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  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Bergström, Fredrik, 1983-, et al. (författare)
  • Neural evidence for non-conscious working memory
  • 2018
  • Ingår i: Cerebral Cortex. - : Oxford University Press. - 1047-3211 .- 1460-2199. ; 28:9, s. 3217-3228
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent studies have found that non-consciously perceived information can be retained for several seconds, a feat that has been attributed to non-conscious working memory processes. However, these studies have mainly relied on subjective measures of visual experience, and the neural processes responsible for non-conscious short-term retention remains unclear. Here we used continuous flash suppression to render stimuli non-conscious in a delayed match-to-sample task together with fMRI to investigate the neural correlates of non-conscious short-term (5-15 s) retention. The participants' behavioral performance was at chance level when they reported no visual experience of the sample stimulus. Critically, multivariate pattern analyses of BOLD signal during the delay phase could classify presence versus absence of sample stimuli based on signal patterns in frontal cortex, and its spatial position based on signal patterns in occipital cortex. In addition, univariate analyses revealed increased BOLD signal change in prefrontal regions during memory recognition. Thus, our findings demonstrate short-term maintenance of information presented non-consciously, defined by chance performance behaviorally. This non-consciously retained information seems to rely on persistent neural activity in frontal and occipital cortex, and may engage further cognitive control processes during memory recognition.
  • Boyle, Julie A., et al. (författare)
  • The Human Brain Distinguishes between Single Odorants and Binary Mixtures
  • 2009
  • Ingår i: Cerebral Cortex. - 1047-3211 .- 1460-2199. ; 19:1, s. 66-71
  • Tidskriftsartikel (refereegranskat)abstract
    • Single odors are processed differently from odor mixtures in the cortex of rodents. We investigated whether single and binary odor mixtures activate different regions also in the human brain. We analyzed data from positron emission tomography scans using pyridine, citral, and 5 mixtures of pyridine and citral in proportions varying from 10/90 to 90/10, with 50/50 being the most impure. Comparing mixtures with single odorants gave activation in the left cingulate and right parietal and superior frontal cortices and bilateral activation in the anterior and lateral orbitofrontal cortices. We also found that brain activity in the lateral orbitofrontal cortex (OFC) increased with odorant impurity, whereas the anterior OFC was activated for binary odor mixtures and deactivated for single components. We conclude that binary odor mixtures and their individual components are processed differently by the human brain. The lateral portion of the OFC responds to mixture impurity in a graded fashion, whereas the anterior portion acts like an on-off detector of odor mixtures.
  • Burzynska, A Z, et al. (författare)
  • Microstructure of frontoparietal connections predicts cortical responsivity and working memory performance
  • 2011
  • Ingår i: Cerebral Cortex. - 1047-3211 .- 1460-2199. ; 21:10, s. 2261-2271
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated how the microstructure of relevant white matter connections is associated with cortical responsivity and working memory (WM) performance by collecting diffusion tensor imaging and verbal WM functional magnetic resonance imaging data from 29 young adults. We measured cortical responsivity within the frontoparietal WM network as the difference in blood oxygenation level-dependent (BOLD) signal between 3-back and 1-back conditions. Fractional anisotropy served as an index of the integrity of the superior longitudinal fasciculi (SLF), which connect frontal and posterior regions. We found that SLF integrity is associated with better 3-back performance and greater task-related BOLD responsivity. In addition, BOLD responsivity in right premotor cortex reliably mediated the effects of SLF integrity on 3-back performance but did not uniquely predict 3-back performance after controlling for individual differences in SLF integrity. Our results suggest that task-related adjustments of local gray matter processing are conditioned by the properties of anatomical connections between relevant cortical regions. We suggest that the microarchitecture of white matter tracts influences the speed of signal transduction along axons. This in turn may affect signal summation at neural dendrites, action potential firing, and the resulting BOLD signal change and responsivity.
  • Cardin, Velia, et al. (författare)
  • The Organization of Working Memory Networks is Shaped by Early Sensory Experience
  • 2018
  • Ingår i: Cerebral Cortex. - : OXFORD UNIV PRESS INC. - 1047-3211 .- 1460-2199. ; 28:10, s. 3540-3554
  • Tidskriftsartikel (refereegranskat)abstract
    • Early deafness results in crossmodal reorganization of the superior temporal cortex (STC). Here, we investigated the effect of deafness on cognitive processing. Specifically, we studied the reorganization, due to deafness and sign language (SL) knowledge, of linguistic and nonlinguistic visual working memory (WM). We conducted an fMRI experiment in groups that differed in their hearing status and SL knowledge: deaf native signers, and hearing native signers, hearing nonsigners. Participants performed a 2-back WM task and a control task. Stimuli were signs from British Sign Language (BSL) or moving nonsense objects in the form of point-light displays. We found characteristic WM activations in fronto-parietal regions in all groups. However, deaf participants also recruited bilateral posterior STC during the WM task, independently of the linguistic content of the stimuli, and showed less activation in fronto-parietal regions. Resting-state connectivity analysis showed increased connectivity between frontal regions and STC in deaf compared to hearing individuals. WM for signs did not elicit differential activations, suggesting that SL WM does not rely on modality-specific linguistic processing. These findings suggest that WM networks are reorganized due to early deafness, and that the organization of cognitive networks is shaped by the nature of the sensory inputs available during development.
  • Dall'orso, Sofia, 1992, et al. (författare)
  • Cortical Processing of Multimodal Sensory Learning in Human Neonates
  • 2021
  • Ingår i: Cerebral Cortex. - 1047-3211 .- 1460-2199. ; 31:3, s. 1827-1836
  • Tidskriftsartikel (refereegranskat)abstract
    • Following birth, infants must immediately process and rapidly adapt to the array of unknown sensory experiences associated with their new ex-utero environment. However, although it is known that unimodal stimuli induce activity in the corresponding primary sensory cortices of the newborn brain, it is unclear how multimodal stimuli are processed and integrated across modalities. The latter is essential for learning and understanding environmental contingencies through encoding relationships between sensory experiences; and ultimately likely subserves development of life-long skills such as speech and language. Here, for the first time, we map the intracerebral processing which underlies auditory-sensorimotor classical conditioning in a group of 13 neonates (median gestational age at birth: 38 weeks + 4 days, range: 32 weeks + 2 days to 41 weeks + 6 days; median postmenstrual age at scan: 40 weeks + 5 days, range: 38 weeks + 3 days to 42 weeks + 1 days) with blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (MRI) and magnetic resonance (MR) compatible robotics. We demonstrate that classical conditioning can induce crossmodal changes within putative unimodal sensory cortex even in the absence of its archetypal substrate. Our results also suggest that multimodal learning is associated with network wide activity within the conditioned neural system. These findings suggest that in early life, external multimodal sensory stimulation and integration shapes activity in the developing cortex and may influence its associated functional network architecture.
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