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  • 1. Akram, Harith
    et al.
    Sotiropoulos, Stamatios N.
    Jbabdi, Saad
    Georgiev, Dejan
    Mahlknecht, Philipp
    Hyam, Jonathan
    Foltynie, Thomas
    Limousin, Patricia
    De Vita, Enrico
    Jahanshahi, Marjan
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
    Ashburner, John
    Behrens, Tim
    Zrinzo, Ludvic
    Subthalamic deep brain stimulation sweet spots and hyperdirect cortical connectivity in Parkinson's disease2017In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 158, p. 332-345Article in journal (Refereed)
    Abstract [en]

    Objectives: Firstly, to identify subthalamic region stimulation clusters that predict maximum improvement in rigidity, bradykinesia and tremor, or emergence of side-effects; and secondly, to map-out the cortical fingerprint, mediated by the hyperdirect pathways which predict maximum efficacy.

    Methods: High angular resolution diffusion imaging in twenty patients with advanced Parkinson's disease was acquired prior to bilateral subthalamic nucleus deep brain stimulation. All contacts were screened one-year from surgery for efficacy and side-effects at different amplitudes. Voxel-based statistical analysis of volumes of tissue activated models was used to identify significant treatment clusters. Probabilistic tractography was employed to identify cortical connectivity patterns associated with treatment efficacy.

    Results: All patients responded well to treatment (46% mean improvement off medication UPDRS-III [p < 0.0001]) without significant adverse events. Cluster corresponding to maximum improvement in tremor was in the posterior, superior and lateral portion of the nucleus. Clusters corresponding to improvement in bradykinesia and rigidity were nearer the superior border in a further medial and posterior location. The rigidity cluster extended beyond the superior border to the area of the zona incerta and Forel-H-2 field. When the clusters where averaged, the coordinates of the area with maximum overall efficacy was X = -10(-9.5), Y = -3(-1) and Z = -7(-3) in MNI(AC-PC) space. Cortical connectivity to primary motor area was predictive of higher improvement in tremor; whilst that to supplementary motor area was predictive of improvement in bradykinesia and rigidity; and connectivity to prefrontal cortex was predictive of improvement in rigidity.

    Interpretation: These findings support the presence of overlapping stimulation sites within the subthalamic nucleus and its superior border, with different cortical connectivity patterns, associated with maximum improvement in tremor, rigidity and bradykinesia.

  • 2. Becker, Nina
    et al.
    Kalpouzos, Grégoria
    Salami, Alireza
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
    Laukka, Erika J.
    Brehmer, Yvonne
    Structure-function associations of successful associative encoding2019In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 201, article id 116020Article in journal (Refereed)
    Abstract [en]

    Functional magnetic resonance imaging (MRI) studies have demonstrated a critical role of hippocampus and inferior frontal gyrus (IFG) in associative memory. Similarly, evidence from structural MRI studies suggests a relationship between gray-matter volume in these regions and associative memory. However, how brain volume and activity relate to each other during associative-memory formation remains unclear. Here, we used joint independent component analysis (jICA) to examine how gray-matter volume and brain activity would be associated during associative encoding, especially in medial-temporal lobe (MTL) and IFG. T1-weighted images were collected from 27 young adults, and functional MRI was employed during intentional encoding of object pairs. A subsequent recognition task tested participants' memory performance. Unimodal analyses using voxel-based morphometry revealed that participants with better associative memory showed larger gray-matter volume in left anterior hippocampus. Results from the jICA revealed one component that comprised a covariance pattern between gray-matter volume in anterior and posterior MTL and encoding-related activity in IFG. Our findings suggest that gray matter within the MTL modulates distally distinct parts of the associative encoding circuit, and extend previous studies that demonstrated MTL-IFG functional connectivity during associative memory tasks.

  • 3.
    Boraxbekk, Carl-Johan
    et al.
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Salami, Alireza
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Aging Research Center (ARC), Karolinska Institute, Stockholm, Sweden.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Physical activity over a decade modifies age-related decline in perfusion, gray matter volume, and functional connectivity of the posterior default mode network: a multimodal approach2016In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 131, p. 133-141Article in journal (Refereed)
    Abstract [en]

    One step toward healthy brain aging may be to entertain a physically active lifestyle. Studies investigating physical activity effects on brain integrity have, however, mainly been based on single brain markers, and few used a multimodal imaging approach. In the present study, we used cohort data from the Betula study to examine the relationships between scores reflecting current and accumulated physical activity and brain health. More specifically, we first examined if physical activity scores modulated negative effects of age on seven resting state networks previously identified by Salami, Pudas, and Nyberg (2014). The results revealed that one of the most age-sensitive RSN was positively altered by physical activity, namely, the posterior default-mode network involving the posterior cingulate cortex (PCC). Second, within this physical activity-sensitive RSN, we further analyzed the association between physical activity and gray matter (GM) volumes, white matter integrity, and cerebral perfusion using linear regression models. Regions within the identified DMN displayed larger GM volumes and stronger perfusion in relation to both current and 10-years accumulated scores of physical activity. No associations of physical activity and white matter integrity were observed. Collectively, our findings demonstrate strengthened PCC–cortical connectivity within the DMN, larger PCC GM volume, and higher PCC perfusion as a function of physical activity. In turn, these findings may provide insights into the mechanisms of how long-term regular exercise can contribute to healthy brain aging.

  • 4. Brehmer, Yvonne
    et al.
    Rieckmann, Anna
    Bellander, Martin
    Westerberg, Helena
    Fischer, Håkan
    Bäckman, Lars
    Neural correlates of training-related working-memory gains in old age.2011In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 58, no 4, p. 1110-20Article in journal (Refereed)
    Abstract [en]

    Working memory (WM) functioning declines in old age. Due to its impact on many higher-order cognitive functions, investigating whether training can modify WM performance has recently been of great interest. We examined the relationship between behavioral performance and neural activity following five weeks of intensive WM training in 23 healthy older adults (M=63.7 years). 12 participants received adaptive training (i.e. individually adjusted task difficulty to bring individuals to their performance maximum), whereas the others served as active controls (i.e. fixed low-level practice). Brain activity was measured before and after training, using fMRI, while subjects performed a WM task under two difficulty conditions. Although there were no training-related changes in WM during scanning, neocortical brain activity decreased post training and these decreases were larger in the adaptive training group than in the controls under high WM load. This pattern suggests intervention-related increases in neural efficiency. Further, there were disproportionate gains in the adaptive training group in trained as well as in non-trained (i.e. attention, episodic memory) tasks assessed outside the scanner, indicating the efficacy of the training regimen. Critically, the degree of training-related changes in brain activity (i.e. neocortical decreases and subcortical increases) was related to the maximum gain score achieved during the intervention period. This relationship suggests that the decreased activity, but also specific activity increases, observed were functionally relevant.

  • 5.
    Burzynska, A Z
    et al.
    Max Planck Institute for Human Development, Berlin.
    Preuschhof, C
    Max Planck Institute for Human Development, Berlin.
    Bäckman, L
    Max Planck Institute for Human Development, Berlin, Karolinska Institute.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Li, S-C
    Max Planck Institute for Human Development, Berlin.
    Lindenberger, U
    Max Planck Institute for Human Development, Berlin, .
    Heekeren, H R
    Max Planck Institute for Human Development, Berlin, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig.
    Age-related differences in white matter microstructure: region-specific patterns of diffusivity.2010In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 49, no 3, p. 2104-2112Article in journal (Refereed)
    Abstract [en]

    We collected MRI diffusion tensor imaging data from 80 younger (20-32 years) and 63 older (60-71 years) healthy adults. Tract-based spatial statistics (TBSS) analysis revealed that white matter integrity, as indicated by decreased fractional anisotropy (FA), was disrupted in numerous structures in older compared to younger adults. These regions displayed five distinct region-specific patterns of age-related differences in other diffusivity properties: (1) increases in both radial and mean diffusivity; (2) increases in radial diffusivity; (3) no differences in parameters other than FA; (4) a decrease in axial and an increase in radial diffusivity; and (5) a decrease in axial and mean diffusivity. These patterns suggest different biological underpinnings of age-related decline in FA, such as demyelination, Wallerian degeneration, gliosis, and severe fiber loss, and may represent stages in a cascade of age-related degeneration in white matter microstructure. This first simultaneous description of age-related differences in FA, mean, axial, and radial diffusivity requires histological and functional validation as well as analyses of intermediate age groups and longitudinal samples.

  • 6. Carmichael, David W
    et al.
    Pinto, Serge
    Limousin-Dowsey, Patricia
    Thobois, Stephane
    Allen, Philip J
    Lemieux, Louis
    Yousry, Tarek
    Thornton, John S
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    Functional MRI with active, fully implanted, deep brain stimulation systems: safety and experimental confounds2007In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Neuroimage, Vol. 37, no 2, p. 508-517Article in journal (Other academic)
  • 7. Ebner, Natalie C
    et al.
    Johnson, Matthew R
    Rieckmann, Anna
    Durbin, Kelly A
    Johnson, Marcia K
    Fischer, Håkan
    Processing own-age vs. other-age faces: neuro-behavioral correlates and effects of emotion.2013In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 78, p. 363-71Article in journal (Refereed)
    Abstract [en]

    Age constitutes a salient feature of a face and signals group membership. There is evidence of greater attention to and better memory for own-age than other-age faces. However, little is known about the neural and behavioral mechanisms underlying processing differences for own-age vs. other-age faces. Even less is known about the impact of emotion expressed in faces on such own-age effects. Using fMRI, the present study examined brain activity while young and older adult participants identified expressions of neutral, happy, and angry young and older faces. Across facial expressions, medial prefrontal cortex, insula, and (for older participants) amygdala showed greater activity to own-age than other-age faces. These own-age effects in ventral medial prefrontal cortex and insula held for neutral and happy faces, but not for angry faces. This novel and intriguing finding suggests that processing of negative facial emotions under some conditions overrides age-of-face effects.

  • 8.
    Eriksson, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Stiernstedt, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Öhlund, Maria
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Changing Zaire to Congo: The fate of no-longer relevant mnemonic information.2014In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 101, p. 1-7Article in journal (Refereed)
    Abstract [en]

    In an ever-changing world there is constant pressure on revising long-term memory, such when people or countries change name. What happens to the old, pre-existing information? One possibility is that old associations gradually are weakened and eventually lost. Alternatively, old and no longer relevant information may still be an integral part of memory traces. To test the hypothesis that old mnemonic information still becomes activated when people correctly retrieve new, currently relevant information, brain activity was measured with fMRI while participants performed a cued-retrieval task. Paired associates (symbol-sound and symbol-face pairs) were first learned during two days. Half of the associations were then updated during the next two days, followed by fMRI scanning on day 5 and also 18months later. As expected, retrieval reactivated sensory cortex related to the most recently learned association (visual cortex for symbol-face pairs, auditory cortex for symbol-sound pairs). Critically, retrieval also reactivated sensory cortex related to the no-longer relevant associate. Eighteen months later, only non-updated symbol-face associations were intact. Intriguingly, a subset of the updated associations was now treated as though the original association had taken over, in that memory performance was significantly worse than chance and that activity in sensory cortex for the original but not the updated associate correlated (negatively) with performance. Moreover, the degree of "residual" reactivation during day 5 inversely predicted memory performance 18months later. Thus, updating of long-term memory involves adding new information to already existing networks, in which old information can stay resilient for a long time.

  • 9.
    Jonasson, Lars S.
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Social Sciences, Centre for Population Studies (CPS).
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Braver, Todd S.
    Department of Psychology,Washington University, St Louis, MO 63130, USA.
    Ögren, Mattias
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Bäckman, Lars
    Aging Research Center, Karolinska Institute, SE-113 30 Stockholm, Sweden.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Dopamine release in nucleus accumbens during rewarded task switching measured by [11C]raclopride2014In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 99, p. 357-364Article in journal (Refereed)
    Abstract [en]

    Reward and motivation have positive influences on cognitive-control processes in numerous settings. Models of reward implicate corticostriatal loops and the dopamine (DA) system, with special emphasis on D2 receptors in nucleus accumbens (NAcc). In this study, 11 right-handed males (35-40 years) were scanned with positron emission tomography (PET) in a single [(11)C]raclopride dynamic scan during rewarded and non-rewarded task switching. Rewarded task switching (relative to baseline task switching) decreased [(11)C]raclopride binding in NAcc. Decreasing NAcc [(11)C]raclopride binding was strongly associated with task reaction time measures that reflect individual differences in effort and control strategies. Voxelwise analyses additionally revealed reward-related DA release in anterodorsal caudate, a region previously associated with task-switching. These PET findings provide evidence for striatal DA release during motivated cognitive control, and further suggest that NAcc DA release predicts the task reaction time benefits of reward incentives.

  • 10.
    Jonasson, Lars S.
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Kramer, Arthur F.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark.
    Higher striatal D2-receptor availability in aerobically fit older adults but non-selective intervention effects after aerobic versus resistance training2019In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 202, article id 116044Article in journal (Refereed)
    Abstract [en]

    There is much evidence that dopamine is vital for cognitive functioning in aging. Here we tested the hypothesis that aerobic exercise and fitness influence dopaminergic neurotransmission in the striatum, and in turn performance on offline working-memory updating tasks. Dopaminergic neurotransmission was measured by positron emission tomography (PET) and the non-displacable binding potential (BPND) of [11C]raclopride, i.e. dopamine (DA) D2-receptor (D2R) availability. Fifty-four sedentary older adults underwent a six-months exercise intervention, performing either aerobic exercise or stretching, toning, and resistance active control training. At baseline, higher aerobic fitness levels (VO2peak) were associated with higher BPND in the striatum, providing evidence of a link between an objective measure of aerobic fitness and D2R in older adults. BPND decreased substantially over the intervention in both groups but the intervention effects were non-selective with respect to exercise group. The decrease was several times larger than any previously estimated annual decline in D2R, potentially due to increased endogenous DA. Working-memory was unrelated to D2R both at baseline and following the intervention. To conclude, we provide partial evidence for a link between physical exercise and DA. Utilizing a PET protocol able to disentangle both D2R and DA levels could shed further light on whether, and how, aerobic exercise impacts the dopaminergic system in older adults.

  • 11.
    Karlsson, Sari
    et al.
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Karlsson, Per
    Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, Stockholm, Sweden.
    Fischer, Håkan
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Thilers, Petra
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    MacDonald, Stuart
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Brehmer, Yvonne
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Rieckmann, Anna
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Halldin, Christer
    Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, Stockholm, Sweden.
    Farde, Lars
    Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, Stockholm, Sweden.
    Bäckman, Lars
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Modulation of striatal dopamine D1 binding by cognitive processing2009In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 48, no 2, p. 398-404Article in journal (Refereed)
    Abstract [en]

    There is strong evidence that dopamine (DA) is implicated in higher-order cognitive functioning, but it remains controversial whether D1 receptor binding can be modified by cognitive activity. We examined striatal D1 binding potential (BP) in 20 younger (22-30 years) and 20 older (65-75 years) persons who underwent two [(11)C] SCH 23390 PET measurements, one while resting and one while performing a cognitive task taxing inhibitory functioning. The younger persons showed significant task-related BP reductions in sensorimotor, limbic, and associative striatum during cognitive activity compared to rest. Older persons showed no reliable BP reductions in any striatal subregion. These findings demonstrate that D1 receptor binding can be modified by cognitive activity in younger persons, but also provide novel evidence for the notion that human aging is associated not only with lower DA receptor density but also with altered modifiability of the DA system.

  • 12.
    Karlsson, Sari
    et al.
    Karolinska Institute.
    Rieckmann, Anna
    Karolinska Institute.
    Karlsson, Per
    Karolinska Hospital.
    Farde, Lars
    Karolinska Hospital.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Bäckman, Lars
    Karolinska Institute.
    Relationship of dopamine D1 receptor binding in striatal and extrastriatal regions to cognitive functioning in healthy humans2011In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 57, no 2, p. 346-351Article in journal (Refereed)
    Abstract [en]

    Dopamine (DA) availability in both striatal and extrastriatal brain regions has been implicated in cognitive performance. Given that different brain regions are neuroanatomically and functionally different, DA receptor binding in different brain regions may be selectively important to specific cognitive functions. Using PET and the radioligand SCH23390, we measured D1 receptor binding potential (BP(ND)) in dorsolateral prefrontal cortex (DLPFC), hippocampus (HC), as well as in sensorimotor (SMST), associative (AST), and limbic (LST) striatum in 20 healthy younger persons. Subjects completed tasks assessing executive functioning, episodic memory, speed, and general knowledge. Unlike previous reports, we found no linear or curvilinear relationships between D1 receptor binding in DLPFC and performance in any cognitive task. However, BP(ND) in HC was positively linked to executive performance as well as to speed and knowledge. With regard to the striatal subregions, D1 BP(ND) in SMST was more strongly related to speed compared to the other striatal subregions, whereas D1 BP(ND) in AST was more strongly linked to general knowledge. These findings provide support for the notion that D1 receptors in separate brain regions are differentially related to performance in tasks tapping various cognitive domains.

  • 13.
    Kauppi, Karolina
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University,106 91 Stockholm, Stockholm Brain Institute, Sweden.
    Persson, Jonas
    Aging Research Center (ARC), Karolinska Institutet, Gävlegatan 16, SE-11330 Stockholm, Stockholm University, Sweden.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Additive genetic effect of APOE and BDNF on hippocampus activity2014In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 89, no 1, 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 ε4 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 ε4 and BDNF 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.

  • 14. Koehncke, Ylva
    et al.
    Papenberg, Goran
    Jonasson, Lars S.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Karalija, Nina
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Salami, Alireza
    Andersson, Micael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Bäckman, Lars
    Lindenberger, Ulman
    Lövdén, Martin
    Self-rated intensity of habitual physical activities is positively associated with dopamine D-2/3 receptor availability and cognition2018In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 181, p. 605-616Article in journal (Refereed)
    Abstract [en]

    Between-person differences in cognitive performance in older age are associated with variations in physical activity. The neurotransmitter dopamine (DA) contributes to cognitive performance, and the DA system deteriorates with advancing age. Animal data and a patient study suggest that physical activity modulates DA receptor availability, but data from healthy humans are lacking. In a cross-sectional study with 178 adults aged 64-68 years, we investigated links among self-reported physical activity, D(2/3)DA receptor (D2/3DR) availability, and cognitive performance. D2/3DR availability was measured with [C-11]raclopride positron emission tomography at rest. We used structural equation modeling to obtain latent factors for processing speed, episodic memory, working memory, physical activity, and D2/3DR availability in caudate, putamen, and hippocampus. Physical activity intensity was positively associated with D2/3DR availability in caudate, but not putamen and hippocampus. Frequency of physical activity was not related to D2/3DR availability. Physical activity intensity was positively related to episodic memory and working memory. D2/3DR availability in caudate and hippocampus was positively related to episodic memory. Taken together, our results suggest that striatal DA availability might be a neurochemical correlate of episodic memory that is also associated with physical activity.

  • 15.
    Lindgren, Lenita
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Westling, Göran
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Brulin, Christine
    Umeå University, Faculty of Medicine, Department of Nursing.
    Lehtipalo, Stefan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Andersson, Micael
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Pleasant human touch is represented in pregenual anterior cingulate cortex2012In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 59, no 4, p. 3427-3432Article in journal (Refereed)
    Abstract [en]

    Touch massage (TM) is a form of pleasant touch stimulation used as treatment in clinical settings and found to improve well-being and decrease anxiety, stress, and pain. Emotional responses reported during and after TM have been studied, but the underlying mechanisms are still largely unexplored. In this study, we used functional magnetic resonance (fMRI) to test the hypothesis that the combination of human touch (i.e. skin-to-skin contact) with movement is eliciting a specific response in brain areas coding for pleasant sensations. The design included four different touch conditions; human touch with or without movement and rubber glove with or without movement. Force (2.5N) and velocity (1.5cm/s) were held constant across conditions. The pleasantness of the four different touch stimulations was rated on a visual analog scale (VAS-scale) and human touch was rated as most pleasant, particularly in combination with movement. The fMRI results revealed that TM stimulation most strongly activated the pregenual anterior cingulate cortex (pgACC). These results are consistent with findings showing pgACC activation during various rewarding pleasant stimulations. This area is also known to be activated by both opioid analgesia and placebo. Together with these prior results, our finding furthers the understanding of the basis for positive TM treatment effects.

  • 16.
    Marklund, Petter
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Fransson, P.
    Cognitive Neurophysiology Research Group, Department of Clinical Neuroscience, Karolinska Institute, Sweden.
    Cabeza, R.
    Center for Cognitive Neuroscience, Duke University, USA.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Ingvar, M.
    Cognitive Neurophysiology Research Group, Department of Clinical Neuroscience, Karolinska Institute, Sweden.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Unity and diversity of tonic and phasic executive control in episodic and working memory2007In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 36, no 4, p. 1361-1373Article in journal (Refereed)
    Abstract [en]

    The present study aimed to delineate the extent to which unitary executive functions might be shared across the separate domains of episodic and working memory. A mixed blocked/event-related functional magnetic resonance imaging (fMRI) design was employed to assess sustained (tonic control) and transient (phasic control) brain responses arising from incrementing executive demand (source versus item episodic memory - vis-à-vis - two-back versus one-back working memory) using load-dependent activation overlaps as indices of common components. Although an extensive portion of the regional load effects constituted differential control modulations in both sustained and transient responses, commonalities were also found implicating a subset of executive core mechanisms consistent with unitary or domain general control. 'Unitary' control modulations were temporally dissociated into (1) shared tonic components involving medial and lateral prefrontal cortex, striatum, cerebellum and superior parietal cortex, assumed to govern enhanced top-down context processing, monitoring and sustained attention throughout task periods and (2) stimulus-synchronous phasic components encompassing posterior intraparietal sulcus, hypothesized to support dynamic shifting of the 'focus of attention' among internal representations. Taken together, these results converge with theoretical models advocating both unity and diversity among executive control processes.

  • 17. Martensson, Johan
    et al.
    Eriksson, Johan
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Bodammer, Nils Christian
    Lindgren, Magnus
    Johansson, Mikael
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Lovden, Martin
    Growth of language-related brain areas after foreign language learning2012In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 63, no 1, p. 240-244Article in journal (Refereed)
    Abstract [en]

    The influence of adult foreign-language acquisition on human brain organization is poorly understood. We studied cortical thickness and hippocampal volumes of conscript interpreters before and after three months of intense language studies. Results revealed increases in hippocampus volume and in cortical thickness of the left middle frontal gyrus, inferior frontal gyrus, and superior temporal gyrus for interpreters relative to controls. The right hippocampus and the left superior temporal gyrus were structurally more malleable in interpreters acquiring higher proficiency in the foreign language. Interpreters struggling relatively more to master the language displayed larger gray matter increases in the middle frontal gyrus. These findings confirm structural changes in brain regions known to serve language functions during foreign-language acquisition. (C) 2012 Elsevier Inc. All rights reserved.

  • 18.
    Nyberg, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Andersson, Micael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Jakobson Mo, Susanna
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Marklund, Petter
    Nilsson, Lars-Göran
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Bäckman, Lars
    Striatal dopamine D2 binding is related to frontal BOLD response during updating of long-term memory representations.2009In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 46, no 4, p. 1194-1199Article in journal (Refereed)
    Abstract [en]

    Multi-modal brain imaging was used to examine the relation between individual differences in resting-state striatal dopamine D2 binding and the magnitude of prefrontal BOLD activation during updating of long-term memory (LTM) representations. Increased activity in the left prefrontal cortex was observed when LTM updating was required, and there was a positive correlation between striatal D2 activity and the magnitude of left prefrontal activity during updating. These findings support predictions from neurocomputational models of a relation of dopaminergic neurotransmission to transient cognitive operations and related brain activity.

  • 19. Prinelli, Federica
    et al.
    Fratiglioni, Laura
    Kalpouzos, Gregoria
    Musicco, Massimo
    Adorni, Fulvio
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Marseglia, Anna
    Xu, Weili
    Specific nutrient patterns are associated with higher structural brain integrity in dementia-free older adults2019In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 199, p. 281-288Article in journal (Refereed)
    Abstract [en]

    Optimal nutrition may play a beneficial role in maintaining a healthy brain. However, the relationship between nutrient intake and brain integrity is largely unknown. We investigated the association of specific nutrient dietary patterns with structural characteristics of the brain. Within the population-based Swedish National study on Aging and Care-Kungsholmen (SNAC-K), a cross-sectional study of 417 dementia-free participants aged >= 60 years who underwent structural magnetic resonance imaging (MRI) scans during 2001-2003, was carried-out. Data on dietary intake were collected using a food frequency questionnaire, from which intake of 21 nutrients was estimated. By principal component analysis, five nutrient patterns were extracted: (1) NP1 was characterized by fiber, vitamin C, E, beta-carotene, and folate [Fiber&Antioxidants], (2) NP2 by eicosapentaenoic (EPA, 20:5 omega-3) and docosahexaenoic (DHA, 22:6 omega-3) polyunsaturated fatty acids (PUFAs), proteins, cholesterol, vitamin B3, B12, and D [long chain (LC) omega-3PUFAs&Proteins], (3) NP3 by alpha-linoleic (18:2 omega-6) and alpha-linolenic (18:3 omega-3) PUFAs, monounsaturated fatty acids (MUFAs), and vitamin E [MUFAs &omega-3,6PUFAs], (4) NP4 by saturated fatty acids (SFAs), trans fats, MUFAs, and cholesterol [SFAs&Trans fats], (5) NP5 by B-vitamins, retinol, and proteins [B-Vitamins&Retinol]. Nutrient patterns scores were tertiled with the lowest tertile as reference, and were related to total brain volume (TBV) and white matter hyperintensities volume (WMHV) using linear regression models adjusting for potential confounders. In the multi-adjusted model, compared to the lowest intake for each pattern, the highest intake of NP1 (beta = 11.11, P = 0.009), NP2 (beta = 7.47, P = 0.052), and NP3 (beta = 10.54, P = 0.005) was associated with larger TBV whereas NP5 was related to smaller TBV (beta = -12.82, P = 0.001). The highest intake of NP1 was associated with lower WMHV (beta = -0.32, P = 0.049), whereas NP4 was associated with greater WMHV (beta = 0.31, P = 0.036). In sum, our results suggest that the identified brain-health specific nutrient combinations characterized by higher intake of fruit, vegetables, legumes, olive and seed oils, fish, lean red meat, poultry and low in milk and dairy products, cream, butter, processed meat and offal, were strongly associated with greater brain integrity among older adults.

  • 20. Rieckmann, Anna
    et al.
    Fischer, Håkan
    Bäckman, Lars
    Activation in striatum and medial temporal lobe during sequence learning in younger and older adults: relations to performance.2010In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 50, no 3, p. 1303-12Article in journal (Refereed)
    Abstract [en]

    The striatum and connected cortical areas have been implicated in sequence learning (SL) tasks, in which performance increments are gradual and learning typically occurs in the absence of awareness. It has recently been shown that increasing striatal activation during SL may be accompanied by decreasing activation in the medial temporal lobe (MTL) across time, but the specific contribution of the MTL to SL remains unclear. In the current age-comparative fMRI study, we show that gradual SL in the serial reaction time task is associated with activation increases in the striatum and activation decreases in the MTL across time in younger adults. However, in older adults, SL is positively related to activation increases in both the striatum and the MTL. The results are discussed in terms of the functional role of the MTL in SL, and offer a novel explanation of the fact that SL is little affected in aging.

  • 21.
    Salami, Alireza
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
    Avelar-Pereira, Barbara
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Garzon, Benjamin
    Sitnikov, Rouslan
    Kalpouzos, Gregoria
    Functional coherence of striatal resting-state networks is modulated by striatal iron content2018In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 183, p. 495-503Article in journal (Refereed)
    Abstract [en]

    Resting-state spontaneous fluctuations have revealed individual differences in the functional architecture of brain networks. Previous research indicates that the striatal network shows alterations in neurological conditions but also in normal aging. However, the neurobiological mechanisms underlying individual differences in striatal resting-state networks (RSNs) have been less explored. One candidate that may account for individual differences in striatal spontaneous activity is the level of local iron accumulation. Excessive iron in the striatum has been linked to a loss of structural integrity and reduced brain activity during task performance in aging. Using independent component analysis in a sample of 42 younger and older adults, we examined whether higher striatal iron content, quantified using relaxometry, underlies individual differences in spontaneous fluctuations of RSNs in general, and of the striatum in particular. Higher striatal iron content was linked to lower spontaneous coherence within both caudate and putamen RSNs regardless of age. No such links were observed for other RSNs. Moreover, the number of connections between the putamen and other RSNs was negatively associated with iron content, suggesting that iron modulated the degree of cross-talk between the striatum and cerebral cortex. Importantly, these associations were primarily driven by the older group. Finally, a positive association was found between coherence in the putamen and motor performance, suggesting that this spontaneous activity is behaviorally meaningful. A follow-up mediation analysis also indicated that functional connectivity may mediate the link between striatal iron and motor performance. Our preliminary findings suggest that striatal iron potentially accounts for individual differences in spontaneous striatal fluctuations, and might be used as a locus of intervention.

  • 22.
    Salami, Alireza
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Eriksson, Johan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Kompus, Kristiina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Habib, Reza
    Southern Illinois University , Carbondale.
    Kauppi, Karolina
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Characterizing the neural correlates of modality-specific and modality-independent accessibility and availability signals in memory using partial-least squares2010In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 52, no 2, p. 686-698Article in journal (Refereed)
    Abstract [en]

    Previous studies have shown that information that currently cannot be retrieved but will be retrieved on a subsequent, more supported task (i.e. is available but not accessible) has a distinct neural signature compared with non-available information. For verbal paired-associates, an availability signal has been revealed in left middle temporal cortex, an area potentially involved in the storage of such information, raising the possibility that availability signals are expressed in modality-specific storage sites. In the present study subjects encoded pictures and sounds representing concrete objects. One day later, during fMRI scanning, a verbal cued-recall task was administrated followed by a post-scan recognition task. Items remembered on both tasks were classified as accessible; items not remembered on the first but on the second task were classified as available; and items not remembered on any of the tasks were classified as not available. Multivariate partial-least-squares analyses revealed a modality-independent accessibility network with dominant contributions of left inferior parietal cortex, left inferior frontal cortex, and left hippocampus. Additionally, a modality-specific availability network was identified which included increased activity in visual regions for available pictorial information and in auditory regions for available sound information. These findings show that availability in memory, at least in part, is characterized by systematic changes in brain activity in sensory regions whereas memory access reflects differential activity in a modality-independent, conceptual network, thus indicating qualitative differences between availability and accessibility in memory.

  • 23.
    Salami, Alireza
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Karolinska Inst, Aging Res Ctr, SE-11330 Stockholm, Sweden.
    Rieckmann, Anna
    Fischer, Håkan
    Bäckman, Lars
    A multivariate analysis of age-related differences in functional networks supporting conflict resolution2014In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 86, p. 150-163Article in journal (Refereed)
    Abstract [en]

    Functional neuroimaging studies demonstrate age-related differences in recruitment of a large-scale attentional network during interference resolution, especially within dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). These alterations in functional responses have been frequently observed despite equivalent task performance, suggesting age-related reallocation of neural resources, although direct evidence for a facilitating effect in aging is sparse. We used the multi-source interference task and multivariate partial-least-squares to investigate age-related differences in the neuronal signature of conflict resolution, and their behavioral implications in younger and older adults. There were interference-related increases in activity, involving fronto-parietal and basal ganglia networks that generalized across age. In addition an age-by-task interaction was observed within a distributed network, including DLPFC and ACC, with greater activity during interference in the old. Next, we combined brain-behavior and functional connectivity analyses to investigate whether compensatory brain changes were present in older adults, using DLPFC and ACC as regions of interest (i.e. seed regions). This analysis revealed two networks differentially related to performance across age groups. A structural analysis revealed age-related gray-matter losses in regions facilitating performance in the young, suggesting that functional reorganization may partly reflect structural alterations in aging. Collectively, these findings suggest that age-related structural changes contribute to reductions in the efficient recruitment of a youth-like interference network, which cascades into instantiation of a different network facilitating conflict resolution in elderly people.

  • 24.
    Sigray, Pontus Plavén
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Gustavsson, Petter
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Farde, Lars
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Borg, Jacqueline
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Stenkrona, Per
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Bäckman, Lars
    Aging Research Center, Karolinska Institutet, Sweden.
    Cervenka, Simon
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Dopamine D1 receptor availability is related to social behavior: a positron emission tomography study2014In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 102, no 2, p. 590-595Article in journal (Refereed)
    Abstract [en]

    Dysfunctional interpersonal behavior is thought to underlie a wide spectrum of psychiatric disorders; however, the neurobiological underpinnings of these behavioral disturbances are poorly understood. Previous molecular imaging studies have shown associations between striatal dopamine (DA) D2-receptor binding and interpersonal traits, such as social conformity. The objective of this study was to explore, for the first time, the role of DA D1-receptors (D1-R) in human interpersonal behavior. Twenty-three healthy subjects were examined using Positron Emission Tomography and the radioligand [11C]SCH23390, yielding D1-R binding potential values. Striatal D1-R binding was related to personality scales selected to specifically assess one dimension of interpersonal behavior, namely a combination of affiliation and dominance (i.e., the Social Desirability, Verbal Trait Aggression and Physical Trait Aggression scales from Swedish Universities Scales of Personality). An exploratory analysis was also performed for extrastriatal brain regions. D1-R binding potential values in limbic striatum (r=.52; p=.015), associative striatum (r=.55; p=.009), and sensorimotor striatum (r=.67; p=.001) were positively related to Social Desirability scores. D1-R binding potential in limbic striatum (r=-.51; p=.019) was negatively associated with Physical Trait Aggression scores. For extrastriatal regions, Social Desirability scores showed positive correlations in amygdala (r=.60; p=.006) and medial frontal cortex (r=.60; p=.004). This study provides further support for the role of DA function in the expression of disaffiliative and dominant traits. Specifically, D1-R availability may serve as a marker for interpersonal behavior in humans. Associations were demonstrated for the same dimension of interpersonal behavior as for D2-R, but in the opposite direction, suggesting that the two receptor subtypes are involved in the same behavioral processes, but with different functional roles.

  • 25.
    Säfström, Daniel
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Domellöf, Erik
    Umeå University, Faculty of Social Sciences, Department of Psychology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Brain activations supporting linking of action phases in a sequential manual task2018In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, ., Vol. 172, p. 608-619Article in journal (Refereed)
    Abstract [en]

    Most everyday manual tasks, like grabbing a cup of coffee to drink, are comprised of a sequence of action phases. Efficient phase transitions, or linking, are achieved using a predictive control policy where motor commands for the next phase are specified and released in anticipation of sensory confirmation of goal completion of the current phase. If there is a discrepancy between predicted and actual sensory feedback about goal completion, corrective actions are employed to complete the current action phase before proceeding to the next. However, we lack understanding about brain activations supporting such predictive linking and corrective actions in manual tasks. In this study, during 3-T MRI-scanning, sixteen participants (5 males, 11 females; mean age 27.3 years, range 23–37) performed a sequential manual task, with or without the possibility for predictive linking. We found that predictive linking of action phases was associated with increased activation in a network that included right-sided fronto-parietal areas related to visuospatial attention, eye movements and motor planning, left-sided parietal areas related to implicit timing and shifts of motor attention, occipital regions bilaterally reflecting visual processing related to the attended next target, and finally, the anterior midcingulate cortex involved in continuous performance monitoring. Corrective actions were associated with increased activation in the left dorsolateral prefrontal cortex involved in reestablishing executive control over previously automatized behavior.

  • 26.
    Theorin, Anna
    et al.
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Johansson, Roland
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Zones of bimanual and unimanual preference within human primary sensorimotor cortex during object manipulation2007In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 36, no Suppl 2, p. T2-T15Article in journal (Refereed)
    Abstract [en]

    We asked which brain areas are engaged in the coordination of our hands in dexterous object manipulations where they cooperate for achieving a common goal. Well-trained right-handers steered a cursor on a screen to hit successively displayed targets by applying isometric forces and torques to a rigid tool. In two bimanual conditions, the object was held freely in the air and the hands thus generated coupled opposing forces. Yet, depending on the mapping rule linking hand forces and cursor movements, all subjects selected either the left or the right hand as prime actor. In two unimanual conditions, the subjects performed the same task with either the left or the right hand operating on a fixed tool. Functional magnetic resonance imaging revealed common activation across all four conditions in a dorsal fronto-parietal network biased to the left hemisphere and in bilateral occipitotemporal cortex. Contrary to the notion that medial wall premotor areas are especially active in complex bimanual actions, their activation depended on acting hand (left, right) rather than on grip type (bimanual, unimanual). We observed effects of grip type only in the primary sensorimotor cortex (SMC). In particular, with either hand as prime actor, bimanual actions preferentially activated subregions of the SMC contralateral to the acting hand. A sizeable subregion with preference for unimanual activity was found only in the left SMC in our right-handed subjects. Collectively, these results indicate a hemispheric asymmetry for the SMC and that partially different neural populations support the control of bimanual versus unimanual object manipulations.

  • 27.
    Trulsson, M
    et al.
    Karolinska Institute.
    Francis, S T
    University of Nottingham.
    Kelly, E F
    University of North Carolina.
    Westling, Göran
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Bowtell, R
    University of Nottingham.
    McGlone, F
    Port Sunlight Laboratory, Unilever Research, Wirral, University of Wales, Bangor, United Kingdom, .
    Cortical responses to single mechanoreceptive afferent microstimulation revealed with fMRI2001In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 13, no 4, p. 613-622Article in journal (Refereed)
    Abstract [en]

    The technique of intraneural microneurography/microstimulation has been used extensively to study contributions of single, physiologically characterized mechanoreceptive afferents (MRAs) to properties of somatosensory experience in awake human subjects. Its power as a tool for sensory neurophysiology can be greatly enhanced, however, by combining it with functional neuroimaging techniques that permit simultaneous measurement of the associated CNS responses. Here we report its successful adaptation to the environment of a high-field MR scanner. Eight median-nerve MRAs were isolated and characterized in three subjects and microstimulated in conjunction with fMRI at 3.0 T. Hemodynamic responses were observed in every case, and these responses were robust, focal, and physiologically orderly. The combination of fMRI with microstimulation will enable more detailed studies of the representation of the body surface in human somatosensory cortex and further studies of the relationship of that organization to short-term plasticity in the human SI cortical response to natural tactile stimuli. It can also be used to study many additional topics in sensory neurophysiology, such as CNS responses to additional classes of afferents and the effects of stimulus patterning and unimodal/crossmodal attentional manipulations. Finally, it presents unique opportunities to investigate the basic physiology of the BOLD effect and to compare the operating characteristics of fMRI and EEG as human functional neuroimaging modalities in an unusually specific and well-characterized neurophysiological setting.

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