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Biomedical subjects

Martin Ingvar

Publications and source records attributed to Martin Ingvar.

At least 37 records · Page 2Linked to original sources

Neural correlates of working memory for sign language.

Eight, early bilingual, sign language interpreters participated in a PET study, which compared working memory for Swedish Sign Language (SSL) with working memory for audiovisual Swedish speech. The interaction between language modality and memory task was manipulated in a within-subjects design. Overall, the results show a previously undocumented, language modality-specific working memory neural architecture for SSL, which relies on a network of bilateral temporal, bilateral parietal and left premotor activation. In addition, differential activation in the right cerebellum was found for the two language modalities. Similarities across language modality are found in Broca's area for all tasks and in the anterior left inferior frontal lobe for semantic retrieval. The bilateral parietal activation pattern for sign language bears similarity to neural activity during, e.g., nonverbal visuospatial tasks, and it is argued that this may reflect generation of a virtual spatial array. Aspects of the data suggesting an age of acquisition effect are also considered. Furthermore, it is discussed why the pattern of parietal activation cannot be explained by factors relating to perception, production or recoding of signs, or to task difficulty. The results are generally compatible with Wilson's [Psychon. Bull. Rev. 8 (2001) 44] account of working memory.

Adult↗

Brainstem involvement in the initial response to pain.

The autonomic responses to acute pain exposure usually habituate rapidly while the subjective ratings of pain remain high for more extended periods of time. Thus, systems involved in the autonomic response to painful stimulation, for example the hypothalamus and the brainstem, would be expected to attenuate the response to pain during prolonged stimulation. This suggestion is in line with the hypothesis that the brainstem is specifically involved in the initial response to pain. To probe this hypothesis, we performed a positron emission tomography (PET) study where we scanned subjects during the first and second minute of a prolonged tonic painful cold stimulation (cold pressor test) and nonpainful cold stimulation. Galvanic skin response (GSR) was recorded during the PET scanning as an index of autonomic sympathetic response. In the main effect of pain, we observed increased activity in the thalamus bilaterally, in the contralateral insula and in the contralateral anterior cingulate cortex but no significant increases in activity in the primary or secondary somatosensory cortex. The autonomic response (GSR) decreased with stimulus duration. Concomitant with the autonomic response, increased activity was observed in brainstem and hypothalamus areas during the initial vs. the late stimulation. This effect was significantly stronger for the painful than for the cold stimulation. Activity in the brainstem showed pain-specific covariation with areas involved in pain processing, indicating an interaction between the brainstem and cortical pain networks. The findings indicate that areas in the brainstem are involved in the initial response to noxious stimulation, which is also characterized by an increased sympathetic response.

Adult↗

The irrelevant speech effect and working memory load.

Irrelevant speech impairs the immediate serial recall of visually presented material. Previously, we have shown that the irrelevant speech effect (ISE) was associated with a relative decrease of regional blood flow in cortical regions subserving the verbal working memory, in particular the superior temporal cortex. In this extension of the previous study, the working memory load was increased and an increased activity as a response to irrelevant speech was noted in the dorsolateral prefrontal cortex. We suggest that the two studies together provide some basic insights as to the nature of the irrelevant speech effect. Firstly, no area in the brain can be ascribed as the single locus of the irrelevant speech effect. Instead, the functional neuroanatomical substrate to the effect can be characterized in terms of changes in networks of functionally interrelated areas. Secondly, the areas that are sensitive to the irrelevant speech effect are also generically activated by the verbal working memory task itself. Finally, the impact of irrelevant speech and related brain activity depends on working memory load as indicated by the differences between the present and the previous study. From a brain perspective, the irrelevant speech effect may represent a complex phenomenon that is a composite of several underlying mechanisms, which depending on the working memory load, include top-down inhibition as well as recruitment of compensatory support and control processes. We suggest that, in the low-load condition, a selection process by an inhibitory top-down modulation is sufficient, whereas in the high-load condition, at or above working memory span, auxiliary adaptive cognitive resources are recruited as compensation.

Adult↗

Fear and the amygdala: manipulation of awareness generates differential cerebral responses to phobic and fear-relevant (but nonfeared) stimuli.

Rapid response to danger holds an evolutionary advantage. In this positron emission tomography study, phobics were exposed to masked visual stimuli with timings that either allowed awareness or not of either phobic, fear-relevant (e.g., spiders to snake phobics), or neutral images. When the timing did not permit awareness, the amygdala responded to both phobic and fear-relevant stimuli. With time for more elaborate processing, phobic stimuli resulted in an addition of an affective processing network to the amygdala activity, whereas no activity was found in response to fear-relevant stimuli. Also, right prefrontal areas appeared deactivated, comparing aware phobic and fear-relevant conditions. Thus, a shift from top-down control to an affectively driven system optimized for speed was observed in phobic relative to fear-relevant aware processing.

Adult↗

The effects of literacy and education on the quantitative and qualitative aspects of semantic verbal fluency.

Semantic verbal fluency tasks are commonly used in neuropsychological assessment. Investigations of the influence of level of literacy have not yielded consistent results in the literature. This prompted us to investigate the ecological relevance of task specifics, in particular, the choice of semantic criteria used. Two groups of literate and illiterate subjects were compared on two verbal fluency tasks using different semantic criteria. The performance on a food criterion (supermarket fluency task), considered more ecologically relevant for the two literacy groups, and an animal criterion (animal fluency task) were compared. The data were analysed using both quantitative and qualitative measures. The quantitative analysis indicated that the two literacy groups performed equally well on the supermarket fluency task. In contrast, results differed significantly during the animal fluency task. The qualitative analyses indicated differences between groups related to the strategies used, especially with respect to the animal fluency task. The overall results suggest that there is not a substantial difference between literate and illiterate subjects related to the fundamental workings of semantic memory. However, there is indication that the content of semantic memory reflects differences in shared cultural background--in other words, formal education--, as indicated by the significant interaction between level of literacy and semantic criterion.

Aged↗

Keeping it short: a comparison of methods for brief picture presentation.

Research has shown that backward masking is a powerful tool for studying unconscious mental processes. Whereas studies have traditionally presented stimuli using cathode-ray tube (CRT) monitors or mechanical shutters together with slide projectors, recent studies (mainly in functional magnetic resonance imaging, fMRI) have begun to use methods based on liquid crystal displays (LCDs) and thin-film transistor (TFT) technology. However, because of differences in technology, all methods may not be equally suited for masking. When methods were compared for their accuracy in presenting pictures at short durations, LCD and TFT presentations had poor accuracy, but shutter and CRT presentations had better accuracy. Because CRTs interfere with the imaging process in fMRI, we recommend the use of mechanical shutters. However, our results may not generally apply to all displays, so we advise researchers to validate the presentation parameters of their displays. The procedure described here may be useful for that purpose.

Consciousness↗

Context-dependent deactivation of the amygdala during pain.

The amygdala has been implicated in fundamental functions for the survival of the organism, such as fear and pain. In accord with this, several studies have shown increased amygdala activity during fear conditioning and the processing of fear-relevant material in human subjects. In contrast, functional neuroimaging studies of pain have shown a decreased amygdala activity. It has previously been proposed that the observed deactivations of the amygdala in these studies indicate a cognitive strategy to adapt to a distressful but in the experimental setting unavoidable painful event. In this positron emission tomography study, we show that a simple contextual manipulation, immediately preceding a painful stimulation, that increases the anticipated duration of the painful event leads to a decrease in amygdala activity and modulates the autonomic response during the noxious stimulation. On a behavioral level, 7 of the 10 subjects reported that they used coping strategies more intensely in this context. We suggest that the altered activity in the amygdala may be part of a mechanism to attenuate pain-related stress responses in a context that is perceived as being more aversive. The study also showed an increased activity in the rostral part of anterior cingulate cortex in the same context in which the amygdala activity decreased, further supporting the idea that this part of the cingulate cortex is involved in the modulation of emotional and pain networks.

Adaptation, Psychological↗

Neural correlates of training-related memory improvement in adulthood and aging.

Cognitive studies show that both younger and older adults can increase their memory performance after training in using a visuospatial mnemonic, although age-related memory deficits tend to be magnified rather than reduced after training. Little is known about the changes in functional brain activity that accompany training-induced memory enhancement, and whether age-related activity changes are associated with the size of training-related gains. Here, we demonstrate that younger adults show increased activity during memory encoding in occipito-parietal and frontal brain regions after learning the mnemonic. Older adults did not show increased frontal activity, and only those elderly persons who benefited from the mnemonic showed increased occipito-parietal activity. These findings suggest that age-related differences in cognitive reserve capacity may reflect both a frontal processing deficiency and a posterior production deficiency.

Adult↗

Isolating the retrieval of imagined pictures during episodic memory: activation of the left precuneus and left prefrontal cortex.

The posterior medial parietal cortex and the left prefrontal cortex have both been implicated in the recollection of past episodes. In order to clarify their functional significance, we performed this functional magnetic resonance imaging study, which employed event-related source memory and item recognition retrieval of words paired with corresponding imagined or viewed pictures. Our results suggest that episodic source memory is related to a functional network including the posterior precuneus and the left lateral prefrontal cortex. This network is activated during explicit retrieval of imagined pictures and results from the retrieval of item-context associations. This suggests that previously imagined pictures provide a context with which encoded words can be more strongly associated.

Adult↗

Common prefrontal activations during working memory, episodic memory, and semantic memory.

Regions of the prefrontal cortex (PFC) are typically activated in many different cognitive functions. In most studies, the focus has been on the role of specific PFC regions in specific cognitive domains, but more recently similarities in PFC activations across cognitive domains have been stressed. Such similarities may suggest that a region mediates a common function across a variety of cognitive tasks. In this study, we compared the activation patterns associated with tests of working memory, semantic memory and episodic memory. The results converged on a general involvement of four regions across memory tests. These were located in left frontopolar cortex, left mid-ventrolateral PFC, left mid-dorsolateral PFC and dorsal anterior cingulate cortex. These findings provide evidence that some PFC regions are engaged during many different memory tests. The findings are discussed in relation to theories about the functional contribution of the PFC regions and the architecture of memory.

Adult↗

The irrelevant speech effect: a PET study.

Positron emission tomography (PET) was performed in normal volunteers during a serial recall task under the influence of irrelevant speech comprising both single item repetition and multi-item sequences. An interaction approach was used to identify brain areas specifically related to the irrelevant speech effect. We interpreted activations as compensatory recruitment of complementary working memory processing, and decreased activity in terms of suppression of task relevant areas invoked by the irrelevant speech. The interaction between the distractors and working memory revealed a significant effect in the left, and to a lesser extent in the right, superior temporal region, indicating that initial phonological processing was relatively suppressed. Additional areas of decreased activity were observed in an a priori defined cortical network related to verbal working memory, incorporating the bilateral superior temporal and inferior/middle frontal cortices extending into Broca's area on the left. We also observed a weak activation in the left inferior parietal cortex, a region suggested to reflect the phonological store, the subcomponent where the interference is assumed to take place. The results suggest that the irrelevant speech effect is correlated with and thus tentatively may be explained in terms of a suppression of components of the verbal working memory network as outlined. The results can be interpreted in terms of inhibitory top-down attentional mechanisms attenuating the influence of the irrelevant speech, although additional studies are clearly necessary to more fully characterize the nature of this phenomenon and its theoretical implications for existing short-term memory models.

Acoustic Stimulation↗

Instruction-specific brain activations during episodic encoding. a generalized level of processing effect.

In a within-subject design we investigated the levels-of-processing (LOP) effect using visual material in a behavioral and a corresponding PET study. In the behavioral study we characterize a generalized LOP effect, using pleasantness and graphical quality judgments in the encoding situation, with two types of visual material, figurative and nonfigurative line drawings. In the PET study we investigate the related pattern of brain activations along these two dimensions. The behavioral results indicate that instruction and material contribute independently to the level of recognition performance. Therefore the LOP effect appears to stem both from the relative relevance of the stimuli (encoding opportunity) and an altered processing of stimuli brought about by the explicit instruction (encoding mode). In the PET study, encoding of visual material under the pleasantness (deep) instruction yielded left lateralized frontoparietal and anterior temporal activations while surface-based perceptually oriented processing (shallow instruction) yielded right lateralized frontoparietal, posterior temporal, and occipitotemporal activations. The result that deep encoding was related to the left prefrontal cortex while shallow encoding was related to the right prefrontal cortex, holding the material constant, is not consistent with the HERA model. In addition, we suggest that the anterior medial superior frontal region is related to aspects of self-referential semantic processing and that the inferior parts of the anterior cingulate as well as the medial orbitofrontal cortex is related to affective processing, in this case pleasantness evaluation of the stimuli regardless of explicit semantic content. Finally, the left medial temporal lobe appears more actively engaged by elaborate meaning-based processing and the complex response pattern observed in different subregions of the MTL lends support to the suggestion that this region is functionally segregated.

Adolescent↗

Truncation of the Shaker-like voltage-gated potassium channel, Kv1.1, causes megencephaly.

The megencephaly mouse, mceph/mceph, displays dramatically increased brain volume and hypertrophic brain cells. Despite overall enlargement, the mceph/mceph brain appears structurally normal, without oedema, hydrocephaly or leukodystrophy, and with only minor astrocytosis. Furthermore, it presents striking disturbances in expression of trophic and neuromodulating factors within the hippocampus and cortex. Using a positional cloning approach we have identified the mceph mutation. We show that mceph/mceph mice carry an 11-base-pair deletion in the gene encoding the Shaker-like voltage-gated potassium channel subtype 1, Kcna1. The mutation leads to a frame shift and the predicted MCEPH protein is truncated at amino acid 230 (out of 495), terminating with six aberrant amino acids. The expression of Kcna1 mRNA is increased in the mceph/mceph brain. However, the C-terminal domains of the corresponding Kv1.1 protein are absent. The putative MCEPH protein retains only the N-terminal domains for channel assembly and may congregate nonfunctional complexes of multiple Shaker-like subunits. Indeed, whereas Kcna2 and Kcna3 mRNA expression is normal, the mceph/mceph hippocampus displays decreased amounts of Kv1.2 and Kv1.3 proteins, suggesting interactions at the protein level. We show that mceph/mceph mice have disturbed brain electrophysiology and experience recurrent behavioural seizures, in agreement with the abnormal electrical brain activity found in Shaker mutants. However, in contrast to the commonly demonstrated epilepsy-induced neurodegeneration, we find that the mceph mutation leads to seizures with a concomitant increase in brain size, without overt neural atrophy.

Amino Acid Sequence↗

In vivo biodistribution and pharmacokinetics of (18)F-labeled human C-peptide: evaluation in monkeys using positron emission tomography.

The recently observed beneficial effects exerted by C-peptide in insulin-dependent diabetes patients (IDDM) have instigated research into the mechanisms of C-peptide action as well as the location for it. Here we report in vivo biodistribution studies performed in monkeys using positron emission tomography (PET) and C-peptide labeled in the N-terminal with fluorine-18. Following iv injection of the radiotracer, dynamic decay data were collected over the chest and/or abdomens of the monkeys. The radioactivity distributed mainly to the kidneys, less to the heart and to some extent to the liver. Excretion of radioactivity into the urinary bladder was observed. Brain uptake was not detected in a static emission scan of the head performed at late times. Accumulation of radioactivity in the skeleton as a result of in vivo defluorination was not observed. Pharmacokinetic modeling of the regional concentrations of radioactivity over time resulted, for most organs, in two-compartment models. The organs with the highest radioactivity concentrations have been identified, enabling dose estimations for studies in humans with low or no C-peptide.

Amino Acid Sequence↗

Placebo and opioid analgesia-- imaging a shared neuronal network.

It has been suggested that placebo analgesia involves both higher order cognitive networks and endogenous opioid systems. The rostral anterior cingulate cortex (rACC) and the brainstem are implicated in opioid analgesia, suggesting a similar role for these structures in placebo analgesia. Using positron emission tomography, we confirmed that both opioid and placebo analgesia are associated with increased activity in the rACC. We also observed a covariation between the activity in the rACC and the brainstem during both opioid and placebo analgesia, but not during the pain-only condition. These findings indicate a related neural mechanism in placebo and opioid analgesia.

Adult↗

A regression analysis study of the primary somatosensory cortex during pain.

Several functional imaging studies of pain, using a number of different experimental paradigms and a variety of reference states, have failed to detect activations in the somatosensory cortices, while other imaging studies of pain have reported significant activations in these regions. The role of the somatosensory areas in pain processing has therefore been debated. In the present study the left hand was immersed in painfully cold water (standard cold pressor test) and in nonpainfully cold water during 2 min, and PET-scans were obtained either during the first or the second minute of stimulation. We observed no significant increase of activity in the somatosensory regions when the painful conditions were directly compared with the control conditions. In order to better understand the role of the primary somatosensory cortex (S1) in pain processing we used a regression analysis to study the relation between a ROI (region of interest) in the somatotopic S1-area for the stimulated hand and other regions known to be involved in pain processing. We hypothesized that although no increased activity was observed in the S1 during pain, this region would change its covariation pattern during noxious input as compared to the control stimulation if it is involved in or affected by the processing of pain. In the nonpainful cold conditions widespread regions of the ipsilateral and contralateral somatosensory cortex showed a positive covariation with the activity in the S1-ROI. However, during the first and second minute of pain this regression was significantly attenuated. During the second minute of painful stimulation there was a significant positive covariation between the activity in the S1-ROI and the other regions that are known to be involved in pain processing. Importantly, this relation was significantly stronger for the insula and the orbitofrontal cortex bilaterally when compared to the nonpainful state. The results indicate that the S1-cortex may be engaged in or affected by the processing of pain although no differential activity is observed when pain is compared with the reference condition.

Brain Mapping↗

On the effects of spatial filtering--a comparative fMRI study of episodic memory encoding at high and low resolution.

The effects of spatial filtering in functional magnetic resonance imaging were investigated by reevaluating the data of a previous study of episodic memory encoding at 2 x 2 x 4-mm(3) resolution with use of a SPM99 analysis involving a Gaussian kernel of 8-mm full width at half maximum. In addition, a multisubject analysis of activated regions was performed by normalizing the functional images to an approximate Talairach brain atlas. In individual subjects, spatial filtering merged activations in anatomically separated brain regions. Moreover, small foci of activated pixels which originated from veins became blurred and hence indistinguishable from parenchymal responses. The multisubject analysis resulted in activation of the hippocampus proper, a finding which could not be confirmed by the activation maps obtained at high resolution. It is concluded that the validity of multisubject fMRI analyses can be considerably improved by first analyzing individual data sets at optimum resolution to assess the effects of spatial filtering and minimize the risk of signal contamination by macroscopically visible vessels.

Adult↗