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Neural correlates of automatic beliefs about gender and race.

Functional MRI was used to identify the brain areas underlying automatic beliefs about gender and race, and suppression of those attitudes. Participants (n = 20; 7 females) were scanned at 3 tesla while performing the Implicit Association Test (IAT), an indirect measure of race and gender bias. We hypothesized that ventromedial prefrontal cortex areas (PFC) would mediate gender and racial stereotypic attitudes, and suppression of these beliefs would recruit dorsolateral prefrontal cortex (DLPFC) and the anterior cingulate cortex (ACC). Performance data on the IAT revealed gender and racial biases. Racial bias was correlated with an explicit measure of racism. Results showed activation of anteromedial PFC and rostral ACC while participants implicitly made associations consistent with gender and racial biases. In contrast, associations incongruent with stereotypes recruited DLPFC. Implicit gender bias was correlated with amygdala activation during stereotypic conditions. Results suggest there are dissociable roles for anteromedial and dorsolateral PFC circuits in the activation and inhibition of stereotypic attitudes.

Adult↗

Dissociable roles of mid-dorsolateral prefrontal and anterior inferotemporal cortex in visual working memory.

Functional neuroimaging in human subjects and studies of monkeys with lesions limited to the mid-dorsolateral (MDL) prefrontal cortex have shown that this specific region of the prefrontal cortex is involved in visual working memory, although its precise role remains a matter of debate. The present study compared the effect on visual working memory of lesions restricted to the mid-dorsolateral prefrontal cortex of the monkey with that of lesions to the anterior inferotemporal cortex, a region of the temporal cortex specialized for visual memory. Increasing the delay during which information had to be maintained in visual working memory impaired performance after lesions of the anterior inferotemporal cortex, but not after mid-dorsolateral prefrontal lesions. By contrast, increasing the number of stimuli that had to be monitored impaired the performance of animals with mid-dorsolateral prefrontal lesions, but not that of animals with anterior inferotemporal lesions. This demonstration of a double dissociation between the effects of these two lesions provides strong evidence that the role of the mid-dorsolateral prefrontal cortex in visual working memory does not lie in the maintenance of information per se, but rather in the executive process of monitoring this information. In addition, the present study demonstrated that lesions limited to area 9, which constitutes the superior part of the mid-dorsolateral prefrontal region, give rise to a mild impairment in the monitoring of information, whereas lesions of the complete mid-dorsolateral prefrontal region yield a very severe impairment.

Analysis of Variance↗

Sequential rTMS for MDD and OCD in a patient with left parietal perinatal ischemic infarct: a case report.

Major depressive disorder (MDD) commonly co-occurs with obsessive-compulsive disorder (OCD), resulting in greater symptom severity, functional impairment, and suboptimal response to standard pharmacologic and psychotherapeutic interventions. These challenges underscore the need for neuromodulation strategies to target distinct neural networks implicated in mood regulation and compulsivity. This report describes outcomes of high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC), and low-frequency (LF) rTMS of the right orbitofrontal cortex (OFC), in a patient with comorbid MDD, OCD, and a left parietal perinatal ischemic infarct. Over the course of treatment, serial psychometric assessments demonstrated progressive reductions in frequency and intensity of depressive symptoms, anxiety, and obsessive-compulsive behaviors, measured via Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7-Item Scale (GAD-7), and Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). This case adds to the growing body of literature demonstrating efficacy of DLPFC and OFC stimulation for depression and OCD. Further large-scale, blinded, and randomized trials are warranted to examine the efficacy of sequential DLPFC and OFC stimulation for comorbid MDD and OCD compared with single-site DLPFC stimulation.

dorsolateral prefrontal cortex (DLPFC)↗

Age-related changes in regional cerebral blood flow during working memory for faces.

Young and old adults underwent positron emission tomography during the performance of a working memory task for faces (delayed match-to-sample), in which the delay between the sample and choice faces was varied from 1 to 21 s. Reaction time was slower and accuracy lower in the old group, but not markedly so. Values of regional cerebral blood flow (rCBF) were analyzed for sustained activity across delay conditions, as well as for changes as delay increased. Many brain regions showed similar activity during these tasks in both young and old adults, including left anterior prefrontal cortex, which had increased rCBF with delay, and ventral extrastriate cortex, which showed decreased rCBF with delay. However, old adults had less activation overall and less modulation of rCBF across delay in right ventrolateral prefrontal cortex than did the young adults. Old adults also showed greater rCBF activation in left dorsolateral prefrontal cortex across all WM delays and increased rCBF at short delays in left occipitoparietal cortex compared to young adults. Activity in many of these regions was differentially related to performance in that it was associated with decreasing response times in the young group and increasing response times in the older individuals. Thus despite the finding that performance on these memory tasks and associated activity in a number of brain areas are relatively preserved in old adults, differences elsewhere in the brain suggest that different strategies or cognitive processes are used by the elderly to maintain memory representations over short periods of time.

Adult↗

Unchanged packing density but altered size of neurofilament immunoreactive neurons in the prefrontal cortex in schizophrenia and major depression.

Morphometric changes in the general population of Nissl-stained neurons in area 9 of the dorsolateral prefrontal cortex have been reported in major depressive disorder (MDD) and schizophrenia. These alterations include lamina-specific reductions in the packing density of neuronal somata in MDD, increases or reductions in the density of neuronal somata in schizophrenia, and reductions in average size of neuronal somata in both MDD and schizophrenia. These changes are prominent in deep layer III, where pyramidal excitatory neurons establishing cortico-cortical association connections are localized. To test whether deep layer III pyramidal neurons are differentially affected in MDD or schizophrenia, an antibody was used that labels both phosphorylated and non-phosphorylated forms of the 200 kD neurofilament protein (NF200) in pyramidal cells of layer III in area 9. The packing density and somal size of NF200-immunoreactive (IR) pyramidal neurons were measured in area 9 in 13 subjects with nonpsychotic MDD, 11 subjects with schizophrenia and 13 psychiatrically normal controls. Analysis of covariance did not reveal a difference in packing density among groups. However, the mean size of NF200-IR somata was significantly larger in subjects with schizophrenia than in controls. These results indicate that this neuronal subpopulation does not contribute to the smaller average size of neuronal somata in layer III of prefrontal cortical area 9 in schizophrenia or MDD. In addition, the enlarged somal size in schizophrenia as compared to controls suggests that NF200 neurons may contribute differentially to unique cognitive disturbances present in schizophrenia and not in MDD subjects.

Adult↗

GABAergic neurons immunoreactive for calcium binding proteins are reduced in the prefrontal cortex in major depression.

Post-mortem morphometric studies report reductions in the average density and size of cortical neurons in the dorsolateral prefrontal cortex (dlPFC) and orbitofrontal cortex (ORB) in major depressive disorder (MDD). The contribution of specific neuronal phenotypes to this general pathology in depression is still unclear. Post-mortem sections from the dlPFC and ORB regions of 14 subjects with MDD and 11 controls were immunostained to visualize calbindin-immunoreactive (CB-IR) and parvalbumin-immunoreactive (PV-IR) presumptive GABAergic neurons. A three-dimensional cell counting probe was used to assess the cell packing density and size of CB-IR neurons in layers II+IIIa and PV-IR neurons in layers III-VI. The density of CB-IR neurons was significantly reduced by 50% in depression in the dlPFC and there was a trend toward reduction in the ORB. The size of CB-IR somata was significantly decreased (18%) in depression in the dlPFC with a trend toward reduction in the ORB. In contrast, there was no difference in the density of PV-IR neurons between the depressed and control groups in the dlPFC. The size of PV-IR neuronal soma was unchanged in depressed compared to control subjects in either dlPFC or ORB. In depression, subpopulations of GABAergic neurons may be affected differently in dlPFC and ORB. A significant reduction in the density and size of GABAergic interneurons immunoreactive for calcium binding proteins was found predominantly in the dlPFC region. These cellular changes are consistent with recent neuroimaging studies revealing a reduction in the cortical levels of GABA in depression.

Adult↗

Novelty seeking and rapid symptom improvement across active and sham accelerated iTBS conditions: A pooled individual-patient data analysis.

INTRODUCTION: Major depressive disorder (MDD) is highly prevalent and often treatment-resistant. Accelerated intermittent theta burst stimulation (aiTBS) is a promising intervention for treatment-resistant depression (TRD), though outcomes vary. Personality traits have been examined in relation to rTMS outcomes, yet their role in aiTBS remains underexplored. This pooled individual-patient-data analysis of two randomized, sham-controlled trials examined associations between baseline Temperament and Character Inventory (TCI) traits and one-week symptom change, and whether they differed by condition. METHODS: The left dorsolateral prefrontal cortex was targeted for 20 sessions over 4 days. Personality was assessed with the TCI, depression severity with the 17-item Hamilton Depression Rating Scale (HDRS-17). TCI-symptom-change associations were examined with a robust linear mixed-effects model, adjusting for age, gender, repeated measurements, and study membership. RESULTS: 104 participants were included (M/F 45/59; mean age 40.9 ± 12.7; active/sham 50/54). The model yielded a Time × Novelty Seeking interaction (β = -1.70, p = 0.021): higher baseline Novelty Seeking was associated with faster symptom reduction, without a between-arm difference. However, the interaction did not survive Holm correction across 14 trait-interaction tests (adjusted p = 0.294) and is therefore exploratory. No other interaction reached the uncorrected threshold. CONCLUSIONS: Higher baseline Novelty Seeking showed a nominal association with faster symptom reduction, without a difference between active and sham conditions. Because it did not survive multiplicity correction and was not reproduced in within-arm analyses, it is preliminary and may reflect contextual or nonspecific processes. Independent replication is required before temperament assessment can be clinically informative.

Humans↗

Pilot randomized trial of intermittent theta-burst stimulation versus H-Coil transcranial magnetic stimulation for treatment-resistant depression.

BACKGROUND: Intermittent theta burst stimulation (figure-8-coil iTBS) and H7-coil repetitive transcranial magnetic stimulation (rTMS) are FDA-cleared treatments for major depression; yet their comparative effectiveness in treatment-resistant depression (TRD) has not been evaluated in randomized trials. This pilot randomized trial was designed to obtain preliminary comparative estimates and to explore whether baseline cognitive functioning relates to early remission. METHODS: Twenty-eight adults with TRD were randomized to six weeks of figure-8-coil iTBS delivered to the dorsolateral prefrontal cortex (DLPFC) (n = 15) or H7-coil rTMS delivered to the dorsomedial prefrontal cortex (DMPFC) (n = 13). The primary outcome was change in 17-item Hamilton Depression Rating Scale (HRSD-17) score from baseline to week 6, analyzed with ANCOVA. Additional outcomes included response, remission, and symptom trajectories through week 18. Exploratory analyses examined the association between baseline cognitive functioning, such as executive functions and memory, and remission. RESULTS: Twenty-five participants completed all 30 sessions. Adjusted week-6 HRSD-17 scores did not differ between groups (mean difference -0.40, 95% CI -5.23 to 4.43; p=.865). Response rates were 40.0% for figure-8-coil iTBS and 50.0% for H7-coil rTMS (p>.60), and remission rates were identical across groups (20.0%). Remitters showed higher baseline executive functioning than non-remitters in exploratory analyses, although these associations were not confirmed in adjusted models. CONCLUSION: In this pilot trial, figure-8-coil iTBS and H7-coil rTMS showed symptom improvement, with no clear between-group differences. Exploratory findings suggest a potential signal involving executive functioning that warrants further investigation. These results inform the feasibility and design of larger comparative trials. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05902312).

Adult↗

Integrative methylation and miRNA dysregulation in dlPFC reveal distinct molecular signatures of suicide and non-suicide subtypes in major depressive disorder.

AIM: Major depressive disorder (MDD) is a leading cause of disability and carries a high risk of suicide. MicroRNAs (miRNAs) are epigenetic regulators implicated in MDD and can be regulated by DNA methylation, potentially reshaping downstream gene networks. We investigated methylation-linked miRNA dysregulation and explored whether these changes are specifically associated with suicide among MDD patients. METHODS: Genome-wide DNA methylation profiling of the dorsolateral prefrontal cortex from 15 MDD patients who died by suicide (MDD+S), 17 MDD patients who died from causes other than suicide (MDD-S), and 16 controls (C) using the Illumina 850K MethylationEPIC array was integrated with small RNA sequencing-based miRNA quantification to identify miRNA-associated differentially methylated probes (DMPs), link methylation to miRNA expression, and infer downstream targets and pathways. RESULTS: Differential methylation analysis (P ≤ 0.05) revealed 139 miRNA-linked DMPs in C vs. MDD+/-S, 135 in C vs. MDD-S, 179 in C vs. MDD+S, and the highest in MDD+S vs. MDD-S (235). CpG-miRNA pairing (within 1500kb promoter) followed by Spearman correlation identified inverse associations between CpG β values and miRNA expression, with the most consistent signals in suicide-status-stratified subsets, including cg06341821-hsa-miR-574-3p and cg25451306-hsa-miR-2110 in MDD+S-related contrasts, and cg06179179-hsa-miR-595 in MDD-S-related contrasts. High-confidence target prediction and ClueGO enrichment indicated distinct biology: miR-595 target genes in MDD-S were enriched for interferon/innate immune signaling, whereas miR-2110 target genes in MDD+S were enriched for ligand-gated ion channel activity and synaptic/receptor signaling. CONCLUSION: This integrated approach identifies methylation-regulated miRNA pathways that may play key roles in the molecular pathogenesis of MDD and suicide.

Humans↗

Acute prefrontal cortex TMS in healthy volunteers: effects on brain 11C-alphaMtrp trapping.

High-frequency repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (LDLPFC) is a technique with purported efficacy as a treatment for major depression. Here, we assessed in vivo, in healthy volunteers, the effect of acute rTMS of the LDLPFC, relative to the stimulation of the left occipital cortex (LOC), on brain regional serotonin synthesis capacity, using the [(11)C]-alpha-methyl-tryptophan ((11)C-alphaMtrp)/PET method. Ten subjects were studied twice, once following rTMS of the LDLPFC and once following rTMS of the LOC in a randomized counterbalanced order. Three blocks of 15 trains of 10 Hz rTMS were delivered 10 min apart. Behavioural and autonomic measures were recorded before and after each rTMS session. Comparisons of TMS-related changes in regional normalized brain uptake and trapping of (11)C-alphaMtrp (K*) values were carried out using SPM99. Statistically significant regional differences were identified on the basis of an extent threshold of 50 voxels, with a peak threshold of p=0.005 uncorrected. Behavioural and autonomic measures were unaffected by rTMS. Relative to LOC stimulation, LDLPFC rTMS was associated with marked changes in normalized K* in limbic areas, with significantly lower values in the left parahippocampal gyrus (BA 28) and the right insula (BA 13), and higher values in the right cingulate gyrus (BA 31) and cuneus (BA 18). These findings indicate that acute rTMS of the LDLPFC in healthy volunteers modulates aspects of tryptophan/5-HT metabolism in limbic areas. Such adaptive changes may contribute to the mechanism of action of prefrontal rTMS in major depression.

Adult↗

Transcriptional profiling in the human prefrontal cortex: evidence for two activational states associated with cocaine abuse.

CNS-focused cDNA microarrays were used to examine gene expression profiles in dorsolateral prefrontal cortex (dlPFC, Area 46) from seven individual sets of age- and post-mortem interval-matched male cocaine abusers and controls. The presence of cocaine and related metabolites was confirmed by gas chromatography-mass spectrometry. Sixty-five transcripts were differentially expressed, indicating alterations in energy metabolism, mitochondria and oligodendrocyte function, cytoskeleton and related signaling, and neuronal plasticity. There was evidence for two distinct states of transcriptional regulation, with increases in gene expression predominating in subjects testing positive for a metabolite indicative of recent 'crack' cocaine abuse and decreased expression profiles in the remaining cocaine subjects. This pattern was confirmed by quantitative polymerase chain reaction for select transcripts. These data suggest that cocaine abuse targets a distinct subset of genes in the dlPFC, resulting in either a state of acute activation in which increased gene expression predominates, or a relatively destimulated, refractory phase.

Adult↗

Right lateralized motor cortex activation during volitional blinking.

Using H2 15O positron emission tomography in 6 healthy volunteers, we found that self-initiated and externally cued blinking activated the right primary motor cortex and supplementary motor area (SMA). The left dorsolateral prefrontal cortex (DLPFC) and the rostral SMA showed greater activation during the self-initiated task compared to the externally cued task. This study confirms the hypothesis of right hemispheric lateralization of volitional blinking derived from observations in stroke patients. Furthermore, it underscores the role of DLPFC and rostral SMA in self-initiated movements, which has been found in similar experiments with hand movements.

Aged↗

The neural mechanisms of object working memory: what is where in the infant brain?

The question of how representational capacities develop in humans has been engaging cognitive psychologists for decades. Looking time studies have explored when infants start to show signs of perceiving and remembering the properties of specific objects at specific locations. Here we integrate these findings into the neuroscientific framework of human visual working memory. We suggest that the development of a system involving the temporal cortex, thalamic and hippocampal structures and possibly the dorsolateral prefrontal cortex (later in development) can account for these behavioral results. Our explanation differs from most of the current approaches in developmental science as we put less emphasis on the contribution of lateral prefrontal areas. We discuss shortcomings of the theories that propose a functional subdivision of these areas and their difficulty in accounting for results from monkey lesion and infant studies. We believe that this shift in focus is desirable both in light of what recent results on medial temporal lobe processing reveal about object working memory, and given how well these results fit the behavioral developmental data.

Animals↗

Functional neuroimaging indicators of successful executive control in the oldest old.

Attentional control, motor planning abilities, and executive cognitive functions (ECF) rapidly decline with age. In particular, older adults experience difficulty in manipulating selected motor responses in the presence of conflicting or distracting information. To examine age-related changes in the neural substrates of the attentional and motor planning components of ECF, we assessed the patterns of brain activation in 8 cognitively normal older adults (mean age 81.5) and 20 young individuals (mean age 23.0) while they responded to low and high loads of attentional demands of the Preparing to Overcome Prepotency (POP) task. In the POP task, the selection of one out of two possible motor responses in the presence of increasing attentional task loads determines the accuracy of the performance. Older individuals were slower than young adults (P < 0.001) but achieved a strikingly high accuracy similar to the young group (P = 0.2), regardless of the task load. Both groups showed a load-related fMRI signal increase in the anterior cingulate cortex (ACC), posterior parietal cortex (PPC: Brodmann areas 7 and 40), and dorsolateral prefrontal cortex (dLPFC: Brodmann areas 9, 45, and 46) bilaterally. Compared to young individuals, older adults had lower activation in dLPFC (Brodmann areas 9, 45, and 46: P = 0.007, P = 0.043, and P = 0.040) and Brodmann area 7, P = 0.002. Activation in Brodmann areas 40 and ACC was similar in the two groups (P > 0.05). Among older adults, the most successful performers were those who responded to increasing task loads with greater activation in PPC (Brodmann area 40), despite lower dLPFC activation. Older adults who are able to perform executive control tasks as well as young adults, also seem to implement speed-accuracy trade-off strategies which may rely on increased parietal activation.

Adolescent↗

Effects of long-term antipsychotic treatment on NMDA receptor binding and gene expression of subunits.

Postmortem studies in schizophrenic patients revealed alterations in NMDA receptor binding and gene expression of specific subunits. Because most of the patients had been treated with antipsychotics over long periods, medication effects might have influenced those findings. We treated animals with haloperidol and clozapine in clinical doses to investigate the effects of long-term antipsychotic treatment on NMDA receptor binding and gene expression of subunits. Rats were treated with either haloperidol (1.5 mg/kg/day) or clozapine (45 mg/kg/day) given in drinking water over a period of 6 months. Quantitative receptor autoradiography with [3H]-MK-801 was used to examine NMDA receptor binding. In situ hybridization was performed for additional gene expression studies of the NR1, NR2A, NR2B, NR2C, and NR2D subunits. [3H]-MK-801 binding was found to be increased after haloperidol treatment in the striatum and nucleus accumbens. Clozapine was shown to up-regulate NMDA receptor binding only in the nucleus accumbens. There were no alterations in gene expression of NMDA subunits in any of the three regions. However, the NR2A subunit was down-regulated in the hippocampus and prefrontal cortex by both drugs, whereas only clozapine induced a down-regulation of NR1 in the dorsolateral prefrontal cortex. NR2B, 2C, and 2D subunits did not differ between treatment groups and controls. Both altered NMDA receptor binding and subunit expression strengthen a hyperglutamatergic function after haloperidol treatment and may contribute to some of our postmortem findings in antipsychotically treated schizophrenic patients. Because the effects seen in different brain areas clearly vary between haloperidol and clozapine, they may also be responsible for some of the differences in efficacy and side effects.

Animals↗

The cerebellum and cognition: cerebellar lesions do not impair spatial working memory or visual associative learning in monkeys.

Anatomical studies in non-human primates have shown that the cerebellum has prominent connections with the dorsal, but not the ventral, visual pathways of the cerebral cortex. Recently, it has been shown that the dorsolateral prefrontal cortex (DPFC) and cerebellum are interconnected in monkeys. This has been cited in support of the view that the cerebellum may be involved in cognitive functions, e.g. working memory. Six monkeys (Macaca fascicularis) were therefore trained on a classic test of working memory, the spatial delayed alternation (SDA) task, and also on a visual concurrent discrimination (VCD) task. Excitotoxic lesions were made in the lateral cerebellar nuclei, bilaterally, in three of the animals. When retested after surgery the lesioned animals were as quick to relearn both tasks as the remaining unoperated animals. However, when the response times (RT) for each task were directly compared, on the SDA task the monkeys with cerebellar lesions were relatively slow to decide where to respond. We argue that on the SDA task animals can prepare their responses between trials whereas this is not possible on the VCD task, and that the cerebellar lesions may disrupt this response preparation. We subsequently made bilateral lesions in the DPFC of the control animals and retested them on the SDA task. These monkeys failed to relearn the task. The results show that, unlike the dorsal prefrontal cortex, the cerebellum is not essential for working memory or the executive processes that are necessary for correct performance, though it may contribute to the preparation of responses.

Animals↗

Aging alters regional multichemical profile of the human brain: an in vivo 1H-MRS study of young versus middle-aged subjects.

Age-related differences in the multichemical proton magnetic resonance spectroscopy (1H-MRS) profile of the human brain have been reported for several age groups, and most consistently for ages from neonates to 16-year-olds. Our recent 1H-MRS study demonstrated a significant age-related increase of total chemical concentration (relative to creatine) in the prefrontal and sensorimotor cortices within young adulthood (19-31-year-olds). In the present study we test the hypothesis that the level of brain chemicals in the same cortices, which show increased chemical levels during normal development, are reduced with normal aging after young adulthood. The multichemical 1H-MRS profile of the brain was compared between 19 young and 16 middle-aged normal subjects across multiple brain regions for all chemicals of 1H-MRS spectra. Chemical concentrations were measured relative to creatine. Over all age groups the total relative chemical concentration was highest in the prefrontal cortex. Middle-aged subjects demonstrated a significant decrease of total relative chemical concentration in the dorsolateral prefrontal (F = 54.8, p < 10(-7), ANOVA), orbital frontal (F = 3.7, p < 0.05) and sensorimotor (F = 15.1, p < 0.0001) cortices, as compared with younger age. Other brain regions showed no age-dependent differences. The results indicate that normal aging alters multichemical 1H-MRS profile of the human brain and that these changes are region-specific, with the largest changes occuring in the dorsolateral prefrontal cortex. These findings provide evidence that the processes of neuronal maturation of the human brain, and neurotransmitters and other chemical changes as the marker of these neuronal changes are almost finished by young adulthood and then reduced during normal aging toward middle age period of life. The present data also support the notion of heterochronic regressive changes of the aging human brain, where the multichemical brain regional profile seems to inversely recapitulate cortical chemical maturation within normal development.

Adult↗

Task-dependent selectivity of movement-related neuronal activity in the primate prefrontal cortex.

Task-dependent selectivity of movement-related neuronal activity in the primate prefrontal cortex. J. Neurophysiol. 80: 3392-3397, 1998. We studied movement-related neuronal activity in the dorsolateral prefrontal cortex from the perspective of a general role for the prefrontal cortex in controlling motor behavior to achieve a specific goal according to the requirements of a given task. Monkeys were trained to perform two delayed motor tasks. The first task involved reaching for a target that matched the shape of a cue. The second task involved reaching for a target that matched the location of the cue. A majority (54%) of 175 movement-related prefrontal neurons exhibited preference for either the target shape or the type of task requirements. Sixty-four neurons (36%) were selectively active while reaching for a circle or a triangle. On the other hand, the activity of 59 neurons (34%) depended on whether the task required matching the shape or the location. These properties, characterizing the movement-related neuronal activity in the prefrontal cortex, rarely were found in the arm area of the primary motor cortex. Only 1 of 130 movement-related neurons (0.8%) showed task selectivity, and none showed target-shape selectivity.

Animals↗