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PubMed1987

Immunocytochemical localization of dopamine in the prefrontal cortex of the rat at the light and electron microscopical level.

In the present study the dopaminergic innervation of the prefrontal cortex was studied by means of a recently developed anti-dopamine serum. This method can demonstrate endogenous dopamine in a specific way, and offers the opportunity to study the distribution of dopaminergic fibres in the cortex in detail in counterstained sections. Furthermore, dopaminergic nerve endings can be visualized at the electron microscopic level. Light microscopic observations demonstrated that the highest density of dopaminergic fibres in the frontal cortex is found in the prefrontal cortex and the infralimbic cortex. Within the prefrontal cortex, a good correlation is found between regional differences in distribution of dopaminergic fibres and the cytoarchitectonic parcellation of this part of the cortex. Outside the prefrontal cortex dopaminergic fibres were observed in adjacent frontal areas, the cortex surrounding the entire rhinal sulcus and the retrosplenial cortex. Electron microscopic observations demonstrated dopaminergic terminals through all cortical layers. The majority of dopaminergic terminals in the prefrontal cortex from synaptic contacts with dendritic processes. The synaptic profiles were usually symmetric and were characterized by the presence of many clear vesicles and an occasional dense-core vesicle.

Animals↗
PubMed2004

Lesions to the basolateral amygdala and the orbitofrontal cortex but not to the medial prefrontal cortex produce an abnormally persistent latent inhibition in rats.

Repeated nonreinforced preexposure to a stimulus interferes with the establishment of conditioned responding to this stimulus when it is subsequently paired with reinforcement. This stimulus-preexposure effect is known as latent inhibition (LI). Rather remarkably, LI appears to be resistant to the effects of numerous lesions, including the prefrontal cortex (PFC) and the basolateral amygdala (BLA). However, intact behavioral expression of LI following damage to given brain regions does not preclude the possibility that such regions participate in the regulation of LI expression in the intact brain. The present study showed that lesions of the BLA and the orbitofrontal cortex (OFC) but not of the medial PFC (mPFC) led to an abnormally persistent LI which emerged under conditions that disrupted LI in control rats. LI was measured in a thirst motivated conditioned emotional response procedure by comparing suppression of drinking in response to a tone in rats which received 0 (nonpreexposed) or 40 tone presentations (preexposed) followed by either two or five tone-shock pairings. Control rats showed LI with 40 preexposures and two conditioning trials, but raising the number of conditioning trials to five disrupted LI. OFC- and BLA-lesioned rats showed LI under the former condition but in addition persisted in exhibiting LI under the latter condition. Rats with lesion of the mPFC did not show persistent LI. Thus, although LI does not depend on the integrity of BLA and OFC (because it is present in BLA- and OFC- lesioned rats even under conditions disrupting the phenomenon in normal rats), these regions play an important role in the modulation of its expression, more specifically, in the control of the non-expression of LI when the impact of conditioning increases beyond a certain level.

Amygdala↗
PubMed2005

Hypocretin and nicotine excite the same thalamocortical synapses in prefrontal cortex: correlation with improved attention in rat.

Thalamic projections to prefrontal cortex are important for executive aspects of attention. Using two-photon imaging in prefrontal brain slices, we show that nicotine and the wakefulness neuropeptide hypocretin (orexin) excite the same identified synapses of the thalamocortical arousal pathway within the prefrontal cortex. Although it is known that attention can be improved when nicotine is infused directly into the midlayer of the prefrontal cortex in the rat, the effects of hypocretin on attention are not known. The overlap in thalamocortical synapses excited by hypocretin and nicotine and the lack of direct postsynaptic effects prompted us to compare their effects on a sustained and divided attention task in the rat. Similar to nicotine, infusions of hypocretin-2 peptide into the prefrontal cortex significantly improved accuracy under high attentional demand without effects on other performance measures. We show for the first time that hypocretin can improve attentional processes relevant to executive functions of the prefrontal cortex.

Action Potentials↗
PubMed1998

Synaptic targets of pyramidal neurons providing intrinsic horizontal connections in monkey prefrontal cortex.

xũ I sLxxJ In monkey prefrontal cortex, the intrinsic axon collaterals of supragranular pyramidal neurons extend horizontally for considerable distances through the gray matter and give rise to stripe-like clusters of axon terminals (Levitt et al. [1993] J. Comp. Neurol. 338:360-376). Because understanding the functional role of these connections requires knowledge of their synaptic targets, we made injections of biotinylated dextran amine (BDA) into layer 3 of macaque prefrontal area 9 and examined the labeled intrinsic axon collaterals by electron microscopy. Labeled axon terminals formed exclusively asymmetric synapses, and 95.6% of the postsynaptic structures were dendritic spines, presumably belonging to other pyramidal neurons. The remaining postsynaptic structures were dendritic shafts, many of which had the morphological characteristics of local circuit neurons. The prefrontal injections also labeled associational projections that traveled through the white matter to terminate in other areas of prefrontal cortex. All of the synapses formed by these associational axons were asymmetric, and 91.9% were onto dendritic spines. The similarities in synaptic targets of the prefrontal intrinsic and associational axon terminals suggested that these projections might arise from the same neurons, an interpretation confirmed in dual label, retrograde tracing studies. To determine the specificity of the synaptic targets of these prefrontal connections, two additional comparisons were made. In the posterior parietal cortex (area 7a), 94.2% of the synapses furnished by BDA-labeled intrinsic collaterals of supragranular pyramidal neurons were also with dendritic spines. In contrast, only 75.6% of unlabeled asymmetric synapses in the prefrontal cortex were onto dendritic spines. These comparisons suggest that the axons of supragranular pyramidal neurons in primate association cortices are preferentially directed to specific targets. Finally, after injections of BDA, a small number of retrogradely labeled pyramidal neurons were observed within the anterogradely labeled clusters of intrinsic axon terminals. At the ultrastructural level, synapses between anterogradely labeled axon terminals and retrogradely labeled dendritic spines were identified. These findings suggest that reciprocal, monosynaptic connections may exist between pyramidal neurons located in different stripe-like clusters, providing a potential anatomical substrate for reverberating excitatory circuits within the primate association cortices.

Animals↗
PubMed2003

Transient activation of superior prefrontal cortex during inhibition of cognitive set.

The prefrontal cortex implements a set-shifting function that includes inhibition of a previously acquired cognitive set. The impairment of the inhibitory function results in perseverative behavior that forms one characteristic feature of frontal lobe dysfunction. Previous neuroimaging studies have revealed inhibitory mechanisms in the inferior prefrontal cortex. The present functional magnetic resonance imaging study devised "dual-match" stimuli in a set-shifting paradigm that allowed us to temporally isolate the inhibitory processes recruited during exposure to a previously acquired set. Transient activation time-locked to the isolated inhibition was revealed in the left middle frontal gyrus near the superior frontal sulcus. In a control experiment conducted after subjects had been informed and made aware of the exposure, however, the superior prefrontal activation disappeared, and prominent activation was revealed in a set of brain regions that included the left posterior inferior frontal sulcus. These double dissociation results indicate inhibitory mechanisms in the superior prefrontal cortex, alternative to the inferior prefrontal ones, that are activated depending on the subjects' strategy for inhibition of cognitive set.

Adult↗
PubMed2004

Decreased expression of mineralocorticoid receptor mRNA in the prefrontal cortex in schizophrenia and bipolar disorder.

Abnormal prefrontal cortical activity, activation of the hypothalamic-pituitary-adrenal (HPA) axis, and deficits in slow-wave sleep (SWS) have been extensively reported in patients with affective disorders and schizophrenia, yet the underlying pathophysiological mechanisms have not been completely elucidated. Mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) are two nuclear hormone receptors of primary importance in the control of stress-related and circadian HPA activity. A recent study showed that blocking brain MR activity not only enhances CRF-induced ACTH and cortisol release, but also significantly reduces SWS in humans. We hypothesized that the expression of MR would be deficient in the prefrontal cortex of patients with schizophrenia and affective disorders. The MR mRNA expression in the post-mortem prefrontal cortex of patients with major depression (MD), bipolar (BP), and schizophrenic (SZ) disorders and non-psychiatric controls (n=15 for each patient group, and n=14 for controls) was determined by in-situ hybridization. In the dorsolateral prefrontal cortex Brodmann's area 9 (BA 9), MR mRNA was significantly lower (p<0.05) in all laminae (I-VI) in BP, and in laminae I, III, IV and VI in SZ than in the controls. MR mRNA in BA 9 was negatively correlated with the duration of psychiatric illnesses. In BA 46, MR mRNA was not significantly different among groups, but was positively correlated with brain pH. These results provide the first evidence of deficient prefrontal MR mRNA expression in BP and SZ. Whether these findings may be linked to the abnormal prefrontal function, HPA axis activation, or the deficits in SWS found in these major psychiatric illnesses remains to be further explored.

Adult↗
PubMed1995

Role of human prefrontal cortex in attention control.

Without a functioning dorsolateral prefrontal cortex, humans are stimulus bound and have little confidence in their ability to interact with the environment. Deficits in inhibitory control of external and internal processes coupled with impaired temporal coding of stimuli and detection capacity for novel events leave the patient functioning in a noisy internal environment without critical spatiotemporal cues. Some of these proposals are similar to those of Nauta (104). Based on connectivity of the prefrontal cortex, Nauta suggested that this region was ideally suited to generate and evaluate internal models of action. It is proposed that, in addition to this generation function, the prefrontal cortex is crucial for detecting changes in the external environment and for discriminating internally and externally derived models of the world. This chapter has described a cascade of deficits that result from damage to the dorsolateral prefrontal cortex. Awareness of the sensory world, and of the apparent stream of internal and external events, is impaired by deficits in novelty detection. Changes in the world, internal or external, may not be noticed in a noisy internal milieu. These deficits contribute to impaired reality monitoring and to a subsequent lack of confidence in behavior. An inability to bridge temporal gaps and temporally sequence internal events, together with deficits in inhibitory control systems, contribute to an impairment in the ability to generate coherent representations of alternate or counterfactual realities.

Animals↗
PubMed2005

Dissociable controlled retrieval and generalized selection mechanisms in ventrolateral prefrontal cortex.

How does ventrolateral prefrontal cortex (VLPFC) control mnemonic processing? Alternative models propose that VLPFC guides top-down (controlled) retrieval of knowledge from long-term stores or selects goal-relevant products of retrieval from among competitors. A paucity of evidence supports a retrieval/selection distinction, raising the possibility that these models reduce to a common mechanism. Here, four manipulations varied semantic control demands during fMRI: judgment specificity, cue-target-associative strength, competitor dominance, and number of competitors. Factor analysis revealed evidence for a metafactor that accounted for common behavioral variance across manipulations and for functional variance in left mid-VLPFC. These data support a generalized control process that selects relevant knowledge from among competitors. By contrast, left anterior VLPFC and middle temporal cortex were sensitive to cue-target-associative strength, but not competition, consistent with a control process that retrieves knowledge stored in lateral temporal cortex. Distinct PFC mechanisms mediate top-down retrieval and postretrieval selection.

Adolescent↗
PubMed1993

Postnatal development of the cholecystokinin innervation of monkey prefrontal cortex.

Although the structure and function of primate prefrontal cortex undergo substantial modifications during postnatal development, relatively little is known about the maturation of neurotransmitter systems in these cortical regions. In the primate brain, cholecystokinin is present in the greatest concentrations in prefrontal regions. Thus, in this study, we used immunohistochemical techniques to investigate the postnatal development of the cholecystokinin innervation of monkey prefrontal cortex. In animals aged 4 days through adult, cholecystokinin immunoreactivity was present in nonpyramidal neurons that appeared to represent at least two distinct cell types. The most common type was a vertically oval bitufted neuron, located in layers II-superficial III, which typically had a radially descending axon that gave rise to short collaterals in layer IV. Another frequently observed cell type was a larger multipolar neuron located in the superficial half of layer III. The axon of these neurons branched locally in the vicinity of the cell body. The greatest density of cholecystokinin-containing neurons and processes was present in monkeys less than 1 month of age. The density of immunoreactive structures in every prefrontal region then progressively declined with increasing age, with the most marked changes occurring during the first postnatal year. As a result, the density of labeled neurons in adult monkeys was less than one-third of that in neonatal monkeys. However, labeled structures were significantly more dense in some ventromedial and orbital regions than in dorsal regions of the prefrontal cortex in neonatal, but not in older animals. In all animals, cholecystokinin-containing neurons were present in highest density in layers II-superficial III, and labeled terminal fields were observed in layers II, IV, and VI. In animals less than 1 month of age, fascicles of radial fibers traversed through layers III and V, whereas in animals 1 to 3 months of age, individual radial fibers rather than fiber bundles were present in layers III and V. In addition, immunoreactive pericellular arrays, which appeared to surround unlabeled nonpyramidal cells, were present in layers V and VI and the subcortical white matter in the youngest monkeys. Although many aspects of the cholecystokinin innervation of monkey prefrontal cortex remain constant during postnatal life, the distinct developmental changes in the cholecystokinin innervation of these regions suggest that it may play an important role in the maturation of the cortical circuitry that mediates the acquisition of certain cognitive abilities.

Animals↗
PubMed2002

Segregation of areas related to visual working memory in the prefrontal cortex revealed by rTMS.

The functional organization of working memory (WM) in the human prefrontal cortex remains unclear. Storage and processing functions might be segregated in ventral and dorsal areas of the prefrontal cortex, respectively. If so, storage functions might be spared, irrespective of informational domain, following damage or dysfunction in dorsolateral areas. Alternatively, WM and prefrontal function in general might be segregated according to informational domains (e.g. spatial versus object-based information). In the present study we used repetitive transcranial magnetic stimulation (rTMS) to directly test these competing hypotheses. We applied rTMS to transiently and selectively disrupt the function of the dorsomedial, dorsolateral or ventral prefrontal cortex in normal human volunteers performing either a spatial or a face-recognition delayed-response task. Performance in the spatial task was impaired by rTMS of the dorsomedial prefrontal cortex. Performance in the face-recognition (non-spatial) task was impaired by rTMS of the ventral prefrontal cortex. Transient disruption of the dorsolateral prefrontal cortex affected performance in both tasks. These findings provide evidence of domain-specific segregation of WM functions in widely separated areas of prefrontal cortex.

Adult↗
PubMed2003

Acute mania is accompanied by elevated glutamate/glutamine levels within the left dorsolateral prefrontal cortex.

RATIONALE: The dorsolateral prefrontal cortex (DLPFC) participates in the pathophysiology of mania. In particular, left-sided structural and metabolic abnormalities have been described. OBJECTIVES: Clinical symptoms may be due to hyperactivity of cortical glutamatergic neurons, resulting in increased excitatory neurotransmitter flux and thus enhanced Glx levels. METHODS: Glutamate/glutamine (Glx) levels were assessed by proton magnetic resonance spectroscopy ((1)H-MRS) in eight acute manic patients compared with age- and gender-matched controls. RESULTS: Manic patients had significantly elevated Glx levels ( t-test; t=-3.1, P=0.008) within the left DLPFC. CONCLUSIONS: Our results indicate that the prefrontal cortical glutamatergic system is involved in the pathophysiology of acute mania. This may have implications for the treatment of mania.

Acute Disease↗
PubMed1989

Phencyclidine-induced activation of ventral tegmental A10 dopamine neurons is differentially affected by lesions of the nucleus accumbens and medial prefrontal cortex.

The nucleus accumbens and medial prefrontal cortex contain high concentrations of phencyclidine (PCP) binding sites as well as supply inhibitory and excitatory inputs to the ventral tegmental area (VTA). Thus these two regions could be instrumental in mediating the unique bimodal response of A10 neurons to systemically administered PCP. Therefore we evaluated electrophysiologically the effects of lesions of these two areas on this pattern of response. In sham-lesioned controls, i.v. injections of PCP elicited a typical dose-dependent bimodal effect which was characterized by an activation of A10 firing at low dose (reaching a maximum of +44% at 1 mg/kg) followed by a slowing of this response with larger doses. However, in animals with kainic acid or radiofrequency lesions of the nucleus accumbens, PCP produced only a unimodal response resulting in sustained and elevated (+88% in kainate and +55% in radiofrequency lesioned groups) firing rates. Notably, neither basal activity nor the degree of activation of the A10's at doses of PCP less than 1 mg/kg were affected by the lesions. In contrast, excitotoxic destruction of the medial prefrontal cortex had no effect on the response of A10 neurons to PCP even though basal activity was slightly elevated in this group. These results suggest that the inhibitory component of the bimodal response of VTA neurons to systemic PCP is mediated via feedback pathways from the nucleus accumbens, but that the mesocortical prefrontal cortex does not appear to modulate any portion of this bimodal response.

Animals↗
PubMed2004

Dopamine enhances spatiotemporal spread of activity in rat prefrontal cortex.

Dopaminergic modulation of prefrontal cortex (PFC) is important for neuronal integration in this brain region known to be involved in cognition and working memory. Because of the complexity and heterogeneity of the effect of dopamine on synaptic transmission across layers of the neocortex, dopamine's net effect on local circuits in PFC is difficult to predict. We have combined whole cell patch-clamp recording and voltage-sensitive dye imaging to examine the effect of dopamine on the excitability of local excitatory circuits in rat PFC in vitro. Whole cell voltage-clamp recording from visually identified layer II/III pyramidal neurons in rat brain slices revealed that, in the presence of bicuculline (10 microM), bath-applied dopamine (30-60 microM) increased the amplitude of excitatory postsynaptic currents (EPSCs) evoked by weak intracortical stimulus. The effect was mimicked by the selective D1 receptor agonist SKF 81297 (1 microM). Increasing stimulation resulted in epileptiform discharges. SKF 81297 (1 microM) significantly lowered the threshold stimulus required for generating epileptiform discharges to 83% of control. In the imaging experiments, bath application of dopamine or SKF 81297 enhanced the spatiotemporal spread of activity in response to weak stimulation and previously subthreshold stimulation resulted in epileptiform activity that spread across the whole cortex. These effects could be blocked by the selective D1 receptor antagonist SCH 23390 (10 microM) but not by the D2 receptor antagonist eticlopride (5 microM). These results indicate that dopamine, by a D1 receptor-mediated mechanism, enhances spatiotemporal spread of synaptic activity and lowers the threshold for epileptiform activity in local excitatory circuits within PFC.

Animals↗
PubMedDate not supplied

No deficit in total number of neurons in the prefrontal cortex in schizophrenics.

The prefrontal cortex (PFC), defined as the cortical region which has the major reciprocal connections with the mediodorsal thalamic nucleus (MD), has often been implicated in schizophrenia. Morphometric studies have shown altered neuronal density and structure in parts of the PFC in schizophrenic brains. In addition, the MD and nucleus accumbens have shown a significant deficit in total neuron number. The purpose of the present study was to estimate the total neuron number in the PFC in schizophrenics and controls. Using a stereological design, the PFC was studied in eight brains from schizophrenic patients and 10 age-matched control brains. The bilateral average total number of neurons in the PFC was estimated to be 2.76 x 10(9) (CV=S.D./mean=0.15) in the schizophrenic brains whereas that of controls was a non-significantly different value of 3.11 x 10(9) (CV=0.22; P=0.23). Furthermore, no significant differences were found between the two groups in neuronal density (P=0.10) or volume of the PFC (P=0.49). It is of course possible that a neuronal deficit, which cannot be revealed when estimating the total global number of neurons in the whole PFC, might exist in a subregion of the PFC. In conclusion, uniform loss of neuronal soma in the PFC does not appear to constitute the neural substrate of the pathological process in schizophrenia.

Adult↗
PubMed2006

Selective representation of task-relevant objects and locations in the monkey prefrontal cortex.

In the monkey prefrontal cortex (PFC), task context exerts a strong influence on neural activity. We examined different aspects of task context in a temporal search task. On each trial, the monkey (Macaca mulatta) watched a stream of pictures presented to left or right of fixation. The task was to hold fixation until seeing a particular target, and then to make an immediate saccade to it. Sometimes (unilateral task), the attended pictures appeared alone, with a cue at trial onset indicating whether they would be presented to left or right. Sometimes (bilateral task), the attended picture stream (cued side) was accompanied by an irrelevant stream on the opposite side. In two macaques, we recorded responses from a total of 161 cells in the lateral PFC. Many cells (75/161) showed visual responses. Object-selective responses were strongly shaped by task relevance - with stronger responses to targets than to nontargets, failure to discriminate one nontarget from another, and filtering out of information from an irrelevant stimulus stream. Location selectivity occurred rather independently of object selectivity, and independently in visual responses and delay periods between one stimulus and the next. On error trials, PFC activity followed the correct rules of the task, rather than the incorrect overt behaviour. Together, these results suggest a highly programmable system, with responses strongly determined by the rules and requirements of the task performed.

Action Potentials↗
PubMed2004

Repeated cocaine administration increases membrane excitability of pyramidal neurons in the rat medial prefrontal cortex.

Although the medial prefrontal cortex (mPFC) plays a critical role in cocaine addiction, the effects of chronic cocaine on mPFC neurons remain poorly understood. Here, we performed visualized current-clamp recordings to determine the effects of repeated cocaine administration on the membrane excitability of mPFC pyramidal neurons in rat brain slices. Following repeated cocaine administration (15 mg/kg/day i.p. for 5 days) with a 3-day withdrawal, alterations in membrane properties, including increased input resistance, reduced intensity of intracellular injected currents required for generation of Na(+)-dependent spikes (rheobase), and an increased number of spikes evoked by depolarizing current pulses were observed in mPFC neurons. The current-voltage relationship was also altered in cocaine-pretreated neurons showing reduced outward rectification during membrane depolarization and decreased inward rectification during membrane hyperpolarization. Application of the K(+) channel blocker Ba(2+) depolarized the resting membrane potential (RMP) and enhanced membrane potential response to injection of hyperpolarizing current pulses. However, the effects of Ba(2+) on RMP and hyperpolarized membrane potentials were significantly attenuated in cocaine-withdrawn neurons compared with saline-pretreated cells. These findings indicate that repeated cocaine administration increased the excitability of mPFC neurons after a short-term withdrawal, possibly via reducing the activity of the potassium inward rectifiers (K(ir)) and voltage-gated K(+) currents. Similar changes were also observed in cocaine-pretreated mPFC neurons after a long-term (2-3 weeks) withdrawal, revealing a persistent increase in excitability. These alterations in mPFC neuronal excitability may contribute to the development of behavioral sensitization and withdrawal effects following chronic cocaine exposure.

Action Potentials↗
PubMed2005

Behavioral and morphological alterations following neonatal excitotoxic lesions of the medial prefrontal cortex in rats.

The prefrontal cortex (PFC) is essential for executive functions in mammals. Damage of the developing PFC may partly be compensated over time, but may also lead to structural and functional deficits due to neurodevelopmental disturbances. The present study investigated the effects of excitotoxic lesions of the medial PFC (mPFC) in neonatal rats on brain morphology, myelination and behavior. Neonatal lesions were induced with ibotenate on postnatal day (pd) 7 and all animals were tested pre- and postpubertally for prepulse inhibition (PPI) of the acoustic startle reflex (ASR), locomotor activity and food preference. Furthermore, adult rats were tested for apomorphine sensitivity of PPI and for their performance in a progressive ratio operant response task. Neonatally lesioned animals showed a reduced volume of the mPFC, enlarged ventricles and a deficient myelination in some projection areas of the mPFC, including the thalamus, hippocampus, nucleus accumbens (NAC) and amygdala. PPI was enhanced in lesioned rats when tested as juveniles, but PPI-deficits induced by the dopamine receptor agonist apomorphine were exacerbated in adult rats after neonatal mPFC lesion. Furthermore, the break point in a progressive ratio task was lower in lesioned animals, whereas the total number of lever presses was initially increased, indicating an impulsive response of rats for food reward under a progressive ratio schedule after neonatal mPFC lesion. No effects were found on food preference and open field performance. These data support the hypothesis that neonatal mPFC lesions lead to disruptions of neurodevelopmental processes in a cortico-limbic-striatal network, which are manifested in adult animals as morphological and behavioral disturbances.

Analysis of Variance↗
PubMed2002

Retrieval of relational information: a role for the left inferior prefrontal cortex.

Neuroimaging studies have implicated different areas of prefrontal cortex and medial temporal lobe structures (MTL) in episodic retrieval tasks. However, the role of specific regions in particular aspects of episodic memory is still unclear. In this experiment we studied changes in regional cerebral blood flow (rCBF) associated with relational and nonrelational retrieval of studied pairs of words. For relational retrieval, a list of either studied or rearranged pairs was presented and subjects (n = 8) were asked to indicate whether pairs had appeared on the study list. Under the nonrelational retrieval condition they indicated whether one or both words of the pair had appeared on the study list. As compared to the baseline condition (looking at a cross-mark), increased rCBF was observed in the left inferior prefrontal cortex (LIPFC) for both studied pairs and rearranged pairs under the relational retrieval condition. Under the nonrelational condition, an increase was observed in right inferior frontal gyrus. The MTL showed a trend for increased rCBF in the rearranged-pair condition. This increase was probably associated with the encoding that accompanies retrieval of novel stimuli. Results suggest that the lateralized activation of prefrontal cortex observed in episodic memory tasks may be related to the degree of relational processing involved. The LIPFC appears to be associated with relational retrieval and the right prefrontal cortex with nonrelational retrieval.

Adolescent↗