Dynamic pattern of brain activation during sequencing of word strings evaluated by fMRI

An impaired ability to recite highly automated word strings (e.g., the names of the months of the year) in reverse order concomitant with preserved production of the conventional sequence has been considered a salient sign of frontal lobe dysfunction. Using functional magnetic resonance imaging (fMRI), the spatial and temporal pattern of brain activation during covert performance of these tasks was evaluated in healthy subjects. As compared to the response obtained during forward recitation, re-sequencing of the word string yielded additional activation of the bilateral middle and inferior frontal gyri, the posterior parietal cortex and the left anterior cingulate gyrus. The prefrontal responses are in accordance with the clinical findings referred to. However, the set of activated areas, as a whole, presumably reflects contribution of the various components of the working memory system to the sequencing of word strings. During successive periods of task administration, subjects showed a linear increase of production speed. Analysis of corresponding dynamic changes of regional hemodynamic responses revealed a significant increase at the level of the left inferior parietal cortex and a decrease within the mesial aspect of the left superior frontal gyrus. Presumably, the former finding reflects increasing demands on the phonological short-term memory store, due to faster updating of its content under increased word production rate. Decreasing activation within the superior frontal gyrus might indicate contribution of this area to the initiation of the cognitive processes subserving the sequencing of verbal items. These findings demonstrate the capability of fMRI as a powerful tool for the analysis of dynamic brain activation.     

Neural correlates of semantic and episodic memory retrieval

To investigate the functional neuroanatomy associated with retrieving semantic and episodic memories, we measured changes in regional cerebral blood flow (rCBF) with positron emission tomography (PET) while subjects generated single word responses to achromatic line drawings of objects. During separate scans, subjects either named each object, retrieved a commonly associated color of each object (semantic condition), or recalled a previously studied uncommon color of each object (episodic condition). Subjects were also scanned while staring at visual noise patterns to provide a low level perceptual baseline. Relative to the low level baseline, all three conditions revealed bilateral activations of posterior regions of the temporal lobes, cerebellum, and left lateralized activations in frontal regions. Retrieving semantic information, as compared to object naming, activated left inferior temporal, left superior parietal, and left frontal cortices. In addition, small regions of right frontal cortex were activated. Retrieving episodic information, as compared to object naming, activated bilateral medial parietal cortex, bilateral retrosplenial cortex, right frontal cortex, thalamus, and cerebellum. Direct comparison of the semantic and episodic conditions revealed bilateral activation in temporal and frontal lobes in the semantic task (left greater than right), and activation in medial parietal cortex, retrosplenial cortex, thalamus, and cerebellum (but not right frontal regions) in the episodic task. These results support the assertion that distinct neural structures mediate semantic and episodic memory retrieval. However, they also raise questions regarding the specific roles of left temporal and right frontal cortices during episodic memory retrieval, in particular.     

Infectious causes of atherosclerosis

Brain imaging studies have suggested a critical role for prefrontal cortex in working memory (WM) tasks that require both maintainenance and manipulation of information over time in delayed-response WM tasks. In the present study, functional magnetic resonance imaging (fMRI) was used to examine whether prefrontal areas are activated when only maintenance is required in a delayed-response WM task, without the overt requirement to manipulate the stored information. In two scans, six subjects performed WM tasks in which, on each trial, they (1) encoded 1, 3, or 6 to-be-remembered letters, (2) maintained these letters across a 5-second unfilled delay, and (3) determined whether a single probe letter was or was not part of the memory set. Activation of left caudal inferior frontal gyrus was observed, relative to the 1-letter task, when subjects were required to maintain 3 letters in WM. When subjects were required to maintain 6 letters in WM, additional prefrontal areas, most notably middle and superior frontal gyri, were activated bilaterally. Thus, increasing the amount of to-be-maintained information, without any overt manipulation requirement, resulted in the recruitment of wide-spread frontal-lobe regions. Inferior frontal gyrus activation was left-hemisphere dominant in both the 3- and 6-letter conditions, suggesting that such activation reflected material-specific verbal processes. Activation in middle and superior frontal gyri appeared only in the 6-letter condition and was right-hemisphere dominant, suggesting that such activation reflected material-independent executive processes.     

Cortical networks implicated in semantic and episodic memory: common or unique?

While previous functional neuroimaging studies have shown that semantic and episodic memory tasks activate different cortical regions, they never compared regional cerebral blood flow (rCBF) patterns associated with semantic and episodic memory within the same experimental design. In this study, we used H2(15)O PET to study subjects in the course of semantic and episodic memory tasks. rCBF was measured in 9 normal volunteers during a resting baseline condition and two cognitive tasks. In the semantic categorisation task subjects heard a list of concrete words and had to respond to words belonging to the "animals" or "food" category. In the episodic recognition task subjects heard a list of concrete words, half "old", i.e. belonging to the list of the semantic categorisation task, and half "new", i.e. presented for the first time. Subjects had to respond to the "old" words. Both tasks were compared to a resting condition. Statistical analysis was performed with Statistical Parametric Mapping (SPM). Compared to the resting condition, the semantic tasks, activated the superior temporal gyri bilaterally, the left frontal cortex, and right premotor cortex. The episodic tasks activated the left superior temporal gyrus, the frontal cortex bilaterally, and the right inferior parietal cortex. Compared to the episodic memory tasks, the semantic memory tasks activated the superior temporal/insular cortex bilaterally and the right premotor cortex. Compared to the semantic memory tasks, the episodic memory tasks activated the right frontal cortex. These results suggest that cortical networks implicated in semantic and episodic memory show both common and unique regions, with the right prefrontal cortex being the neural correlate specific of episodic remembering.     

The role of prefrontal cortex in working memory: examining the contents of consciousness

Working memory enables us to hold in our 'mind's eye' the contents of our conscious awareness, even in the absence of sensory input, by maintaining an active representation of information for a brief period of time. In this review we consider the functional organization of the prefrontal cortex and its role in this cognitive process. First, we present evidence from brain-imaging studies that prefrontal cortex shows sustained activity during the delay period of visual working memory tasks, indicating that this cortex maintains on-line representations of stimuli after they are removed from view. We then present evidence for domain specificity within frontal cortex based on the type of information, with object working memory mediated by more ventral frontal regions and spatial working memory mediated by more dorsal frontal regions. We also propose that a second dimension for domain specificity within prefrontal cortex might exist for object working memory on the basis of the type of representation, with analytic representations maintained preferentially in the left hemisphere and image-based representations maintained preferentially in the right hemisphere. Furthermore, we discuss the possibility that there are prefrontal areas brought into play during the monitoring and manipulation of information in working memory in addition to those engaged during the maintenance of this information. Finally, we consider the relationship of prefrontal areas important for working memory, both to posterior visual processing areas and to prefrontal areas associated with long-term memory.     

Working memory for complex figures: An fMRI comparison of letter and fractal n-back tasks.

n-back letter and fractal tasks were administered to I I participants during functional magnetic resonance imaging to test process specificity theories of prefrontal cortex (PFC) function and assess task validity. Tasks were matched on accuracy, but fractal n-back responses were slower and more conservative. Maintenance (1-back minus O-back) activated inferior parietal and dorsolateral PFC, with additional activation in right ventrolateral PFC during letter n-back and left lingual gyrus during fractal n-back. Maintenance plus manipulation (2-back minus 0-back) activated inferior parietal, Broca's area, insula, and dorsolateral and ventral PFC, with greater right dorsolateral PFC activation for letter n-back. Manipulation only (2-back minus 1-back) produced additional and equivalent dorsolateral PFC and anterior cingulate activation in both tasks. Results support fractal n-back validity and indicate substantial overlap in working memory functions of dorsal and ventral PFC. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Functional mapping of human memory using PET: Comparisons of conceptual and perceptual tasks.

Tested whether different neurological regions subserved the conceptual and perceptual memory components by using positron emission tomography (PET). Regional cerebral blood flow (RCBF) of 14 Ss (mean age 25 yrs) during 2 conceptual tasks of semantic cued recall and semantic association was compared to a control condition in which Ss made semantic associations to nonstudied words. RCBF during 2 perceptual tasks of word fragment cued recall and word fragment completion was also compared to a word fragment nonstudied control condition. There were clear dissociations in RCBF that reflected differences in brain regions subserving the 2 types of memory processes. Conceptual processing produced more activation in the left frontal and temporal cortex and the lateral aspect of the bilateral inferior parietal lobule. Perceptual memory processing activated the right frontal and temporal cortex and the bilateral posterior areas. (French abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An fMRI Study of Episodic Memory: Retrieval of Object, Spatial, and Temporal Information.

Sixteen participants viewed a videotaped tour of 4 houses that highlighted a series of objects and their spatial locations. Participants were tested for memory of object, spatial, and temporal-order information while undergoing functional magnetic resonance imaging. Preferential activation was observed in the right parahippocampal gyrus during the retrieval of spatial-location information. Retrieval of contextual information (spatial location and temporal order) was associated with activation in the right dorsolateral prefrontal cortex. In bilateral posterior parietal regions, greater activation was associated with processing of visual scenes regardless of the memory judgment. These findings support current theories positing roles for frontal and medial temporal regions during episodic retrieval and suggest a specific role for the hippocampal complex in the retrieval of spatial-location information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Saccadic eye movement and working memory deficits following damage to human prefrontal cortex

A patient with a lesion confined largely to the right inferior frontal gyrus was found to be impaired on tests of spatial working memory and executive functioning. By contrast, his pattern recognition was good. The patient's selective impairments are consistent with the view that prefrontal cortex contributes to processes involved in spatial working memory. The patient was also tested on a range of oculomotor paradigms, some of which required the temporary suppression of a saccadic response. He was unable to suppress making contra- or ipsilesional reflexive glances to peripheral stimuli on the "anti-saccade" paradigm, but his performance improved on delayed saccade, memory-guided saccade and fixation tasks. Although reflexive glances were observed under these conditions they occurred more frequently in response to contralesional stimuli than ipsilesional ones. Furthermore, the patient had no difficulty in performing anti-point movements with his ipsilesional hand. Thus, his inability to suppress reflexive glances on the anti-saccade task is not due to a generalised problem of "distractibility". The patient's deficits are discussed in terms of models of anti-saccade generation and are related to recent findings regarding the role of prefrontal cortex in working memory and visual attention.     

Neural mechanisms of interference control underlie the relationship between fluid intelligence and working memory span.

Fluid intelligence (gF) and working memory (WM) span predict success in demanding cognitive situations. Recent studies show that much of the variance in gF and WM span is shared, suggesting common neural mechanisms. This study provides a direct investigation of the degree to which shared variance in gF and WM span can be explained by neural mechanisms of interference control. The authors measured performance and functional magnetic resonance imaging activity in 102 participants during the n-back WM task, focusing on the selective activation effects associated with high-interference lure trials. Brain activity on these trials was correlated with gF, WM span, and task performance in core brain regions linked to WM and executive control, including bilateral dorsolateral prefrontal cortex (middle frontal gyrus; BA9) and parietal cortex (inferior parietal cortex; BA 40/7). Interference-related performance and interference-related activity accounted for a significant proportion of the shared variance in gF and WM span. Path analyses indicate that interference control activity may affect gF through a common set of processes that also influence WM span. These results suggest that individual differences in interference-control mechanisms are important for understanding the relationship between gF and WM span. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Functional organization of spatial and nonspatial working memory processing within the human lateral frontal cortex

The present study used functional magnetic resonance imaging to demonstrate that performance of visual spatial and visual nonspatial working memory tasks involve the same regions of the lateral prefrontal cortex when all factors unrelated to the type of stimulus material are appropriately controlled. These results provide evidence that spatial and nonspatial working memory may not be mediated, respectively, by mid-dorsolateral and mid-ventrolateral regions of the frontal lobe, as widely assumed, and support the alternative notion that specific regions of the lateral prefrontal cortex make identical executive functional contributions to both spatial and nonspatial working memory.     

The anatomy of language revisited

The language areas have been classically viewed as a posterior, perceptual Wernicke's region connected with an anterior, motor Broca's area via a tract of long fibers denominated the arcuate fasciculus. Recent connectional studies in the monkey indicate that there may be few direct connections between the regions strictly corresponding to Broca's or Wernicke's areas, and that inferior parietal areas may serve as a link between them. The proposed connectional pattern of the language regions fits the network of parietotemporal-prefrontal connections that participate in working memory, a type of memory used in immediate cognitive processing. Supporting this concept, brain activation studies in the human during linguistic working memory tasks have determined a close relation between the supramarginal gyrus (parietal area 40) and Broca's area. We suggest that language processing is closely related to working memory networks, and that the language regions in fact originated in evolution from a working memory network for linguistic utterances.     

PET regional cerebral blood flow change during working and declarative memory: relationship with task performance

Functional and anatomical relationships between working and declarative memory were investigated by contrasting regional cerebral blood flow (rCBF) change during standard working (Wisconsin Card Sorting Test, WCST) and declarative memory (Paired Associate Recognition Test, PART) tasks using identical stimulus-response modalities. The tasks and a resting baseline were administered to 30 participants (16 men, 14 women) during successive 10-min positron emission tomography 15O-water measures of rCBF. For both tasks, rCBF increased over baseline in inferior frontal and occipitotemporal regions, with more consistent dorsolateral prefrontal activation for WCST than PART. Additional orbitofrontal increases and dorsomedial decreases were seen for the PART. Activation patterns diverged when performance was considered. For the WCST, high performers activated dorsolateral and inferior frontal regions, whereas top PART performers activated only the occipitotemporal region. These results suggest operation of a frontotemporal network subserving both types of memory function that becomes more focal as performance increases.     

Frontotemporal cerebral blood flow change during executive and declarative memory tasks in schizophrenia: A positron emission tomography study.

Schizophrenia affects prefrontal and temporal-limbic networks. These regions were examined by contrasting regional cerebral blood flow (rCBF) during executive (Wisconsin Card Sorting Test [WCST]), and declarative memory tasks (Paired Associate Recognition Test [PART]). The tasks, and a resting baseline, were administered to 15 patients with schizophrenia and 15 healthy controls during 10 min positron emission tomography 1?O-water measures of rCBE Patients were worse on both tasks. Controls activated inferior frontal, occipitotemporal, and temporal pole regions for both tasks. Similar results were obtained for controls matched to level of patient performance. Patients showed no activation of hypothesized regions during the WCST and activated the dorsolateral prefrontal cortex during the PART. On the PART, occipitotemporal activation correlated with better performance for controls only. Better WCST performance correlated with CBF increase in prefrontal regions for controls and in the parahippocampal gyrus for patients. Results suggest that schizophrenia may involve a breakdown in the integration of a frontotemporal network that is responsive to executive and declarative memory demands in healthy individuals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Activation of multi-modal cortical areas underlies short-term memory

We wanted to examine whether there are cortical fields active in short-term retention of sensory information, independent of the sensory modality. To control for selective attention, response selection and motor output, the cortical activity during short-term memory (STM) tasks was compared with that during detection (DT) tasks. Using positron emission tomography and [15O]-butanol as a tracer, we measured the regional cerebral blood flow in ten subjects during three STM tasks in which the subjects had to keep in mind: (i) the pitch of tones; (ii) frequencies of a vibrating stylus; and (iii) luminance levels of a monochrome light. Another group of ten subjects undertook three tasks in which subjects detected changes in similar stimuli. Six cortical fields were significantly more activated during STM than during DT. These fields were activated irrespective of sensory modality, and were located in the left inferior frontal gyrus, right superior frontal gyrus, right inferior parietal cortex, anterior cingulate, left frontal operculum and right ventromedial prefrontal cortex. Since the DT tasks and the STM tasks differed only with respect to the STM component, we conclude that the neuronal activity specifically related to retention of the stimuli during the delays was located in these six multi-modal cortical areas. Since no differences were observed in the sensory-specific association cortices, the results indicate further that the activity in the sensory-specific association cortices due to selective attention is not different from the activity underlying short-term retention of sensory information.     

PET regional cerebral blood flow during working and declarative memory: Relationship with task performance.

Functional and anatomical relationships between working and declarative memory were investigated by contrasting regional cerebral blood flow (rCBF) change during standard working (Wisconsin Card Sorting Test, WCST) and declarative memory (Paired Associate Recognition Test, PART) tasks using identical stimulus-response modalities. The tasks and a resting baseline were administered to 30 participants (16 men, 14 women) during successive 10-min positron emission tomography –2–5O-water measures of rCBF. For both tasks, rCBF increased over baseline in inferior frontal and occipitotemporal regions, with more consistent dorsolateral prefrontal activation for WCST than PART. Additional orbitofrontal increases and dorsomedial decreases were seen for the PART. Activation patterns diverged when performance was considered. For the WCST, high performers activated dorsolateral and inferior frontal regions, whereas top PART performers activated only the occipitotemporal region. These results suggest operation of a frontotemporal network subserving both types of memory function that becomes more focal as performance increases. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sensorimotor cerebral activation during optokinetic nystagmus. A functional MRI study

Self-motion or object motion can elicit optokinetic nystagmus (OKN), which is an integral part of dynamic spatial orientation. We used functional MR imaging during horizontal OKN to study cerebral activation patterns in sensory and ocular motor areas in 10 subjects. We found activation bilaterally in the primary visual cortex, the motion-sensitive areas in the occipitotemporal cortex (the middle temporal and medial superior temporal areas), and in areas known to control several types of saccades such as the precentral and posterior median frontal gyrus, the posterior parietal cortex, and the medial part of the superior frontal gyrus (frontal, parietal, and supplementary eye fields). Additionally, we observed cortical activation in the anterior and posterior parts of the insula and in the prefrontal cortex. Bilateral activation of subcortical structures such as the putamen, globus pallidus, caudate nucleus, and the thalamus traced the efferent pathways of OKN down to the brainstem. Functional MRI during OKN revealed a complex cerebral network of sensorimotor cortical and subcortical activation.     

Safety and immunogenicity of HIV recombinant envelope vaccines in HIV-infected infants and children. National Institutes of Health-sponsored Pediatric AIDS Clinical Trials Group (ACTG-218)

We applied structural equation modeling to positron emission tomography data in humans to examine functional interactions between the right medial temporal lobe (MTL) and selected right neocortical regions in relation to visual recognition memory. Using a priori knowledge about anatomical connections between these regions as a guiding constraint, we modeled the pattern of interactions [i.e. covariances in regional cerebral blood flow (rCBF)] associated with episodic memory retrieval of spatial location and compared it with the pattern for retrieval of object identity. We also compared these patterns with those associated with perceptual matching of spatial location and object identity. Although displaying no difference in average rCBF across tasks, the right MTL showed domain-specific qualitative differences in interactions with posterior dorsal (parieto-occipital sulcus, supramarginal gyrus) and ventral regions (fusiform gyrus, superior temporal sulcus) but not with a prefrontal region. MTL interactions involving dorsal regions were positive in the spatial retrieval task but negative for object retrieval. Interactions involving ventral regions showed the reverse pattern. No comparable changes were observed during perceptual matching. Using control models, we demonstrated the neuroanatomical specificity of these results. Our results provide support for the notion that the nature of interactions between the MTL and posterior neocortex depends on the domain of information to-be-recovered.     

Changes in limbic and prefrontal functional interactions in a working memory task for faces

Regional cerebral blood flow, measured with positron emission tomography, was used to identify brain regions that play a special role(s) in a working memory task for faces. Perceptual matching (no retention interval), short-delay (average = 3.5 s retention interval), intermediate-delay (average = 12.5 s), and long-delay (21 s) tasks were considered. From the idea that brain function is the result of neural interactions, the data were analysed using anatomically based, covariance structural equation modeling. In perceptual matching, the dominant functional interactions were observed among the ventral cortical areas, from extrastriate regions, to the anterior temporal, and into the inferior prefrontal cortex. These interactions decreased with longer delay intervals. In the short-delay functional model, interactions along this ventral stream in the right hemisphere appeared to be rerouted through limbic areas with strong interactions among the hippocampal region, the anterior and posterior cingulate, and the inferior prefrontal cortices. For the intermediate-delay model, the hippocampocingulate interactions continued, but showed a shift to more left hemisphere involvement. In the long-delay network, interactions within the right limbic circuit were reduced in favor of strong bilateral inferior prefrontal and frontocingulate interactions. Effects from the prefrontal cortex, especially from the left hemisphere, to temporal and occipito-temporal cortices were particularly strong in the long-delay model, suggesting recruitment of some of the same circuits primarily involved in face perception. The strong corticolimbic interactions at short and intermediate delays may represent maintenance of an iconic representation of the face during the retention interval. However, at longer delays, where image was more difficult to maintain, a frontocingulate-occipital network was used that could represent an expanded encoding strategy resulting in a more resilient memory.