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  • 1.
    Arshamian, Artin
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Iannilli, Emilia
    Gerber, Johannes C.
    Willander, Johan
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Persson, Jonas
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Seo, Han-Seok
    Hummel, Thomas
    Larsson, Maria
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    The functional neuroanatomy of odor evoked autobiographical memories cued by odors and words2013In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 51, no 1, p. 123-131Article in journal (Refereed)
    Abstract [en]

    Behavioral evidence indicates that odor evoked autobiographical memories (OEAMs) are older, more emotional, less thought of and induce stronger time traveling characteristics than autobiographical memories (AMs) evoked by other modalities. The main aim of this study was to explore the neural correlates of AMs evoked by odors as a function of retrieval cue. Participants were screened for specific OEAMs and later presented with the odor cue and its verbal referent in an fMRI paradigm. Because the same OEAM was retrieved across both cue formats (odor and word), potential cue dependent brain activations were investigated. The overall results showed that odor and word cued OEAMs activated regions typically associated with recollection of autobiographical information. Although no odors were presented, a verbal cuing of the OEAMs activated areas associated with olfactory perception (e.g., piriform cortex). However, relative to word cuing, an odor cuing of OEAMs resulted in more activity in MTL regions such as the parahippocampus, and areas involved in visual vividness (e.g., occipital gyrus and precuneus). Furthermore, odor cues activated areas related to emotional processing, such as limbic and tempopolar regions significantly more. In contrast, word cues relative to odor cues recruited a more widespread and bilateral prefrontal activity. Hippocampus activity did not vary as function of the remoteness of the memory, but recollection of OEAMs from the 1st vs the 2nd decade of life showed specific activation in the right OFC, whereas the 2nd reflected a higher activation in the left inferior frontal gyrus.

  • 2.
    Bellander, Martin
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Brehmer, Yvonne
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Westerberg, Helena
    Karlsson, Sari
    Fürth, Daniel
    Bergman, Olle
    Eriksson, Elias
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Preliminary evidence that allelic variation in the LMX1A gene influences training-related working memory improvement2011In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 49, no 7, p. 1938-42Article in journal (Refereed)
    Abstract [en]

    LMX1A is a transcription factor involved in the development of dopamine (DA)-producing neurons in midbrain. Previous research has shown that allelic variations in three LMX1A single nucleotide polymorphisms (SNPs) were related to risk of Parkinson's disease (PD), suggesting that these SNPs may influence the number of mesencephalic DA neurons. Prompted by the established link between striatal DA functions and working memory (WM) performance, we examined two of these SNPs in relation to the ability to benefit from 4 weeks of WM training. One SNP (rs4657412) was strongly associated with the magnitude of training-related gains in verbal WM. The allele linked to larger gains has previously been suggested to be associated with higher dopaminergic nerve cell density. No differential gains of either SNP were observed for spatial WM, and the genotype groups were also indistinguishable in tests of attention, interference control, episodic memory, perceptual speed, and reasoning for both SNPs. This pattern of data is in agreement with previous findings from our group, suggesting that cognitive effects of DA-related genes may be more easily detected in a training context than for single-assessment performance scores.

  • 3. Boraxbekk, C. J.
    et al.
    Hagkvist, Filip
    Lindner, Philip
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Clinical psychology. Umeå University, Sweden; Karolinska Institutet, Sweden.
    Motor and mental training in older people: Transfer, interference, and associated functional neural responses2016In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 89, p. 371-377Article in journal (Refereed)
    Abstract [en]

    Learning new motor skills may become more difficult with advanced age. In the present study, we randomized 56 older individuals, including 30 women (mean age 70.6 years), to 6 weeks of motor training, mental (motor imagery) training, or a combination of motor and mental training of a finger tapping sequence. Performance improvements and post-training functional magnetic resonance imaging (fMRI) were used to investigate performance gains and associated underlying neural processes. Motor only training and a combination of motor and mental training improved performance in the trained task more than mental-only training. The fMRI data showed that motor training was associated with a representation in the premotor cortex and mental training with a representation in the secondary visual cortex. Combining motor and mental training resulted in both premotor and visual cortex representations. During fMRI scanning, reduced performance was observed in the combined motor and mental training group, possibly indicating interference between the two training methods. We concluded that motor and motor imagery training in older individuals is associated with different functional brain responses. Furthermore, adding mental training to motor training did not result in additional performance gains compared to motor-only training and combining training methods may result in interference between representations, reducing performance.

  • 4. Kauppi, Karolina
    et al.
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Adolfsson, Rolf
    Lundquist, Anders
    Eriksson, Elias
    Nyberg, Lars
    Decreased medial temporal lobe activation in BDNF 66Met allele carriers during memory encoding2013In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 51, no 12, p. 2462-2468Article in journal (Refereed)
    Abstract [en]

    The Met allele of the Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with impaired activity-dependent secretion of BDNF protein and decreased memory performance. Results from imaging studies relating Val66Met to brain activation during memory processing have been inconsistent, with reports of both increased and decreased activation in the Medial Temporal Lobe (MTL) in Met carriers relative to Val homozygotes. Here, we extensively studied BDNF Val66Met in relation to brain activation and white matter integrity as well as memory performance in a large imaging (n=194) and behavioral (n=2229) sample, respectively. Functional magnetic resonance imaging (fMRI) was used to investigate MTL activation in healthy participants in the age of 55–75 years during a face-name episodic encoding and retrieval task. White matter integrity was measured using diffusion tensor imaging.

    BDNF Met allele carriers had significantly decreased activation in the MTL during encoding processes, but not during retrieval processes. In contrast to previous proposals, the effect was not modulated by age and the polymorphism was not related to white matter integrity. Met carriers had lower memory performance than Val homozygotes, but differences were subtle and not significant. In conclusion, the BDNF Met allele has a negative influence on MTL functioning, preferentially during encoding processes, which might translate into impaired episodic memory function.

  • 5.
    Lövdén, Martin
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Bodammer, Nils Christian
    Kühn, Simone
    Kaufmann, Jörn
    Schütze, Hartmut
    Tempelmann, Claus
    Heinze, Hans-Jochen
    Düzel, Emrah
    Schmiedek, Florian
    Lindenberger, Ulman
    Experience-dependent plasticity of white-matter microstructure extends into old age2010In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 48, no 13, p. 3878-3883Article in journal (Refereed)
    Abstract [en]

    Experience-dependent alterations in the human brain's white-matter microstructure occur in early adulthood, but it is unknown whether such plasticity extends throughout life. We used cognitive training, diffusion-tensor imaging (DTI), and structural MRI to investigate plasticity of the white-matter tracts that connect the left and right hemisphere of the frontal lobes. Over a period of about 180 days, 20 younger adults and 12 older adults trained for a total of one hundred and one 1-h sessions on a set of three working memory, three episodic memory, and six perceptual speed tasks. Control groups were assessed at pre- and post-test. Training affected several DTI metrics and increased the area of the anterior part of the corpus callosum. These alterations were of similar magnitude in younger and older adults. The findings indicate that experience-dependent plasticity of white-matter microstructure extends into old age and that disruptions of structural interhemispheric connectivity in old age, which are pronounced in aging, are modifiable by experience and amenable to treatment.

  • 6.
    Olofsson, Jonas K.
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Perception and psychophysics. Swedish Collegium for Advanced Study, Sweden.
    Josefsson, Maria
    Ekström, Ingrid
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Perception and psychophysics.
    Wilson, Donald
    Nyberg, Lars
    Nordin, Steven
    Nordin Adolfsson, Annelie
    Adolfsson, Rolf
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Cognitive psychology.
    Larsson, Maria
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Perception and psychophysics.
    Long-term episodic memory decline is associated with olfactory deficits only in carriers of ApoE-є42016In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 85, p. 1-9Article in journal (Refereed)
    Abstract [en]

    The ɛ4 allele of the Apolipoprotein E gene is a genetic risk factor for late-onset dementia of the Alzheimers' type (DAT), which is characterized by loss of both episodic memoryand olfactory functions. Little is known about the possible role of ɛ4 in the association between ongoing episodic memory decline and olfactory deficits in the general population, but such information is relevant in determining the relevance of olfaction as a marker of DAT risk. The present study was based on a large, population-based sample (n=1087, aged 45–90 years, of which 324 were ɛ4-carriers). Episodic memory change rates were established using data collected every 5 years for a 10–20 year interval leading up to an olfactory assessment using the Scandinavian Odor Identification Test at the last wave of data collection. Participants were classified according to whether or not their episodic memory ability declined more rapidly than the age-typical norm (by >1SD). Our main result is that only in ɛ4-carriers was episodic memory decline associated with odor identification impairment. In individuals without ɛ4, odor identification was unrelated to episodic memory decline status. Follow-up analyses indicated that this moderation by ɛ4 was due to the olfactory nature of the identification test, and that the effect was not caused by 63 individuals with dementia. Our results suggest that the ɛ4 determines the functional association between ongoing episodic memory decline and olfaction. These findings are consistent with the notion that ɛ4-carriers with DAT, compared to non-carriers, display a cortical atrophy pattern that is more focused on mediotemporal lobe regions supporting olfactory and episodic memory functions. Olfactory and memory assessments might provide complementary information on mediotemporal atrophy prior to clinical dementia onset, but the ɛ4 should be considered when using olfactory assessment as an early-stage indicator.

  • 7.
    Pantzar, Alexandra
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Laukka, Erika J.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Atti, Anna Rita
    Papenberg, Göran
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Max Planck Society, Germany.
    Keller, Lina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Karolinska Institutet, Sweden.
    Graff, Caroline
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontology Research Center, Sweden.
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontology Research Center, Sweden.
    Interactive effects of KIBRA and CLSTN2 polymorphisms on episodic memory in old-age unipolar depression2014In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 62, p. 137-142Article in journal (Refereed)
    Abstract [en]

    The KIBRA (rs17070145) C-allele and the CLSTN2 (rs6439886) T-allele have both been associated with poorer episodic memory performance. Given that episodic memory is affected in depression, we hypothesized that the combination of these risk alleles would be particularly detrimental to episodic memory performance in depressed persons. In the population-based SNAC-K study, 2170 participants (>= 60 years) without dementia (DSM-IV criteria) and antidepressant pharmacotherapy were clinically examined and diagnosed following ICD-10 criteria for unipolar depression, and genotyped for KIBRA and CLSTN2. Participants were categorized according to unipolar depression status (yes, no) and genotype combinations (KIBRA: CC, any T; CLSTN2: TT, any C). Critically, a three-way interaction effect showed that the CC/TT genotype combination was associated with poorer episodic recall and recognition performance only in depressed elderly persons, with depressed CC/TT carriers consistently performing at the lowest level. This finding supports the view that effects of genetic polymorphisms on cognitive functioning may be most easily disclosed at suboptimal levels of cognitive ability, such as in old-age depression.

  • 8. Papenberg, Goran
    et al.
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Chicherio, Christian
    Nagel, Irene E
    Heekeren, Hauke R
    Lindenberger, Ulman
    Li, Shu-Chen
    Higher intraindividual variability is associated with more forgetting and dedifferentiated memory functions in old age2011In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 49, no 7, p. 1879-1888Article in journal (Refereed)
    Abstract [en]

    Intraindividual trial-to-trial reaction time (RT) variability is commonly found to be higher in clinical populations or life periods that are associated with impaired cognition. In the present study, higher within-person trial-to-trial RT variability in a perceptual speed task is related to more forgetting and dedifferentiation of memory functions in older adults (aged 60-71 years). More specifically, our study showed that individuals in a high-variability group (n=175) forgot more memory scenes over a 1-week retention interval than individuals in the low-variability group (n=174). In contrast, slower RT speed was associated with poorer episodic memory in general, but unrelated to the amount of forgetting. Moreover, results from multiple group latent factor analyses showed that episodic memory and working memory functions were more highly correlated in the high-variability (r=.63) than in the low-variability (r=.25) group. Given that deficits in dopamine (DA) modulation may underlie increases in RT variability, the present findings are in line with (i) recent animal studies implicating DA in long-term episodic memory consolidation and (ii) neurocomputational work linking DA modulation of performance variability to dedifferentiation of cognitive functions in old age.

  • 9.
    Persson, Jonas
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Lind, J.
    Larsson, A.
    Ingvar, Martin
    Sleegers, K.
    Van Broeckhoven, C.
    Adolfsson, R.
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Nyberg, Lars
    Altered deactivation in individuals with genetic risk for Alzheimer's disease2008In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 46, no 6, p. 1679-1687Article in journal (Refereed)
    Abstract [en]

    Regions that show task-induced deactivations may be part of a default-mode network related to processes that are more engaged during passive than active task conditions. Alteration of task-induced deactivations with age and dementia is indicated by atypical engagement of default-mode network regions. Genetic studies show a relation between the apolipoprotein E4 (<i>APOE4</i>) allele and the common form of Alzheimer’s disease (AD), and altered functional brain activation has been observed in non-demented <i>APOE4</i> carriers compared to non-carriers. Here we investigate the hypothesis of altered default-mode network brain responses in individuals with genetic risk for AD. Functional MRI was used to assess task-induced deactivation in 60 subjects of which 30 carried at least one copy of the <i>APOE4</i> allele, and 30 non-carriers. Subjects were scanned while performing a semantic categorization task shown to promote episodic memory encoding. The results show patterns of deactivation consistent with the default-mode network. We also found reduced deactivation in non-demented <i>APOE4</i> carriers compared to non-carriers, suggesting alterations in the default-mode network in the absence of dementia. These results implicate possibilities for investigatin altered properties of task-induced deactivations in individuals with genetic risk for AD, and may prove useful for pre-clinical identification of individuals susceptible to memory problems and AD.

  • 10. Preuschhof, Claudia
    et al.
    Heekeren, Hauke R
    Li, Shu-Chen
    Sander, Thomas
    Lindenberger, Ulman
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    KIBRA and CLSTN2 polymorphisms exert interactive effects on human episodic memory2010In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 48, no 2, p. 402-408Article in journal (Refereed)
    Abstract [en]

    Individual differences in episodic memory are highly heritable. Several studies have linked a polymorphism in the gene encoding the KIBRA protein to episodic memory performance. Results regarding CLSTN2, the gene encoding the synaptic protein calsyntenin 2, have been less consistent, possibly pointing to interactions with other genes. Given that both KIBRA and CLSTN2 are expressed in the medial temporal lobe and have been linked to synaptic plasticity, we investigated whether KIBRA and CLSTN2 interactively modulate episodic memory performance (n=383). We replicated the beneficial effect of the KIBRA T-allele on episodic memory, and discovered that this effect increases with the associative demands of the memory task. Importantly, the memory-enhancing effect of the KIBRA T-allele was boosted by the presence of the CLSTN2 C-allele, which positively affected memory performance in some previous studies. In contrast, the presence of CLSTN2 C-allele led to reduced performance in subjects homozygous for the KIBRA C-allele. Overall, these findings suggest that KIBRA and CLSTN2 interactively modulate episodic memory performance, and underscore the need for delineating the interactive effects of multiple genes on brain and behavior.

  • 11.
    Rönnlund, Michael
    et al.
    Umeå universitet.
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Stockholm Brain Institute, Stockholm, Sweden.
    Flynn effects on sub-factors of episodic and semantic memory: Parallel gains over time and the same set of determining factors2009In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 47, no 11, p. 2174-2180Article in journal (Refereed)
    Abstract [en]

    The study examined the extent to which time-related gains in cognitive performance, so-called Flynn effects, generalize across sub-factors of episodic memory (recall and recognition) and semantic memory (knowledge and fluency). We conducted time-sequential analyses of data drawn from the Betula prospective cohort study, involving four age-matched samples (35–80 years; N = 2996) tested on the same battery of memory tasks on either of four occasions (1989, 1995, 1999, and 2004). The results demonstrate substantial time-related improvements on recall and recognition as well as on fluency and knowledge, with a trend of larger gains on semantic as compared with episodic memory [Rönnlund, M., & Nilsson, L. -G. (2008). The magnitude, generality, and determinants of Flynn effects on forms of declarative memory: Time-sequential analyses of data from a Swedish cohort study. Intelligence], but highly similar gains across the sub-factors. Finally, the association with markers of environmental change was similar, with evidence that historical increases in quantity of schooling was a main driving force behind the gains, both on the episodic and semantic sub-factors. The results obtained are discussed in terms of brain regions involved.

  • 12. Ziaei, Maryam
    et al.
    Salami, Alireza
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Umeå University, Sweden.
    Persson, Jonas
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Age-related alterations in functional connectivity patterns during working memory encoding of emotional items2017In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 94, p. 1-12Article in journal (Refereed)
    Abstract [en]

    Previous findings indicate age-related differences in frontal-amygdala connectivity during emotional processing. However, direct evidence for age differences in brain functional activation and connectivity during emotional processing and concomitant behavioral implications is lacking. In the present study, we examined the impact of aging on the neural signature of selective attention to emotional information during working memory (WM) encoding. Participants completed an emotional WM task in which they were asked to attend to emotional targets and ignore irrelevant distractors. Despite an overall reduction in accuracy for older relative to younger adults, no behavioral age effect was observed as a function of emotional valence. The functional connectivity patterns of left ventrolateral prefrontal cortex showed that younger adults recruited one network for encoding of both positive and negative emotional targets and this network contributed to higher memory accuracy in this cohort. Older adults, on the other hand, engaged two distinct networks for encoding of positive and negative targets. The functional connectivity analysis using left amygdala further demonstrated that older adults recruited one single network during encoding of positive as well as negative targets whereas younger adults recruited this network only for encoding of negative items. The engagement of amygdala functional network also contributed to higher memory performance and faster response times in older adults. Our findings provide novel insights into the differential roles of functional brain networks connected to the medial PFC and amygdala during encoding of emotionally-valenced items with advancing age.

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