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Results for “Dorsolateral Prefrontal Cortex”

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PubMed2007

Increased left prefrontal activation in patients with unipolar depression: an event-related, parametric, performance-controlled fMRI study.

BACKGROUND: Executive deficits associated with frontal lobe dysfunction are prominent in depression. We applied a newly developed WM task to investigate the neural correlates of executive processes with functional magnetic resonance imaging (fMRI) at comparable performance levels analyzing correct trials only. METHODS: We studied 12 partially remitted, medicated inpatients meeting DSM-IV criteria for major depressive disorder and 17 healthy controls. We used a parametric version of a delayed match-to-sample WM task requiring manipulation of verbal material during a delay period in an event-related fMRI design. RESULTS: Depressed patients were generally slower and load-dependently less accurate than healthy controls. Patients showed significantly more activation of left dorsolateral prefrontal cortex with highest cognitive load. Additionally, they showed higher activation in ventromedial prefrontal cortex during the control condition. LIMITATIONS: The fact that patients were taking different antidepressant drugs could limit the explanatory power of the present results. CONCLUSIONS: Increased lateral prefrontal activation despite comparably successful performance - when only correct trials were analyzed - in patients with depression can be interpreted as evidence for compensatory recruitment of prefrontal cortical resources.

Adult↗

PubMed2007

Repetitive Transcranial Magnetic Stimulation (rTMS) in the treatment of panic disorder (PD) with comorbid major depression.

BACKGROUND: Studies suggest that the dorsolateral prefrontal cortex (DLPFC) participates in neural circuitry that is dysregulated in Panic Disorder (PD) and Major Depressive Disorder (MDD). We tested whether low-frequency repetitive Transcranial Magnetic Stimulation (rTMS) could normalize the overactivity of right frontal regions and thereby improve symptoms. METHODS: Six patients with PD and comorbid MDD were treated with daily active 1-Hz rTMS to the right DLPFC for 2 weeks in this open-label trial. RESULTS: Clinical improvements were apparent as early as the first week of treatment. After the second week, 5/6 of patients showed improvements in panic and anxiety, and 4/6 showed a decrease in depression, with sustained improvement at 6 months of follow-up. Right hemisphere resting motor threshold increased significantly after rTMS. LIMITATIONS: Limitations of this study are the open design and the small sample size. CONCLUSIONS: Slow rTMS to the right DLPFC resulted in significant clinical improvement and reduction of ipsilateral motor cortex excitability. Replications in larger sample will help to clarify the relevance of this preliminary data and to define the potential role of right DLPFC rTMS in panic with major depression.

Adult↗

PubMed2006

Improved methods for fMRI studies of combined taste and aroma stimuli.

Previous neuroimaging studies of the cortical representation of gustatory and olfactory stimuli have often delivered tastants to the mouth in very small quantities or stimulated olfaction orthonasally. In studies of retro-nasal olfaction, swallowing was generally delayed to reduce head motion artefacts. The present fMRI study aims to improve upon such methodological limitations to allow investigation of the cortical representation of flavour (taste and aroma combination) as it typically occurs during the consumption of liquid foods. For this purpose we used (1) a novel, automated, sprayed stimulus delivery system and a larger volume of liquid sample (containing sweet tastants and banana/pear aroma volatiles) to achieve more extensive stimulation of the oral cavity taste receptors, (2) a pseudo-natural delivery paradigm that included prompt swallowing after each sample delivery to obtain physiological retro-nasal olfactory stimulation, (3) fMRI acquisition with wide brain coverage and double-echo EPI to improve sensitivity. We validated our paradigm for the delivery of volatiles using atmospheric pressure chemical ionisation mass spectrometry. This showed that the main retro-nasal delivery of volatiles in the paradigm occurs immediately after the swallow. Several brain areas were found to be activated, including the insula, frontal operculum, rolandic operculum/parietal lobe, piriform, dorsolateral prefrontal cortex, anterior cingulate cortex, ventro-medial thalamus, hippocampus and medial orbitofrontal cortex.

Adult↗

PubMed2004

Cognitive functioning after repetitive transcranial magnetic stimulation in patients with cerebrovascular disease without dementia: a pilot study of seven patients.

AIMS: Examine whether one session of high frequency repetitive transcranial magnetic stimulation (rTMS) applied over the left dorsolateral prefrontal cortex (DLPFC) would induce any measurable cognitive changes in patients with cerebrovascular disease and mild cognitive deficits. PATIENTS AND METHOD: Seven patients with cerebrovascular disease and mild executive dysfunction entered the randomised, controlled, blinded study with a crossover design. rTMS was applied either over the left DLPFC (an active stimulation site) or over the left motor cortex (MC; a control stimulation site) in one session. Each patient participated in both stimulation sessions (days 1 and 4) and the order of stimulation sites (DLPFC or MC) was randomised. A short battery of neuropsychological tests was performed by a blinded psychologist prior to and after each rTMS session. Psychomotor speed, executive function, and memory were evaluated. RESULTS: The only mild but significant stimulation site-specific effect of rTMS was observed in the Stroop interference results (i.e. improvement) after the stimulation of DLPFC but not MC in comparison with the baseline scores (Wilcoxon, Z=-2.03, p=0.04). Patients improved in the digit symbols subtest of the Wechsler adult intelligence scale-revised after both rTMS sessions regardless of the stimulation site (DLPFC or MC; Z=-2.06, p=0.04 and Z=-2.06, p=0.04, respectively). There was no measurable effect of rTMS in any other neuropsychological test. CONCLUSION: Our pilot study results showed that one session of the high frequency rTMS applied over the left DLPFC was safe in patients with cerebrovascular disease and mild executive deficits, and may induce measurable positive effects on executive functioning.

Aged↗

PubMed2006

Functional imaging of sequence learning in Parkinson's disease.

Sequence learning, a cognitive task linked to cortico-striatal function, is impaired in Parkinson's disease (PD). We chose this task as a behavioral paradigm to study the functional architecture of PD in treated and untreated conditions. In our studies, participants were scanned with H(2)(15)O while performing a kinematically controlled motor sequence learning task and a matching motor baseline task. Experiments revealed that a specific sequence learning network predicts learning in normal subjects, and in independent cohorts of early and advanced PD patients. The analysis of the relationship of network activity to learning performance revealed diverging influences of dopaminergic therapy and deep brain stimulation (DBS). DBS of the internal GP and of STN increased network activity and task performance, while levodopa decreased both measures. In separate studies, we investigated the role of dopaminergic modulation on brain activation during sequence learning. In healthy subjects dopamine transporter (DAT) binding correlated with learning-related brain activation in prefrontal, premotor and cingulate cortices, and in the thalamus. By contrast, in PD most of these regional relationships were lost. Only ventral and dorsolateral prefrontal cortex activation correlated with caudate dopaminergic input. In a final set of studies, we found a significant decline in learning performance in early stage PD patients followed over the course of 2 years. Longitudinal declines in learning-related activation were found in parietal areas, while concomitant increases were localized to the left hippocampus. These observations support hypotheses on disease-stage and task-specific effects within the different cortico-striato-pallido-thalamocortical loops and the mesocortical system in PD.

Aged↗

PubMed2006

Differential activation of frontal lobe areas by lexical and semantic language tasks: a functional magnetic resonance imaging study.

To determine whether frontal lobe regions, including Broca's area, dorsolateral prefrontal cortex (DLPFC) and supplementary motor area (SMA), are differentially activated during lexical and semantic language tasks, we used functional magnetic resonance imaging in eight healthy right-handed subjects silently performing two semantic tasks (adjective and verb generation) and a lexical retrieval task (noun recall). Activation was observed in Broca's area, DLPFC and SMA for all tasks. Broca's area activation was approximately doubled during the semantic tasks compared with the lexical task (verbs vs nouns: 19.1+/-4.5 vs 8.9+/-1.6 voxels, p=0.02; adjectives vs nouns 24.4+/-7.5 vs 10.1+/-2.8 voxels, p=0.04); however, there were no significant differences in the DLFPC or SMA across tasks. We conclude that Broca's area is more active during tasks that have a semantic content, whereas areas involved in preparatory processing (SMA) and memory retrieval (DLPFC) are engaged equally during both types of task.

Adult↗

PubMed2006

Motor learning in man: a review of functional and clinical studies.

This chapter reviews results of clinical and functional imaging studies which investigated the time-course of cortical and subcortical activation during the acquisition of motor a skill. During the early phases of learning by trial and error, activation in prefrontal areas, especially in the dorsolateral prefrontal cortex, is has been reported. The role of these areas is presumably related to explicit working memory and the establishment of a novel association between visual cues and motor commands. Furthermore, motor associated areas of the right hemisphere and distributed cerebellar areas reveal strong activation during the early motor learning. Activation in superior-posterior parietal cortex presumably arises from visuospatial processes, while sensory feedback is coded in the anterior-inferior parietal cortex and the neocerebellar structures. With practice, motor associated areas of the left-hemisphere reveal increased activity. This shift to the left hemisphere has been observed regardless of the hand used during training, indicating a left-hemispheric dominance in the storage of visuomotor skills. Concerning frontal areas, learned actions of sequential character are represented in the caudal part of the supplementary motor area (SMA proper), whereas the lateral premotor cortex appears to be responsible for the coding of the association between visuo-spatial information and motor commands. Functional imaging studies which investigated the activation patterns of motor learning under implicit conditions identified for the first, a motor circuit which includes lateral premotor cortex and SMA proper of the left hemisphere and primary motor cortex, for the second, a cognitive loop which consists of basal ganglia structures of the right hemisphere. Finally, activity patterns of intermanual transfer are discussed. After right-handed training, activity in motor associated areas maintains during performance of the mirror version, but is increased during the performance of the original-oriented version with the left hand. In contrary, increased activity during the mirror reversed action, but not during the original-oriented performance of the untrained right hand is observed after left-handed training. These results indicate the transfer of acquired right-handed information which reflects the mirror symmetry of the body, whereas spatial information is mainly transferred after left-handed training. Taken together, a combined approach of clinical lesion studies and functional imaging is a promising tool for identifying the cerebral regions involved in the process of motor learning and provides insight into the mechanisms underlying the generalisation of actions.

Brain↗

PubMedDate not supplied

Effect of 5 Hz repetitive transcranial magnetic stimulation on cognition during a Go/NoGo task.

Repetitive transcranial magnetic stimulation (rTMS) has been developed as a novel tool for modulating cognition by delivering stimulation in the brain. However, the effects of rTMS on cognition are still controversial. This randomized, sham-controlled, crossover study was designed to determine whether rTMS of the left dorsolateral prefrontal cortex (DLPFC) interferes with the Go/NoGo task and whether personal parameters such as age affect rTMS. A total of 24 healthy subjects (12 male and 12 female, aged 20-37 years) underwent one session of active rTMS followed by sham rTMS (total of 1600 pulses, 100% of motor threshold, 5 Hz, 8 s), or vice versa. The results did not show any differences between active and sham rTMS stimulation in terms of performance accuracy, response speed, or choice reaction time (cRT) implicating that short-term rTMS will not enhance or deteriorate cognition. However, percentage cRT shortening induced by active rTMS was negatively correlated with age (r = -0.57, P = 0.005), whereas that induced by sham rTMS was not (r = -0.23, P > 0.05), suggesting that cognition of younger subjects might have greater modulation by active stimulation than older ones. This finding may help explain some of the controversies or paradoxical results observed in studies of the effect of left DLPFC rTMS on cognition.

Adult↗

PubMed2005

Striatal dopamine release after prefrontal repetitive transcranial magnetic stimulation in major depression: preliminary results of a dynamic [123I] IBZM SPECT study.

Though there is considerable evidence that prefrontal repetitive transcranial magnetic stimulation (rTMS) exerts antidepressant effects, the neurobiological action of rTMS in patients with depression is poorly understood. Preclinical studies in animals and humans have demonstrated that prefrontal rTMS can induce dopamine release in mesostriatal and mesolimbic regions. We therefore investigated whether rTMS also modulates striatal dopaminergic neurotransmission in depressed patients using a dynamic [123I] iodobenzamide (IBZM) single photon emission computed tomography (SPECT) approach. Five patients with a major depressive episode (DSM-IV) underwent an acute 10 Hz rTMS challenge with 3000 stimuli over the left dorsolateral prefrontal cortex during an [123I] IBZM-SPECT bolus and constant infusion protocol. In four subjects the protocol was repeated after a three week rTMS standard treatment. Striatal IBZM binding to dopamine D2 receptors was assessed with a region-of-interest (ROI) technique. The change in striatal IBZM binding after the rTMS challenge was regarded as measure of change in endogenous striatal dopamine. Data of nine SPECT investigations showed a significant reduction by 9.6+/-6.2% in IBZM binding to striatal dopamine D2 receptors after rTMS challenge compared to baseline (p=0.01, Wilcoxon test). In this preliminary study, the reduction of IBZM binding observed after rTMS challenge is suggestive of a release in endogenous dopamine induced by prefrontal rTMS. In future, this approach can be used to differentiate specific and non-specific reward-related effects of rTMS on dopaminergic neurotransmission.

Aged↗

PubMed2006

Positive predictors for antidepressive response to prefrontal repetitive transcranial magnetic stimulation (rTMS).

Repetitive transcranial magnetic stimulation (rTMS) is a brain stimulation technique which had recently been investigated as a putative antidepressant intervention. However, there is little agreement about clinically useful predictors of rTMS outcome. Therefore, the objective of the present study was to determine whether specific biographical, clinical, and psychopathological parameters are associated with the antidepressant response to rTMS in a large sample of 70 depressive patients. We performed a logistic regression analysis in 70 patients with major depressive disorder treated with rTMS of the left dorsolateral prefrontal cortex testing the predictive value of various domains of the depression syndrome as well as the variables episode duration, degree of treatment resistance, and CORE criteria. Response was defined as a 50% reduction of the initial Hamilton score (HAMD). After two weeks of treatment, 21% of the patients showed a response to rTMS. The binary logistic regression model correctly assigned 86.7% of the responders and 96.4% of the non-responders to their final response group. In the model, a high level of sleep disturbances was a significant predictor for treatment response to rTMS. Also, a low score of treatment resistance and a short duration of episode were positive predictors. These findings provide new evidence that especially pronounced sleep disturbances may be a significant clinical predictor of a response to rTMS. Prospective rTMS studies are necessary to validate the predictive value of the derived model.

Antidepressive Agents↗

PubMed2006

Immunological aspects in the neurobiology of suicide: elevated microglial density in schizophrenia and depression is associated with suicide.

OBJECTIVES: Suicide has a high prevalence in patients with schizophrenia and affective disorder. Our recent postmortem study [Steiner J, Mawrin C, Ziegeler A, Bielau H, Ullrich O, Bernstein HG, Bogerts B. Distribution of HLA-DR-positive microglia in schizophrenia reflects impaired cerebral lateralization. Acta Neuropathologica (Berl) 2006;112:305-16.] revealed increased microglial densities in two schizophrenic patients who had committed suicide. Therefore, the hypothesis of microglial activation during acute psychosis was proposed. Alternatively, "suicide" could be a diagnosis-independent factor leading to microgliosis. METHODS: To clarify this question, microglial HLA-DR expression was analyzed by immunohistochemistry in the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), mediodorsal thalamus (MD) and hippocampus of 16 schizophrenics, 14 depressed patients with affective disorder and 10 matched controls. A subgroup of six schizophrenics and seven patients with affective disorder who committed suicide was included. RESULTS: ANOVA revealed no effect of diagnosis on microglial density (DLPFC: P=0.469; ACC: P=0.349; MD: P=0.569; hippocampus: P=0.497). However, significant microgliosis was observed in the DLPFC (P=0.004), ACC (P=0.012) and MD (P=0.004) of suicide patients. A similar trend was seen in the hippocampus (P=0.057). CONCLUSION: In conclusion, immunological factors may play a hitherto underestimated role in suicide. First, microglial activation might be interpreted as a consequence of presuicidal stress. Second, one might speculate a causal link between microglial activation and suicidal behaviour, such as neuroendocrine factors, cytokines, and nitric oxide, which are released from microglial cells and are known to modulate noradrenergic or serotonergic neurotransmission and thus may trigger suicidality.

Adult↗

PubMed2026

The effect of tDCS on emotion-related risk-taking behavior and delay discounting in adults with ADHD.

INTRODUCTION: Adults with Attention Deficit Hyperactivity Disorder (ADHD) often engage in risky behaviors due to impaired decision-making processes. This study aims to investigate the effects of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC) on emotion-related risk-taking behavior and delay discounting in adults with ADHD. METHODS: Thirty adults with ADHD underwent three tDCS conditions, administered in a randomized order with at least one week between sessions: (1) left dlPFC anode/right vmPFC cathode, (2) left dlPFC cathode/right vmPFC anode, and (3) sham stimulation. In each session, participants completed the Delay Discounting Task (DDT) and the Modified Balloon Analogue Risk Task (mBART) under three emotional conditions (neutral, positive, and negative) which were induced using emotionally congruent photographs and sounds. Galvanic skin responses (GSR) were also recorded. In the DDT, both area under the curve (AUC) values and log-transformed discounting rates (log k) were calculated for small, medium, and large reward magnitudes (RM). Exploratory electric field modeling was also performed to characterize current distribution. RESULTS: The findings demonstrated task-specific effects of tDCS on decision-making. Although no overall tDCS effect was observed on DDT performance, significant tDCS × RM interactions emerged, particularly for smaller rewards. In contrast, exploratory analyses suggested that tDCS affected all mBART scores. Emotional condition did not influence consistently behavioral performance in either task, whereas both emotional stimulation and tDCS significantly affected GSR responses. However, exploratory electric field modeling indicated a broad prefrontal current distribution extending beyond the intended cortical targets. CONCLUSIONS: These findings suggest preliminary evidence that prefrontal tDCS can influence risk-related decision-making and autonomic responses in adults with ADHD. However, its effects on delay discounting appear to be context-dependent and limited to specific RMs. Future studies combining neuroimaging with individualized electric field modeling are needed to clarify the neural mechanisms underlying the observed effects of tDCS and to optimize stimulation protocols in adults with ADHD.

Humans↗

PubMed2006

Therapeutic and neurophysiologic aspects of transcranial magnetic stimulation in schizophrenia.

The use of repetitive transcranial magnetic stimulation (rTMS) in psychiatry provides the therapeutic field with a new tool. Since its introduction in the mid 1980s, the vast majority of studies have focussed on depression. A growing body of evidence suggests that rTMS is effective in the treatment of depression if dorsolateral prefrontal cortex is stimulated. Less is known about its efficacy in schizophrenia. Neuroimaging investigations in schizophrenia suggest abnormalities in the prefrontal and temporoparietal cortex (TPC), which are correlated with psychopathological dimensions. Based on its modulatory effect, rTMS seems to be a promising tool in exploring cortical excitability and reducing auditory hallucinations (AH) and negative symptoms. Neurophysiologic studies of patients suffering from schizophrenia using rTMS indicate high cortical excitability and a lack of transcallosal inhibition. In the therapeutic field, researches provide encouraging results, even though some studies indicate limited benefits. The most promising therapeutic effect seems to be the capability of rTMS to reduce AH if TPC is targeted using slow-frequency. The current paper aims to provide a review of the literature of the use of rTMS in schizophrenia.

Antipsychotic Agents↗

PubMed2005

Assessing functioning of the prefrontal cortical subregions with auditory evoked potentials in sleep-wake cycle.

Our previously observations showed that the amplitude of cortical evoked potentials to irrelevant auditory stimulus (probe) recorded from several different cerebral areas was differentially modulated by brain states. At present study, we simultaneously recorded auditory evoked potentials (AEPs) from the dorsolateral prefrontal cortex (DLPFC) and the ventromedial prefrontal cortex (VMPFC) in the freely moving rhesus monkey to investigate state-dependent changes of the AEPs in the two subregions of prefrontal cortex. AEPs obtained during passive wakefulness (PW), active wakefulness (AW), slow wave sleep (SWS) and rapid-eye-movement sleep (REM) were compared. Results showed that AEPs from two subregions of prefrontal cortex were modulated by brain states. Moreover, a significantly greater increase of the peak-to-peak amplitude (PPA) of N1-P1 complexes appears in the DLPFC during PW compared to that during AW. During REM, the PPA of N1-P1 complexes presents a contrary change in the two subregions with significant difference: a significant increase in the DLPFC and a slight decrease in the VMPFC compared to that during AW. These results indicate that the modulation of brain states on AEPs from two subregions of the prefrontal cortex investigated is also not uniform, which suggests that different subregions of the prefrontal cortex have differential functional contributions during sleep-wake cycle.

Animals↗

PubMed2006

Contributions of prefrontal cue-, delay-, and response-period activity to the decision process of saccade direction in a free-choice ODR task.

To examine how the dorsolateral prefrontal cortex (DLPFC) contributes to the decision process of the saccade direction, we recorded single-neuron activity while two monkeys performed two oculomotor delayed-response (ODR) tasks. In an ordinary ODR task, monkeys were required to make a memory-guided saccade to the cue location after a 3-s delay. In a self-selection version of the ODR task (S-ODR), four identical visual cues were presented simultaneously at the cue period, and monkeys were required to make a saccade toward any one of four directions after a 3-s delay. By comparing the same neuron's activity between two tasks, we found (1) neurons having directional cue-period activity in the ODR task did not show directionally selective activity in the S-ODR task, (2) neurons having directional pre-saccadic activity showed highly similar directional preferences in two tasks and exhibited temporal coupling between the onset of pre-saccadic activity and the initiation of saccadic eye movements, (3) neurons with directional delay-period activity in the ODR task exhibited similar directional preferences and showed gradual increase in the strength of the directional selectivity toward the end of the delay period in the S-ODR task. These results suggest that directional delay-period activity contributes to the decision process of the saccade direction in the S-ODR task, while directional cue-period and pre-saccadic activities do not. The gradual increase of the directional selectivity in delay-period activity might correspond to neural correlates of the decision process of the saccade direction in the S-ODR task.

Action Potentials↗

PubMed2004

Brain potentials index executive functions during random number generation.

The generation of random sequences is considered to tax different executive functions. To explore the involvement of these functions further, brain potentials were recorded in 16 healthy young adults while either engaging in random number generation (RNG) by pressing the number keys on a computer keyboard in a random sequence or in ordered number generation (ONG) necessitating key presses in the canonical order. Key presses were paced by an external auditory stimulus to yield either fast (1 press/800 ms) or slow (1 press/1300 ms) sequences in separate runs. Attentional demands of random and ordered tasks were assessed by the introduction of a secondary task (key-press to a target tone). The P3 amplitude to the target tone of this secondary task was reduced during RNG, reflecting the greater consumption of attentional resources during RNG. Moreover, RNG led to a left frontal negativity peaking 140 ms after the onset of the pacing stimulus, whenever the subjects produced a true random response. This negativity could be attributed to the left dorsolateral prefrontal cortex and was absent when numbers were repeated. This negativity was interpreted as an index for the inhibition of habitual responses. Finally, in response locked ERPs a negative component was apparent peaking about 50 ms after the key-press that was more prominent during RNG. Source localization suggested a medial frontal source. This effect was tentatively interpreted as a reflection of the greater monitoring demands during random sequence generation.

Adult↗

PubMed2005

Cortical 6-[18F]fluoro-L-dopa uptake and frontal cognitive functions in early Parkinson's disease.

Patients with Parkinson's disease (PD) have already at the early stages of the disease impaired performance especially in tests measuring frontal lobe functions such as attention. The pathophysiological basis of these deficits is unclear. In the present study, 21 non-demented, non-medicated patients at the early stage of PD and 24 healthy controls underwent a positron emission tomography (PET) scan with 6-[18F]fluoro-L-dopa (Fdopa) as the tracer. In addition, the PD patients performed a neuropsychological test battery, including a test measuring sustained attention (VIG) and a test requiring suppressed attention (Stroop). Both voxel-based Statistical Parametric Mapping (SPM) and automated region of interest (ROI) analysis were employed. Compared to controls, the PD patients had decreased Fdopa uptake in the striatum and a large cortical area of increased Fdopa uptake. The reaction time in the VIG test correlated positively with the Fdopa uptake of the dorsolateral prefrontal cortex and the performance in the Stroop test correlated negatively with the Fdopa uptake in an area including the medial frontal cortex and the anterior cingulate. The results show that cortical Fdopa uptake is increased in early non-medicated PD and suggest that the changes in frontal Fdopa uptake are related to cognitive impairments found in early PD.

Aging↗

PubMed2003

Cortical capacity constraints for visual working memory: dissociation of fMRI load effects in a fronto-parietal network.

Working memory (WM) capacity limitations and their neurophysiological correlates are of special relevance for the understanding of higher cognitive functions. Evidence from behavioral studies suggests that restricted attentional resources contribute to these capacity limitations. In an event-related functional magnetic resonance imaging (fMRI) study, we probed the capacity of the human visual WM system for up to four complex nonnatural objects using a delayed discrimination task. A number of prefrontal and parietal areas bilaterally showed increased blood oxygen level-dependent activity, relative to baseline, throughout the task when more than one object had to be held in memory. Monotonic increases in response to memory load were observed bilaterally in the dorsolateral prefrontal cortex (DLPFC) and the presupplementary motor area (pre-SMA). Conversely, activity in the frontal eye fields (FEFs) and in areas along the intraparietal sulcus (IPS) peaked when subjects had to maintain only two or three objects and decreased in the highest load condition. This dissociation of memory load effects on cortical activity suggests that the cognitive operations subserved by the IPS and FEF, which are most likely related to attention, fail to support visual WM when the capacity limit is approached. The correlation of brain activity with performance implies that only the operations performed by the DLPFC and pre-SMA, which support an integrated representation of visual information, helped subjects to maintain a reasonable level of performance in the highest load condition. These results indicate that at least two distinct cortical subsystems are recruited for visual WM, and that their interplay changes when the capacity limit is reached.

Adult↗