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.     

Multiwell 14CO2-capture assay for evaluation of substrate oxidation rates of cells in culture

The functional anatomy of the interactions between spoken language and visual mental imagery was investigated with PET in eight normal volunteers during a series of three conditions: listening to concrete word definitions and generating their mental images (CONC), listening to abstract word definitions (ABST) and silent REST. The CONC task specifically elicited activations of the bilateral inferior temporal gyri, of the left premotor and left prefrontal regions, while activations in the bilateral superior temporal gyri were smaller than during the ABST task, during which an additional activation of the anterior part of the right middle temporal gyrus was observed. No activation of the occipital areas was observed during the CONC task when compared either to the REST or to the ABST task. The present study demonstrates that a network including part of the bilateral ventral stream and the frontal working memory areas is recruited when mental imagery of concrete words is performed on the basis of continuous spoken language.     

A multimodal language region in the ventral visual pathway

Reading words and naming pictures involves the association of visual stimuli with phonological and semantic knowledge. Damage to a region of the brain in the left basal posterior temporal lobe (BA37), which is strategically situated between the visual cortex and the more anterior temporal cortex, leads to reading and naming deficits. Additional evidence implicating this region in linguistic processing comes from functional neuroimaging studies of reading in normal subjects and subjects with developmental dyslexia. Here we test whether the visual component of reading is essential for activation of BA37 by comparing cortical activations elicited by word processing in congenitally blind, late-blind and sighted subjects using functional neuroimaging. Despite the different modalities used (visual and tactile), all groups of subjects showed a common activation of BA37 by words relative to non-word letter-strings. These findings agree with the proposal that BA37 is an association area that integrates converging inputs from many regions. Our study confirms a prediction of theories of brain function that depend on convergence zones; the absence of one input (that is, visual) does not alter the response properties of such a convergence region.     

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.     

Receptive and expressive language activations for sentences: a PET study

Most language mapping studies have focussed on activations for single-word tasks. We examined activations for verbal auditory and generation tasks using sentence stimuli. [15O]-water PET was performed in 4 female and 5 male normal adults. Listening to sentences (minus rest) activated the superior and middle temporal gyri bilaterally, but mean activation was significantly stronger on the left. The strongest activation for sentence generation (minus repetition) was seen in the left middle and inferior frontal gyri (area 46). This focus appears to be anterior to activations reported for single-word generation, possibly due to greater verbal working memory demands of the sentential task. Additional activation of the left inferior temporal lobe can be attributed to lexicosemantic processing.     

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.     

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)     

Characterization of two rice MADS box genes that control flowering time

This study utilised positron emission tomography (PET) to identify the cortical areas involved in verbal initiation and suppression in normal subjects whilst performing a sentence completion test (the Hayling Test). In the first condition (response initiation) subjects were required to complete a sentence from which the last word was omitted, whereas in the second condition (response suppression) subjects were asked to complete a sentence with a word which made no sense in the context of the sentence. Subjects were also required to perform a control task in which they had to read out the last word of given sentences. Compared to the control task, response initiation was associated with left-sided activation of the frontal operculum, inferior frontal gyrus, middle temporal gyrus and the right anterior cingulate gyrus, whereas response suppression was associated with left frontal operculum, inferior frontal gyrus and right anterior cingulate gyrus activation. The difference in activation between the two conditions of the Hayling Test lay in the increased activation of the left middle temporal gyrus and the left inferior frontal gyrus during response initiation.     

Identification of distinct elements of the stromal microenvironment that control human hematopoietic stem/progenitor cell growth and differentiation

The role of left prefrontal cortex in lexical-semantic processing remains a matter of some debate. Functional neuroimaging experiments have reported blood flow changes in left inferior prefrontal cortex (LIPC) during tasks that involve word retrieval and semantic processing. Some of these studies have also implicated LIPC in repetition priming. To determine the necessity of prefrontal cortex for these types of memory and to elucidate their time-course, behavioral and event-related potential (ERP) correlates of lexical processing and repetition priming were examined in 11 stroke patients with lesions centered in dorsolateral prefrontal cortex (areas 9 and 46). Damage extended inferiorly and posteriorly to areas 6, 8, 44, and 45 in some subjects, so patients were subdivided into anterior and posterior frontal subgroups. Visually presented words and pronounceable non-words were repeated after one of three delays. Subjects categorized stimuli as either words or non-words in a lexical decision task. Controls showed significant word priming at all three delays. Old words elicited more positive-going potentials than new words, beginning at 300 ms and lasting until 500-700 ms. This ERP repetition effect was reduced, but not eliminated, by both anterior and posterior frontal lesions. However, behavioral priming was intact in the patients, suggesting that prefrontal cortex may modulate the neural generators in posterior cortical regions that are critical for priming. Left posterior frontal lesions resulted in impaired performance in the lexical decision task and a reduction in the amplitude of the late positive component (LPC). These latter findings suggest that left posterior prefrontal cortex is important for the categorization and selection processes required by lexical-semantic tasks.     

A comparison of rCBF patterns during letter and semantic fluency.

To evaluate the functional neuroanatomies underlying letter and category fluency, 18 normal controls were studied with oxygen-15 water regional cerebral blood flow positron emission tomography. Three counterbalanced conditions each consisted of 6 trials (45 s each): letter fluency (generating words when cued with a particular letter), semantic fluency (generating words when cued with a particular category), and a control condition (generating days of the week and months of the year). Relative to the control, participants activated similar brain regions during both fluency tasks, including the anterior cingulate, left prefrontal regions, thalamus, and cerebellum; reductions were found in parietal and temporal regions. In a direct comparison of the 2 fluency tasks, inferior frontal cortex and temporoparietal cortex (hypothesized to participate in a phonologic loop for accessing word pronunciation) were activated more during letter than semantic fluency, whereas left temporal cortex (associated with access to semantic storage) was activated more during semantic than letter fluency. This study identifies subtle differences in the neural networks underlying letter and semantic fluency that may underlie the dissociation of these abilities in patients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Aging effects on memory encoding in the frontal lobes.

Functional magnetic resonance imaging (fMRI) was used to compare frontal-lobe activation in younger and older adults during encoding of words into memory. Participants made semantic or nonsemantic judgements about words. Younger adults exhibited greater activation for semantic relative to nonsemantic judgements in several regions, with the largest activation in the left inferior frontal gyrus. Older adults exhibited greater activation for semantic judgments in the same regions, but the extent of activation was reduced in left prefrontal regions. In older adults, there was a significant association between behavioral tests of declarative and working memory and extent of frontal activation. These results suggest that age-associated decreases in memory ability may be due to decreased frontal-lobe contributions to the initial encoding of experience. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modelling of intraperitoneal chemohyperthermia: experimental study and identification of certain thermal aspects

The purpose of this study was to examine regional cerebral blood flow using positron emission tomography (PET) during the performance of tasks related to visual confrontation naming. Ten healthy, young participants were scanned twice in each of 5 conditions; blood flow was measured using standard PET [15O]-water technology. Two major findings have replicated previous studies. First, the naming of visually presented objects, whether covert or overt, requires a region of the left inferior cortex including the fusiform gyrus. Second, during overt naming, there is an increase in activity in the inferior or frontal cortex and insula as a consequence of generating speech code. These data are consistent with other studies demonstrating the importance of the inferior temporal regions for semantic processing, and the frontal cortex for word form generation.     

Cerebral interregional correlations of associative language processing: a positron emission tomography activation study using fluorine-18 fluorodeoxyglucose

Even though there have been numerous positron emission tomography (PET) activation studies on the perfusional and metabolic bases of language processing, little is known about the intracerebral functional network of language and cognitive processes. It was the aim of this study to investigate the cerebral interregional correlations during voluntary word association versus word repetition in healthy subjects to gain insight into the functional connectivity of associative speech processing. Due to individual variability in functional anatomy, the study protocol was designed as an averaged single-subject study. Eight healthy volunteers performed a verbal association task during fluorine-18 fluorodeoxyglucose (18F-FDG) PET scanning. Two different tasks were performed in randomized order: (a) word repetition (after auditory presentation of nouns) as a control condition, and (b) word association (after auditory presentation of nouns) as a specific semantic activation. The regional metabolic rate of glucose (rMRGlu) was calculated after brain regionalization [112 regions of interest on individual 3D flash magnetic resonance imaging (MRI)] and PET/MRI realignment. Statistical analysis was performed for comparison of association and repetition and for calculation of interregional correlation coefficients during both tasks. Compared with word repetition, word association was associated with significant increases in rMRGlu in the left prefrontal cortex, the left frontal operculum (Broca's area) and the left insula, indicating involvement of these areas in associative language processing. Decreased rMRGlu was found in the left posterior cingulum during word association. During word repetition, highly significant negative correlations were found between the left prefrontal cortex, the contralateral cortex areas and the ipsilateral posterior cingulum. These negative correlations were almost completely eliminated during the association task, suggesting a functional decoupling of the strict intercorrelation pattern.     

Age differences in incidental learning.

Examined the effects of age and of incidental-learning tasks on recall of a categorized word list. Ss were 50 18-30 yr old college students and 50 55-65 yr old teachers. The control groups were instructed to remember the words; incidental-learning groups performed orienting tasks, but were not informed that they would have to recall the words. 2 orienting tasks required that Ss process the meaning of the words; the other 2 orienting tasks did not involve semantic processing. Analysis of the free-recall data indicates that the semantic processing tasks led to much greater recall and organization of recall than the nonsemantic orienting tasks. In recall, there was a significant interaction between age and orienting task, with old Ss only manifesting incidental learning that was inferior to young Ss, whose orienting task involved semantic processing. The findings indicate that the presence or absence of an age-related decrement in incidental learning is predictable from the depth of processing of the incidentally acquired material. (23 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.     

Attention and semantic priming: a review of prime task effects

The single-word semantic priming paradigm is a tool for investigating how and when word meaning (semantic) activation occurs during visual word recognition. The prime task effect refers to the elimination of the typically robust semantic priming effect by a nonsemantic prime task (e.g., subjects search the prime word for a letter). The purpose of this paper is to provide a tutorial review of the literature examining the prime task effect. Understanding the nature of this effect has implications for delineating how selective attention modulates evidence for semantic activation during word reading. These implications are outlined. Additionally, speculations for how these issues of selective attention relate to awareness are offered.     

Adult age differences in regional cerebral blood flow during visual world identification: evidence from H215O PET

We used H215O PET to investigate adult age differences in regional cerebral blood flow (rCBF) during the performance of a visual word identification task. The study participants were 20 healthy, right-handed men: 10 young adults between 18 and 27 years of age, and 10 older adults between 63 and 75 years of age. The word identification task comprised six blocks of test trials representing four task conditions; subjects responded manually. The task conditions varied with regard to whether semantic retrieval was required (e.g., word/nonword discrimination vs simple response to each stimulus) and with regard to the difficulty of visual encoding (e.g., words presented normally vs words with asterisks inserted between adjacent letters). Each subject performed all six trial blocks, concurrently with each of six H215O PET scans. Analyses of quantitative CBF data obtained from the arterial time-activity curve demonstrated a significant age-related decline in global CBF rate. Analyses of the changes in rCBF between task conditions indicated that retrieval of semantic information sufficient to distinguish words from nonwords is mediated by a ventral occipitotemporal cortical pathway. Specific areas within this pathway were also associated with visual encoding processes. Several rCBF activations were significantly greater for young adults than for older adults, indicating an age-related decline in processing efficiency within this ventral occipitotemporal pathway. Although the performance data demonstrated a greater age-related slowing for visual encoding than for semantic retrieval, these age-related performance changes were not associated with corresponding changes in rCBF activation.     

Dynamics of co-infection with M. Tuberculosis and HIV-1

The functional anatomy of perceptual and semantic processings for odors was studied using positron emission tomography (PET). The first experiment was a pretest in which 71 normal subjects were asked to rate 185 odorants in terms of intensity, familiarity, hedonicity, and comestibility and to name the odorants. This pretest was necessary to select the most appropriate stimuli for the different cognitive tasks of the second experiment. The second one was a PET experiment in which 15 normal subjects were scanned using the water bolus method to measure regional cerebral blood flow (rCBF) during the performance in three conditions. In the first (perceptual) condition, subjects were asked to judge whether an odor was familiar or not. In the second (semantic) condition, subjects had to decide whether an odor corresponded to a comestible item or not. In the third (detection) condition, subjects had to judge whether the perceived stimulus was made of an odor or was just air. It was hypothetized that the three tasks were hierarchically organized from a superficial detection level to a deep semantic level. Odorants were presented with an air-flow olfactometer, which allowed the stimulations to be synchronized with breathing. Subtraction of activation images obtained between familiarity and control judgments revealed that familiarity judgments were mainly associated with the activity of the right orbito-frontal area, the subcallosal gyrus, the left inferior frontal gyrus, the left superior frontal gyrus, and the anterior cingulate (Brodmann's areas 11, 25, 47, 9, and 32, respectively). The comestibility minus familiarity comparison showed that comestibility judgments selectively activated the primary visual areas. In contrast, a decrease in rCBF was observed in these same visual areas for familiarity judgments and in the orbito-frontal area for comestibility judgments. These results suggest that orbito-frontal and visual regions interact in odor processing in a complementary way, depending on the task requirements.     

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.     

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.