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1.
  • Adams, Rick A., et al. (författare)
  • Variability in Action Selection Relates to Striatal Dopamine 2/3 Receptor Availability in Humans : A PET Neuroimaging Study Using Reinforcement Learning and Active Inference Models
  • 2020
  • Ingår i: Cerebral Cortex. - 1047-3211 .- 1460-2199. ; 30:6, s. 3573-3589
  • Tidskriftsartikel (refereegranskat)abstract
    • Choosing actions that result in advantageous outcomes is a fundamental function of nervous systems. All computational decision-making models contain a mechanism that controls the variability of (or confidence in) action selection, but its neural implementation is unclear-especially in humans. We investigated this mechanism using two influential decision-making frameworks: active inference (AI) and reinforcement learning (RL). In AI, the precision (inverse variance) of beliefs about policies controls action selection variability-similar to decision 'noise' parameters in RL-and is thought to be encoded by striatal dopamine signaling. We tested this hypothesis by administering a 'go/no-go' task to 75 healthy participants, and measuring striatal dopamine 2/3 receptor (D2/3R) availability in a subset (n = 25) using [C-11]-(+)-PHNO positron emission tomography. In behavioral model comparison, RL performed best across the whole group but AI performed best in participants performing above chance levels. Limbic striatal D2/3R availability had linear relationships with AI policy precision (P = 0.029) as well as with RL irreducible decision 'noise' (P = 0.020), and this relationship with D2/3R availability was confirmed with a 'decision stochasticity' factor that aggregated across both models (P = 0.0006). These findings are consistent with occupancy of inhibitory striatal D(2/3)Rs decreasing the variability of action selection in humans.
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3.
  • Andin, Josefine, et al. (författare)
  • Working Memory for Signs with Poor Visual Resolution : fMRI Evidence of Reorganization of Auditory Cortex in Deaf Signers
  • 2021
  • Ingår i: Cerebral Cortex. - 1047-3211 .- 1460-2199. ; 31:7, s. 3165-3176
  • Tidskriftsartikel (refereegranskat)abstract
    • Stimulus degradation adds to working memory load during speech processing. We investigated whether this applies to sign processing and, if so, whether the mechanism implicates secondary auditory cortex. We conducted an fMRI experiment where 16 deaf early signers (DES) and 22 hearing non-signers performed a sign-based n-back task with three load levels and stimuli presented at high and low resolution. We found decreased behavioral performance with increasing load and decreasing visual resolution, but the neurobiological mechanisms involved differed between the two manipulations and did so for both groups. Importantly, while the load manipulation was, as predicted, accompanied by activation in the frontoparietal working memory network, the resolution manipulation resulted in temporal and occipital activation. Furthermore, we found evidence of cross-modal reorganization in the secondary auditory cortex: DES had stronger activation and stronger connectivity between this and several other regions. We conclude that load and stimulus resolution have different neural underpinnings in the visual–verbal domain, which has consequences for current working memory models, and that for DES the secondary auditory cortex is involved in the binding of representations when task demands are low.
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4.
  • Andin, Josefine, 1979-, et al. (författare)
  • Working Memory for Signs with Poor VisualResolution : fMRI Evidence of Reorganizationof Auditory Cortex in Deaf Signers
  • 2021
  • Ingår i: Cerebral Cortex. - : Oxford University Press. - 1047-3211 .- 1460-2199. ; , s. 1-12
  • Tidskriftsartikel (refereegranskat)abstract
    • Stimulus degradation adds to working memory load during speech processing.We investigated whether this applies to signprocessing and, if so, whether the mechanism implicates secondary auditory cortex.We conducted an fMRI experimentwhere 16 deaf early signers (DES) and 22 hearing non-signers performed a sign-based n-back task with three load levels andstimuli presented at high and low resolution.We found decreased behavioral performance with increasing load anddecreasing visual resolution, but the neurobiological mechanisms involved differed between the two manipulations and didso for both groups. Importantly, while the load manipulation was, as predicted, accompanied by activation in thefrontoparietal working memory network, the resolution manipulation resulted in temporal and occipital activation.Furthermore, we found evidence of cross-modal reorganization in the secondary auditory cortex: DES had strongeractivation and stronger connectivity between this and several other regions.We conclude that load and stimulus resolutionhave different neural underpinnings in the visual–verbal domain, which has consequences for current working memorymodels, and that for DES the secondary auditory cortex is involved in the binding of representations when task demandsare low.
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6.
  • B. Pereira, Joana, 1982, et al. (författare)
  • Amyloid Network Topology Characterizes the Progression of Alzheimer’s Disease During the Predementia Stages
  • 2018
  • Ingår i: Cerebral Cortex. - 1047-3211 .- 1460-2199. ; 28:1, s. 340-349
  • Tidskriftsartikel (refereegranskat)abstract
    • There is increasing evidence showing that the accumulation of the amyloid-β (Aβ) peptide into extracellular plaques is a central event in Alzheimer's disease (AD). These abnormalities can be detected as lowered levels of Aβ42 in the cerebrospinal fluid (CSF) and are followed by increased amyloid burden on positron emission tomography (PET) several years before the onset of dementia. The aim of this study was to assess amyloid network topology in nondemented individuals with early stage Aβ accumulation, defined as abnormal CSF Aβ42 levels and normal Florbetapir PET (CSF+/PET−), and more advanced Aβ accumulation, defined as both abnormal CSF Aβ42 and Florbetapir PET (CSF+/PET+). The amyloid networks were built using correlations in the mean 18F-florbetapir PET values between 72 brain regions and analyzed using graph theory analyses. Our findings showed an association between early amyloid stages and increased covariance as well as shorter paths between several brain areas that overlapped with the default-mode network (DMN). Moreover, we found that individuals with more advanced amyloid accumulation showed more widespread changes in brain regions both within and outside the DMN. These findings suggest that amyloid network topology could potentially be used to assess disease progression in the predementia stages of AD.
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7.
  • Bazov, Igor, 1973-, et al. (författare)
  • Neuronal Expression of Opioid Gene is Controlled by Dual Epigenetic and Transcriptional Mechanism in Human Brain
  • 2018
  • Ingår i: Cerebral Cortex. - : Oxford University Press. - 1047-3211 .- 1460-2199. ; 28:9, s. 3129-3142
  • Tidskriftsartikel (refereegranskat)abstract
    • Molecular mechanisms that define patterns of neuropeptide expression are essential for the formation and rewiring of neural circuits. The prodynorphin gene (PDYN) gives rise to dynorphin opioid peptides mediating depression and substance dependence. We here demonstrated that PDYN is expressed in neurons in human dorsolateral prefrontal cortex (dlPFC), and identified neuronal differentially methylated region in PDYN locus framed by CCCTC-binding factor binding sites. A short, nucleosome size human-specific promoter CpG island (CGI), a core of this region may serve as a regulatory module, which is hypomethylated in neurons, enriched in 5-hydroxymethylcytosine, and targeted by USF2, a methylation-sensitive E-box transcription factor (TF). USF2 activates PDYN transcription in model systems, and binds to nonmethylated CGI in dlPFC. USF2 and PDYN expression is correlated, and USF2 and PDYN proteins are co-localized in dlPFC. Segregation of activatory TF and repressive CGI methylation may ensure contrasting PDYN expression in neurons and glia in human brain.
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10.
  • Bergersen, L H, et al. (författare)
  • Immunogold detection of L-glutamate and D-serine in small synaptic-like microvesicles in adult hippocampal astrocytes.
  • 2012
  • Ingår i: Cerebral Cortex. - : Oxford University Press. - 1047-3211 .- 1460-2199. ; 22:7, s. 1690-1697
  • Tidskriftsartikel (refereegranskat)abstract
    • Glutamate and the N-methyl-D-aspartate receptor ligand D-serine are putative gliotransmitters. Here, we show by immunogold cytochemistry of the adult hippocampus that glutamate and D-serine accumulate in synaptic-like microvesicles (SLMVs) in the perisynaptic processes of astrocytes. The estimated concentration of fixed glutamate in the astrocytic SLMVs is comparable to that in synaptic vesicles of excitatory nerve terminals (≈ 45 and ≈ 55 mM, respectively), whereas the D-serine level is about 6 mM. The vesicles are organized in small spaced clusters located near the astrocytic plasma membrane. Endoplasmic reticulum is regularly found in close vicinity to SLMVs, suggesting that astrocytes contain functional nanodomains, where a local Ca(2+) increase can trigger release of glutamate and/or D-serine.
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