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Biomedical subjects

M E Raichle

Publications and source records attributed to M E Raichle.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

Impaired non-motor learning and error detection associated with cerebellar damage. A single case study.

A previously conducted positron emission tomography (PET) study of normal humans suggested that the cerebellum makes important non-motor contributions to language processing. Beginning with the task which produced right cerebellar PET activation, we studied a 49-yr-old male (RC1) with right cerebellar damage on a variety of tasks involving complex non-motor processing. Whereas RC1's performance on standard tests of memory, intelligence, 'frontal function' and language skills was excellent, he had profound deficits in two areas: (1) practice-related learning; (2) detection of errors. Considered in relation to cerebellar contributions to motor tasks, the results suggest some functions performed by the cerebellum may be generalized beyond a purely motor domain.

Cerebellar Diseases↗
PubMed1992

Neuroanatomical circuits in depression: implications for treatment mechanisms.

We previously investigated the functional neuroanatomy of familial pure depressive disease (FPDD) using positron emission tomography (PET) measurements of regional blood flow and obtained evidence that flow is increased in the left prefrontal cortex, amygdala, and medial thalamus and is decreased in the medial caudate. These data along with other evidence suggested that circuits involving the prefrontal cortex, amygdala, and related parts of the striatum, pallidum, and medial thalamus are involved in the pathophysiology of FPDD. One of these circuits, the limbic-thalamo-cortical circuit, which includes the amygdala, the medio-dorsal thalamus, and parts of the ventral and medial prefrontal cortex, may be engaged in abnormal reverberatory activity that maintains the cognitive and emotional set of depression. Using this hypothesis as a neural model to investigate antidepressant treatment mechanisms, we review evidence that the changes in dopaminergic, serotonergic, and noradrenergic function induced by somatic antidepressant therapies may yield modulatory effects on limbic-thalamo-cortical activity. We also discuss preliminary findings of treatment-associated changes in this circuit in studies comparing PET images acquired before and during antidepressant treatment.

Depressive Disorder↗
PubMed1992

A functional anatomical study of unipolar depression.

The functional neuroanatomy of unipolar major depression was investigated using positron emission tomography to measure differences in regional cerebral blood flow (BF). A relatively homogeneous subject group was obtained using criteria for familial pure depressive disease (FPDD), which are based upon family history as well as upon symptoms and course. Because of the absence of certain knowledge about the pathophysiology of mood disorders and their underlying functional neuroanatomy, we used data obtained from the subtraction of composite images from one-half of depressed and control subjects to identify candidate regions of interest. The major cortical region defined in this manner was statistically tested on a second set of subjects. Using this strategy, we found increased BF in an area that extended from the left ventrolateral prefrontal cortex onto the medial prefrontal cortical surface. Based upon the connectivity between these portions of the prefrontal cortex and the amygdala and evidence that the amygdala is involved in emotional modulation, activity was measured in the left amygdala and found to be significantly increased in the depressed group. A separate group of subjects with FPDD who were currently asymptomatic were also imaged to determine whether these findings represented abnormalities associated with the depressed state, or with a trait difference that might underlie the tendency to become depressed. Only the depressed group had increased activity in the left prefrontal cortex, suggesting that this abnormality represents a state marker of FPDD. Both the depressed and the remitted groups demonstrated increased activity in the left amygdala, though this difference achieved significance only in the depressed group. This suggests that the abnormality involving the left amygdala may represent a trait marker of FPDD, though further assessment in a larger sample size is necessary to establish this. These data along with other evidence suggest that a circuit involving the prefrontal cortex, amygdala, and related parts of the striatum, pallidum, and medial thalamus is involved in the functional neuroanatomy of depression.

Adult↗
PubMed1991

Localization of a human system for sustained attention by positron emission tomography.

Positron emission tomographic (PET) studies of human attention have begun to dissect isolable components of this complex higher brain function, including a midline attentional system in a region of the anterior cingulate cortex. The right hemisphere may play a special part in human attention; neglect, an important phenomenon associated with damage to attentional systems, is more severe, extensive and long-lasting after lesions to the right hemisphere. Here we use PET measurements of brain blood flow in healthy subjects to identify changes in regional brain activity during simple visual and somatosensory tasks of sustained attention or vigilance. We find localized increases in blood flow in the prefrontal and superior parietal cortex primarily in the right hemisphere, regardless of the modality or laterality of sensory input. The anterior cingulate was not activated during either task. These data localize the vigilance aspects of normal human attention to sensory stimuli, thereby clarifying the biology underlying asymmetries of attention to such stimuli that have been reported in clinical lesions.

Adult↗
PubMed1991

Memory mechanisms in the processing of words and word-like symbols.

Modern functional imaging techniques such as positron emission tomography (PET) provide the opportunity to examine in some detail the implementation of mental activities in the human brain. Using measurements of changes in local brain blood flow obtained with PET as a marker of changes in local neuronal activity we have examined the processing of single words and word-like symbols. These studies reveal the very distributed, modular nature of this implementation and provide some preliminary insights into the role of memory mechanisms in the process.

Brain Mapping↗
PubMed1990

Activation of extrastriate and frontal cortical areas by visual words and word-like stimuli.

Visual presentation of words activates extrastriate regions of the occipital lobes of the brain. When analyzed by positron emission tomography (PET), certain areas in the left, medial extrastriate visual cortex were activated by visually presented pseudowords that obey English spelling rules, as well as by actual words. These areas were not activated by nonsense strings of letters or letter-like forms. Thus visual word form computations are based on learned distinctions between words and nonwords. In addition, during passive presentation of words, but not pseudowords, activation occurred in a left frontal area that is related to semantic processing. These findings support distinctions made in cognitive psychology and computational modeling between high-level visual and semantic computations on single words and describe the anatomy that may underlie these distinctions.

Adult↗
PubMed1990

The anterior cingulate cortex mediates processing selection in the Stroop attentional conflict paradigm.

Regional cerebral blood flow, an index of local neuronal activity, was measured using positron emission tomography (PET) during the performance of the classic Stroop color/word task in eight healthy right-handed subjects. In the first condition of this paradigm, subjects name the color of the words presented on a video monitor. All the words are the color names congruent to the color presented (e.g., the noun "red" displayed in red color). In the second condition, subjects also name the color of the words presented on the monitor. However, during these trials all words are color names incongruent to the color presented (e.g., the noun "red" displayed in green color). The difference in brain activity between these two conditions (i.e., incongruent minus congruent) could reveal brain systems involved in the attentionally mediated resolution of the conflict between the habitual response of reading words vs. the task demands of naming the color of the words--i.e., the Stroop interference effect. The most robust responses occurred in the anterior cingulate cortex. Other responses noted were in the left premotor cortex, left postcentral cortex, left putamen, supplementary motor area, right superior temporal gyrus, and bilateral peristriate cortices. These data provide support for the role of the anterior cingulate cortex in attentional processing through the selection and recruitment of processing centers appropriate for task execution. Furthermore, the extensive distributed network of activated regions suggests that the Stroop interference effect cannot be explained simply in terms of stimulus encoding or response interference.

Adult↗
PubMed1990

Cerebral blood flow in acute mountain sickness.

Changes in cerebral blood flow (CBF) were measured using the radioactive xenon technique and were related to the development of acute mountain sickness (AMS). In 12 subjects, ascending from 150 to 3,475 m, CBF was 24% increased at 24 h [45.1 to 55.9 initial slope index (ISI) units] and 4% increased at 6 days (47.1 ISI units). Four subjects had similar increases of CBF when ascending to 3,200 m 3 mo later, indicating the reproducibility of the measurements. In nine subjects, ascending from 3,200 to 4,785-5,430 m, CBF increased to 76.4 ISI units, 53% above estimated sea-level values. CBF and increases in CBF were similar in subjects with or without AMS. In six subjects, CBF was measured before and after therapeutic intervention. At 2 h CBF increased 22% (71.3 to 87.3 ISI units) above pretreatment values in three subjects given 1.5 g acetazolamide, while three subjects given placebo showed no change. Symptoms remained unaltered in all subjects during the 2 h of the study. Overall, the results indicated that increases in CBF were similar in subjects with or without AMS while acetazolamide-provoked increases of CBF in AMS subjects caused no acute change in symptoms. Alterations in CBF cannot be directly implicated in the pathogenesis of AMS.

Acetazolamide↗
PubMed1990

Copper-62-labeled pyruvaldehyde bis(N4-methylthiosemicarbazonato)copper(II): synthesis and evaluation as a positron emission tomography tracer for cerebral and myocardial perfusion.

Generator produced positron-emitting radionuclides could potentially expand the application of positron emission tomography (PET) to centers that do not have access to a local cyclotron. The zinc-62/copper-62 radionuclide generator system could serve as a source of positron-emitting copper-62 (62Cu) (t1/2 = 9.74 min) for physiologic imaging. Accordingly, we have prepared zinc-62/copper-62 generators capable of high output (greater than 300 mCi) and used the no-carrier-added eluate in a rapid high yield synthesis of [62Cu] Cu(PTSM) that provides the radiopharmaceutical in a form suitable for intravenous injection (where Cu(PTSM) = pyruvaldehyde bis(N4-methylthiosemicarbazonato) copper(II]. We then demonstrated in pilot studies that [62Cu]Cu(PTSM) provides high quality brain and heart images with PET, accurately delineating cerebral and myocardial perfusion in both experimental animals and in humans (corroborating results of previous experimental studies utilizing longer-lived copper isotopes). The results of this work demonstrate that 62Cu can be conveniently obtained from high-level generators and, when used to label Cu(PTSM), provides a generator-produced radiopharmaceutical capable of providing estimates of cerebral and myocardial perfusion independent of cyclotron-produced radionuclides.

Animals↗
PubMed1990

Evaluation of a potential generator-produced PET tracer for cerebral perfusion imaging: single-pass cerebral extraction measurements and imaging with radiolabeled Cu-PTSM.

Copper(II) pyruvaldehyde bis(N4-methylthiosemicarbazone) (Cu-PTSM), copper(II) pyruvaldehyde bis(N4-dimethylthiosemicarbazone) (Cu-PTSM2), and copper(II) ethylglyoxal bis(N4-methylthiosemicarbazone) (Cu-ETSM), have been proposed as PET tracers for cerebral blood flow (CBF) when labeled with generator-produced 62Cu (t1/2 = 9.7 min). To evaluate the potential of Cu-PTSM for CBF PET studies, baboon single-pass cerebral extraction measurements and PET imaging were carried out with the use of 67Cu (t1/2 = 2.6 days) and 64Cu (t1/2 = 12.7 hr), respectively. All three chelates were extracted into the brain with high efficiency. There was some clearance of all chelates in the 10-50-sec time frame and Cu-PTSM2 continued to clear. Cu-PTSM and Cu-ETSM have high residual brain activity. PET imaging of baboon brain was carried out with the use of [64Cu]-Cu-PTSM. For comparison with the 64Cu brain image, a CBF (15O-labeled water) image (40 sec) was first obtained. Qualitatively, the H2(15)O and [64Cu]-Cu-PTSM images were very similar; for example, a comparison of gray to white matter uptake resulted in ratios of 2.42 for H2(15)O and 2.67 for Cu-PTSM. No redistribution of 64Cu was observed in 2 hr of imaging, as was predicted from the single-pass study results. Quantitative determination of blood flow using Cu-PTSM showed good agreement with blood flow determined with H2(15)O. This data suggests that [62Cu]-Cu-PTSM may be a useful generator-produced radiopharmaceutical for blood flow studies with PET.

Animals↗
PubMed1989

Neuroanatomical correlates of anticipatory anxiety.

Positron emission tomographic measurements of regional blood flow, a marker of local neuronal activity, were used to investigate the neuroanatomical correlates of a normal emotion. Healthy volunteers were studied before, during, and after anticipation of a painful electric shock. During anticipatory anxiety, there were significant blood flow increases in bilateral temporal poles, the same regions recently implicated in a lactate-induced anxiety attack in patients with panic disorder. Thus, the temporal poles seem to be involved in normal and pathological forms of human anxiety.

Anxiety↗
PubMed1989

Neuroanatomical correlates of a lactate-induced anxiety attack.

Positron emission tomographic measurements of regional blood flow were used to assess local neuronal activity in patients with panic disorder and in normal control subjects before and during the infusion of sodium lactate. A new technique for the analysis of positron emission tomographic data was employed to identify significant changes in regional blood flow associated with lactate infusion in the panicking patients, nonpanicking patients, and controls. Lactate-induced panic was associated with significant blood flow increases bilaterally in the temporal poles; bilaterally in insular cortex, claustrum, or lateral putamen; bilaterally in or near the superior colliculus; and in or near the left anterior cerebellar vermis. Lactate infusion was not associated with significant changes in regional blood flow in the nonpanicking patients or control subjects. Thus, the identified regions seemed to be involved in an anxiety attack.

Adult↗