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Neural correlates of retrieval processing in the prefrontal cortex during recognition and exclusion tasks.

Event-related fMRI was employed to contrast the neural activity elicited in prefrontal cortex during recognition memory and exclusion tests. The study phases preceding each memory test were identical, involving the presentation of study items (visually presented words) in one of two study contexts. For the recognition test subjects were required to respond positively to all old items regardless of study context, and to respond negatively to new items. For the exclusion task, positive responses were required to old items presented in one of the study contexts only; negative responses were required both to unstudied items and studied items from the alternative context (non-targets). No prefrontal region demonstrated greater activity for new items in the exclusion task. Thus, there was no evidence that retrieval cues were processed differently according to the specificity of the sought-for information. In several regions, most notably bilateral anterior prefrontal cortex, activity was greater for old than for new items regardless of task. Activity in right dorsolateral prefrontal cortex was also greater for old than for new items; these effects however were larger in the exclusion task. The findings are consistent with previous reports that activity in anterior prefrontal cortex elicited by recognition retrieval cues is sensitive to retrieval success, and extend these findings to the exclusion task. The findings for the right dorsolateral cortex add further weight to the proposal that this region supports post-retrieval monitoring of retrieved information.

Adult↗

Sex-related differences in IBS patients: central processing of visceral stimuli.

BACKGROUND & AIMS: Women have a higher prevalence of irritable bowel syndrome (IBS) and possible differences in response to treatment, suggesting sex-related differences in underlying pathophysiology. The aim of this study was to determine possible sex-related differences in brain responses to a visceral and a psychological stressor in IBS. METHODS: Regional cerebral blood flow measurements using H(2)(15)O positron emission tomography were compared across 23 female and 19 male nonconstipated patients with IBS during a visceral stimulus (moderate rectal inflation) and a psychological stimulus (anticipation of a visceral stimulus). RESULTS: In response to the visceral stimulus, women showed greater activation in the ventromedial prefrontal cortex, right anterior cingulate cortex, and left amygdala, whereas men showed greater activation of the right dorsolateral prefrontal cortex, insula, and dorsal pons/periaqueductal gray. Similar differences were observed during the anticipation condition. Men also reported higher arousal and lower fatigue. CONCLUSIONS: Male and female patients with IBS differ in activation of brain networks concerned with cognitive, autonomic, and antinociceptive responses to delivered and anticipated aversive visceral stimuli.

Adult↗

In vivo assessment of basal and drug-induced dopamine release in cortical and subcortical regions of the anesthetized primate.

There is an acute interest in studying the functional characteristics of dopamine systems in the cortex of primates. In particular, the prefrontal cortical dopamine projections have received a great deal of attention. This system is essential for proper functioning of the prefrontal cortex, and dysfunction within the system may be involved in some psychiatric and neurological illnesses. In vivo assessments of cortical dopamine in the primate have been scarce. This has been due, in part, to technical difficulties associated with these studies and with quantifying the relatively low levels of dopamine found in cortical regions. In the present study, intracerebral microdialysis was utilized to assess the extracellular concentration of dopamine in cortical and subcortical areas of the pentobarbital-anesthetized rhesus monkey. Basal extracellular dopamine levels were consistently detected in the medial prefrontal cortex, premotor cortex, and caudate-putamen. The basal extracellular concentration of dopamine in the dorsolateral prefrontal cortex was reliably detected in 1 of 4 animals. Intravenous administration of amphetamine (1 mg/kg) enhanced extracellular dopamine levels in the caudate-putamen area by more than 20-fold. In cortical areas, amphetamine's effect was less profound: An increase of 400-500 percent over basal extracellular dopamine levels was observed in each region. These studies demonstrate the feasibility of microdialysis for detecting extracellular fluxes of dopamine in the cortex of nonhuman primates. They further provide direct evidence that the dopamine released within the prefrontal cortex and the premotor cortex of nonhuman primates responds to pharmacological manipulation.

Amphetamine↗

Gating of somatosensory input by human prefrontal cortex.

Somatosensory evoked potentials (SEPs) to median nerve stimulation were recorded in controls and in patients with focal lesions in dorsolateral prefrontal cortex (PFCx). Unilateral PFCx lesions increased the amplitude of the P26 component generated in postcentral areas 1 and 2. The amplitudes of the N28, P45 and N67 SEP components recorded over post-rolandic and frontal electrodes were also enhanced by PFCx damage. In contrast, the N19 component generated in postcentral area 3b was unaffected by PFCx lesions. The results indicate that PFCx exerts inhibitory modulation on sensory processing that may be mediated by corticocortical PFCx-parietal connections.

Aged↗

Prefrontal-subcortical dissociations underlying inhibitory control revealed by event-related fMRI.

Using event-related fMRI, this study investigated the neural dynamics of response inhibition under fluctuating task demands. Fourteen participants performed a GO/NOGO task requiring inhibition of a prepotent motor response to NOGO events that occurred as part of either a Fast or Slow presentation stream of GO stimuli. We compared functional activations associated with correct withholds (Stops) required during the Fast presentation stream of stimuli to Stops required during the Slow presentation stream. A predominantly right hemispheric network was activated across conditions, consistent with previous studies. Furthermore, a functional dissociation of activations between conditions was observed. Slow Stops elicited additional activation in anterior dorsal and polar prefrontal cortex and left inferior parietal cortex. Fast Stops showed additional activation in a network that included right dorsolateral prefrontal cortex, insula and dorsal striatum. These results are discussed in terms of our understanding of the impact of preparation on the distributed network underlying response inhibition and the contribution of subcortical areas, such as the basal ganglia, to executive control processes.

Adult↗

Enhancing analogic reasoning with rTMS over the left prefrontal cortex.

The authors utilized repetitive transcranial magnetic stimulation (rTMS) in 16 normal volunteers to investigate the role of the left dorsolateral prefrontal cortex (PFC) in analogic reasoning. rTMS over the left and right PFC, over the left motor cortex, and sham stimulation over the left PFC were administered during memory and analogic reasoning conditions. rTMS over the left PFC led to a significant reduction in response times only in the analogy condition without affecting accuracy. These results indicate that the left PFC is relevant for analogic reasoning and that rTMS applied to the PFC can speed up solution time.

Adult↗

Hemispheric dissociation of visual-pattern processing and visual rotation.

We aimed at investigating whether on-line and delayed visual pattern processing activated different areas in human prefrontal and parietal cortex. For this purpose we measured the regional cerebral blood flow (rCBF) during simultaneous and successive visual matrix processing in 10 right-handed subjects. Delayed matching to sample activated predominantly left hemispheric ventrolateral prefrontal cortex, Broca's area and parts of the parietal cortex. In contrast, visuospatial matrix rotation showed activation of the right dorsolateral prefrontal cortex and parietal lobe. The present results suggest a hemispheric dissociation of fronto-parietal circuits with a left dominance for visual pattern processing like storage and a right dominance for visuospatial processing.

Adult↗

Stimulus-response incompatibility activates cortex proximate to three eye fields.

We used functional magnetic resonance imaging (fMRI) to investigate cortical activation during the performance of three oculomotor tasks that impose increasing levels of cognitive demand. (1) In a visually guided saccade (VGS) task, subjects made saccades to flashed targets. (2) In a compatible task, subjects made leftward and rightward saccades in response to foveal presentation of the uppercase words "LEFT" or "RIGHT." (3) In a mixed task, subjects made rightward saccades in response to the lowercase word "left" and leftward saccades in response to the lowercase word "right" on incompatible trials (60%). The remaining 40% of trials required compatible responses to uppercase words. The VGS and compatible tasks, when compared to fixation, activated the three cortical eye fields: the supplementary eye field (SEF), the frontal eye field (FEF), and the parietal eye field (PEF). The mixed task, when compared to the compatible task, activated three additional cortical regions proximate to the three eye fields: (1) rostral to the SEF in medial frontal cortex; (2) rostral to the FEF in dorsolateral prefrontal cortex (DLPFC); (3) rostral and lateral to the PEF in posterior parietal cortex. These areas may contribute to the suppression of prepotent responses and in holding novel visuomotor associations in working memory.

Adult↗

Neural networks of response shifting: influence of task speed and stimulus material.

Functional magnetic resonance imaging (fMRI) was used in 14 healthy subjects to measure brain activation, while response shifting was performed. In the activation phase, subjects were asked to shift their attention between two different types of visually presented stimuli. In the baseline phase, subjects were required to attend to one stimulus type only. Subjects responded by pressing a left or right key according to the side of presentation of the target stimuli. In a verbal task, subjects were required to switch between letters and numbers. In a figural task, subjects reacted to round and square shapes. Stimuli were presented for 750 or 1500 ms. Response shifting revealed significantly increased activation compared to non-switching in the bilateral superior parietal cortex, right occipital cortex, left inferior frontal cortex, left and right striatum, and bilateral dorsolateral prefrontal cortex (DLPFC). Superior parietal and occipital cortex activation may be due to spatial analysis during response shifting. Subvocal rehearsal of the task instructions may have led to activation in the left inferior frontal cortex. Activation in the striatum was related to prefrontal activation and may represent the association between basal ganglia and prefrontal activation during executive control. However, the most important brain region involved in the execution of response shifting was the bilateral DLPFC. Higher task speed increased executive top-down attentional control and, therefore, significantly increased activity in the bilateral DLPFC. Brain activation did not differ significantly between verbal and figural stimulus material. This result suggests that brain activation in the present study illustrates the brain regions involved in the basic cognitive mechanisms of response shifting.

Adult↗

Cortical activation during a spatiotemporal tactile comparison task.

Tactile sensory memory is needed to infer shape or motion from the spatiotemporal pattern of sensory input during manual exploration. Here we applied triplets of pressure pulses to the fingertips of subjects who were asked to respond when successive triplets were the same (COMPARE task) or when a particular stimulus was included in a triplet (CONTROL task). Stimulus sequences (30 s) alternated with rest blocks (30 s) and functional magnetic resonance images (fMRIs) were acquired in a 1.5-T scanner. During the COMPARE task, we found enhanced activation in inferior parietal cortex, supplementary motor area (SMA), and right dorsolateral prefrontal cortex (DLPFC). Activation of DLPFC is likely to be related to the attempt to memorize the stimulus sequences and activations of SMA and inferior parietal cortex to the analysis of temporospatial tactile patterns and, more generally, to guidance of haptic exploration. In addition, task-specific activation was seen in anterior cingulate gyrus, possibly related to the high mental effort required by the comparison task. Our rhythmic tactile stimulus as such, without any task-specific enhancement, activated also left cerebellum and (mainly left) putamen, supporting the idea that these structures are related to perception of temporal order of tactile stimuli.

Adult↗

Different extraretinal neuronal mechanisms of smooth pursuit eye movements in schizophrenia: An fMRI study.

Smooth pursuit eye movements (SPEM) are necessary to follow slowly moving targets while maintaining foveal fixation. In about 50% of schizophrenic patients SPEM velocity is reduced. In this study we were interested in identifying the cortical mechanisms associated with extraretinal processing of SPEM in schizophrenic patients. During condition A, patients and healthy subjects had to pursue a constantly visible target (10 degrees /s). During condition B the target was blanked out for 1000 ms while subjects were instructed to continue SPEM. Eye movement data were assessed during scanning sessions by a limbus tracker. During condition A, reduced SPEM velocity in patients was associated with reduced activation of the right ventral premotor cortex and increased activation of the left dorsolateral prefrontal cortex, the right thalamus and the Crus II of the left cerebellar hemisphere. During condition B, SPEM velocity was reduced to a similar extent in both groups. While in patients a decrease in activation was observed in the right cerebellar area VIIIA, the activation of the right anterior cingulate, the right superior temporal cortex, and the bilateral frontal eye fields was increased. The results implicate that schizophrenic patients employ different strategies during SPEM both with and without target blanking than healthy subjects. These strategies predominantly involve extraretinal mechanisms.

Adult↗

Inhibition and the right inferior frontal cortex.

It is controversial whether different cognitive functions can be mapped to discrete regions of the prefrontal cortex (PFC). The localisationist tradition has associated one cognitive function - inhibition - by turns with dorsolateral prefrontal cortex (DLPFC), inferior frontal cortex (IFC), or orbital frontal cortex (OFC). Inhibition is postulated to be a mechanism by which PFC exerts its effects on subcortical and posterior-cortical regions to implement executive control. We review evidence concerning inhibition of responses and task-sets. Whereas neuroimaging implicates diverse PFC foci, advances in human lesion-mapping support the functional localization of such inhibition to right IFC alone. Future research should investigate the generality of this proposed inhibitory function to other task domains, and its interaction within a wider network.

Animals↗

Olfactory identification deficiency and WCST performance in men with schizophrenia.

Several studies using the University of Pennsylvania Smell Identification Test (UPSIT), which requires forced choice olfactory identifications, have reported olfactory identification deficits in patients with schizophrenia. This report examines the possible links between olfactory identification (usually attributed to the orbitofrontal cortex) and executive functions (usually attributed to dorsolateral prefrontal cortex) in 24 male patients with schizophrenia and 21 male comparison subjects. Olfactory performance was investigated under two conditions: spontaneous identification and forced choice identification. Executive function was assessed with the Wisconsin Card Sorting Test (WCST). Compared with controls, patients with schizophrenia exhibited a higher average number of cigarettes smoked per day, lower spontaneous identification scores on olfactory performance, and a higher percentage of perseverative errors on the WCST; there was a significant relationship between the two performance measures. Simpson-Angus scores, neuroleptic drug treatment levels, and scores on the Positive and Negative Syndrome Scale were not correlated with either olfactory measure. The lack of correlation between the forced choice olfactory identification score and the WCST score is consistent with findings in previous studies that used the UPSIT. By contrast, use of a spontaneous identification condition to assess olfactory performance did produce a significant association with WCST performance.

Adult↗

Adaptive changes in early and late blind: a fMRI study of Braille reading.

Braille reading depends on remarkable adaptations that connect the somatosensory system to language. We hypothesized that the pattern of cortical activations in blind individuals reading Braille would reflect these adaptations. Activations in visual (occipital-temporal), frontal-language, and somatosensory cortex in blind individuals reading Braille were examined for evidence of differences relative to previously reported studies of sighted subjects reading print or receiving tactile stimulation. Nine congenitally blind and seven late-onset blind subjects were studied with fMRI as they covertly performed verb generation in response to reading Braille embossed nouns. The control task was reading the nonlexical Braille string "######". This study emphasized image analysis in individual subjects rather than pooled data. Group differences were examined by comparing magnitudes and spatial extent of activated regions first determined to be significant using the general linear model. The major adaptive change was robust activation of visual cortex despite the complete absence of vision in all subjects. This included foci in peri-calcarine, lingual, cuneus and fusiform cortex, and in the lateral and superior occipital gyri encompassing primary (V1), secondary (V2), and higher tier (VP, V4v, LO and possibly V3A) visual areas previously identified in sighted subjects. Subjects who never had vision differed from late blind subjects in showing even greater activity in occipital-temporal cortex, provisionally corresponding to V5/MT and V8. In addition, the early blind had stronger activation of occipital cortex located contralateral to the hand used for reading Braille. Responses in frontal and parietal cortex were nearly identical in both subject groups. There was no evidence of modifications in frontal cortex language areas (inferior frontal gyrus and dorsolateral prefrontal cortex). Surprisingly, there was also no evidence of an adaptive expansion of the somatosensory or primary motor cortex dedicated to the Braille reading finger(s). Lack of evidence for an expected enlargement of the somatosensory representation may have resulted from balanced tactile stimulation and gross motor demands during Braille reading of nouns and the control fields. Extensive engagement of visual cortex without vision is discussed in reference to the special demands of Braille reading. It is argued that these responses may represent critical language processing mechanisms normally present in visual cortex.

Adaptation, Physiological↗

Temporally irregular mnemonic persistent activity in prefrontal neurons of monkeys during a delayed response task.

An important question in neuroscience is whether and how temporal patterns and fluctuations in neuronal spike trains contribute to information processing in the cortex. We have addressed this issue in the memory-related circuits of the prefrontal cortex by analyzing spike trains from a database of 229 neurons recorded in the dorsolateral prefrontal cortex of 4 macaque monkeys during the performance of an oculomotor delayed-response task. For each task epoch, we have estimated their power spectrum together with interspike interval histograms and autocorrelograms. We find that 1). the properties of most (about 60%) neurons approximated the characteristics of a Poisson process. For about 25% of cells, with characteristics typical of interneurons, the power spectrum showed a trough at low frequencies (<20 Hz) and the autocorrelogram a dip near zero time lag. About 15% of neurons had a peak at <20 Hz in the power spectrum, associated with the burstiness of the spike train; 2). a small but significant task dependency of spike-train temporal structure: delay responses to preferred locations were characterized not only by elevated firing, but also by suppressed power at low (<20 Hz) frequencies; and 3). the variability of interspike intervals is typically higher during the mnemonic delay period than during the fixation period, regardless of the remembered cue. The high irregularity of neural persistent activity during the delay period is likely to be a characteristic signature of recurrent prefrontal network dynamics underlying working memory.

Action Potentials↗

Frontal lobe contributions to theory of mind.

"Theory of mind," the ability to make inferences about others" mental states, seems to be a modular cognitive capacity that underlies humans" ability to engage in complex social interaction. It develops in several distinct stages, which can be measured with social reasoning tests of increasing difficulty. Individuals with Asperger"s syndrome, a mild form of autism, perform well on simpler theory of mind tests but show deficits on more developmentally advanced theory of mind tests. We tested patients with bilateral damage to orbito-frontal cortex (n = 5) and unilateral damage in left dorsolateral prefrontal cortex (n = 5) on a series of theory of mind tasks varying in difficulty. Bilateral orbito-frontal lesion patients performed similarly to individuals with Asperger"s syndrome, performing well on simpler tests and showing deficits on tasks requiring more subtle social reasoning, such as the ability to recognize a faux pas. In contrast, no specific theory of mind deficits were evident in the unilateral dorsolateral frontal lesion patients. The dorsolateral lesion patients had difficulty only on versions of the tasks that placed demands on working memory.

Adult↗

Prefrontal cortex fMRI signal changes are correlated with working memory load.

We investigated whether a nonspatial working memory (WM) task would activate dorsolateral prefrontal cortex (DLPFC) and whether activation would be correlated with WM load. Using functional magnetic resonance imaging we measured regional brain signal changes in 12 normal subjects performing a continuous performance, choice reaction time task that requires WM. A high WM load condition was compared with a non-WM choice reaction time control condition (WM effect) and a low WM load condition (load effect). Significant changes in signal intensity occurred in the DLPFC, frontal motor regions and the intraparietal sulcus (IPS) in both comparisons. These findings support the role of DLPFC and IPS in WM and suggest that signal changes in DLPFC correlate with WM load.

Adult↗

Depth distribution of neuronal activity related to a visual reaction time task in the monkey prefrontal cortex.

1. The depth distributions of neurons with changes in activity during a visual reaction time task were investigated in the dorsolateral prefrontal cortex of the macaque monkey, using glass micropipettes. The task was initiated by the monkey pressing a lever and consisted of an initial waiting phase (3.0-s period); a warning phase (green lamp, a variable period of 1.5-3.5 s); a lever-release GO phase (red lamp); and a final reward phase. The locations of neurons, in terms of the cortical layer, whose activities were recorded during performance of the task, were estimated histologically by marks made during the recording session. Marks were made by passing a DC current (anodal, 10-20 microA, 10-20 s) through the tip of an electrode which contained carbon fibers. Manipulator readings during the experiments and measurements of the distance of the marks from the cortical surface for 28 electrode penetrations showed a discrepancy of 2.0 +/- 5.0%, indicating that the depths at which task-related neurons were located could be estimated with errors of less than 10%. 2. Out of 162 task-related neurons recorded during 31 electrode penetrations, 53 showed changes in activity only during the warning phase (W-type; 19 phasic, 10 phasic-tonic, and 24 tonic), 37 showed changes only during the GO phase (GO-type; 4 Cue-coupled, 27 Intermediate, and 6 Movement-coupled), 34 showed changes during both the warning and GO phases (WG-type; 9 phasic, 10 phasic-tonic, and 15 tonic), and 38 showed changes during the reward phase (RE-type; 22 phasic and 16 tonic). 3. The various task-related neurons were distributed differently in different layers. Most neurons were recorded from layers III through V. In layer I, no neurons were recorded. In layer II, only a small number of neurons, with changes during the warning phase, were recorded (n = 7, 4%). One-third of the neurons were recorded in layer III (n = 51, 32%); neurons with changes during the warning phase were the most numerous (n = 24) and were significantly more numerous than neurons with changes associated with other phases of the task. One-fourth of the neurons were recorded in layer IV (n = 43, 27%); neurons with changes during the reward phase were the most numerous (n = 19), and were significantly more numerous than neurons with changes during both the warning and GO phases and also more numerous than neurons with changes during the GO phase.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗