmetry of brainstem motivating systems, which anticipate experience, a key role. Spontaneous asymmetries of gesture and emotion can be observed in infants, who entirely lack language and visuo-constructive skills. Motives for communication in early life may direct subsequent development of complementary cognitive systems in left and right hemispheres. In split-brain monkeys, lateralized motive sets, intentions for manipulation by one hand, can determine which hemisphere will see and learn. Evolutionary antecedents of cerebral appear to affect motivation, social signalling and bimanual coordination, with secondary effects in perceptual processing and learning. The hemispheres of adult humans differ in links with neurochemical systems that regulate motor initiatives, exploration and attention, and the approach/withdrawal balance in social encounters. Asymmetries in emotional and communicative behaviour in infancy support evidence that an Intrinsic Motive Formation emerging in the embryo human brain stem regulates asymmetries in development and in functioning of the cerebral cortex. Copyright © 1996 Elsevier Science Ltd.

Control of proximal and distal components of prehension in callosal agenesis.

Classic work with split-brain monkeys suggests that the reaching limb can be controlled by either cerebral hemisphere, but that finger control is largely crossed (Haaxma and Kuypers, 1974). Accordingly, one might predict that acallosal subjects should have little difficulty grasping objects presented in the visual field ipsilateral to the hand used, but should have great difficulty forming their grasp when reaching into crossed space. In the present study, we carried out a kinematic analysis of reaching and grasping movements executed by four acallosal subjects and four matched control subjects. Subjects maintained central fixation while reaching with either hand for objects placed in left, central and right space. Relative to controls, acallosal subjects took longer to complete reaches directed across the body midline, and spent more time decelerating. Moreover, unlike controls, their grip formation appeared to be impaired in all regions of space, although this deficit was most pronounced during reaches into crossed space. These results suggest that congenital absence of the corpus callosum is associated with deficits in the control of both the proximal and distal musculature.

Bi-versus monohemispheric performance in split-brain and partially split-brain macaques

Experiments comparing binocular with monocular abilities of monkeys working on visual mnemonic tasks were performed. First, it was shown that even in split-brain monkeys performance was more accurate when both hemispheres were utilized than when the task was performed with only the single (better) hemisphere. Some form of noncommissural integration is thus possible. However, when the forebrain commissures are present, as in four other animals (with only optic chiasm transected) it was shown that integration occurs via callosal mechanisms as well. This was demonstrated by the fact that here, too, binocular performance was normally more accurate than monocular performance, but when different images to be remembered were presented concurrently to the two eyes, the binocular advantage was lost. Finally, in three monkeys with only the anterior commissure allowing interhemispheric communication the superiority of binocular assessment remained even when the two hemispheres simultaneously received such differing images.

Hemispheric differences in split-brain monkeys viewing and responding to videotape recordings

Eight split-brain monkeys were tested for hemispheric differences in their viewing of and responses to colored videotape recordings of monkeys, people, animals, and scenery. The number of facial expressions elicited from the right hemisphere was significantly greater than the number made when using the left hemisphere. Monkeys also tended to look longer when viewing with their right hemispheres than when viewing with the left.

Lateralization for orientation in split-brain monkeys

Split-brain monkeys learned with each cerebral hemisphere to discriminate lines differing in slope by 15°. This type of spatial discrimination is usually performed better by the right hemisphere of humans. The left hemisphere of 8 monkeys learned this type of problem much more readily than did the right hemisphere. Learning to discriminate simple patterns in the same apparatus was done equally well by either hemisphere, demonstrating that the lateralized ability is specific to the stimuli employed.

Discrimination of monkey faces by split-brain monkeys

Eighteen split-brain rhesus monkeys were tested with each hemisphere for the ability to learn to discriminate photographs of the faces of other monkeys. Seven subjects also ran tests of generalization to new photographs of the discriminated monkeys; these tests confirmed that facial features pertaining to individual monkeys were learned. Equal numbers of male and female monkeys and nearly equal numbers of right and left handed monkeys were tested. Over all the monkeys there was no significant advantage in learning with either the left or right hemisphere or with the hemisphere contralateral or ipsilateral to the preferred hand. The group of 9 female monkeys, however, did show a significant advantage in learning with the left hemisphere. Furthermore, there was a tendency for monkeys older at the time of surgery to show greater hemispheric specialization.

Hemispheric differences in split-brain monkeys learning sequential comparisons

Twelve split-brain rhesus monkeys were tested for differences in the abilities of their two cerebral hemispheres to learn discriminations based on the comparison of sequentially-presented visual stimuli. Overall there was no generalized advantage for either the left or right hemisphere. There was, however, a significant correlation between each monkey's handedness and the hemisphere that learned more readily; the more proficient hemisphere tended to be contralateral to the pre- operatively preferred hand. This result raises the possibility that handedness in monkeys may be more closely related to cognitive processing than is usually believed.