Biomedical subjects

Lars Nyberg

Publications and source records attributed to Lars Nyberg.

At least 19 recordsLinked to original sources

PubMed2021

1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans.

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.

Brain↗

PubMed2006

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↗

PubMed2006

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↗

PubMed2006

The correlative triad among aging, dopamine, and cognition: current status and future prospects.

The brain neuronal systems defined by the neurotransmitter dopamine (DA) have since long a recognized role in the regulation of motor functions. More recently, converging evidence from patient studies, animal research, pharmacological intervention, and molecular genetics indicates that DA is critically implicated also in higher-order cognitive functioning. Many cognitive functions and multiple markers of striatal and extrastriatal DA systems decline across adulthood and aging. Research examining the correlative triad among adult age, DA, and cognition has found strong support for the view that age-related DA losses are associated with age-related cognitive deficits. Future research strategies for examining the DA-cognitive aging link include assessing (a) the generality/specificity of the effects; (b) the relationship between neuromodulation and functional brain activation; and (c) the release of DA during actual task performance.

Aging↗

PubMed2006

Intra-individual variability in behavior: links to brain structure, neurotransmission and neuronal activity.

Intra-individual variability reflects a transient, within-person change in behavioral performance. It is a common component of aging-related cognitive decline and the behavioral changes associated with neurodegenerative and other brain-related disorders such as traumatic brain injury and schizophrenia. Behavioral changes within an individual can reflect alterations at a systems or a cellular level in the brain, and monitoring intra-individual variability can therefore provide a warning of underlying pathology. Despite frequent reports of intra-individual variability, there is little synthesis, and no direct examination of the neural underpinnings. Here, we integrate seminal findings from cognitive research across lifespans of individuals, and also neuropsychological and neurobiological findings, to identify key questions and some potential answers, and to set challenges for fostering future research into intra-individual variability.

Aging↗

PubMed2006

How a lateralized brain supports symmetrical bimanual tasks.

A large repertoire of natural object manipulation tasks require precisely coupled symmetrical opposing forces by both hands on a single object. We asked how the lateralized brain handles this basic problem of spatial and temporal coordination. We show that the brain consistently appoints one of the hands as prime actor while the other assists, but the choice of acting hand is flexible. When study participants control a cursor by manipulating a tool held freely between the hands, the left hand becomes prime actor if the cursor moves directionally with the left-hand forces, whereas the right hand primarily acts if it moves with the opposing right-hand forces. In neurophysiological (electromyography, transcranial magnetic brain stimulation) and functional magnetic resonance brain imaging experiments we demonstrate that changes in hand assignment parallels a midline shift of lateralized activity in distal hand muscles, corticospinal pathways, and primary sensorimotor and cerebellar cortical areas. We conclude that the two hands can readily exchange roles as dominant actor in bimanual tasks. Spatial relationships between hand forces and goal motions determine hand assignments rather than habitual handedness. Finally, flexible role assignment of the hands is manifest at multiple levels of the motor system, from cortical regions all the way down to particular muscles.

Brain↗

PubMed2006

Altered cerebral blood flow in chronic neck pain patients but not in whiplash patients: a 99mTc-HMPAO rCBF study.

A cross-sectional study to investigate regional cerebral blood flow (rCBF) in patients with chronic whiplash syndrome and chronic neck pain patients without previous history of trauma along with a healthy control group. Chronic neck pain is a common disorder and a history of cervical spine injury including whiplash trauma constitute a risk factor for persistent neck pain. The aetiology of the late whiplash syndrome is unknown with no specific diagnostic criteria based on imaging, physiological, or psychological examination. Earlier studies indicate a parieto-occipital hypoperfusion but it is unclear if the hypoperfusion represents a response to chronic pain. The rCBF was monitored in 45 patients with chronic neck pain: 27 cases with chronic whiplash syndrome and 18 age and gender matched cases with non-traumatic chronic neck pain. The rCBF was estimated with single-photon emission computed tomography (SPECT) using technetium-99m hexamethylpropylene amine oxime (HMPAO). The non-traumatic patients displayed rCBF changes in comparison with the whiplash group and the healthy control group. These changes included rCBF decreases in a right temporal region close to hippocampus, and increased rCBF in left insula. The whiplash group displayed no significant differences in rCBF in comparison with the healthy controls. The present study suggests different pain mechanisms in patients with chronic neck pain of non-traumatic origin compared to those with chronic neck pain due to a whiplash trauma.

Adult↗

PubMed2006

Inpatient falls and injuries in older patients treated for femoral neck fracture.

A prospective inpatient study was performed at the Orthopedic and Geriatric Departments at the Umeå University Hospital, Sweden, to study inpatient falls, fall-related injuries, and risk factors for falls following femoral neck fracture surgery. Ninety-seven patients with femoral neck fracture aged 70 years or older were included, background characteristics, falls, injuries, and other postoperative complications were assessed and registered during the hospitalization. There were 60 postoperative falls among 26/97 patients (27%). The postoperative fall event rate was 16.3/1000 Days (95% CI 12.2-20.4). Thirty two percent of the falls resulted in injuries, 25% minor, and 7% serious ones. In multiple regression analyses, delirium after Day 7, HRR 4.62 (95% CI 1.24-16.37), male sex 3.92 (1.58-9.73), and sleeping disturbances 3.49 (1.24-9.86), were associated with inpatient falls. Forty-five percent of the patients were delirious the day they fell. Intervention programs, including prevention and treatment of delirium and sleeping disturbances, as well as better supervision of male patients, could be possible fall prevention strategies. Improvement of the quality of care and rehabilitation, with the focus on fall prevention based on these results, should be implemented in postoperative care of older people.

Accidental Falls↗

PubMed2006

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↗

PubMed2006

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↗

PubMed2006

High-intensity functional exercise program and protein-enriched energy supplement for older persons dependent in activities of daily living: a randomised controlled trial.

The aims of this randomised controlled trial were to determine if a high-intensity functional exercise program improves balance, gait ability, and lower-limb strength in older persons dependent in activities of daily living and if an intake of protein-enriched energy supplement immediately after the exercises increases the effects of the training. One hundred and ninety-one older persons dependent in activities of daily living, living in residential care facilities, and with a Mini-Mental State Examination (MMSE) score of ? 10 participated. They were randomised to a high-intensity functional exercise program or a control activity, which included 29 sessions over 3 months, as well as to protein-enriched energy supplement or placebo. Berg Balance Scale, self-paced and maximum gait speed, and one-repetition maximum in lower-limb strength were followed-up at three and six months and analysed by 2 x 2 factorial ANCOVA, using the intention-to-treat principle. At three months, the exercise group had improved significantly in self-paced gait speed compared with the control group (mean difference 0.04 m/s, p = 0.02). At six months, there were significant improvements favouring the exercise group for Berg Balance Scale (1.9 points, p = 0.05), self-paced gait speed (0.05 m/s, p = 0.009), and lower-limb strength (10.8 kg, p = 0.03). No interaction effects were seen between the exercise and nutrition interventions. In conclusion, a high-intensity functional exercise program has positive long-term effects in balance, gait ability, and lower-limb strength for older persons dependent in activities of daily living. An intake of protein-enriched energy supplement immediately after the exercises does not appear to increase the effects of the training.

Activities of Daily Living↗

PubMed2006

Altered brain activity in healthy seniors: what does it mean?

Age-related performance decreases are frequently observed on various memory tasks. Recent brain imaging studies using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) suggest a link between altered patterns of brain activity in older adults and memory performance. Convergent neuroimaging evidence shows that older adults have decreased activity in multiple regions important for memory tasks. Such relative under-activation in older adults is likely related to age-related reductions in cognitive performance. Age-comparative neuroimaging studies have also provided convincing support for regional over-activation by older adults. Such findings indicate that the older brain can re-organize to better cope with cognitive and other challenges. Although over-activation may play a compensatory role when cognitive decline is limited, under-activation seems to be the typical pattern when cognitive impairment is in a more progressed state. This pattern of age-related changes suggests that compensation through over-activation is restricted to the early stages of cognitive impairment in aging.

Aged↗

PubMed2006

The influence of APOE status on episodic and semantic memory: data from a population-based study.

In a prospective cohort study, the authors demonstrated a more pronounced epsilon4-related deficit for participants 70 years of age and older in tasks assessing episodic recall. Apolipoprotein E (APOE) and age interacted for episodic memory tasks, whereas the interaction for semantic memory tasks was between APOE and test wave. Heterozygotes of epsilon4 between middle-age and young-old participants performed at a higher level than noncarriers of this allele in recall tasks. A dose effect was found such that carriers of 2 epsilon4 alleles failed more profoundly in acquiring and recollecting episodic information than carriers of 1 epsilon4 allele, who in turn failed more than carriers of non-epsilon4 alleles. The pattern of findings observed for older epsilon4 carriers suggests that these individuals have particular difficulty when the executive task demands are high. Several factors (e.g., smaller hippocampal volumes, less effective neural repair mechanisms) may account for these findings. On the basis of the data obtained, the authors argue that analyses of the effect of specific genes in cognition should be accompanied by assessment of performance at a specific level, with due attention to the individual's age.

Adult↗

PubMed2006

Using a virtual reality system to study balance and walking in a virtual outdoor environment: a pilot study.

Falls and fall-related injuries are a major problem for elderly persons. Most falls occur during walking and turning, and the risk of falling increases when attention is diverted to something besides walking. It is often difficult to standardize methods for testing balance and fall tendency in a clinically relevant setting. We describe the development of a system using a virtual environment (VE) to assess how attention demanding and unexpected events influence a person's capacity to control balance and movement. The hardware in the system consists of a head-mounted display (HMD), a magnetic tracker system, and two SGI computers. The software consists of the image generation of the VE and the management and visualization of motion tracking data. In a preliminary pilot study eight subjects (age 23-80) participated. Each subject walked on a normal floor and was visually presented a familiar outdoor environment in the HMD. They were exposed to different unexpected events, such as a virtual snowfall and tilting of the VE. Disturbances of balance and walking patterns such as changes in speed, stride length and balance reactions like slipping were observed. Two subjects experienced symptoms of cyber sickness with a SSQ score above 25 points. Walking with sensors only did not affect walking time, but in VE the subjects generally walked more slowly. Virtual tilting of the environment had an impact on balance performance during walking. This effect was not observed while the test subjects were walking in a virtual snowfall. The model needs further development but may hold a potential for clinical use.

Accidental Falls↗

PubMed2006

A high-intensity functional weight-bearing exercise program for older people dependent in activities of daily living and living in residential care facilities: evaluation of the applicability with focus on cognitive function.

BACKGROUND AND PURPOSE: Knowledge concerning the applicability and the effect of high-intensity exercise programs is very limited for older people with severe cognitive and physical impairments. The primary aim of this study was to evaluate the applicability of a high-intensity functional weight-bearing exercise program among older people who are dependent in activities of daily living and living in residential care facilities. A second aim was to analyze whether cognitive function was associated with the applicability of the program. SUBJECTS: The subjects were 91 older people (mean age=85.3 years, SD=6.1, range=68-100) who were dependent in personal activities of daily living and randomly assigned to participate in an exercise intervention. Their mean score for the Mini-Mental State Examination (MMSE) was 17.5 (SD=5.0, range=10-29). METHODS: A high-intensity functional weight-bearing exercise program was performed in groups of 3 to 7 participants who were supervised by physical therapists. There were 29 exercise sessions over 13 weeks. Attendance, intensity of lower-limb strength and balance exercises, and occurrence and seriousness of adverse events were the outcome variables in evaluating the applicability of the program. RESULTS: The median attendance rate was 76%. Lower-limb strength exercises with high intensity were performed in a median of 53% of the attended exercise sessions, and balance exercises with high intensity were performed in a median of 73% of the attended exercise sessions. The median rate of sessions with adverse events was 5%. All except 2 adverse events were assessed as minor and temporary, and none led to manifest injury or disease. No significant differences were observed in applicability when comparing participants with dementia and participants without dementia. In addition, there was no significant correlation between applicability and the MMSE score. DISCUSSION AND CONCLUSION: The results suggest that a high-intensity functional weight-bearing exercise program is applicable for use, regardless of cognitive function, among older people who are dependent in activities of daily living, living in residential care facilities, and have an MMSE score of 10 or higher.

Activities of Daily Living↗

PubMed2005

Learning by doing versus learning by thinking: An fMRI study of motor and mental training.

Previous studies have documented that motor training improves performance on motor skill tasks and related this to altered functional brain activity in cerebellum, striatum, and frontal motor cortical areas. Mental training can also improve the performance on motor tasks, but the neural basis of such facilitation is unclear. The purpose of the present study was to identify neural correlates of training-related changes on a finger-tapping task. Subjects were scanned twice, 1 week apart, with fMRI while they performed two finger-tapping sequences with the left hand. In-between scans, they practiced daily on one of the sequences. Half of the participants received motor training and the other half received mental training (motor imagery). Both training procedures led to significant increases in tapping performance. This was seen for both the trained and the untrained sequence (non-specific effect), although the gain was larger for the trained sequence (sequence-specific effect). The non-specific training effect corresponded to a reduction in the number of activated areas from an extensive set of brain regions prior to training to mainly motor cortex and cerebellum after training. The sequence-specific training effect involved the supplementary motor area and the cerebellum for motor training and visual association cortex for mental training. We conclude that gains following motor and mental training are based on distinct neuroplastic changes in the brain.

Adult↗

PubMed2005

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↗