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Biomedical subjects

M E Raichle

Publications and source records attributed to M E Raichle.

At least 55 records · Page 3Linked to original sources

Detection of cortical activation during averaged single trials of a cognitive task using functional magnetic resonance imaging.

Functional neuroimaging studies in human subjects using positron emission tomography or functional magnetic resonance imaging (fMRI) are typically conducted by collecting data over extended time periods that contain many similar trials of a task. Here methods for acquiring fMRI data from single trials of a cognitive task are reported. In experiment one, whole brain fMRI was used to reliably detect single-trial responses in a prefrontal region within single subjects. In experiment two, higher temporal sampling of a more limited spatial field was used to measure temporal offsets between regions. Activation maps produced solely from the single-trial data were comparable to those produced from blocked runs. These findings suggest that single-trial paradigms will be able to exploit the high temporal resolution of fMRI. Such paradigms will provide experimental flexibility and time-resolved data for individual brain regions on a trial-by-trial basis.

Adolescent↗

Functional anatomic studies of memory retrieval for auditory words and visual pictures.

Functional neuroimaging with positron emission tomography was used to study brain areas activated during memory retrieval. Subjects (n = 15) recalled items from a recent study episode (episodic memory) during two paired-associate recall tasks. The tasks differed in that PICTURE RECALL required pictorial retrieval, whereas AUDITORY WORD RECALL required word retrieval. Word REPETITION and REST served as two reference tasks. Comparing recall with repetition revealed the following observations. (1) Right anterior prefrontal activation (similar to that seen in several previous experiments), in addition to bilateral frontal-opercular and anterior cingulate activations. (2) An anterior subdivision of medial frontal cortex [pre-supplementary motor area (SMA)] was activated, which could be dissociated from a more posterior area (SMA proper). (3) Parietal areas were activated, including a posterior medial area near precuneus, that could be dissociated from an anterior parietal area that was deactivated. (4) Multiple medial and lateral cerebellar areas were activated. Comparing recall with rest revealed similar activations, except right prefrontal activation was minimal and activations related to motor and auditory demands became apparent (e.g., bilateral motor and temporal cortex). Directly comparing picture recall with auditory word recall revealed few notable activations. Taken together, these findings suggest a pathway that is commonly used during the episodic retrieval of picture and word stimuli under these conditions. Many areas in this pathway overlap with areas previously activated by a different set of retrieval tasks using stem-cued recall, demonstrating their generality. Examination of activations within individual subjects in relation to structural magnetic resonance images provided an-atomic information about the location of these activations. Such data, when combined with the dissociations between functional areas, provide an increasingly detailed picture of the brain pathways involved in episodic retrieval tasks.

Adolescent↗

Preserved speech abilities and compensation following prefrontal damage.

Lesions to left frontal cortex in humans produce speech production impairments (nonfluent aphasia). These impairments vary from subject to subject and performance on certain speech production tasks can be relatively preserved in some patients. A possible explanation for preservation of function under these circumstances is that areas outside left prefrontal cortex are used to compensate for the injured brain area. We report here a direct demonstration of preserved language function in a stroke patient (LF1) apparently due to the activation of a compensatory brain pathway. We used functional brain imaging with positron emission tomography (PET) as a basis for this study.

Aged↗

A positron emission tomography study of the short-term maintenance of verbal information.

Positron emission tomography (PET) was used to investigate the functional brain anatomy associated with the short-term maintenance of linguistic information. Subjects were asked to retain five related words, unrelated words, or pseudowords silently for the duration of a 40 sec PET scan. When brain activity during these short-term maintenance tasks was compared with a visual fixation control task, increases were found bilaterally in the dorsolateral prefrontal cortex and cerebellum, and medially in the supplementary motor area. Furthermore, effects of stimulus condition and recall performance were found in the left frontal operculum. To investigate the role of articulatory systems in the maintenance of verbal information, regional activation was compared across the maintenance tasks and a covert articulation task (silent counting). The cerebellum was active in both task conditions, whereas activation in prefrontal regions was specific to the maintenance condition. Conversely, greater activation was found in a left middle insular region in the silent counting than in the maintenance tasks. Based on converging results in this and previous studies, dorsolateral prefrontal cortical areas appear to contribute to the maintenance of both verbal and nonverbal information, whereas left frontal opercular regions appear to be involved specifically in the rehearsal of verbal material. Contrary to results found in other studies of working memory, activation was not found in the inferior parietal cortex, suggesting that this area is involved in aspects of stimulus encoding and retrieval, which were minimized in the present study.

Adult↗

What words are telling us about the brain.

Modern functional brain imaging with PET and fMRI provides a new perspective on the organization of language in the human brain. A better definition of the distributed nature of the brain circuits involved, an appreciation of the flexibility of these circuits in adapting to the different aspects of speech production, an identification of areas not previously associated with the cognitive aspects of language, and a new understanding of the implications of specific brain lesions on the lives and behavior of patients are all early suggestions of the benefits to be derived from this work. Much exciting work lies ahead.

Humans↗

Scalp electrical potentials reflect regional cerebral blood flow responses during processing of written words.

Functional brain imaging studies with positron emission tomography (PET) have identified blood flow changes in widely separated areas of the brain during the performance of word-related tasks. In the present study, we have utilized event-related electrical potentials (ERPs) to investigate the temporal relationships among cortical areas previously identified by PET to be differentially activated when performing a task involving generating the uses of visually presented nouns versus reading aloud. ERPs showed strong task-related differences over left and middle inferior frontal and left parietotemporal regions. Frontal and left parietotemporal channels revealed these differences around 200 and 700 msec, respectively, after word presentation. These results provide the time course for parts of the anatomical circuit involved in generating the meaning of a word. Our results also demonstrate how combining the spatial localization of PET with the temporal resolution of ERPs greatly enhances the capacity to understand the mechanisms involved in human cognition.

Adult↗

Blood flow changes in human somatosensory cortex during anticipated stimulation.

Positron emission tomography (PET) measurements of brain blood flow were used to monitor changes in the human primary and secondary somatosensory cortices during the period when somatosensory stimuli were expected. In anticipation of either focal or innocuous touching, or localized, painful shocks, blood flow decreased in parts of the primary somatosensory cortex map located outside the representation of the skin area that was the target of the expected stimulus. Specifically, attending to an impending stimulus to the fingers produced a significant decrease in blood flow in the somatosensory zones for the face, whereas attending to stimulation of the toe produced decreases in the zones for the fingers and face. Decreases were more prominent in the side ipsilateral to the location of the expected stimulus. No significant changes in blood flow occurred in the region of the cortex representing the skin locus of the awaited stimulation. These results are concurrent with a model of spatial attention in which potential signal enhancement may rely on generalized suppression of background activity.

Adult↗

Dissociation of human prefrontal cortical areas across different speech production tasks and gender groups.

1. Data from a series of positron emission tomography (PET) experiments were analyzed with two goals. The first goal was to determine whether there were reliable differences in prefrontal cortex activation across two different speech production tasks. Such differences are important in determining functional subdivisions within prefrontal cortex. The second goal was to determine whether there were any gender differences across the two speech production tasks. 2. To accomplish these goals, PET subtraction images were generated for each of two speech production tasks (stem completion and verb generation). For the stem completion task, subjects viewed word stems (e.g., "GRE") and said aloud words that could complete the stems (e.g., "green"). For the verb generation task, subjects viewed nouns (e.g., "CHAIR") and said aloud words that were meaningfully related verbs (e.g., "sit"). Different groups of subjects performed the stem completion (N = 29) and verb generation (N = 32) tasks. 3. Data from each task subtraction were further divided by gender group (i.e., verb generation: male group; verb generation: female group, etc.). PET activations were separately identified in prefrontal cortex for each of the four resulting images. Activations were identified primarily in left prefrontal cortex for both tasks and both gender groups. Activations in right prefrontal cortex were small or absent. 4. Across tasks, the subtraction images showed both common activations in prefrontal cortex and one clear difference. Activations in left inferior prefrontal cortex (near Brodmann's areas 44 or 45) were observed in both male and female group images for both task subtractions. Activations in left anterior prefrontal cortex (near Brodmann's areas 10 or 46) were only observed for the verb generation subtraction images, formally demonstrating a functional dissociation between left inferior prefrontal cortex and more anterior prefrontal cortex. 5. This dissociation between prefrontal areas was highly robust and reliable across both gender groups. The left inferior prefrontal area(s) common to all of the subtraction images appears to be activated by tasks that demand high-level word retrieval and production processes. This area is distinct from the more anterior area(s), which is not always activated by such tasks. Dissociations in prefrontal areas are important because current descriptions of human functional anatomy often treat activations within large regions of cortex (e.g., dorsolateral prefrontal cortex) as single entities. 6. No qualitative differences in activation between gender groups were detected. For both subtractions, all activations identified within one gender group generalized to the other gender group. For the verb generation subtraction image, however, activations in male subjects were larger in magnitude than in female subjects.

Adolescent↗

Functional anatomical studies of explicit and implicit memory retrieval tasks.

Across three experiments, PET scans were obtained while subjects performed different word-stem completion and FIXATION control tasks designed to study the functional anatomy of memory retrieval. During each of three different word-stem completion scans, word-stem cues were visually presented in uppercase letters. The RECALL task required explicit retrieval of study words presented prior to the PET scan. The PRIMING task addressed the implicit effects of the prior study words without requiring intentional recall. The BASELINE task encouraged retrieval of information from a general knowledge store. Across experiments, the similarity between study words and word stems was manipulated by presenting prescan study words in either uppercase letters identical to the stems, in lowercase letters, or auditorily. The PRIMING task was not studied with auditory presentation. Many activations were consistent across experiments. The BASELINE task activated several regions in response to the reading and verbal-response demands of the task (visual, motor, and premotor cortices, cerebellum), as well as a left prefrontal region. The RECALL task additionally activated regions in anterior right prefrontal cortex. Bilateral occipitotemporal regions showed blood flow reductions during the PRIMING task as compared to the BASELINE task. Activation in the right hippocampal/parahippocampal region was observed only in one experiment, and no experiment showed activation in the left medial temporal lobe. These experiments suggest that areas of frontal cortex play a role in explicit recall and that an effect of priming may be to require less activation of perceptual regions for the processing of recently presented information.

Adult↗

First-pass extraction fraction of iodine-123 labeled perfusion tracers in living primate brain.

The cerebral extraction and retention of three radioiodinatéd SPECT perfusion tracers were measured using residue detection in a baboon. A permeability-surface area product PS' with special relevance to SPECT was calculated from the retention of tracer in the brain after 10 min. PS' differs from the traditional PS value, which is calculated from the tracer clearance curve at 2 min. The PS' values ranged from 50 to 95 mL/min/100 g, decreased in the order [123I]IMP > [123I]iodoperidol approximately [123I]HIPDM, and did not differ for specific activities of 10 MBq/mmol to 74 TBq/mmol. These radioiodinated compounds exhibited extraction characteristics superior to those of [99mTc]HMPAO but underestimated cerebral blood flow when flows were above 20-30 mL/min/100 g, underscoring the need for development of a more ideal SPECT perfusion tracer.

Animals↗

Measurement of regional cerebral blood flow with positron emission tomography: a comparison of [15O]water to [11C]butanol with distributed-parameter and compartmental models.

To further our understanding of the best way to measure regional CBF with positron emission tomography (PET), we directly compared two candidate tracers ([15O]water and [11C]butanol, administered intravenously) and two popular implementations of the one-compartment (1C) model: the autoradiographic implementation representing a single PET measurement of tissue radioactivity over 1 min and a dynamic implementation representing a sequence of measurements of tissue radioactivity over 200 s. We also examined the feasibility of implementing a more realistic, and thus more complex, distributed-parameter (DP) model by assigning fixed values for all of its parameters other than CBF and tracer volume of distribution (Vd), a requirement imposed by the low temporal resolution and statistical quality of PET data. The studies were performed in three normal adult human subjects during paired rest and visual stimulation. In each subject seven regions of interest (ROIs) were selected, one of which was the primary visual cortex. The corresponding ROI were anatomically equivalent in the three subjects. Regional CBF, Vd, tracer arrival delay, and dispersion were estimated for the dynamic data curves. A total of 252 parameter sets were estimated. With [11C]butanol both implementations of the 1C model provided similar results (r = 0.97). Flows estimated using the 1C models were lower (p < 0.01) with [15O]water than with [11C]butanol. In comparison with the 1C model, the constrained version of the DP used in these studies performed inadequately, overestimating high flow and underestimating low flow with both tracers, possibly as the result of the necessity of assigning fixed values for all of its parameters other than CBF and Vd.

Adult↗

Neural correlates of self-induced dysphoria.

OBJECTIVE: The authors explored the question of whether acute, transient changes in mood are reflected in activation of discrete neuronal systems in the human brain. METHOD: Using positron emission tomography, they measured the regional cerebral blood flow (CBF) of seven psychiatrically healthy subjects under two conditions. During the control condition the subjects were resting with their eyes closed. During the active condition, with their eyes still closed, they were asked to imagine or recall a situation that would make them feel very sad. They were explicitly asked to experience sadness and to avoid any feelings of anger or anxiety. RESULTS: There were significant differences in regional CBF measured during the control condition and during the active condition, particularly in the inferior and orbitofrontal cortices. Women showed bilateral inferior and orbitofrontal activation, but men displayed predominantly left-sided activation in these areas. CONCLUSIONS: The authors conclude that the inferior and orbitofrontal cortices play an important role in normal emotional cognitive processes.

Cerebral Cortex↗

Tactile-vibration-activated foci in insular and parietal-opercular cortex studied with positron emission tomography: mapping the second somatosensory area in humans.

Positron emission tomographic measurements were used to study the distribution of focal changes in cerebral blood flow (CBF) induced by vibrotactile stimulation of the hands and feet in 22 normal humans. Subjects received bolus intravenous saline injections containing approximately 60 mCi 15O-labeled water. Active regions during stimulation were defined relative to resting, nonstimulated states. Scan data from different subjects were averaged after stereotactic standardization. The results identified previously described foci of increased CBF in postrolandic sensory cortex (primary somatosensory cortex) and supplementary motor cortex. New statistical testing procedures provided independent demonstrations of two additional increases in regional CBF, bilaterally, within the sylvian fissure. One site along the parietal operculum corresponded to previous conjectures about a second somatosensory cortical area (SII) in humans. Another site also was found on the insula. No topographic organization was found in either location. The discussion considers these responsive areas to innocuous tactile stimuli in reference to suggestions about a role for SII in the perception of pain.

Adult↗

Activation of the hippocampus in normal humans: a functional anatomical study of memory.

We studied regional cerebral blood flow using the H2(15)O method while normal subjects performed four similar tasks involving three-letter word beginnings (stems). Prior to each task, subjects studied a list of words. Local blood flow was then monitored during a 40-sec period while subjects (i) silently viewed word stems, (ii) completed stems to form the first words to come to mind, but the stems were not the beginnings of any study words (baseline), (iii) completed stems and half of them could form study words (priming), or (iv) tried to recall study words, and half of the stems could form these words (memory). There were three major findings. (i) The memory task engaged the right hippocampal region when the memory task was compared to either the baseline or the priming condition. The right hemispheric locus suggests that performance is driven by the visual characteristics of the words rather than by semantic or phonetic analysis. (ii) In the priming-minus-baseline comparison, there was reduction in blood flow in the right posterior cortex. (iii) Right prefrontal cortex was activated in the memory-minus-baseline condition. The results provide evidence for selective activation of the human hippocampal region in association with memory function. The results also lead to a suggestion about the neural basis of repetition priming: following presentation of a stimulus, less neural activity is required to process the same stimulus.

Adult↗