Subdivisions of auditory cortex and levels of processing in primates

In a series of experiments on New World and Old World monkeys, architectonic features of auditory cortex were related to tone frequency maps and patterns of connections to generate and evaluate theories of cortical organization. The results suggest that cortical processing of auditory information involves a number of functionally distinct fields that can be broadly grouped into four or more levels of processing. At the first level, there are three primary-like areas, each with a discrete pattern of tonotopic organization, koniocortical histological features, and direct inputs from the ventral division of the medial geniculate complex. These three core areas are interconnected and project to a narrow surrounding belt of perhaps seven areas which receive thalamic input from the major divisions of the medial geniculate complex, the suprageniculate/limitans complex, and the medial pulvinar. The belt areas connect with a lateral parabelt region of two or more fields that are almost devoid of direct connections with the core and the ventral division of the medial geniculate complex. The parabelt fields connect with more distant cortex in the superior temporal gyrus, superior temporal sulcus, and prefrontal cortex. The results indicate that auditory processing involves 15 or more cortical areas, each of which is interconnected with a number of other fields, especially adjoining fields of the same level.     

Topographic organization of connections between the hypothalamus and prefrontal cortex in the rhesus monkey

Prefrontal cortices have been implicated in autonomic function, but their role in this activity is not well understood. Orbital and medial prefrontal cortices receive input from cortical and subcortical structures associated with emotions. Thus, the prefrontal cortex may be an essential link for autonomic responses driven by emotions. Classic studies have demonstrated the existence of projections between prefrontal cortex and the hypothalamus, a central autonomic structure, but the topographic organization of these connections in the monkey has not been clearly established. We investigated the organization of bidirectional connections between these areas in the rhesus monkey by using tracer injections in orbital, medial, and lateral prefrontal areas. All prefrontal areas investigated received projections from the hypothalamus, originating mainly in the posterior hypothalamus. Differences in the topography of hypothalamic projection neurons were related to both the location and type of the target cortical area. Injections in lateral eulaminate prefrontal areas primarily labeled neurons in the posterior hypothalamus that were equally distributed in the lateral and medial hypothalamus. In contrast, injections in orbitofrontal and medial limbic cortices labeled neurons in the anterior and tuberal regions of the hypothalamus and in the posterior region. Projection neurons targeting orbital limbic cortices were more prevalent in the lateral part of the hypothalamus, whereas those targeting medial limbic cortices were more prevalent in the medial hypothalamus. In comparison to the ascending projections, descending projections from prefrontal cortex to the hypothalamus were highly specific, originating mostly from orbital and medial prefrontal cortices. The ascending and descending connections overlapped in the hypothalamus in areas that have autonomic functions. These results suggest that specific orbitofrontal and medial prefrontal areas exert a direct influence on the hypothalamus and may be important for the autonomic responses evoked by complex emotional situations.     

Dissociable forms of inhibitory control within prefrontal cortex with an analog of the Wisconsin Card Sort Test: restriction to novel situations and independence from "on-line" processing

Attentional set-shifting and discrimination reversal are sensitive to prefrontal damage in the marmoset in a manner qualitatively similar to that seen in man and Old World monkeys, respectively (Dias et al., 1996b). Preliminary findings have demonstrated that although lateral but not orbital prefrontal cortex is the critical locus in shifting an attentional set between perceptual dimensions, orbital but not lateral prefrontal cortex is the critical locus in reversing a stimulus-reward association within a particular perceptual dimension (Dias et al., 1996a). The present study presents this analysis in full and extends the results in three main ways by demonstrating that (1) mechanisms of inhibitory control and "on-line" processing are independent within the prefrontal cortex, (2) impairments in inhibitory control induced by prefrontal damage are restricted to novel situations, and (3) those prefrontal areas involved in the suppression of previously established response sets are not involved in the acquisition of such response sets. These findings suggest that inhibitory control is a general process that operates across functionally distinct regions within the prefrontal cortex. Although damage to lateral prefrontal cortex causes a loss of inhibitory control in attentional selection, damage to orbitofrontal cortex causes a loss of inhibitory control in affective processing. These findings provide an explanation for the apparent discrepancy between human and nonhuman primate studies in which disinhibition as measured on the Wisconsin Card Sort Test is associated with dorsolateral prefrontal damage, whereas disinhibition as measured on discrimination reversal is associated with orbitofrontal damage.     

Matching patterns of activity in primate prefrontal area 8a and parietal area 7ip neurons during a spatial working memory task

Single-unit recording studies of posterior parietal neurons have indicated a similarity of neuronal activation to that observed in the dorsolateral prefrontal cortex in relation to performance of delayed saccade tasks. A key issue addressed in the present study is whether the different classes of neuronal activity observed in these tasks are encountered more frequently in one or the other area or otherwise exhibit region-specific properties. The present study is the first to directly compare these patterns of neuronal activity by alternately recording from parietal area 7ip and prefrontal area 8a, under the identical behavioral conditions, within the same hemisphere of two monkeys performing an oculomotor delayed response task. The firing rate of 222 posterior parietal and 235 prefrontal neurons significantly changed during the cue, delay, and/or saccade periods of the task. Neuronal responses in the two areas could be distinguished only by subtle differences in their incidence and timing. Thus neurons responding to the cue appeared earliest and were more frequent among the task-related neurons within parietal cortex, whereas neurons exhibiting delay-period activity accounted for a larger proportion of task-related neurons in prefrontal cortex. Otherwise, the task-related neuronal activities were remarkably similar. Cue period activity in prefrontal and parietal cortex exhibited comparable spatial tuning and temporal duration characteristics, taking the form of phasic, tonic, or combined phasic/tonic excitation in both cortical populations. Neurons in both cortical areas exhibited sustained activity during the delay period with nearly identical spatial tuning. The various patterns of delay-period activity-tonic, increasing or decreasing, alone or in combination with greater activation during cue and/or saccade periods-likewise were distributed to both cortical areas. Finally, similarities in the two populations extended to the proportion and spatial tuning of presaccadic and postsaccadic neuronal activity occurring in relation to the memory-guided saccade. The present findings support and extend evidence for a faithful duplication of receptive field properties and virtually every other dimension of task-related activity observed when parietal and prefrontal cortex are recruited to a common task. This striking similarity attests to the principal that information shared by a prefrontal region and a sensory association area with which it is connected is domain specific and not subject to hierarchical elaboration, as is evident at earlier stages of visuospatial processing.     

In vivo assessment of basal and drug-induced dopamine release in cortical and subcortical regions of the anesthetized primate

There is an acute interest in studying the functional characteristics of dopamine systems in the cortex of primates. In particular, the prefrontal cortical dopamine projections have received a great deal of attention. This system is essential for proper functioning of the prefrontal cortex, and dysfunction within the system may be involved in some psychiatric and neurological illnesses. In vivo assessments of cortical dopamine in the primate have been scarce. This has been due, in part, to technical difficulties associated with these studies and with quantifying the relatively low levels of dopamine found in cortical regions. In the present study, intracerebral microdialysis was utilized to assess the extracellular concentration of dopamine in cortical and subcortical areas of the pentobarbital-anesthetized rhesus monkey. Basal extracellular dopamine levels were consistently detected in the medial prefrontal cortex, premotor cortex, and caudate-putamen. The basal extracellular concentration of dopamine in the dorsolateral prefrontal cortex was reliably detected in 1 of 4 animals. Intravenous administration of amphetamine (1 mg/kg) enhanced extracellular dopamine levels in the caudate-putamen area by more than 20-fold. In cortical areas, amphetamine's effect was less profound: An increase of 400-500 percent over basal extracellular dopamine levels was observed in each region. These studies demonstrate the feasibility of microdialysis for detecting extracellular fluxes of dopamine in the cortex of nonhuman primates. They further provide direct evidence that the dopamine released within the prefrontal cortex and the premotor cortex of nonhuman primates responds to pharmacological manipulation.     

Prefrontal control of conditioned suppression and associated cardiovascular variables in the monkey (Macaca mulatta).

Trained 17 male rhesus monkeys in a discriminated conditioned emotional responses paradigm. The discriminated conditioned response (CR) complex consisted of barpress suppression, increased terminal aortic blood flow, and increased arterial pressure. Barpress suppression and blood-flow responses were temporarily eliminated by single-stage bilateral prefrontal lobectomy but not by extensive posterior cortical ablation, 2-stage prefrontal lobe removal, or 3-stage prefrontal cortical surface ablation. The blood pressure CR was attenuated by almost every surgical operation. The changes in heart rate paralleled changes in general activity. Data indicate that the prefrontal lobes influenced the conditioned suppression of ongoing rewarded behavior and the vascular responses accompanying the suppression. The time course for recovery of the somatic CR after lobectomy differed from those of the cardiovascular CRs. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression

BACKGROUND: Lesion and neuroimaging studies suggest that left prefrontal lobe dysfunction is pathophysiologically linked to depression. Rapid-rate transcranial magnetic stimulation (rTMS) to prefrontal structures has a lateralised effect on mood in normal volunteers, and several preliminary studies suggest a beneficial effect of rTMS on depression. However, adequately controlled studies have not been conducted. METHODS: We have studied the effects of focal rTMS on the depressive symptoms in 17 patients with medication-resistant depression of psychotic subtype. The study was designed as a multiple cross-over, randomised placebo-controlled trial. Sham rTMS and stimulation of different cortical areas were used as controls. FINDINGS: Left dorsolateral prefrontal cortex rTMS resulted in a significant decrease in scores on the Hamilton depression rating scale HDRS (from 25.2 to 13.8) and the self-rated Beck questionnaire BQ (from 47.9 to 25.7). 11 of the 17 patients showed pronounced improvement that lasted for about 2 weeks after 5 days of daily rTMS sessions. No patient experienced any significant undesirable side-effects. INTERPRETATION: Our findings emphasise the role of the left dorsolateral prefrontal cortex in depression, and suggest that rTMS of the left dorsolateral prefrontal cortex might become a safe, non-convulsive alternative to electroconvulsive treatment in depression.     

Effects of selective neonatal hippocampal lesions on tests of object and spatial recognition memory in monkeys.

Earlier studies in monkeys have reported mild impairment in recognition memory after nonselective neonatal hippocampal lesions. To assess whether the memory impairment could have resulted from damage to cortical areas adjacent to the hippocampus, we tested adult monkeys with neonatal focal hippocampal lesions and sham-operated controls in three recognition tasks: delayed nonmatching-to-sample, object memory span, and spatial memory span. Further, to rule out that normal performance on these tasks may relate to functional sparing following neonatal hippocampal lesions, we tested adult monkeys that had received the same focal hippocampal lesions in adulthood and their controls in the same three memory tasks. Both early and late onset focal hippocampal damage did not alter performance on any of the three tasks, suggesting that damage to cortical areas adjacent to the hippocampus was likely responsible for the recognition impairment reported by the earlier studies. In addition, given that animals with early and late onset hippocampal lesions showed object and spatial recognition impairment when tested in a visual paired comparison task, the data suggest that not all object and spatial recognition tasks are solved by hippocampal-dependent memory processes. The current data may not only help explain the neural substrate for the partial recognition memory impairment reported in cases of developmental amnesia, but they are also clinically relevant given that the object and spatial memory tasks used in monkeys are often translated to investigate memory functions in several populations of human infants and children in which dysfunction of the hippocampus is suspected. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Dopamine innervation of a subclass of local circuit neurons in monkey prefrontal cortex: ultrastructural analysis of tyrosine hydroxylase and parvalbumin immunoreactive structures

The ability of dopamine to regulate the cognitive functions of the prefrontal cortex (PFC) involves complex modulatory actions on GABA-containing local circuit neurons in addition to pyramidal cells. However, the subclasses of cortical neurons that receive direct dopamine input are not known. We sought to determine whether dopamine terminals innervate the subclasses of local circuit neurons that contain the calcium-binding protein parvalbumin (PV), namely the wide arbor and chandelier neurons that target pyramidal cell soma and axon initial segments respectively. Sections through area 9 of five monkeys were labeled with immunoperoxidase for tyrosine hydroxylase (TH), to identify dopamine terminals, and with immunogold-silver for PV. Electron microscopic examination of the middle cortical layers (IIIb-IV) revealed that TH-positive terminals were sometimes directly apposed to PV-labeled dendrites, and approximately one-third of these contacts exhibited morphological features that are typically associated with symmetric synapses. In contrast, TH-immunolabeled terminals in the superficial layers (I-IIIa) were less frequently apposed to PV-positive dendrites, and none of these contacts exhibited synapse-like morphology. These findings, in concert with previous studies of GABA- or calretinin-containing local circuit neurons, suggest that dopamine's modulatory action in the PFC involves selective effects on only certain interneuron populations, including those that mediate potent inhibitory actions on pyramidal cells.     

The distribution of neurons in the substantia nigra pars reticulata with input from the motor, premotor and prefrontal areas of the cerebral cortex in monkeys

We investigated the distribution of neurons in the substantia nigra pars reticulata (SNr) which received cortical input. The activities of single SNr neurons were studied extracellulary in awake monkeys. SNr neurons showed excitatory and/or inhibitory responses to cortical stimulation. These responses were considered to be mediated by the subthalamic nucleus and striatum, respectively. The neurons receiving inhibitory input from the motor, premotor and supplementary motor areas (Motor-related cortical areas) were located in the lateral part of the SNr, whereas those with input from the medial, dorsal and orbital areas of the prefrontal cortex (PFmdo) were frequently found in the rostro-medial part of this nucleus. SNr neurons with inhibitory input from the ventral periprincipal area (PSv) were mainly distributed in the intermedio-lateral portion, with some degree of overlap with input from other cortical areas. The distribution of the excitatory input was almost similar to that of inhibitory one, but the excitatory input from the PSv was much stronger than that from the PFmdo. Some SNr neurons receiving cortical input were proved to project to the thalamus. Our results support the existence of several parallel organization of the cortico-basal ganglia loop circuits [G.E. Alexander, M.R. DeLong, P.L. Strick, Parallel organization of functionally segregated circuits linking basal ganglia and cortex, Ann. Rev. Neurosci., 9, 1986, pp. 357-381.], but interaction between the loops can not be ignored.     

Prefrontal cortex and rule abstraction: Where and whether? Theoretical comment on Moore et al. (2009).

The primate dorsolateral prefrontal cortex is implicated in diverse aspects of behavioral regulation, cognitive control, and memory. However, direct neuropsychological evidence supporting a requirement of this area in functions other than spatial working memory has been scarce. T. L. Moore, S. P. Schettler, R. J. Killiany, D. L. Rosene, and M. B. Moss (see record 2009-04037-001) have shown, for the first time, that lesions of dorsolateral prefrontal cortex in the rhesus monkey (including areas 9 and 46) substantially impair performance in a test of executive function modeled on the Wisconsin Card Sorting Task. The pattern of impairment is consistent with a role for dorsolateral prefrontal areas in rule abstraction but may relate to a role for this area in rule maintenance as well. Interestingly, monkeys with dorsolateral prefrontal lesions do not appear to perseverate in their use of particular rules in the task, different from the common impairment associated with frontal lobe damage in humans. These findings indicate that dorsolateral prefrontal cortex is necessary for some aspects of rule-guided behavior in the primate brain and help illuminate the involvement of different prefrontal areas in different aspects of executive function and rule-guided behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Primate analogue of the Wisconsin card sorting test: Effects of excitotoxic lesions of the prefrontal cortex in the marmoset.

Using a primate analogue of the Wisconsin Card Sort Test, this study demonstrated, for the first time, that lesions of the prefrontal cortex in monkeys produce a qualitatively similar impairment in attentional set-shifting to that seen following prefrontal cortical damage in humans. Although damage to the prefrontal cortex did not disrupt the ability of marmosets, a New World monkey, to maintain an attentional set, it did disrupt their ability to shift an attentional set. It also impaired their performance on discrimination reversal, object retrieval, and spatial delayed response, consistent with the effects of prefrontal damage in Old World monkeys. Comparison of the cognitive processes underlying discrimination reversal, object retrieval, and attentional set-shifting reveals the various types of inhibitory control provided by the prefrontal cortex. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contralateral cortical projection to the mediodorsal thalamic nucleus: origin and synaptic organization in the rat

The origin of the corticothalamic projections to the contralateral mediodorsal nucleus, the collateralization of cortical fibers and their synaptic organization in the ipsi- and contralateral mediodorsal nuclei were investigated in adult rats with double retrograde fluorescent and anterograde tracing. After tracer injections in the mediodorsal nuclei on either side, neurons were retrogradely labeled in all the areas of the contralateral prefrontal cortex in which ipsilateral labeling was also observed. Contralateral corticothalamic cells accounted for 15% of the labeled neurons in the orbital and agranular insular areas, while their proportion was lower (3%) in the anterior cingulate cortex. Up to 70% of the contralateral cortical neurons were double labeled by bilateral injections in the mediodorsal nuclei. At the electron microscopic level, unilateral injections of biotinylated dextran-amine in the orbitofrontal cortex resulted in anterograde labeling of small terminals and a few large boutons in the ipsilateral mediodorsal nucleus, while only small boutons were identified contralaterally. The diameter of postsynaptic dendritic profiles contacted by labeled small cortical endings was significantly larger in the ipsilateral mediodorsal nucleus than contralaterally. These findings demonstrate that dense contralateral cortical projections to the mediodorsal nucleus derive from the orbital and agranular insular areas, and that crossed corticothalamic afferents are mostly formed by collaterals of the ipsilateral connections. Our observations also point out the heterogeneity of corticothalamic boutons in the rat mediodorsal nucleus and morphological differences in the synaptic organization of prefrontal fibers innervating the two sides, indicating that ipsilateral cortical afferents may be more proximally distributed than crossed cortical fibers on dendrites of mediodorsal neurons.     

Increase of extracellular dopamine in primate prefrontal cortex during a working memory task

Increase of extracellular dopamine in primate prefrontal cortex during a working memory task. J. Neurophysiol. 78: 2795-2798, 1997. The dopamine innervation of the prefrontal cortex is involved importantly in cognitive processes, such as tested in working memory tasks. However, there have been no studies directly investigating prefrontal dopamine levels in relation to cognitive processes. We measured frontal extracellular dopamine concentration using in vivo microdialysis in monkeys performing in a delayed alternation task as a typical working memory paradigm and in a sensory-guided control task. We observed a significant increase in dopamine level in the delayed alternation task as compared both with the sensory-guided control task and the basal resting level. The increase was seen in the dorsolateral prefrontal but not in the arcuate or orbitofrontal areas. The increase appeared to reflect the working memory component of the task and was observed mainly in the lip areas of principal sulcus. Although there was no significant difference in dopamine level between delayed alternation and sensory-guided control tasks in the premotor area, significant increases in dopamine concentration were observed during both tasks as compared with the basal resting level, indicating the importance of premotor dopamine for the motor response itself.     

Cortical pathways to the mammalian amygdala

The amygdaloid nuclear complex is critical for producing appropriate emotional and behavioral responses to biologically relevant sensory stimuli. It constitutes an essential link between sensory and limbic areas of the cerebral cortex and subcortical brain regions, such as the hypothalamus, brainstem, and striatum, that are responsible for eliciting emotional and motivational responses. This review summarizes the anatomy and physiology of the cortical pathways to the amygdala in the rat, cat and monkey. Although the basic anatomy of these systems in the cat and monkey was largely delineated in studies conducted during the 1970s and 1980s, detailed information regarding the cortico-amygdalar pathways in the rat was only obtained in the past several years. The purpose of this review is to describe the results of recent studies in the rat and to compare the organization of cortico-amygdalar projections in this species with that seen in the cat and monkey. In all three species visual, auditory, and somatosensory information is transmitted to the amygdala by a series of modality-specific cortico-cortical pathways ("cascades") that originate in the primary sensory cortices and flow toward higher order association areas. The cortical areas in the more distal portions of these cascades have stronger and more extensive projections to the amygdala than the more proximal areas. In all three species olfactory and gustatory/visceral information has access to the amygdala at an earlier stage of cortical processing than visual, auditory and somatosensory information. There are also important polysensory cortical inputs to the mammalian amygdala from the prefrontal and hippocampal regions. Whereas the overall organization of cortical pathways is basically similar in all mammalian species, there is anatomical evidence which suggests that there are important differences in the extent of convergence of cortical projections in the primate versus the nonprimate amygdala.     

Temporal dynamics of brain activation during a working memory task

Working memory is responsible for the short-term storage and online manipulation of information necessary for higher cognitive functions, such as language, planning and problem-solving. Traditionally, working memory has been divided into two types of processes: executive control (governing the encoding manipulation and retrieval of information in working memory) and active maintenance (keeping information available 'online'). It has also been proposed that these two types of processes may be subserved by distinct cortical structures, with the prefrontal cortex housing the executive control processes, and more posterior regions housing the content-specific buffers (for example verbal versus visuospatial) responsible for active maintenance. However, studies in non-human primates suggest that dorsolateral regions of the prefrontal cortex may also be involved in active maintenance. We have used functional magnetic resonance imaging to examine brain activation in human subjects during performance of a working memory task. We used the temporal resolution of this technique to examine the dynamics of regional activation, and to show that prefrontal cortex along with parietal cortex appears to play a role in active maintenance.     

Introduction to the special section on “translational models of prefrontal cortical function”.

Impaired functioning of the prefrontal cortex is particularly prominent in many forms of psychopathology and in degenerative brain diseases. Because it is challenging to draw causal links between specific brain abnormalities and impaired cognition in these conditions, research using nonhuman animals has a key role to play in elucidating the neurobiological mechanisms of prefrontal cortex function and aiding the search for treatments. This role is clearly illustrated in the review articles and original research reports in this special section. Taken together, these papers demonstrate the insights that have already been gained from research with nonhuman animals as well as the work that still needs to be done to attain the goal of understanding human prefrontal cortical function in both health and disease. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Episodic multiregional cortical coherence at multiple frequencies during visual task performance

The way in which the brain integrates fragmentary neural events at multiple locations to produce unified perceptual experience and behaviour is called the binding problem. Binding has been proposed to involve correlated activity at different cortical sites during perceptuomotor behaviour, particularly by synchronization of narrow-band oscillations in the gamma-frequency range (30-80 Hz). In the rabbit olfactory system, inhalation induces increased gamma-correlation between sites in olfactory bulb and cortex. In the cat visual system, coherent visual stimuli increase gamma-correlation between sites in both the same and different visual cortical areas. In monkeys, some groups have found that gamma-oscillations transiently synchronize within striate cortex, superior temporal sulcus and somatosensorimotor cortex. Others have reported that visual stimuli produce increased broad-band power, but not gamma-oscillations, in several visual cortical areas. But the absence of narrow-band oscillations in itself does not disprove interregional synchronization, which may be a broad-band phenomenon. We now describe episodes of increased broad-band coherence among local field potentials from sensory, motor and higher-order cortical sites of macaque monkeys performing a visual discrimination task. Widely distributed sites become coherent without involving other intervening sites. Spatially selective multiregional cortical binding, in the form of broad-band synchronization, may thus play a role in primate perceptuomotor behaviour.     

Madagascar: esophagogastroduodenoscopy. Descriptive analysis of 12,000 examinations and problems encountered in the tropics

Regional cerebral blood flow was measured with H2(15)O-positron emission tomography during the performance of visually presented calculation tasks to clarify cortical areas involved in arithmetic operations. The findings on a calculation task were compared with those on a covert reading task and with those of a fixation control task. Region of interest-based analysis showed that the left prefrontal area was activated in visual calculation relative to covert reading and the posterior superior temporal gyrus including part of Wernicke's area was activated in calculation relative to fixation control. The role of the prefrontal area in computation (arithmetic operations) and that of the posterior superior temporal gyrus in both comprehension of the stimuli and computation were suggested.     

Animal models of prefrontal-executive function.

Executive function allows us to interact with the world in a purposive, goal-directed manner. It relies on several cognitive control operations that are mediated by different regions of the prefrontal cortex. While much of our knowledge about the functional subdivisions of the prefrontal cortex comes from the systematic assessment of patients with brain damage, animal models have served as the predominant tool for investigating specific structure–function relationships within the prefrontal cortex, especially as they relate to complex executive behaviors. These studies generally involve the targeted disruption of neural circuits combined with behavioral testing using carefully designed cognitive paradigms. In this review, I will describe a broad range of such experiments conducted in rats and monkeys that together reveal the distinct contributions of dorsal, medial, and ventral prefrontal cortex to different aspects of executive function. The effects of lesions and local pharmacological manipulations have provided valuable insights into the neural underpinnings of executive function and its neurochemical modulation. Despite the challenges associated with establishing a precise homology between animal models of prefrontal function and the human brain, such models currently offer the best means to systematically investigate the cognitive building blocks of executive function. This helps define the neural circuits that lead to a range of neurological and psychiatric disorders and facilitate the development of effective therapeutic strategies to ameliorate the associated cognitive impairments. (PsycINFO Database Record (c) 2011 APA, all rights reserved)