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No change in the density of the serotonin1A receptor, the serotonin4 receptor or the serotonin transporter in the dorsolateral prefrontal cortex from subjects with schizophrenia.

Changes in serotonin receptors and the serotonin transporter have been reported in the dorsolateral prefrontal cortex from subjects with schizophrenia, an area of the brain thought to be important in the pathology of the illness. To further our understanding on how such changes could play a role in the pathology of the illness, in situ radioligand binding with autoradiography was used to measure the density of the serotonin1A receptor, the serotonin4 receptor and the serotonin transporter in the dorsolateral prefrontal cortex, obtained at autopsy, from 10 schizophrenic and 10 control subjects. The binding of [3H]8-OH-DPAT to serotonin1A receptor, [3H]GR113808 to the 5HT4 receptor and [3H]citalopram to serotonin transporter was not altered in subjects with schizophrenia. significantly, only in tissue from the control subjects was there a relationship between age and the density of the serotonin4 receptor in Brodmann's areas 8 (r = 0.71, P = 0.02) and 10 (r = -0.67, P = 0.03). Importantly, this confounding factor did not influence the comparison of the density of serotonin4 receptor in the tissue from the schizophrenic and control subjects. This study has failed to show a difference in the density of serotonin1A receptor, the serotonin4 receptor or the serotonin transporter in the dorsolateral prefrontal cortex (Brodmann's areas 8, 9 and 10) from subjects with schizophrenia. These data suggest that not all serotonergic markers are altered in the dorsolateral prefrontal cortex from schizophrenic subjects.

Carrier Proteins↗

Elevation in late-life depression of intercellular adhesion molecule-1 expression in the dorsolateral prefrontal cortex.

OBJECTIVE: Late-life depression may be associated with vascular disease. The authors investigated this association by determining whether intercellular adhesion molecule-1 (ICAM-1), a marker of ischemia-induced inflammation, is elevated in the dorsolateral prefrontal cortex in depression. METHOD: The authors studied postmortem tissue from 20 depressed subjects and a matched comparison group of 20 nondepressed subjects. They used immunocytochemistry to stain ICAM-1 in blood vessels on sections of the dorsolateral prefrontal cortex and occipital cortex and quantitative true color image analysis to measure the proportion of vessels expressing ICAM-1. RESULTS: ICAM-1 was significantly higher in both the gray and white matter of the depressed subjects' dorsolateral prefrontal cortex than the comparison subjects' dorsolateral prefrontal cortex. The difference between these groups was much smaller in the gray and white matter of the occipital cortex. CONCLUSIONS: These findings support the vascular depression hypothesis, which has important implications for the understanding and management of late-life depression.

Age Factors↗

Dual pathways connecting the dorsolateral prefrontal cortex with the hippocampal formation and parahippocampal cortex in the rhesus monkey.

Anterograde and retrograde tracing methods including autoradiography, horseradish peroxidase histochemistry and fluorescent dye transport were used to demonstrate that the dorsolateral prefrontal cortex is connected with the hippocampal formation and associated cortical regions by two distinct pathways. Fibers forming a lateral pathway travel in the fronto-occipital fasciculus and connect the dorsolateral prefrontal cortex with the fundus of the rhinal sulcus, posterior subdivisions of the parahippocampal gyrus, and the presubiculum. A larger medial pathway forms in the cingulum bundle and terminates in the most caudal part of the presubiculum, as well as in adjacent transitional cortices. These cortices form a caudomedial promontory that is located between the posterior cingulate and prestriate areas. In all allo- and mesocortical targets of prefrontal cortex, labeled terminals form banding patterns reminiscent of the columnar organization of afferent fiber columns in neocortex. The same cytoarchitectonic areas that receive prefrontal afferents issue reciprocal projections. The largest source is the caudomedial lobule including its presubicular portion. Neurons in the parahippocampal gyrus and adjacent presubiculum also are retrogradely labeled following implants of horseradish peroxidase or injection of fluorescent dyes into prefrontal cortex. In addition, subicular neurons project to the prefrontal cortex although the subiculum does not appear to receive prefrontal afferent input. These findings emphasize that multiple channels of communication link the dorsolateral prefrontal cortex and the hippocampus via the parahippocampal gyrus, subiculum, presubiculum and adjacent transitional cortices. We speculate that each of these prefrontal projections may carry highly specific information into the hippocampus, whereas the reciprocal projections may allow retrieval by prefrontal cortex of memories stored in the hippocampus.

Animals↗

Repetitive transcranial magnetic stimulation over the right dorsolateral prefrontal cortex affects strategic decision-making.

Although decision-making is typically seen as a rational process, emotions play a role in tasks that include unfairness. Recently, activation in the right dorsolateral prefrontal cortex during offers experienced as unfair in the Ultimatum Game was suggested to subserve goal maintenance in this task. This is restricted to correlational evidence, however, and it remains unclear whether the dorsolateral prefrontal cortex is crucial for strategic decision-making. The present study used repetitive transcranial magnetic stimulation in order to investigate the causal role of the dorsolateral prefrontal cortex in strategic decision-making in the Ultimatum Game. The results showed that repetitive transcranial magnetic stimulation over the right dorsolateral prefrontal cortex resulted in an altered decision-making strategy compared with sham stimulation. We conclude that the dorsolateral prefrontal cortex is causally implicated in strategic decision-making in healthy human study participants.

Adult↗

Implications for altered glutamate and GABA metabolism in the dorsolateral prefrontal cortex of aged schizophrenic patients.

OBJECTIVE: Pharmacological, clinical, and postmortem studies suggest altered gamma-aminobutyric acid (GABA)-ergic and glutamatergic function in patients with schizophrenia. The dorsolateral prefrontal cortex is one key locus of abnormality. The precise neurochemical mechanisms underlying neurotransmitter alterations, such as hypoglutamatergia or GABA dysfunction, are not well understood. This study investigated key biochemical elements of GABA and glutamate metabolism in brain specimens from schizophrenic patients. The activities of nine principal GABA and glutamate-associated metabolic enzymes were measured concurrently in the dorsolateral prefrontal cortex of antemortem-assessed and neuropathologically characterized schizophrenic and comparison subjects. METHOD: Postmortem dorsolateral prefrontal cortex specimens from schizophrenia, Alzheimer's disease, and normal nonpsychiatric comparison subjects were assayed to determine activities of the principal glutamate and GABA-metabolizing enzymes glutamine synthetase, glutamate dehydrogenase, alpha-ketoglutarate dehydrogenase, phosphate-activated glutaminase, alanine aminotransferase, aspartate aminotransferase, glutamic acid decarboxylase, GABA-transaminase, and succinic semialdehyde dehydrogenase. RESULTS: Glutamic acid decarboxylase activities were twofold greater and phosphate-activated glutaminase activities were fourfold greater in the schizophrenic group than in the comparison group. Differences in postmortem interval, tissue pH, inhibition of phosphate-activated glutaminase, and medication effects could not account for the differences. Differences in phosphate-activated glutaminase and glutamic acid decarboxylase activities in equivalent specimens from Alzheimer's patients were not observed. The activities of the remaining enzymes were unchanged. CONCLUSIONS: Greater phosphate-activated glutaminase and glutamic acid decarboxylase activities, specific to schizophrenia patients, provide additional biochemical evidence that dorsolateral prefrontal cortex glutamate and GABA metabolism is altered in schizophrenic subjects. These greater activities are consistent with models of a dysregulated glutamatergic/GABA-ergic state in schizophrenia.

Age Factors↗

Differential activation of the human orbital, mid-ventrolateral, and mid-dorsolateral prefrontal cortex during the processing of visual stimuli.

There is considerable uncertainty about the precise functional contribution of the different parts of the prefrontal cortex to mnemonic processing. Changes in regional cerebral blood flow were measured with positron emission tomography in normal human subjects exposed to abstract visual designs under various conditions. It was demonstrated that the processing of stimuli that deviate from expectations involves selectively the orbitofrontal cortex, namely the part of the frontal cortex that is preferentially linked with the limbic system. By contrast, when the subject is making an explicit decision on the contents of memory (e.g., judgments of relative stimulus familiarity), the mid-ventrolateral prefrontal cortex is involved. The mid-dorsolateral prefrontal cortex is engaged when monitoring of information within working memory is required.

Adult↗

Decreased levels of N-acetylaspartate in dorsolateral prefrontal cortex in a case of intractable severe sympathetically mediated chronic pain (complex regional pain syndrome, type I).

In our previous in vivo proton magnetic resonance spectroscopy ((1)H MRS) study we found reduced levels of N-acetylaspartate in dorsolateral prefrontal cortex of chronic back pain patients. This study tests whether these chemical abnormalities can be detected in other pain states. Using (1)H MRS, we measured levels for N-acetylaspartate and other identifiable chemicals relative to creatine in four bilateral brain regions, including dorsolateral prefrontal cortex, orbitofrontal cortex, cingulate, and thalamus, in a case of intractable severe sympathetically mediated chronic pain [complex regional pain syndrome (CRPS) type I]. The subject's chemical variations in the brain were compared to the same regional chemicals in 10 normal subjects (age- and sex-matched). Univariate statistics showed reduced levels of N-acetylaspartate in bilateral dorsolateral prefrontal cortex and increased levels of myo-inositol in left orbitofrontal cortex of the patient with intractable severe CRPS type I. These data support our original hypothesis that depletion of N-acetylaspartate in dorsolateral prefrontal cortex is a chemical marker of chronic pain, indicating for neuronal degeneration. Unpredicted changes of orbitofrontal myo-inositol may be related to the specific mood/affective state in an extreme pain perception. This is the first report, which identifies chemical markers in the prefrontal cortex for objective measurement and monitoring of CRPS type I. This information might lead to valuable insights into diagnosis and future effective interventions of CRPS type I (e.g., prefrontal brain stimulation).

Adult↗

Metabolic changes within the left dorsolateral prefrontal cortex occurring with electroconvulsive therapy in patients with treatment resistant unipolar depression.

BACKGROUND: The dorsolateral prefrontal cortex (DLPFC) is involved in the pathophysiology of major depression. In particular, metabolic (functional hypometabolism) and structural alterations have been described. In this study metabolic changes within the DLPFC of severely depressed patients before and after electroconvulsive therapy (ECT) were evaluated by proton STEAM spectroscopy (1H-MRS). METHOD: Twelve severely depressed patients with a diagnosis of major depressive episode, unipolar with melancholic features (DSM-IV), were enrolled, and the left dorsolateral prefrontal cortex (DLPFC) was investigated before and after unilateral ECT by 1H-MRS. Three of the four non-responding patients were remeasured a third time after a combined ECT/antidepressant pharmacotherapy. The results were compared with 12 age- and gender-matched controls. RESULTS: In depressed patients reduced glutamate/glutamine (Glx) levels were measured pre-ECT; Glx concentrations correlated negatively with severity of depression. After successful treatment, Glx increased significantly and levels no longer differed from those of age-matched controls. CONCLUSIONS: Our results indicate that major depressive disorder is accompanied by state-dependent metabolic alterations, especially in glutamate/glutamine metabolism, which can be reversed by successful ECT.

Aged↗

Reduced NAA levels in the dorsolateral prefrontal cortex of young bipolar patients.

OBJECTIVE: Converging evidence implicates prefrontal circuits in the pathophysiology of bipolar disorder. Proton spectroscopy studies performed in adult bipolar patients assessing prefrontal regions have suggested decreased levels of N-acetylaspartate (NAA), a putative marker of neuronal integrity. In order to examine whether such abnormalities would also be found in younger patients, a 1H spectroscopy study was conducted that focused on the dorsolateral prefrontal cortex of children and adolescents with bipolar disorder. METHOD: The authors examined the levels of NAA, creatine plus phosphocreatine, and choline-containing molecules in the left dorsolateral prefrontal cortex of 14 bipolar disorder patients (mean age=15.5 years, SD=3, eight female) and 18 healthy comparison subjects (mean age=17.3, SD=3.7, seven female) using short echo time, single-voxel in vivo 1H spectroscopy. Absolute metabolite levels were determined using the water signal as an internal reference. RESULTS: Bipolar patients presented significantly lower NAA levels and a significant inverse correlation between choline-containing molecules and number of previous affective episodes. No differences were found for other metabolites. CONCLUSIONS: These findings suggest that young bipolar patients have decreased NAA levels in the dorsolateral prefrontal cortex, similar to what was previously reported in adult patients. Such changes may reflect an underdevelopment of dendritic arborizations and synaptic connections. These neuronal abnormalities in the dorsolateral prefrontal cortex of bipolar disorder youth are unlikely to represent long-term degenerative processes, at least in the subgroup of patients where the illness had relatively early onset.

Adolescent↗

Regional distribution of functions in dorsolateral prefrontal cortex of the the monkey.

Single-cell responses were obtained from 352 neurons in dorsolateral prefrontal cortex (Walker's areas 9 and 46) of three monkeys. The neurons were classified functionally according to their responsiveness to visual, auditory and somatosensory stimulation, and to correlation of their activity with spontaneous eye or limb movements. A comparison between the distribution of different functions and known modality-specific anatomical connections to various sectors of this area showed a good correspondence. On average somatosensory and motor neurons were located more ventrally than the remaining ones, and were concentrated to the middle third of the inferior bank of principal sulcus and adjacent inferior convexity, where a number of somatosensory projections overlap. Oculomotor neurons were found caudally in both banks of principal sulcus and in a narrow band on the dorsal convexity, coinciding with the projection fields of areas 7a and 7ip of posterior parietal cortex, superior colliculus, and paramedian pontine tegmentum. Other functions were scatteredly distributed. Visual neurons which preferred moving to stationary stimuli were located more caudally and dorsally than other visual neurons. The present study shows that a parcellation of dorsolateral prefrontal cortex proposed on the basis of anatomical connectivity is also functionally evident.

Animals↗

Metabolic alterations in the dorsolateral prefrontal cortex after treatment with high-frequency repetitive transcranial magnetic stimulation in patients with unipolar major depression.

Neuroimaging studies suggest a specific role of anterior cingulate cortex (ACC) and left dorsolateral prefrontal cortex (DLPFC) in major depression. Stimulation of the latter by means of repetitive transcranial magnetic stimulation (rTMS) as an antidepressant intervention has increasingly been investigated in the past. The objective of the present study was to examine in vivo neurochemical alterations in both brain regions in 17 patients with unipolar major depression before and after 10 days of high-frequency (20Hz) rTMS of the left DLPFC using 3-tesla proton magnetic resonance spectroscopy. Six out of seventeen patients were treatment responders, defined as a 50% reduction of the Hamilton depression rating scale. No neurochemical alterations in the ACC were detected after rTMS. As compared to the non-responders, responders had lower baseline concentrations of DLPFC glutamate which increased after successful rTMS. Correspondingly, besides a correlation between clinical improvement and an increase in glutamate concentration, an interaction between glutamate concentration changes and stimulation intensity was observed. Our results indicate that metabolic, state-dependent changes within the left DLPFC in major depressive disorder involve the glutamate system and can be reversed in a dose-dependent manner by rTMS.

Adult↗

Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex and cortical excitability in patients with major depressive disorder.

Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex is a relatively non-invasive technique with putative therapeutic effects in major depression. However, the exact neurophysiological basis of these effects needs further clarification. Therefore, we studied the impact of ten daily sessions of left, dorsolateral prefrontal rTMS on motor cortical excitability, as revealed by transcranial magnetic stimulation-elicited motor-evoked potentials in 30 patients. As compared to the non-responders, responders (33%) showed changes in parameters pointing towards a reduced cortical excitability. These results suggest that repetitive transcranial magnetic stimulation of the dorsolateral, prefrontal cortex may have inhibitory effects on motor cortical neuronal excitability in patients with major depressive disorder. Furthermore, measurement of motor cortical excitability may be a useful tool for investigating and monitoring inhibitory brain effects of antidepressant stimulation techniques like rTMS.

Adult↗

Changes in serotonin2A and GABA(A) receptors in schizophrenia: studies on the human dorsolateral prefrontal cortex.

Having shown a decrease in serotonin2A receptors in the dorsolateral prefrontal cortex (DLPFC) from schizophrenic subjects, we have now determined if this change was reflective of widespread changes in neurochemical markers in DLPFC in schizophrenia. In Brodmann's area (BA) 9 from 19 schizophrenic and 19 control subjects, we confirmed a decrease in the density of [3H]ketanserin binding to serotonin2A receptors in tissue from the schizophrenic subjects [39 +/- 3.3 vs. 60 +/- 3.6 fmol/mg estimated tissue equivalents (ETE); p < 0.005]. In addition, the density of [3H]muscimol binding to GABA(A) receptors was increased in the schizophrenic subjects (526 +/- 19 vs. 444 +/- 28 fmol/mg ETE; p < 0.02). [3H]YM-09151-2, N-[1-(2-thienyl)cyclohexyl]-3,4-[3H]piperidine, [3H]SCH 23390, [3H]mazindol, and N(G)-nitro-L-[3H]arginine binding to BA 9 did not differ between groups, and there was no specific binding of [3H]raclopride or 7-hydroxy-2-(di-n-[3H]propylamino)tetralin to BA 9 from either cohort of subjects. This suggests the density of dopamine D1-like and NMDA receptors, the dopamine transporter, and nitric oxide synthase activity are not altered in BA 9 from schizophrenic subjects. The selective nature of the changes in serotonin2A and GABA(A) receptors in DLPFC could indicate that these changes are involved in the pathology of schizophrenia.

Adult↗

Auditory memory cells in dorsolateral prefrontal cortex.

The activity of single neurons was recorded extracellularly from dorsolateral prefrontal cortex (DPC) of monkeys during the performance of a cross-modal audio-visual short-term memory task. Cells in DPC show sustained elevated firing levels (higher than spontaneous discharge) during the retention of the auditory stimulus. In some cells this elevated firing was significantly different depending on the particular auditory memorandum of each trial. These results support the notion that DPC participates in auditory short-term memory and the integration of auditory and visual information for prospective action.

Animals↗

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

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

Adult↗

Association of storage and processing functions in the dorsolateral prefrontal cortex of the nonhuman primate.

The prominent role of the prefrontal cortex (PFC) in working memory (WM) is widely acknowledged both in nonhuman primates and in humans. However, less agreement exists on the issue of functional segregation within different subregions of the PFC with regard to the domains of spatial and nonspatial processing or involvement in simpler versus more complex aspects of WM, e.g., maintenance versus processing function. To address these issues, six monkeys were trained to perform four WM tasks that differed with respect to domain (spatial vs nonspatial) and level of WM demand (recall of one vs three items). The delayed response format was used to assess simple one-item memory, whereas self-ordering tasks were used to require the monkey to maintain and organize three items of information within WM. After training, the monkeys received bilateral PFC lesions in one of two different areas, Walker's areas 9 and 8B (dorsomedial convexity; n = 3) or areas 46 and 8A (dorsolateral cortex, n = 3) and then tested postoperatively on all tasks. Monkeys with lesions of the dorsomedial convexity were not impaired either on spatial or nonspatial WM tasks, whether the task required simple storage or sequential processing. By contrast, lesions of the dorsolateral cortex produced a significant and persistent impairment in both simple and complex spatial WM but no impairment in the two nonspatial WM tasks. These results support a functional segregation within the dorsolateral prefrontal cortex for WM: the dorsolateral prefrontal cortex (area 46/8A) is selectively involved in spatial WM, whereas the dorsomedial convexity (area 9/8B) is not critically engaged in either spatial or nonspatial working memory. Furthermore, the specific involvement of area 46/8A in spatial sequencing as well as in single-item storage WM tasks supports, in the nonhuman primate, an areal dissociation based on domain rather than on processing demand.

Animals↗

Properties of delay-period neuronal activity in the monkey dorsolateral prefrontal cortex during a spatial delayed matching-to-sample task.

The dorsolateral prefrontal cortex (PFC) has been implicated in visuospatial memory, and its cellular basis has been extensively studied with the delayed-response paradigm in monkeys. However, using this paradigm, it is difficult to dissociate neuronal activities related to visuospatial memory from those related to motor preparation, and few studies have provided evidence for the involvement of PFC neurons in visuospatial memory of a sensory cue, rather than in motor preparation. To extend this finding, we examined neuronal activities in the dorsolateral PFC while a rhesus monkey performed a spatial delayed matching-to-sample (SDMTS) task, which allows us to adequately access visuospatial memory independent of any sensorimotor components. The SDMTS task required the subject to make a lever-holding NOGO response or a lever-releasing GO response when a visuospatial matching cue (white spot, one of four peripheral locations, 15 degrees in eccentricity) matched or did not match a sample cue (physically the same as the matching cue) that had been presented prior to a delay period (3 s). Thus, the SDMTS task requires the subject to remember visuospatial information regarding the sample cue location during the delay period and is suitable for accessing visuospatial memory independent of any sensorimotor components, such as motor preparation, for directed movements. Of a total of 385 task-related neurons, 184 showed a sustained increase in activity during the delay period ("delay-period activity"). Most of these neurons (n = 165/184, 90%) showed positional delay-period activity, i.e., delay-period activity where the magnitude differed significantly with the position of the sample cue. This activity appears to be involved in visuospatial memory and to form a "memory field." To quantitatively examine the properties of positional delay-period activity, we introduced a tuning index (TI) and a discriminative index (DI), which represent the sharpness of tuning and the discriminative ability, respectively, of positional delay-period activity. Both TI and DI varied among neurons with positional delay-period activity and were closely related to the time from the onset of the sample cue to the onset of positional delay-period activity; positional delay-period activity with sharper tuning and a greater discriminative ability had a slower onset. Furthermore, at the population level, both TI and DI were increased during the delay period in the neuronal population with a high DI value. These results extend previous findings to suggest that integrative, convergent processes of neuronal activities for increasing the accuracy of visuospatial memory may occur in the dorsolateral PFC. Thus, a critical role of the dorsolateral PFC in visuospatial memory may be to sharpen it to guide behaviors/decisions requiring accurate visuospatial memory.

Animals↗

Single neuron activity in dorsolateral prefrontal cortex of monkey during operant behavior sustained by food reward.

The activity of 190 neurons was recorded from the dorsolateral prefrontal cortex of monkeys during an operant task that consisted of 3 phases: visual discrimination of food and non-food, bar pressing to gain access to the food and ingestion. In area 8, a fairly large proportion of the 49 recorded neurons responded in both the visual discrimination (37%) and motor initiation (35%) phases. Some functional heterogeneity seems evident within area 8 since visual discrimination responses were rostral, visuokinesis was central and motor initiation was in the caudal bank of the arcuate sulcus. Neurons in area 9 responded primarily (37%) during the bar pressing phase and less during the visual discrimination phase. Neurons in area 10 responded variously during most phases of the task--food discrimination, bar pressing, and ingestion. Neurons in the periprincipal sulcal area usually responded in the visual discrimination phase, but some which did not respond to food presented in front of the subject responded to meaningful visual or auditory cues that were related to food reward. The data suggest that neurons in the dorsolateral prefrontal cortex have multiple functions related to all phases of complex, learned feeding behavior. Functional roles of the prefrontal cortex and the lateral hypothalamus in development of feeding behavior are discussed.

Animals↗