A study on the effect of lesions of area 7 of the parietal cortex on the short-term visual spatial memory of rhesus monkeys (Macaca mulatta)

This research is focused on the contribution of area 7 to the short-term visual spatial memory. Three rhesus monkeys (Macaca mulatta) were trained in the direct delayed response task in which 5 delay intervals were used in each session. When each monkey reached the criterion of 90% correct responses in 5 successive sessions, two monkeys underwent a surgery while the other one received a sham operation as a control. In the first stage of the surgery, bilateral areas 7a, 7b and 7ip of the parietal cortex of two monkeys were precisely lesioned. After 7 days of recuperation, the monkeys were required to do the same task. The average percentage of correct responses in the lesioned animals decreased from 94.7% to 89.3% and 93.3% to 82.0% respectively (no significance,P > 0.05, n = 2). In addition, the monkeys' complex movements were mildly impaired. The lesioned monkeys were found to have difficulty picking up food from the wells. In the second stage, bilateral area 7m was lesioned. In the 5 postoperative sessions, the average percentage of correct responses in one monkey, with a relatively precise 7m lesion, decreased from 94.7% to 92.2% (no significance,P > 0.05). while the other monkey, with widely spread necrosis of lateral parietal cortex, showed an obvious decline in performance, but still over the chance level. After 240 trials this monkey reattained the normal criterion. The results of this research suggest that the lesions of area 7 of the parietal cortex did not significantly affect the short-term visual spatial memory, which has been shown to be sensitive to lesions of the prefrontal cortex; they also support the notion of dissociation of spatial functions in the prefrontal and parietal cortices.     

Impairments in route negotiation through a maze after dorsolateral frontal,inferior parietal or premotor lesions in cynomolgus monkeys

Ten cynomolgus monkeys were trained to follow a fixed route through a whole-body maze consisting of 3 × 3 matrix of 9 compartments, all with interconnecting doors. Two monkeys learned to use proprioceptive guidance such that they tended to produce the same sequence of movements even if they entered the maze by a different door. They were not impaired by bilateral lesions to inferior parietal cortex (Area 7a/PG). The rest used non-proprioceptive guidance relying on external cues in the environment, probably outside the maze. These were impaired by bilateral lesions of either dorsolateral frontal or posterior parietal cortex. At least 3 different strategies may be used for route negotiation. Postoperative comparisons of the frontal and parietal groups on the effects of rearranging the external cues and on learning a new route through the maze suggested that the groups were differentially impaired in the use of different strategies. In a subsequent study, bilateral lesions to premotor cortex (Area 6) resulted in an impaired ability to follow a route using either proprioceptive or external cues.     

The role of frontal and parietal cortex in cognitive processing: tests of spatial and sequence functions.

Normal monkeys and monkeys with resection of anterior frontal or posterior parietal cortex were trained to press a panel next to a green panel as a test of extrapersonal spatial orientation and to press a panel next to their own prior press as a test of personal spatial orientation. All monkeys also learned two sets of sequence problems in which the solutions were made independent of spatial location by randomly shifting the locations of the stimuli after each response within a trial. The Parietal Group was significantly impaired on the extrapersonal 'next-to' task but not the more difficult personal 'next-to' task. The Frontal Group was impaired on both the personal and the extrapersonal 'next-to' tasks but only when the relevant cues shifted spatial locations from trial to trial. The performance of the Parietal Group completely overlapped that of the Normal Group on the sequence problems regardless of the level of testing sophistication the monkeys had attained. In contrast, the Frontal Group demonstrated a significant impairment in learning sequences but only when the monkeys were naive. Once they became sophisticated they learned each sequence at a normal rate. Their poor performance was attributed to the lack of stability in the spatial location of the stimuli. The data support the view that a distinction between personal and extrapersonal spatial orientation is relevant to posterior parietal function but indicate that neither sequencing per se nor personal spatial orientation or spatial memory per se is dependent on intact frontal functioning. Rather, the frontal cortex is involved with a higher-order control essential to allow the monkey to perceive the reliable aspects of stimuli contained in a stimulus context full of unreliable noise and to further allow for flexible response pattern appropriate to the demands of a variable context.     

Do parietal cortical lesions impair spatial attention or allocentric spatial perception?

It remains unclear whether monkeys with large parietal cortical lesions fail "landmark" tasks because they cannot judge the relative distances between landmark and response locations, or because they fail to attend to, or even to notice, the landmark. Monkeys with small posterior parietal (SPP), large posterior parietal (LPP), superior temporal sulcus (STS), or frontal eye field (FEF) lesions were tested on a landmark task in which the physical salience of the landmark and its location varied. Only the LPP monkeys were impaired, seemingly because they overtly failed to shift attention during each trial, responding to whichever food well they looked at first. A task based on one used with neurological patients was therefore introduced in which the monkeys had to discriminate between two white square plaques each containing a spot, where the spot on the positive stimulus was centrally placed. Solving this task requires an allocentric judgement about the relative location of each spot to the edges of the plaque. Even on the most difficult discrimination, monkeys with large parietal lobe lesions were unimpaired. The deficits previously reported on landmark tasks probably reflect a failure of spatial attention or attention to objects rather than an inability to judge allocentric spatial relationships.     

Visuo-spatial performance following posterior parietal and lateral frontal lesions in stumptail macaques.

Three groups of four monkeys were trained to negotiate a small hand ("stylus") maze, and to use a "pointer" to guide response in a two-choice position discrimination task. One group was given bilateral lesions of posterior parietal cortex, and the second bilateral lesions of lateral frontal cortex. Postoperative impairment on the maze was evident in three of the four parietal animals, and both operated groups showed impairment on the pointer task. Since maze performance was positively associated with speed of stylus recovery in a control version of the task but was not correlated with pointer task performance, it is suggested that the parietal deficit resulted primarily from a sensory-motor dyscoordination rather than a spatial perceptual disorder. The latter could however be the cause of parietal impairment on the pointer task. Error analysis suggests an interpretation of the frontal deficit on the pointer task in terms of perseveration on position.     

Domain-related differentiation of working memory in the Japanese macaque (Macaca fuscata) frontal cortex: a positron emission tomography study

The lateral prefrontal cortex (LPFC) is important for working memory (WM) task performance. Neuropsychological and neurophysiological studies in monkeys suggest that the lateral prefrontal cortex is functionally segregated based on the working memory domain (spatial vs. non-spatial). However, this is not supported by most human neuroimaging studies, and the discrepancy might be due to differences in methods and/or species (monkey neuropsychology/physiology vs. human neuroimaging). We used positron emission topography to examine the functional segregation of the lateral prefrontal cortex of Japanese macaques (Macaca fuscata) that showed near 100% accuracy on spatial and non-spatial working memory tasks. Compared with activity during the non-working memory control tasks, the dorsolateral prefrontal cortex (DLPFC) was more active during the non-spatial, but not during the spatial, working memory task, although a muscimol microinjection into the dorsolateral prefrontal cortex significantly impaired the performance of both working memory tasks. A direct comparison of the brain activity between the two working memory tasks revealed no differences within the lateral prefrontal cortex, whereas the premotor area was more active during the spatial working memory task. Comparing the delay-specific activity, which did not include task-associated stimulus/response-related activity, revealed more spatial working memory-related activity in the posterior parietal and premotor areas, and more non-spatial working memory-related activity in the dorsolateral prefrontal cortex and hippocampus. These results suggest that working memory in the monkey brain is segregated based on domain, not within the lateral prefrontal cortex but rather between the posterior parietal-premotor areas and the dorsolateral prefrontal-hippocampus areas.     

Buccal hemineglect

OBJECTIVES: To determine whether the peripersonal and intrapersonal buccal space can be affected by a hemispheric stroke and to evaluate the clinical signs resulting from buccal neglect. METHODS: A prospective study comparing 2 groups of patients with hemiplegia, 1 with a right hemispheric lesion and the other with a left hemispheric lesion. Patients were selected consecutively on the basis of specific criteria at least 1 month after stroke. RESULTS: Buccal hemineglect was usually concomitant with other hemineglect phenomena resulting from lesions of the right hemisphere (10 of 12 in right lesions and 1 of 12 in left lesions). Clinical signs associated with this condition consisted of impaired swallowing (retention, defective insalivation, presence of food debris in the left hemibuccal space, loss of saliva from the left side of the mouth, and choking); loss of the ability to perceive salty, sweet, or acid tastes; and impaired buccal representation. These problems were usually incorrectly diagnosed initially. Outcome was usually favorable, but functional disorders persisted in some patients for more than 18 months. The underlying attention and representation mechanisms are discussed with reference to experimental lesions of the postarcuate (area 6) cortex in rhesus monkeys. The area around the mouth may be considered to be, as in monkeys, a peripersonal space, ie, probably of little functional importance. The lesion may involve area 6 or its projections to the thalamus or posterior parietal cortex. CONCLUSIONS: Buccal hemineglect, which is likely to cause social embarrassment, should be considered whenever the oral phase of swallowing is impaired in a context of neglect syndromes. Prophylactic measures and rehabilitation can reduce the impact and complications of the condition (food bolus).     

Place and taste aversion learning: role of basal forebrain, parietal cortex, and amygdala.

Animals with nucleus basalis magnocellularis (NBM), parietal cortex, dorsolateral frontal cortex, amygdala or control lesions were tested in a neophobia and taste aversion learning task. Only animals with basolateral amygdala lesions were impaired in taste aversion learning and in displaying neophobia to a novel flavor. This finding suggested a dissociation between the function of the NBM component of the basal forebrain cholinergic system and the amygdala. The same animals with NBM or control lesions were then tested for acquisition of a spatial navigation task using a dry-land version (cheese board) of the Morris water maze. Animals with NBM lesions were impaired in this task relative to control animals. Animals with parietal cortex lesions displayed a comparable deficit in the place navigation task. These findings suggest parallel functions for the NBM component of the basal forebrain system and the parietal cortex. The role of the NBM in mediating memory appears to be limited in that it does not play a role in all learning situations.     

Loss of motor habits after cortical lesions.

After damage to discrete regions of association cortex in man, the condition called “apraxia” may ensue. Apraxia is commonly defined as the inability to perform complex, purposeful movements in the absense of primary motor and sensory deficits. In an attempt to develop an animal model of this condition, eight monkeys were trained to open a complex latch-box, and then had bilateral periarcuate, precentral, or parietal cortical removals. Despite rapid return of other motor functions to normal, latch-box opening remained profoundly impaired after periarcuate or precentral lesions, but not after parietal lesions. Disconnection of the precentral motor system from certain other cortical regions may underlie this apraxia- like syndrome of the monkey.     

Spatial memory impairments following damage to the mediodorsal nucleus of the thalamus in rhesus monkeys

The present study assessed whether the mediodorsal nucleus (MD) of the primate thalamus subserves some of the same learning and memory functions mediated by its prefrontal cortical projection areas. Behavioral effects of MD lesions were evaluated in 14 young adult rhesus monkeys, using tests known to be sensitive to damage in different regions of the prefrontal cortex. Performance on a spatial delayed alternation task was significantly (P < 0.01) impaired by MD lesions, and this impairment was significantly correlated (r_s = 0.52) with damage to the posterior half of the mediodorsal nucleus. Such damage was also correlated significantly (r_s = 0.51) with performance on another spatial memory task, delayed response; monkeys that sustained the largest lesions of the posterior mediodorsal nucleus were significantly (P < 0.05) impaired on this task relative to operated animals suffering the least posterior MD damage. In contrast to their performance on spatial memory tasks, operated animals were not impaired on tests of object reversal or visual pattern discrimination. These results indicate that lesions of the mediodorsal nucleus can elicit a specific syndrome of spatial memory loss qualitatively similar to that observed after damage to the dorsolateral prefrontal cortex.     

Disorders of visual attention and the posterior parietal cortex

Traditionally, both the monkey and human posterior parietal cortex (PPC) have been considered to have a privileged role in spatial perception or action. Lesions to this region of the human brain, particularly of the right hemisphere, undoubtedly lead to spatially lateralised deficits such as visual extinction or neglect. However, although studies in monkeys have revealed much about the spatial functions of the parietal lobe, the monkey PPC may not be a good model system with which to understand fully the disorders of attention that follow damage to the human parietal cortex. Several lines of evidence, from functional imaging as well as investigations of patients with parietal damage, demonstrate that parts of the human inferior parietal lobe (IPL) have non-spatial functions. Here, we argue that it is important to distinguish spatially lateralised from spatial deficits. Both spatial and non-spatial impairments might, in principle, contribute to a spatially lateralised behavioural syndrome such as neglect. In this review, we discuss the evidence for such a proposal and suggest that a better understanding of human parietal syndromes may emerge from considering both the spatial and non-spatial functions of this region.     

The effect of selective anterior and posterior association cortex lesions in the monkey on performance of a visual-auditory compound discrimination test.

Monkeys with selective bilateral lesions to the prefrontal cortex were tested on a visual-auditory compound discrimination task. Lesions to the banks and depths of the arcuate sulcus impaired performance whereas lesions to the banks and depths of the sulcus principalis did not. The suggestion is made that the arcuate cortex is concerned in the programming of certain types of responses. The suggestion is based on neuropsychological evidence and the neuroanatomical finding that the arcuate cortex receives input from the visual, auditory and somaesthetic association cortex and is also closely connected to various “motor” areas. The effects of lesions to posterior association cortical areas that also receive multi-modal input, the inferior parietal lobule (Brodmann's area 7) and the banks and depths of the superior temporal sulcus, were also examined on the visual-auditory compound task. The results suggest that the superior temporal sulcus cortex may also be involved in this task.     

Tactual discrimination learning in monkeys

Results of studies of tactual discrimination learning in monkeys indicate that tactual learning is more difficult than visual for the naive monkey. The posterior parietal cortex, but not other cortical association areas, appears to be necessary for full utilization of tactual input, and lesions of this area produce deficits in discrimination learning which are analogous to tactual agnosia in man. A model is presented in terms of which discrimination learning, and deficits in discrimination learning, are described.     

The striate projection zone in the superior temporal sulcus of Macaca mulatta: location and topographic organization.

In the rhesus monkey, the caudal portion of the superior temporal sulcus (STS) receives a direct projection from lateral striate cortex, the striate are representing central vision. The present study was undertaken to determine whether STS also receives a direct projection from areas of striate cortex representing peripheral vision, with the intent of defining the entire striate projection zone in STS as well as providing information regarding a possible topographic organization within this secondary visual area. A series of five rhesus monkeys was prepared with unilateral lesions of lateral, posterior, or medial striate cortex, such that, collectively, the lesions in the series included all of striate cortex with little or no invasion of prestriate cortex. The monkeys were sacrificed seven days after surgery and their brains were processed by the Fink-Heimer procedure. An analysis of the distribution of terminal degeneration within STS indicated: (1) All areas of striate cortex project to a restricted region along the caudal portion of STS. The ventral limit of this region can be demarcated by an imaginary line connecting the ventral tips of the lunate and intraparietal sulci; from this limit the region extends dorsocaudally for approximately 12 mm to the point at which STS frequently bifurcates, sending one spur forward into the inferior parietal lobule. (2) Within this portion of STS there is an orderly mapping of the visual field; progression from central vision to the far periphery is represented by a progression down the posterior bank of STS and continuing along the entire floor, or insula-like portion, of the sulcus. (3) Projections from striate cortex to STS terminate predominantly in layer IV and the deep part of layer III. (4) There is a distinctive pattern of myelination contained within the striate projection zone of STS. These anatomical findings concerning the striate projection zone of STS in the rhesus monkey are remarkably similar to those that have been described for the middle temporal visual area (MT) in New World monkeys, and thus support earlier proposals that the two areas are homologous.     

Tactile and visuo-spatial discrimination performance in the monkey: the effects of total and partial posterior parietal removals.

Sixteen rhesus monkeys were trained on a variety of tactile and visual tasks, and most animals were later tested for retention of most of the tasks. Four animals received bilateral posterior parietal ablations; 4 bilateral prestriate ablations; 4 bilateral posterior parieto-prestriate lesions at the beginning of training; and 4 acted as unoperated controls during initial training but then received bilateral posterior parieto-prestriate lesions before retention testing. Animals with posterior parietal or prestriate lesions were virtually unimpaired. However, animals with posterior parieto-prestriate lesions showed significant impairment on post-operative learning of various tactile tasks, on post-operative retention of pre-operatively learnt tactile tasks and on one visual spatial task.     

The effects of inferotemporal cortex lesions on Konorski delayed pair comparison in monkeys

Rhesus monkeys were trained on a pair comparison recognition memory task, running concurrently with a signal detection (attention) problem. The animals were given bilateral posterior or anterior inferotemporal cortex lesions once satisfactory performance had been reached. The former group sustained attentional but only transient mnemonic impairments. Anterior lesions impaired visual learning and memory, but not attention. We confirm that inferotemporal cortex is sub-divided into at least two distinct regions, serving visual attention and other cognitive processes. The role of inferotemporal cortex in recognition memory is discussed, and it is concluded that task-related problems do not permit an unambiguous resolution of this question.     

Pattern discrimination thresholds after partial inferior temporal or lateral striate lesions in monkeys.

Ablation of inferior temporal (IT) cortex, particularly of the posterior region, produces severe impairment in pattern discrimination learning. The present study examined whether this impairment is associated with raised pattern discrimination thresholds. Groups of three monkeys each were given either anterior IT, posterior IT, or foveal striate lesions, or kept as controls. They were trained after surgery on a threshold task in which a 90 degrees white angle on a gray ground was the standard, and 15 angles ranging from 10 degrees through 88.5 degrees were the comparisons. As expected, monkeys with posterior IT lesions were the most severely impaired in learning the initial discrimination (90 degrees vs. 10 degrees). However, only the monkeys with foveal striate lesions showed significant impairment on the subsequent threshold determinations. The results indicate that raised pattern discrimination thresholds are not the cause of the pattern discrimination learning deficits produced by inferior temporal lesions. Data from additional visual discriminations presented after threshold testing was completed point, instead, to a loss of attention to stimulus features as the explanation for the learning deficit.     

Motor conditional associative-learning after selective prefrontal lesions in the monkey

Rhesus monkeys with selective lesions of the frontal cortex were tested on a motor conditional associative-learning task. Monkeys with lesions of the periarcuate area were severely impaired in acquiring this task, whilst monkeys with lesions of the principalis region showed only a mild retardation in learning.     

Functional organization of monkey brain for abstract operation

When humans manipulate a control device under operational rules, with the goal of indirectly controlling a remote tool to achieve a desired outcome, they may rely on the power of internal representation to organize individual moves of the controller and tool into a set of sequences by mapping the motor space among hand, controller and tool. We recently used functional brain imaging (PET) to investigate activations in monkey brain associated with joystick-controlled remote operation of a shovel to obtain food. Activated areas included the prefrontal cortex, posterior parietal cortex and cerebellum, regardless of the rules relating movements of the joystick to those of the shovel (Obayashi et al., 2004). If those areas are engaged in the mental manipulation of internal representation, then we should expect brain activity in the same regions during any similar remote operation, even with different controllers and/or operational rules. To address the above hypothesis in the current study, we used PET to measure regional cerebral blood flow (rCBF) of two monkeys during a task in which they were required to control a shovel remotely (to fetch a food pellet) by manipulating dual dials. Compared to unplanned movement of the dials, the active dual-dial operation was associated with robust activation of the prefrontal cortex, higher-order motor cortex, posterior parietal cortex and cerebellum, quite similar to that observed during remote operation with a joystick. The present study suggests that monkeys might be able to organize abstract sequential operations according to learned rules, and perhaps indeed to have insight into the nature of the causal relationships, implying the existence of a relatively sophisticated system of internal representation in the absence of language. The fact that the present results are consistent with our previous PET studies strengthens the view that the underlying mechanism for implicit manipulation of internal representations may involve a cerebro-cerebellar neural circuit including the frontal and parietal cortex.     

Lesions of perirhinal and parahippocampal cortex that spare the amygdala and hippocampal formation produce severe memory impairment

In monkeys, bilateral damage to the medial temporal region produces severe memory impairment. This lesion, which includes the hippocampal formation, amygdala, and adjacent cortex, including the parahippocampal gyrus (the H+A+ lesion), appears to constitute an animal model of human medial temporal lobe amnesia. Reexamination of histological material from previously studied monkeys with H+A+ lesions indicated that the perirhinal cortex had also sustained significant damage. Furthermore, recent neuroanatomical studies show that the perirhinal cortex and the closely associated parahippocampal cortex provide the major source of cortical input to the hippocampal formation. Based on these 2 findings, we evaluated the severity of memory impairment in a group of monkeys that received bilateral lesions limited to the perirhinal cortex and parahippocampal gyrus (the PRPH lesion). The performance of the PRPH group was compared with that of monkeys with H+A+ lesions, who had been studied previously, and with a group of normal monkeys. Monkeys with PRPH lesions were severely impaired on 3 amnesia-sensitive tasks: delayed nonmatching to sample, object retention, and 8-pair concurrent discrimination. On pattern discrimination, a task analogous to ones that amnesic patients perform well, monkeys in the PRPH group performed normally. Overall, monkeys with PRPH lesions were as impaired or more impaired than the comparison group of monkeys with H+A+ lesions. These and other recent findings (Zola-Morgan et al., 1989b) suggest that the severe memory impairment in monkeys and humans associated with bilateral medial temporal lesions results from damage to the hippocampal formation and adjacent, anatomically related cortex, not from conjoint hippocampus-amygdala damage.