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1.
  • Adams, Rick A., et al. (author)
  • 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
  • In: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 30:6, s. 3573-3589
  • Journal article (peer-reviewed)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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4.
  • Andin, Josefine, 1979-, et al. (author)
  • Working Memory for Signs with Poor Visual Resolution : fMRI Evidence of Reorganization of Auditory Cortex in Deaf Signers
  • 2021
  • In: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 31:7, s. 3165-3176
  • Journal article (peer-reviewed)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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  • Arvidsson, Caroline, et al. (author)
  • Conversational production and comprehension: fMRI-evidence reminiscent of but deviant from the classical Broca–Wernicke model
  • 2024
  • In: Cerebral Cortex. - 1047-3211 .- 1460-2199. ; 34:3
  • Journal article (peer-reviewed)abstract
    • A key question in research on the neurobiology of language is to which extent the language production and comprehension systems share neural infrastructure, but this question has not been addressed in the context of conversation. We utilized a public fMRI dataset where 24 participants engaged in unscripted conversations with a confederate outside the scanner, via an audio-video link. We provide evidence indicating that the two systems share neural infrastructure in the left-lateralized perisylvian language network, but diverge regarding the level of activation in regions within the network. Activity in the left inferior frontal gyrus was stronger in production compared to comprehension, while comprehension showed stronger recruitment of the left anterior middle temporal gyrus and superior temporal sulcus, compared to production. Although our results are reminiscent of the classical Broca–Wernicke model, the anterior (rather than posterior) temporal activation is a notable difference from that model. This is one of the findings that may be a consequence of the conversational setting, another being that conversational production activated what we interpret as higher-level socio-pragmatic processes. In conclusion, we present evidence for partial overlap and functional asymmetry of the neural infrastructure of production and comprehension, in the above-mentioned frontal vs temporal regions during conversation.
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8.
  • Bazov, Igor, 1973-, et al. (author)
  • Neuronal Expression of Opioid Gene is Controlled by Dual Epigenetic and Transcriptional Mechanism in Human Brain
  • 2018
  • In: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 28:9, s. 3129-3142
  • Journal article (peer-reviewed)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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11.
  • Bergersen, L H, et al. (author)
  • Immunogold detection of L-glutamate and D-serine in small synaptic-like microvesicles in adult hippocampal astrocytes.
  • 2012
  • In: Cerebral Cortex. - : Oxford University Press. - 1047-3211 .- 1460-2199. ; 22:7, s. 1690-1697
  • Journal article (peer-reviewed)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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  • Bergström, Fredrik, 1983-, et al. (author)
  • Neural evidence for non-conscious working memory
  • 2018
  • In: Cerebral Cortex. - : Oxford University Press. - 1047-3211 .- 1460-2199. ; 28:9, s. 3217-3228
  • Journal article (peer-reviewed)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.
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14.
  • Boyle, Julie A., et al. (author)
  • The Human Brain Distinguishes between Single Odorants and Binary Mixtures
  • 2009
  • In: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 19:1, s. 66-71
  • Journal article (peer-reviewed)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.
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  • Bramao, Ines, et al. (author)
  • Encoding contexts are incidentally reinstated during competitive retrieval and track the temporal dynamics of memory interference
  • 2022
  • In: Cerebral Cortex. - : Oxford University Press (OUP). - 1460-2199 .- 1047-3211. ; 32:22, s. 5020-5035
  • Journal article (peer-reviewed)abstract
    • The ability to remember an episode from our past is often hindered by competition from similar events. For example, if we want to remember the article a colleague recommended during the last lab-meeting, we may need to resolve interference from other article recommendations from the same colleague. This study investigates if the contextual features specifying the encoding episodes are incidentally reinstated during competitive memory retrieval. Competition between memories was created through the AB/AC interference paradigm. Individual word-pairs were presented embedded in a slowly drifting real-word like context. Multivariate pattern analysis (MVPA) of high temporal-resolution electroencephalographic (EEG) data was used to investigate context reactivation during memory retrieval. Behaviorally, we observed proactive (but not retroactive) interference; that is, performance for AC competitive retrieval was worse compared to a control DE non-competitive retrieval, whereas AB retrieval did not suffer from competition. Neurally, proactive interference was accompanied by an early reinstatement of the competitor context and interference resolution was associated with the ensuing reinstatement of the target context. Together, these findings provide novel evidence showing that the encoding contexts of competing discrete events are incidentally reinstated during competitive retrieval and that such reinstatement tracks retrieval competition and subsequent interference resolution.
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  • Burzynska, A Z, et al. (author)
  • Microstructure of frontoparietal connections predicts cortical responsivity and working memory performance
  • 2011
  • In: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 21:10, s. 2261-2271
  • Journal article (peer-reviewed)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.
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  • Cabeza, Roberto, et al. (author)
  • Task-independent and task-specific age effects on brain activity during working memory, visual attention and episodic retrieval.
  • 2004
  • In: Cerebral Cortex. - 1047-3211. ; 14:4, s. 364-75
  • Journal article (peer-reviewed)abstract
    • It is controversial whether the effects of aging on various cognitive functions have the same common cause or several different causes. To investigate this issue, we scanned younger and older adults with functional magnetic resonance imaging (fMRI) while performing three different tasks: working memory, visual attention and episodic retrieval. There were three main results. First, in all three tasks, older adults showed weaker occipital activity and stronger prefrontal and parietal activity than younger adults. The occipital reduction is consistent with the view that sensory processing decline is a common cause in cognitive aging, and the prefrontal increase may reflect functional compensation. Secondly, older adults showed more bilateral patterns of prefrontal activity than younger adults during working memory and visual attention tasks. These findings are consistent with the Hemispheric Asymmetry Reduction in Older Adults (HAROLD) model. Finally, compared to younger adults, older adults showed weaker hippocampal formation activity in all three tasks but stronger parahippocampal activity in the episodic retrieval task. The former finding suggests that age-related hippocampal deficits may have a global effect in cognition, and the latter is consistent with an age-related increase in familiarity-based recognition. Taken together, the results indicate that both common and specific factors play an important role in cognitive aging.
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  • Cacciaglia, Raffaele, et al. (author)
  • APOE-ε4 Shapes the Cerebral Organization in Cognitively Intact Individuals as Reflected by Structural Gray Matter Networks.
  • 2020
  • In: Cerebral cortex. - : Oxford University Press (OUP). - 1460-2199 .- 1047-3211. ; 30:7, s. 4110-4120
  • Journal article (peer-reviewed)abstract
    • Gray matter networks (GMn) provide essential information on the intrinsic organization of the brain and appear to be disrupted in Alzheimer's disease (AD). Apolipoprotein E (APOE)-ε4 represents the major genetic risk factor for AD, yet the association between APOE-ε4 and GMn has remained unexplored. Here, we determine the impact of APOE-ε4 on GMn in a large sample of cognitively unimpaired individuals, which was enriched for the genetic risk of AD. We used independent component analysis to retrieve sources of structural covariance and analyzed APOE group differences within and between networks. Analyses were repeated in a subsample of amyloid-negative subjects. Compared with noncarriers and heterozygotes, APOE-ε4 homozygotes showed increased covariance in one network including primarily right-lateralized, parietal, inferior frontal, as well as inferior and middle temporal regions, which mirrored the formerly described AD-signature. This result was confirmed in a subsample of amyloid-negative individuals. APOE-ε4 carriers showed reduced covariance between two networks encompassing frontal and temporal regions, which constitute preferential target of amyloid deposition. Our data indicate that, in asymptomatic individuals, APOE-ε4 shapes the cerebral organization in a way that recapitulates focal morphometric alterations observed in AD patients, even in absence of amyloid pathology. This suggests that structural vulnerability in neuronal networks associated with APOE-ε4 may be an early event in AD pathogenesis, possibly upstream of amyloid deposition.
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  • Cacciaglia, R., et al. (author)
  • Genotypic effects of APOE-epsilon 4 on resting-state connectivity in cognitively intact individuals support functional brain compensation
  • 2022
  • In: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 33:6, s. 2748-60
  • Journal article (peer-reviewed)abstract
    • The investigation of resting-state functional connectivity (rsFC) in asymptomatic individuals at genetic risk for Alzheimer's disease (AD) enables discovering the earliest brain alterations in preclinical stages of the disease. The APOE-epsilon 4 variant is the major genetic risk factor for AD, and previous studies have reported rsFC abnormalities in carriers of the epsilon 4 allele. Yet, no study has assessed APOE-epsilon 4 gene-dose effects on rsFC measures, and only a few studies included measures of cognitive performance to aid a clinical interpretation. We assessed the impact of APOE-epsilon 4 on rsFC in a sample of 429 cognitively unimpaired individuals hosting a high number of epsilon 4 homozygotes (n = 58), which enabled testing different models of genetic penetrance. We used independent component analysis and found a reduced rsFC as a function of the APOE-epsilon 4 allelic load in the temporal default-mode and the medial temporal networks, while recessive effects were found in the extrastriate and limbic networks. Some of these results were replicated in a subsample with negative amyloid markers. Interaction with cognitive data suggests that such a network reorganization may support cognitive performance in the epsilon 4-homozygotes. Our data indicate that APOE-epsilon 4 shapes the functional architecture of the resting brain and favor the idea of a network-based functional compensation.
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  • Canal-Garcia, Anna, et al. (author)
  • Dynamic multilayer functional connectivity detects preclinical and clinical Alzheimer's disease
  • 2024
  • In: CEREBRAL CORTEX. - 1047-3211 .- 1460-2199.
  • Journal article (peer-reviewed)abstract
    • Increasing evidence suggests that patients with Alzheimer's disease present alterations in functional connectivity but previous results have not always been consistent. One of the reasons that may account for this inconsistency is the lack of consideration of temporal dynamics. To address this limitation, here we studied the dynamic modular organization on resting-state functional magnetic resonance imaging across different stages of Alzheimer's disease using a novel multilayer brain network approach. Participants from preclinical and clinical Alzheimer's disease stages were included. Temporal multilayer networks were used to assess time-varying modular organization. Logistic regression models were employed for disease stage discrimination, and partial least squares analyses examined associations between dynamic measures with cognition and pathology. Temporal multilayer functional measures distinguished all groups, particularly preclinical stages, overcoming the discriminatory power of risk factors such as age, sex, and APOE epsilon 4 carriership. Dynamic multilayer functional measures exhibited strong associations with cognition as well as amyloid and tau pathology. Dynamic multilayer functional connectivity shows promise as a functional imaging biomarker for both early- and late-stage Alzheimer's disease diagnosis.
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  • Canal-Garcia, A., et al. (author)
  • Multiplex Connectome Changes across the Alzheimer's Disease Spectrum Using Gray Matter and Amyloid Data
  • 2022
  • In: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 32:16, s. 3501-3515
  • Journal article (peer-reviewed)abstract
    • The organization of the Alzheimer's disease (AD) connectome has been studied using graph theory using single neuroimaging modalities such as positron emission tomography (PET) or structural magnetic resonance imaging (MRI). Although these modalities measure distinct pathological processes that occur in different stages in AD, there is evidence that they are not independent from each other. Therefore, to capture their interaction, in this study we integrated amyloid PET and gray matter MRI data into a multiplex connectome and assessed the changes across different AD stages. We included 135 cognitively normal (CN) individuals without amyloid-beta pathology (A beta-) in addition to 67 CN, 179 patients with mild cognitive impairment (MCI) and 132 patients with AD dementia who all had A beta pathology (A beta+) from the Alzheimer's Disease Neuroimaging Initiative. We found widespread changes in the overlapping connectivity strength and the overlapping connections across A beta-positive groups. Moreover, there was a reorganization of the multiplex communities in MCI A beta + patients and changes in multiplex brain hubs in both MCI A beta + and AD A beta + groups. These findings offer a new insight into the interplay between amyloid-beta pathology and brain atrophy over the course of AD that moves beyond traditional graph theory analyses based on single brain networks.
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  • Cardin, Velia, et al. (author)
  • The Organization of Working Memory Networks is Shaped by Early Sensory Experience
  • 2018
  • In: Cerebral Cortex. - : OXFORD UNIV PRESS INC. - 1047-3211 .- 1460-2199. ; 28:10, s. 3540-3554
  • Journal article (peer-reviewed)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.
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27.
  • Carlisi, CO, et al. (author)
  • Shared and Disorder-Specific Neurocomputational Mechanisms of Decision-Making in Autism Spectrum Disorder and Obsessive-Compulsive Disorder
  • 2017
  • In: Cerebral cortex (New York, N.Y. : 1991). - : Oxford University Press (OUP). - 1460-2199 .- 1047-3211. ; 27:12, s. 5804-5816
  • Journal article (peer-reviewed)abstract
    • Autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) often share phenotypes of repetitive behaviors, possibly underpinned by abnormal decision-making. To compare neural correlates underlying decision-making between these disorders, brain activation of boys with ASD (N = 24), OCD (N = 20) and typically developing controls (N = 20) during gambling was compared, and computational modeling compared performance. Patients were unimpaired on number of risky decisions, but modeling showed that both patient groups had lower choice consistency and relied less on reinforcement learning compared to controls. ASD individuals had disorder-specific choice perseverance abnormalities compared to OCD individuals. Neurofunctionally, ASD and OCD boys shared dorsolateral/inferior frontal underactivation compared to controls during decision-making. During outcome anticipation, patients shared underactivation compared to controls in lateral inferior/orbitofrontal cortex and ventral striatum. During reward receipt, ASD boys had disorder-specific enhanced activation in inferior frontal/insular regions relative to OCD boys and controls. Results showed that ASD and OCD individuals shared decision-making strategies that differed from controls to achieve comparable performance to controls. Patients showed shared abnormalities in lateral-(orbito)fronto-striatal reward circuitry, but ASD boys had disorder-specific lateral inferior frontal/insular overactivation, suggesting that shared and disorder-specific mechanisms underpin decision-making in these disorders. Findings provide evidence for shared neurobiological substrates that could serve as possible future biomarkers.
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  • Chen, Meng, et al. (author)
  • Neural Progenitor Cells in Cerebral Cortex of Epilepsy Patients do not Originate from Astrocytes Expressing GLAST.
  • 2017
  • In: Cerebral cortex (New York, N.Y. : 1991). - : Oxford University Press (OUP). - 1460-2199 .- 1047-3211. ; 27:12, s. 5672-5682
  • Journal article (peer-reviewed)abstract
    • Adult neurogenesis in human brain is known to occur in the hippocampus, the subventricular zone, and the striatum. Neural progenitor cells (NPCs) were reported in the cortex of epilepsy patients; however, their identity is not known. Since astrocytes were proposed as the source of neural progenitors in both healthy and diseased brain, we tested the hypothesis that NPCs in the epileptic cortex originate from reactive, alternatively, de-differentiated astrocytes that express glutamate aspartate transporter (GLAST). We assessed the capacity to form neurospheres and the differentiation potential of cells dissociated from fresh cortical tissue from patients who underwent surgical treatment for pharmacologically intractable epilepsy. Neurospheres were generated from 57% of cases (8/14). Upon differentiation, the neurosphere cells gave rise to neurons, oligodendrocytes, and astrocytes. Sorting of dissociated cells showed that only cells negative for GLAST formed neurospheres. In conclusion, we show that cells with neural stem cell properties are present in brain cortex of epilepsy patients, and that these cells are not GLAST-positive astrocytes.
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  • Dall'orso, Sofia, 1992, et al. (author)
  • Cortical Processing of Multimodal Sensory Learning in Human Neonates
  • 2021
  • In: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 31:3, s. 1827-1836
  • Journal article (peer-reviewed)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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35.
  • Darki, F, et al. (author)
  • Inter-Individual Differences in Striatal Connectivity Is Related to Executive Function Through Fronto-Parietal Connectivity
  • 2020
  • In: Cerebral cortex (New York, N.Y. : 1991). - : Oxford University Press (OUP). - 1460-2199 .- 1047-3211. ; 30:2, s. 672-681
  • Journal article (peer-reviewed)abstract
    • The striatum has long been associated with cognitive functions, but the mechanisms behind this are still unclear. Here we tested a new hypothesis that the striatum contributes to executive function (EF) by strengthening cortico-cortical connections. Striatal connectivity was evaluated by measuring the resting-state functional connectivity between ventral and dorsal striatum in 570 individuals, aged 3–20 years. Using structural equation modeling, we found that inter-individual differences in striatal connectivity had an indirect effect (via fronto-parietal functional connectivity) and a direct effect on a compound EF measure of working memory, inhibition, and set-shifting/flexibility. The effect of fronto-parietal connectivity on cognition did not depend on age: the influence was as strong in older as younger children. In contrast, striatal connectivity was closely related to changes in cognitive ability during childhood development, suggesting a specific role of the striatum in cognitive plasticity. These results support a new principle for striatal functioning, according to which striatum promotes cognitive development by strengthening of cortico-cortical connectivity.
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  • Darki, Fahimeh, et al. (author)
  • T1-Weighted/T2-Weighted Ratio Mapping at 5 Months Captures Individual Differences in Behavioral Development and Differentiates Infants at Familial Risk for Autism from Controls
  • 2021
  • In: Cerebral Cortex. - : Oxford University Press. - 1047-3211 .- 1460-2199. ; 31:9, s. 4068-4077
  • Journal article (peer-reviewed)abstract
    • Identifying structural measures that capture early brain development and are sensitive to individual differences in behavior is a priority in developmental neuroscience, with potential implications for our understanding of both typical and atypical populations. T1-weighted/T2-weighted (T1w/T2w) ratio mapping, which previously has been linked to myelination, represents an interesting candidate measure in this respect, as an accessible measure from standard magnetic resonance imaging (MRI) sequences. Yet, its value as an early infancy measure remains largely unexplored. Here, we compared T1w/T2w ratio in 5-month-old infants at familial risk (n = 27) for autism spectrum disorder (ASD) to those without elevated autism risk (n =16). We found lower T1w/T2w ratio in infants at high risk for ASD within widely distributed regions, spanning both white and gray matter. In regions differing between groups, higher T1w/T2w ratio was robustly associated with higher age at scan (range: similar to 4-6.5 months), implying sensitivity to maturation at short developmental timescales. Further, higher T1w/T2w ratio within these regions was associated with higher scores on measures of concurrent developmental level. These findings suggest that T1w/T2w ratio is a developmentally sensitive measure that should be explored further in future studies of both typical and atypical infant populations.
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  • Davenport, ML, et al. (author)
  • Altered Brain Structure in Infants with Turner Syndrome
  • 2020
  • In: Cerebral cortex (New York, N.Y. : 1991). - : Oxford University Press (OUP). - 1460-2199 .- 1047-3211. ; 30:2, s. 587-596
  • Journal article (peer-reviewed)abstract
    • Turner syndrome (TS) is a genetic disorder affecting approximately 1:2000 live-born females. It results from partial or complete X monosomy and is associated with a range of clinical issues including a unique cognitive profile and increased risk for certain behavioral problems. Structural neuroimaging studies in adolescents, adults, and older children with TS have revealed altered neuroanatomy but are unable to identify when in development differences arise. In addition, older children and adults have often been exposed to years of growth hormone and/or exogenous estrogen therapy with potential implications for neurodevelopment. The study presented here is the first to test whether brain structure is altered in infants with TS. Twenty-six infants with TS received high-resolution structural MRI scans of the brain at 1 year of age and were compared to 47 typically developing female and 39 typically developing male infants. Results indicate that the typical neuroanatomical profile seen in older individuals with TS, characterized by decreased gray matter volumes in premotor, somatosensory, and parietal-occipital cortex, is already present at 1 year of age, suggesting a stable phenotype with origins in the prenatal or early postnatal period.
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39.
  • de Boer, Lieke, et al. (author)
  • Corticostriatal White Matter Integrity and Dopamine D1 Receptor Availability Predict Age Differences in Prefrontal Value Signaling during Reward Learning
  • 2020
  • In: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 30:10, s. 5270-5280
  • Journal article (peer-reviewed)abstract
    • Probabilistic reward learning reflects the ability to adapt choices based on probabilistic feedback. The dopaminergically innervated corticostriatal circuit in the brain plays an important role in supporting successful probabilistic reward learning. Several components of the corticostriatal circuit deteriorate with age, as it does probabilistic reward learning. We showed previously that D1 receptor availability in NAcc predicts the strength of anticipatory value signaling in vmPFC, a neural correlate of probabilistic learning that is attenuated in older participants and predicts probabilistic reward learning performance. We investigated how white matter integrity in the pathway between nucleus accumbens (NAcc) and ventromedial prefrontal cortex (vmPFC) relates to the strength of anticipatory value signaling in vmPFC in younger and older participants. We found that in a sample of 22 old and 23 young participants, fractional anisotropy in the pathway between NAcc and vmPFC predicted the strength of value signaling in vmPFC independently from D1 receptor availability in NAcc. These findings provide tentative evidence that integrity in the dopaminergic and white matter pathways of corticostriatal circuitry supports the expression of value signaling in vmPFC which supports reward learning, however, the limited sample size calls for independent replication. These and future findings could add to the improved understanding of how corticostriatal integrity contributes to reward learning ability.
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40.
  • de Manzano, O, et al. (author)
  • Action-Perception Coupling and Near Transfer: Listening to Melodies after Piano Practice Triggers Sequence-Specific Representations in the Auditory-Motor Network
  • 2020
  • In: Cerebral cortex (New York, N.Y. : 1991). - : Oxford University Press (OUP). - 1460-2199 .- 1047-3211. ; 30:10, s. 5193-5203
  • Journal article (peer-reviewed)abstract
    • Understanding how perception and action are coupled in the brain has important implications for training, rehabilitation, and brain–machine interfaces. Ideomotor theory postulates that willed actions are represented through previously experienced effects and initiated by the anticipation of those effects. Previous research has accordingly found that sensory events, if previously associated with action outcomes, can induce activity in motor regions. However, it remains unclear whether the motor-related activity induced during perception of more naturalistic sequences of actions actually represents “sequence-specific” information. In the present study, nonmusicians were firstly trained to play two melodies on the piano; secondly, they performed an fMRI experiment while listening to these melodies as well as novel, untrained melodies; thirdly, multivariate pattern analysis was used to test if voxel-wise patterns of brain activity could identify trained, but not novel melodies. The results importantly show that after associative learning, a series of sensory events can trigger sequence-specific representations in both sensory and motor networks. Interestingly, also novel melodies could be classified in multiple regions, including default mode regions. A control experiment confirmed these outcomes to be training-dependent. We discuss how action-perception coupling may enable spontaneous near transfer and action simulation during action observation.
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41.
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42.
  • Deluca, Vincent, et al. (author)
  • Mapping individual aspects of bilingual experience to adaptations in brain structure
  • 2024
  • In: Cerebral Cortex. - 1047-3211 .- 1460-2199. ; 34:2
  • Journal article (peer-reviewed)abstract
    • Individual differences in using multiple languages are thought to differentially affect brain structure and function. The present study assessed the neuroanatomical predictions of an emerging theory, the Unifying the Bilingual Experience Trajectories framework, which provides the most comprehensive set of predictions of how individual differences in bilingual experiences lead to specific neural and cognitive adaptations. A total of 140 young adults with variable language experiences were scanned using magnetic resonance imaging and completed demographic questionnaires. Brain structure measures implicated in predictions of the Unifying the Bilingual Experience Trajectories model were extracted and regressed against the model's experiential factors. Consistent with the model's predictions, greater intensity and diversity of bilingual language use resulted in changes in gray matter volume in cortical regions involved in executive control (including inferior frontal gyrus, middle temporal gyrus, angular gyrus, and medial frontal gyrus), indicating adaptations toward handling increased executive control demands. Conversely, duration of bilingual engagement resulted in changes within white matter microstructure (bilateral superior longitudinal fasciculus) and increases in subcortical gray matter (left caudate), indicative of adaptations toward increased efficiency of control. Overall, this research enhances our understanding of how bilingual experiences influence brain structure and provides the first direct empirical evidence for the predictions made by the Unifying the Bilingual Experience Trajectories framework.
  •  
43.
  • Denker, M, et al. (author)
  • The local field potential reflects surplus spike synchrony
  • 2011
  • In: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 21:12, s. 2681-2695
  • Journal article (peer-reviewed)abstract
    •  While oscillations of the local field potential (LFP) are commonly attributed to the synchronization of neuronal firing rate on the same time scale, their relationship to coincident spiking in the millisecond range is unknown. Here, we present experimental evidence to reconcile the notions of synchrony at the level of spiking and at the mesoscopic scale. We demonstrate that only in time intervals of significant spike synchrony that cannot be explained on the basis of firing rates, coincident spikes are better phase locked to the LFP than predicted by the locking of the individual spikes. This effect is enhanced in periods of large LFP amplitudes. A quantitative model explains the LFP dynamics by the orchestrated spiking activity in neuronal groups that contribute the observed surplus synchrony. From the correlation analysis, we infer that neurons participate in different constellations but contribute only a fraction of their spikes to temporally precise spike configurations. This finding provides direct evidence for the hypothesized relation that precise spike synchrony constitutes a major temporally and spatially organized component of the LFP.
  •  
44.
  • Di Bello, F., et al. (author)
  • Prefrontal Control of Proactive and Reactive Mechanisms of Visual Suppression
  • 2022
  • In: Cerebral Cortex. - : Oxford University Press. - 1047-3211 .- 1460-2199. ; 32:13, s. 2745-2761
  • Journal article (peer-reviewed)abstract
    • In everyday life, we are continuously struggling at focusing on our current goals while at the same time avoiding distractions. Attention is the neuro-cognitive process devoted to the selection of behaviorally relevant sensory information while at the same time preventing distraction by irrelevant information. Distraction can be prevented proactively, by strategically prioritizing task-relevant information at the expense of irrelevant information, or reactively, by suppressing the ongoing processing of distractors. The distinctive neuronal signature of these suppressive mechanisms is still largely unknown. Thanks to machine-learning decoding methods applied to prefrontal cortical activity, we monitor the dynamic spatial attention with an unprecedented spatial and temporal resolution. We first identify independent behavioral and neuronal signatures for long-term (learning-based spatial prioritization) and short-term (dynamic spatial attention) mechanisms. We then identify distinct behavioral and neuronal signatures for proactive and reactive suppression mechanisms. We find that while distracting task-relevant information is suppressed proactively, task-irrelevant information is suppressed reactively. Critically, we show that distractor suppression, whether proactive or reactive, strongly depends on the implementation of both long-term and short-term mechanisms of selection. Overall, we provide a unified neuro-cognitive framework describing how the prefrontal cortex deals with distractors in order to flexibly optimize behavior in dynamic environments. 
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45.
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46.
  • Dong, Hongyan, et al. (author)
  • Transient Maternal Hypothyroxinemia Potentiates the Transcriptional Response to Exogenous Thyroid Hormone in the Fetal Cerebral Cortex Before the Onset of Fetal Thyroid Function : A Messenger and MicroRNA Profiling Study
  • 2015
  • In: Cerebral Cortex. - : Oxford University Press. - 1047-3211 .- 1460-2199. ; 25:7, s. 1735-1745
  • Journal article (peer-reviewed)abstract
    • Thyroid hormone (TH) is essential for brain development both before and after birth. We have used gene expression microarrays to identify TH-regulated genes in the fetal cerebral cortex prior to the onset of fetal thyroid function to better understand the role of TH in early cortical development. TH levels were transiently manipulated in pregnant mice by treatment with goitrogens from gestational day (GD) 13-16 and/or by injection of TH 12 h before sacrifice on GD 16. The transcriptional response to exogenous TH in the GD 16 fetal cortex was potentiated by transient goitrogen treatment, suggesting that the hypothyroxinemic brain is a different substrate upon which TH can act, or that robust compensatory mechanisms are induced by transient hypothyroxinemia. Several known TH-responsive genes were identified including Klf9, and several novel TH-responsive genes such as Appbp2, Ppap2b, and Fgfr1op2 were identified in which TH response elements were confirmed. We also identified specific microRNAs whose expression in the fetal cortex was affected by TH treatment, and determined that Ppap2b and Klf9 are the target genes of miR-16 and miR-106, respectively. Thus, a complex redundant functional network appears to coordinate TH-mediated gene expression in the developing brain.
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47.
  •  
48.
  • Dunås, Tora, et al. (author)
  • Multimodal Image Analysis of Apparent Brain Age Identifies Physical Fitness as Predictor of Brain Maintenance
  • 2021
  • In: Cerebral Cortex. - : Oxford University Press. - 1047-3211 .- 1460-2199. ; 31:7, s. 3393-3407
  • Journal article (peer-reviewed)abstract
    • Maintaining a youthful brain structure and function throughout life may be the single most important determinant ofsuccessful cognitive aging. In this study, we addressed heterogeneity in brain aging by making image-based brain agepredictions and relating the brain age prediction gap (BAPG) to cognitive change in aging. Structural, functional, anddiffusion MRI scans from 351 participants were used to train and evaluate 5 single-modal and 4 multimodal predictionmodels, based on 7 regression methods. The models were compared on mean absolute error and whether they were relatedto physical fitness and cognitive ability, measured both currently and longitudinally, as well as study attrition and years ofeducation. Multimodal prediction models performed at a similar level as single-modal models, and the choice of regressionmethod did not significantly affect the results. Correlation with the BAPG was found for current physical fitness, currentcognitive ability, and study attrition. Correlations were also found for retrospective physical fitness, measured 10 years priorto imaging, and slope for cognitive ability during a period of 15 years. The results suggest that maintaining a high physicalfitness throughout life contributes to brain maintenance and preserved cognitive ability.
  •  
49.
  • Eriksson, Johan, et al. (author)
  • Similar frontal and distinct posterior cortical regions mediate visual and auditory perceptual awareness
  • 2007
  • In: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 17:4, s. 760-765
  • Journal article (peer-reviewed)abstract
    • Activity in ventral visual cortex is a consistent neural correlate of visual consciousness. However, activity in this area seems insufficient to produce awareness without additional involvement of frontoparietal regions. To test the generality of the frontoparietal response, neural correlates of auditory awareness were investigated in a paradigm that previously has revealed frontoparietal activity during conscious visual perception. A within-experiment comparison showed that frontal regions were related to both visual and auditory awareness, whereas parietal activity was correlated with visual awareness and superior temporal activity with auditory awareness. These results indicate that frontal regions interact with specific posterior regions to produce awareness in different sensory modalities.
  •  
50.
  • Ferri, Stefania, et al. (author)
  • Stereoscopically Observing Manipulative Actions
  • 2016
  • In: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199.
  • Journal article (peer-reviewed)abstract
    • The purpose of this study was to investigate the contribution of stereopsis to the processing of observed manipulative actions. To this end, we first combined the factors “stimulus type” (action, static control, and dynamic control), “stereopsis” (present, absent) and “viewpoint” (frontal, lateral) into a single design. Four sites in premotor, retro-insular (2) and parietal cortex operated specifically when actions were viewed stereoscopically and frontally. A second experiment clarified that the stereo-action-specific regions were driven by actions moving out of the frontoparallel plane, an effect amplified by frontal viewing in premotor cortex. Analysis of single voxels and their discriminatory power showed that the representation of action in the stereo-action-specific areas was more accurate when stereopsis was active. Further analyses showed that the 4 stereo-action-specific sites form a closed network converging onto the premotor node, which connects to parietal and occipitotemporal regions outside the network. Several of the specific sites are known to process vestibular signals, suggesting that the network combines observed actions in peripersonal space with gravitational signals. These findings have wider implications for the function of premotor cortex and the role of stereopsis in human behavior.
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