Behavioral effects of sequential and one-stage ablations of orbital prefrontal cortex in the monkey

The purpose of this investigation was to determine whether sequential (i.e., serial) ablation of the monkey's orbital prefrontal cortex would lead to a reduction in the severity of the behavioral impairment usually associated with one-stage bilateral removal of this tissue. The lateral orbital cortex was ablated in four operations spaced 3 weeks apart or in a one-stage procedure. The monkeys were examined on a visual go-no go differentiation task, spatial delayed-alternation, and object reversal learning. The results reveal no differences between the effects of sequential and one-stage ablations. These findings differ from previous experiments that demonstrated a degree of functional recovery after the sequential removal of a sector of the dorsolateral prefrontal cortex. Since lesion studies with infant monkeys have also demonstrated that functional recovery occurs after early ablation of dorsolateral cortex but not after early removal of orbital frontal cortex, recovery of behavioral functions after infant and sequential lesions may involve similar neural mechanisms.     

The role of prefrontal cortex in object-in-place learning in monkeys

Previous ablation studies in monkeys suggest that prefrontal cortex is involved in a wide range of learning and memory tasks. However, monkeys with crossed unilateral lesions of frontal and temporal cortex are unimpaired at concurrent object-reward association learning but are impaired at conditional learning and the implementation of memory-based performance rules. We trained seven monkeys preoperatively on an associative learning task that required them to associate objects embedded in unique complex scenes with reward. Three monkeys then had crossed unilateral lesions of frontal and inferior temporal cortex and the remaining monkeys had bilateral prefrontal cortex ablation. Both groups were severely impaired postoperatively. These results show that both bilateral prefrontal cortex ablation and frontal-temporal disconnection impair associative learning for objects embedded in scenes. The results provide evidence that the function of frontal-temporal interactions in memory is not limited to conditional learning tasks and memory-dependent performance rules. We propose that rapid object-in-place learning requires the interaction of frontal cortex with inferotemporal cortex because visual object and contextual information which is captured over multiple saccades must be processed as a unique complex event that is extended in time. The present results suggest a role for frontal-temporal interaction in the integration of visual information over time.     

Effects of successive unilateral ablations of principalis cortex upon performances of delayed alternations and delayed response by monkeys

Monkeys were trained on delayed alternation (DA), and were then subjected to serial unilateral or simultaneous bilateral ablations of the banks of the sulcus principalis of each frontal lobe. When subjects with unilateral lesions were retrained on DA, their performances were intermediate to those of normal and bilateral animals. This interoperative training failed to protect the serially operated monkeys from losses of DA following their second-stage ablations, for they then performed as poorly as one-stage subjects and subjects prepared with serial ablations that were not given practice on the task between the two operations.Additional postoperative tests of delayed responding (DR) showed that both serially and simultaneously ablated subjects also had severe impairments of performance of DR. This result confirmed, in principle, a finding that monkey with large unilateral ablations, if reoperated after many months for the removal of the contralateral dorsolateral prefrontal cortex, will thereafter exhibit DR deficits that are both severe and endure for a period of years. It contrasted sharply with a recent observation that DR is retained by monkeys subjected to two-stage symmetrical ablations of the principalis cortex, which suggests that recoveries of frontal-lobe functions are powerfully affected by the orders in which serial extirpations are performed.     

Contralateral 'neglect' after unilateral dorsomedial prefrontal lesions in rats

After determining the side preferences of rats in a Y-maze either the dorsomedial or dorsolateral prefrontal cortex was removed unilaterally. The latter operation had no effect on choice behaviour whereas the former was followed by a significant reduction of turns to the side contralateral to the lesion. The results are discussed in relation to recent anatomical experiments which indicate that the dorsomedial prefrontal cortex in the rat may be homologous to the frontal eye-fields of monkeys, unilateral removal of which causes a contralateral neglect.     

Prenatal specification of callosal connections in rhesus monkey

Anatomical tracing and quantitative techniques were used to examine the tempo and pattern of maturation for callosal projection neurons in the monkey prefrontal cortex (PFC) during fetal and postnatal development. Nineteen monkeys were injected with retrograde tracers (fluorescent dyes, horseradish peroxidase conjugated to wheat germ agglutinin [WGA-HRP] or HRP crystals) at various ages between embryonic day 82 (E82) and adulthood. The size of injection sites was varied in fetal, newborn, and adult cases. In adults, labeled neurons were found in greatest density in the homotopic cortex of the opposite hemisphere and considerable numbers were also observed in a constellation of heterotopic areas including the medial and lateral orbital cortex, the dorsomedial convexity, and the pregenual cortex. The majority of labeled neurons were consistently concentrated in the lower half of layer III in all areas. In cases with large injection sites, callosal neurons of layer III formed a continuous and uninterrupted band that extended over the entire lateral surface of the prefrontal cortex spanning both homotopic and heterotopic areas. In contrast, in cases with small injection sites, the labeling of layer III neurons exhibited discontinuities. Between embryonic ages E82 and E89, injections limited to the cortical layers labeled only a small number of neurons in the opposite hemisphere, indicating that few callosal axons have invaded the cortex by this age. However, by E111 comparable injections labeled a large number of callosal neurons and many features of their distribution were adult-like. The number and constellation of cytoarchitectonic areas that were labeled in the frontal cortex of the opposite hemisphere were the same as in adults and the majority of callosal neurons were found in supragranular layer III. Finally, in fetal animals beyond E111, labeled neurons extended as a nearly unbroken band over a wide expanse of the dorsolateral PFC, resembling the pattern seen in adult monkeys with large injections. The conclusion we draw from these results, together with our earlier findings (Schwartz and Goldman-Rakic: Nature 299:154, 1982), is that callosal neurons whose axons enter the cortical layers of the primate prefrontal cortex achieve their mature laminar and areal distribution prior to birth and do so largely by cumulative processes.     

Brain volume and dysexecutive behavior in schizophrenia

Objective

Behaviors associated with frontal/executive impairments are common in patients with schizophrenia. Our aim was to reconfirm that morphological brain abnormalities in schizophrenia patients would overlap the areas underpinning frontal systems behavior, and examine whether any specific association exists between abnormalities of brain structures and frontal behavioral deficits in schizophrenia patients.

Method

Twenty-six schizophrenia patients and 26 matched healthy controls underwent structural magnetic resonance imaging and their frontal function was assessed by a self-rating questionnaire, Frontal Systems Behavior Scale (FrSBe). We applied voxel-based morphometry (VBM) to investigate regional brain volume alternations.

Result

Compared with healthy controls, schizophrenia patients showed reduced gray matter volume in multiple frontal and temporal structures, namely, the bilateral dorsolateral prefrontal cortices (DLPFC), bilateral medial prefrontal cortices, left ventrolateral prefrontal cortex, bilateral anterior cingulate cortices, and bilateral superior temporal gyri. The scores on the executive dysfunction subscale of the FrSBe were correlated with volume reduction in the bilateral DLPFC in the patient group.

Conclusion

Our result suggests that pathology of the DLPFC could be the neural basis of real-life dysexecutive behaviors in schizophrenia patients.     

Differential activation in parahippocampal and prefrontal cortex during word and face encoding tasks

Episodic encoding is the first step in the formation of a memory trace. The relation between type of stimulus material and regional brain activation is not fully understood. We measured brain activation using fMRI in 12 healthy subjects during two experiments, word and face encoding. A widespread network of common activations in both tasks was present in the bilateral frontal (BA44/45), occipital (BA17/18/19) and fusiform gyri (BA37) as well as the right hippocampal formation (BA30). A region-of-interest-analysis for the hippocampal formation and dorsolateral prefrontal cortex (DLPFC) was performed additionally. During face encoding the right dorsal and during word encoding the bilateral ventral hippocampal region was activated. In the prefrontal cortex a lateralization to the left side was present only for word encoding. During encoding, activation in the inferior frontal and hippocampal cortex is modulated by the type of stimulus material.     

Reward-related reversal learning after surgical excisions in orbito-frontal or dorsolateral prefrontal cortex in humans

Neurophysiological studies in primates and neuroimaging studies in humans suggest that the orbito-frontal cortex is involved in representing the reward value of stimuli and in the rapid learning and relearning of associations between visual stimuli and rewarding or punishing outcomes. In the present study, we tested patients with circumscribed surgical lesions in different regions of the frontal lobe on a new visual discrimination reversal test, which, in an fMRI study (O'Doherty, Kringelbach, Rolls, Hornak, & Andrews, 2001), produced bilateral orbito-frontal cortex activation in normal subjects. In this task, touching one of two simultaneously presented patterns produced reward or loss of imaginary money delivered on a probabilistic basis to minimize the usefulness of verbal strategies. A number of types of feedback were present on the screen. The main result was that the group of patients with bilateral orbito-frontal cortex lesions were severely impaired at the reversal task, in that they accumulated less money. These patients often failed to switch their choice of stimulus after a large loss and often did switch their choice although they had just received a reward. The investigation showed that bilateral lesions were required for this deficit, since patients with unilateral orbito-frontal cortex (or medial prefrontal cortex) lesions were not impaired in the probabilistic reversal task. The task ruled out a simple motor disinhibition as an explanation of the deficit in the bilateral orbito-frontal cortex patients, in that the patients were required to choose one of two stimuli on each trial. A comparison group of patients with dorsolateral prefrontal cortex lesions was in some cases able to do the task, and in other cases, was impaired. Posttest debriefing showed that all the dorsolateral prefrontal patients who were impaired at the task had failed to pay attention to the crucial feedback provided on the screen after each trial about the amount won or lost on each trial. In contrast, all dorsolateral patients who paid attention to this crucial feedback performed normally on the reversal task. Further, it was confirmed that the bilateral orbito-frontal cortex patients had also paid attention to this crucial feedback, but in contrast had still performed poorly at the task. The results thus show that the orbital prefrontal cortex is required bilaterally for monitoring changes in the reward value of stimuli and using this to guide behavior in the task; whereas the dorsolateral prefrontal cortex, if it produces deficits in the task, does so for reasons related to executive functions, such as the control of attention. Thus, the ability to determine which information is relevant when making a choice of pattern can be disrupted by a dorsolateral lesion on either side, whereas the ability to use this information to guide behavior is not disrupted by a unilateral lesion in either the left or the right orbito-frontal cortex, but is severely impaired by a bilateral lesion in this region. Because both abilities are important in many of the tasks and decisions that arise in the course of daily life, the present results are relevant to understanding the difficulties faced by patients after surgical excisions in different frontal brain regions.     

Functional development of the dorsolateral prefrontal cortex: an analysis utlizing reversible cryogenic depression.

The dorsolateral prefrontal cortex of rhesus monkeys was functionally inactivated by local hypothermia as the monkeys performed spatial delayed-response and spatial delayed-alternation tasks at different stages of postnatal development. Cryogenic depression of prefrontal cortex at a temperature sufficient to induce 21--25% decrements in delayed-response performance in 34--36-month-old-monkeys, produced deficits of only 7--8% in 19--31-month-old and no detectable loss in younger monkeys, 9--16 months of age. Delayed-alternation performance was impaired by local hypothermia as early as 8.5 months of age, but maximal cooling-induced deficits on this task were not observed before 33 months of age. Thermal gradients mapped in representative monkeys at different stages of development were remarkable similar, indicating that the age-dependent differences in behavior were not attributable to technical factors. The results obtained in the present study on normal developing monkeys confirm the interpretation of previous research on brain-damaged infants that functional maturation of the dorsolateral prefrontal cortex is protracted over several years of postnatal life, and extends the earlier studies by indicating that the lower limit for maturity of dorsolateral function is close to puberty in this species. Further, the present study revealed that delayed-response and delayed-alternation performance are dissociable dorsolateral functions which achieve maturity at different rates. The convergence of evidence from reversible neural depression and permanent lesion methods provides strong validation for neurobehavioral analysis as a general approach to the study of regional maturation of the brain.     

Functional development of the dorsolateral prefrontal cortex: An analysis utilizing reversible cryogenic depression

The dorsolateral prefrontal cortex of rhesus monkeys was functionally inactivated by local hypothermia as the monkeys performed spatial delayed-response and spatial delayed-alternation tasks at different stages of postnatal development. Cryogenic depression of prefrontal cortex at a temperature sufficient to induce 21–25% decrements in delayed-response performance in 34–36-month-old monkeys, produced deficits of only 7–8% in 19–31-month-olds and no detectable loss in younger monkeys, 9–16 months of age. Delayed-alternation performance was impaired by local hypothermia as early as 8.5 months of age, but maximal cooling-induced deficits on this task were not observed before 33 months of age. Thermal gradients mapped in representative monkeys at different stages of development were remarkably similar, indicating that the age-dependent differences in behavior were not attributable to technical factors. The results obtained in the present study on normal developing monkeys confirm the interpretation of previous research on brain-damaged infants that functional maturation of the dorsolateral prefrontal cortex is protracted over several years of postnatal life, and extends the earlier studies by indicating that the lower limit for maturity of dorsolateral function is close to puberty in this species. Further, the present study revealed that delayed-response and delayed-alternation performance are dissociable dorsolateral functions which achieve maturity at different rates. The convergence of evidence from reversible neural depression and permanent lesion methods provides strong validation for neurobehavioral analysis as a general approach to the study of regional maturation of the brain.     

A distributed cortical network for auditory sensory memory in humans

Auditory sensory memory is a critical first stage in auditory perception that permits listeners to integrate incoming acoustic information with stored representations of preceding auditory events. Here, we investigated the neural circuits of sensory memory using behavioral and electrophysiological measures of auditory processing in patients with unilateral brain damage to dorsolateral prefrontal cortex, posterior association cortex, or the hippocampus. We used a neurophysiological marker of an automatic component of sensory memory, the mismatch negativity (MMN), which can be recorded without overt attention. In comparison with control subjects, temporal-parietal patients had impaired auditory discrimination and reduced MMN amplitudes with both effects evident only following stimuli presented in the ear contralateral to the lesioned hemisphere. This suggests that auditory sensory memories are predominantly stored in auditory cortex contralateral to the ear of presentation. Dorsolateral prefrontal damage impaired performance and reduced MMNs elicited by deviant stimuli presented in either ear, implying that dorsolateral prefrontal cortices have a bilateral facilitatory effect on sensory memory storage. Hippocampal lesions did not affect either performance or electrophysiological measures. The results provide evidence of a temporal-prefrontal neocortical network critical for the transient storage of auditory stimuli.     

Dorsolateral prefrontal lesions do not impair tests of scene learning and decision-making that require frontal-temporal interaction

Theories of dorsolateral prefrontal cortex (DLPFC) involvement in cognitive function variously emphasize its involvement in rule implementation, cognitive control, or working and/or spatial memory. These theories predict broad effects of DLPFC lesions on tests of visual learning and memory. We evaluated the effects of DLPFC lesions (including both banks of the principal sulcus) in rhesus monkeys on tests of scene learning and strategy implementation that are severely impaired following crossed unilateral lesions of frontal cortex and inferotemporal cortex. Dorsolateral lesions had no effect on learning of new scene problems postoperatively, or on the implementation of preoperatively acquired strategies. They were also without effect on the ability to adjust choice behaviour in response to a change in reinforcer value, a capacity that requires interaction between the amygdala and frontal lobe. These intact abilities following DLPFC damage support specialization of function within the prefrontal cortex, and suggest that many aspects of memory and strategic and goal-directed behaviour can survive ablation of this structure.     

An fMRI study of the interface between affective and cognitive neural circuitry in pediatric bipolar disorder

The pathophysiology of pediatric bipolar disorder (PBD) impacts both affective and cognitive brain systems. Understanding disturbances in the neural circuits subserving these abilities is critical for characterizing developmental aberrations associated with the disorder and developing improved treatments. Our objective is to use functional neuroimaging with pediatric bipolar disorder patients employing a task that probes the functional integrity of attentional control and affect processing. Ten euthymic unmedicated pediatric bipolar patients and healthy controls matched for age, sex, race, socioeconomic status, and IQ were scanned using functional magnetic resonance imaging. In a pediatric color word matching paradigm, subjects were asked to match the color of a word with one of two colored circles below. Words had a positive, negative or neutral emotional valence, and were presented in 30-s blocks. In the negative affect condition, relative to the neutral condition, patients with bipolar disorder demonstrated greater activation of bilateral pregenual anterior cingulate cortex and left amygdala, and less activation in right rostral ventrolateral prefrontal cortex (PFC) and dorsolateral PFC at the junction of the middle frontal and inferior frontal gyri. In the positive affect condition, there was no reduced activation of PFC or increased amygdala activation. The pattern of reduced activation of ventrolateral PFC and greater amygdala activation in bipolar children in response to negative stimuli suggests both disinhibition of emotional reactivity in the limbic system and reduced function in PFC systems that regulate those responses. Higher cortical cognitive areas such as the dorsolateral PFC may also be adversely affected by exaggerated emotional responsivity to negative emotions. This pattern of functional alteration in affective and cognitive circuitry may contribute to the reduced capacity for affect regulation and behavioral self-control in pediatric bipolar disorder.     

S-adenosyl-l-methionine facilitates recovery from deficits in delayed response and hand movement tasks following brain lesions in monkeys

Effects of S-adenosyl-l-methionine (SAMe) on deficits in a trained delayed response task or trained hand movement tasks after lesions in bilateral dorsolateral prefrontal cortices or the hand-arm area of the unilateral motor cortex in monkeys were studied. Lesions disturbed the delayed response task or hand movement tasks moderately or severely for 1 week to several months depending on the extent of the lesion and nature of the task. Although treatment with small doses of SAMe (10 mg/kg/day, i.m.) had no effect on these disturbances, treatment with moderate doses of SAMe (20 or 30 mg/kg/day, i.m.) reduced impairments and promoted recovery from both disturbances. Pretreatment with SAMe (30 mg/kg/day, i.m.) facilitated recovery from delayed response task deficits due to administration of reserpine (0.3 mg/kg, i.m.) in monkey with bilateral prefrontal cortical lesions, but not in intact monkey. The data suggest that SAMe improves recovery from behavioral disturbances due to brain damage, and this is partly due to increased monoamine turnover rate.     

S-adenosyl-L-methionine facilitates recovery from deficits in delayed response and hand movement tasks following brain lesions in monkeys

Effects of S-adenosyl-L-methionine (SAMe) on deficits in a trained delayed response task or trained hand movement tasks after lesions in bilateral dorsolateral prefrontal cortices or the hand-arm area of the unilateral motor cortex in monkeys were studied. Lesions disturbed the delayed response task or hand movement tasks moderately or severely for 1 week to several months depending on the extent of the lesion and nature of the task. Although treatment with small doses of SAMe (10 mg/kg/day, i.m.) had no effect on these disturbances, treatment with moderate doses of SAMe (20 or 30 mg/kg/day, i.m.) reduced impairments and promoted recovery from both disturbances. Pretreatment with SAMe (30 mg/kg/day, i.m.) facilitated recovery from delayed response task deficits due to administration of reserpine (0.3 mg/kg, i.m.) in monkey with bilateral prefrontal cortical lesions, but not in intact monkey. The data suggest that SAMe improves recovery from behavioral disturbances due to brain damage, and this is partly due to increased monoamine turnover rate.     

Cognitive Outcomes in Patients with Frontal Lobe Epilepsy

Summary:  A typical "cognitive profile" or defining behavioral syndrome for patients with frontal lobe epilepsy (FLE) has not been described. While there have been numerous reports of impaired "executive functions" in this population, the nature and severity of these deficits is highly variable, ranging from impaired attention to difficulty with the more complex behaviors involved in planning, selecting goals, anticipating outcomes, and initiating action. These findings have been more difficult to demonstrate in children, in part due to the later appearance of these abilities in normal development. When a clear focal seizure onset is identified, or in cases of a structural lesion, cognitive impairment may be specific to the side, size, and localization of the abnormal cortex. Children who have undergone surgical resection of the dominant frontal lobe frequently show declines in verbal fluency, and sometimes verbal IQ, visual confrontation naming, and conceptual reasoning. Adult surgical cases have shown the most specific frontal lobe findings, including reduced word fluency with relatively small lesions of the dominant dorsolateral frontal cortex, the analogous finding of impaired nonverbal fluency with nondominant frontal lesions, and other executive deficits following large resections of prefrontal cortex bilaterally. These reports support the likelihood that it may not be possible to identify a specific cognitive syndrome associated with FLE in the absence of a structural lesion.     

Delayed alternation impairments following selective prefrontal cortical ablations in monkeys

Several investigators have considered cortex in the principal sulcus of the prefrontal lobes as the “neural focus” for tasks such as delayed alternation. This concept was examined experimentally by training monkeys on several variations of locomotor delayed alternation tasks in a maze and subjecting them to bilateral ablations of either the traditional dorsolateral prefrontal cortex (TOTAL), cortex in the banks and floor of the principal sulcus (PRINC), or the surrounding dorsolateral cortical strips (DAL). The postoperative results indicate the most severe deficits by the TOTAL and the least by the DAL group. The TOTAL monkeys were appreciably more severely impaired than the PRINC, especially with regard to their high rates of perseverative responses. The ablated monkeys were then trained to either crawl beneath or jump over a barrier before making the choice response. All groups responded better on this than on the standard DA task. However, on intervening tests on the standard DA task only the PRINC, but not the TOTAL, group was able to attain criterion performance. Consideration was given to a possible functional dissociation between the PRINC and DAL cortical segments, but the present results did not clearly support such a distinction. We concluded that a full expression of the DA deficits requires ablation of TOTAL prefrontal cortex, i.e., all dorsolateral cortex within the traditional boundaries.     

Functional neuroanatomy of visuospatial working memory in fragile X syndrome: relation to behavioral and molecular measures.

OBJECTIVE: Fragile X syndrome is a neurogenetic disorder that is the most common known heritable cause of neurodevelopmental disability. This study examined the neural substrates of working memory in female subjects with fragile X syndrome. Possible correlations among behavioral measures, brain activation, and the FMR1 gene product (FMRP expression), as well as between IQ and behavioral measures, were investigated. METHOD: Functional magnetic resonance imaging was used to examine visuospatial working memory in 10 female subjects with fragile X syndrome and 15 typically developing female subjects (ages 10-23 years). Subjects performed standard 1-back and 2-back visuospatial working memory tasks. Brain activation was examined in four regions of the cortex known to play a critical role in visuospatial working memory. Correlations between behavioral, neuroimaging, and molecular measures were examined. RESULTS: Relative to the comparison group, subjects with fragile X syndrome performed significantly worse on the 2-back task but not on the 1-back task. In a region-of-interest analysis focused on the inferior frontal gyrus, middle frontal gyrus, superior parietal lobule, and supramarginal gyrus, comparison subjects showed significantly increased brain activation between the 1-back and 2-back tasks, but subjects with fragile X syndrome showed no change in activation between the two tasks. Significant correlations were found in comparison subjects between activation in the frontal and parietal regions and the rate of correct responses on the 2-back task, but not on the 1-back task. In subjects with fragile X syndrome, significant correlations were found during the 2-back task between FMRP expression and activation in the right inferior and bilateral middle frontal gyri and the bilateral supramarginal gyri. CONCLUSIONS: Subjects with fragile X syndrome are unable to modulate activation in the prefrontal and parietal cortex in response to an increasing working memory load, and these deficits are related to a lower level of FMRP expression in fragile X syndrome subjects than in normal comparison subjects. The observed correlations between biological markers and brain activation provide new evidence for links between gene expression and cognition.     

Neural correlates of memory for items and for associations: an event-related functional magnetic resonance imaging study

Although results from cognitive psychology, neuropsychology, and behavioral neuroscience clearly suggest that item and associative information in memory rely on partly different brain regions, little is known concerning the differences and similarities that exist between these two types of information as a function of memory stage (i.e., encoding and retrieval). We used event-related functional magnetic resonance imaging to assess neural correlates of item and associative encoding and retrieval of simple images in 18 healthy subjects. During encoding, subjects memorized items and pairs. During retrieval, subjects made item recognition judgments (old vs. new) and associative recognition judgments (intact vs. rearranged). Relative to baseline, item and associative trials activated bilateral medial temporal and prefrontal regions during both encoding and retrieval. Direct contrasts were then performed between item and associative trials for each memory stage. During en- coding, greater prefrontal, hippocampal, and parietal activation was observed for associations, but no significant activation was observed for items at the selected threshold. During recognition, greater activation was observed for associative trials in the left dorsolateral prefrontal cortex and superior parietal lobules bilaterally, whereas item recognition trials showed greater activation of bilateral frontal regions, bilateral anterior medial temporal areas, and the right temporo-parietal junction. Post hoc analyses suggested that the anterior medial temporal activation observed during item recognition was driven mainly by new items, confirming a role for this structure in novelty detection. These results suggest that although some structures such as the medial temporal and prefrontal cortex play a general role in memory, the pattern of activation in these regions can be modulated by the type of information (items or associations) interacting with memory stages.     

Interaction of the Amygdala with the Frontal Lobe in Reward Memory

Five cynomolgus monkeys (Macaca fascicularis) were assessed for their ability to associate visual stimuli with food reward. They learned a series of new two-choice visual discriminations between coloured patterns displayed on a touch-sensitive monitor screen; the feedback for correct choice was delivery of food. Normal learning in this task is known to be dependent on the amygdala. The monkeys received brain lesions which were designed to disconnect the amygdala from interaction with other brain structures thought to be involved in this memory task. All the monkeys received an amygdalectomy in one hemisphere and lesions in the other hemisphere of some of the projection targets of the amygdala, namely the ventral striatum, the mediodorsal thalamus and the ventromedial prefrontal cortex. The rate of learning new problems was assessed before and after each operation. Disconnection of the amygdala from the ventral striatum was without effect on learning rate. An earlier study had shown that disconnection of the amygdala from either the mediodorsal thalamus or the ventromedial prefrontal cortex produced only a mild impairment, significantly less severe than that produced by bilateral lesions of any of these three structures. The present results show, however, that disconnection of the amygdala from both the mediodorsal thalamus and the ventromedial prefrontal cortex in the same animal, by crossed unilateral lesions of the amygdala in one hemisphere and of both the mediodorsal thalamus and the ventromedial prefrontal cortex in the other hemisphere, produces an impairment as severe as that which follows bilateral lesions of any of these three structures. These results show that, in stimulus – reward associative memory, the role of the amygdala is entirely dependent on its interaction with the frontal lobe, either by direct projections or by indirect subcortical pathways including the mediodorsal nucleus of the thalamus; and that there are at least two partially independent pathways by which the amygdala can influence the frontal lobe.