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Lars Bäckman
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Journal Articles
Publisher: Journals Gateway
Journal of Cognitive Neuroscience (2019) 31 (10): 1491–1505.
Published: 01 October 2019
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Goal-irrelevant information may interfere with ongoing task activities if not controlled properly. Evidence suggests that the ability to control interference is connected mainly to the prefrontal cortex (pFC). However, it remains unclear whether gray matter (GM) volume in prefrontal regions influences individual differences in interference control (IC) and if these relationships are affected by aging. Using cross-sectional and longitudinal estimates over a 4- to 5-year period, we examined the relationship between relative IC scores, obtained from a 2-back working memory task, GM volumes, and performance in different cognitive domains. By identifying individuals with either no or high levels of interference, we demonstrated that participants with superior IC had larger volume of the ventrolateral pFC, regardless of participant demographics. The same pattern was observed both at baseline and follow-up. Cross-sectional estimates further showed that interference increased as a function of age, but interference did not change between baseline and follow-up. Similarly, across-sample associations between IC and pFC volume were found in the cross-sectional data, along with no longitudinal change–change relationships. Moreover, relative IC scores could be linked to composite scores of fluid intelligence, indicating that control of interference may relate to performance in expected cognitive domains. These results provide new evidence that a relative IC score can be related to volume of specific and relevant regions within pFC and that this relationship is not modulated by age. This supports a view that the GM volume in these regions plays a role in resisting interference during a working memory task.
Journal Articles
Publisher: Journals Gateway
Journal of Cognitive Neuroscience (2019) 31 (9): 1422–1429.
Published: 01 September 2019
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Episodic memory is a polygenic trait influenced by different molecular mechanisms. We used PET and a candidate gene approach to investigate how individual differences at the molecular level translate into between-person differences in episodic memory performance of elderly persons. Specifically, we examined the interactive effects between hippocampal dopamine D2 receptor (D2DR) availability and candidate genes relevant for hippocampus-related memory functioning. We show that the positive effects of high D2DR availability in the hippocampus on episodic memory are confined to carriers of advantageous genotypes of the brain-derived neurotrophic factor ( BDNF , rs6265) and the kidney and brain expressed protein ( KIBRA , rs17070145) polymorphisms. By contrast, these polymorphisms did not modulate the positive relationship between caudate D2DR availability and episodic memory.
Journal Articles
Publisher: Journals Gateway
Journal of Cognitive Neuroscience (2019) 31 (2): 314–325.
Published: 01 February 2019
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The dopamine (DA) system plays an important role in cognition. Accordingly, normal variation in DA genes has been found to predict individual differences in cognitive performance. However, little is known of the impact of genetic differences on the link between empirical indicators of the DA system and cognition in humans. The present work used PET with 11 C-raclopride to assess DA D2-receptor binding potential (BP) and links to episodic memory, working memory, and perceptual speed in 179 healthy adults aged 64–68 years. Previously, the T-allele of a DA D2-receptor single-nucleotide polymorphism, C957T , was associated with increased apparent affinity of 11 C-raclopride, giving rise to higher BP values despite similar receptor density values between allelic groups. Consequently, we hypothesized that 11 C-raclopride BP measures inflated by affinity rather than D2-receptor density in T-allele carriers would not be predictive of DA integrity and therefore prevent finding an association between 11 C-raclopride BP and cognitive performance. In accordance with previous findings, we show that 11 C-raclopride BP was increased in T-homozygotes. Importantly, 11 C-raclopride BP was only associated with cognitive performance in groups with low or average ligand affinity (C-allele carriers of C957T , n = 124), but not in the high-affinity group (T-homozygotes, n = 55). The strongest 11 C-raclopride BP–cognition associations and the highest level of performance were found in C-homozygotes. These findings show that genetic differences modulate the link between BP and cognition and thus have important implications for the interpretation of DA assessments with PET and 11 C-raclopride in multiple disciplines ranging from cognitive neuroscience to psychiatry and neurology.
Journal Articles
Publisher: Journals Gateway
Journal of Cognitive Neuroscience (2017) 29 (2): 245–253.
Published: 01 February 2017
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Previous research shows that associative memory declines more than item memory in aging. Although the underlying mechanisms of this selective impairment remain poorly understood, animal and human data suggest that dopaminergic modulation may be particularly relevant for associative binding. We investigated the influence of dopamine (DA) receptor genes on item and associative memory in a population-based sample of older adults ( n = 525, aged 60 years), assessed with a face–scene item associative memory task. The effects of single-nucleotide polymorphisms of DA D1 ( DRD1 ; rs4532), D2 ( DRD2/ANKK1/Taq1A ; rs1800497), and D3 ( DRD3 / Ser9Gly ; rs6280) receptor genes were examined and combined into a single genetic score. Individuals carrying more beneficial alleles, presumably associated with higher DA receptor efficacy ( DRD1 C allele; DRD2 A2 allele; DRD3 T allele), performed better on associative memory than persons with less beneficial genotypes. There were no effects of these genes on item memory or other cognitive measures, such as working memory, executive functioning, fluency, and perceptual speed, indicating a selective association between DA genes and associative memory. By contrast, genetic risk for Alzheimer disease (AD) was associated with worse item and associative memory, indicating adverse effects of APOE ε4 and a genetic risk score for AD ( PICALM , BIN1 , CLU ) on episodic memory in general. Taken together, our results suggest that DA may be particularly important for associative memory, whereas AD-related genetic variations may influence overall episodic memory in older adults without dementia.
Journal Articles
Publisher: Journals Gateway
Journal of Cognitive Neuroscience (2013) 25 (4): 571–579.
Published: 01 April 2013
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Emerging evidence from animal studies suggests that suboptimal dopamine (DA) modulation may be associated with increased forgetting of episodic information. Extending these observations, we investigated the influence of DA-relevant genes on forgetting in samples of younger ( n = 433, 20–31 years) and older ( n = 690, 59–71 years) adults. The effects of single nucleotide polymorphisms of the DA D2 (DRD2) and D3 (DRD3) receptor genes as well as the DA transporter gene (DAT1; SLC6A3) were examined. Over the course of one week, older adults carrying two or three genotypes associated with higher DA signaling (i.e., higher availability of DA and DA receptors) forgot less pictorial information than older individuals carrying only one or no beneficial genotype. No such genetic effects were found in younger adults. The results are consistent with the view that genetic effects on cognition are magnified in old age. To the best of our knowledge, this is the first report to relate genotypes associated with suboptimal DA modulation to more long-term forgetting in humans. Independent replication studies in other populations are needed to confirm the observed association.
Journal Articles
Publisher: Journals Gateway
Journal of Cognitive Neuroscience (2011) 23 (8): 2030–2045.
Published: 01 August 2011
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Individual differences in working memory (WM) performance have rarely been related to individual differences in the functional responsivity of the WM brain network. By neglecting person-to-person variation, comparisons of network activity between younger and older adults using functional imaging techniques often confound differences in activity with age trends in WM performance. Using functional magnetic resonance imaging, we investigated the relations among WM performance, neural activity in the WM network, and adult age using a parametric letter n -back task in 30 younger adults (21–31 years) and 30 older adults (60–71 years). Individual differences in the WM network's responsivity to increasing task difficulty were related to WM performance, with a more responsive BOLD signal predicting greater WM proficiency. Furthermore, individuals with higher WM performance showed greater change in connectivity between left dorsolateral prefrontal cortex and left premotor cortex across load. We conclude that a more responsive WM network contributes to higher WM performance, regardless of adult age. Our results support the notion that individual differences in WM performance are important to consider when studying the WM network, particularly in age-comparative studies.
Journal Articles
Publisher: Journals Gateway
Journal of Cognitive Neuroscience (2010) 22 (10): 2164–2173.
Published: 01 October 2010
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The brain-derived neurotrophic factor (BDNF) plays an important role in activity-dependent synaptic plasticity, which underlies learning and memory. In a sample of 948 younger and older adults, we investigated whether a common Val 66 Met missense polymorphism (rs6265) in the BDNF gene affects the serial position curve—a fundamental phenomenon of associative memory identified by Hermann Ebbinghaus more than a century ago. We found a BDNF polymorphism effect for backward recall in older adults only, with Met-allele carriers (i.e., individuals with reduced BDNF signaling) recalling fewer items than Val homozygotes. This effect was specific to the primacy and middle portions of the serial position curve, where intralist interference and associative demands are especially high. The poorer performance of older Met-allele carriers reflected transposition errors, whereas no genetic effect was found for omissions. These findings indicate that effects of the BDNF polymorphism on episodic memory are most likely to be observed when the associative and executive demands are high. Furthermore, the findings are in line with the hypothesis that the magnitude of genetic effects on cognition is greater when brain resources are reduced, as is the case in old age.
Journal Articles
Publisher: Journals Gateway
Journal of Cognitive Neuroscience (2010) 22 (7): 1614–1622.
Published: 01 July 2010
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The catechol O -methyltransferase (COMT) gene—encoding an enzyme that is essential for the degradation of dopamine (DA) in prefrontal cortex (PFC)—contains a single nucleotide polymorphism (val/met) important for cognition. According to the tonic–phasic hypothesis, individuals carrying the low-enzyme-activity allele (met) are characterized by enhanced tonic DA activity in PFC, promoting sustained cognitive representations in working memory. Val carriers have reduced tonic but enhanced phasic dopaminergic activity in subcortical regions, enhancing cognitive flexibility. We tested the tonic–phasic DA hypothesis by dissociating sustained and transient brain activity during performance on a 2-back working memory test using mixed blocked/event-related functional magnetic resonance imaging. Participants were men recruited from a random sample of the population (the Betula study) and consisted of 11 met/met and 11 val/val carriers aged 50 to 65 years, matched on age, education, and cognitive performance. There were no differences in 2-back performance between genotype groups. Met carriers displayed a greater transient medial temporal lobe response in the updating phase of working memory, whereas val carriers showed a greater sustained PFC activation in the maintenance phase. These results support the tonic–phasic theory of DA function in elucidating the specific phenotypic influence of the COMT val 158 met polymorphism on different components of working memory.
Journal Articles
Publisher: Journals Gateway
Journal of Cognitive Neuroscience (2008) 20 (5): 779–786.
Published: 01 May 2008
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Intraindividual variability (IIV) in cognitive performance shares systematic associations with aging-related processes, brain injury, and neurodegenerative pathology. However, little research has examined the neural underpinnings of IIV, with no studies investigating brain correlates of IIV in relation to retrieval success. Using functional magnetic resonance imaging, we examined links between IIV, recognition memory performance, and blood oxygenation level dependent activations. Nineteen older adults (70–79 years) were presented with 80 words at encoding, with brain scans and response latencies obtained during subsequent recognition. An index of IIV, the intraindividual standard deviation (ISD), was computed across successful latency trials. Decreasing ISDs were systematically associated with better recognition, faster latencies, and increased activation in the inferior parietal cortex (BA 40). Demonstrated links between less behavioral variability and parietal activations are consistent with the known importance of the parietal cortex for retrieval success. In support of extant findings and theory from neuroscience, neuropsychology, and cognitive aging, the present results suggest that behavioral IIV represents a proxy for neural integrity.
Journal Articles
Publisher: Journals Gateway
Journal of Cognitive Neuroscience (2000) 12 (1): 134–141.
Published: 01 January 2000
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Patients with Alzheimer's disease (AD) are often impaired on certain forms of implicit memory, such as word-stem completion priming (WSCP). Lesion data suggest that deficient WSCP may be associated with abnormal functioning in the posterior neocortex. Using positron emission tomography (PET), we here provide direct support for this view. Compared with normal old adults, AD patients showed reduced priming on a word-stem completion task. The normal old showed decreased activity in right occipital cortex (area 19), whereas the AD patients showed increased activity in this region during priming. To the extent that decreased activity during priming reflects an experience-dependent reduction of the neuronal population involved, these results indicate that shaping of the relevant neurons is slower in AD, possibly as a result of inadequate initial-stimulus processing.
Journal Articles
Publisher: Journals Gateway
Journal of Cognitive Neuroscience (1997) 9 (3): 378–391.
Published: 01 May 1997
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Positron emission tomography was used to study regional cerebral blood flow (H 2 15 O method) in groups of young and older adults during implicit and explicit retrieval, following a procedure devised by Squire et al. (1992). At study, subjects were exposed to four lists of words. Following list presentation, subjects were presented with three-letter word stems under four conditions: (1) silent viewing, (2) completion of word stems that could not form words from the study list, with the instruction to provide the first word that came to mind (baseline), (3) completion of word stems, half of which could form words from the study list, with the instruction to provide the first word that came to mind (priming), and (4) completion of word stems, half of which could form words from the study list, with the instruction to use the stems as cues for recall of list words (memory). The behavioral data indicated an agerelated deficit in cued recall that was reduced in priming. Both age groups showed a similar decrease of blood flow in right posterior cortex during priming relative to baseline. During cued recall, bilateral increases of blood flow were observed in prefrontal cortex and anterior cingulate gyrus for both age groups. The young adults showed selective increases of activity in left cerebellum and Wernicke's area, whereas the older adults showed a selective bilateral activation in the perirhinal region of the medial-temporal cortex during cued recall. The results suggest a simiiar biological basis of priming in both age groups: a decrease in the neural activity required to process a particular stimulus during a subsequent encounter compared with a previous one. In addition, the importance of prefrontal regions for conscious retrieval was substantiated and extended to late adulthood. Finally, the agedifferential activations observed during cued recall were discussed relative to prominent concepts in the current literature on cognitive aging (e.g., speed of processing, self-initiated operations, cross-modal recoding).