| 1. |
- Adams, Rick A., et al.
(författare)
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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
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 30:6, s. 3573-3589
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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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| 2. |
- Andin, Josefine, 1979-, et al.
(författare)
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Working Memory for Signs with Poor Visual Resolution : fMRI Evidence of Reorganization of Auditory Cortex in Deaf Signers
- 2021
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 31:7, s. 3165-3176
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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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| 3. |
- Arvidsson, Caroline, et al.
(författare)
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Conversational production and comprehension: fMRI-evidence reminiscent of but deviant from the classical Broca–Wernicke model
- 2024
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Ingår i: Cerebral Cortex. - 1047-3211 .- 1460-2199. ; 34:3
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Bramao, Ines, et al.
(författare)
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Encoding contexts are incidentally reinstated during competitive retrieval and track the temporal dynamics of memory interference
- 2022
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1460-2199 .- 1047-3211. ; 32:22, s. 5020-5035
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Cacciaglia, Raffaele, et al.
(författare)
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APOE-ε4 Shapes the Cerebral Organization in Cognitively Intact Individuals as Reflected by Structural Gray Matter Networks.
- 2020
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Ingår i: Cerebral cortex. - : Oxford University Press (OUP). - 1460-2199 .- 1047-3211. ; 30:7, s. 4110-4120
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Tidskriftsartikel (refereegranskat)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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| 6. |
- Cacciaglia, R., et al.
(författare)
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Genotypic effects of APOE-epsilon 4 on resting-state connectivity in cognitively intact individuals support functional brain compensation
- 2022
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 33:6, s. 2748-60
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Tidskriftsartikel (refereegranskat)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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| 7. |
- Canal-Garcia, Anna, et al.
(författare)
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Dynamic multilayer functional connectivity detects preclinical and clinical Alzheimer's disease
- 2024
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Ingår i: CEREBRAL CORTEX. - 1047-3211 .- 1460-2199.
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Tidskriftsartikel (refereegranskat)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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| 8. |
- Canal-Garcia, A., et al.
(författare)
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Multiplex Connectome Changes across the Alzheimer's Disease Spectrum Using Gray Matter and Amyloid Data
- 2022
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 32:16, s. 3501-3515
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Tidskriftsartikel (refereegranskat)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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| 9. |
- Dall'orso, Sofia, 1992, et al.
(författare)
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Cortical Processing of Multimodal Sensory Learning in Human Neonates
- 2021
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 31:3, s. 1827-1836
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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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| 10. |
- Darki, F, et al.
(författare)
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Inter-Individual Differences in Striatal Connectivity Is Related to Executive Function Through Fronto-Parietal Connectivity
- 2020
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Ingår i: Cerebral cortex (New York, N.Y. : 1991). - : Oxford University Press (OUP). - 1460-2199 .- 1047-3211. ; 30:2, s. 672-681
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Tidskriftsartikel (refereegranskat)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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