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.     

Neuroimaging a single thought: dorsolateral PFC activity associated with refreshing just-activated information.

Neuroimaging studies of human working memory (WM) show conflicting results regarding whether dorsolateral prefrontal cortex (PFC) contributes to maintaining information in consciousness or is recruited primarily when information must be manipulated. Using functional magnetic resonance imaging (fMRI), we looked at a minimal maintenance process--thinking back to a single, just-seen stimulus (refreshing). We found greater activity in left dorsolateral PFC (BA9) when participants refreshed a word compared to reading a word once or a second time. Furthermore, recognition memory was subsequently more accurate and faster for items that had been refreshed, demonstrating that a single thought that maintains activation can have consequences for long-term memory. Our fMRI results call into question any class of models of the functional organization of PFC and WM that associates simple and/or maintenance processes only with ventrolateral PFC or that associates dorsolateral PFC only with more complex processes such as manipulation.     

Spatiotemporal characteristics of hemodynamic changes in the human lateral prefrontal cortex during working memory tasks

The prefrontal cortex (PFC) is widely believed to subserve mental manipulation and monitoring processes ascribed to the central executive (CE) of working memory (WM). We attempted to examine and localize the CE by functional imaging of the frontal cortex during tasks designed to require the CE. Using near-infrared spectroscopy, we studied the spatiotemporal dynamics of oxygenated hemoglobin (oxy-Hb), an indicator of changes in regional cerebral blood flow, in both sides of lateral PFC during WM intensive tasks. In most participants, increases in oxy-Hb were localized within one subdivison during performance of the n-back task, whereas oxy-Hb increased more diffusely during the random number generation (RNG) task. Activation of the ventrolateral PFC (VLPFC) was prominent in the n-back task; both sustained and transient dynamics were observed. Transient dynamics means that oxy-Hb first increases but then decreases to less than 50% of the peak value or below the baseline level before the end of the task. For the RNG task sustained activity was also observed in the dorsolateral PFC (DLPFC), especially in the right hemisphere. However, details of patterns of activation varied across participants: subdivisions commonly activated during performance of the two tasks were the bilateral VLPFCs, either side of the VLPFC, and either side of the DLPFC in 4, 2, and 4 of the 12 participants, respectively. The remaining 2 of the 12 participants had no regions commonly activated by these tasks. These results suggest that although the PFC is implicated in the CE, there is no stereotyped anatomical PFC substrate for the CE.     

Maintenance versus manipulation in verbal working memory revisited: an fMRI study

Working memory (WM) is the ability to keep a limited amount of information "on line" for immediate use during short intervals. Verbal WM has been hypothesized to consist of neuroanatomically segregated components, i.e., maintenance (storage, rehearsal, and matching) and manipulation (reordering or updating), corresponding to ventrolateral and dorsolateral prefrontal cortex. Previous imaging studies of maintenance vs manipulation processes in WM have produced inconsistent results, which may have been due to methodological issues such as low statistical power and the use of insertion (subtraction) designs. In the present functional magnetic resonance imaging study we used parametric versions of both a prototypical maintenance task (Sternberg) and a prototypical manipulation task (n-letter back task) in 21 healthy subjects. Increased signal correlated with load common for both tasks was found in bilateral dorsolateral and anterior prefrontal, left ventrolateral prefrontal, and bilateral parietal regions. Workload x task interactions were found in bilateral dorsolateral prefrontal cortex for manipulation vs maintenance, but also for responding vs encoding (storage) in the maintenance task. Therefore, our data support a functional rather than a neuroanatomical distinction between maintenance and manipulation, given our finding that these tasks differentially activate virtually identical systems.     

Using fMRI to decompose the neural processes underlying the Wisconsin Card Sorting Test

The specific role of particular cerebral regions with regard to executive functions remains elusive. We conducted a functional magnetic resonance imaging (fMRI) study to segregate different network components underlying the Wisconsin Card Sorting Test (WCST), a test widely applied clinically to assess executive abilities. Three different test variants of the WCST, differing in task complexity (A > B > C), were contrasted with a high-level baseline condition (HLB). Cognitive subcomponents were extracted in a serial subtraction approach (A-C, A-B, B-C). Imaging data were further subjected to a correlational analysis with individual behavioral parameters. Contrasting A with the HLB revealed the entire neural network underlying WCST performance, including frontoparietal regions and the striatum. Further analysis showed that, within this network, right ventrolateral prefrontal cortex related to simple working memory operations, while right dorsolateral prefrontal cortex related to more complex/manipulative working memory operations. The rostral anterior cingulate cortex (ACC) and the temporoparietal junction bilaterally represented an attentional network for error detection. In contrast, activation of the caudal ACC and the right dorsolateral prefrontal cortex was associated with increased attentional control in the context of increasing demands of working memory and cognitive control. Non-frontal activations were found to be related to (uninstructed relative to instructed) set-shifting (cerebellum) and working memory representations (superior parietal cortex, retrosplenium). The data provide neural correlates for the different cognitive components involved in the WCST. They support a central role of the right dorsolateral prefrontal cortex in executive working memory operations and cognitive control functions but also suggest a functional dissociation of the rostral and caudal ACC in the implementation of attentional control.     

Co-ordination within and between verbal and visuospatial working memory: network modulation and anterior frontal recruitment

Attention switching between items being stored and manipulated in working memory (WM) is proposed to be an elementary executive function. Experiment 1 reveals a similar attentional limitation within and between verbal and visuospatial WM and identifies a supramodal switching process required for switching between WM items. By using functional magnetic resonance imaging, Experiment 2 investigated brain activation correlates of parametrically varied attention switching within and between these two WM modalities. Attention switching activation was broadly distributed, was quite similar across the three conditions, and, in almost all areas, increased with increasing switching demand, indicating that attention switching recruits and modulates the entire WM network. Dorsolateral prefrontal cortex was implicated in both within- and between-modality attention switching, but no significant activation was found in ventrolateral areas, supporting dorsal-ventral process models of prefrontal organization. A functional dissociation between anterior frontal and dorsolateral prefrontal cortex was found with the former being more activated when switching attention between modalities was required. The data challenge the notion of an anatomically separate attention switching executive function, but suggest that anterior frontal areas are recruited for the additional demand of coordinating the verbal and visuospatial WM slave systems.     

Working memory in another dimension: functional imaging of human olfactory working memory

The majority of working memory research has been carried out within the visual and auditory modalities, leaving it unclear how other modalities would map onto currently proposed working memory models. In this study we examined the previously uninvestigated area of olfactory working memory. Our aim was to investigate if olfactory working memory would engage prefrontal regions known to be involved in working memory for other sensory modalities. Using positron emission tomography we measured cerebral blood flow changes in 12 volunteers during an olfactory working memory task and a comparison visual working memory task. Our findings indicate that both olfactory and face working memory engaged dorsolateral and ventrolateral frontal cortex when the task requirements were matched; a conjunction analysis indicated overlap in the distribution of activity in the two tasks. Similarities and differences in activity were noted in parietal lobe regions, with both tasks engaging inferior areas of 40/7, but only visual working memory showing increased activity within left superior parietal cortex. The findings support the idea that working memory processes engage frontal cortical areas independent of the modality of input, but do not rule out the possibility of modality-specific neural populations within dorsolateral or ventrolateral cortex.     

Dissociation of working memory processing associated with native and second languages: PET investigation

Verbal working memory plays a significant role in language comprehension and problem-solving. The prefrontal cortex has been suggested as a critical area in working memory. Given that domain-specific dissociations of working memory may exist within the prefrontal cortex, it is possible that there may also be further functional divisions within the verbal working memory processing. While differences in the areas of the brain engaged in native and second languages have been demonstrated, little is known about the dissociation of verbal working memory associated with native and second languages. We have used H2(15)O positron emission tomography in 14 normal subjects in order to identify the neural correlates selectively involved in working memory of native (Korean) and second (English) languages. All subjects were highly proficient in the native language but poorly proficient in the second language. Cognitive tasks were a two-back task for three kinds of visually presented objects: simple pictures, English words, and Korean words. The anterior portion of the right dorsolateral prefrontal cortex and the left superior temporal gyrus were activated in working memory for the native language, whereas the posterior portion of the right dorsolateral prefrontal cortex and the left inferior temporal gyrus were activated in working memory for the second language. The results suggest that the right dorsolateral prefrontal cortex and left temporal lobe may be organized into two discrete, language-related functional systems. Internal phonological processing seems to play a predominant role in working memory processing for the native language with a high proficiency, whereas visual higher order control does so for the second language with a low proficiency.     

The influence of explicit instructions and stimulus material on lateral frontal responses to an encoding task

In this functional magnetic resonance imaging study, we explored the effects of both stimulus material and encoding task demands on activation in lateral prefrontal cortex (PFC). Two factors were manipulated: material type and task instructions. Subjects encoded words or abstract figures (factor 1: stimulus type) and were required to make either a meaning-based or a form-based (letter or shape) decision about each stimulus (factor 2: task instructions). Abstract figures engendered significantly higher levels of right PFC activity than did words. This effect was seen for meaning-based and form-based processing tasks and was significantly greater for the former. We did not observe a differential response of left lateral PFC to verbal and pictorial material. A double dissociation, however, was found within left PFC. A ventrolateral region (within left inferior frontal gyrus) showed the highest levels of activity when words were processed according to their meaning whereas activity in a more dorsolateral region (within left middle frontal gyrus) was greatest when words were processed according to their form (constituent letters). We have therefore observed a main effect of material type in producing lateralized activation of frontal lobes, although the strength of this effect is sensitive to the nature of the task that subjects are asked to perform. Left-side lateral PFC activity is also sensitive to task instructions but this effect was specific to verbal material. The complex patterns of frontal effect counsel against any simple dichotomy of frontal function at the level of either material or task type.     

Hemispheric specialization of the lateral prefrontal cortex for strategic processing during spatial and shape working memory

OBJECTIVE: We investigated whether spatial working memory (WM) is associated with functional specialization of the right prefrontal cortex (PFC) relative to WM for shapes. We designed spatial and shape WM tasks that are relatively easy to perform and that minimize both task-switching and manipulation demands. The tasks use identical stimuli and require the same motor response. METHODS: We presented 12 subjects with target shapes that appeared in particular locations. Subjects maintained either the location or the shape of the targets in WM and responded to each probe by indicating whether it was a target. During a non-WM control task, subjects indicated whether the probe appeared on the right or left side of the screen. Subjects were scanned with a 3.0 T Siemens scanner and data were analyzed using SPM99. The WM tasks were compared to identify PFC activation that was different for spatial versus shape WM. Each WM task was also compared to the control task. RESULTS: compared with shape WM, spatial WM performance was faster and more accurate and was associated with increased right ventrolateral and frontopolar PFC activation. In contrast, compared to spatial WM, shape WM was associated with increased left ventrolateral PFC activity. CONCLUSIONS: These findings demonstrate hemispheric specialization for spatial versus shape WM in the ventrolateral PFC. The increased activity in the right PFC for spatial WM cannot be attributed to increased task difficulty, the stimuli used, or the response requirements. Rather, we propose that differences in performance and activation reflect the use of configural processing strategies for spatial WM.     

Age-related changes in neural activity during performance matched working memory manipulation

A long-standing assumption in the cognitive aging literature is that performance on working memory (WM) tasks involving serial recall is relatively unaffected by aging, whereas tasks that require the rearrangement of items prior to recall are more age-sensitive. Previous neuroimaging studies of WM have found age-related increases in neural activity in frontoparietal brain regions during simple maintenance tasks, but few have examined whether there are age-related differences that are specific to rearranging WM items. In the current study, older and younger adults' brain activity was monitored using functional magnetic resonance imaging (fMRI) as they performed WM tasks involving either maintenance or manipulation (letter–number sequencing). The paradigm was developed so that performance was equivalent across age groups in both tasks, and the manipulation condition was not more difficult than the maintenance condition. In younger adults, manipulation-related increases in activation occurred within a very focal set of regions within the canonical brain WM network, including left posterior prefrontal cortex and bilateral inferior parietal cortex. In contrast, older adults showed a much wider extent of manipulation-related activation within this WM network, with significantly increased activity relative to younger adults found within bilateral PFC. The results suggest that activation and age-differences in lateral PFC engagement during WM manipulation conditions may reflect strategy use and controlled processing demands rather than reflect the act of manipulation per se.     

Similarities and differences in the neural correlates of episodic memory retrieval and working memory

Functional neuroimaging studies have shown that different cognitive functions activate overlapping brain regions. An activation overlap may occur because a region is involved in operations tapped by different cognitive functions or because the activated area comprises subregions differentially involved in each of the functions. To investigate these issues, we directly compared brain activity during episodic retrieval (ER) and working memory (WM) using event-related functional MRI (fMRI). ER was investigated with a word recognition test, and WM was investigated with a word delayed-response test. Two-phase trials distinguished between retrieval mode and cue-specific aspects of ER, as well as between encoding/maintenance and retrieval aspects of WM. The results revealed a common fronto-parieto-cerebellar network for ER and WM, as well as subregions differentially involved in each function. Specifically, there were two main findings. First, the results differentiated common and specific subregions within the prefrontal cortex: (i) left dorsolateral areas were recruited by both functions, possibly reflecting monitoring operations; (ii) bilateral anterior and ventrolateral areas were more activated during ER than during WM, possibly reflecting retrieval mode and cue-specific ER operations, respectively; and (iii) left posterior/ventral (Broca's area) and bilateral posterior/dorsal areas were more activated during WM than during ER, possibly reflecting phonological and generic WM operations, respectively. Second, hippocampal and parahippocampal regions were activated not only for ER but also for WM. This result suggests that indexing operations mediated by the medial temporal lobes apply to both long-term and short-term memory traces. Overall, our results show that direct cross-function comparisons are critical to understand the role of different brain regions in various cognitive functions.     

Prefrontal cortex activity in self-initiated movements is condition-specific, but not movement-related

Activity of the prefrontal cortex (PFC) has been observed in previous block-design brain imaging studies of self-initiated movements. However, the meaning of these activations remained unclear. A functional MRI experiment was carried out, which utilized an epoch and an event-related analysis approach to the data. We hypothesized that event-related activity of the PFC would argue for a contribution to movement preparation. In contrast, epoch-, but not event-related activity pointed to tonic activations, probably reflecting enhanced attentional states or working memory processing. Twenty-one subjects were examined with 845 T2*-weighted images. During active phases, subjects were instructed to perform self-initiated movements of the right index finger with intertrial intervals of about 8 s. On single subject level, epoch- and event-related regressors were entered into a combined model, estimating the exclusive contribution of either regressor. For statistical inference on multisubject level, random effects analyses were performed. For the epoch regressor, activity within the right dorso- and ventrolateral prefrontal cortex, the bilateral insula, and the right inferior parietal lobe was observed. The event-related regressor detected activity within the right inferior parietal lobe, ventral from the activity found with the epoch regressor. The present results indicate a condition-, but not a movement-related function of the PFC in self-initiated movements. Furthermore, anatomically distinct regions within the inferior parietal cortex seem to be involved in condition-specific and movement-related processes. The observed condition-specific activations are suggested to reflect attentional or working memory processes, supervising task performance, rather than movement preparation or initiation.     

Probing the transformation of discontinuous associations into episodic memory: an event-related fMRI study

Using event-related functional magnetic resonance imaging, we identified brain regions involved in storing associations of events discontinuous in time into long-term memory. Participants were scanned while memorizing item-triplets including simultaneous and discontinuous associations. Subsequent memory tests showed that participants remembered both types of associations equally well. First, by constructing the contrast between the subsequent memory effects for discontinuous associations and simultaneous associations, we identified the left posterior parahippocampal region, dorsolateral prefrontal cortex, the basal ganglia, posterior midline structures, and the middle temporal gyrus as being specifically involved in transforming discontinuous associations into episodic memory. Second, we replicated that the prefrontal cortex and the medial temporal lobe (MTL) especially the hippocampus are involved in associative memory formation in general. Our findings provide evidence for distinct neural operation(s) that supports the binding and storing discontinuous associations in memory. We suggest that top-down signals from the prefrontal cortex and MTL may trigger reactivation of internal representation in posterior midline structures of the first event, thus allowing it to be associated with the second event. The dorsolateral prefrontal cortex together with basal ganglia may support this encoding operation by executive and binding processes within working memory, and the posterior parahippocampal region may play a role in binding and memory formation.     

Functional network in the prefrontal cortex during episodic memory retrieval

A recent consistent finding in neuroimaging studies of human memory is that the prefrontal cortex (PFC) is activated during episodic memory retrieval. To date, however, there has been no direct evidence to explain how activity in the right and left PFC and in the anterior and posterior PFC are functionally interconnected. The goal of the present study was to obtain such evidence by event-related functional magnetic resonance imaging (MRI) and the functional connectivity method. Subjects were first asked to try to remember a series of associate-word lists outside the MRI scanner in preparation for a later recognition test. In the MRI scanning phase, they were asked to make recognition judgments in regard to old words, semantically related lure words, and unrelated new words. The analysis of functional connectivity revealed that the posterior PFC in each hemisphere had strong functional interconnections with the contralateral posterior PFC, whereas the anterior PFC in each hemisphere had only weak functional interconnections with the contralateral anterior PFC. No strong functional interconnections were found between the anterior and posterior PFC in either hemisphere. These findings support the hypothesis of an associative contribution of the bilateral posterior PFC to episodic memory retrieval and a dissociative contribution of the bilateral anterior PFC.     

Prefrontal hemodynamic activity predicts false memory--a near-infrared spectroscopy study

Evidence from lesion studies suggests an important role of the prefrontal cortex (PFC) in the reconstructive processes of episodic memory or memory distortion. Results from functional imaging studies imply PFC involvement during the illusionary recollection of non-experienced events. Here, we used a two-channel near-infrared spectroscopy (NIRS) system and conducted real-time monitoring of PFC hemodynamics, while subjects studied word lists and subsequently recognized unstudied items (false recognition). Bilateral increases in the oxygenated hemoglobin concentration ([oxy-Hb]) were observed during false recognition compared to true recognition, and a left PFC dominant increase of [oxy-Hb] was observed during encoding phases where subjects later claimed that they recognized unstudied words. Traces of semantic processing, reflected primarily in the left PFC activity, could eventually predict whether subjects falsely recognize non-experienced events.     

Cerebellar contributions to episodic memory encoding as revealed by fMRI

Event-related functional Magnetic Resonance Imaging (fMRI) allows for the comparison of hemodynamic responses evoked by items that are remembered in a subsequent memory task vs. items that are forgotten. In this way, brain regions that assumingly contribute to successful memory encoding have been identified, including the left inferior prefrontal cortex (LIPC) and the medial temporal lobe. Although a cerebellar involvement in verbal working memory is well-established, a contribution of the cerebellum to episodic long-term encoding has only sporadically been described, and mechanisms underlying cerebellar memory effects are unclear. We conducted a typical incidental verbal memory fMRI experiment with three different encoding tasks varying the depth of semantic processing. Slice positioning allowed for the coverage of the entire cerebellum. We observed a significant subsequent memory effect within the superior and posterior right cerebellar hemisphere that was task independent. Additionally, we found a different area within the superior right cerebellum displaying a memory effect specifically for semantically processed words and a bilateral cerebellar activation specifically associated with encoding success only for a non-semantic task. Our results suggest that besides its known role in verbal working memory, the cerebellum contributes to episodic long-term encoding and should therefore be considered in future fMRI studies dealing with episodic memory.     

Functional topography in the human cerebellum: a meta-analysis of neuroimaging studies

Clinical, experimental and neuroimaging studies indicate that the cerebellum is involved in neural processes beyond the motor domain. Cerebellar somatotopy has been shown for motor control, but topographic organization of higher-order functions has not yet been established. To determine whether existing literature supports the hypothesis of functional topography in the human cerebellum, we conducted an activation likelihood estimate (ALE) meta-analysis of neuroimaging studies reporting cerebellar activation in selected task categories: motor (n=7 studies), somatosensory (n=2), language (n=11), verbal working memory (n=8), spatial (n=8), executive function (n=8) and emotional processing (n=9). In agreement with previous investigations, sensorimotor tasks activated anterior lobe (lobule V) and adjacent lobule VI, with additional foci in lobule VIII. Motor activation was in VIIIA/B; somatosensory activation was confined to VIIIB. The posterior lobe was involved in higher-level tasks. ALE peaks were identified in lobule VI and Crus I for language and verbal working memory; lobule VI for spatial tasks; lobules VI, Crus I and VIIB for executive functions; and lobules VI, Crus I and medial VII for emotional processing. Language was heavily right-lateralized and spatial peaks left-lateralized, reflecting crossed cerebro-cerebellar projections. Language and executive tasks activated regions of Crus I and lobule VII proposed to be involved in prefrontal-cerebellar loops. Emotional processing involved vermal lobule VII, implicated in cerebellar-limbic circuitry. These data provide support for an anterior sensorimotor vs. posterior cognitive/emotional dichotomy in the human cerebellum. Prospective studies of multiple domains within single individuals are necessary to better elucidate neurobehavioral structure-function correlations in the cerebellar posterior lobe.     

Involvement of the cerebellar cortex and nuclei in verbal and visuospatial working memory: a 7 T fMRI study

The first aim of the present study was to extend previous findings of similar cerebellar cortical areas being involved in verbal and spatial n-back working memory to the level of the cerebellar nuclei. The second aim was to investigate whether different areas of the cerebellar cortex and nuclei contribute to different working memory tasks (n-back vs. Sternberg tasks). Young and healthy subjects participated in two functional magnetic resonance imaging (fMRI) studies using a 7 T MR scanner with its increased signal-to-noise ratio. One group of subjects (n=21) performed an abstract and a verbal version of an n-back task contrasting a 2-back and 0-back condition. Another group of subjects (n=23) performed an abstract and a verbal version of a Sternberg task contrasting a high load and a low load condition. A block design was used. For image processing of the dentate nuclei, a recently developed region of interest (ROI) driven normalization method of the dentate nuclei was applied (Diedrichsen et al., 2011). Whereas activated areas of the cerebellar cortex and dentate nuclei were not significantly different comparing the abstract and verbal versions of the n-back task, activation in the abstract and verbal Sternberg tasks was significantly different. In both n-back tasks activation was most prominent at the border of lobules VI and Crus I, within lobule VII, and within the more caudal parts of the dentate nucleus bilaterally. In Sternberg tasks the most prominent activations were found in lobule VI extending into Crus I on the right. In the verbal Sternberg task activation was significantly larger within right lobule VI compared to the abstract Sternberg task and compared to the verbal n-back task. Activations of rostral parts of the dentate were most prominent in the verbal Sternberg task, whereas activation of caudal parts predominated in the abstract Sternberg task. On the one hand, the lack of difference between abstract and verbal n-back tasks and the lack of significant lateralization suggest a more general contribution of the cerebellum to working memory regardless of the modality. On the other hand, the focus of activation in right lobule VI in the verbal Sternberg task suggests specific cerebellar contributions to verbal working memory. The verbal Sternberg task emphasizes maintenance of stimuli via phonological rehearsal, whereas central executive demands prevail in n-back tasks. Based on the model of working memory by Baddeley and Hitch (1974), the present results show that different regions of the cerebellum support functions of the central executive system and one of the subsidiary systems, the phonological loop.     

Relationship of dopamine D1 receptor binding in striatal and extrastriatal regions to cognitive functioning in healthy humans

Dopamine (DA) availability in both striatal and extrastriatal brain regions has been implicated in cognitive performance. Given that different brain regions are neuroanatomically and functionally different, DA receptor binding in different brain regions may be selectively important to specific cognitive functions. Using PET and the radioligand SCH23390, we measured D1 receptor binding potential (BP(ND)) in dorsolateral prefrontal cortex (DLPFC), hippocampus (HC), as well as in sensorimotor (SMST), associative (AST), and limbic (LST) striatum in 20 healthy younger persons. Subjects completed tasks assessing executive functioning, episodic memory, speed, and general knowledge. Unlike previous reports, we found no linear or curvilinear relationships between D1 receptor binding in DLPFC and performance in any cognitive task. However, BP(ND) in HC was positively linked to executive performance as well as to speed and knowledge. With regard to the striatal subregions, D1 BP(ND) in SMST was more strongly related to speed compared to the other striatal subregions, whereas D1 BP(ND) in AST was more strongly linked to general knowledge. These findings provide support for the notion that D1 receptors in separate brain regions are differentially related to performance in tasks tapping various cognitive domains.