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Activation of the prefrontal cortex during judgments of recency: a functional MRI study.

Animal and human lesion studies have consistently shown that damage to the prefrontal lobe disrupts performance on tasks requiring memory for temporal context. In this study, functional magnetic resonance imaging (fMRI) was used to explore the brain regions associated with judgements of relative recency in healthy humans. Bilateral dorsolateral prefrontal cortex (Brodmann's area [BA] 9) was more active during a verbal recency judgment task than during a non-mnemonic control task. Activation related to temporal context recognition was also observed in midline supplementary motor area (BA 6) and left precuneus (BA 7). This study provides further evidence that memory for temporal context requires the prefrontal cortex and is the first to demonstrate this association in healthy humans. The current findings also suggest the possibility that recognition of context and recognition of episodic content may involve similar brain systems.

Adult↗

Severity of neuropsychological impairment in cocaine and alcohol addiction: association with metabolism in the prefrontal cortex.

We used exploratory and confirmatory statistical approaches to study the severity of neuropsychological (NP) impairment in 42 crack/cocaine addicted subjects and in 112 comparison subjects (40 alcoholics and 72 controls). Twenty neuropsychological test indices most reliably defining predetermined cognitive domains were submitted to exploratory factor analysis. A four-dimensional model of neurocognitive function was derived: Verbal Knowledge, Visual Memory, Verbal Memory, and Attention/Executive functioning accounted for 63% of the variance. We then examined this model's association with resting glucose metabolism in the brain reward circuit measured with 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography. Results revealed that (1) cocaine addicted individuals had a generalized mild level of neurocognitive impairment (<1 S.D. below control mean); and (2) controlling for age and education, relative metabolism in the dorsolateral prefrontal cortex significantly predicted the Visual Memory and Verbal Memory factors and relative metabolism in the anterior cingulate gyrus significantly predicted the Attention/Executive factor. Nevertheless, it remains to be determined whether metabolic changes in these regions are associated with addiction. Our results also suggest that compared to cocaine, alcohol has a more detrimental effect on Attention/Executive functioning, as assessed with traditional NP measures. We conclude that relative to other psychopathological disorders (such as schizophrenia), the severity of neuropsychological impairment in cocaine addiction is modest, albeit not indicative of the absence of neurocognitive dysfunction. The impact of such small differences in performance on quality of life, and possibly on craving and relapse, may be substantial. Tasks that simulate real-life decision-making or that target specific putative cognitive-behavioral or motivational-emotional mechanisms might offer greater sensitivity in characterizing the changes that accompany addiction to drugs. Obtaining valid estimates of alcohol use in cocaine addicted subjects is essential in characterizing neurocognitive functioning in individuals addicted to drugs.

Adult↗

Insight and prefrontal cortex in first-episode Schizophrenia.

Few studies have investigated the neurobiological basis of impaired insight in antipsychotic-naive schizophrenia. However, the relationship between insight and specific prefrontally mediated cognitive functions suggests that insight deficits may be an expression of prefrontal cortical dysfunction. This study was designed to examine the relationship among insight, neurocognition, and dorsolateral prefrontal cortex (DLPFC) volumes in first-episode antipsychotic-naive schizophrenia subjects. DLPFC volumes were compared between 35 first-episode schizophrenia subjects with good (n = 17) and poor insight (n = 18). Morphometric measurements were based on MRI scans by trained raters blind to clinical information. First-episode schizophrenia subjects with poor insight showed decreased right DLPFC volumes relative to those with good insight. In addition, those with poor insight had higher levels of perseverative errors (PEs) on the Wisconsin Card Sort Test (WCST). No differences in other neuropsychological measures were found between the good and poor insight groups. Similarly, no differences were found between schizophrenia subjects with good versus poor insight on any of the psychopathological measures employed in this study. These findings suggest that poor insight in schizophrenia may be a function of specific prefrontally mediated neurocognitive deficits rather than a global impairment in neuropsychological functioning or different profiles of psychopathology.

Adult↗

High frequency repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral cortex: EEG topography during waking and subsequent sleep.

Repetitive transcranial magnetic stimulation (rTMS) is a novel research tool in neurology and psychiatry. It is currently being evaluated as a conceivable alternative to electroconvulsive therapy for the treatment of mood disorders. Eight healthy young (age range 21-25 years) right-handed men without sleep complaints participated in the study. Two sessions at a 1-week interval, each consisting of an adaptation night (sham stimulation) and an experimental night (rTMS in the left dorsolateral prefrontal cortex or sham stimulation; crossover design), were scheduled. In each subject, 40 trains of 2-s duration of rTMS (inter-train interval 28 s) were applied at a frequency of 20 Hz (i.e. 1600 pulses per session) and at an intensity of 90% of the motor threshold. Stimulations were scheduled 80 min before lights off. The waking EEG was recorded for 10-min intervals approximately 30 min prior to and after the 20-min stimulations, and polysomnographic recordings were obtained during the subsequent sleep episode (23.00-07.00 h). The power spectra of two referential derivations, as well as of bipolar derivations along the antero-posterior axis over the left and right hemispheres, were analyzed. rTMS induced a small reduction of sleep stage 1 (in min and percentage of total sleep time) over the whole night and a small enhancement of sleep stage 4 during the first non-REM sleep episode. Other sleep variables were not affected. rTMS of the left dorsolateral cortex did not alter the topography of EEG power spectra in waking following stimulation, in the all-night sleep EEG, or during the first non-REM sleep episode. Our results indicate that a single session of rTMS using parameters like those used in depression treatment protocols has no detectable side effects with respect to sleep in young healthy males.

Adult↗

Evolution of increased glia-neuron ratios in the human frontal cortex.

Evidence from comparative studies of gene expression and evolution suggest that human neocortical neurons may be characterized by unusually high levels of energy metabolism. The current study examined whether there is a disproportionate increase in glial cell density in the human frontal cortex in comparison with other anthropoid primate species (New World monkeys, Old World monkeys, and hominoids) to support greater metabolic demands. Among 18 species of anthropoids, humans displayed the greatest departure from allometric scaling expectations for the density of glia relative to neurons in layer II/III of dorsolateral prefrontal cortex (area 9L). However, the human glia-neuron ratio in this prefrontal region did not differ significantly from allometric predictions based on brain size. Further analyses of glia-neuron ratios across frontal areas 4, 9L, 32, and 44 in a sample of humans, chimpanzees, and macaque monkeys showed that regions involved in specialized human cognitive functions, such as "theory of mind" (area 32) and language (area 44) have not evolved differentially higher requirements for metabolic support. Taken together, these findings suggest that greater metabolic consumption of human neocortical neurons relates to the energetic costs of maintaining expansive dendritic arbors and long-range projecting axons in the context of an enlarged brain.

Animals↗

Attenuated frontal activation in schizophrenia may be task dependent.

UNLABELLED: Functional magnetic resonance imaging was used to examine the neural correlates of two linguistic tasks in schizophrenia. METHOD: Five dextral male schizophrenic patients and five volunteers matched for demographic variables and task performance participated. Echoplanar images were acquired over 5 min at 1.5 T while subjects performed two paced, covert tasks; (1) verbal fluency: silent generation of words beginning with an aurally presented cue letter, contrasted with silent repetition of the aurally presented word 'rest'; (2) semantic decision: deciding whether a visually presented cue word was 'living or non-living' and silently articulating the response, contrasted with rest. Both tasks entailed language processing; only verbal fluency requires the intrinsic generation of verbal material. Between-group differences in the mean power of experimental response to the semantic decision task were identified by a one-way analysis of covariance (ANCOVA), with a measure of stimulus-correlated motion as a covariate. Voxels demonstrating a significant interaction between task and group were identified using a two-way ANCOVA. RESULTS: In controls, both tasks were associated with activation of prefrontal cortex. In patients with schizophrenia there was a significantly reduced power of response in several prefrontal regions during verbal fluency relative to controls, a difference that was not evident for the semantic decision task. There was a significant group x task interaction in the left inferior frontal gyrus, left dorsolateral prefrontal cortex and the supplementary motor area at voxel and regional levels of analysis. CONCLUSIONS: Attenuation of frontal activation during cognitive task performance in schizophrenia does not represent a fixed deficit in frontal function, but may depend on the specific cognitive demands of the experimental task employed.

Adult↗

Abnormal FMRI brain activation in euthymic bipolar disorder patients during a counting Stroop interference task.

BACKGROUND: Bipolar disorder is characterized by disturbed mood homeostasis accompanied by cognitive impairments that appear to persist during euthymia. Cognitive probes, coupled with neuroimaging, provide an approach toward clarifying the neurophysiology of bipolar disorder. METHOD: Sixteen patients with euthymic bipolar disorder and 16 healthy subjects underwent functional magnetic resonance imaging (fMRI) while performing a counting Stroop interference task and a control condition. Task performance was correlated with regional brain activation differences between groups, and the effect on brain activation of receiving versus not receiving medications was evaluated. RESULTS: Bipolar patients exhibited impaired task performance relative to the healthy subjects. In addition, the two groups demonstrated significantly different patterns of brain activation during the interference task. Healthy subjects exhibited relatively increased activation in temporal cortical regions, middle frontal gyrus, putamen, and midline cerebellum. Bipolar subjects exhibited relatively greater activation in the medial occipital cortex. The groups demonstrated different associations between task performance and fMRI activation in these brain regions. No differences in activation in these regions were observed between patients who were versus those who were not receiving medications; however, patients receiving medications exhibited greater activation in the anterior cingulate and dorsolateral prefrontal cortex. CONCLUSIONS: These differences suggest that patients with euthymic bipolar disorder fail to activate brain regions associated with performance of an interference task, which may contribute to impaired task performance. Medications do not explain these differences but may influence activation of brain regions primarily associated with performing an interference task.

Adult↗

Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults: implications for the monoaminergic basis of impulsive behaviour.

RATIONALE: Altered serotonergic and dopaminergic function have been widely implicated in behavioural disorders associated with impulsivity and risk-taking. However, little research has addressed the specific cognitive consequences of changed monoaminergic function that might contribute to the production of impulsive behaviour. OBJECTIVES AND METHODS: We compared the effects of rapid plasma tryptophan depletion, acute doses of the mixed indirect catecholamine agonist, methylphenidate (40 mg), and acute doses of the alpha(1)/alpha(2 )agonist, clonidine (1.5 microg/kg), on aspects of visual discrimination learning involving either acquisition of altered stimulus-reward associations (i.e. updating the affective valence of exteroceptive stimuli) or the control of attention towards relevant as opposed to irrelevant stimulus dimensions. RESULTS: Relative to subjects who received placebo, subjects with reduced tryptophan exhibited a deficit in the ability to learn changed stimulus-reward associations, but were still able to shift an acquired attentional set away from a now-irrelevant stimulus dimension towards a newly relevant dimension. By contrast, subjects who received methylphenidate were able to learn effectively about changing stimulus-reward associations, but showed an enhanced ability to shift an attentional bias, in combination with slowed response times. Subjects who received clonidine showed neither of these changes. CONCLUSIONS: These results suggest that reduction in central serotonin leads to altered neuromodulation of the cortical and subcortical regions (e.g. orbitofrontal cortex, striatum and anterior temporal structures) that mediate important aspects of associative learning whereby exteroceptive stimuli acquire altered incentive motivational value. On the other hand, facilitation of catecholamine neurotransmitters may disrupt the allocation of attention between relevant and irrelevant features of the environment, perhaps through altered modulation of the dorsolateral prefrontal cortex. The implications of these results for understanding the differential neuromodulation of cognitive functions are discussed.

Adolescent↗

Anticipation of emotionally aversive visual stimuli activates right insula.

Understanding the neural substrates of anticipation is required for a comprehensive model of the ways in which anxiety influences information processing. While it is apparent that the insula and medial frontal cortex are involved in processing anticipation of physical (i.e., painful) stimuli, their role in processing anticipation of aversive affective stimuli has yet to be determined. Twenty-eight healthy non-phobic volunteers observed aversive affective images (spiders and snakes) that were preceded by an auditory signal. The insula, dorsolateral prefrontal cortex, and parahippocampal gyrus activated during anticipation of aversive affective images. These findings indicate that common neural circuitry is involved in the anticipation of (and, perhaps, the subjective experience of anticipating) aversive affective and noxious physical stimuli.

Adolescent↗

What is odd in the oddball task? Prefrontal cortex is activated by dynamic changes in response strategy.

In the "oddball" target detection task, subjects respond to target stimuli that occur infrequently and irregularly within a series of standard stimuli. Although detection of these targets reliably evokes transient activity in prefrontal cortical regions, it has not been established whether this activity is due to selection of an infrequent response or to changes in response strategy. We investigated this issue using a novel variant of the oddball task that incorporated the Simon effect, while measuring hemodynamic brain activity in prefrontal cortex using functional magnetic resonance imaging (fMRI). Subjects viewed a series of circles and squares that required left and right button presses, respectively. On 90% of trials ("standard" trials), the stimuli were presented in the same visual hemifield as the hand of response, but on 10% of trials ("strategy-change" trials) they were presented in the opposite visual hemifield. Significant activation to the infrequent strategy-change trials was found in the anterior middle frontal gyrus (MFG), the posterior inferior frontal gyrus (IFG) and adjacent insular cortex, and in the anterior cingulate gyrus (ACG). These regions, which correspond to previous reports of oddball-related activation, were consistent across subjects. Behavioral results supported our interpretation that subjects potentiated a position-based response strategy, which was inhibited on the strategy-change trials. Activity within the MFG and ACG was much greater on error trials than on correct trials, while IFG activity was similar between error and correct trials. We conclude that the dorsolateral prefrontal cortex (dlPFC) is associated with dynamic changes in the mapping of stimuli to responses (e.g. response strategies), independently of any changes in behavior.

Adolescent↗

Motor imagery in Parkinson's disease: a PET study.

We used positron emission tomography (PET) with 15O-labelled water to record patterns of cerebral activation in six patients with Parkinson's disease (PD), studied when clinically "off" and after turning "on" as a result of dopaminergic stimulation. They were asked to imagine a finger opposition movement performed with their right hand, externally paced at a rate of 1 Hz. Trials alternating between motor imagery and rest were measured. A pilot study of three age-matched controls was also performed. We chose the task as a robust method of activating the supplementary motor area (SMA), defects of which have been reported in PD. The PD patients showed normal degrees of activation of the SMA (proper) when both "off" and "on." Significant activation with imagining movement also occurred in the ipsilateral inferior parietal cortex (both "off" and when "on") and ipsilateral premotor cortex (when "off" only). The patients showed significantly greater activation of the rostral anterior cingulate and significantly less activation of the left lingual gyrus and precuneus when performing the task "on" compared with their performance when "off." PD patients when imagining movement and "off" showed less activation of several sites including the right dorsolateral prefrontal cortex (DLPFC) when compared to the controls performing the same task. No significant differences from controls were present when the patients imagined when "on." Our results are consistent with other studies showing deficits of pre-SMA function in PD with preserved function of the SMA proper. In addition to the areas of reduced activation (anterior cingulate, DLPFC), there were also sites of activation (ipsilateral premotor and inferior parietal cortex) previously reported as locations of compensatory overactivity for PD patients performing similar tasks. Both failure of activation and compensatory changes are likely to contribute to the motor deficit in PD.

Aged↗

Reorganization of frontal systems used by alcoholics for spatial working memory: an fMRI study.

Chronic alcoholism is associated with impairment in sustained attention and visual working memory. Thus, alcoholics have reduced ability, but not necessarily inability, to perform these executive tasks, assumed to be subserved by regions of prefrontal cortex. To identify neural substrates associated with this impairment, we used functional MRI (fMRI) to determine whether alcoholics invoke the same or different brain systems as controls when engaged in working memory tasks that the two groups were able to perform at equivalent levels. The fMRI spatial working memory paradigm instructed subjects to respond with a button press when a target position was either in the center of the field (match to center) or matched the spatial position of one presented two items previously (match 2-back) or to rest. Using whole-brain fMRI, alcoholics showed diminished activation frontal cortical systems compared to controls (bilateral dorsolateral prefrontal cortex) when responding 2-back vs rest. In the center vs rest contrast, the control group compared with the alcoholic group activated a large expanse of prefrontal cortex (including Brodmann areas 9, 10, and 45), whereas there was significantly greater activation by the alcoholic group relative to the control group localized more posteriorly and inferiorly in the frontal cortex (area 47). Examination of within group activation patterns revealed two different patterns of activation: the control group exhibited activation of the dorsal ("Where?") stream for visual spatial working memory processing, whereas the alcoholic group exhibited activation of the ventral ("What?") stream and declarative memory systems to accomplish the spatial working memory task. The differences in the pattern of brain activations exhibited by the alcoholic and control groups, despite equivalence in behavioral performance, is consistent with a functional reorganization of the brain systems invoked by alcoholic individuals or invocation of an inappropriate brain system when engaged in a visual spatial task requiring working memory.

Adult↗

Prefrontal [correction of Prefontal] cortex in long-term memory: an "interference" approach using magnetic stimulation.

Neuroimaging has consistently shown engagement of the prefrontal cortex during episodic memory tasks, but the functional relevance of this metabolic/hemodynamic activation in memory processing is still to be determined. We used repetitive transcranial magnetic stimulation (rTMS) to transiently interfere with either left or right prefrontal brain activity during the encoding or retrieval of pictures showing complex scenes. We found that the right dorsolateral prefrontal cortex (DLPFC) was crucial for the retrieval of the encoded pictorial information, whereas the left DLPFC was involved in encoding operations. This 'interference' approach allowed us to establish whether a cortical area activated by a memory task actually contributes to behavioral performance.

Adult↗

Using the international 10-20 EEG system for positioning of transcranial magnetic stimulation.

BACKGROUND: The International 10-20 system for EEG electrode placement is increasingly applied for the positioning of transcranial magnetic stimulation (TMS) in cognitive neuroscience and in psychiatric treatment studies. The crucial issue in TMS studies remains the reliable positioning of the coil above the skull for targeting a desired cortex region. In order to asses the precision of the 10-20 system for this purpose, we tested its projections onto the underlying cortex by using neuronavigation. METHODS: In 21 subjects, the 10-20 positions F3, F4, T3, TP3, and P3, as determined by a 10-20 positioning cap, were targeted stereotactically. The corresponding individual anatomical sites were identified in the Talairach atlas. RESULTS: The main targeted regions were: for F3 Brodmann areas (BA) 8/9 within the dorsolateral prefrontal cortex, for T3 BA 22/42 on the superior temporal gyrus, for TP3 BA 40/39 in thearea of the supramarginal and angular gyrus, and for P3 BA 7/40 on the inferior parietal lobe. However, in about 10% of the measurements adjacent and possibly functionally distinct BAs were reached. The ranges were mainly below 20 mm. CONCLUSION: Using the 10-20 system for TMS positioning is applicable at low cost and may reach desired cortex regions reliably on a larger scale level. For finer grained positioning, possible interindividual differences, and therefore the application of neuroimaging based methods, are to be considered.

Adult↗

Functional MRI study of diencephalic amnesia in Wernicke-Korsakoff syndrome.

Anterograde amnesia in Wernicke-Korsakoff syndrome is associated with diencephalic lesions, mainly in the anterior thalamic nuclei. Whether diencephalic and temporal lobe amnesias are distinct entities is still not clear. We investigated episodic memory for faces using functional MRI (fMRI) in eight controls and in a 34-year-old man with Wernicke-Korsakoff syndrome and diencephalic lesions but without medial temporal lobe (MTL) involvement at MRI. fMRI was performed with a 1.5 tesla unit. Three dual-choice tasks were employed: (i) face encoding (18 faces were randomly presented three times and subjects were asked to memorize the faces); (ii) face perception (subjects indicated which of two faces matched a third face); and (iii) face recognition (subjects indicated which of two faces belonged to the group they had been asked to memorize during encoding). All activation was greater in the right hemisphere. In controls both the encoding and recognition tasks activated two hippocampal regions (anterior and posterior). The anterior hippocampal region was more activated during recognition. Activation in the prefrontal cortex was greater during recognition. In the subject with Wernicke-Korsakoff syndrome, fMRI did not show hippocampal activation during either encoding or recognition. During recognition, although behavioural data showed defective retrieval, the prefrontal regions were activated as in controls, except for the ventrolateral prefrontal cortex. fMRI activation of the visual cortices and the behavioural score on the perception task indicated that the subject with Wernicke-Korsakoff syndrome perceived the faces, paid attention to the task and demonstrated accurate judgement. In the subject with Wernicke-Korsakoff syndrome, although the anatomical damage does not involve the MTL, the hippocampal memory encoding has been lost, possibly as a consequence of the hippocampal-anterior thalamic axis involvement. Anterograde amnesia could therefore be the expression of damage to an extended hippocampal system, and the distinction between temporal lobe and diencephalic amnesia has limited value. In the subject with Wernicke-Korsakoff syndrome, the preserved dorsolateral prefrontal cortex activation during incorrect recognition suggests that this region is more involved in either the orientation or attention at retrieval than in retrieval. The lack of activation of the prefrontal ventrolateral cortex confirms the role of this area in episodic memory formation.

Adult↗

Differential activation of right superior parietal cortex and intraparietal sulcus by spatial and nonspatial attention.

Neuropsychological and functional neuroimaging studies have implicated the right posterior parietal cortex (PPC) in human spatial attention. We tested the hypothesis that this area is also involved in nonspatial aspects of attention and working memory using positron emission tomography in healthy volunteers. In an initial experiment, digits were presented in pseudo-random spatial locations, and subjects attended either to locations or digits in order to detect single targets (attention condition) or to sequences of stimuli (working memory (WM) condition). Right superior parietal cortex (BA7) and intraparietal sulcus (IPS) were active during both spatial (locations) and nonspatial (digits) tasks compared to rest, although more so for the former. Additionally, right PPC was activated to an even greater extent during tests of WM than of attention, especially for tests of spatial WM. There were no differences in activation of dorsolateral prefrontal cortex in the spatial versus nonspatial versions of the task, contrary to many previous studies. A follow-up experiment which presented abstract objects in a fixed, central location confirmed that right IPS was active during tests of nonspatial attention and also that this activation is not due to incidental spatial representation of digit stimuli. However, BA7 was not activated by this nonspatial, nondigit attentional task. Overall, these data suggest first that right IPS is recruited for both nonspatial and spatial attention and WM. Second, right BA7 is recruited specifically for spatial (both direct and indirect) forms of attentional processing. Finally, PPC activations in spatial WM tasks are likely to be due to a combination of spatial perception, attention, and WM, rather than to any of these individually.

Adult↗

Evidence for a dysfunctional retrosplenial cortex in patients with schizophrenia: a functional magnetic resonance imaging study with a semantic-perceptual contrast.

We investigated whether the retrosplenial and the posterior cingulate cortex (RS-PCC) is functionally impaired in schizophrenia patients. Therefore, we measured functional magnetic resonance imaging (fMRI) signal changes associated with a synonym-judgment task known to activate, among other areas, the RS-PCC. Compared to 12 matched control subjects, 12 schizophrenia patients exhibited reliably weaker activations in the RS-PCC, the dorsolateral prefrontal cortex and the left orbitofrontal cortex (P < 0.05, corrected). Differences in frontal activations are in line with previous studies showing a structurally and functionally affected prefrontal cortex in schizophrenia. The impaired RS-PCC functionality in a semantic task may relate to verbal memory deficits frequently observed in schizophrenia patients, because this region is pivotal for gating information into the medial temporal lobe memory system.

Brain Mapping↗

Positron emission tomography study of voluntary saccadic eye movements and spatial working memory.

1. The purpose of this study is to define the cortical regions that subserve voluntary saccadic eye movements and spatial working memory in humans. 2. Regional cerebral blood flow (rCBF) during performance of oculomotor tasks was measured with [15O]-H2O positron emission tomography (PET). Eleven well-trained, healthy young adults performed the following tasks: visual fixation, visually guided saccades, antisaccades (a task in which subjects made saccades away from rather than toward peripheral targets), and either an oculomotor delayed response (ODR, a task requiring memory-guided saccades after a delay period) or a conditional antisaccade task (a task in which the color of the peripheral target determined whether a saccade toward or away from the target was required). An additional six subjects performed a sequential hand movement task to compare localization of hand-related motor cortex and the frontal eye fields (FEFs) and of the hand- and eye-movement-related regions of the supplementary motor area (SMA). 3. Friston's statistical parametric mapping (SPM) method was used to identify significant changes in rCBF associated with task performance. Because SPM does not take advantage of the anatomic information available in magnetic resonance (MR) scans, each subject's PET scan was registered to that individual's MR scan, after which all PET and MR studies were transformed to conform to a standard reference MR image set. Subtraction images were visually inspected while overlayed on the reference MR scan to which PET images had been aligned, in order to confirm anatomic localization of significant rCBF changes. 4. Compared with visual fixation, performing visually guided saccades led to a significant bilateral activation in FEF, cerebellum, striate cortex, and posterior temporal cortex. Right posterior thalamus activation was also observed. 5. The visually guided saccade task served as the comparison task for the ODR, antisaccade, and conditional antisaccade tasks for identification of task-related changes in rCBF beyond those associated with saccade execution. Performance on the ODR task was associated with a bilateral increase of rCBF in FEFs, SMA, dorsolateral prefrontal cortex (DLPFC), and posterior parietal cortex. The cortical regions of increased regional blood flow during the ODR task also showed increased rCBF during the antisaccade task; however, FEF and SMA activations were significant only in the right hemisphere. These findings closely parallel those of single-cell recording studies with behaving monkeys in indicating that FEF, DLPFC, SMA, and posterior parietal cortex perform computational activity for voluntary purposive saccades. 6. Comparison of PET scans obtained during performance of eye movement and hand movement tasks indicated that peak activations in FEF were located approximately 2 cm lateral and 1 cm anterior to those of hand-related motor cortex. The oculomotor area of SMA, the supplementary eye field (SEF), was located approximately 7-8 mm anterior and superior to the hand-related area of SMA. 7. During performance of antisaccade and ODR tasks, rCBF was significantly lower in ventromedial prefrontal cortex (PFC), along the rectus gyrus, and in ventral anterior cingulate cortex than during the visually guided saccade and fixation tasks. During the antisaccade task, the ventral region of lower rCBF involved medial structures including left ventral striatum and bilateral medial temporal-limbic cortex. During the ODR task, the ventral aspect of the region of lower rCBF extended laterally, rather than medially, to include the temporal poles. The lower blood flow observed in ventromedial PFC during both the antisaccade and ODR tasks, relative to the visually guided saccade and fixation tasks, suggests that modulation of output from ventromedial PFC to limbic cortex and the striatum may play a role in the voluntary control of saccadic eye movements, possibly in the suppression of responses that would interrupt

Adult↗