Crossed unilateral lesions of the medial forebrain bundle and either inferior temporal or frontal cortex impair object-reward association learning in Rhesus monkeys

In an accompanying paper we showed that combined transection of the fornix, amygdala and temporal stem in monkeys produced dense amnesia, including an impairment in visual object-reward association learning. We proposed that this combined surgical section had its effect by isolating temporal cortex from the ascending projections of the basal forebrain and midbrain structures. To test this hypothesis, in the present experiment we disconnected the inferior temporal cortex from these basal forebrain and midbrain structures, while sparing cortical white matter, by crossed unilateral lesions of the medial forebrain bundle in one hemisphere and inferior temporal cortex in the opposite hemisphere. The aim of the medial forebrain bundle lesion was to section axons of cells, both those that project to the cortex via the medial forebrain bundle, and those which control the activity of these same structures. A single unilateral lesion alone had no effect on the ability to learn and remember visual object-reward associations, but the crossed unilateral lesions produced an impairment in this task which was equal in severity to the impairment seen earlier after bilateral section of the fornix, amygdala and temporal stem. The impairment was not an effect of interrupting fibres to the cortex from the ventromedial hypothalamus, or of unilateral sensory neglect. This supports the hypothesis that these midbrain and basal forebrain afferents to the inferior temporal cortex are important for new visual learning. Furthermore, an impairment of equal severity was demonstrated in a separate group of animals that received crossed unilateral lesions of the medial forebrain bundle in one hemisphere and of the frontal cortex in the opposite hemisphere. We propose that the frontal cortex acts to modulate basal forebrain activity which in turn reinforces object representations in the inferior temporal cortex during learning.     

Dense amnesia in the monkey after transection of fornix, amygdala and anterior temporal stem

The traditional explanation of dense amnesia after medial temporal lesions is that the amnesia is caused by damage to the hippocampus and related structures. An alternative view is that dense amnesia after medial temporal lesions is caused by the interruption of afferents to the temporal cortex from the basal forebrain. These afferents travel to the temporal cortex through three pathways, namely the anterior temporal stem, the amygdala and the fornix-fimbria, and all these three pathways are damaged in dense medial temporal amnesia. In four experiments using different memory tasks, we tested the effects on memory of sectioning some or all of these three pathways in macaque monkeys. In a test of scene-specific memory for objects, which is analogous in some ways to human episodic memory, section of fornix alone, or section of amygdala and anterior temporal stem sparing the fornix, each produced a significant but mild impairment. When fornix section was added to the section of anterior temporal stem and amygdala in this task, however, a very severe impairment resulted. In an object recognition memory task (delayed matching-to-sample) a severe impairment was seen after section of anterior temporal stem and amygdala alone, with or without the addition of fornix section; this impairment was significantly more severe than that which was seen in the same task after amygdalectomy leaving the temporal stem intact, with or without fornix section. Animals with combined section of anterior temporal stem, amygdala and fornix were also impaired in object-reward association learning. However, the retention of pre-operatively acquired object-reward associations was at a high level. These results show that the pattern of impairments after section of anterior temporal stem, amygdala and fornix in the monkey, leaving hippocampus intact, resembles human dense amnesia and is different from the effects of hippocampal lesions in the monkey.     

A cholinergic explanation of dense amnesia

Traditionally, dense amnesia in humans has been thought to be caused by damage to memory structures within the medial temporal lobe, either the hippocampus, the perirhinal cortex or a combination of the two. Recent work in animals has indicated that damage to the hippocampus results in memory impairments that are specific to memories for events. In contrast, damage to the perirhinal cortex impairs object memories in primates, which are likely to be analogous to human semantic memory. Discrete damage to either of these structures does not appear to result in severe and global memory impairments. We propose an alternative to this medial temporal lobe explanation of dense amnesia, based on our recent work. We have shown that the cholinergic cells of the basal forebrain are essential for new learning of both object and event-like memories in the monkey. Our model of learning in the primate brain rests on the proposal that there is a route of communication between the frontal cortex and inferior temporal cortex and hippocampus via the basal forebrain, which is critical for memory encoding. Interruption to this circuit at any stage will result in a severe and global anterograde amnesia.     

Basal Forebrain Cholinergic Neurons Selectively Drive Coordinated Motor Learning in Mice

Motor control requires precise temporal and spatial encoding across distinct motor centers that is refined through the repetition of learning. The recruitment of motor regions requires modulatory input to shape circuit activity. Here, we identify a role for the baso-cortical cholinergic pathway in the acquisition of a coordinated motor skill in mice. Targeted depletion of basal forebrain cholinergic neurons results in significant impairments in training on the rotarod task of coordinated movement. Cholinergic neuromodulation is required during training sessions as chemogenetic inactivation of cholinergic neurons also impairs task acquisition. Rotarod learning is known to drive refinement of corticostriatal neurons arising in both medial prefrontal cortex (mPFC) and motor cortex, and we have found that cholinergic input to both motor regions is required for task acquisition. Critically, the effects of cholinergic neuromodulation are restricted to the acquisition stage, as depletion of basal forebrain cholinergic neurons after learning does not affect task execution. Our results indicate a critical role for cholinergic neuromodulation of distant cortical motor centers during coordinated motor learning.SIGNIFICANCE STATEMENT Acetylcholine release from basal forebrain cholinergic neuron terminals rapidly modulates neuronal excitability, circuit dynamics, and cortical coding; all processes required for processing complex sensory information, cognition, and attention. We found that depletion or transient silencing of cholinergic inputs to anatomically isolated motor areas, medial prefrontal cortex (mPFC) and motor cortex, selectively led to significant impairments on coordinated motor learning; disrupting this baso-cortical network after acquisition elicited no effect on task execution. Our results indicate a pivotal role for cholinergic neuromodulation of distant cortical motor centers during coordinated motor learning. These findings support the concept that cognitive components (such as attention) are indispensable in the adjustment of motor output and training-induced improvements in motor performance.     

Insights into the nature of fronto-temporal interactions from a biconditional discrimination task in the monkey

Previous work in monkeys has shown that both frontal and inferior temporal cortices are required to solve visual learning tasks. When communication between these cortical areas is prevented within the same hemisphere by crossed lesions of the frontal cortex in one hemisphere and the inferior temporal cortex in the opposite hemisphere, most learning tasks are impaired, but learning of object-reward associations is unimpaired. The current experiment aims to understand further the role of the interaction between the frontal and inferior temporal cortices in learning tasks. We trained monkeys on a biconditional discrimination task, in which different visual cues guided behaviour towards choice objects. One visual cue predicted immediate delivery of reward to a correct response, the other visual cue predicted a delayed delivery of reward to a correct response. Pre-operative behavioural data clearly shows that the monkeys form expectations of the reward outcome for the individual cues and choice objects. Crossed lesions of frontal and inferior temporal cortices, however, produce no impairment on this task. The result suggests (in combination with previous experiments) that task difficulty does not determine the reliance of a task on interactions between the frontal cortex and the inferior temporal cortex within the same hemisphere. Instead, we propose that tasks that can be solved by using expectation of the reward outcome do not require interaction of frontal and inferior temporal cortices within the same hemisphere. The results are discussed in the context of other data on frontal interactions with inferior temporal cortex in learning tasks.     

Contribution of striate inputs to the visuospatial functions of parieto-preoccipital cortex in monkeys

In Experiments 1 and 2, monkeys received 3-stage operations intended to serially disconnect parieto-preoccipital from striate cortex. At each stage (unilateral parieto-preoccipital removal, contralateral striate removal and posterior callosal transection) the monkeys were tested for retention of the landmark task, a visuospatial discrimination sensitive to the effects of bilateral parieto-preoccipital damage. To check the effectiveness of the disconnection, the monkeys were also tested after removal of the remaining parieto-preoccipital cortex. The results demonstrated that corticocortical inputs from striate cortex are crucial for the visuospatial functions of parieto-preoccipital cortex, just as they had been shown earlier to be crucial for the pattern discrimination functions of inferior temporal cortex. Relative to inferior temporal cortex, however, parieto-preoccipital cortex was found to be especially dependent on ipsilateral (as compared with contralateral) striate inputs. In Experiment 3, monkeys received bilateral lesions of either lateral or medial striate cortex and were tested on both a pattern discrimination task, to assess residual inferior temporal function, and the landmark task, to assess residual parieto-preoccipital function. The results indicated that the pattern discrimination functions of inferior temporal cortex are especially dependent on inputs from lateral striate cortex, whereas the visuospatial functions of parieto-preoccipital cortex are equally dependent on inputs from lateral and medial striate cortex. The relatively greater contribution to parieto-preoccipital than to inferior temporal cortex made by ipsilateral and medial striate inputs (representing contralateral and peripheral visual fields, respectively) can also be seen in the receptive field properties of parieto-preoccipital and inferior temporal neurons. The differences in the organization of striate inputs to these two cortical association areas presumably reflect differences in the processing required for spatial vs object vision.     

Basal forebrain efferents to the medial dorsal thalamic nucleus in the rhesus monkey

Thalamic efferent connections of the basal forebrain (BF); medial septal nucleus (MS), vertical limb of the diagonal band (VDB), horizontal limb of the diagonal band (HDB), nucleus basalis (NB), and ventral pallidum (VP) were investigated in twelve rhesus monkeys. In five animals, injections of radioactively labeled amino acids were placed in the BF. In four animals, the injections involved different divisions of the NB, HDB, and the most ventral part of the VDB. In those four cases, labeled fibers in the medial forebrain bundle were observed traveling caudally towards the hypothalamus where some turned dorsally to enter the inferior thalamic peduncle. These fibers terminated in the ventral half of the magnocellular part of the medial dorsal thalamic nucleus (MDmc). In a fifth case, the amino acid injection involved most of the MS and the VDB. Labeled fibers traveled caudally from the injection site and entered the stria medullaris. These fibers then traveled caudally before turning ventrally to terminate in the dorsal half of MDmc. To determine which of the diverse neuronal types in the BF gives rise to these thalamic projections, in two monkeys injections of horseradish peroxidase (HRP) were placed into MDmc. Labeled neurons were observed throughout the full extent of the NB, the VDB, the MS, and part of the VP. In order to determine the extent of the cholinergic input to MDmc from the BF, one of the HRP cases was processed for the simultaneous visualization of HRP, and acetylcholinesterase (AChE), the hydrolytic enzyme for acetylcholine, and a second case was processed for simultaneous visualization of HRP, and choline acetyltransferase (ChAT), the synthetic enzyme for acetylcholine. We observed that 30-50% of the HRP-labeled neurons were putatively cholinergic. In order to determine if the NB projection to MD is a collateral of the NB projection to orbital frontal cortex, one fluorescent retrograde tracer was injected into the orbital frontal cortex and one into MD. This case showed that approximately 5% of the BF neurons that project to MDmc also project to the orbital frontal cortex. These results confirm a significant subcortical projection by which the cholinergic system of the basal forebrain may influence higher cortical functions through the thalamus.     

Global retrograde amnesia but selective anterograde amnesia after frontal-temporal disconnection in monkeys

Prefrontal cortex and inferior temporal cortex interact in support of a wide variety of learning and memory functions. In macaque monkeys, a disconnection of prefrontal and temporal cortex produces severe new learning impairments in a range of complex learning tasks such as visuo-motor conditional learning and object-in-place scene learning. The retrograde effects of this disconnection, however, have never been fully examined. We therefore assessed the postoperative retention of 128 preoperatively learned object discrimination problems in monkeys with prefrontal-temporal disconnection using 1 trial postoperative retention tests. Because previous experiments have suggested that both spatial and temporal factors may be important in engaging frontal-temporal interaction we used object discrimination problems with a variety of spatial and temporal properties. Postoperatively, although monkeys with prefrontal-temporal disconnection displayed a retrograde amnesia for all problem types, subsequent assessments of new learning revealed selective anterograde amnesia, which was limited to problems in which objects were presented as serial compound stimuli. The pattern of broad retrograde amnesia with selective anterograde amnesia contrasts with recent data from monkeys with lesions which disrupt subcortical-cortical connectivity and which show the opposite pattern, namely no retrograde amnesia but severe anterograde amnesia. These results support the hypothesis that visual memory acquisition is supported by subcortical-cortical interactions while the retrieval of visual memories normally depends on the interaction between prefrontal cortex and inferior temporal cortex.     

Removal of cholinergic input to perirhinal cortex disrupts object recognition but not spatial working memory in the rat

The perirhinal cortex of the temporal lobe has a crucial role in object recognition memory. Cholinergic transmission within perirhinal cortex also seems to be important for this function, as the muscarinic receptor antagonist scopolamine disrupts object recognition performance when administered systemically or directly into perirhinal cortex. In the present study, we directly assessed the contribution of cholinergic basal forebrain input to perirhinal cortex in object recognition. Selective bilateral removal of the cholinergic basal forebrain inputs to perirhinal cortex was accomplished by injecting the immunotoxin 192 IgG-saporin directly into perirhinal cortex in rats. These animals were significantly impaired relative to vehicle-injected controls in a spontaneous object recognition task despite intact spatial alternation performance. These results are consistent with recent reports of object recognition impairment following acute cholinergic receptor blockade and extend these findings by demonstrating that chronic removal of cholinergic basal forebrain input to an otherwise intact perirhinal cortex causes a severe object recognition deficit similar to that associated with more extensive cell body lesions of perirhinal cortex.     

The basal ganglia of Testudo Graeca

The basal ganglia of Testudo Graeca consist of upper and lower elevations in the side wall of the cerebral hemisphere. In the lower elevation is the medial forebrain bundle, and its hypothalamic connections suggest it may be concerned with visceral activities. In the upper elevation is the lateral forebrain bundle suggesting its connections are thalamic, and from experimental material there is little evidence that any are olfactory. The cells of the outer part of the lower elevation form a curved lamina pierced by the lateral forebrain bundle, resembling the formation of the human lentiform nucleus and internal capsule. Between the dorsal cortex and lower elevation or further caudally the upper elevation, is a curved band of cells, continuous with the upper end of the piriform cortex, which has been called the pallial thickening. It is suggested that this represents the outer of the three elevations forming the developing human caudate nucleus. Transecting this are fibers connecting the cortex and lateral forebrain bundle, and it is proposed that the entire length of these fibers is equivalent to part of the human internal capsule.     

Connections of inferior temporal areas TE and TEO with medial temporal-lobe structures in infant and adult monkeys

As part of a long-term study designed to examine the ontogeny of visual memory in monkeys and its underlying neural circuitry, we have examined the connections between inferior temporal cortex and medial temporal-lobe structures in infant and adult monkeys. Inferior temporal cortical areas TEO and TE were injected with WGA conjugated to HRP and tritiated amino acids, respectively, or vice versa, in 1-week-old and 3-4-yr-old Macaca mulatta, and the distributions of labeled cells and terminals were examined in both limbic structures and temporal-lobe cortical areas. In adult monkeys, inferior temporal-limbic connections included projections from area TEO to the dorsal portion of the lateral nucleus of the amygdala and from area TE to the lateral and lateral basal nuclei; inputs to both areas TEO and TE included those from the lateral, lateral basal, and medial basal nuclei of the amygdala and to area TE from the accessory basal nucleus. Additional limbic inputs to both areas TEO and TE arose from the posterior portion of the presubiculum. In infant monkeys, we found, in addition to these adultlike connections, a projection from area TEO to the lateral basal nucleus of the amygdala. Inferior temporal cortical connections in adult monkeys included projections from area TEO to area TE and, in turn, from area TE to area TG and perirhinal area 36, as well as from area TE back to area TEO; inputs to both areas TEO and TE included those from area TG, perirhinal areas 35 and 36, and parahippocampal areas TF and TH. All of these adultlike connections were also observed in infant monkeys, but, in addition, the infants showed projections from area TE to perirhinal area 35 as well as to parahippocampal areas TF and TH, and from area TEO to area TF. Moreover, in infants, the projection from area TE to perirhinal area 36 was considerably more widespread than in adults, both in areal extent and in laminar distribution. The results therefore indicate the existence of projections in infant monkeys from inferior temporal areas to the amygdala, perirhinal cortex, and parahippocampal cortex that are either totally eliminated in adults or more refined in their distribution. Both elimination and refinement of projections thus appear to characterize the maturation of axonal pathways between the inferior temporal cortex and medial temporal-lobe structures in monkeys.     

Fos expression following self-stimulation of the medial prefrontal cortex

Self-stimulation of the medial prefrontal cortex and medial forebrain bundle appears to be mediated by different directly activated fibers. However, reward signals from the medial prefrontal cortex do summate with signals from the medial forebrain bundle, suggesting some overlap in the underlying neural circuitry. We have previously used Fos immunohistochemistry to visualize neurons activated by rewarding stimulation of the medial forebrain bundle. In this study, we assessed Fos immunolabeling after self-stimulation of the medial prefrontal cortex. Among the structures showing a greater density of labeled neurons in the stimulated hemisphere were the prelimbic and cingulate cortex, nucleus accumbens, lateral preoptic area, substantia innominata, lateral hypothalamus, anterior ventral tegmental area, and pontine nuclei. Surprisingly, little or no labeling was seen in the mediodorsal thalamic nucleus or the locus coeruleus. Double immunohistochemistry for tyrosine hydroxylase and Fos showed that within the ventral tegmental area, a substantial proportion of dopaminergic neurons did not express Fos. Despite previous suggestions to the contrary, comparison of the present findings with those of our previous Fos studies reveals a number of structures activated by rewarding stimulation of both the medial prefrontal cortex and the medial forebrain bundle. Some subset of activated cells in the common regions showing Fos-like immunoreactivity may contribute to the rewarding effect produced by stimulating either site.     

Basal forebrain efferents reach the whole cerebral cortex of the cat

Efferent projections from the basal forebrain to the cat's cerebral cortex were traced with the retrograde horseradish peroxidase technique. Different areas of the cerebral cortex of 51 cats were injected with small amounts of horseradish peroxidase. The entire basal forebrain was screened for labeled neurons. Following all injections, retrogradely labeled neurons could be detected in either the medial septum, or the vertical and horizontal limb of the diagonal band of Broca, or the substantia innominata, or in several of these structures. All three basal forebrain structures project heavily to allocortical regions, but only weakly to neocortical regions. An exception is the medial prefrontal cortex which is densily innervated by the substantia innominata (i.e., comparably dense as allocortical regions are innervated by the substantia innominata). Large injections into he basal temporal cortex (including the perirhinal cortex) and into the insular cortex also led to a considerable number of labeled cells in the substantia innominata. The results indicate a widespread innervation of the cat's cerebral cortex by the basal forebrain. This diffuse projection to the cortex has recently been found also in monkeys and rats. Anatomical and functional implications of these projections in the cat are discussed and related to findings in other species.     

Neuroimaging findings in Alzheimer's disease

In the present article, the neuroimaging findings in Alzheimer's disease are summarized and experimental data from animals relating to metabolic changes in Alzheimer's disease (AD), particularly in the frontobasal cholinergic projections onto the cerebral cortex, are reviewed. Changes in glucose metabolism as well as in cerebral blood flow (CBF) are specific for AD, in which the parietotemporal association cortex shows metabolic suppression. This finding is used as a diagnostic aid in the clinical application of single photon emission computed tomography. In rare cases, limited suppression of metabolism and blood flow is also found in the unilateral medial temporal lobe or parietal lobe. Statistically, approximately 80% of cases of AD show a typical parietotemporal suppression pattern of CBF. This cortical metabolic and circulatory suppression has been attributed to cholinergic deprivation from the basal forebrain Mynert nucleus. Animal experiments have revealed transient cortical suppression of glucose metabolism in the frontal cortex after destruction of the basal forebrain cholinergic neurons by ibotenic acid. This suppression persists for approximately 1 week and returns to normal 1 month after operation. Thus, the typical neuroimaging findings in AD would not be due to deficient cholinergic projections from the basal forebrain.     

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.     

Basal forebrain amnesia: does the nucleus accumbens contribute to human memory?

OBJECTIVE: To analyse amnesia caused by basal forebrain lesions. METHODS: A single case study of a patient with amnesia after bleeding into the anterior portion of the left basal ganglia. Neuropsychological examination included tests of attention, executive function, working memory, recall, and recognition of verbal and non-verbal material, and recall from remote semantic and autobiographical memory. The patient's MRI and those of other published cases of basal forebrain amnesia were reviewed to specify which structures within the basal forebrain are crucial for amnesia. RESULTS: Attention and executive function were largely intact. There was anterograde amnesia for verbal material which affected free recall and recognition. With both modes of testing the patient produced many false positive responses and intrusions when lists of unrelated words had been memorised. However, he confabulated neither on story recall nor in day to day memory, nor in recall from remote memory. The lesion affected mainly the nucleus accumbens, but encroached on the inferior limb of the capsula interna and the most ventral portion of the nucleus caudatus and globus pallidus, and there was evidence of some atrophy of the head of the caudate nucleus. The lesion spared the nucleus basalis Meynert, the diagnonal band, and the septum, which are the sites of cholinergic cell concentrations. CONCLUSIONS: It seems unlikely that false positive responses were caused by insufficient strategic control of memory retrieval. This speaks against a major role of the capsular lesion which might disconnect the prefrontal cortex from the thalamus. It is proposed that the lesion of the nucleus accumbens caused amnesia.     

Prefrontal cortical projections to the cholinergic neurons in the basal forebrain

The prefrontal cortex (PFC) projections to the basal forebrain cholinergic cell groups in the medial septum (MS), vertical and horizontal limbs of the diagonal band of Broca (VDB and HDB), and the magnocellular basal nucleus (MBN) in the rat were investigated by anterograde transport of Phaseolus vulgaris leuco-agglutinin (PHA-L) combined with acetylcholinesterase (AChE) histochemistry or choline acetyltransferase (ChAT) immunocytochemistry. The experiments revealed rich PHA-L-labeled projections to discrete parts of the basal forebrain cholinergic system (BFChS) essentially originating from all prefrontal areas investigated. The PFC afferents to the BFChS display a topographic organization, such that medial prefrontal areas project to the MS, VDB, and the medial part of the HDB, whereas the orbital and agranular insular areas predominantly innervate the HDB and MBN, respectively. Since the recurrent BFChS projection to the prefrontal cortex is arranged according to a similar topography, the relationship between the BFChS and the prefrontal cortex is characterized by reciprocal connections. Furthermore, tracer injections in the PFC resulted in anterograde labeling of numerous "en passant" and terminal boutons apposing perikarya and proximal dendrites of neurons in the basal forebrain, which were stained for the cholinergic marker enzymes. These results indicate that prefrontal cortical afferents make direct synaptic contacts upon the cholinergic neurons in the basal forebrain, although further analysis at the electron microscopic level will be needed to provide conclusive evidence.     

Fiber pathways of basal forebrain cholinergic neurons in monkeys

In rhesus monkeys, autoradiographic tracing methods, complemented by immunocytochemical and histochemical techniques, were used to delineate pathways by which cholinergic neurons of the nucleus basalis of Meynert (nbM) and nucleus of the diagonal band of Broca (ndbB) project to forebrain targets. Following injections of [3H]amino acids into these nuclei, 5 major fiber pathways were identified: axons of the nbM and ndbB project medially, principally within the cingulum bundle, to dorsomedial portions of the hemispheres; nbM and ndbB fibers exit laterally beneath the pallidum and striatum, enter the external and extreme capsules, and pass within the corona radiata to terminate in lateral and caudal regions of neocortex; axons coursing ventrally from the nbM project to portions of the temporal lobe, including the amygdala; some fibers pass through the fibrae pass orbitofrontales to the orbitofrontal cortex; and, finally axons of the nbM/ndbB project via the fimbria/rornix and a ventral pathway to the hippocampus. The presence of these 5 radiolabeled pathways arising from basal forebrain cholinergic neurons was confirmed by acetylcholinesterase histochemistry and choline acetyltransferase immunocytochemistry.     

Crossed unilateral lesions of temporal lobe structures and cholinergic cell bodies impair visual conditional and object discrimination learning in monkeys

Monkeys with excitotoxic lesions of the CA1/subiculum region in the right hemisphere and with immunotoxic lesions of the cholinergic cells of the diagonal band in the left hemisphere were impaired on a visual conditional task. In this task, correct choice of one of two objects depends on which of two background fields both objects are presented against, irrespective of the spatial positions of the objects. They were not impaired on simple object or shape discrimination tasks. The pattern of impairments is the same as that seen after bilateral excitotoxic lesions of CA1/subiculum, implying that the diagonal band lesion disables the ipsilateral CA1/subiculum. It also argues that CA1/subiculum, sustained by its cholinergic input, is necessary for some forms of nonspatial conditional learning. Addition of an inferotemporal (IT) cortical ablation to the left hemisphere did not affect simple visual discrimination learning, although all the monkeys then failed to learn a new visual conditional task. This demonstrates that intact IT cortex in only one hemisphere is sufficient to sustain simple visual discrimination learning but implies that the cholinergic input and the inferotemporal cortical input to the hippocampus both contribute to visual conditional learning. The subsequent addition of an immunotoxic lesion of the basal nucleus of Meynert in the right hemisphere resulted in an additional impairment on a difficult shape discrimination. This argues that it is the cholinergic projection to the inferotemporal cortex, rather than to the rest of the cortex, which contributes to visual discrimination learning and memory.     

Effects of Inferior Temporal Lesions on Two Types of Orientation Discrimination in the Macaque Monkey

Rhesus monkeys with transection of the forebrain commissures were trained in two different tasks in which grating orientation was the discriminandum. In the temporal same—different task, the monkeys had to judge whether or not two successively presented gratings differed in orientation. In the identification task, we measured how well the monkey could judge the orientation of the grating. The performance in any task was affected neither by a unilateral anterior temporal cortical area lesion nor by a subsequent posterior temporal cortical area lesion in the same hemisphere resulting in a two-stage inferior temporal (IT) lesion. However, a single stage IT (combined anterior and posterior temporal cortical areas) lesion of the other hemisphere severely disrupted the performance in the temporal same-different task, but only barely increased just noticeable differences in orientation in the identification task. This indicates that the impairment in a temporal comparison task after an IT lesion is not due to a perceptual coding deficit, but is related to the temporal comparison per se. Thus, IT is involved in the temporal comparison of successively presented stimuli. On the other hand, the two IT lesions, each having a different history (single versus two stage) had dramatically different behavioural effects, suggesting an important role for adult brain plasticity in determining the behavioural outcome of a brain lesion.