Biology subjects

Raud, L.

Publications and source records attributed to Raud, L..

13 recordsLinked to original sources

bioRxiv2025

Differential expression of spatiotemporal sleep spindle clusters in ageing

ObjectivesSleep spindles are potential biomarkers for memory decline in aging. However, significant within-person variability in spindle attributes complicates their utility in predicting cognitive deterioration. This study aimed to uncover distinct spindle types and their relevance to memory decline using data-driven clustering. MethodsPolysomnography was collected from younger (n = 43, ages 20-45 years) and older cognitively healthy adults (n = 34, ages 60-81 years). Spindles were clustered into four groups using multiple features and spatiotemporal context, irrespective of participant age. ResultsResulting clusters were hierarchically defined by the sleep stage, slow oscillation concurrence, and hemisphere. Stage N3 spindles (15%; predominantly coinciding with slow oscillations) formed a distinct group, followed by N2 spindles coinciding with slow oscillations (27%). Remaining N2 spindles were categorized into unilateral (41%) and bilateral clusters (17%). In older adults, there was a reduced proportion of N2 bilateral spindles and an increased proportion of N2 spindles concurrent with slow oscillations. Reduced proportion of N2 bilateral spindles was associated with better composite memory performance in younger adults, whereas higher spindle power, regardless of cluster belonging, was associated with reduced memory benefit from sleep compared with wakefulness. ConclusionsOur results indicate differing expression of spatiotemporal spindle clusters in older age, as well as intertwined dynamics between spindle propagation, SO concurrence, and frequency shifts in ageing. In addition, spindle heterogeneity aligned with global sleep stage dynamics. These results emphasize the interconnectedness of spindle activity with overall sleep patterns, underscoring the importance of spatiotemporal context within and across sleep stages. Statement of significanceThis study used data-driven clustering to explore sleep spindles as potential markers for age-related memory decline. We identified spindle clusters determined by sleep stage, slow oscillation concurrence, and hemisphere propagation. Notably, older adults showed altered expression of these clusters, indicating age-specific dynamics. Further research should focus on distinguishing spindle deterioration from broader sleep changes in older age. Such insights could pave the way for early detection and intervention strategies in cognitive decline, highlighting sleeps crucial role in maintaining cognitive health and resilience in aging populations. These findings hold promise for developing targeted approaches to enhance mental wellness and quality of life in older adults.

neuroscience↗

bioRxiv2024

Network Segregation During Episodic Memory Shows Age-Invariant Relations with Memory Performance From 7 to 82 Years

Lower episodic memory capability, as seen in development and aging compared with younger adulthood, may partly depend on lower brain network segregation. Here, our objective was twofold: (1) test this hypothesis using within- and between-network functional connectivity (FC) during episodic memory encoding and retrieval, in two independent samples (n=734, age 7-82 years). (2) Assess associations with age and the ability to predict memory comparing task-general FC and memory-modulated FC. In a multiverse-inspired approach, we performed tests across multiple analytic choices. Results showed that relationships differed based on these analytic choices, were often weak, and mainly present in the cohort with the most data. Significant relationships indicated that (i) memory-modulated FC predicted memory performance and associated with memory in an age-invariant manner. (ii) In line with the so- called neural dedifferentiation view, task-general FC showed lower segregation with higher age in adults which was associated with worse memory performance. In development, although there were only weak signs of a neural differentiation, that is, gradually higher segregation with higher age, we observed similar lower segregation-worse memory relationships. This age-invariant relationships between FC and episodic memory suggest that network segregation is pivotal for memory across the healthy lifespan. Declarations of interestnone. HighlightsO_LIWithin- and between network functional connectivity predict memory performance. C_LIO_LIMultiverse-inspired analyses showed varying results depending on analytic choices. C_LIO_LIMemory associations particularly in the cohort with most data were age-invariant across the lifespan. C_LIO_LIDedifferentiation might be better characterized as degrees of differentiation. C_LI

neuroscience↗

bioRxiv2022

Hippocampal-cortical functional connectivity during memory encoding and retrieval

Memory encoding and retrieval are critical sub-processes of episodic memory. While the hippocampus is involved in both, its connectivity with the neocortex during memory processing in humans has been elusive. This is partially due to variations in demands in common memory tasks, which inevitably recruit cognitive processes other than episodic memory. Conjunctive analysis of data from different tasks with the same core elements of encoding and retrieval can reduce the intrusion of patterns related to subsidiary perceptual and cognitive processing. Leveraging data from two large-scale functional resonance imaging studies with different episodic memory tasks (514 and 237 participants), we identified core hippocampal-cortical networks active during memory processing. Anterior and posterior hippocampus had distinct connectivity profiles, which were stable across resting state and memory tasks. Whereas no encoding-specific connectome emerged across tasks, during retrieval hippocampal connectivity was increased with areas known to be active during recollection, including medial prefrontal, inferior parietal, and parahippocampal cortices. This indicates that the stable functional connectivity of the hippocampus along its longitudinal axis is superposed by increased functional connectivity with the recollection network during retrieval, while encoding connectivity likely reflects contextual factors.

neuroscience↗

bioRxiv2022

Sustained upregulation of widespread hippocampal-neocortical coupling following memory encoding

Systems consolidation of new experiences into lasting episodic memories involves interactions between hippocampus and the neocortex. Evidence of this process is seen already during early awake post-encoding rest periods. Functional MRI (fMRI) studies have demonstrated increased hippocampal coupling with task-relevant perceptual regions and reactivation of stimulus-specific encoding patterns following intensive encoding tasks. Here we investigate the spatial and temporal characteristics of these hippocampally anchored post-encoding neocortical modulations. Eighty-nine adults participated in an experiment consisting of interleaved memory task- and resting-state periods. As expected, we observed increased post-encoding functional connectivity between hippocampus and individually localized neocortical regions responsive to stimulus categories encountered during memory encoding. Post-encoding modulations were however not restricted to stimulus-selective cortex, but manifested as a nearly system-wide upregulation in hippocampal coupling with all major functional networks. The spatial configuration of these extensive modulations resembled hippocampal-neocortical interaction patterns estimated from active encoding operations, suggesting hippocampal post-encoding involvement by far exceeds reactivation of perceptual aspects. This reinstatement of encoding patterns during immediate post-encoding rest was not observed in resting-state scans collected 12 hours later, nor in control analyses estimating post-encoding neocortical modulations in functional connectivity using other candidate seed regions. The broad similarity in hippocampal functional coupling between online memory encoding and offline post-encoding rest suggests reactivation in humans may involve a spectrum of cognitive processes engaged during experience of an event. Significance statementStabilization of newly acquired information into lasting memories occurs through systems consolidation - a process which gradually spreads the locus of memory traces from hippocampus to more distributed neocortical representations. One of the earliest signs of consolidation is the upregulation of hippocampal-neocortical interactions during periods of awake rest following an active encoding task. We here show that these modulations involve much larger parts of the brain than previously reported in humans. Comparing changes in hippocampal coupling during post-encoding rest with those observed under active encoding, we find evidence for encoding-like hippocampal reinstatement throughout cortex during task-free periods. This suggests early systems consolidation of an experience involves reactivating not only core sensory details but multiple additional aspects of the encoding event.

neuroscience↗

bioRxiv2021

Whole-brain connectivity during encoding: age-related differences and associations with cognitive and brain structural decline

There is a limited understanding of age differences in functional connectivity during memory encoding. In the present study, a sample of cognitively healthy adult participants (n=488), a subsample of whom had longitudinal cognitive and brain structural data spanning 8 years back, underwent fMRI while performing an associative memory encoding task. We investigated 1) age changes in whole-brain connectivity during memory encoding; whether 2) encoding connectivity patterns overlap with the activity signatures of specific cognitive processes and whether 3) connectivity changes associated with memory encoding related to longitudinal brain structural and cognitive changes. Age was associated with decreased intranetwork connectivity and increased connectivity during encoding. Task-connectivity between mediotemporal and posterior parietal regions - which overlapped with areas involved in mental imagery - was related to better memory performance only in older age. The connectivity patterns supporting memory performance in older age reflected preservation of thickness of the medial temporal cortex. These investigations collectively indicate that functional patterns of connectivity should be interpreted in accordance with a maintenance rather than a compensation account.

neuroscience↗

bioRxiv2021

Partial response electromyography as a markerof the individual stopping latency

Response inhibition is among the core constructs of cognitive control. It is notoriously difficult to quantify from overt behavior, since the outcome of successful inhibition is the lack of a behavioral response. Currently, the most common measure of action stopping, and by proxy response inhibition, is the model-based stop signal reaction time (SSRT) derived from the stop signal task. Recently, partial response electromyography (prEMG) has been introduced as a complementary physiological measure to capture individual stopping latencies. PrEMG refers to muscle activity initiated by the go signal that plummets after the stop signal before its accumulation to a full response. Whereas neither the SSRT nor the prEMG is an unambiguous marker for neural processes underlying response inhibition, our analysis indicates that the prEMG peak latency is better suited to investigate brain mechanisms of action stopping. This study is a methodological resource with a comprehensive overview of the psychometric properties of the prEMG in a stop signal task, and further provides practical tips for data collection and analysis.

neuroscience↗

bioRxiv2020

Genetic models suggest single and multiple origins of dihydrofolate reductase mutations in Plasmodium vivax

Pyrimethamine was first introduced for the treatment of malaria in Asia and Africa during the early 1980s, replacing chloroquine, and has become the first line of drugs in many countries. In recent years, development of pyrimethamine resistance in Plasmodium vivax has become a barrier to effective malaria control strategies. Here, we describe the use of meta-barcoded deep amplicon sequencing technology to assess the evolutionary origin of pyrimethamine resistance by analysing the flanking region of dihydrofolate reductase (dhfr) locus. The genetic modelling suggests that 58R and 173L single mutants and 58R/117N double mutants are present on a single lineage; suggesting a single origin of these mutations. The triple mutants (57L/58R/117N, 58R/61M/117N and 58R/117N/173L) share the lineage of 58R/117N, suggesting a common origin. In contrast, the 117N mutant is present on two separate lineages suggesting that there are multiple origins of this mutation. We characterised the allele frequency of the P. vivax dhfr locus. Our results support the view that the single mutation of 117N and double mutations of 58R/117N arise commonly, whereas the single mutation of 173L and triple mutations of 57L/58R/117N, 58R/61M/117N and 58R/117N/173L are less common. Our work will help to inform mitigation strategies for pyrimethamine resistance in P. vivax.

genetics↗

bioRxiv2020

Inhibitory control and the structural parcellation of the right inferior frontal gyrus

The right inferior frontal gyrus (rIFG) has most strongly, although not exclusively, been associated with response inhibition, not least based on covariations of behavioral performance measures and local grey matter characteristics. However, the white matter microstructure of the rIFG as well as its connectivity has been less in focus, especially when it comes to the consideration of potential subdivisions within this area. The present study reconstructed the structural connections of the three main subregions of the rIFG (i.e. pars opercularis, pars triangularis and pars orbitalis) using diffusion tensor imaging, and further assessed their associations with behavioral measures of inhibitory control. The results revealed a marked heterogeneity of the three subregions with respect to the pattern and extent of their connections, with the pars orbitalis showing the most widespread inter-regional connectivity, while the pars opercularis showed the least amount of connections. When relating behavioral performance measures of a stop signal task to brain structure, the data indicated a differential association of dorsal and ventral opercular connectivity with the go reaction time and the stopping accuracy, respectively.

neuroscience↗

bioRxiv2020

A single mechanism for global and selective response inhibition under the influence of motor preparation

In our everyday behavior, we frequently cancel one movement while continuing others. Two competing models have been suggested for the cancellation of such specific actions: 1) the abrupt engagement of a unitary global inhibitory mechanism followed by reinitiation of the continuing actions, or 2) a balance between distinct global and selective inhibitory mechanisms. To evaluate these models, we examined behavioral and physiological markers of proactive control, motor preparation, and response inhibition using a combination of behavioral task performance measures, electromyography, electroencephalography, and motor evoked potentials elicited with transcranial magnetic stimulation. Healthy participants performed two versions of a stop signal task with cues incorporating proactive control: A unimanual task involving the initiation and inhibition of a single response, and a bimanual task involving the selective stopping of one of two prepared responses. Stopping latencies, motor evoked potentials, and frontal beta power (13-20 Hz) did not differ between the uni- and bimanual tasks. However, evidence for selective proactive control before stopping was manifest in the bimanual condition as changes in corticomotor excitability, mu (9-14 Hz), and beta (15-25 Hz) oscillations over sensorimotor cortex. Altogether, our results favor the recruitment of a single inhibitory stopping mechanism with the net behavioral output depending on the levels of action-specific motor preparation. Significance statementResponse inhibition is a core function of cognitive flexibility and movement control. Previous research has suggested separate mechanisms for selective and global inhibition, yet the evidence is inconclusive. Another line of research has examined the influence of preparation for action stopping, or what is called proactive control, on stopping performance, yet the neural mechanisms underlying this interaction are unknown. We combined transcranial magnetic stimulation, electroencephalography, electromyography and behavioral measures to compare selective and global inhibition models and to investigate markers of proactive control. The results favor a single inhibitory mechanism over separate selective and global mechanisms, but indicate a vital role for preceding motor activity in determining whether and which actions will be stopped.

neuroscience↗

bioRxiv2019

Stimulating stopping? Investigating the effects of tDCS over the inferior frontal gyri and visual cortices.

The ability to cancel an already initiated response is central to flexible behavior. While several different behavioral and neural markers have been suggested to quantify the latency of the stopping process, it remains unclear if they quantify the stopping process itself, or other supporting mechanisms such as visual and/or attentional processing. The present study sought to investigate the contributions of inhibitory and sensory processes to stopping latency markers by combining transcranial direct current stimulation (tDCS), electroencephalography (EEG) and electromyography (EMG) recordings in a within-subject design. Active and sham tDCS were applied over the inferior frontal gyri (IFG) and visual cortices (VC), combined with both online and offline EEG and EMG recordings. We found evidence that neither of the active tDCS condition affected stopping latencies relative to sham stimulation. Our results challenge previous findings suggesting that anodal tDCS over the IFG can reduce stopping latency and demonstrates the necessity of adequate control conditions in tDCS research. Additionally, while the different putative markers of stopping latency showed generally positive correlations with each other, they also showed substantial variation in the estimated latency of inhibition, making it unlikely that they all capture the same construct exclusively.

neuroscience↗

bioRxiv2019

Differences in unity: the go/no-go and stop signal tasks rely on different inhibitory mechanisms

Response inhibition refers to the suppression of prepared or initiated actions. Typically, the go/no-go task (GNGT) or the stop signal task (SST) are used interchangeably to capture individual differences in response inhibition. Yet, there is some controversy if these tasks assess similar inhibitory processes. We extracted the time-courses of sensory, motor, attentional, and cognitive control networks by group independent component (G-ICA) analysis of electroencephalography (EEG) data from both tasks. Additionally, electromyography (EMG) from the responding effector muscles was recorded to detect the timing of response inhibition. The results indicated that inhibitory performance in the GNGT may be comparable to response selection mechanisms, reaching peripheral muscles at around 316 ms. In contrast, inhibitory performance in the SST is achieved via biasing of the sensory-motor system in preparation for stopping, followed by fast sensory, motor and frontal integration during outright stopping. Inhibition can be detected at the peripheral level at 140 ms after stop stimulus presentation. The GNGT and the SST therefore seem to recruit widely different neural dynamics, implying that the interchangeable use of superficially similar inhibition tasks in both basic and clinical research is unwarranted.

neuroscience↗

bioRxiv2019

The P300 as marker of inhibitory control - fact or fiction?

Inhibitory control, i.e., the ability to stop or suppress actions, thoughts, or memories, represents a prevalent and popular concept in basic and clinical neuroscience as well as psychology. At the same time, it is notoriously difficult to study as successful inhibition is characterized by the absence of a continuously quantifiable direct behavioral marker. It has been suggested that the P3 latency, and here especially its onset latency, may serve as neurophysiological marker of inhibitory control as it correlates with the stop signal reaction time (SSRT). The SSRT estimates the average stopping latency, which itself is unobservable since no overt response is elicited in successful stop trials, based on differences in the distribution of go reaction times and the delay of the stop- relative to the go-signal in stop trials.\n\nIn a meta-analysis and an independent EEG experiment, we found that correlations between the P3-latency and the SSRT are indeed replicable, but also unspecific. Not only does the SSRT also correlate with the N2-latency, but both P3- and N2-latency measures show similar or even higher correlations with other behavioral parameters such as the go reaction time or stopping accuracy. The missing specificity of P3-SSRT correlations, together with the general pattern of associations, suggests that these manifest effects are driven by underlying latent processes other than inhibition, such as those associated with the speed-accuracy trade-off.

neuroscience↗

bioRxiv2018

First estimation of the scale of canonical 5’ splice site GT>GC mutations generating wild-type transcripts and their medical genetic implications

It has long been known that canonical 5 splice site (5SS) GT>GC mutations may be compatible with normal splicing. However, to date, the true scale of canonical 5SS GT>GC mutations generating wild-type transcripts, both in the context of the frequency of such mutations and the level of wild-type transcripts generated from the mutation alleles, remain unknown. Herein, combining data derived from a meta-analysis of 45 informative disease-causing 5SS GT>GC mutations (from 42 genes) and a cell culture-based full-length gene splicing assay of 103 5SS GT>GC mutations (from 30 genes), we estimate that [~]15-18% of the canonical GT 5SSs are capable of generating between 1 and 84% normal transcripts as a consequence of the substitution of GT by GC. We further demonstrate that the canonical 5SSs whose substitutions of GT by GC generated normal transcripts show stronger complementarity to the 5 end of U1 snRNA than those sites whose substitutions of GT by GC did not lead to the generation of normal transcripts. We also observed a correlation between the generation of wild-type transcripts and a milder than expected clinical phenotype but found that none of the available splicing prediction tools were able to accurately predict the functional impact of 5SS GT>GC mutations. Our findings imply that 5SS GT>GC mutations may not invariably cause human disease but should also help to improve our understanding of the evolutionary processes that accompanied GT>GC subtype switching of U2-type introns in mammals.

genetics↗