Delayed Non-matching To Position Research Articles

Exercise influences spatial learning in the radial arm maze

Previous studies indicate that the hippocampus is active during exercise, and that neurotrophin expression, receptor density, and survival of dentate gyrus granule cells in the hippocampus can be modified by moderate voluntary exercise. The present study was designed to test the consequences of voluntary exercise on a hippocampal-related behavior. Exercising and control rats were tested on the standard and delayed nonmatch-to-position (DNMTP) version of the eight-arm radial maze, both of which are sensitive to hippocampal damage. Voluntarily exercising rats ran in running wheels attached to their home cage for 7 weeks prior to and throughout testing, and took 30% fewer trials to acquire criterion performance than sedentary controls. Both groups spent the same average time per arm. Once the eight-arm maze had been learned to criterion, group differences were not apparent. Exercise can facilitate acquisition of a hippocampal-related spatial learning task, but does not affect performance following acquisition. Further work will be necessary to link these effects to hippocampal-related variables shown to be influenced by exercise.

Effects of nitric oxide synthase inhibitors on timing and short-term memory in rats.

Nitric oxide synthase (NOS) inhibitors have been shown to affect the development of long-term potentiation and the acquisition of new learning. In the present study, we investigated the effects of NOS inhibitors in two animal models in which aspects of cognition are measured in well-learned operant tasks - a delayed non-match-to-position (DNMTP) task and a multiple signalled-unsignalled differential reinforcement of low rates (DRL) 15 s schedule - models of short-term memory and behavioral inhibition/timing, respectively. Since an overlap in the behavioral effects of NOS inhibitors and phencyclidine (PCP)-like N-methyl-D-aspartate (NMDA) antagonists has been observed previously, we compared our results with NOS inhibitors to those obtained with PCP. Whereas PCP produced a delay-independent decrease in the DNMTP task and increased burst responding (consecutive responses with inter-response intervals of < 3 s) in both the signalled and unsignalled components of the DRL procedure, 7-nitroindazole did not affect accuracy in the DNMTP task nor did it alter the pattern of responding in either component of the DRL schedule. Similarly, NG-nitro-L-arginine (L-NOARG) and NG-nitro-L-arginine-methyl-ester (L-NAME) did not affect accuracy in the DNMTP task. These results suggest that NOS inhibitors do not produce PCP-like disruption of behavioral inhibition or timing, nor do they decrease accuracy in a conditional discrimination task, as has been observed with PCP. The present results lend further support to the hypothesis that nitric oxide modulation does not affect retention of well-learned tasks, although it may affect acquisition of novel behavior.

Specificity of memory measures in an adjusting delayed nonmatching-to-position task for rats

While the delayed nonmatching-to-position (DNMTP) behavioral paradigm has often been used by neuroscientists to assess working memory in rats, its measure of working memory is compromised by floor and ceiling effects. Specifically, these floor and ceiling effects undermine the ability to detect a significant interaction in a two-factor repeated-measures ANOVA, which is required in order to conclude that impaired performance has resulted from disrupted working memory and not from a change in another psychological process (i.e. that the impairment is ‘specific’ to working memory). The present study was conducted to evaluate if these limitations could be overcome in a DNMTP by adjusting the length of time that the rat was required to remember (the ‘delay’) so as to avoid the floor and ceiling. The general procedure for two experiments presented subjects with trials where there was either a minimal (1 s) delay or a longer delay of varying length, with the goal of maintaining nonmatch-to-position accuracy near 75%. The procedure was such, that if the average accuracy was at or above 75%, then the next trial would be a long-delay trial. If it were below 75%, then the next trial would be a 1 s delay trial. In the first experiment, the subjects were presented with trials where the value of the longer delay was systematically varied between-sessions. This was done to simulate the faster rate of forgetting found in persons with amnesia. DNMTP accuracy diminished at the longer delay but not the short delay as the second interval was lengthened. However, other measures, including accuracy at the 1 s delay, discrimination accuracy during the sample phase, and the number of trials completed per session, did not change. This experiment suggested that this DNMTP could precisely measure small changes in the rate of forgetting. In a second experiment, a potential non-mnemonic confound, the level of motivation, was directly manipulated by giving the water-restricted subjects access to water immediately prior to the start of the session. The number of trials completed per session diminished, but the accuracy at both the 1 s and the longer delays did not change. These results indicated that the measures of working memory in this DNMTP were insensitive to changes in motivation. Together, these experiments confirmed that adjusting the delay in the DNMTP improves the validity of the measures in this task.

Use of a delayed non-matching to position task to model age-dependent cognitive decline in the dog

Spatial learning and memory in young and old dogs was studied in a series of experiments using a delayed non-matching to position (DNMP) paradigm. Past research from our laboratory has suggested that aged dogs perform more poorly on a version of the DNMP task compared to young dogs [Head et al., Spatial learning and memory as a function of age in the dog, Behav. Neurosci. 1995;109(5):851–585]. We have now extended these findings by testing a large number of dogs on three different variations of the DNMP paradigm to evaluate different aspects of spatial learning and memory. Our results indicate that: (1) aged dogs show impaired spatial learning compared to young dogs, (2) aged dogs display spatial working memory deficits compared to young dogs, (3) young dogs have a greater maximum working spatial memory capacity than old dogs and (4) we can use the DNMP paradigm to cognitively categorize different subsets of aged dogs. These data indicate that the DNMP paradigm can serve as a valuable tool to evaluate age-dependent cognitive dysfunction in the canine.

The acetylcholinesterase inhibitor, ENA 713 (Exelon), attenuates the working memory impairment induced by scopolamine in an operant DNMTP task in rats.

The disruption of working memory in the delayed non-matching to position (DNMTP) task by the muscarinic antagonist, scopolamine, is considered to be a model of the spatial working memory deficit in Alzheimer's disease (AD) patients. To investigate whether ENA 713 (Exelon) (0.1, 0.5 mg/kg, IP), an acetylcholinesterase inhibitor, would reverse the effects of scopolamine in the DNMTP task. Male Lister Hooded rats were trained to criterion in an operant DNMTP task (0- to 16-s delay intervals) before receiving vehicle, scopolamine (0.05 mg/kg, SC) alone, ENA 713 (0.1, 0.5 mg/kg, IP) alone, or combinations of scopolamine and ENA 713, in two variations of the task - with and without barriers inserted between the food magazine and the two levers. Barriers were inserted to prevent the use of positional strategies to perform the task, since this behaviour may confound the conclusions of the effect of drugs on working memory. It was found that: (i) scopolamine significantly reduced choice accuracy delay-dependently in both test situations while modifying non-mnemonic measures of task performance delay-independently, indicating an impairment of working memory; (ii) ENA 713 (0.5 mg/kg) significantly attenuated the scopolamine-induced impairment of working memory and significantly reduced the scopolamine-induced changes in some non-mnemonic measures of task performance; (iii) the presence of barriers did not alter the effects of scopolamine and ENA 713 on working memory. ENA 713 reversed the working memory deficit induced by scopolamine. These results are consistent with the attenuation of learning and memory disruptions due to cholinergic dysfunction by ENA 713 in other preclinical assays, and predict a drug-induced improvement in working memory in AD patients.

Detecting drug effects on short-term memory function using a combined delayed matching and non-matching to position task

Operant delayed non-matching-to-position (DNMTP) and delayed matching-to-position (DMTP) have become standard techniques to investigate drug effects on short-term memory function in rats. However, these two tasks are normally conducted in isolation. Using two standard drugs, the 5HT1 A agonist 8-hydroxy-2-(di- n-propylamino)tetralin (8-OH-DPAT), and the muscarinic antagonist scopolamine, this study looked at a two-choice operant task that essentially involved a mixed DNMTP/DMTP paradigm. Thus, DNMTP trials were interspersed with DMTP trials in a random sequence for the duration of a session. 8-OH-DPAT (0.03 mg/kg) slightly but significantly improved response accuracy in a delay-dependent fashion during DMTP but not DNMTP trials. The highest dose of 8-OH-DPAT (0.1 mg/kg) impaired accuracy during DNMTP trials independent of delay and had no significant effect during DMTP trials. Scopolamine (0.1 mg/kg) produced delay-dependent deficits in accuracy during DMTP trials but delay-independent impairments during DNMTP trials. Because both 8-OH-DPAT and scopolamine produced delay-dependent effects with DMTP trials types and either had no effect (8-OH-DPAT) or produced delay-independent impairments (scopolamine) during DNMTP trials types, it is suggested that DMTP trials had a greater dependence on short-term working memory function than DNMTP trials that probably relied more on positional (mediating) strategies for solving the task. Therefore, we believe that this mixed DNMTP/DMTP task offers greater potential for more reliable and discerning interpretation of data regarding short-term memory function in rodents than either of the paradigms performed in isolation.

Coadministration of Galanin Antagonist M40 with a Muscarinic M1Agonist Improves Delayed Nonmatching to Position Choice Accuracy in Rats with Cholinergic Lesions

The neuropeptide galanin is overexpressed in the basal forebrain in Alzheimer's disease (AD). In rats, galanin inhibits evoked hippocampal acetylcholine release and impairs performance on several memory tasks, including delayed nonmatching to position (DNMTP). Galanin(1-13)-Pro2-(Ala-Leu)2-Ala-NH2 (M40), a peptidergic galanin receptor ligand, has been shown to block galanin-induced impairment on DNMTP in rats. M40 injected alone, however, does not improve DNMTP choice accuracy deficits in rats with selective cholinergic immunotoxic lesions of the basal forebrain. The present experiments used a strategy of combining M40 with an M1 cholinergic agonist in rats lesioned with the cholinergic immunotoxin 192IgG-saporin. Coadministration of intraventricular M40 with intraperitoneal 3-(3-S-n-pentyl-1,2,5-thiadiazol-4-yl)-1,2,5, 6-tetrahydro-1-methylpyridine (TZTP), an M1 agonist, improved choice accuracy significantly more than a threshold dose of TZTP alone. These results suggest that a galanin antagonist may enhance the efficacy of cholinergic treatments for the cognitive deficits of AD.

Microinjection of GABA-A agonist muscimol into the dorsal but not the ventral hippocampus impairs non-mnemonic measures of delayed non-matching-to-position performance in rats

Anatomical studies of afferent and efferent connections suggest that the hippocampus may have more than one information processing role that varies along the septo–hippocampal axis. The present study was conducted to test whether a distinct functional specialization for the dorsal versus ventral extents of the hippocampus could be detected. The effects of a GABA-A receptor agonist, muscimol, microinjected into either the dorsal or ventral hippocampus on an operant, spatial delayed non-matching-to-position (DNMTP) task were measured. A decrease in the number of trials completed per session and disruption of several DNMTP discrimination parameters were produced by muscimol microinjected into the dorsal hippocampus but not into the ventral hippocampus. Muscimol injected into either site did not impair the measure of working memory, delayed choice accuracy. These results are consistent with the view that hippocampal function varies along the septo–temporal axis, and that the dorsal hippocampus is relatively more critical to visual discrimination performance than the ventral hippocampus.

Analysis of the automated delayed nonmatching-to-position task: The effects of changing contiguity between stimulus, response and reinforcement, and of providing a salient spatial cue within the apparatus

The present report examines two factors that may affect the acquisition and performance of a delayed nonmatching to position (DNMP) task. Both of these concern the design and layout of the apparatus. The first is the contiguity between stimulus, response and reinforcement while the second concerns the impact of asymmetry within the behavioural apparatus. In the standard version of the task, food rewards are dispensed at a central well, equidistant from the stimuli to be discriminated and from the site of the animals' responses. The present experiment demonstrated that acquisition of the task is significantly quicker when there is greater continguity between the stimuli and rewards i.e. when rats are reinforced in the same location as where they respond. We also studied the potential impact of the fact that the standard two-lever operant chamber is asymmetrical as the transparent access door is typically at the side of the box i.e. adjacent to one lever. By comparing test chambers with or without single Plexiglas walls we found clear evidence that the door/wall provides a salient cue that aids DNMP performance. This casts light on the nature of the actual memory demands in the DNMP task.

Pharmacological models of amnesia: A reexamination of the effects of cholinergic muscarinic antagonist scopolamine and NMDA-receptor antagonist MK-801 on delayed nonmatching-to-position in rats

Cholinergic muscarinic receptor antagonist scopolamine and glutamatergic NMDA receptor antagonist MK-801 have been used as pharmacological agents to assess the contributions of their respective neurotransmitter systems to memory processing, but they produce sedative and motor disruption that may mask effects on memory measures. To explore the influence of these nonspecific effects on delayed nonmatching-to-position (DNMTP), the effects of scopolamine were compared with those of MK-801 on a DNMTP paradigm modified to simultaneously assess discrimination and working memory. Both scopolamine and MK-801 produced significant reductions in rate at which trials were completed, largely accounted for in the case of scopolamine by a failure in responding to the sample stimulus. Scopolamine also produced an increase in position bias and increased responding on a random-ratio schedule during the retention interval. MK-801 produced no effects on these measures. Neither drug produced significant effects on DNMTP choice accuracy, the measure of working memory. These results suggest that effects on nonmnemonic behavioral parameters may have contributed to previously reported working memory disruptions.

Differential effects on delayed non-matching-to-position in rats of microinjections of muscarinic receptor antagonist scopolamine or NMDA receptor antagonist MK-801 into the dorsal or ventral extent of the hippocampus

Glutamatergic NMDA and cholinergic muscarinic receptors are thought to contribute to cognitive processes mediated by the hippocampus. Evidence from lesion studies suggests that, despite cytoarchitectural uniformity within the hippocampus, information processing may not be uniform along the septo-temporal axis. The present study examined whether blockade of NMDA or muscarinic receptors in hippocampal subregions produced regional dissociations in the disruption of performance on an operant, spatial delayed non-matching-to-position (DNMTP) paradigm that also assessed vigilance. Rats were extensively pretrained on DNMTP, then bilaterally cannulated into either the dorsal or ventral hippocampus. Following retraining, scopolamine or MK-801 were administered prior to sessions. MK-801 administered into dorsal hippocampus produced delay-independent deficits in DNMTP delayed choice. Neither scopolamine administered into the dorsal or ventral hippocampus, nor MK-801 administered into the ventral hippocampus, produced significant disruption of DNMTP delayed choice. However, some dissociations were evident in other measures of vigilance. Scopolamine into the dorsal and ventral hippocampus increased errors of omission, scopolamine into the ventral hippocampus decreased sample response accuracy, and MK-801 into the dorsal hippocampus decreased sample response accuracy and increased response bias. These results are consistent with the suggestion that subregions of the hippocampus may be involved in different aspects of information processing and also suggest that the cholinergic inputs to the hippocampus may be functionally independent of NMDA receptor-mediated neurotransmission.

Analysis of galanin and the galanin antagonist M40 on delayed non-matching-to-position performance in rats lesioned with the cholinergic immunotoxin ¹⁹²IgG-Saporin.

Galanin is a 29-amino-acid neuropeptide that is overexpressed in Alzheimer's disease (AD) and impairs performance on rodent learning and memory tasks. M40, a peptidergic galanin receptor ligand, blocks galanin-induced impairments on delayed non-matching-to-position (DNMTP). The present experiments used the 192IgG-saporin lesion model of AD to evaluate the actions of galanin and M40 on DNMTP when cholinergic transmission was reduced. Hippocampal choline acetyltransferase levels were correlated with DNMTP choice accuracy in lesioned rats. Intracerebroventricular (icv) galanin reduced choice accuracy in both the lesioned and sham groups. M40 alone, either icv or intrahippocampal, did not affect choice accuracy in either group. These results suggest that excess galanin can produce further deficits in DNMTP performance in a lesion model of AD, but blocking endogenous galanin is not sufficient alone to improve performance in lesioned rats.

Differential effects of three 5-HT receptor antagonists on the performance of rats in attentional and working memory tasks

The effects of three different serotonin (5-HT) receptor antagonists (ketanserin, methysegide, methiothepin) in the modulation of attention, working memory and behavioural activity were investigated in this study by assessing the performance of rats in two separate cognitive models; the 5-choice serial reaction time (5-CSRT) task, which measures attention, and the delayed non-matching to position (DNMTP) task, which measures working memory. Methysergide and methiothepin bind at the 5-HT 1 and 5-HT 2 as well as the 5-HT 5–7 receptors, with varying degrees of selectivity, and ketanserin binds at the 5-HT 2A receptors rather selectively. None of these agents bind to any significant extent to 5-HT 3 or 5-HT 4 receptors. In the 5-CSRT task, neither methiothepin (0.15 mg/kg) nor ketanserin (1.0 and 3.0 mg/kg) impaired the choice accuracy of rats, although they induced sedation. The low doses of methysergide (1.5 and 3.0 mg/kg) slightly increased the behavioural activity of rats, whereas the high dose of methysergide (15.0 mg/kg) reduced behavioural activity and slightly reduced choice accuracy of the rats in the attentional task (monitoring of visual stimuli) under the baseline conditions or curtailed stimulus duration. This effect was not augmented at the reduced stimulus intensity. These findings suggest that the high dose of methysergide did not interfere with the visual discrimination of rats. Furthermore, methysergide did not reduce motivation for this task, since it did not increase food collection latencies. In the DNMTP task, methiothepin (0.15 mg/kg) induced a delay non-dependent deficit in choice accuracy. This could be due to an impaired alternation ability or akinesia, which increases an actual delay between sample and choice. Methiothepin (0.15 mg/kg) also interfered with behavioural activity of rats. Interestingly, ketanserin (1.0 mg/kg and 3.0 mg/kg) and methysergide (3.0–15.0 mg/kg) neither impaired the choice accuracy nor reduced the behavioural activity of rats in the DNMTP task. These results suggest that the blockade of 5-HT 2A receptors does not interfere with attention and working memory per se. However, all three serotonin receptor antagonists interfered with behavioural activity of rats in the 5-CSRT task more severely than in the DNMTP task. The possible role of serotonin and non-serotonin receptors underlying the influence of these antagonists on behavioural activity will be discussed.

Contrasting effects of systemic and intracerebral infusions of the 5-HT 1A receptor agonist 8-OH-DPAT on spatial short-term working memory in rats

The present study compared the effects of systemic 8-OH-DPAT (0.05, 0.1 and 1.0 mg/kg) with intra-raphe and intra-hippocampul infusions of 8-hydroxy-2-(di- n-propylamino)tetralin (8-OH-DPAT) (10, 30 100 ng) on delayed non-matching-to-position (DNMP) performance in rats. The highest dose of 8-OH-DPAT administered systemically impaired DNMP performance in a delayindependent manner, increased premature responding and increased response bias. Infusions of 8-OH-DPAT (100 ng) into the median raphé nucleus improved performance accuracy, independent of delay whilst having no effect on any other response measure. Infusions of 8-OH-DPAT into the dorsal raphe nucleus had no effect on performance at any dose tested. Infusions of 8-OH-DPAT into the dorsal hippocampus produced a small impairment in performance which was also independent of delay. However, this decrement in performance accuracy was not accompanied by any changes in other response measures. These findings demonstrate a dissociation between the effects of stimulation of pre- and post-synaptic 5-HTIA receptors on performance of a DNMP task although the changes in performance cannot be accounted for by changes in mnemonic function.

Analysis of galanin and the galanin antagonist M40 on delayed non-matching-to-position performance in rats lesioned with the cholinergic immunotoxin 192 IgG-saporin.

Galanin is a 29-amino-acid neuropeptide that is overexpressed in Alzheimer's disease (AD) and impairs performance on rodent learning and memory tasks. M40, a peptidergic galanin receptor ligand, blocks galanin-induced impairments on delayed non-matching-to-position (DNMTP). The present experiments used the 192IgG-saporin lesion model of AD to evaluate the actions of galanin and M40 on DNMTP when cholinergic transmission was reduced. Hippocampal choline acetyltransferase levels were correlated with DNMTP choice accuracy in lesioned rats. Intracerebroventricular (icv) galanin reduced choice accuracy in both the lesioned and sham groups. M40 alone, either icv or intrahippocampal, did not affect choice accuracy in either group. These results suggest that excess galanin can produce further deficits in DNMTP performance in a lesion model of AD, but blocking endogenous galanin is not sufficient alone to improve performance in lesioned rats.

Effect of a thyrotrophin-releasing hormone analogue, RX77368, on AMPA-induced septal-hippocampal lesioned rats in an operant delayed non-matching to position test

The aim of the present study was to determine the effect of a thyrotrophin-releasing hormone (TRH) analogue, RX77368, on performance of a working memory test, using a delayed non-matching to position (DNMTP) procedure, in (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-induced septal-hippocampal lesioned rats. Following a post-surgery recovery period, pretrained rats were tested once daily on DNMTP, 30 min post-administration of RX77368 (1.0 mg kg-1, i.p.) or saline. AMPA-induced lesions significantly reduced percent correct responses during the second week of testing. Comparison of percent correct responses between days 1 and 13 of testing showed that sham rats significantly improved DNMTP performance, whereas lesioned rats did not. RX77368 significantly reduced general locomotor activity in sham rats in activity boxes, but did not disrupt non-mnemonic measures, such as locomotion and motivation, in the DNMTP test. RX77368 increased percent correct responses in AMPA-lesioned rats on days 8-10 and 11-13. There was also a significant improvement in percent correct responses achieved between day 1 and 13 in RX77368-treated lesioned and sham rats. These results showed that: (i) septal-hippocampal lesioned rats did not improve over the testing period; and (ii) on test days when a significant impairment was present, RX77368 partially improved DNMTP performance.

192IgG-Saporin immunotoxin and ibotenic acid lesions of nucleus basalis and medial septum produce comparable deficits on delayed nonmatching to position in rats

The recently developed immunotoxin, 192IgG-Saporin (192-SAP), was compared with the standard excitotoxin, ibotenic acid, on two measures: (1) the extent of deficits on performance of a working memory task, delayed nonmatching-to-position (DNMTP), and (2) sensitivity to scopolamine on this task. Rats were extensively pretrained in an operant, spatial DNMTP memory task, then given combined site-specific lesions of the medial septum/diagonal band and nucleus basalis magnocellularis using either ibotenic acid (IBO) or low doses of the selective cholinergic immunotoxin 192-SAP. When compared with sham controls, both IBO and 192-SAP lesioned rats showed significant delay-independent reductions in DNMTP choice accuracy. Both 192-SAP and IBO lesioned rats showed increased sensitivity to a threshold dose of scopolamine, 0.15 mg/kg i.p., on DNMTP, as compared with sham-lesioned controls. When the rats were assessed at 18 weeks postlesioning, levels of choline acetyltransferase were depleted in the hippocampus in both IBO and 192-SAP lesioned groups. These findings suggest that 192-SAP, a cholinergically selective neurotoxin, is as effective as an excitotoxin when microinjected into cholinergic cell bodies of the basal forebrain, producing deficits in behavioral tasks that persist for several weeks.

Galanin receptor antagonist M40 blocks galanin-induced choice accuracy deficits on a delayed-nonmatching-to-position task.

Galanin is a 29-amino acid neuropeptide that coexists with acetylcholine in the medial septum/diagonal band in the rat and impairs choice accuracy on an operant delayed-nonmatching-to-position (DNMTP) working-memory task. M40, a peptidergic galanin antagonist, has previously been shown to block several physiological actions of galanin. The present experiments tested the ability of M40 to block the effects of galanin on DNMTP performance. M40 completely blocked choice-accuracy deficits induced by galanin administration in both the lateral ventricle and ventral hippocampus, at doses of M40 approximately 5-fold the molar dose of galanin. M40 appears to be an effective galanin antagonist in a rodent memory paradigm, indicating that this compound may prove useful in investigating the role of endogenous galanin in learning and memory.

A comparison of the effects of medial prefrontal, cingulate cortex, and cingulum bundle lesions on tests of spatial memory: evidence of a double dissociation between frontal and cingulum bundle contributions

Rats were trained on an automated delayed nonmatching-to-position (DNMP) task. They then received cytotoxic lesions in either the medial prefrontal cortex (n = 13) or the cingulate and retrosplenial cortices (n = 8), or radiofrequency lesions in either the fornix (n = 6) or the cingulum bundle (n = 8). Twelve animals served as surgical controls. Only the fornical and medial prefrontal lesions disrupted DNMP performance, both groups showing a loss of accuracy and an increase in bias. The rats were then trained on a lever discrimination and reversal task, the medial prefrontal and fornical groups showing evidence of an increase in bias when compared with the cingulate cortex group. Finally, the rats were trained on a forced alternation task in a T-maze. Marked deficits were observed in the fornix and cingulum bundle groups, but the medial prefrontal and cingulate groups were unimpaired. The double dissociation between the effects of the prefrontal and cingulum bundle lesions highlights the very different nature of the two spatial tasks (DNMP and T-maze alternation), even though both involved a nonmatching rule. These findings may reflect the involvement of divergent outputs from the fornix-anterior thalamic pathway. One possibility is that anterior thalamic projections to the medial prefrontal cortex are concerned with processing egocentric information, while anterior thalamic projections to temporal regions via the cingulum bundle are concerned with allocentric information. The results also indicate that the effects of conventional lesions in the cingulate cortex and medial prefrontal cortex may be compromised by additional damage to the cingulum bundle.