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Results for “Prefrontal Cortex”

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At least 631 records · Page 35Linked to original sources

PubMed2005

Essential role of D1 but not D2 receptors in methamphetamine-induced impairment of long-term potentiation in hippocampal-prefrontal cortex pathway.

Methamphetamine (MA) abuse induces deficits in cognitive performance that are related to dysfunction of the prefrontal cortex (PFC). The medial portion of the prefrontal cortex (mPFC) in rats that is crucial for cognitive function has been shown to undergo long-term potentiation (LTP) in the projections from the hippocampus. However, no study has been performed to evaluate the influence of MA on synaptic plasticity in the hippocampal-mPFC pathways. In the present experiments, we investigated the effects of repeated MA administration on hippocampal-mPFC LTP, together with MA-induced stereotyped behaviors. Repeated MA administration produced behavioral sensitization and LTP impairment in the hippocampal-mPFC pathways. The MA-induced impairment of hippocampal-mPFC LTP was prevented by the pretreatment of dopamine 1 (D1) but not dopamine 2 (D2) receptor antagonists, while D1 and D2 receptor antagonists attenuated the MA-induced stereotyped behaviors. These findings suggest that D1 receptors are crucial for the MA-induced deterioration of synaptic plasticity in the hippocampal-mPFC circuits. Impairment of LTP associated with D1 receptor dysfunction may underlie cognitive deficits in MA-dependent subjects.

Analysis of Variance↗

PubMed2006

A study of the serotonin transporter in the prefrontal cortex in late-life depression and Alzheimer's disease with and without depression.

Previous studies investigating the serotonin transporter (SERT) in depression have been inconsistent and included a large proportion of subjects who had committed suicide. In Alzheimer's disease studies have generally reported a reduction in SERT density but have not compared Alzheimer's disease subjects with and without comorbid major depression. We conducted a post mortem study of SERT density in the prefrontal cortex in normal elderly, a group of elderly depressed subjects and in Alzheimer's disease subjects with and without major depression. A post mortem study comparing SERT density in the prefrontal cortex in elderly controls (n = 10), subjects with major depression (n = 8) and subjects with Alzheimer's disease with (n = 9) and without (n = 5) comorbid major depression. We used autoradiography to measure the density of [3H]CN-IMI binding (non-specific binding determined with citalopram) to the SERT in the prefrontal cortex. We found a marked reduction in specific SERT binding in the prefrontal cortex in Alzheimer's disease subjects compared with both control (P = 0.002) and depressed subjects (P = 0.004) but no difference in SERT binding between depressed and control subjects or between Alzheimer's disease subjects with and without depression. Our study confirms previous reports of a reduction in SERT binding in Alzheimer's disease but indicates this reduction is not greater in Alzheimer's disease subjects who also have had major depression. In a group of subjects more typical of late-life depression we did not identify any alterations in SERT density.

Age of Onset↗

PubMed1996

Inescapable stress enhances extracellular acetylcholine in the rat hippocampus and prefrontal cortex but not the nucleus accumbens or amygdala.

A number of experimental results has pointed to a cholinergic involvement in the stress response. Recently, analytical techniques have become available to measure acetylcholine release in vivo during exposure to various stressors. In these experiments, microdialysis was used to monitor acetylcholine output every 15 min in the dorsal hippocampus, amygdala, nucleus accumbens and prefrontal cortex before, during and after 1 h of restraint, including a 15-min session of intermittent tail-shock (1/min, 1 mA, 1-s duration) in rats. In response to the stressful event, acetylcholine release was significantly increased in the prefrontal cortex (186%; p < 0.01) and hippocampus (168%; P < 0.01) but not in the amygdala or nucleus accumbens. The sole effects observed in the amygdala and nucleus accumbens occurred upon release from the restrainer, at which point acetylcholine levels were significantly elevated in both areas (amygdala: 150%; P < 0.05; nucleus accumbens: 13%; P < 0.05). An enhanced acetylcholine release was also evident during this sample period in the hippocampus and prefrontal cortex. These data demonstrate an enhancement of cholinergic activity in response to stress in two acetylcholine projection systems (hippocampus and prefrontal cortex) but not in the intrinsic acetylcholine system of the nucleus accumbens or the extrinsic innervation of the amygdala. Moreover, the data showed that relief from stress was accompanied by a more ubiquitous acetylcholine response that extended to each site tested.

Acetylcholine↗

PubMed2004

GABAA receptor gamma subunits in the prefrontal cortex of patients with schizophrenia and bipolar disorder.

Immunohistochemical and immunoblot techniques were employed in order to examine alterations of the GABAA receptor gamma subunits in the prefrontal cortex from postmortem subjects with schizophrenia and bipolar disorder. Immunohistochemically, gamma 1/3 immunolabeling in the neuronal soma in the prefrontal cortex from subjects with bipolar disorder was more intense than that of the controls and the subjects with schizophrenia. The intensity of gamma 1/3 immunolabeling of the schizophrenic subjects was comparable with that of the controls. Immunoblot analysis demonstrated a significant increase in the gamma 1 subunit in the bipolar subjects, whereas no remarkable difference was detected in the schizophrenic subjects. The present study suggests that the GABAA receptor gamma subunit is differentially involved in schizophrenia and bipolar disorder, and that the gamma subunit is up-regulated in the prefrontal cortex of subjects with bipolar disorder.

Adult↗

PubMed1989

Stimulation in prefrontal cortex area inhibits cardiovascular and motor components of the defence reaction in rats.

In the present investigation it was shown that electrical or chemical (D,L-homocysteic acid, DLH) stimulation in a defined area of the medial prefrontal cortex inhibits cardiovascular components of the defence reaction elicited by stimulation in the basal nucleus of the amygdala or in the hypothalamus in rats anaesthetized by Saffan. Electrical stimulation in the dorsal part of the nucleus accumbens or ventral part of the nucleus caudate had the same effect, while chemical stimulation (DLH) in these areas was not effective. In unanaesthetized rats stimulation in the prefrontal cortex or the nucleus accumbens inhibited cardiovascular and motor components of the defence reaction induced from the amygdala or hypothalamus. Stimulation in the described areas of the medial prefrontal cortex or nucleus accumbens does not induce general inhibition of motor activity since it did not affect operant, appetitive bar pressing. It is therefore concluded that the inhibition is selectively addressed to the motor activities associated with the defence reaction. It is suggested that inhibition of the cardiovascular components of the defence reaction must occur below hypothalamic level. The inhibition is most likely presynaptic since stimulation in the prefrontal cortex or nucleus accumbens alone did not produce any cardiovascular changes. It is unlikely that the efferent pathway originating in the prefrontal inhibitory area relays in the nucleus accumbens since microinjection of DLH into this nucleus was ineffective. Stimulation in "sympatho-inhibitory' areas (anterior hypothalamus, anterior cingulum) or in the nucleus raphe obscurus had no inhibitory effect on the cardiovascular components of the defence reaction.

Animals↗

PubMed2003

Dopaminergic involvement in medial prefrontal cortex and core of the nucleus accumbens in the regulation of ethanol self-administration: a dual-site microinjection study in the rat.

The complex mesolimbic-mesocortical system involved with behavioral selection has been implicated in the control of ethanol self-administration. However, the nature of the interactions within this multiple-structured system in ethanol intake regulation remains unclear. Although the role of dopamine (DA) in the prefrontal cortex and the nucleus accumbens has been examined individually, the interaction of DA activity in both structures at the same time remains to be examined. Male, Long-Evans rats were initiated to self-administer ethanol in an operant situation using the sucrose-substitution procedure. Following initiation, bilateral cannula guides were located to allow microinjection in the medial prefrontal cortex (mPFC) and the core of the nucleus accumbens. The DA D2/D3 agonist quinpirole (10.0-microg dose in the prefrontal cortex; 4.0-microg dose in n. accumbens) and the D2 antagonist raclopride (0.05-microg dose in prefrontal cortex; 1.0-microg dose in the nucleus accumbens) were then tested in each site alone and in combination in both sites in each rat. Changes in total responding, ethanol intake, and the pattern of responding were analyzed. Single-site injections replicated most of our previous findings for these doses. Changes in single-site effects were found when dual-site injections were performed, with altered input from the prefrontal areas impacting the effects of accumbens injections. Based on these interactions, our hypothesis that the prefrontal area is involved with the onset and offset of drinking, while the nucleus accumbens is involved with maintaining the ongoing behavior, remains viable.

Alcohol Drinking↗

PubMed2007

Phosphorylation of CREB and DARPP-32 during late LTP at hippocampal to prefrontal cortex synapses in vivo.

Specific patterns of stimulation applied in the ventral hippocampus produce long-term potentiation (LTP) of postsynaptic synapses in the prefrontal cortex in vivo. The induction of LTP is dependent on NMDA receptors and cAMP-dependant kinase (PKA) activation. Yet little is known concerning the cellular mechanisms underlying the expression of this neocortical form of LTP. In the present study, we tested whether LTP at hippocampal to prefrontal cortex synapses leads to activation of DARPP-32 and CREB as well as defined the temporal regulation of the phosphorylation states of both proteins. Our data indicate a peak in CREB and DARPP-32 phosphorylation during the late phase of prefrontal LTP (2 h posttetanus). These findings support the hypothesis that prolonged expression of hippocampal-prefrontal cortex LTP depends on a synergistic mechanism involving phosphorylation of both CREB and DARPP-32 via activation of the cAMP/PKA-dependent pathway.

Animals↗

PubMed2003

Excitotoxic lesions of the prelimbic-infralimbic areas of the rodent prefrontal cortex disrupt motor preparatory processes.

The medial prefrontal cortex (mPFC) is involved in a variety of cognitive and emotional processes; in rodents its implication in motor planning is less known, however. We therefore investigated how the mPFC contributes to the information processes involved in the execution of a reaction time task in rats. Subjects were trained to rapidly release a lever at the onset of a cue light, which was presented after an unpredictable period of variable duration (500, 750, 1000 and 1250 ms). Excitotoxic lesions of the whole mPFC or two mPFC subregions [e.g. the dorsal anterior cingulate and the prelimbic-infralimbic (PL-IL) areas] were achieved by intracerebral infusions of ibotenic acid (9.4 micro g/ micro L) at different volumes. Extensive mPFC lesions produced increased premature responding and disrupted motor readiness, e.g. the distribution of preparatory patterns during the variable preparatory periods. The deficits lasted for 3 weeks and could be reinstated 2 months after the lesion by varying the duration of the preparatory periods to increase time uncertainty. Furthermore, lesions restricted to the PL-IL cortex areas reproduced all the deficits of mPFC lesions, whereas pregenual anterior cingulate cortex lesions had no effect. The results emphasize a critical role of the rat PL-IL region in motor preparatory processes. Hence, discrete lesions of this area reproduce some deficits such as impairment of time estimation and disinhibitory behaviours observed in humans with frontal hypoactivity.

Animals↗

PubMed1999

Choosing between small, likely rewards and large, unlikely rewards activates inferior and orbital prefrontal cortex.

Patients sustaining lesions of the orbital prefrontal cortex (PFC) exhibit marked impairments in the performance of laboratory-based gambling, or risk-taking, tasks, suggesting that this part of the human PFC contributes to decision-making cognition. However, to date, little is known about the particular regions of the orbital cortex that participate in this function. In the present study, eight healthy volunteers were scanned, using H(2)(15)0 PET technology, while performing a novel computerized risk-taking task. The task involved predicting which of two mutually exclusive outcomes would occur, but critically, the larger reward (and penalty) was associated with choice of the least likely outcome, whereas the smallest reward (and penalty) was associated with choice of the most likely outcome. Resolving these "conflicting" decisions was associated with three distinct foci of regional cerebral blood flow increase within the right inferior and orbital PFC: laterally, in the anterior part of the middle frontal gyrus [Brodmann area 10 (BA 10)], medially, in the orbital gyrus (BA 11), and posteriorly, in the anterior portion of the inferior frontal gyrus (BA 47). By contrast, increases in the degree of conflict inherent in these decisions was associated with only limited changes in activity within orbital PFC and the anterior cingulate cortex. These results suggest that decision making recruits neural activity from multiple regions of the inferior PFC that receive information from a diverse set of cortical and limbic inputs, and that the contribution of the orbitofrontal regions may involve processing changes in reward-related information.

Adult↗

PubMedDate not supplied

Interactions of prefrontal cortex during eyeblink conditioning as a function of age.

Changes in regional cerebral blood flow (rCBF) in eleven elderly subjects during pairings of tone and air puff were compared to rCBF changes during pairings in young subjects. Although all subjects reported being aware of the relationship between tone and air puff, elderly subjects did not condition as well as young subjects and their rCBF measures were attenuated. Covarying the performance differences between young and old subjects did not change this conclusion suggesting that differences in neural activation during learning are related to binding of CS-US information prior to the impact of the association on performance. Both groups showed learning-specific rCBF changes in cerebellum, inferior right prefrontal cortex and posterior cingulate. However, only in young subjects were there learning-specific changes in rCBF in left temporal cortex, midbrain, caudate, and inferior left prefrontal cortex. Analysis of learning-dependent patterns of functional connectivity of inferior left prefrontal cortex showed only young subjects had a strong left prefrontal functional connectivity with cerebellum, hippocampus, thalamus and temporal cortex. Thus, beyond changes in regional activity, these data also suggest that age may alter the operations of functional networks underlying learning and memory.

Adolescent↗

PubMed2004

The neuropsychology of ventral prefrontal cortex: decision-making and reversal learning.

Converging evidence from human lesion, animal lesion, and human functional neuroimaging studies implicates overlapping neural circuitry in ventral prefrontal cortex in decision-making and reversal learning. The ascending 5-HT and dopamine neurotransmitter systems have a modulatory role in both processes. There is accumulating evidence that measures of decision-making and reversal learning may be useful as functional markers of ventral prefrontal cortex integrity in psychiatric and neurological disorders. Whilst existing measures of decision-making may have superior sensitivity, reversal learning may offer superior selectivity, particularly within prefrontal cortex. Effective decision-making on existing measures requires the ability to adapt behaviour on the basis of changes in emotional significance, and this may underlie the shared neural circuitry with reversal learning.

Animals↗

PubMed1999

Dissociative effects of apomorphine infusions into the medial prefrontal cortex of rats on latent inhibition, prepulse inhibition and amphetamine-induced locomotion.

Impaired ability to "gate out" sensory and cognitive information is considered to be a central feature of schizophrenia and is manifested, among others, in disrupted prepulse inhibition and latent inhibition. The present study investigated, in rats, the effects of increasing dopamine receptor activation within the medial prefrontal cortex by local administration of the dopamine receptor agonist apomorphine (9 microg/side) on prepulse inhibition and latent inhibition, as well as on spontaneous and amphetamine-induced activity. Apomorphine infusions decreased spontaneous locomotor activity and blocked amphetamine-induced increase in locomotor activity in the open field, which is in line with the suggestion that dopamine receptor activation in the medial prefrontal cortex inhibits mesolimbic dopamine activity. However, apomorphine infusions induced a disruption of prepulse inhibition, an effect associated with increased dopaminergic activity in the nucleus accumbens, and left the latent inhibition effect intact. While these results support previous evidence that the medial prefrontal cortex is a component of the neural circuitry mediating prepulse inhibition but plays no role in latent inhibition, they show that dopamine receptor activation in the medial prefrontal cortex of the rat produces behavioural outcomes that cannot be explained by postulating a simple reciprocal relationship between the mesocortical and mesolimbic dopamine systems.

Amphetamine↗

PubMed1999

Rostral and orbital prefrontal cortex dysfunction in the manic state of bipolar disorder.

OBJECTIVE: This study investigated prefrontal cortex function in the manic state of bipolar disorder. METHOD: High-sensitivity [15O]H2O positron emission tomography and a word generation activation paradigm were used to study regional cerebral blood flow in five manic and six euthymic individuals with bipolar disorder and in five healthy individuals. RESULTS: Decreased right rostral and orbital prefrontal cortex activation during word generation and decreased orbitofrontal activity during rest were associated with mania. CONCLUSIONS: The data support the presence of rostral and orbital prefrontal dysfunction in primary mania. These findings, when seen in the context of the human brain lesion and the behavioral neuroanatomic literatures, may help to explain some of the neurobehavioral abnormalities characteristic of the manic state.

Adult↗

PubMed1998

Dopamine and acetylcholine elevation on lever-press acquisition in rat prefrontal cortex.

To determine whether the rat medial prefrontal cortex (PFC) is involved in acquiring operant learning, we observed changes in extracellular concentration of dopamine (DA) and acetylcholine (ACh) in the rat medial PFC during lever-press acquisition (acquisition group) or retrieval (retention group) using in vivo microdialysis. We found that DA or ACh elevation related to acquisition occurred. DA elevation was observed in the acquisition group only. These results indicate that the medical PFC is related to acquisition, and suggest that interaction between DA and ACh may be involved in learning acquisition.

Acetylcholine↗

PubMed2000

Prefrontal cortex activation in task switching: an event-related fMRI study.

When a switch between two tasks has to be carried out, performance is slower than in trials where the same task is performed repeatedly. This finding has been attributed to time-consuming control processes required for task switching. Previous results of other paradigms investigating cognitive control processes suggested that prefrontal cortex is involved in executive control. We used event-related fMRI to investigate prefrontal cortex involvement in task switching. Regions in the lateral prefrontal and premotor cortex bilaterally, the anterior insula bilaterally, the left intraparietal sulcus, the SMA/pre-SMA region and the cuneus/precuneus were activated by the task repetition condition and showed additional activation in the task switch condition. This confirmed the hypothesis that lateral prefrontal cortex is involved in task switching. However, the results also showed that this region is neither the only region involved in task switching nor a region specifically involved in task switching.

Adult↗

PubMed2005

Delay-period activity in the prefrontal cortex: one function is sensory gating.

The prefrontal cortex (PFC) contributes to working memory functions via executive control processes that do not entail the storage, per se, of mnemonic representations. One of these control processes may be a sensory gating mechanism that facilitates retention of representations in working memory by down-regulating the gain of the sensory processing of intervening irrelevant stimuli. This idea was tested by scanning healthy young adults with functional magnetic resonance imaging while they performed a delayed face-recognition task. The 2 x 2 factorial design varied the factors of Memory (present, absent) and Distraction (present, absent). During memory-present trials, target and probe stimuli were individual gray-scale male faces. Memory-absent trials were identical, except that they employed the same recurring female faces (denoting a "no memory" trial). Distraction-present trials featured rapid serial visual presentation of bespectacled male faces during the two middle seconds of the delay. The first step of the analyses identified dorsolateral PFC (dlPFC) and inferior occipitotemporal cortex (IOTC) voxels exhibiting delay-period activity in memory-present/distraction-absent trials, that is, the "unfilled" delay. Within these voxels, distraction-evoked activity in the dlPFC was markedly higher during trials that required the concurrent short-term retention of information than on those that did not, whereas the opposite effect was seen in the IOTC. These results are consistent with the view that processes related to sensory gating account for a portion of the delay-period activity that is routinely observed in the dlPFC.

Adult↗

PubMed2000

Functional asymmetry of human prefrontal cortex in verbal and non-verbal episodic memory as revealed by fMRI.

Functional neuroimaging studies have demonstrated preferential involvement of bilateral prefrontal cortex during episodic memory encoding and retrieval. The aim of the present study is to address the question whether left prefrontal model for encoding holds when highly non-verbal material is used, and which region of the brain is critically related to successful retrieval. To do this, seven normal subjects were investigated using functional magnetic resonance imaging (fMRI) during encoding and retrieval of word and checkerboard pattern. Our results revealed that word encoding activated the left prefrontal cortices and right cerebellum, whereas pattern encoding activated the bilateral middle frontal gyrus, superior parietal lobule, premotor area, and occipital visual cortex. Word-specific activation was found in the ventral prefrontal cortices, and pattern-specific activation located in the right dorsal prefrontal cortex. Conjunction analysis during encoding of word and pattern showed that activity in the left dorsal prefrontal cortex and the right cerebellum might relate to common neural network for encoding regardless of the type of material. Finally, the present study demonstrates strong association between the left ventral prefrontal cortex and retrieval success for word. The evidence, that both encoding and retrieval of words activated the left ventral prefrontal cortex, indicates that this area is involved in active and strategic operation of the mnemonic representation. A lack of the right prefrontal activation during retrieval was interpreted as that activity in this region might relate to retrieval effort rather than success.

Adult↗

PubMed2000

Increased noradrenergic activity in prefrontal cortex slices of an animal model for attention-deficit hyperactivity disorder--the spontaneously hypertensive rat.

Spontaneously hypertensive rats (SHR) are used as a model for attention-deficit/hyperactivity disorder (ADHD) since SHR are hyperactive and they show defective sustained attention in behavioral tasks. Using an in vitro superfusion technique we showed that norepinephrine (NE) release from prefrontal cortex slices of SHR was not different from that of their Wistar-Kyoto (WKY) control rats when stimulated either electrically or by exposure to buffer containing 25 mM K(+). The monoamine vesicle transporter is, therefore, unlikely to be responsible for the deficiency in DA observed in SHR, since, in contrast to DA, vesicle stores of NE do not appear to be depleted in SHR. In addition, alpha(2)-adrenoceptor mediated inhibition of NE release was reduced in SHR, suggesting that autoreceptor function was deficient in prefrontal cortex of SHR. So, while DA neurotransmission appears to be down-regulated in SHR, the NE system appears to be under less inhibitory control than in WKY suggesting hypodopaminergic and hypernoradrenergic activity in prefrontal cortex of SHR. These findings are consistent with the hypothesis that the behavioral disturbances of ADHD are the result of an imbalance between NE and DA systems in the prefrontal cortex, with inhibitory DA activity being decreased and NE activity increased relative to controls.

Adrenergic alpha-Agonists↗