Dorsolateral Prefrontal Regions Research Articles

Neurochemical and structural correlates of executive dysfunction in schizophrenia

Background Executive dysfunction is a core feature of schizophrenia. The neurochemical and structural changes associated with this deficit are, however, largely unclear. This study tested the hypothesis that changes in glutamate, glutamine and N-acetyl-aspartate (NAA) in hippocampal and dorsolateral prefrontal (DLPFC) regions as well as hippocampal, amygdalar and DLPFC volume reductions are associated with executive dysfunction. Methods Twenty-nine subjects with schizophrenia and 31 healthy controls were examined by short-echo single voxel magnetic resonance spectroscopy of the left anterior hippocampus and the left DLPFC. Volumes of the hippocampi, amygdalae and DLPFC were measured bilaterally using manual volumetry. Executive functioning was assessed by the Wisconsin Card Sorting Test (WCST). Results Poor WCST performance was associated with increased hippocampal glutamate concentrations among subjects with schizophrenia, not among healthy controls. Glutamate in the DLPFC as well as NAA or glutamine in the hippocampus or the DLPFC were not related to executive functioning in schizophrenia or healthy controls. Reduced amygdalar volume was associated with impaired executive functioning in subjects with schizophrenia ( p = .06) and healthy controls ( p = .04). Conclusions Altered hippocampal glutamatergic neurotransmission and amygdalar volume loss may be associated with executive dysfunction in schizophrenia.

Reward-Sensitivity, Inhibition of Reward-Seeking, and Dorsolateral Prefrontal Working Memory Function in Problem Gamblers not in Treatment

Given the central role of perseverative chasing in problem gambling, the present study sought to find evidence for three hypothesized components of perseveration in problem gamblers: reward-sensitivity dominance, deficient inhibition of reward-seeking behavior, and working memory deficits. This was the first attempt to examine working memory deficits in problem gamblers using a conditional association task, which is associated with posterior-dorsolateral prefrontal functioning. In a sample that was not in treatment, and representative in terms of comorbidity, problem gamblers performed significantly worse on the conditional association working memory tasks after controlling for general memory function, compared to demographically-matched controls. This is significant because deficits in the dorsolateral prefrontal region have been consistently associated with perseveration, which suggests that problem gamblers' perseverative chasing may be associated with a working memory deficit. Problem gamblers were not significantly higher than at-risk gamblers in terms of reward-sensitivity dominance (measured as a personality trait in terms of extraversion) suggesting that it may not be specifically associated with problem gambling. Sensation-seeking was also not associated with problem gambling in a sample that corrected for the methodological problems of previous studies which examined it. The need for gambling research to focus specifically on the perseverative inability to stop gambling is emphasized, and the present findings of specific working memory deficits in problem gamblers suggest the need for further examination of working memory as a potential risk factor for problem gambling. We propose that subsequent studies examine working memory in terms of the self-regulatory capacity for goal maintenance where attention must specifically be allocated to resist interference.

Proteome analysis of the dorsolateral prefrontal region from healthy individuals

The frontal lobes, particularly the prefrontal region, have been of a great interest to researchers examining human behaviour and the origins of medical conditions involving disturbances in cognitive functions. However, further characterisation of this brain region is necessary to help understand the mechanisms of its disturbance in various disease processes. The work presented here demonstrates the first normative proteomic comparison of the soluble fractions of adjacent grey and white matter of a single brain area with a specific cytoarchitecture, Brodmann area 9 (BA9; part of the dorsolateral prefrontal region). BA9 grey and white matter samples from healthy human brains (i.e. absence of any CNS diseases), were subjected to 2D gel electrophoresis-based proteomics analysis to investigate differential protein expression. The results described herein highlight the importance of correct tissue sampling (i.e. proper separation of grey and white matters) and the necessity for future molecular brain mapping studies. Such studies may provide important information for understanding the molecular basis of the functional differences between grey and white matter and their response to various disease states.

No Association between Dorsolateral Prefrontal Gray Matter Deficit and N-Acetyl Aspartate Ratios in Schizophrenia

The cellular substrates of cortical volume deficit in schizophrenia are unclear. We may hypothesize that, if that deficit was related to a decrease in the amount in neuronal tissue, it should correlate with N-acetyl aspartate levels. We studied a group of 34 schizophrenia patients (of them, 17 first episodes) with both structural and spectroscopic magnetic resonance (MR). Using the data of 50 controls, we were able to calculate for each case residuals of gray matter and cortical cerebrospinal fluid (CSF) in the dorsolateral prefrontal (DLPF) region, representing the deviation from the expected values in normals, given individual intracranial volume and age. Although our patients showed a significant deficit in gray matter and excess in cortical CSF in the DLPF region, that deficit was unrelated to N-acetyl aspartate levels. This was also true for the chronic and first episode groups analyzed separately. These results do not support a neuronal tissue deficit as contributing to the cortical volume deficit in schizophrenia, at least in the DLPF region.

Regulation of Corticolimbic Reactivity via the 5-HT 1A Autoreceptor in the Pathophysiology and Treatment of Depression

According to the National Institute of Mental Health, major depressive disorder (MDD) is among the leading causes of mortality and disability in the USA. In a given year, nearly 7% of Americans experience at least one clinically significant episode of MDD, manifested by a combination of symptoms that interfere with the ability to work, study, sleep, eat and enjoy once pleasurable activities. While an MDD episode may occur only once, they are typically recurring and result in lifetime disability. Although there are a number of widely applied pharmacological and psychological approaches to the treatment of MDD, the efficacy of these is poor, with less than 50% of individuals experiencing a therapeutic response [1]. Combination therapies may lead to higher rates of therapeutic response for a few individuals, but many others will experience severe side effects leading to treatment discontinuation [2]. In light of the immense personal and public health burden of MDD, the existing poor efficacy of available treatments has precipitated dedicated research efforts to better understand the pathophysiology of MDD with the aim of identifying predictive markers of disease liability and generating more effective intervention. Although the neurobiological mechanisms through which disturbances in emotional behavior, mood and temperament emerge and contribute to the development of MDD are not wholly understood, a myriad of converging evidence inextricably links these phenomena with functioning of the central serotonin (5-HT) system and its inter-related subsystems. Multiple mechanisms contribute to the regulation of 5-HT neurotransmission and variability in these regulatory mechanisms is associated with individual differences in temperament and risk for MDD. Key among these is the 5-HT type 1A (5-HT1A) somatodendritic autoreceptor, which is expressed on a population of serotonergic neurons projecting from the brainstem raphe nuclei to cortical and limbic target regions. The 5-HT1A autoreceptor mediates negative-feedback regulation of 5-HT neurons through G-protein coupled signaling cascades, resulting in diminished neuronal activity and subsequent 5-HT release at postsynaptic targets. These postsynaptic targets include the amygdala and prefrontal cortex, key nodes of a corticolimbic circuitry supporting emotional reactivity and control. In the context of emotional behavior, the subcortical amygdala mediates rapid physiological and behavioral arousal in response to salient, biological stimuli (e.g., threat-related facial expressions, such as anger and fear). In addition to regulating the activity of numerous hypothalamic and brainstem autonomic centers, the amygdala can stimulate the activity of the ventromedial and orbitofrontal cortices [3]. These prefrontal regions are critical for the integration of amygdala-mediated arousal in the service of complex, adaptive behavioral responses to environmental challenges [4,5]. The subsequent stimulation of dorsomedial, ventrolateral and dorsolateral prefrontal regions, resulting from such engagement of the ventromedial and orbitofrontal cortices, then precipitates top-down inhibition of the amygdala [6–8]. The coordinated activity within this distributed corticolimbic circuitry largely governs emotional arousal and regulation, and dysfunction of circuit components are pathological markers of MDD [9,10].

Dissociable correlates of two classes of retrieval processing in prefrontal cortex

Although substantial evidence suggests that the prefrontal cortex (PFC) implements processes that are critical for accurate episodic memory judgments, the specific roles of different PFC subregions remain unclear. Here, we used event-related functional magnetic resonance imaging to distinguish between prefrontal activity related to operations that (1) influence processing of retrieval cues based on current task demands, or (2) are involved in monitoring the outputs of retrieval. Fourteen participants studied auditory words spoken by a male or female speaker and completed memory tests in which the stimuli were unstudied foil words and studied words spoken by either the same speaker at study, or the alternate speaker. On “general” test trials, participants were to determine whether each word was studied, regardless of the voice of the speaker, whereas on “specific” test trials, participants were to additionally distinguish between studied words that were spoken in the same voice or a different voice at study. Thus, on specific test trials, participants were explicitly required to attend to voice information in order to evaluate each test item. Anterior (right BA 10), dorsolateral prefrontal (right BA 46), and inferior frontal (bilateral BA 47/12) regions were more active during specific than during general trials. Activation in anterior and dorsolateral PFC was enhanced during specific test trials even in response to unstudied items, suggesting that activation in these regions was related to the differential processing of retrieval cues in the two tasks. In contrast, differences between specific and general test trials in inferior frontal regions (bilateral BA 47/12) were seen only for studied items, suggesting a role for these regions in post-retrieval monitoring processes. Results from this study are consistent with the idea that different PFC subregions implement distinct, but complementary processes that collectively support accurate episodic memory judgments.

Brain activation patterns during a selective attention test — a functional MRI study in healthy volunteers and unmedicated patients during an acute episode of schizophrenia

In a previous functional magnetic resonance imaging (fMRI) study of high functioning outpatients with remitted schizophrenia, we found increased activity compared with healthy subjects across multiple areas of the brain, including the dorsolateral frontal cortex and the anterior cingulate, during a modified Stroop task. The same fMRI procedure was used in this subsequent study to investigate eight unmedicated patients during an acute episode of schizophrenia and eight healthy control subjects. Patients showed a reduced activation in dorsolateral prefrontal, anterior cingulate and parietal regions and a higher activation in temporal regions and posterior cingulate compared to healthy controls. Healthy controls showed a trend towards higher accuracy in the modified Stroop task compared to schizophrenia patients. Treatment with second generation antipsychotics may improve executive performance in patients with schizophrenia and facilitate a normalization of functional hypofrontality after symptomatic improvement.

The neural regions sustaining episodic encoding and recognition of objects

In this functional MRI experiment, encoding of objects was associated with activation in left ventrolateral prefrontal/insular and right dorsolateral prefrontal and fusiform regions as well as in the left putamen. By contrast, correct recognition of previously learned objects (R judgments) produced activation in left superior frontal, bilateral inferior frontal, and right cerebellar regions, whereas correct rejection of distractor objects (N judgments) was associated with activation in bilateral prefrontal and anterior cingulate cortices, in right parietal and cerebellar regions, in the left putamen, and in the right caudate nucleus. The R minus N comparison showed activation in the left lateral prefrontal cortex and in bilateral cingulate cortices and precunei, while the N minus R comparison did not reveal any positive signal change. These results support the view that similar regions of the frontal lobe are involved in episodic encoding and retrieval processes, and that the successful episodic retrieval of newly learned objects is mainly based on a frontoparietal network.

How necessary are the stripes of a tiger?: Diagnostic and characteristic features in an fMRI study of word meaning

This study contrasted two approaches to word meaning: the statistically determined role of high-contribution features like striped in the meaning of complex nouns like “tiger” typically used in studies of semantic memory, and the contribution of diagnostic features like parent's brother that play a critical role in the meaning of nominal kinds like “uncle.” fMRI monitored regional brain activity while participants read complex noun descriptions consisting of statistically high-contribution and low-contribution features; and nominal kind descriptions consisting of diagnostic and characteristic features. We found different patterns of activation depending on the type of noun and the type of feature contributing to the noun. Complex nouns recruited significantly greater bilateral superior temporal and left prefrontal activation compared to nominal kind nouns, while nominal kind nouns activated bilateral medial parietal and right inferior parietal regions more than complex nouns. Moreover, features making a statistically high contribution to complex noun meaning activated right inferior frontal cortex relative to low-contribution features, while diagnostic features of nominal kinds activated left dorsolateral prefrontal and right parietal regions more than characteristic features. These findings are consistent with the hypothesis that at least two different neural mechanisms appear to support word meaning: one driven by a statistically determined approach to feature knowledge, and the other sensitive to the qualitatively critical role that a specific diagnostic feature plays in word meaning.

Neural mechanisms for response selection: comparing selection of responses and items from working memory

Recent functional imaging studies of working memory (WM) have suggested a relationship between the requirement for response selection and activity in dorsolateral prefrontal (DLPFC) and parietal regions. Although a number of WM operations are likely to occur during response selection, the current study was particularly interested in the contribution of this neural network to WM-based response selection when compared to the selection of an item from a list being maintained in memory, during a verbal learning task. The design manipulated stimulus–response mappings so that selecting an item from memory was not always accompanied with selecting a motor response. Functional activation during selection supported previous findings of fronto-parietal involvement, although in contrast to previous findings left, rather than right, DLPFC activity was significantly more active for selecting a memory-guided motor response, when compared to selecting an item currently maintained in memory or executing a memory-guided response. Our results contribute to the debate over the role of fronto-parietal activity during WM tasks, suggesting that this activity appears particularly related to response selection, potentially supporting the hypothesized role of prefrontal activity in biasing attention toward task-relevant material in more posterior regions.

Kinesthetic but not visual imagery assists in normalizing the CNV in Parkinson’s disease

Objective This study investigated whether kinesthetic and/or visual imagery could alter the contingent negative variation (CNV) for patients with Parkinson’s disease (PD). Methods The CNV was recorded in six patients with PD and seven controls before and after a 10 min block of imagery. There were two types of imagery employed: kinesthetic and visual, which were evaluated on separate days. Results The global field power (GFP) of the late CNV did not change after the visual imagery for either group, nor was there a significant difference between the groups. In contrast, kinesthetic imagery resulted in significant group differences pre-, versus post-imagery GFPs, which was not present prior to performing the kinesthetic imagery task. In patients with PD, the CNV amplitudes post-, relative to pre-kinesthetic imagery, increased over the dorsolateral prefrontal regions and decreased in the ipsilateral parietal regions. There were no such changes in controls. Conclusions A 10-min session of kinesthetic imagery enhanced the GFP amplitude of the late CNV for patients but not for controls. Significance While the study needs to be replicated with a greater number of participants, the results suggest that kinesthetic imagery may be a promising tool for investigations into motor changes, and may potentially be employed therapeutically, in patients with Parkinson’s disease.

Alteration of the in vivo nicotinic receptor density in ADNFLE patients: a PET study

Nicotinic acetylcholine receptors (nAChRs) are involved in a familial form of frontal lobe epilepsy, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). In several ADNFLE families, mutations were identified in the nAChR alpha4 or beta2 subunit, which together compose the main cerebral nAChR. Electrophysiological assessment using in vitro expression systems indicated a gain of function of the mutant receptors. However the precise mechanisms by which they contribute to the pathogenesis of a focal epilepsy remain obscure, especially since alpha4beta2 nAChRs are known to be widely distributed within the entire brain. PET study using [18F]-F-A-85380, a high affinity agonist at the alpha4beta2 nAChRs, allows the determination of the regional distribution and density of the nAChRs in healthy volunteers and in ADNFLE patients, thus offering a unique opportunity to investigate some in vivo consequences of the molecular defect. We have assessed nAChR distribution in eight non-smoking ADNFLE patients (from five families) bearing an identified mutation in nAChRs and in seven age-matched non-smoking healthy volunteers using PET and [(18)F]-F-A-85380. Parametric images of volume of distribution (Vd) were generated as the ratio of tissue to plasma radioactivities. The images showed a clear difference in the pattern of the nAChR density in the brains of the patients compared to the healthy volunteers. Vd values revealed a significant increase (between 12 and 21%, P < 0.05) in the ADNFLE patients in the mesencephalon, the pons and the cerebellum when compared to control subjects. Statistical parametric mapping (SPM) was then used to better analyse subtle regional differences. This analysis confirmed clear regional differences between patients and controls: patients had increased nAChR density in the epithalamus, ventral mesencephalon and cerebellum, but decreased nAChR density in the right dorsolateral prefrontal region. In five patients who underwent an additional [(18)F]-fluorodeoxyglucose (FDG) PET experiment, hypometabolism was observed in the neighbouring area of the right orbitofrontal cortex. The demonstration of a regional nAChR density decrease in the prefrontal cortex, despite the known distribution of these receptors throughout the cerebral cortex, is consistent with a focal epilepsy involving the frontal lobe. We also propose that the nAChR density increase in mesencephalon is involved in the pathophysiology of ADNFLE through the role of brainstem ascending cholinergic systems in arousal.

The Neuropsychological Correlates of Borderline Personality Disorder and Suicidal Behaviour

In subjects with borderline personality disorder (BPD), compared with subjects who attempted suicide, to review neuropsychological (NP) function that may predispose to suicidal behaviour along a continuum of high and low lethality. We undertook electronic searches of MEDLINE, PsycINFO, EMBASE, Biosos Reviews, and Cinhal. The searches were restricted to English-language publications from 1985 onward. The search terms borderline personality disorder, suicide, suicide attempt, self-harm behaviour, neuropsychological, executive function (EF), neurocognitive, and neuropsychological function produced 29 neuropsychology studies involving BPD and 7 neuropsychology studies of suicide attempters, regardless of psychiatric diagnosis. Of the BPD studies, 83% found NP impairment in one or more cognitive domains, irrespective of depression, involving specific or generalized deficits linked to the dorsolateral prefrontal and orbitofrontal regions. The functions most frequently reported (in 71% to 86% of BPD studies) are response-inhibitory processes affecting executive function performance that requires speeded attention and visuomotor skills. Decision making and visual memory impairment are also most frequently affected; 60% to 67% of BPD studies report attentional impairment, verbal memory impairment, and visuospatial organizational impairment. Least affected processes in BPD appear to involve spatial working memory, planning, and possibly, IQ. The similarities in NP deficits found in BPD and suicide-attempt studies involve decision making and Trails performances. BPD studies, however, reflect more frequent impairment on the Stroop Test and Wisconsin Card Sort Test performance than the suicide-attempt studies, whereas verbal fluency appears to be more frequently impaired in those attempting suicide. Impaired EF and disinhibitory processes, as indicated by verbal fluency, Trails, and Stroop performance, primarily associated with dorsolateral prefrontal cortical regions may represent a dominant executive pathway to suicide attempt. A primary motivational inhibitory pathway involving conflictual, affective, and reflexive decision-making processes associated with orbitofrontal brain regions, in combination with significant cognitive rigidity, may influence the repetitive expression of self-harm or low-lethality suicidal behaviour. The hypothesis of a specific trait-like cognitive vulnerability for suicidal behaviour involving dysregulatory, disinhibiting pathways awaits confirmation.

Basal Ganglia-Thalamocortical Circuitry Disruptions in Schizophrenia During Delayed Response Tasks

Schizophrenia is characterized by executive functioning deficits, presumably mediated by prefrontal cortex dysfunction. For example, schizophrenia participants show performance deficits on ocular motor delayed response (ODR) tasks, which require both inhibition and spatial working memory for correct performance. The present functional magnetic resonance imaging (fMRI) study compared neural activity of 14 schizophrenia and 14 normal participants while they performed ODR tasks. Schizophrenia participants generated: 1) more trials with anticipatory saccades (saccades made during the delay period), 2) memory saccades with longer latencies, and 3) memory saccades of decreased accuracy. Increased blood oxygenation level-dependent (BOLD) signal changes were observed in both groups in ocular motor circuitry (e.g., supplementary eye fields [SEF], lateral frontal eye fields [FEF], inferior parietal lobule [IPL], cuneus, and precuneus). The normal, but not the schizophrenia, group demonstrated BOLD signal changes in dorsolateral prefrontal regions (right Brodmann area [BA] 9 and bilateral BA 10), medial FEF, insula, thalamus, and basal ganglia. Correlations between percentage of anticipatory saccade trials and BOLD signal changes were more similar between groups for subcortical regions and less similar for cortical regions. These results suggest that executive functioning deficits in schizophrenia may be associated with dysfunction of the basal ganglia-thalamocortical circuitry, evidenced by decreased prefrontal cortex, basal ganglia, and thalamus activity in the schizophrenia group during ODR task performance.

Improvement-related functional plasticity following pitch memory training

Functional activation patterns of an auditory working memory task were examined prior to and after 5 days of training (1 h/day). A control group with no training was scanned twice at the same intervals to assess test–retest effects. Based on behavioral improvement scores, the training group ( n = 14) was divided into “Strong-Learners (SL)” and “Weak-Learners (WL)”. No significant functional or structural brain differences were seen between the SL and WL groups prior to training. Imaging contrasts comparing post- with pre-training sessions showed a significant signal increase in the left Heschl's gyrus (HG) as well as in the left posterior superior temporal and supramarginal gyrus for the SL group, while the WL group showed significant signal increases in the left HG and anterior insular cortex as well as in a lingual–orbitofrontal–parahippocampal network. The test–retest analysis in the control group revealed only minimal signal increases in a right dorsolateral prefrontal region. A random effects analysis comparing the SL group with the WL group using the post- and pre-training contrast images showed increased activation only in the left supramarginal gyrus but not in HG. The importance of HG in pitch discrimination has been established in previous studies. The pitch memory component differentiated our task from a straight pitch discrimination task. It is most likely that the activation of the SMG reflects its importance in the short-term storage of auditory material, and it was this activation that best differentiated between subjects' levels of performance.

The Role of a Right Fronto-Parietal Network in Cognitive Control

Seemingly distinct cognitive tasks often activate similar anatomical networks. For example, the right fronto-parietal cortex is active across a wide variety of paradigms suggesting that these regions may subserve a general cognitive function. We utilized fMRI and a GO/NOGO task consisting of two conditions, one with intermittent unpredictive “cues-to-attend” and the other without any “cues-to-attend,” in order to investigate areas involved in inhibition of a prepotent response and top-down attentional control. Sixteen subjects (5 male, ages ranging from 20 to 30 years) responded to an alternating sequence of the letters X and Y and withheld responding when the alternating sequence was broken (e.g., when X followed an X). Cues were rare stimulus font-color changes, which were linked to a simple instruction to attend to the task at hand. We hypothesized that inhibitions and cues, despite requiring quite different responses from subjects, might engage similar top-down attentional control processes and would thus share a common network of anatomical substrates. Although inhibitions and cues activated a number of distinct brain regions, a similar network of right dorsolateral prefrontal and inferior parietal regions was active for both. These results suggest that this network, commonly activated for response inhibition, may subserve a more general cognitive control process involved in allocating top-down attentional resources.

Effects of Divided Attention on fMRI Correlates of Memory Encoding

Performing a secondary task concurrently with a study task has a detrimental effect on later memory for studied items. To investigate the mechanisms underlying this effect, the processing resources available for an incidental encoding task were varied by manipulating secondary task difficulty. fMRI data were acquired as volunteers (n = 16) made animacy decisions to visually presented study words while concurrently performing either an easy or a hard auditory monitoring task. "Subsequent memory effects"--greater activity at study for words later remembered versus words later forgotten--were identified in the left ventral inferior frontal gyrus and the left anterior hippocampus. These effects did not vary according to whether the encoding task was performed concurrently with the easy or the hard secondary task. However, as secondary task difficulty increased, study-item activity declined and auditory-item activity increased in dorsolateral prefrontal and superior parietal regions that have been implicated in the support of executive and control functions. The findings suggest that dividing attention during encoding influences the probability of engaging the encoding operations that support later episodic memory, but does not alter the nature of the operations themselves. The findings further suggest that the probability of engaging these encoding operations depends on the level of general processing resources engaged in service of the study task.

Spatial attention: more than intrinsic alerting?

It has been proposed that the right hemisphere alerting network co-activates, either directly or via the brainstem, the attention system in the parietal cortex involved in spatial attention. The observation that impaired alertness and sustained attention can predict the outcome of neglect might suggest such a relationship, too. In the present fMRI study, we intended to analyse and compare the functional anatomy of two attentional conditions both involving intrinsic (endogenous) alerting and fixation but differing with respect to the degree of spatially distributed attention by using the same paradigm under two different attentional conditions. In a group of ten participants, both a focused and a distributed visuospatial attention condition evoked similar patterns of activation in dorsolateral prefrontal regions, in the anterior cingulate gyrus, in the superior and inferior parietal cortex as well as in the superior temporal gyrus and in the thalamus. These activation foci were stronger in the right hemisphere under both conditions. After subtraction of the alertness condition with focused spatial attention, distributed spatial attention with stimuli appearing at unpredictable locations within both visual fields induced additional bilateral activations only in the left and right superior parietal cortex and in the right precuneus suggesting that these regions are specific for a more widespread dispersion of spatial attention.

Dorsolateral prefrontal cortex contribution to abnormalities of the P300 component of the event-related potential in schizophrenia

Abnormalities of the P300 component of the event-related potential are a common finding in schizophrenia. It seems possible that the dysfunction in the dorsolateral prefrontal (DLPF) region that has been reported in schizophrenia contributes to this finding. To explore this possibility, we calculated the relationship between, on the one hand, P300 latency and amplitude and, on the other hand, the degree of DLPF atrophy (as measured by magnetic resonance imaging) and metabolic activity during an attentional task (as measured by positron emission tomography). Seventeen schizophrenia patients with a brief duration of illness and minimal exposition to treatment and 25 healthy controls were studied. Patients exhibited significantly lower metabolic activity in the DLPF region, but they did not show cortical atrophy. P300 amplitude was also significantly reduced in the schizophrenia patients compared with the controls. Right DLPF region metabolic activity correlated significantly with P300 amplitude. This pattern remained after partialling out the influence of activity in the hippocampus, superior temporal gyrus and parietal lobe. It is therefore suggested that the prefrontal cortex could be implicated in the P300 amplitude reduction in schizophrenia.

Frontal Brain Asymmetry and Reward Responsiveness

The influence of approach and avoidance tendencies on affect, reasoning, and behavior has attracted substantial interest from researchers across various areas of psychology. Currently, frontal electroencephalographic (EEG) asymmetry in favor of left prefrontal regions is assumed to reflect the propensity to respond with approach-related tendencies. To test this hypothesis, we recorded resting EEG in 18 subjects, who separately performed a verbal memory task under three incentive conditions (neutral, reward, and punishment). Using a source-localization technique, we found that higher task-independent alpha2 (10.5-12 Hz) activity within left dorsolateral prefrontal and medial orbitofrontal regions was associated with stronger bias to respond to reward-related cues. Left prefrontal resting activity accounted for 54.8% of the variance in reward bias. These findings not only confirm that frontal EEG asymmetry modulates the propensity to engage in appetitively motivated behavior, but also provide anatomical details about the underlying brain systems.