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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. Hedenius, Martina
    et al.
    Persson, Jonas
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Alm, Per A.
    Ullman, Michael T.
    Howard, James H., Jr.
    Howard, Darlene V.
    Jennische, Margareta
    Impaired implicit sequence learning in children with developmental dyslexia2013In: Research in Developmental Disabilities, ISSN 0891-4222, E-ISSN 1873-3379, Vol. 34, no 11, p. 3924-3935Article in journal (Refereed)
    Abstract [en]

    It has been proposed that an impairment of procedural memory underlies a range of linguistic, cognitive and motor impairments observed in developmental dyslexia (DD). However, studies designed to test this hypothesis using the implicit sequence learning paradigm have yielded inconsistent results. A fundamental aspect of procedural learning is that it takes place over an extended time-period that may be divided into distinct stages based on both behavioural characteristics and neural correlates of performance. Yet, no study of implicit sequence learning in children with DD has included learning stages beyond a single practice session. The present study was designed to fill this important gap by extending the investigation to include the effects of overnight consolidation as well as those of further practice on a subsequent day. The results suggest that the most pronounced procedural learning impairment in DD may emerge only after extended practice, in learning stages beyond a single practice session.

  • 3. Hedenius, Martina
    et al.
    Persson, Jonas
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Tremblay, Antoine
    Adi-Japha, Esther
    Verissimo, João
    Dye, Cristina D.
    Alm, Per
    Jennische, Margareta
    Tomblin, J. Bruce
    Ullman, Michael
    Grammar predicts procedural learning and consolidation deficits in children with Specific Language Impairment2011In: Research in Developmental Disabilities, ISSN 0891-4222, E-ISSN 1873-3379, Vol. 32, no 6, p. 2362-2375Article in journal (Refereed)
    Abstract [en]

    The Procedural Deficit Hypothesis (PDH) posits that Specific Language Impairment (SLI) can be largely explained by abnormalities of brain structures that subserve procedural memory. The PDH predicts impairments of procedural memory itself, and that such impairments underlie the grammatical deficits observed in the disorder. Previous studies have indeed reported procedural learning impairments in SLI, and have found that these are associated with grammatical difficulties. The present study extends this research by examining consolidation and longer-term procedural sequence learning in children with SLI. The Alternating Serial Reaction Time (ASRT) task was given to children with SLI and typically developing (TD) children in an initial learning session and an average of three days later to test for consolidation and longer-term learning. Although both groups showed evidence of initial sequence learning, only the TD children showed clear signs of consolidation, even though the two groups did not differ in longer-term learning. When the children were re-categorized on the basis of grammar deficits rather than broader language deficits, a clearer pattern emerged. Whereas both the grammar impaired and normal grammar groups showed evidence of initial sequence learning, only those with normal grammar showed consolidation and longer-term learning. Indeed, the grammar-impaired group appeared to lose any sequence knowledge gained during the initial testing session. These findings held even when controlling for vocabulary or a broad non-grammatical language measure, neither of which were associated with procedural memory. When grammar was examined as a continuous variable over all children, the same relationships between procedural memory and grammar, but not vocabulary or the broader language measure, were observed. Overall, the findings support and further specify the PDH. They suggest that consolidation and longer-term procedural learning are impaired in SLI, but that these impairments are specifically tied to the grammatical deficits in the disorder. The possibility that consolidation and longer-term learning are problematic in the disorder suggests a locus of potential study for therapeutic approaches. In sum, this study clarifies our understanding of the underlying deficits in SLI, and suggests avenues for further research.

  • 4. Hedenius, Martina
    et al.
    Ullman, Michael T.
    Alm, Per
    Jennische, Margareta
    Persson, Jonas
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Enhanced Recognition Memory after Incidental Encoding in Children with Developmental Dyslexia2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 5, p. e63998-Article in journal (Refereed)
    Abstract [en]

    Developmental dyslexia (DD) has previously been associated with a number of cognitive deficits. Little attention has been directed to cognitive functions that remain intact in the disorder, though the investigation and identification of such strengths might be useful for developing new, and improving current, therapeutical interventions. In this study, an old/new recognition memory paradigm was used to examine previously untested aspects of declarative memory in children with DD and typically developing control children. The DD group was not only not impaired at the task, but actually showed superior recognition memory, as compared to the control children. These findings complement previous reports of enhanced cognition in other domains (e. g., visuo-spatial processing) in DD. Possible underlying mechanisms for the observed DD advantage in declarative memory, and the possibility of compensation by this system for reading deficits in dyslexia, are discussed.

  • 5.
    Kalpouzos, Gregoria
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Persson, Jonas
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Nyberg, Lars
    Local brain atrophy accounts for functional activity differences in normal aging2012In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 33, no 3, p. 623.e1-Article in journal (Refereed)
    Abstract [en]

    Functional brain imaging studies of normal aging typically show age-related under-and overactivations during episodic memory tasks. Older individuals also undergo nonuniform gray matter volume (GMv) loss. Thus, age differences in functional brain activity could at least in part result from local atrophy. We conducted a series of voxel-based blood oxygen level-dependent (BOLD)-GMv analyses to highlight whether age-related under-and overrecruitment was accounted for by GMv changes. Occipital GMv loss accounted for underrecruitment at encoding. Efficiency reduction of sensory-perceptual mechanisms underpinned by these areas may partly be due to local atrophy. At retrieval, local GMv loss accounted for age-related overactivation of left dorsolateral prefrontal cortex, but not of left dorsomedial prefrontal cortex. Local atrophy also accounted for age-related overactivation in left lateral parietal cortex. Activity in these frontoparietal regions correlated with performance in the older group. Atrophy in the overrecruited regions was modest in comparison with other regions as shown by a between-group voxel-based morphometry comparison. Collectively, these findings link age-related structural differences to age-related functional under-as well as overrecruitment.

  • 6. Kauppi, Karolina
    et al.
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Stockholm Brain Institute, Sweden.
    Persson, Jonas
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Nyberg, Lars
    Additive genetic effect of APOE and BDNF on hippocampus activity2014In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 89, p. 306-313Article in journal (Refereed)
    Abstract [en]

    Human memory is a highly heritable polygenic trait with complex inheritance patterns. To study the genetics of memory and memory-related diseases, hippocampal functioning has served as an intermediate phenotype. The importance of investigating gene-gene effects on complex phenotypes has been emphasized, but most imaging studies still focus on single polymorphisms. APOE epsilon 4 and BDNF Met, two of the most studied gene variants for variability in memory performance and neuropsychiatric disorders, have both separately been related to poorer episodic memory and altered hippocampal functioning. Here, we investigated the combined effect of APOE and BDNF on hippocampal activation (N = 151). No non-additive interaction effects were seen. Instead, the results revealed decreased activation in bilateral hippocampus and parahippocampus as a function of the number of APOE e4 and.BDNE Met alleles present (neither, one, or both). The combined effect was stronger than either of the individual effects, and both gene variables explained significant proportions of variance in BOLD signal change. Thus, there was an additive gene-gene effect of APOE and BDNF on medial temporal lobe (MTL) activation, showing that a larger proportion of variance in brain activation attributed to genetics can be explained by considering more than one gene variant This effect might be relevant for the understanding of normal variability in memory function as well as memory-related disorders associated with APOE and BDNF.

  • 7. Lind, Johanna
    et al.
    Larsson, Anne
    Persson, Jonas
    Ingvar, Martin
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Reduced hippocampal volume in non-demented carriers of the Apolipoprotein E ε4: Relation to chronological age and recognition memory.2006In: Neuroscience Letters, ISSN 0304-3940, Vol. 396, no 1, p. 23-27Article in journal (Refereed)
    Abstract [en]

    Apolipoprotein E ε4 (APOE ε4) is the main known genetic risk factor for Alzheimers’ disease (AD). Some previous studies have reported structural brain changes as well as cignitive changes in non-demented APOE ε4 carriers, but the pattern of results is incosistent 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 ε4 (age range: 49-79 years). We observed reduced right hippocampal volume in APOE ε4 carriers, and found that the difference was most pronounced before the age of 65 years. Further, the results revealed that APOE ε4 carriers made significantly more false alarms in the recognition-memory test, and that the number of false alarms correlated significantly with right hippocampus volume. These results indicate that younger individuals at genetic risk for AD have smaller hippocampal volume and lower performance on hippocampal-dependent cognitive tasks. An important question for the future is whether smaller hippocampal volume represents early AD-pathology or a pre-existing trait.

  • 8. Lind, Johanna
    et al.
    Persson, Jonas
    Ingvar, Martin
    Larsson, Anne
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Reduced functional brain activity response in cognitively intact apolipoprotein E ε4 carriers.2006In: Brain: A Journal of Neurology, ISSN 0006-8950, Vol. 129, no 5, p. 1240-1248Article in journal (Refereed)
    Abstract [en]

    The Apolipoprotein E ε4 (APOE ε4) is the main known genetic risk factor for Alzheimer’s disease (AD). Genetic assessments in combination with other diagnostic tools, such as neuroimaging, have the potential to facilitate early diagnosis of AD. We have conducted a large-scale fMRI study, where we contrasted 30 APOE ε4 carriers and 30 non-carriers with regard to brain activity during a semantic categorization task. Critically, both groups were cognitively intact and AD-symptom free. APOE ε4 carriers showed redued 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 to heterozygous carriers. In addition, contrasts of processing novel vs. familiar items revealed an abnormal response in the right hippocampus in the APOE ε4 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 AD, well before alterations can be detected at the behavioral level.

  • 9.
    Marklund, Petter
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Persson, Jonas
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Context dependent switching between proactive and reactive working memory control mechanisms in the right inferior frontal gyrus2012In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 63, no 3, p. 1552-1560Article in journal (Refereed)
    Abstract [en]

    A critical feature of higher cognitive functioning is the capacity to flexibly tailor information processing and behaviors to current situational demands. Recent neurocognitive models have been postulated to account for the dynamic nature of human executive processing by invoking two dissociable cognitive control modes, proactive and reactive control. These may involve partially overlapping, but temporally distinct neural implementation in the prefrontal cortex. Prior brain imaging studies exploring proactive control have mainly used tasks requiring only information about single-items to be retained over unfilled delays. Whether proactive control can also be utilized to facilitate performance in more complex working memory tasks, in which concurrent processing of intervening items and updating is mandatory during contextual cue maintenance remains an open question. To examine this issue and to elucidate the extent to which overlapping neural substrates underlie proactive and reactive control we used fMRI and a modified verbal 3-back paradigm with embedded cues predictive of high-interference trials. This task requires context information to be retained over multiple intervening trials. We found that performance improved with item-specific cues predicting forthcoming lures despite increased working memory load. Temporal dynamics of activation in the right inferior frontal gyrus suggest flexible switching between proactive and reactive control in a context-dependent fashion, with greater sustained responses elicited in the 3-back task involving context maintenance of cue information and greater transient responses elicited in the 3-back task absent of cues.

  • 10.
    Nelson, James K.
    et al.
    University of Michigan.
    Reuter-Lorenz, Patricia A.
    University of Michigan.
    Persson, Jonas
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Sylvester, Ching-Yune C.
    University of Michigan.
    Jonides, John
    University of Michigan.
    Mapping interference resolution across task domains: A shared control process in left inferior frontal gyrus2009In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1256, p. 92-100Article in journal (Refereed)
    Abstract [en]

    Work in functional neuroimaging has mapped interference resolution processing onto left inferior frontal regions for both verbal working memory and a variety of semantic processing tasks. The proximity of the identified regions from these different tasks suggests the existence of a common, domain-general interference resolution mechanism. The current research specifically tests this idea in a within-subject design using fMRI to assess the activation associated with variable selection requirements in a semantic retrieval task (verb generation) and a verbal working memory task with a trial-specific proactive interference manipulation (recent-probes). High interference trials on both tasks were associated with activity in the midventrolateral region of the left inferior frontal gyrus, and the regions activated in each task strongly overlapped. The results indicate that an elemental component of executive control associated with interference resolution during retrieval from working memory and from semantic memory can be mapped to a common portion of the left inferior frontal gyrus.

  • 11. Nyberg, Lars
    et al.
    Andersson, Micael
    Kauppi, Karolina
    Lundquist, Anders
    Persson, Jonas
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Karolinska Institute, Sweden; Stockholm Brain Institute, Sweden; Umeå center for Functional Brain Imaging, Sweden.
    Pudas, Sara
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Stockholm Brain Institute, Sweden; Umeå center for Functional Brain Imaging, Sweden.
    Age-related and Genetic Modulation of Frontal Cortex Efficiency2014In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 26, no 4, p. 746-754Article in journal (Refereed)
    Abstract [en]

    The dorsolateral pFC (DLPFC) is a key region for working memory. It has been proposed that the DLPFC is dynamically recruited depending on task demands. By this view, high DLPFC recruitment for low-demanding tasks along with weak DLPFC upregulation at higher task demands reflects low efficiency. Here, the fMRI BOLD signal during working memory maintenance and manipulation was examined in relation to aging and catechol-O-methyltransferase (COMT) Val(158)Met status in a large representative sample (n = 287). The efficiency hypothesis predicts a weaker DLPFC response during manipulation, along with a stronger response during maintenance for older adults and COMT Val carriers compared with younger adults and COMT Met carriers. Consistent with the hypothesis, younger adults and met carriers showed maximal DLPFC BOLD response during manipulation, whereas older adults and val carriers displayed elevated DLPFC responses during the less demanding maintenance condition. The observed inverted relations support a link between dopamine and DLPFC efficiency.

  • 12.
    Nyberg, Lars
    et al.
    Umeå universitet, Umeå, Sweden.
    Salami, Alireza
    Umeå universitet, Umeå, Sweden.
    Andersson, Mikael
    Umeå universitet, Umeå, Sweden.
    Eriksson, Johan
    Umeå universitet, Umeå, Sweden.
    Kalpouzos, Grégoria
    Umeå universitet, Umeå, Sweden.
    Kauppi, Karolina
    Umeå universitet, Umeå, Sweden.
    Lind, Johanna
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Stockholm Brain Institute, Stockholm, Sweden; University of Oslo, Oslo, Norway.
    Pudas, Sara
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Stockholm Brain Institute, Stockholm, Sweden; Umeå Center for Functional Brain Imaging, Umeå, Sweden.
    Persson, Jonas
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Stockholm Brain Institute, Stockholm, Sweden.
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Stockholm Brain Institute, Stockholm, Sweden.
    Longitudinal evidence for diminished frontal-cortex function in aging2010In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 107, no 52, p. 22682-22686Article in journal (Refereed)
    Abstract [en]

    Cross-sectional estimates of age-related changes in brain structure and function were compared with 6-y longitudinal estimates. The results indicated increased sensitivity of the longitudinal approach as well as qualitative differences. Critically, the cross-sectional analyses were suggestive of age-related frontal overrecruitment, whereas the longitudinal analyses revealed frontal underrecruitment with advancing age. The cross-sectional observation of overrecruitment reflected a select elderly sample. However, when followed over time, this sample showed reduced frontal recruitment. These findings dispute inferences of true age changes on the basis of age differences, hence challenging some contemporary models of neurocognitive aging, and demonstrate age-related decline in frontal brain volume as well as functional response.

  • 13.
    Papenberg, Goran
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Max Planck Institute for Human Development, Germany.
    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).
    Lindenberger, Ulman
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Genetics and Functional Imaging: Effects of APOE, BDNF, COMT, and KIBRA in Aging2015In: Neuropsychology Review, ISSN 1040-7308, E-ISSN 1573-6660, Vol. 25, no 1, p. 47-62Article, review/survey (Refereed)
    Abstract [en]

    Increasing evidence from cross-sectional and longitudinal molecular-genetic studies suggests that effects of common genetic variations on cognitive functioning increase with aging. We review the influence of candidate genes on brain functioning in old age, focusing on four genetic variations that have been extensively investigated: APOE, BDNF, COMT, and KIBRA. Similar to the behavioral evidence, there are reports from age-comparative studies documenting stronger genetic effects on measures of brain functioning in older adults compared to younger adults. This pattern suggests disproportionate impairments of neural processing among older individuals carrying disadvantageous genotypes. We discuss various factors, including gene-gene interactions, study population characteristics, lifestyle factors, and diseases, that need to be considered in future studies and may help understand inconsistent findings in the extant literature.

  • 14. Persson, J
    et al.
    Lind, J
    Larsson, A
    Ingvar, M
    Cruts, M
    Van Broeckhoven, C
    Adolfsson, R
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Nyberg, L
    Altered brain white-matter integrity in non-demented carriers of the APOE ε4 allele: A risk for Alzheimer’s disease.2006In: Neurology, ISSN 0028-3878, Vol. 66, no 7, p. 1029-1033Article in journal (Refereed)
    Abstract [en]

    Previous research has shown that polymorphisms of the apolipoprotein E (APOE) represent genetic risk factors for dementia and for cognitive impairment in the elderly. The neural mechanisms by which these genetic variations influence behavioral performance or clinical severity are not well understood. We used diffusion tensor imaging to investigate ultrastructural properties in brain white-matter to detect pathological processes that modify tissue integrity. Sixty participants were included in the study of which 30 were homozygous for the APOE ε3 allele, 10 were homozygous for the APOE ε4 allele, and 20 had the APOE ε34 allele combination. All individuals were non-demented, and the groups were matched on demographic variables and cognitive performance. The results showed a decline in fractional anisotropy, a marker for white-matter integrity, in the posterior corpus callosum of ε4 carriers compared to non-carriers. Additional sites of altered white-matter integrity included the medial temporal lobe. Conclusions: Although the mechanism underlying vulnerability of white matter tracts in APOE ε4 carriers is still unknown, our findings suggest that increased genetic risk for developing AD is associated with changes in microscopic white-matter integrity well before the onset of dementia.

  • 15. Persson, Jonas
    et al.
    Bringlöv, E
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Nyberg, Lars
    Herbal extracts and memory enhancement: Response to Scholey et al.2005In: Psychopharmacology, ISSN 0033-3158, Vol. 179, no 3, p. 708-709Article in journal (Refereed)
    Abstract [en]

    Reply by the current author to the comments made by Scholey et al. (see record 2005-04969-023) on the original article (see record 2004-13858-010). The letter by Scholey et al. contains several accounts of criticism. The principal claim that they make is that, although negative findings of cognition-enhancing effects have been found in several studies, this is not enough evidence to conclude that these products do not improve cognitive performance. The authors emphasize that the methods used in these studies need careful examination and they identify a number of criteria that, preferably, should be met for these studies to be "adequately powered". The problem is (and this is also discussed by Scholey et al.) that even if these criteria are met, there are still negative findings.

  • 16.
    Persson, Jonas
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Kalpouzos, Gregoria
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Ryberg, Mats
    Nyberg, Lars
    Preserved Hippocampus Activation in Normal Aging as Revealed by fMRI2011In: Hippocampus, ISSN 1050-9631, E-ISSN 1098-1063, Vol. 21, no 7, p. 753-766Article in journal (Refereed)
    Abstract [en]

    The hippocampus is deteriorated in various pathologies such as Alzheimer's disease (AD) and such deterioration has been linked to memory impairment. By contrast, the structural and functional effects of normal aging on the hippocampus is a matter of debate, with some findings suggesting deterioration and others providing evidence of preservation. This constitutes a crucial question since many investigations on AD are based on the assumption that the deterioration of the hippocampus is the breaking point between normal and pathological aging. A growing number of fMRI studies specifically aimed at investigating hippocampal engagement in various cognitive tasks, notably memory tasks, but the results have been inconclusive. Here, we optimized the episodic face-name paired-associates task in order to test the functioning of the hippocampus in normal aging. Critically, we found no difference in the activation of the hippocampus between the young and a group of older participants. Analysis of individual patterns of activation substantiated this impression. Collectively, these findings provide evidence of preserved hippocampal functioning in normal aging.

  • 17.
    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.

  • 18.
    Persson, Jonas
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Lustig, Cindy
    Nelson, James K
    Reuter-Lorenz, Patricia A
    Age differences in deactivation: a link to cognitive control?2007In: J Cogn Neurosci, ISSN 0898-929X, Vol. 19, no 6, p. 1021-32Article in journal (Refereed)
  • 19.
    Persson, Jonas
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Nyberg, Lars
    Structure–function correlates of episodic memory in aging2008In: Handbook of Episodic Memory, 18, Elsevier , 2008Chapter in book (Refereed)
    Abstract [en]

    Normal aging is accompanied by a wide variety of disturbances in the structure and function of the human brain. It is now well established that normal aging is associated with a progressive decline of episodic-memory function, especially in cued and free recall tasks. Although the primary causes of this decline remain elusive, neuroimaging research have presented an avenue for understanding age-related episodic-memory failure. By integrating behavioral measures and imaging data, the relationship between biological markers of aging and cognitive functions can be explored. In this chapter, we review current knowledge about the effects of normal aging, and its neural correlates as revealed by functional and structural neuroimaging. The importance of reliable cognitive measures in aging research, such as longitudinal behavioral assessment, is also highlighted. We also present results that attempt at characterizing cognitive aging at multiple levels by integrating structural, neuroimaging, and episodicmemory measures.

  • 20.
    Persson, Jonas
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Pudas, Sara
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Lind, Johanna
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Kauppi, Karolina
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Nyberg, Lars
    Longitudinal structure – function correlates in elderly reveal MTL dysfunction with cognitive decline2012In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 22, no 10, p. 2297-2304Article in journal (Refereed)
    Abstract [en]

    By integrating behavioral measures and imaging data, previous investigations have explored the relationship between biological markers of aging and cognitive functions. Evidence from functional and structural neuroimaging has revealed that hippocampal volume and activation patterns in the medial temporal lobe (MTL) may predict cognitive performance in old age. Most past demonstrations of age-related differences in brain structure–function were based on cross-sectional comparisons. Here, the relationship between 6-year intraindividual change in functional magnetic resonance imaging (fMRI) signal and change in memory performance over 2 decades was examined. Correlations between intraindividual change in fMRI signal during episodic encoding and change in memory performance measured outside of scanning were used as an estimate for relating brain–behavior changes. The results revealed a positive relationship between activation change in the hippocampus (HC) and change in memory performance, reflecting reduced hippocampal activation in participants with declining performance. Using a similar analytic approach as for the functional data, we found that individuals with declining performance had reduced HC volume compared with individuals with intact performance. These observations provide a strong link between cognitive change in older adults and MTL structure and function and thus provide insights into brain correlates of individual variability in aging trajectories.

  • 21.
    Persson, Jonas
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Umeå center for Functional Brain Imaging (UFBI), Sweden.
    Pudas, Sara
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Umeå center for Functional Brain Imaging (UFBI), Sweden.
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Nyberg, Lars
    Longitudinal assessment of default-mode brain function in aging2014In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 35, no 9, p. 2107-2117Article in journal (Refereed)
    Abstract [en]

    Age-related changes in the default-mode network (DMN) have been identified in prior cross-sectional functional magnetic resonance imaging studies. Here, we investigated longitudinal change in DMN activity and connectivity. Cognitively intact participants (aged 49-79 years at baseline) were scanned twice, with a 6-year interval, while performing an episodic memory task interleaved with a passive control condition. Longitudinal analyses showed that the DMN (control condition > memory task) could be reliably identified at both baseline and follow-up. Differences in the magnitude of task-induced deactivation in posterior DMN regions were observed between baseline and follow-up indicating reduced deactivation in these regions with increasing age. Although no overall longitudinal changes in within-network connectivity were found across the whole sample, individual differences in memory change correlated with change in connectivity. Thus, our results show stability of whole-brain DMN topology and functional connectivity over time in healthy older adults, whereas within-region DMN analyses show reduced deactivation between baseline and follow-up. The current findings provide novel insights into DMN functioning that may assist in identifying brain changes in patient populations, as well as characterizing factors that distinguish between normal and pathologic aging.

  • 22.
    Persson, Jonas
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Reuter-Lorenz, Patricia A.
    Cognition and Aging: Typical Development2008In: Handbook of Developmental Cognitive Neuroscience, The MIT Press, Cambridge, US, and London, UK. , 2008, p. 591-606Chapter in book (Refereed)
    Abstract [en]

    Declining cognitive functions are a normal and inevitable part of healthy aging. Some changes may stem from global alterations in brain functions, including metabolic changes; others may result from localized decline of specific neural circuits. Current research on cognitive aging aims not only to identify the mechanisms that underlie cognitive change, but also to understand and harness the genetic, experiential and environmental factors that promote the preservation of cognitive abilities. Recent technological advances are leading to new breakthroughs in cognitive aging research, while also posing new challenges to understand the relation between genetic, anatomical, physiological, and cognitive factors and to integrate these levels of analysis. Moreover, the availability of high-resolution neuroimaging methods is revising our perspective on aging and giving way to new ideas about the aging mind and brain. We now know that the aging brain is not simply a depleted and reduced version of the younger brain. Instead, recent cognitive neuroscience evidence points to patterns of preservation and decline, along with functional reorganization and plasticity.

  • 23.
    Persson, Jonas
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Reuter-Lorenz, Patricia A.
    Gaining Control: Training Executive Function and Far Transfer of the Ability to Resolve Interference [retracted]2008In: Psychological Science, ISSN 0956-7976, E-ISSN 1467-9280, Vol. 19, no 9, p. 881-888Article in journal (Refereed)
    Abstract [en]

    Functional brain-imaging data document overlapping sites of activation in prefrontal cortex across memory tasks, suggesting that these tasks may share common executive components. We leveraged this evidence to develop a training regimen and a set of transfer tasks to examine the trainability of a putative executive-control process: interference resolution. Eight days of training on high-interference versions of three different working memory tasks increased the efficiency with which proactive interference was resolved on those particular tasks. Moreover, an improved ability to resolve interference was also transferred to different working memory, semantic memory, and episodic memory tasks, a demonstration of far-transfer effects from process-specific training. Participants trained with noninterference versions of the tasks did not exhibit transfer. We infer that the transfer we demonstrated resulted from increased efficiency of the interference-resolution process. Therefore, this aspect of executive control is plastic and adaptive, and can be improved by training.

  • 24.
    Persson, Jonas
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Umeå University, Sweden.
    Rieckmann, Anna
    Kalpouzos, Grégoria
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fischer, Håkan
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Influences of a DRD2 polymorphism on updating of long-term memory representations and caudate BOLD activity: magnification in aging2015In: Human Brain Mapping, ISSN 1065-9471, E-ISSN 1097-0193, Vol. 36, no 4, p. 1325-1334Article in journal (Refereed)
    Abstract [en]

    A number of genetic polymorphisms are related to individual differences in cognitive performance. Striatal dopamine (DA) functions, associated with cognitive performance, are linked to the TaqIA polymorphism of the DRD2/ANKK1 gene. In humans, presence of an A1 allele of the DRD2/ANKK1-TaqIA polymorphism is related to reduced density of striatal DA D2 receptors. The resource-modulation hypothesis assumes that aging-related losses of neurochemical and structural brain resources modulate the extent to which genetic variations affect cognitive functioning. Here, we tested this hypothesis using functional MRI during long-term memory (LTM) updating in younger and older carriers and noncarriers of the A1-allele of the TaqIa polymorphism. We demonstrate that older A1-carriers have worse memory performance, specifically during LTM updating, compared to noncarriers. Moreover, A1-carriers exhibited less blood oxygen level-dependent (BOLD) activation in left caudate nucleus, a region critical to updating. This effect was only seen in older adults, suggesting magnification of genetic effects on functional brain activity in aging. Further, a positive relationship between caudate BOLD activation and updating performance among non-A1 carriers indicated that caudate activation was behaviorally relevant. These results demonstrate a link between the DRD2/ANKK1-TaqIA polymorphism and neurocognitive deficits related to LTM updating, and provide novel evidence that this effect is magnified in aging.

  • 25.
    Persson, Jonas
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Welsh, Kathryn M
    Jonides, John
    Reuter-Lorenz, Patricia A
    Cognitive fatigue of executive processes: interaction between interference resolution tasks.2007In: Neuropsychologia, ISSN 0028-3932, Vol. 45, no 7, p. 1571-9Article in journal (Refereed)
  • 26.
    Persson, Ninni
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Persson, Jonas
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Fischer, Håkan
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Neural structural correlates of personality: What has aging got to do with it?2015Conference paper (Other academic)
    Abstract [en]

    Introduction: Personality traits such as neuroticism and extraversion affect how we perceive and interact with the outer world. Hence, personality is an important component across the life-span. Little is known about the neural basis of personality, and how it is related to adult age-related variations (but see Wright et al., 2007). The current study investigates structural brain correlates of psychological measures of personality in a sample of younger (n= 30, 20-31 years) and older adults (n=30, 65-74 years) with an even gender distribution. Methods: The behavioural measures included neuroticism, extraversion and openness, assessed by a standard questionnaire (NEO-PI). Grey and white matter volumes were derived from gradient echo T1-weighted images from a 3 Tesla scanner. We selected brain regions of interest (ROIs) based on their theoretical and empirical relevance for the studied personality domains (see eg. Carrera et al., 2006, Fischer et al., 1997; Koelsch et al, 2013; Montag et al, 2013). The following ROIs were defined using voxel based morphology and the FreeSurfer software : the basal ganglia (BG) (caudate nucleus, putamen, globus pallidus), the thalamus (TH), amygdala (AM), and subcortical white matter in the insula (INw), the orbitofrontal region (OFw) and the anterior corpus callosum (aCC). We applied a series of structural equation models were each ROI was defined as a latent variable, represented by bi-hemispheric volumes, to predict personality and age related differences therein. Results: Larger volumes in the BG (p=.007) and TH (p = .000) were related to higher degree of neuroticism, but the association for BG was gone once age was accounted for (p =.401). The positive association between TH volumes and neuroticism was only significant in the older group (p = .003). Younger subjects with greater volumes in the aCC scored lower on openness (p = .001), while greater INw volumes predicted higher degree of neuroticism (p = .031). No significant associations were found between extraversion and the ROIs. OFw, or AM were not linked to personality. Conclusions: Our study highlights the role of the TH in relation to personality in older adults. The selective relationships between openness, neuroticism and white matter volumes in the younger participants may in part reflect late brain maturation.

  • 27.
    Persson, Ninni
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Biological psychology. Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Persson, Jonas
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Lavebratt, Catharina
    Fischer, Håkan
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Biological psychology. Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Effects of DARPP-32 genetic variation on prefrontal cortex volume and episodic memory performance2017In: Frontiers in Neuroscience, ISSN 1662-4548, E-ISSN 1662-453X, Vol. 11, article id 244Article in journal (Refereed)
    Abstract [en]

    Despite evidence of a fundamental role of DARPP-32 in integrating dopamine and glutamate signaling, studies examining gene coding for DARPP-32 in relation to neural and behavioral cor-relates in humans are scarce. Post mortem findings evidence genotype specific expressions of DARPP-32 in the dorsal frontal lobes. We therefore investigated the effects of genomic variation in DARPP-32 coding on frontal lobe volumes and episodic memory. Volumetric data from the dorsolateral (DLPFC), and visual cortices (VC) were obtained from 61 younger and older adults (♀54%). The major homozygote G, T or A genotypes in single nucleotide polymorphisms (SNPs: rs879606; rs907094; rs3764352), at the DARPP-32 regulating PPP1R1B gene influenced frontal gray matter volume and episodic memory (EM). Homozygous carriers of allelic variants with lower DARPP-32 expression had overall larger prefrontal volumes, in addition to greater EM recall accuracy. The SNPs did not influence VC volume. The genetic effects on DLPFC were greater in younger adults, and selective to this group for EM. Our findings suggest that genomic variation maps on to individual differences in frontal brain volumes, and cognitive functions. Larger DLPFC volumes were also related to better EM performance, suggesting that gene-related differences in frontal gray matter may contribute to individual differences in EM. These results need further replication from experimental and longitudinal reports to determine directions of causality.

  • 28.
    Pudas, Sara
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Persson, Jonas
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Josefsson, Maria
    de Luna, Xavier
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Nyberg, Lars
    Brain characteristics of individuals resisting age-related cognitive decline over two decades2013In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 33, no 20, p. 8668-8677Article in journal (Refereed)
    Abstract [en]

    Some elderly appear to resist age-related decline in cognitive functions, but the neural correlates of successful cognitive aging are not well known. Here, older human participants from a longitudinal study were classified as successful or average relative to the mean attrition-corrected cognitive development across 15-20 years in a population-based sample (n = 1561). Fifty-one successful elderly and 51 age-matched average elderly (mean age: 68.8 years) underwent functional magnetic resonance imaging while performing an episodic memory face-name paired-associates task. Successful older participants had higher BOLD signal during encoding than average participants, notably in the bilateral PFC and the left hippocampus (HC). The HC activation of the average, but not the successful, older group was lower than that of a young reference group (n = 45, mean age: 35.3 years). HC activation was correlated with task performance, thus likely contributing to the superior memory performance of successful older participants. The frontal BOLD response pattern might reflect individual differences present from young age. Additional analyses confirmed that both the initial cognitive level and the slope of cognitive change across the longitudinal measurement period contributed to the observed group differences in BOLD signal. Further, the differences between the older groups could not be accounted for by differences in brain structure. The current results suggest that one mechanism behind successful cognitive aging might be preservation of HC function combined with a high frontal responsivity. These findings highlight sources for heterogeneity in cognitive aging and may hold useful information for cognitive intervention studies.

  • 29.
    Pudas, Sara
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Persson, Jonas
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Nyberg, Lars
    Umeå universitet.
    Maintenance and Manipulation in Working Memory: Differential Ventral and Dorsal Frontal Cortex fMRI Activity2009In: Acta Psychologica Sinica, ISSN 0439-755X, Vol. 41, no 11, p. 1054-1062Article in journal (Refereed)
    Abstract [en]

    A verbal working memory protocol was designed and evaluated on a group of healthy younger adults in preparation for a large-scale functional magnetic resonance (fMRI) study on aging and memory. Letters were presented in two critical conditions: (i) maintenance, in which letters were to be memorized and kept in mind over a four second interval, and (ii) manipulation, in which letters were shifted forward in alphabetical order, and the new order was kept in mind. Analyses of fMRI data showed that the protocol elicited reliable activation in the frontal cortex, with manipulation producing more extensive activation patterns, both in whole-brain analyses and in predefined regions of interest (ROIs). There was also a distinction between dorsal and ventral lateral prefrontal regions, such that manipulation elicited more dorsolateral prefrontal activation. The protocol also elicited activation in various subcortical areas, previously associated with working-memory tasks. It was concluded that this working memory protocol is appropriate for investigating age-related changes in frontal-cortex functioning.

  • 30.
    Pudas, Sara
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Umeå universitet.
    Persson, Jonas
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Nilsson, Lars-Göran
    ARC och Umeå universitet.
    Nyberg, Lars
    Umeå universitet.
    Midlife memory ability accounts for brain activity differences in healthy aging2014In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 35, no 11, p. 2495-2503Article in journal (Refereed)
    Abstract [en]

    Cross-sectional neuroimaging studies suggest that hippocampal and prefrontal cortex functions underlie individual differences in memory ability in older individuals, but it is unclear how individual differences in cognitive ability in youth contribute to cognitive and neuroimaging measures in older age. Here, we investigated the relative influences of midlife memory ability and age-related memory change on memory-related BOLD-signal variability at one time point, using a sample from a longitudinal population-based aging study (N = 203, aged 55–80 years). Hierarchical regression analyses showed that midlife memory ability, assessed 15–20 years earlier, explained at least as much variance as memory change in clusters in the left inferior prefrontal cortex and the bilateral hippocampus, during memory encoding. Furthermore, memory change estimates demonstrated higher sensitivity than current memory levels in identifying distinct frontal regions where activity was selectively related to age-related memory change, as opposed to midlife memory. These findings highlight challenges in interpreting individual differences in neurocognitive measures as age-related changes in the absence of longitudinal data and also demonstrate the improved sensitivity of longitudinal measures.

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