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Results for “Prefrontal Cortex”

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PubMed1998

Olanzapine increases in vivo dopamine and norepinephrine release in rat prefrontal cortex, nucleus accumbens and striatum.

The in vivo effects of olanzapine on the extracellular monoamine levels in rat prefrontal cortex (Pfc), nucleus accumbens (Acb) and striatum (Cpu) were investigated by means of microdialysis. Sequential doses of olanzapine at 0.5, 3 and 10 mg/kg (s.c.) dose-dependently increased the extracellular dopamine (DA) and norepinephrine (NE) levels in all three brain areas. The increases appeared 30 min after olanzapine administration, reached peaks around 60-90 min and lasted for at least 2 h. The highest DA increases in the Acb and Cpu were induced by olanzapine at 3 mg/kg but at 10 mg/kg in the Pfc. The peak DA increase in the Pfc (421% +/- 46 of the baseline) was significantly larger than those in the Acb (287% +/- 24) and Cpu (278% +/- 28). Similarly, the highest NE increase in the Pfc (414% +/- 40) induced by 10 mg/kg olanzapine was larger than those in the Acb (233% +/- 39) and Cpu (223% +/- 24). The DA and NE increases in the Pfc induced by olanzapine at 3 and 10 mg/kg (s.c.) were slightly larger than those induced by clozapine at the same doses. In contrast, haloperidol (0.5 and 2 mg/kg, s.c.) did not change Pfc DA and NE levels. Extracellular levels of a DA metabolite, DOPAC, and tissue concentrations of a released DA metabolite, 3-methoxytyramine, were also increased by olanzapine, consistent with enhanced DA release. However, olanzapine at the three sequential doses did not alter the extracellular levels of either 5-HT or its metabolite, 5-HIAA, in any of the three brain areas. In conclusion, the present studies demonstrate that in the case of sequential dosing olanzapine more effectively enhances DA and NE release in the Pfc than in the subcortical areas, which may have an impact on its atypical antipsychotic actions.

Animals↗

PubMed2005

Sensitivity to voice in human prefrontal cortex.

We report two functional MRI (fMRI) experiments showing sensitivity to human voice in a region of human left inferior prefrontal cortex, pars orbitalis. The voice-enhanced response was observed for speech as well as non-linguistic vocalizations and was stronger for emotional than neutral vocalizations. This region could constitute a human prefrontal auditory domain similar to the one recently identified in the macaque brain.

Acoustic Stimulation↗

PubMed1999

Electrical stimulation of rat medial prefrontal cortex enhances forebrain serotonin output: implications for electroconvulsive therapy and transcranial magnetic stimulation in depression.

Decreased activity of the prefrontal cortex (PFC), as well as reduced serotonergic neurotransmission, is considered as a characteristic feature of major depression. The mechanism by which electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) achieve their antidepressant effects may involve changes in PFC activity. It is, however, still unclear whether these changes are accompanied by increased synaptic availability of serotonin (5-HT). In the present study, 5-HT efflux in the rat ventral hippocampus and amygdala was analyzed using in vivo microdialysis during low-current electrical stimulation of PFC and other cortical regions. Electrical stimulation of the medial PFC produced current-dependent increases in limbic 5-HT output in both urethane-anesthetized and behaving rats. No effects on 5-HT levels were seen after comparable stimulation of either the lateral parts of the PFC, the medial precentral area, the primary motor cortex or the parietal cortex. This pronounced regional specificity of the effect of medial PFC stimulation on limbic 5-HT output suggests that activation of this particular area might play a crucial role in such antidepressant treatments as ECT and TMS.

Amygdala↗

PubMed2002

Contributions of the prefrontal cortex and basal ganglia to set shifting.

Impairments of set shifting have been associated with damage to both the prefrontal cortex (PFC) and to the basal ganglia. The purpose of these experiments was to determine whether damage to the PFC was associated with shifting impairments per se or whether any switching deficits could be attributed to a reduction of working memory capacity. In contrast, shifting impairments were expected for Parkinson patients regardless of memory load, given that these patients seem to have no cognitive deficits other than when having to shift set. To vary working memory demands, a cue to the relevant dimension (letter or shape) in an odd-man-out task was presented or withheld. Pathology to prefrontal areas associated with normal aging was not linked to shifting deficits when working memory load was reduced in a comparison of older and younger adults (Experiment 1). In contrast, set-shifting abilities were still impaired for stroke patients with prefrontal damage regardless of working memory demands (Experiment 2). Parkinson patients were relatively unimpaired on this task (Experiment 2), but began to display shifting deficits when response competition was present in the display (Experiment 3).

Adult↗

PubMed2004

Domain specificity in the primate prefrontal cortex.

Experimental studies in nonhuman primates and functional imaging studies in humans have underlined the critical role played by the prefrontal cortex (PFC) in working memory. However, the precise organization of the frontal lobes with respect to the different types of information operated upon is a point of controversy, and several models of functional organizations have been proposed. One model, developed by Goldman-Rakic and colleagues, postulates a modular organization of working memory based on the type of information processing (the domain specificity hypothesis). Evidence to date has focused on the encoding of the locations of visual objects by the dorsolateral PFC, whereas the ventrolateral PFC is suggested to be involved in processing the features and identity of objects. In this model, domain should refer to any sensory modality that registers information relevant to that domain--for example, there would be visual and auditory input to a spatial information processing region and a feature analysis system. In support of this model, recent studies have described pathways from the posterior and anterior auditory association cortex that target dorsolateral spatial-processing regions and ventrolateral object-processing regions, respectively. In addition, physiological recordings from the ventrolateral PFC indicate that some cells in this region are responsive to the features of complex sounds. Finally, recordings in adjacent ventrolateral prefrontal regions have shown that the features of somatosensory stimuli can be discriminated and encoded by ventrolateral prefrontal neurons. These discoveries argue that two domains, differing with respect to the type of information being processed, and not with respect to the sensory modality of the information, are specifically localized to discrete regions of the PFC and embody the domain specificity hypothesis, first proposed by Patricia Goldman-Rakic.

Animals↗

PubMed2005

Tyrosine administration does not affect desipramine-induced dopamine levels as measured in vivo in prefrontal cortex.

Using in vivo microdialysis, we examined whether tyrosine administration would potentiate the desipramine (DMI)-induced elevation of medial prefrontal cortex (MPFC) dopamine (DA) levels. DMI (10 or 20 mg/kg IP) increased MPFC DA levels but not DOPA accumulation. Tyrosine (12.5-100 mug/ml) administered by reverse microdialysis did not affect DMI-induced MPFC DA levels. The data support our hypothesis that DA synthesis must be significantly increased in order for administered tyrosine to increase extracellular DA levels.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2003

The prefrontal cortex: insights from functional neuroimaging using cognitive activation tasks.

This review presents neuroimaging studies which have explored the functional anatomy of a variety of cognitive processes represented by the prefrontal cortex (PFC). Overall, these studies have demonstrated that standard prefrontal neuroactivation tasks recruit a widely distributed network within the brain of which the PFC consistently forms a part. As such, these results are in keeping with the notion that executive functions within the PFC rely not only on anterior (mainly prefrontal) brain areas, but also on posterior (mainly parietal) brain regions. Moreover, intervention of similar brain regions in a large number of different executive tasks suggests that higher-level cognitive functions may best be understood in terms of an interactive network of specialised anterior as well as posterior brain regions.

Animals↗

PubMed2001

Lack of adverse cognitive effects of 1 Hz and 20 Hz repetitive transcranial magnetic stimulation at 100% of motor threshold over left prefrontal cortex in depression.

OBJECTIVE: The potential therapeutic effects of repetative transcranial magnetic stimulation (rTMS) are being examined in various neuropsychiatric illnesses. This study assesses the cognitive performance of depressed patients receiving high or low frequency rTMS for 10 days. METHODS: 18 depressed patients participated in a randomized double-blind cross-over study exploring the antidepressant effects of 2 weeks (10 daily) of sham, 1 Hz, or 20 Hz rTMS administered over the left dorsolateral prefrontal cortex at 100% of motor threshold (MT). A subgroup completed a battery of cognitive tests at baseline and following each 2-week phase of treatment, and differences in performance were assessed using paired t -tests and were correlated with the degree of clinical improvement using Hamilton Depression Rating Scale scores. RESULTS: There were no major changes in cognitive test scores as a result of 10 days of either 1 Hz or 20 Hz rTMS. Moreover, any minor attenuations in cognition were not related to the degree of clinical improvement. CONCLUSIONS: Cognitive functioning in many domains following 2 weeks of 1 Hz or 20 Hz rTMS at 100% MT over the left dorsolateral prefrontal cortex in depressed patients is not disrupted.

Adult↗

PubMed2003

Representation of the temporal order of visual objects in the primate lateral prefrontal cortex.

Recollecting a past episode involves remembering the temporal order of events. We studied cellular activity in the lateral prefrontal cortex (PFC) of two monkeys that were required to remember the temporal order in which visual objects appeared and to reach for each object in the same order after a delay. Here, we report the cellular activity in the lateral PFC, focusing on the delay period. We found that 43% of the delay-period activity was selective for the sequence in which the visual objects were presented during the cue period. While the majority of cellular activity was selective for multiple sequences, some cells (31%) were selective for only one of six sequences. Our findings show that PFC cells are involved in holding temporal order information when that information is necessary for planning forthcoming motor behavior.

Animals↗

PubMed1999

Reduced neuropeptide Y mRNA expression in the prefrontal cortex of subjects with bipolar disorder.

In the present study, we compared neuropeptide Y mRNA expression levels in the prefrontal cortex (Brodmann area 9 and 46) of subjects diagnosed with major depression, bipolar disorder and schizophrenia with those in normal controls without a psychiatric history. No correlation was found regarding neuropeptide Y mRNA expression and postmortem interval, age, gender, hemisphere side, suicide as cause of death, or the history of use of substances such as alcohol, marihuana and cocaine/amphetamine. The only significant alteration found was related to the clinical diagnosis; neuropeptide Y mRNA expression was reduced in the group of bipolar subjects as compared to the controls. Overall, the present results confirm an involvement of neuropeptide Y in affective disorders, and show for the first time a specific association between NPY and bipolar disorder.

Adult↗

PubMed1999

Inhibitory effect of clonidine on ketamine-induced norepinephrine release from the medial prefrontal cortex in rats.

We have investigated the effect of clonidine on ketamine-induced norepinephrine release from the medial prefrontal cortex in rats using microdialysis. Twenty-one male Wistar rats weighing 200-300 g were allocated randomly to one of four groups: i.p. injection of ketamine 100 mg kg-1 with clonidine 0 (saline: group C0, n = 6), 3 (group C3, n = 5), 30 (group C30, n = 5) and 300 micrograms kg-1 (group C300, n = 5). As reported previously, ketamine increases norepinephrine release. In groups C0 and C3, marked increases in norepinephrine release were observed with maximum values of mean 483 (SEM 55)% and 412 (53)% compared with basal values, respectively. Although significant increases in norepinephrine release were also observed (276 (43)%) in group C30, they were significantly lower than those in groups C0 and C3 (P < 0.01 and P < 0.05, respectively). In group C300, there was a significant reduction in norepinephrine release (62 (13)%) compared with basal and the three other groups (P < 0.01). This inhibitory effect of clonidine on norepinephrine may be related to reduction in undesirable emergence reactions after ketamine anaesthesia.

Adrenergic alpha-Agonists↗

PubMed1990

Morphology of the cells within the inferior temporal gyrus that project to the prefrontal cortex in the macaque monkey.

The primate neocortex possesses an extraordinary degree of regional specialization. Virtually all cortical functions are dependent upon a complex system of reciprocal connections between related cortical regions that allow for distributed information processing. Although some aspects of the organization of these corticocortical projections are understood, little is known about the morphology and afferents to the cells of origin of long corticocortical projections in primates. We combined intracellular injection of Lucifer Yellow (LY) in fixed tissue with in vivo retrograde transport of fast blue to study the dendritic morphology of neurons within the inferior temporal gyrus (ITG) and the superior temporal sulcus (STS) that furnish corticocortical projections to the prefrontal cortex. The fast blue retrogradely labeled cells formed two clearly defined bands within the inferior temporal cortex: a supragranular band that corresponded to layer III, and an infragranular band that corresponded to layers V and VI. After Lucifer Yellow intracellular filling, these retrogradely labeled cells projecting to the prefrontal cortex were found to be morphologically very heterogeneous. Although all filled cells had spiny dendrites, they presented a wide range of cell body sizes and dendritic tree morphologies. In layer III, the majority of cells were typical pyramids of various sizes. In layers V-VI, numerous typical pyramidal cells were present. In addition, significant numbers of modified pyramidal forms were found, including vertical and horizontal fusiform cells, asymmetrical pyramids and multipolar cells. The entire dendritic arbor of individual subtypes in layers III, V, and VI was restricted to a few cortical layers, but as a group these cells had dendrites spanning the whole cortical depth. We suggest that corticocortically projecting cells are distinct from subcortically projecting cells and consist of a defined set of morphological and functional subgroups, each of which is driven by a distinct set of afferents and likely possesses different response properties.

Animals↗

PubMed2005

Task-related activity in prefrontal cortex and its relation to recognition memory performance in young and old adults.

Older adults often have more widespread prefrontal cortex (PFC) activation during memory retrieval tasks, compared to young adults, particularly in the left hemisphere. Recruitment of additional frontal activity in older adults has been attributed by some researchers to compensation, perhaps for reduced activity elsewhere in the brain, whereas others have described it as a non-selective response that may be due to a failure to inhibit these PFC regions. To address further the impact of PFC activity on memory in older adults, we used PET to measure brain activity during recognition memory tasks. Both young and old adults showed increased activity during recognition, compared to a control task, in bilateral PFC. Young adults showed greater activation of left hippocampus and lateral temporal cortex during recognition, whereas older adults showed greater activity in the right inferior frontal gyrus. Age differences also were seen in correlations between brain activity and memory performance. There were positive correlations between activity in the right parahippocampal gyrus and recognition performance in young adults, whereas positive correlations between activity in PFC and performance were found only in older adults. These positive correlations included the right inferior PFC region where older adults had greater activation. Activity in this right PFC region was negatively correlated with medial temporal activity in both groups. These results provide further evidence for age-specific patterns of brain activity underlying memory performance and are consistent with the idea that PFC assumes a larger role in supporting successful recognition memory with increasing age. The negative correlation between activity in PFC and medial temporal regions, as well as the age differences in how these regions were related to behavior, suggest that those older individuals who recruit PFC to a greater degree may do so as a compensatory response to reductions in medial temporal regions.

Adult↗

PubMedDate not supplied

Prefrontal cortex activity associated with source monitoring in a working memory task.

Using functional magnetic resonance imaging (fMRI), we investigated prefrontal cortex (PFC) activity during remembering specific source information (format, location judgments) versus remembering that could be based on undifferentiated information, such as familiarity (old/new recognition [ON], recency judgments). A working memory (WM) paradigm with an immediate test yielded greater activation in the lateral PFC for format and location source memory (SM) tasks than ON recognition; this SM-related activity was left lateralized. The same regions of PFC were recruited in Experiment 2 when information was tested immediately and after a filled delay. Substituting recency for location judgments (Experiment 3) resulted in an overall shift in task context that produced greater right PFC activity associated with ON and recency tasks compared to the format task, in addition to left SM-related activity. These data extend to WM previous findings from long-term memory (LTM) indicating that the left and right PFC may be differentially involved in memory attributions depending on the specificity of information evaluated. The findings also provide evidence for the continuity of evaluative processes recruited in WM and LTM.

Adult↗

PubMed2006

Performance-related activity in medial rostral prefrontal cortex (area 10) during low-demand tasks.

Neuroimaging studies have frequently observed relatively high activity in medial rostral prefrontal cortex (PFC) during rest or baseline conditions. Some accounts have attributed this high activity to the occurrence of unconstrained stimulus-independent and task-unrelated thought processes during baseline conditions. Here, the authors investigated the alternative possibility that medial rostral PFC supports attention toward the external environment during low-demand conditions. Participants performed a baseline simple reaction time (RT) task, along with 3 other tasks that differed in the requirement to attend to external stimuli versus stimulus-independent thought. Medial rostral PFC activation was observed in the baseline task and in a condition requiring strong engagement with external stimuli, relative to 2 conditions with a greater requirement for stimulus-independent thought. An important finding was that activity in this region was associated with faster RTs in the baseline task, ruling out an explanation in terms of task-unrelated thought processes during this condition. Thus, at least under certain circumstances, medial rostral PFC appears to support attention toward the external environment, facilitating performance in situations that do not require extensive processing of experimental stimuli.

Adult↗

PubMed2005

A direct comparison of anterior prefrontal cortex involvement in episodic retrieval and integration.

Retrieval of information from episodic memory reliably engages regions within the anterior prefrontal cortex (aPFC). This observation has led researchers to suggest that these regions may subserve processes intimately tied to episodic retrieval. However, the aPFC is also recruited by other complex tasks not requiring episodic retrieval. One hypothesis concerning these results is that episodic retrieval recruits a general cognitive process that is subserved by the aPFC. The current study tested a specific version of this hypothesis--namely, that the integration of internally represented information is this process. Event-related fMRI was employed in a 2 (memory task: encoding versus retrieval) x 2 (level of integration: low versus high) factorial within-subjects design. A functional dissociation was observed, with one aPFC subregion uniquely sensitive to level of integration and another jointly sensitive to level of integration and memory task. Analysis of event-related activation latencies indicated that level of integration and memory task effects occurred with significantly different timing. The results provide the first direct evidence regarding the functional specialization within lateral aPFC and the nature of its recruitment during complex cognitive tasks. Moreover, the study highlights the benefits of activation latency analysis for understanding functional contributions and dissociations between closely linked brain regions.

Adolescent↗

PubMed2006

Regional differences of the prefrontal cortex in pediatric PTSD: an MRI study.

Previous studies have revealed altered structural development of the frontal lobes and prefrontal cortex (PFC) in children with symptoms of posttraumatic stress disorder (PTSD). This study is the first to provide a detailed structural analysis of the PFC in children with and without PTSD symptoms. We compared gray and white matter volume in four subregions of the PFC between said groups, then explored whether volume was associated with PTSD symptom severity and functional impairment. PFC measurements were extracted from magnetic resonance imaging (MRI) data from a sample of 23 children (ages 7-14) with a history of trauma and symptoms of PTSD, who had undergone assessment for PTSD symptoms and functional impairment using the Child and Adolescent version of the Clinician-Administered PTSD Scale (CAPS-CA). These measurements were compared to data from an age-equivalent control group of 24 healthy children. Children with PTSD symptoms showed a significantly larger volume of gray matter in the delineated middle-inferior and ventral regions of the PFC than did control children. Decreased volume of gray matter in the dorsal PFC correlated with increased functional impairment scores. Results indicate that increased volume of the middle-inferior and ventral PFC may be associated with trauma and PTSD symptoms in children. Furthermore, the neuroanatomy of the dorsal PFC may influence the degree of functional impairment experienced by children with PTSD symptoms.

Adolescent↗

PubMed2006

Transcranial magnetic stimulation over dorsolateral prefrontal cortex in Parkinson's disease.

OBJECTIVE: Several studies have shown that repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) is effective in the treatment of depression in patients with Parkinson disease (PD). However, since research into the effect of this type of rTMS regime on motor function is limited, we studied the effect of rTMS over the DLPFC on the motor functions in PD patients. METHODS: Thirteen patients were randomly assigned into 2 groups, one receiving real-rTMS (90% of resting motor threshold, 10 Hz, 450 pulses-day for 10 consecutive days) over the DLPFC contralateral to the more affected side, and the other group receiving sham-rTMS. Assessment included a clinical motor evaluation using part III of the Unified Parkinson's Disease Rating Scale (UPDRS), and several motor tasks. The UPDRS was applied before and after 10 days of rTMS. Finger tapping, reach movement, grip movement and gait were measured in each session before and after the rTMS over the 10 day period. RESULTS: Statistical analysis (ANOVA for repeated measures; group *day *side *rTMS) only showed a significant effect for finger tapping, reach movement and gait for the factor day. No significant change was reported for the UPDRS in any group. CONCLUSIONS: Application of rTMS over the DLPFC as a 10 day course had no significant effect on motor functions and clinical motor status, and the improvement in performance of motor tasks can be attributed to the effects of practice. SIGNIFICANCE: rTMS over the DLPFC did not lead to any motor improvement in PD patients.

Aged↗