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)     

Effects of estrogen replacement therapy on PET cerebral blood flow and neuropsychological performance

Reports that estrogen may protect against age-associated memory decline and Alzheimer's Disease have kindled interest in the effects of estrogen replacement therapy (ERT) on cognition and brain function. As part of a 9-year study in the Baltimore Longitudinal Study of Aging, we are performing annual magnetic resonance imaging, positron emission tomography (PET), and neuropsychological assessments to examine brain structure and function in individuals aged 55 and older. PET measurements of regional cerebral blood flow (rCBF) are obtained under 3 conditions: rest and verbal and figural delayed recognition memory tasks. Fifteen women receiving ERT (with or without the addition of progesterone) were compared with a matched sample of 17 untreated women. There were no significant differences between groups in regional brain volumes or ventricular size. However, ERT users and nonusers showed significant differences in PET-rCBF relative activation patterns during the memory tasks. During verbal memory processing, there were significant interactions in rCBF activations for the right parahippocampal gyrus, right precuneus, right frontal regions, and left hypothalamus. During figural memory processing, significant interactions were observed for right parahippocampal and inferior parietal regions and for left visual association and anterior thalamic regions. ERT users also showed better performance on neuropsychological tests of figural and verbal memory and on some aspects of the PET activation tests, although the two groups did not differ in education, overall verbal ability, or performance on other neuropsychological tests. These findings confirm our previous observation of the beneficial effects of ERT on figural memory. Moreover, differences in rCBF activation patterns between ERT users and nonusers suggest an area for future research to examine mechanisms through which ERT may influence memory and other cognitive abilities.     

Specialized systems for the processing of mnemonic information within the primate frontal cortex

The lateral frontal cortex is involved in various aspects of executive processing within short- and long-term memory. It is argued that the different parts of the lateral frontal cortex make distinct contributions to memory that differ in terms of the level of executive processing that is carried out in interaction with posterior cortical systems. According to this hypothesis, the mid-dorsolateral frontal cortex (areas 46 and 9) is a specialized system for the monitoring and manipulation of information within working memory, whereas the mid-ventrolateral frontal cortex (areas 47/12 and 45) is involved in the active retrieval of information from the posterior cortical association areas. Data are presented which support this two-level hypothesis that posits two distinct levels of interaction of the lateral frontal cortex with posterior cortical association areas. Functional activation studies with normal human subjects have demonstrated specific activity within the mid-dorsolateral region of the frontal cortex during the performance of tasks requiring monitoring of self-generated and externally generated sequences of responses. In the monkey, lesions restricted to this region of the frontal cortex yield a severe impairment in performance of the above tasks, this impairment appearing against a background of normal performance on several basic mnemonic tasks. By contrast, a more severe impairment follows damage to the mid-ventrolateral frontal region and functional activation studies have demonstrated specific changes in activity in this region in relation to the active retrieval of information from memory.     

Dissociation of mnemonic and perceptual processes during spatial and nonspatial working memory using fMRI

Neuroimaging studies in humans have consistently found robust activation of frontal, parietal, and temporal regions during working memory tasks. Whether these activations represent functional networks segregated by perceptual domain is still at issue. Two functional magnetic resonance imaging experiments were conducted, both of which used multiple-cycle, alternating task designs. Experiment 1 compared spatial and object working memory tasks to identify cortical regions differentially activated by these perceptual domains. Experiment 2 compared working memory and perceptual control tasks within each of the spatial and object domains to determine whether the regions identified in experiment 1 were driven primarily by the perceptual or mnemonic demands of the tasks, and to identify common brain regions activated by working memory in both perceptual domains. Domain-specific activation occurred in the inferior parietal cortex for spatial tasks, and in the inferior occipitotemporal cortex for object tasks, particularly in the left hemisphere. However, neither area was strongly influenced by task demands, being nearly equally activated by the working memory and perceptual control tasks. In contrast, activation of the dorsolateral prefrontal cortex and the intraparietal sulcus (IPS) was strongly task-related. Spatial working memory primarily activated the right middle frontal gyrus (MFG) and the IPS. Object working memory activated the MFG bilaterally, the left inferior frontal gyrus, and the IPS, particularly in the left hemisphere. Finally, activation of midline posterior regions, including the cingulate gyrus, occurred at the offset of the working memory tasks, particularly the shape task. These results support a prominent role of the prefrontal and parietal cortices in working memory, and indicate that spatial and object working memory tasks recruit differential hemispheric networks. The results also affirm the distinction between spatial and object perceptual processing in dorsal and ventral visual pathways.     

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.     

Brain regions supporting intentional and incidental memory: a PET study

Regional brain activity associated with intentional and incidental memory retrieval was studied with PET. Previously studied and new words were presented in either an intentional or an incidental memory task. Type of task was crossed with an encoding manipulation ('deep' vs 'shallow') which varied the probability that studied items would be remembered. In both tasks, deeply encoded items were associated with greater activation in the left hippocampus than were items that had received shallow encoding, suggesting that the involvement of the hippocampus in memory retrieval is independent of whether remembering is intentional or incidental. Right prefrontal and bilateral parietal cortex were more activated during the international task than during the incidental task, irrespective of encoding condition. Thus, these regions play a more extensive role in memory retrieval when remembering is intentional.     

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.     

Functional MRI activation in children with and without dyslexia during pseudoword aural repeat and visual decode: Before and after treatment.

Children without dyslexia (n=10) received nonphonological treatment, and those with dyslexia received phonological (n=11) or nonphonological (n=9) treatment. Before and after treatment they performed aural repeat, visual decode, and aural match pseudoword tasks during functional MRI scanning that separated stimulus input from response production. Group map analysis indicated that children with dyslexia overactivated compared with good readers during the aural-repeat/aural-match contrast in bilateral frontal (Brodmann's area [BA] 3, 4, 5, 6, 9), left parietal (BA 2, 3), left temporal (BA 38), and right temporal (BA 20, 21, 37) regions (stimulus input) and underactivated in right frontal (BA 24, 32) and right insula (BA 48) regions (response production); they underactivated in BA 19/V5 during the visual-decode/aural-match contrast (response production). Individual brain analysis for children with dyslexia revealed that during the aural-repeat/aural-match contrast (stimulus input), phonological treatment decreased and normalized activation in left supramarginal gyrus and postcentral gyrus. Nonphonological treatment increased and normalized activation during the visual-decode/aural-match contrast (response production) in BA19/V5 and changed activation in the same direction as good readers during aural-repeat/aural-match contrast (stimulus input) in left postcentral gyrus. The significance of the findings for competing theories of dyslexia is discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

PET study of human voluntary saccadic eye movements in darkness: effect of task repetition on the activation pattern

Using H2(15)O 3D Positron Emission Tomography (PET), regional cerebral blood flow (rCBF) was measured in six human subjects under two different conditions: at rest and while performing self-paced horizontal saccadic eye movements in darkness. These two conditions were repeated four times each. First, the comparison between the four saccadic and four resting conditions was investigated in a group and a single subject analysis. Saccades elicited bilateral rCBF increases in the medial part of the superior frontal gyrus (supplementary eye field), precentral gyrus (frontal eye field), superior parietal lobule, anterior medial part of the occipital lobe involving striate and extrastriate cortex (lingual gyrus and cuneus), and in the right inferior parietal lobule. At the subcortical level, activations were found in the left putamen. These results mainly replicate previous PET findings on saccadic control. Second, the interaction between the experimental conditions and their repetition was examined. When activations throughout repetition of the same saccadic task are compared, the supplementary eye fields show a progressive increase of activation. On the contrary, the activation in the cerebellum, left superior parietal lobule and left occipital cortex progressively decreases during the scanning session. Given the existence of such an interaction, the pattern of activations must be interpreted as a function of task repetition. This may be a factor explaining some apparent mismatch between different studies.     

Temporal dynamics of brain activation during a working memory task

Working memory is responsible for the short-term storage and online manipulation of information necessary for higher cognitive functions, such as language, planning and problem-solving. Traditionally, working memory has been divided into two types of processes: executive control (governing the encoding manipulation and retrieval of information in working memory) and active maintenance (keeping information available 'online'). It has also been proposed that these two types of processes may be subserved by distinct cortical structures, with the prefrontal cortex housing the executive control processes, and more posterior regions housing the content-specific buffers (for example verbal versus visuospatial) responsible for active maintenance. However, studies in non-human primates suggest that dorsolateral regions of the prefrontal cortex may also be involved in active maintenance. We have used functional magnetic resonance imaging to examine brain activation in human subjects during performance of a working memory task. We used the temporal resolution of this technique to examine the dynamics of regional activation, and to show that prefrontal cortex along with parietal cortex appears to play a role in active maintenance.     

Cerebral cortical hyperactivation in response to mental stress in patients with coronary artery disease

The central nervous system (CNS) effects of mental stress in patients with coronary artery disease (CAD) are unexplored. The present study used positron emission tomography (PET) to measure brain correlates of mental stress induced by an arithmetic serial subtraction task in CAD and healthy subjects. Mental stress resulted in hyperactivation in CAD patients compared with healthy subjects in several brain areas including the left parietal cortex [angular gyrus/parallel sulcus (area 39)], left anterior cingulate (area 32), right visual association cortex (area 18), left fusiform gyrus, and cerebellum. These same regions were activated within the CAD patient group during mental stress versus control conditions. In the group of healthy subjects, activation was significant only in the left inferior frontal gyrus during mental stress compared with counting control. Decreases in blood flow also were produced by mental stress in CAD versus healthy subjects in right thalamus (lateral dorsal, lateral posterior), right superior frontal gyrus (areas 32, 24, and 10), and right middle temporal gyrus (area 21) (in the region of the auditory association cortex). Of particular interest, a subgroup of CAD patients that developed painless myocardial ischemia during mental stress had hyperactivation in the left hippocampus and inferior parietal lobule (area 40), left middle (area 10) and superior frontal gyrus (area 8), temporal pole, and visual association cortex (area 18), and a concomitant decrease in activation observed in the anterior cingulate bilaterally, right middle and superior frontal gyri, and right visual association cortex (area 18) compared with CAD patients without myocardial ischemia. These findings demonstrate an exaggerated cerebral cortical response and exaggerated asymmetry to mental stress in individuals with CAD.     

Using functional magnetic resonance imaging to understand the mechanisms of consciousness

BACKGROUND: In order to elucidate mental functions that subserve human consciousness, brain activation was investigated in 12 normal, right-handed volunteers who performed tasks of selective attention, working memory, and sensorimotor coordination during the collection of multislice echoplanar functional magnetic resonance images. HYPOTHESIS: These functions are located in (and controlled by) distinct anatomical regions that can be identified by functional magnetic resonance imaging techniques. METHODS: In each subject, 100 10-slice data sets were acquired using a 1.5-T scanner and the blood oxygenation level dependent contrast technique. Time-series regression modeling estimated power in the magnetic resonance signal during the on/off phases of task performance. Comparison between subjects was made possible by the transformation of each data set into standard Talairach space. RESULTS: Activation maps were based on the median value of the fundamental power quotient at each voxel. Results showed the activation of prefrontal and parasagittal cortices in both the selective attention and working memory tasks, but they also revealed activation in both insular cortices and the posterior cingulate gyri. CONCLUSIONS: The results provide evidence for structures in the anterior right hemisphere and left medial frontal lobe for attentional tasks, although there appears to be an engagement of a widespread network of anterior brain structures, possibly with the inhibition of some posterior regions, during task performance. The sensorimotor coordination task showed activation regions similar to those seen in selective attention. Once learned, this task probably demands attention rather than overt conscious motor control. Clearly, the functions of attention, working memory, and sensorimotor coordination are not located in single, discrete brain areas. However, interactions and interplay between related areas were demonstrated, giving supporting evidence that complex mental operations rely on the coordinated activity of widely distributed brain regions that contribute to neural networks.     

Composition and dynamics of articular cartilage: structure, function, and maintaining healthy state

Functional magnetic resonance imaging (fMRI) based on blood oxygen level-dependent (BOLD) contrast has become an increasingly popular technique for mapping the brain. The relationship between BOLD-fMRI imaging and imaging of blood flow activation with positron emission tomography (PET) remains unclear. Moreover, BOLD imaging strategies and analysis procedures vary widely across laboratories. To examine the relationship between these different methods, we compared brain activation maps of a word-stem completion task obtained both using PET and using fMRI across two separate institutions (Washington University and Massachusetts General Hospital) with different acquisitions (gradient-refocused echo and asymmetric spin echo) and different analysis techniques. Overall, activation maps were highly similar across both fMRI methods and PET. A set of activated brain areas, in consistent locations in Talairach atlas space, were identified across all three studies, including visual striate and extrastriate, left prefrontal, supplementary motor area (SMA), and right cerebellar areas. Decreases in activation were also consistently observed in medial parietal, posterior insular, and medial inferior frontal areas. Some differences were noted that may be related to the silent performance of the task with fMRI. The largely consistent results suggest that comparisons can be made appropriately across imaging modalities and laboratory methods. A further implication of the consistencies, which extended to both increases and decreases in signal, is that the underlying brain physiology leading to BOLD contrast may be more similar to blood flow than originally appreciated.     

Neural activation during frequency-memory performance.

Lesion studies have demonstrated that frequency memory, or memory for the frequency of occurrence, is associated with prefrontal and not temporal lobe lesions. This study examined neural activation during performance on a frequency-memory-judgment task and a recognition-memory task, both using words. Relative to a control task, the authors observed peaks of activation during frequency-memory performance in the left ventrolateral prefrontal cortex (BA 45) and other areas typically associated with working memory (dorsolateral prefrontal cortex, posterior parietal cortex). Recognition performance was associated with activation in the same left ventrolateral prefrontal location as was observed with frequency memory. When comparing activation during frequency memory with activation during recognition memory, the authors found a suppression of activation in the hippocampus bilaterally during frequency memory. This study supports a neuroanatomical distinction between frequency and recognition memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

Auditory and visual word processing studied with fMRI

Brain activations associated with semantic processing of visual and auditory words were investigated using functional magnetic resonance imaging (fMRI). For each form of word presentation, subjects performed two tasks: one semantic, and one nonsemantic. The semantic task was identical for both auditory and visual presentation: single words were presented and subjects determined whether the word was concrete or abstract. In the nonsemantic task for auditory words, subjects determined whether the word had one syllable or multiple syllables. In the nonsemantic task for visual words, subjects determined whether the word was presented in lower case or upper case. There was considerable overlap in where auditory and visual word semantic processing occurred. Visual and auditory semantic tasks both activated the left inferior frontal (BA 45), bilateral anterior prefrontal (BA 10, 46), and left premotor regions (BA 6) and anterior SMA (BA 6, 8). Left posterior temporal (middle temporal and fusiform gyrus) and predominantly right-sided cerebellar activations were observed during the auditory semantic task but were not above threshold during visual word presentation. The data, when averaged across subjects, did not show obligatory activation of left inferior frontal and temporal language areas during nonsemantic word tasks. Individual subjects showed differences in the activation of the inferior frontal region while performing the same task, even though they showed similar response latency and accuracy.     

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.     

Relationship of specific EEG frequencies at specific brain areas with performance

This study shows that incorrect responses are preceded by different EEG characteristics than correct responses, and that these differences appear in specific brain regions that participate in each particular task. EEGs were recorded in children during three different tasks: color discrimination (CDT), verbal working memory (VWM), and word categorization task (WCT). EEG segments previous to the presentation of the stimulus were analysed. Incorrect responses were preceded by lower EEG power values at 7.8 Hz in posterior temporal and right parietal leads in CDT, 8.59 and 9.36 Hz in frontal areas in VWM, and 10.72 Hz in the left hemisphere in WCT. In the former task > 1.56 Hz power in frontal areas prior to an incorrect response was also observed.     

Germ-line therapy for mitochondrial disease: some ethical objections

In an effort to examine the functional neuroanatomy of semantic memory, we studied the relative cerebral blood flow of eight healthy young subjects using 15O-water positron emission tomography (PET). Relative to a visual baseline control condition, each of four visual matching-to-sample tasks activated components of the ventral visual processing stream, including the inferior occipital and temporal cortices. Contrasting the task with the highest semantic component, a variation on the Pyramids and Palm Trees paradigm, with a size discrimination task resulted in focal activation in the anterior inferior temporal lobe, focused in the parahippocampal gyrus. There was additional activation in BA47 of the inferior frontal cortex. These data replicate and extend previously reported results using similar paradigms, and are consistent with cognitive neuropsychological models that stress the executive role of BA47 in semantic processing tasks.