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Biomedical subjects

Martin Ingvar

Publications and source records attributed to Martin Ingvar.

At least 19 recordsLinked to original sources

Parietal cortex activation predicts memory decline in apolipoprotein E-epsilon4 carriers.

Apolipoprotein E-epsilon4 is the main known genetic risk factor for Alzheimer's disease. Functional abnormalities in the parietal cortex have been reported for Alzheimer's disease patients and also for those at risk. Hence, a critical question is whether measurements of parietal cortex integrity may predict negative outcome among at-risk persons. We studied nondemented apolipoprotein E-epsilon4 carriers and found a significant relationship between parietal blood-oxygen-level-dependent functional magnetic resonance imaging response during a word categorization task and subsequent episodic memory performance. Thus, the results show that parietal cortex alterations predict memory decline in nondemented apolipoprotein E-epsilon4 carriers, and hence likely progression to Alzheimer's disease.

Aged↗

Interaction between a verbal working memory network and the medial temporal lobe.

The irrelevant speech effect illustrates that sounds that are irrelevant to a visually presented short-term memory task still interfere with neuronal function. In the present study we explore the functional and effective connectivity of such interference. The functional connectivity analysis suggested an interaction between the level of irrelevant speech and the correlation between in particular the left superior temporal region, associated with verbal working memory, and the left medial temporal lobe. Based on this psycho-physiological interaction, and to broaden the understanding of this result, we performed a network analysis, using a simple network model for verbal working memory, to analyze its interaction with the medial temporal lobe memory system. The results showed dissociations in terms of network interactions between frontal as well as parietal and temporal areas in relation to the medial temporal lobe. The results of the present study suggest that a transition from phonological loop processing towards an engagement of episodic processing might take place during the processing of interfering irrelevant sounds. We speculate that, in response to the irrelevant sounds, this reflects a dynamic shift in processing as suggested by a closer interaction between a verbal working memory system and the medial temporal lobe memory system.

Humans↗

Neuroendocrine, cognitive and structural imaging characteristics of women on longterm sickleave with job stress-induced depression.

BACKGROUND: A recent increase in long-term sick leave (LTSL) in Sweden affects mostly women in the public sector. Depression-related diagnoses account for most of the increase, and work-related stress has been implicated. METHODS: We examined dexamethasone/corticotropin-releasing hormone (dex/CRH) test responses, magnetic resonance imaging measures of prefrontocortical and hippocampal volumes, and cognitive performance in 29 female subjects fulfilling three core criteria: 1) LTSL > 90 days; 2) unipolar depression or maladaptive stress reaction with depressed mood; 3) job-related stress given as a reason for disability. This group was compared with 28 healthy matched controls. RESULTS: The cortisol response to CRH differed markedly between the two groups (p = .002), with a dampened response in patients. This difference remained after removing subjects on antidepressant drugs (p = .006) or smokers (p = .003). Neither hippocampal nor prefrontocortical volumes differed. Performance on hippocampus-dependent declarative memory tests did not differ between groups, but the LTSL group had impaired working memory. CONCLUSIONS: Our most salient finding is an attenuated dex-CRH response in patients on LTSL due to job-stress related depression. This is opposite to what has been described in major depression. It remains to be established whether this impairment is the end result of prolonged stress exposure, or a pre-existing susceptibility factor.

Adult↗

Cognitive and neural plasticity in aging: general and task-specific limitations.

There is evidence for cognitive as well as neural plasticity across the adult life span, although aging is associated with certain constraints on plasticity. In the current paper, we argue that the age-related reduction in cognitive plasticity may be due to (a) deficits in general processing resources, and (b) failure to engage in task-relevant cognitive operations. Memory-training research suggests that age-related processing deficits (e.g., executive functions, speed) hinder older adults from utilizing mnemonic techniques as efficiently as the young, and that this age difference is reflected by diminished frontal activity during mnemonic use. Additional constraints on memory plasticity in old age are related to difficulties that are specific to the task, such as creating visual images, as well as in binding together the information to be remembered. These deficiencies are paralleled by reduced activity in occipito-parietal and medial-temporal regions, respectively. Future attempts to optimize intervention-related gains in old age should consider targeting both general processing and task-specific origins of age-associated reductions in cognitive plasticity.

Age Factors↗

Predictability modulates the affective and sensory-discriminative neural processing of pain.

Knowing what is going to happen next, that is, the capacity to predict upcoming events, modulates the extent to which aversive stimuli induce stress and anxiety. We explored this issue by manipulating the temporal predictability of aversive events by means of a visual cue, which was either correlated or uncorrelated with pain stimuli (electric shocks). Subjects reported lower levels of anxiety, negative valence and pain intensity when shocks were predictable. In addition to attenuate focus on danger, predictability allows for correct temporal estimation of, and selective attention to, the sensory input. With functional magnetic resonance imaging, we found that predictability was related to enhanced activity in relevant sensory-discriminative processing areas, such as the primary and secondary sensory cortex and posterior insula. In contrast, the unpredictable more aversive context was correlated to brain activity in the anterior insula and the orbitofrontal cortex, areas associated with affective pain processing. This context also prompted increased activity in the posterior parietal cortex and lateral prefrontal cortex that we attribute to enhanced alertness and sustained attention during unpredictability.

Adult↗

Disruption of order information by irrelevant items: a serial recognition paradigm.

Irrelevant speech effect (ISE) is defined as a decrement in visually presented digit-list short-term memory performance due to exposure to irrelevant auditory material. Perhaps the most successful theoretical explanation of the effect is the changing state hypothesis. This hypothesis explains the effect in terms of confusion between amodal serial order cues, and represents a view based on the interference caused by the processing of similar order information of the visual and auditory materials. An alternative view suggests that the interference occurs as a consequence of the similarity between the visual and auditory contents of the stimuli. An important argument for the former view is the observation that ISE is almost exclusively observed in tasks that require memory for serial order. However, most short-term memory tasks require that both item and order information be retained in memory. An ideal task to investigate the sensitivity of maintenance of serial order to irrelevant speech would be one that calls upon order information but not item information. One task that is particularly suited to address this issue is serial recognition. In a typical serial recognition task, a list of items is presented and then probed by the same list in which the order of two adjacent items has been transposed. Due to the re-presentation of the encoding string, serial recognition requires primarily the serial order to be maintained while the content of the presented items is deemphasized. In demonstrating a highly significant ISE of changing versus steady-state auditory items in a serial recognition task, the present finding lends support for and extends previous empirical findings suggesting that irrelevant speech has the potential to interfere with the coding of the order of the items to be memorized.

Adolescent↗

Neural correlates of artificial syntactic structure classification.

The human brain supports acquisition mechanisms that extract structural regularities implicitly from experience without the induction of an explicit model. It has been argued that the capacity to generalize to new input is based on the acquisition of abstract representations, which reflect underlying structural regularities in the input ensemble. In this study, we explored the outcome of this acquisition mechanism, and to this end, we investigated the neural correlates of artificial syntactic classification using event-related functional magnetic resonance imaging. The participants engaged once a day during an 8-day period in a short-term memory acquisition task in which consonant-strings generated from an artificial grammar were presented in a sequential fashion without performance feedback. They performed reliably above chance on the grammaticality classification tasks on days 1 and 8 which correlated with a corticostriatal processing network, including frontal, cingulate, inferior parietal, and middle occipital/occipitotemporal regions as well as the caudate nucleus. Part of the left inferior frontal region (BA 45) was specifically related to syntactic violations and showed no sensitivity to local substring familiarity. In addition, the head of the caudate nucleus correlated positively with syntactic correctness on day 8 but not day 1, suggesting that this region contributes to an increase in cognitive processing fluency.

Adult↗

Reduced functional brain activity response in cognitively intact apolipoprotein E epsilon4 carriers.

The apolipoprotein E epsilon4 (APOE epsilon4) is the main known genetic risk factor for Alzheimer's disease. Genetic assessments in combination with other diagnostic tools, such as neuroimaging, have the potential to facilitate early diagnosis. In this large-scale functional MRI (fMRI) study, we have contrasted 30 APOE epsilon4 carriers (age range: 49-74 years; 19 females), of which 10 were homozygous for the epsilon4 allele, and 30 non-carriers with regard to brain activity during a semantic categorization task. Test groups were closely matched for sex, age and education. Critically, both groups were cognitively intact and thus symptom-free of Alzheimer's disease. APOE epsilon4 carriers showed reduced task-related responses in the left inferior parietal cortex, and bilaterally in the anterior cingulate region. A dose-related response was observed in the parietal area such that diminution was most pronounced in homozygous compared with heterozygous carriers. In addition, contrasts of processing novel versus familiar items revealed an abnormal response in the right hippocampus in the APOE epsilon4 group, mainly expressed as diminished sensitivity to the relative novelty of stimuli. Collectively, these findings indicate that genetic risk translates into reduced functional brain activity, in regions pertinent to Alzheimer's disease, well before alterations can be detected at the behavioural level.

Aged↗

Reduced hippocampal volume in non-demented carriers of the apolipoprotein E epsilon4: relation to chronological age and recognition memory.

Apolipoprotein E epsilon4 (APOE epsilon4) is the main known genetic risk factor for Alzheimer's disease (AD). Some previous studies have reported structural brain changes as well as cognitive deficits in non-demented APOE epsilon4 carriers, but the pattern of results is inconsistent and studies with larger sample sizes have been called for. Here we compared hippocampal volume and recognition-memory performance between AD-symptom-free carriers (N=30) and non-carriers (N=30) of the APOE epsilon4 (age range: 49-79 years). We observed reduced right hippocampal volume in APOE epsilon4 carriers, and found that the difference was most pronounced before the age of 65. Further, the APOE epsilon4 carriers made significantly more false alarms in the recognition-memory test, and the number of false alarms correlated significantly with right hippocampus volume. These results indicate that relatively young individuals at genetic risk for AD have smaller hippocampal volume and lower performance on hippocampal-dependent cognitive tasks. A question for the future is whether smaller hippocampal volume represents early-onset hippocampal volume reduction or an inherent trait.

Age Factors↗

Morphometric and psychometric comparisons between non-substance-abusing patients with posttraumatic stress disorder and normal controls.

BACKGROUND: Hippocampal decrease in size in response to posttraumatic stress disorder (PTSD) is still a subject of controversy. The aims of this study were to: (1) confirm previous hippocampus findings in PTSD patients compared to controls, using ethnically similar study groups where alcohol and drug abuse were non-existent; (2) test influence of disease duration as well as depression scores on possible morphological changes; (3) test whether the voxel-based morphometry (VBM) data confirm the group differences seen in the region of interest (ROI) analysis, and (4) test the associations between the cognitive test scores and the morphological changes. METHODS: VBM and ROI-based analysis were applied in 23 patients and 17 healthy controls. Culture-neutral cognitive tests were used. RESULTS: The ROI-based method showed significantly decreased gray matter volumes for global hippocampal volume, as in a separate analysis of left and right sides in the PTSD group. Total volume of the hippocampus was significantly decreased on the left side, as in the global assessment. A multiple regression VBM model showed significant voxel clusters for group affiliation in the right hippocampus, modelling lowering of gray matter associated with the PTSD group. Disease duration was shown to be negatively correlated to bilateral hippocampal volume and high depression score to bilateral gray matter parahippocampal volume. No significant correlations were found between hippocampal or parahippocampal volumes and cognitive functions. CONCLUSION: The present and previous studies showed that morphologic differences do not appear to be due to drug or alcohol abuse. The VBM data partially confirm the group differences seen in the ROI-based method in the medial temporal lobe. The fact that the significantly lower score on the short-term memory test in the PTSD group is not correlated to hippocampal volume may suggest a more general basis for such memory impairment.

Adult↗

Color makes a difference: two-dimensional object naming in literate and illiterate subjects.

Previous work has shown that illiterate subjects are better at naming two-dimensional representations of real objects when presented as colored photos as compared to black and white drawings. This raises the question if color or textural details selectively improve object recognition and naming in illiterate compared to literate subjects. In this study, we investigated whether the surface texture and/or color of objects is used to access stored object knowledge in illiterate subjects. A group of illiterate subjects and a matched literate control group were compared on an immediate object naming task with four conditions: color and black and white (i.e., grey-scaled) photos, as well as color and black and white (i.e., grey-scaled) drawings of common everyday objects. The results show that illiterate subjects perform significantly better when the stimuli are colored and this effect is independent of the photographic detail. In addition, there were significant differences between the literacy groups in the black and white condition for both drawings and photos. These results suggest that color object information contributes to object recognition. This effect was particularly prominent in the illiterate group.

Adult↗

The role of precuneus and left inferior frontal cortex during source memory episodic retrieval.

The posterior medial parietal cortex and left prefrontal cortex (PFC) have both been implicated in the recollection of past episodes. In a previous study, we found the posterior precuneus and left lateral inferior frontal cortex to be activated during episodic source memory retrieval. This study further examines the role of posterior precuneal and left prefrontal activation during episodic source memory retrieval using a similar source memory paradigm but with longer latency between encoding and retrieval. Our results suggest that both the precuneus and the left inferior PFC are important for regeneration of rich episodic contextual associations and that the precuneus activates in tandem with the left inferior PFC during correct source retrieval. Further, results suggest that the left ventro-lateral frontal region/frontal operculum is involved in searching for task-relevant information (BA 47) and subsequent monitoring or scrutiny (BA 44/45) while regions in the dorsal inferior frontal cortex are important for information selection (BA 45/46).

Adult↗

Structure-function correlates of cognitive decline in aging.

To explore neural correlates of cognitive decline in aging, we used longitudinal behavioral data to identify two groups of older adults (n = 40) that differed with regard to whether their performance on tests of episodic memory remained stable or declined over a decade. Analysis of structural and diffusion tensor imaging (DTI) revealed a heterogeneous set of differences associated with cognitive decline. Manual tracing of hippocampal volume showed significant reduction in those older adults with a declining memory performance as did DTI-measured fractional anisotropy in the anterior corpus callosum. Functional magnetic resonance imaging during incidental episodic encoding revealed increased activation in left prefrontal cortex for both groups and additional right prefrontal activation for the elderly subjects with the greatest decline in memory performance. Moreover, mean DTI measures in the anterior corpus callosum correlated negatively with activation in right prefrontal cortex. These results demonstrate that cognitive decline is associated with differences in the structure as well as function of the aging brain, and suggest that increased activation is either caused by structural disruption or is a compensatory response to such disruption.

Adaptation, Physiological↗

"Anxiebo", placebo, and postoperative pain.

BACKGROUND: Surgical treatment and its consequences expose patients to stress, and here we investigated the importance of the psychological component of postoperative pain based on reports in the clinical literature. DISCUSSION: Postoperative pain remains a significant clinical problem. Increased pain intensity with increased demand for opioid medication, and/or a relative unresponsiveness to pain treatment was reported both when the analgesia was administered by means of conventional nurse injection regimes and patient-controlled analgesia (PCA). Both the quality of the analgesia, and the sensitivity of postoperative models for assessing analgesic efficacy could be significantly influenced. The findings could be explained by increased penetration of an algesic anxiety-related nocebo influence (which we chose to call "anxiebo") relative to its analgesic placebo counterpart. To counteract this influence, the importance of psychological effects must be acknowledged, and doctors and attending nurses should focus on maintaining trustful therapist-patient relationships throughout the treatment period. The physical mechanism of anxiebo should be further explored, and those at risk for anxiebo better characterized. In addition, future systemic analgesic therapies should be directed towards being prophylactic and continuous to eliminate surgical pain as it appears in order to prevent the anxiebo effect. Addressing anxiebo is the key to developing reproducible models for measuring pain in the postoperative setting, and to improving the accuracy of measurements of the minimum effective analgesic concentration. SUMMARY: Anxiebo and placebo act as counterparts postoperatively. The anxiebo state may impair clinical analgesia and reduce the sensitivity of analgesic trials. Ways to minimize anxiebo are discussed.

Journal Article↗

Placebo in emotional processing--induced expectations of anxiety relief activate a generalized modulatory network.

Placebo analgesia and reward processing share several features. For instance, expectations have a strong influence on the subsequent emotional experience of both. Recent imaging data indicate similarities in the underlying neuronal network. We hypothesized that placebo analgesia is a special case of reward processing and that placebo treatment could modulate emotional perception in the same way as does pain perception. The behavioral part of this study indicates that placebo treatment has an effect on how subjects perceive unpleasant pictures. Furthermore, event-related fMRI demonstrated that the same modulatory network, including the rostral anterior cingulate cortex and the lateral orbitofrontal cortex, is involved in both emotional placebo and placebo analgesia. These effects were correlated with the reported placebo effect and were predicted by the amount of treatment expectation induced on a previous day. Thus, the placebo effect may be considered to be a general process of modulation induced by the subjects' expectations.

Adult↗

Effect of low doses of ionising radiation in infancy on cognitive function in adulthood: Swedish population based cohort study.

OBJECTIVE: To determine whether exposure to low doses of ionising radiation in infancy affects cognitive function in adulthood. DESIGN: Population based cohort study. SETTING: Sweden. PARTICIPANTS: 3094 men who had received radiation for cutaneous haemangioma before age 18 months during 1930-59. MAIN OUTCOME MEASURES: Radiation dose to frontal and posterior parts of the brain, and association between dose and intellectual capacity at age 18 or 19 years based on cognitive tests (learning ability, logical reasoning, spatial recognition) and high school attendance. RESULTS: The proportion of boys who attended high school decreased with increasing doses of radiation to both the frontal and the posterior parts of the brain from about 32% among those not exposed to around 17% in those who received > 250 mGy. For the frontal dose, the multivariate odds ratio was 0.47 (95% confidence interval 0.26 to 0.85, P for trend 0.0003) and for the posterior dose it was 0.59 (0.23 to 1.47, 0.0005). A negative dose-response relation was also evident for the three cognitive tests for learning ability and logical reasoning but not for the test of spatial recognition. CONCLUSIONS: Low doses of ionising radiation to the brain in infancy influence cognitive abilities in adulthood.

Adolescent↗