Activity of primate orbitofrontal and dorsolateral prefrontal neurons: task-related activity during an oculomotor delayed-response task

The orbitofrontal cortex (OFC) has strong reciprocal connections to the dorsolateral prefrontal cortex (DLPFC), which is known to participate in spatial working memory processes. However, it is not known whether or not the OFC also participates in spatial working memory and whether the OFC and DLPFC contribute equally to this process. To address these issues, we collected single-neuron activity from both areas while a monkey performed an oculomotor delayed-response task, and compared the characteristics of task-related activities between the OFC and DLPFC. All of the task-related activities observed in the DLPFC were also observed in the OFC. However, the proportion and response characteristics of task-related activities were different between the two areas. While most delay-period activity observed in the DLPFC was directionally selective and showed tonic sustained activation, most delay-period activity observed in the OFC was omni-directional and showed gradually increasing activity. Reward-period activity was predominant among task-related activities in the OFC. The proportion of neurons showing reward-period activity was significantly higher in the OFC than in the DLPFC. These results suggest that, although both the OFC and DLPFC participate in spatial working memory processes, the OFC is related more to the expectation and the detection of reward delivery, while the DLPFC is related more to the temporary maintenance of spatial information and its processing.     

A mismatch process in brief delayed matching-to-sample task: an fMRI study

Our previous ERP studies have consistently demonstrated that a negativity N270 elicited by incongruent information in visual S1–S2 matching task represents a type of conflict process, which is distinct from that represented by the classic conflict task or other negative components in delayed matching-to-sample stimulus presentation patterns, since the inter-stimulus interval between S1 and S2 was presented as shorter as 500 ms. The N270 component of ERP was shown to reflect conflict processing during the simple working memory operations. In the present study, a functional MRI (fMRI) was used to investigate the visuospatial characteristics of brain activation associated with the task eliciting N270. The fMRI data showed an increased activation in the right anterior cingulate cortex (ACC, BA 24) and right dorsolateral prefrontal cortex (DLPFC, BA 46), and activation biased to the left occipitotemporal cortex (BA 37) in the incongruent condition. It is suggested that the greater activations of the right ACC coupling with right DLPFC to incongruent task reflect functional efficiency of the right cingulo-prefrontal network during the brief visual delayed period discrimination performance and mismatched information processing. This work was approved by the local ethics committee.     

Processing in prefrontal cortex underlies tactile direction discrimination: An fMRI study of a patient with a traumatic spinal cord lesion

We have investigated cortical processing of tactile direction discrimination (TDD) in a patient with unilateral tactile disturbance due to spinal cord lesion. The patient R.A. (male, 45 years old), suffers from a traumatic dorsal column lesion at the level of Th XI–XII on the right side. He was instructed to report the direction of 2 mm long skin pull stimulations applied in a proximal or distal direction on his right or left lower legs during functional magnetic resonance imaging (fMRI). Although R.A. considered himself to have nearly normal tactile sensibility, testing showed severely disturbed TDD on his right leg whereas results were within the range of healthy subjects on his left leg. For both legs TDD activated an extensive cortical network that included opercular parietal area 1 (OP1) of the second somatosensory cortex (S2), as has previously been observed in healthy subjects. However, dorsolateral prefrontal cortex (DLPFC) and anterior insular cortex (AIC) were only activated for the unaffected (left) leg where TDD was normal. A revisit of previously published data showed that healthy subjects consistently had TDD-related activations in DLPFC and AIC. However, in several healthy subjects AIC, but not DLPFC, was also activated for skin pull stimulations per se without the TDD task. Thus, the patient's data, in conjunction with the previous results from healthy subjects, suggest that DLPFC processing is important for tactile decision making based on proper tactile input.     

Changing plans: neural correlates of executive control in monkey and human frontal cortex

Changing plans depends on executive control, the orchestration of behavior based on knowledge of both goal and context. Dorsolateral prefrontal (DLPFC) and anterior cingulate (ACC) cortices are clearly involved in these processes. Intracranial recordings in these regions were obtained from a monkey performing an executive control-challenging task that is widely used in clinic and laboratory to assess the integrity of cognitive function, the AX version of the continuous performance task (AX-CPT), and directly compared to scalp-recorded evoked potentials in humans. In this task the subject presses a button when detecting a frequent cue–target probe sequence in a stream of letters presented on a computer screen, and withholds response following incorrect sequences. Thus correct performance requires correct encoding of cue and probe instruction and inhibitory control. Intracranial recordings showed that DLPFC in the monkey was primarily activated by conditions that required inhibition of imminent action, as had been shown in human event-related potential (ERP) recordings. Different subregions of monkey ACC were activated primarily by either initiating or inhibiting action, whereas human ERP had shown ACC activation in both situations. We suggest that simultaneous activation of both types of subregions in conflict conditions may account the ubiquitous ACC activation observed with fMRI and ERP in those conditions.     

Pre‐adolescent gender differences in associations between temperament,coping, and mood

Relationships between temperament, coping, depressive and aggressive mood in 8–12‐year‐old boys (n = 185) and girls (n = 219) were investigated, with a focus on gender differences. Children completed two self‐report questionnaires: the Early Adolescent Temperament Questionnaire‐Revised and Children's Coping Strategies Checklist‐Revised1. Comparing boys and girls on three temperament dimensions, positive affectivity, negative affectivity and effortful control, girls scored higher than boys on the first two dimensions. Girls also scored higher than boys on avoidant coping and depressive mood. For both boys and girls, aggressive and depressive mood were predicted by negative affectivity. Coping did not add towards this prediction. Gender specific models of temperament, coping and depressive mood were tested. For girls, both effortful control and active problem solving, accounted for the variability in depressive mood. For boys, only effortful control accounted for variance in depressive mood. Results showed that gender specific vulnerability to depression in girls is apparent before adolescence and can be linked to temperament and coping. Copyright © 2009 John Wiley & Sons, Ltd. Key Practitioner Message:

• Pre‐adolescent girls are more vulnerable to depression than boys. Interventions focussing on self‐control, emotion regulation and active coping are tailored towards vulnerabilities in temperament and coping in girls.

     

Factors controlling neural activity during delayed-response task performance: testing a memory organization hypothesis of prefrontal function

Understanding the role of prefrontal cortex in delayed-response task performance has been a central focus of neuroimaging research. The first part of this review will emphasize consistent observations of memory-load-related effects on prefrontal cortex activity that have led me and my colleagues to propose a "memory-organization hypothesis" of prefrontal cortex function. The second part examines how predictions of this hypothesis have borne up to empirical testing. The final part of this review suggests that there is important information contained in between-study variance in the anatomical locus and temporal sequence of neural activity. I will examine how subtle variations in task-structure affect subjects' strategies, producing meaningful variability in neuroimaging data. Systematic manipulation of these variables in future research can assist in elucidating the role of prefrontal cortex in delayed response task performance.     

Coupling of theta activity and glucose metabolism in the human rostral anterior cingulate cortex: an EEG/PET study of normal and depressed subjects

In rodents, theta rhythm has been linked to the hippocampal formation, as well as other regions, including the anterior cingulate cortex (ACC). To test the role of the ACC in theta rhythm, concurrent measurements of brain electrical activity (EEG) and glucose metabolism (PET) were performed in 29 subjects at baseline. EEG data were analyzed with a source localization technique that enabled voxelwise correlations of EEG and PET data. For theta, but not other bands, the rostral ACC (Brodmann areas 24/32) was the largest cluster with positive correlations between current density and glucose metabolism. Positive correlations were also found in right fronto-temporal regions. In control but not depressed subjects, theta within ACC and prefrontal/orbitofrontal regions was positively correlated. The results reveal a link between theta and cerebral metabolism in the ACC as well as disruption of functional connectivity within frontocingulate pathways in depression.     

Age, sex and individual differences in punishment sensitivity: factors influencing the feedback-related negativity

The anterior cingulate cortex (ACC) is central to evaluating performance outcomes and has been linked to individual differences in affective responses to feedback. We used electrophysiological source localization to examine the feedback-related negativity (FRN) and related ACC activity during a gambling task in relation to punishment and reward sensitivity among 16- to 17-year-old adolescents (n=20) and 18- to 29-year-old adults (n=30). The FRN was larger for monetary loss compared to win feedback and larger for high relative to low monetary value feedback, with no age differences in the FRN for win or loss feedback. Self-reported sensitivity to punishment accounted for unique variance (over sex and sensitivity to reward) in FRNs, with higher scores relating to larger FRNs and increased rostral ACC activity. These results support the ACC role in experiencing negative performance feedback, especially for individuals highly sensitive to punishment.     

Intracellular activity and morphology of the prefrontal neurons related to visual attention task in behaving monkeys

Summary Neurons of the prefrontal-premotor cortex, which had been studied electorophysiologically during a modified reaction time task, were identified by intracellular pressure micro-injection of horseradish peroxidase (HRP). The cells were classified into those showing a sustained vs. transient change in activity during performance of the task. Cells showing a sustained response were found to have their somata in layers III and VI and cells showing transient responses were found to have their somata in layers II and III. All cells were pyramidal cells with spiny dendrites.This project was supported by the Japanese Ministry of Education, Grant No. 367026     

The firing activity of pyramidal neurons in medial prefrontal cortex and their response to 5-hydroxytryptamine-1A receptor stimulation in a rat model of Parkinson's disease

The changes in the firing rate and firing pattern of pyramidal neurons in medial prefrontal cortex (mPFC) and the effects of selective 5-hydroxytryptamine-_1A (5-HT_1A) receptor agonist (R)-(+)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT) and antagonist N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-2-pyridylcyclohexane carboxamide maleate salt (WAY-100635) on the firing activity of the neurons were studied in sham-lesioned rats and rats with 6-hydroxydopamine lesions of the substantia nigra pars compacta (SNc). The lesion of the SNc increased the firing rate of pyramidal neurons significantly compared to sham-lesioned rats, and the firing pattern of these neurons also changed significantly towards a more burst-firing. The systemic administration of 8-OH-DPAT at doses in the range of 0.5–128 μg/kg showed an excitatory-inhibitory effect on the firing rate of pyramidal neurons in mPFC of sham-lesioned rats. At lower doses, 0.5–32 μg/kg, it evoked excitation of the neurons, and at a high dose, i.e. 128 μg/kg, inhibited the activity of the neurons. In contrast to sham-lesioned rats, 8-OH-DPAT, at the same doses, showed no excitatory effect in the lesioned rats although the inhibitory phase of the effect of 8-OH-DPAT on the firing rate of pyramidal neurons in mPFC was still present. Furthermore, the local application of 8-OH-DPAT, 5 μg, in mPFC inhibited the firing rate of pyramidal neurons in sham-lesioned rats, while having no effect on firing rate in the lesioned rats. The excitatory or inhibitory effects of 8-OH-DPAT were reversed by WAY-100635, indicating that these effects are mediated by 5-HT_1A receptor. Altogether, these results indicate that the lesion of the SNc leads to hyperactivity of pyramidal neurons in mPFC and the abnormality of response of these neurons to 5-HT_1A receptor stimulation, suggesting that mPFC may be involved in the pathophysiology of the psychiatric disturbance of Parkinson's disease.