Stockholm Brain Institute

Stockholm, Sweden

Stockholm Brain Institute

Stockholm, Sweden
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Heijtz R.D.,Karolinska Institutet | Heijtz R.D.,Stockholm Brain Institute | Wang S.,Genome Institute of Singapore | Anuar F.,Karolinska Institutet | And 9 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2011

Microbial colonization of mammals is an evolution-driven process that modulate host physiology, many of which are associated with immunity and nutrient intake. Here, we report that colonization by gut microbiota impacts mammalian brain development and subsequent adult behavior. Using measures of motor activity and anxiety-like behavior, we demonstrate that germ free (GF) mice display increased motor activity and reduced anxiety, compared with specific pathogen free (SPF) mice with a normal gut microbiota. This behavioral phenotype is associated with altered expression of genes known to be involved in second messenger pathways and synaptic long-term potentiation in brain regions implicated in motor control and anxiety-like behavior. GF mice exposed to gut microbiota early in life display similar characteristics as SPF mice, including reduced expression of PSD-95 and synaptophysin in the striatum. Hence, our results suggest that the microbial colonization process initiates signaling mechanisms that affect neuronal circuits involved in motor control and anxiety behavior.


Marklund P.,University of Stockholm | Marklund P.,Stockholm Brain Institute | Persson J.,University of Stockholm | Persson J.,Umea Center for Functional Brain Imaging
NeuroImage | Year: 2012

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. © 2012 Elsevier Inc.


Schmack K.,Charité - Medical University of Berlin | de Castro A.G.-C.,Charité - Medical University of Berlin | Rothkirch M.,Charité - Medical University of Berlin | Sekutowicz M.,Charité - Medical University of Berlin | And 9 more authors.
Journal of Neuroscience | Year: 2013

Delusions are unfounded yet tenacious beliefs and a symptom of psychotic disorder. Varying degrees of delusional ideation are also found in the healthy population. Here, we empirically validated a neurocognitive model that explains both the formation and the persistence of delusional beliefs in terms of altered perceptual inference. In a combined behavioral and functional neuroimaging study in healthy participants, we used ambiguous visual stimulation to probe the relationship between delusion-proneness and the effect of learned predictions on perception. Delusional ideation was associated with less perceptual stability, but a stronger belief-induced bias on perception, paralleled by enhanced functional connectivity between frontal areas that encoded beliefs and sensory areas that encoded perception. These findings suggest that weakened lower-level predictions that result in perceptual instability are implicated in the emergence of delusional beliefs. In contrast, stronger higher-level predictions that sculpt perception into conformity with beliefs might contribute to the tenacious persistence of delusional beliefs. © 2013 the authors.


Persson N.,University of Stockholm | Persson N.,Stockholm Brain Institute | Ghisletta P.,University of Geneva | Ghisletta P.,Wayne State University | And 9 more authors.
NeuroImage | Year: 2016

We examined relationships between regional brain shrinkage and changes in cognitive performance, while taking into account the influence of chronological age, vascular risk, Apolipoprotein E variant and socioeconomic status. Regional brain volumes and cognitive performance were assessed in 167 healthy adults (age 19-79 at baseline), 90 of whom returned for the follow-up after two years. Brain volumes were measured in six regions of interest (ROIs): lateral prefrontal cortex (LPFC), prefrontal white matter (PFw), hippocampus (Hc), parahippocampal gyrus (PhG), cerebellar hemispheres (CbH), and primary visual cortex (VC), and cognitive performance was evaluated in three domains: episodic memory (EM), fluid intelligence (Gf), and vocabulary (V). Average volume loss was observed in Hc, PhG and CbH, but reliable individual differences were noted in all examined ROIs. Average positive change was observed in EM and V performance but not in Gf scores, yet only the last evidenced individual differences in change. We observed reciprocal influences among neuroanatomical and cognitive variables. Larger brain volumes at baseline predicted greater individual gains in Gf, but differences in LPFC volume change were in part explained by baseline level of cognitive performance. In one region (PFw), individual change in volume was coupled with change in Gf. Larger initial brain volumes did not predict slower shrinkage. The results underscore the complex role of brain maintenance and cognitive reserve in adult development. © 2015 Elsevier Inc.


Kauppi K.,Umeå University | Kauppi K.,Karolinska Institutet | Nilsson L.-G.,Umea Center for Functional Brain Imaging | Nilsson L.-G.,University of Stockholm | And 5 more authors.
NeuroImage | Year: 2014

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. © 2013 Elsevier Inc.


Wiens S.,University of Stockholm | Wiens S.,Stockholm Brain Institute | Sand A.,University of Stockholm | Olofsson J.K.,University of Stockholm | Olofsson J.K.,Stockholm Brain Institute
Biological Psychology | Year: 2011

Neural processing of emotional pictures is often indexed by two electrocortical responses: the early posterior negativity (EPN) and the late positive potential (LPP). Because emotional pictures vary in nonemotional features (e.g., composition, human content, and spatial frequency), researchers often match pictures on nonemotional features to avoid their confounding effects on the EPN and LPP. However, this matching is tedious and might be unnecessary if the confounding effects could be shown to be negligible. In an item-analysis of mean amplitudes to 400 negative to neutral pictures from the International Affective Picture System (IAPS), nonemotional features had larger effects on EPN than LPP. Picture composition suppressed the relationship between emotion and EPN. Further, data simulations showed that for small picture sets, nonemotional features inflated the correlation between emotion and LPP. Therefore, nonemotional features suppress the EPN and enhance the LPP, particularly so in small picture sets. © 2010 Elsevier B.V.


Klaus A.,National Institute of Mental Health | Klaus A.,Karolinska Institutet | Klaus A.,Stockholm Brain Institute | Yu S.,National Institute of Mental Health | Plenz D.,National Institute of Mental Health
PLoS ONE | Year: 2011

The size distribution of neuronal avalanches in cortical networks has been reported to follow a power law distribution with exponent close to -1.5, which is a reflection of long-range spatial correlations in spontaneous neuronal activity. However, identifying power law scaling in empirical data can be difficult and sometimes controversial. In the present study, we tested the power law hypothesis for neuronal avalanches by using more stringent statistical analyses. In particular, we performed the following steps: (i) analysis of finite-size scaling to identify scale-free dynamics in neuronal avalanches, (ii) model parameter estimation to determine the specific exponent of the power law, and (iii) comparison of the power law to alternative model distributions. Consistent with critical state dynamics, avalanche size distributions exhibited robust scaling behavior in which the maximum avalanche size was limited only by the spatial extent of sampling ("finite size" effect). This scale-free dynamics suggests the power law as a model for the distribution of avalanche sizes. Using both the Kolmogorov-Smirnov statistic and a maximum likelihood approach, we found the slope to be close to -1.5, which is in line with previous reports. Finally, the power law model for neuronal avalanches was compared to the exponential and to various heavy-tail distributions based on the Kolmogorov-Smirnov distance and by using a log-likelihood ratio test. Both the power law distribution without and with exponential cut-off provided significantly better fits to the cluster size distributions in neuronal avalanches than the exponential, the lognormal and the gamma distribution. In summary, our findings strongly support the power law scaling in neuronal avalanches, providing further evidence for critical state dynamics in superficial layers of cortex.


Petrovic P.,Stockholm Brain Institute | Kalso E.,University of Helsinki | Petersson K.M.,Stockholm Brain Institute | Petersson K.M.,FARO | And 3 more authors.
Pain | Year: 2010

Behavioral studies have suggested that placebo analgesia is partly mediated by the endogenous opioid system. Expanding on these results we have shown that the opioid-receptor-rich rostral anterior cingulate cortex (rACC) is activated in both placebo and opioid analgesia. However, there are also differences between the two treatments. While opioids have direct pharmacological effects, acting on the descending pain inhibitory system, placebo analgesia depends on neocortical top-down mechanisms. An important difference may be that expectations are met to a lesser extent in placebo treatment as compared with a specific treatment, yielding a larger error signal. As these processes previously have been shown to influence other types of perceptual experiences, we hypothesized that they also may drive placebo analgesia. Imaging studies suggest that lateral orbitofrontal cortex (lObfc) and ventrolateral prefrontal cortex (vlPFC) are involved in processing expectation and error signals. We re-analyzed two independent functional imaging experiments related to placebo analgesia and emotional placebo to probe for a differential processing in these regions during placebo treatment vs. opioid treatment and to test if this activity is associated with the placebo response. In the first dataset lObfc and vlPFC showed an enhanced activation in placebo analgesia vs. opioid analgesia. Furthermore, the rACC activity co-varied with the prefrontal regions in the placebo condition specifically. A similar correlation between rACC and vlPFC was reproduced in another dataset involving emotional placebo and correlated with the degree of the placebo effect. Our results thus support that placebo is different from specific treatment with a prefrontal top-down influence on rACC. © 2010 International Association for the Study of Pain.


Soderqvist S.,Karolinska Institutet | Soderqvist S.,Stockholm Brain Institute | Nutley S.B.,Karolinska Institutet | Nutley S.B.,Stockholm Brain Institute | And 4 more authors.
Frontiers in Human Neuroscience | Year: 2012

Children with intellectual disabilities show deficits in both reasoning ability and working memory (WM) that impact everyday functioning and academic achievement. In this study we investigated the feasibility of cognitive training for improving WM and non-verbal reasoning (NVR) ability in children with intellectual disability. Participants were randomized to a 5- week adaptive training program (intervention group) or non-adaptive version of the program (active control group). Cognitive assessments were conducted prior to and directly after training, and one year later to examine effects of the training. Improvements during training varied largely and amount of progress during training predicted transfer to WM and comprehension of instructions, with higher training progress being associated with greater transfer improvements. The strongest predictors for training progress were found to be gender, co-morbidity and baseline capacity on verbal WM. In particular, females without an additional diagnosis and with higher baseline performance showed greater progress. No significant effects of training were observed at the one-year follow-up, suggesting that training should be more intense or repeated in order for effects to persist in children with intellectual disabilities. A major finding of this study is that cognitive training is feasible in this clinical sample and can help improve their cognitive performance. However, a minimum cognitive capacity or training ability seems necessary for the training to be beneficial, with some individuals showing little improvement in performance. Future studies of cognitive training should take into consideration how inter-individual differences in training progress influence transfer effects and further investigate how baseline capacities predict training outcome. © 2012 Söderqvist, Bergman nutley, Ottersen, Grill and Klingberg.


Kadetoff D.,Stockholm Brain Institute | Kosek E.,Stockholm Brain Institute
Journal of Rehabilitation Medicine | Year: 2010

Objective: To assess activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenocortical axis during static exercise in patients with fibromyalgia. Patients and methods: Sixteen patients with fibromyalgia and 16 healthy controls performed a static knee extension until exhaustion. Plasma catecholamines, adrenocorticotropic hormone and Cortisol, as well as blood pressure and heart rate, were assessed before, during and following contraction. Plasma C reactive protein was analysed at baseline. Results: Blood pressure and heart rate increased during contraction (p < 0.001) and decreased following contraction (p<0.001) in both groups alike. Compared with baseline, plasma catecholamines increased during contraction in both groups (p<0.001), but patients with fibromyalgia had lower levels of plasma adrenaline (p<0.04) and noradrenaline (p<0.08) at all times. Adrenocorticotropic hormone increased at exhaustion in controls (p<0.001), but not in patients with fibromyalgia, who also had lower adrenocorticotropic hormone at exhaustion (p<0.02) compared with controls. There were no group differences, or changes over time in plasma Cortisol. High sensitivity C reactive protein was higher in patients with fibromyalgia compared with controls (p< 0.02). Conclusion: Patients with fibromyalgia exhibited a hypoactive sympatho-adrenal system as well as a hypo-reactive hypothalamic-pituitary axis during static exercise. Journal Compilation © 2010 Foundation of Rehabilitation Information.

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