Brain Areas Research Articles

Altered connectivity of central autonomic network: effects of dysautonomia in hereditary transthyretin amyloidosis with polyneuropathy.

Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a progressive fatal disorder caused by deposition of mutant transthyretin (TTR) amyloids mainly in the nerves and heart. Autonomic dysfunction is a major disabling manifestation, affecting 90% of patients with late-onset ATTRv-PN. The current study aimed to investigate brain functional alterations associated with dysautonomia due to peripheral autonomic nerve degeneration in ATTRv-PN. Resting-state functional MRI data were acquired from 43 ATTRv-PN patients predominantly of A97S (p.A117S) genotype, and the functional connectivity of central autonomic regions was assessed. Compared with age-matched healthy controls, the ATTRv-PN patients exhibited (1) reduced functional connectivity of the central autonomic regions such as hypothalamus, amygdala, anterior insula, and middle cingulate cortex with brain areas of the limbic, frontal, and somatosensory systems, and (2) correlations of reduced functional autonomic connectivity with the severity of autonomic dysfunction especially orthostatic intolerance, decreased heart rate variability, and greater clinical disability. Our findings provide evidence linking peripheral autonomic dysfunction with altered connectivity in the central autonomic network in ATTRv-PN.

Ghrelin, Neuroinflammation, Oxidative Stress, and Mood Disorders: What Are the Connections?

Ghrelin is a gut peptide hormone associated with feeding behavior and energy homeostasis. Acylated ghrelin binds to the growth hormone secretagogue receptor 1a subtype (GHS-R1a) in the hippocampus, leading to GH release from the anterior pituitary. However, in recent years, ghrelin and its receptor have also been implicated in other processes, including the regulation of cardiomyocyte function, muscle trophism, and bone metabolism. Moreover, GHS-R1a is distributed throughout the brain and is expressed in brain areas that regulate the stress response and emotional behavior. Consistently, a growing body of evidence supports the role of ghrelin in regulating stress response and mood. Stress has consistently been shown to increase ghrelin levels, and despite some inconsistencies, both human and rodent studies suggested antidepressant effects of ghrelin. Nevertheless, the precise mechanism by which ghrelin influences stress response and mood remains largely unknown. Intriguingly, ghrelin and GHS-R1a were consistently reported to exert anti-inflammatory, antioxidant, and neurotrophic effects both in vivo and in vitro, although this has never been directly assessed in relation to psychopathology. In the present review we will discuss available literature linking ghrelin with the stress response and depressive-like behavior in animal models as well as evidence describing the interplay between ghrelin and neuroinflammation/oxidative stress. Although further studies are required to understand the mechanisms involved in the action of ghrelin on mood, we hypothesize that the antiinflammatory and anti-oxidative properties of ghrelin may give a key contribution.

Temporal pattern recognition in retinal ganglion cells is mediated by dynamical inhibitory synapses

A fundamental task for the brain is to generate predictions of future sensory inputs, and signal errors in these predictions. Many neurons have been shown to signal omitted stimuli during periodic stimulation, even in the retina. However, the mechanisms of this error signaling are unclear. Here we show that depressing inhibitory synapses shape the timing of the response to an omitted stimulus in the retina. While ganglion cells, the retinal output, responded to an omitted flash with a constant latency over many frequencies of the flash sequence, we found that this was not the case once inhibition was blocked. We built a simple circuit model and showed that depressing inhibitory synapses were a necessary component to reproduce our experimental findings. A new prediction of our model is that the accuracy of the constant latency requires a sufficient amount of flashes in the stimulus, which we could confirm experimentally. Depressing inhibitory synapses could thus be a key component to generate the predictive responses observed in the retina, and potentially in many brain areas.

Integration of valence and conflict processing through cellular-field interactions in human subgenual cingulate during emotional face processing in treatment-resistant depression.

The subgenual anterior cingulate cortex (sgACC) has been identified as a key brain area involved in various cognitive and emotional processes. While the sgACC has been implicated in both emotional valuation and emotional conflict monitoring, it is still unclear how this area integrates multiple functions. We characterized both single neuron and local field oscillatory activity in 14 patients undergoing sgACC deep brain stimulation for treatment-resistant depression. During recording, patients were presented with a modified Stroop task containing emotional face images that varied in valence and congruence. We further analyzed spike-field interactions to understand how network dynamics influence single neuron activity in this area. Most single neurons responded to both valence and congruence, revealing that sgACC neuronal activity can encode multiple processes within the same task, indicative of multifunctionality. During peak neuronal response, we observed increased spectral power in low frequency oscillations, including theta-band synchronization (4-8 Hz), as well as desynchronization in beta-band frequencies (13-30 Hz). Theta activity was modulated by current trial congruency with greater increases in spectral power following non-congruent stimuli, while beta desynchronizations occurred regardless of emotional valence. Spike-field interactions revealed that local sgACC spiking was phase-locked most prominently to the beta band, whereas phase-locking to the theta band occurred in fewer neurons overall but was modulated more strongly for neurons that were responsive to task. Our findings provide the first direct evidence of spike-field interactions relating to emotional cognitive processing in the human sgACC. Furthermore, we directly related theta oscillatory dynamics in human sgACC to current trial congruency, demonstrating it as an important regulator during conflict detection. Our data endorse the sgACC as an integrative hub for cognitive emotional processing through modulation of beta and theta network activity.

Partners in health and disease: pineal gland and purinergic signalling.

In mammal's pineal glands, ATP interacts with the high-affinity P2Y1 and the low-affinity P2X7 receptors. ATP released from sympathetic nerve terminals potentiates noradrenaline-induced serotonin N-acetyltransferase (Snat) transcription, N-acetylserotonin (NAS), and melatonin (MLT) synthesis. Circulating melatonin impairs the expression of adhesion molecules in endothelial cells, blocking the migration of leukocytes. Acute defence response induced by pathogen- and danger/damage-associated molecular patterns (PAMPs and DAMPs) triggers the NF-κB pathway in pinealocytes and blocks the transcription of Snat. Therefore, the darkness hormone is not released, and neutrophils and monocytes migrate to the lesion sites. ATP released in high amounts from apoptotic and death cells was considered a DAMP, and the blockage of P2X7 receptors was tested as a new class of drugs for treating brain damage. However, this is not a simple equation. High ATP injected in a lateral ventricle blocked MLT, but not NAS, synthesis as it impairs the transcription of acetyl serotonin N-methyltransferase. NAS is released in the plasma and the cerebral spinal fluid. NAS also blocks the rolling and adhesion of leukocytes to endothelial cells. Otherwise, it is metabolised specifically in each brain area to provide the requested concentration of MLT as a neuroprotector. As observed in physiological conditions, high extracellular ATP, different from the other DAMPs, reports the environmental light/dark cycle rhythm because NAS substitutes MLT as the nocturnal chemical indicator, the darkness hormone. Thus, blocking the P2X7R should not be considered a universal therapy for improving acute strokes, as MLT and ATP are partners in health and disease.

More than labels: neural representations of emotion words are widely distributed across the brain.

Although emotion words such as "anger," "disgust," "happiness," or "pride" are often thought of as mere labels, increasing evidence points to language as being important for emotion perception and experience. Emotion words may be particularly important for facilitating access to the emotion concepts. Indeed, deficits in semantic processing or impaired access to emotion words interfere with emotion perception. Yet, it is unclear what these behavioral findings mean for affective neuroscience. Thus, we examined the brain areas that support processing of emotion words using representational similarity analysis of functional magnetic resonance imaging data (N = 25). In the task, participants saw 10 emotion words (e.g. "anger," "happiness") while in the scanner. Participants rated each word based on its valence on a continuous scale ranging from 0 (Pleasant/Good) to 1 (Unpleasant/Bad) scale to ensure they were processing the words. Our results revealed that a diverse range of brain areas including prefrontal, midline cortical, and sensorimotor regions contained information about emotion words. Notably, our results overlapped with many regions implicated in decoding emotion experience by prior studies. Our results raise questions about what processes are being supported by these regions during emotion experience.

Same Same, But Different: Brain Areas Underlying the Learning from Repetitive Episodic Prediction Errors

Abstract Prediction errors (PEs) function as learning signals. It is yet unclear how varying compared to repetitive PEs affect episodic memory in brain and behavior. The current study investigated cerebral and behavioral effects of experiencing either multiple alternative versions (“varying”) or one single alternative version (“repetitive”) of a previously encoded episode. Participants encoded a set of episodes (“originals”) by watching videos showing toy stories. During scanning, participants either experienced originals, one single, or multiple alternative versions of the previously encoded episodes. Participants' memory performance was tested through recall of original objects. Varying and repetitive PEs revealed typical brain responses to the detection of mismatching information including inferior frontal and posterior parietal regions, as well as hippocampus, which is further linked to memory reactivation, and the amygdala, known for modulating memory consolidation. Furthermore, experiencing varying and repetitive PEs triggered distinct brain areas as revealed by direct contrast. Among others, experiencing varying versions triggered activity in the caudate, a region that has been associated with PEs. In contrast, repetitive PEs activated brain areas that resembled more those for retrieval of originally encoded episodes. Thus, ACC and posterior cingulate cortex activation seemed to serve both reactivating old and integrating new but similar information in episodic memory. Consistent with neural findings, participants recalled original objects less accurately when only presented with the same, but not varying, PE during fMRI. The current findings suggest that repeated PEs interact more strongly with a recalled original episodic memory than varying PEs.

Deformation-based morphometry: a sensitive imaging approach to detect radiation-induced brain injury?

BackgroundRadiotherapy is a major therapeutic approach in patients with brain tumors. However, it leads to cognitive impairments. To improve the management of radiation-induced brain sequalae, deformation-based morphometry (DBM) could be relevant. Here, we analyzed the significance of DBM using Jacobian determinants (JD) obtained by non-linear registration of MRI images to detect local vulnerability of healthy cerebral tissue in an animal model of brain irradiation.MethodsRats were exposed to fractionated whole-brain irradiation (WBI, 30 Gy). A multiparametric MRI (anatomical, diffusion and vascular) study was conducted longitudinally from 1 month up to 6 months after WBI. From the registration of MRI images, macroscopic changes were analyzed by DBM and microscopic changes at the cellular and vascular levels were evaluated by quantification of cerebral blood volume (CBV) and diffusion metrics including mean diffusivity (MD). Voxel-wise comparisons were performed on the entire brain and in specific brain areas identified by DBM. Immunohistology analyses were undertaken to visualize the vessels and astrocytes.ResultsDBM analysis evidenced time-course of local macrostructural changes; some of which were transient and some were long lasting after WBI. DBM revealed two vulnerable brain areas, namely the corpus callosum and the cortex. DBM changes were spatially associated to microstructural alterations as revealed by both diffusion metrics and CBV changes, and confirmed by immunohistology analyses. Finally, matrix correlations demonstrated correlations between JD/MD in the early phase after WBI and JD/CBV in the late phase both in the corpus callosum and the cortex.ConclusionsBrain irradiation induces local macrostructural changes detected by DBM which could be relevant to identify brain structures prone to radiation-induced tissue changes. The translation of these data in patients could represent an added value in imaging studies on brain radiotoxicity.

Functional connectivity associations with menstrual pain characteristics in adolescents: an investigation of the triple network model.

Menstrual pain is associated with deficits in central pain processing, yet neuroimaging studies to date have all been limited by focusing on group comparisons of adult women with vs without menstrual pain. This study aimed to investigate the role of the triple network model (TNM) of brain networks in adolescent girls with varied menstrual pain severity ratings. One hundred participants (ages 13-19 years) completed a 6-min resting state functional magnetic resonance imaging (fMRI) scan and rated menstrual pain severity, menstrual pain interference, and cumulative menstrual pain exposure. Imaging analyses included age and gynecological age (years since menarche) as covariates. Menstrual pain severity was positively associated with functional connectivity between the cingulo-opercular salience network (cSN) and the sensory processing regions, limbic regions, and insula, and was also positively associated with connectivity between the left central executive network (CEN) and posterior regions. Menstrual pain interference was positively associated with connectivity between the cSN and widespread brain areas. In addition, menstrual pain interference was positively associated with connectivity within the left CEN, whereas connectivity both within the right CEN and between the right CEN and cortical areas outside the network (including the insula) were negatively associated with menstrual pain interference. Cumulative menstrual pain exposure shared a strong negative association with connectivity between the default mode network and other widespread regions associated with large-scale brain networks. These findings support a key role for the involvement of TNM brain networks in menstrual pain characteristics and suggest that alterations in pain processing exist in adolescents with varying levels of menstrual pain.

The blushing brain: neural substrates of cheek temperature increase in response to self-observation.

Darwin proposed that blushing-the reddening of the face owing to heightened self-awareness-is 'the most human of all expressions'. Yet, relatively little is known about the underlying mechanisms of blushing. Theories diverge on whether it is a rapid, spontaneous emotional response that does not involve reflection upon the self or whether it results from higher-order socio-cognitive processes. Investigating the neural substrates of blushing can shed light on the mental processes underlying blushing and the mechanisms involved in self-awareness. To reveal neural activity associated with blushing, 16-20 year-old participants (n = 40) watched pre-recorded videos of themselves (versus other people as a control condition) singing karaoke in a magnetic resonance imaging scanner. We measured participants' cheek temperature increase-an indicator of blushing-and their brain activity. The results showed that blushing is higher when watching oneself versus others sing. Those who blushed more while watching themselves sing had, on average, higher activation in the cerebellum (lobule V) and the left paracentral lobe and exhibited more time-locked processing of the videos in early visual cortices. These findings show that blushing is associated with the activation of brain areas involved in emotional arousal, suggesting that it may occur independently of higher-order socio-cognitive processes. Our results provide new avenues for future research on self-awareness in infants and non-human animals.

The Trouble with Free-Water Elimination using Single-Shell Diffusion MRI Data: A Case-Study in Ageing

Abstract Free-water elimination (FWE) modelling for Diffusion Tensor Imaging (DTI) can be used to estimate the free-water (FW) volume fraction, as well as FW-compensated DTI parameters. Single-shell (SS) diffusion MRI acquisitions are more common in clinical cohorts due to time constraints, but the FWE-DTI model is a two-compartment model, hence only well-posed for multi-shell (MS) data. A regularised gradient descent (RGD) method is often applied to SS datasets and has been used to study healthy ageing, Alzheimer’s and Parkinson’s disease, amongst others, largely ignoring the methodological limitations of this approach. In this study, we compared the performance of RGD fitting with SS data, to a non-linear least squares (NLS) fitting applied to MS data, using simulations and data from 620 participants aged 18 to 88 years. Consistent with previous studies, our simulations show that RGD fitting using SS data flattens the relationship between mean diffusivity (MD) estimates and their ground truth values, and introduces an artificial positive correlation between fractional anisotropy (FA) estimates and the underlying tissue ground truth MD. Neither of these biases were observed when NLS fitting was applied to MS data. In human data, a smaller number of significant voxels with positive correlations between MD and age was observed when the RGD SS algorithm was used, which is consistent with the flattening of MD profiles observed in simulations. FW-compensated FA maps produced strikingly different results depending on the method employed: the maps obtained with RGD SS identified some brain areas with a strong positive association with age, while no such positive correlations were found with MS NLS. While similar positive correlations between age and FW-compensated FA maps obtained with SS RGD have been reported, these results are only replicated when the RGD SS was used, suggesting this apparent FA increase was likely an artefact introduced by inappropriate modelling using SS data. Our study, therefore, suggests that previous findings reported in the literature using the RGD approach should be interpreted with extreme care.

Low-cost, portable, easy-to-use kiosks to facilitate home-cage testing of non-human primates during vision-based behavioral tasks.

Non-human primates (NHPs), especially rhesus macaques, have significantly contributed to our understanding of the neural computations underlying human vision. Besides the established homologies in the visual brain areas between these species and our ability to probe detailed neural mechanisms in monkeys at multiple scales, NHPs' ability to perform human-like visual behavior makes them an extremely appealing animal model of human vision. Traditionally, such behavioral studies have been conducted in controlled laboratory settings, offering experimenters tight control over variables like luminance, eye movements, and auditory interference. However, in-lab experiments have several constraints, including limited experimental time, the need for dedicated human experimenters, additional lab space requirements, invasive surgeries for head-post implants, and extra time and training for chairing and head restraints. To overcome these limitations, we propose adopting home-cage behavioral training and testing of NHPs, enabling the administration of many vision-based behavioral tasks simultaneously across multiple monkeys with reduced human personnel requirements, no NHP head restraint, and monkeys' unrestricted access to experiments. In this article, we present a portable, low-cost, easy-to-use kiosk system developed to conduct home-cage vision-based behavioral tasks in NHPs. We provide details of its operation and build to enable more open-source development of this technology. Furthermore, we present validation results using behavioral measurements performed in the lab and in NHP home cages, demonstrating the system's reliability and potential to enhance the efficiency and flexibility of NHP behavioral research.

Differently increased volumes of multiple brain areas in Npc1 mutant mice following various drug treatments

BackgroundNiemann-Pick disease type C1 (NPC1, MIM 257220) is a heritable lysosomal storage disease characterized by a progressive neurological degeneration that causes disability and premature death. A murine model of Npc1−/− displays a rapidly progressing form of Npc1 disease, which is characterized by weight loss, ataxia, and increased cholesterol storage. Npc1−/− mice receiving a combined therapy (COMBI) of miglustat (MIGLU), the neurosteroid allopregnanolone (ALLO) and the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (HPßCD) showed prevention of Purkinje cell loss, improved motor function and reduced intracellular lipid storage. Although therapy of Npc1−/− mice with COMBI, MIGLU or HPßCD resulted in the prevention of body weight loss, reduced total brain weight was not positively influenced.MethodsIn order to evaluate alterations of different brain areas caused by pharmacotherapy, fresh volumes (volumes calculated from the volumes determined from paraffin embedded brain slices) of various brain structures in sham- and drug-treated wild type and mutant mice were measured using stereological methods.ResultsIn the wild type mice, the volumes of investigated brain areas were not significantly altered by either therapy. Compared with the respective wild types, fresh volumes of specific brain areas, which were significantly reduced in sham-treated Npc1−/− mice, partly increased after the pharmacotherapies in all treatment strategies; most pronounced differences were found in the CA1 area of the hippocampus and in olfactory structures.DiscussionVolumes of brain areas of Npc1−/− mice were not specifically changed in terms of functionality after administering COMBI, MIGLU, or HPßCD. Measurements of fresh volumes of brain areas in Npc1−/− mice could monitor region-specific changes and response to drug treatment that correlated, in part, with behavioral improvements in this mouse model.

Repetitive active and passive cognitive stimulations induce EEG changes in patients with Rett syndrome.

Despite being considered a rare disease, Rett syndrome is a leading cause of profound cognitive impairment in females. This study explores game-based cognitive stimulation to enhance attention during learning tasks, offering an alternative treatment perspective. Fifteen diagnosed Rett syndrome girls participated in four 24-minute sessions, including a 5-minute initial resting state recording. Primary indicators for analysis included relative power and spectral entropy. Significant findings indicated variations among conditions (resting state, active task, passive task) in response to stimulation. Notably, over four days, evolution occurred, characterized by decreasing delta power and increasing theta and beta power. Topographic maps confirmed these shifts, highlighting affected brain areas. Linear regression emphasized the most significant impact on the first day, with subsequent shifts towards higher frequencies, particularly during the resting state. By the fourth day, resting-state patterns resembled those during cognitive activities. Findings suggest cognitive stimulation induces substantial EEG spectral changes, potentially linked to cognitive enhancements in Rett syndrome. The shift towards higher frequency bands and increased spectral entropy align with enhanced brain activation during cognitive sessions, underscoring the potential of cognitive stimulation therapies and calling for further research to optimize abilities in individuals with Rett syndrome. Game-based cognitive stimulation induces substantial EEG changes in individuals with Rett syndrome, enhancing cognitive functions, notably attention during learning. This study conducts a distinctive examination, assessing the habituation paradigm through the combination of game-based cognitive stimulation and learning, providing valuable insights into enhancing attention in Rett syndrome. Impacting understanding of cognitive processes in Rett syndrome, this research reveals significant EEG variations during tasks, emphasizing the potential of cognitive stimulation for attention enhancement and the need for further research in tailored interventions.

Sex differences in the effects of N-ethylpentylone in young CD1 mice: Insights on behaviour, thermoregulation and early gene expression.

New psychoactive substances such as N-ethylpentylone (NEP) are continuously emerging in the illicit drug market, and knowledge of their effects and risks, which may vary between sexes, is scarce. Our present study compares some key effects of NEP in male and female mice. Psychostimulant, rewarding and reinforcing effects were investigated by tracking locomotor activity, conditioned place preference (CPP) paradigm and through a self-administration (SA) procedure, respectively, in CD1 mice. Moreover, the expression of early genes (C-fos, Arc, Csnk1e, Pdyn, Pp1r1b and Bdnf in addiction-related brain areas) was assessed by qPCR. Finally, serum and brain levels of NEP were determined by UHPLC-MS/MS. NEP-treated males experimented locomotor sensitisation and showed higher and longer increases in locomotion as well as higher hyperthermia after repeated administration than females. Moreover, while preference score in the CPP was similar in both sexes, extinction occurred later, and reinstatement was more easily established for males. Female mice self-administered more NEP than males at a higher dose. Differences in early gene expression (Arc, Bdnf, Csnk1e and Ppp1r1b) were found, but the serum and brain NEP levels did not differ between sexes. Our results suggest that male mice are more sensitive to NEP psychostimulant and rewarding effects. These differences may be attributed to different early gene expression but not to pharmacokinetic factors. Moreover, males appear to be more vulnerable to the hyperthermic effects of NEP, while females might be more prone to NEP abuse.

Transcriptomic changes in the posterior pallium of male zebra finches associated with social niche conformance

Animals plastically adjust their physiological and behavioural phenotypes to conform to their social environment—social niche conformance. The degree of sexual competition is a critical part of the social environment to which animals adjust their phenotypes, but the underlying genetic mechanisms are poorly understood. We conducted a study to investigate how differences in sperm competition risk affect the gene expression profiles of the testes and two brain areas (posterior pallium and optic tectum) in breeding male zebra finches (Taeniopygia castanotis). In this pre-registered study, we investigated a large sample of 59 individual transcriptomes. We compared two experimental groups: males held in single breeding pairs (low sexual competition) versus those held in two pairs (elevated sexual competition) per breeding cage. Using weighted gene co-expression network analysis (WGCNA), we observed significant effects of the social treatment in all three tissues. However, only the treatment effects found in the pallium were confirmed by an additional randomisation test for statistical robustness. Likewise, the differential gene expression analysis revealed treatment effects only in the posterior pallium (ten genes) and optic tectum (six genes). No treatment effects were found in the testis at the single gene level. Thus, our experiments do not provide strong evidence for transcriptomic adjustment specific to manipulated sperm competition risk. However, we did observe transcriptomic adjustments to the manipulated social environment in the posterior pallium. These effects were polygenic rather than based on few individual genes with strong effects. Our findings are discussed in relation to an accompanying paper using the same animals, which reports behavioural results consistent with the results presented here.

Dynamic network analysis of electrophysiological task data

Abstract An important approach for studying the human brain is to use functional neuroimaging combined with a task. In electrophysiological data, this often involves a time-frequency analysis, in which recorded brain activity is time-frequency transformed and epoched around task events of interest, followed by trial-averaging of the power. While this simple approach can reveal fast oscillatory dynamics, the brain regions are analysed one at a time. This causes difficulties for interpretation and a debilitating number of multiple comparisons. In addition, it is now recognised that the brain responds to tasks through the coordinated activity of networks of brain areas. As such, techniques that take a whole-brain network perspective are needed. Here, we show how the oscillatory task responses from conventional time-frequency approaches can be represented more parsimoniously at the network level using two state-of-the-art methods: the HMM (Hidden Markov Model) and DyNeMo (Dynamic Network Modes). Both methods reveal frequency-resolved networks of oscillatory activity with millisecond resolution. Comparing DyNeMo, HMM, and traditional oscillatory response analysis, we show DyNeMo can identify task activations/deactivations that the other approaches fail to detect. DyNeMo offers a powerful new method for analysing task data from the perspective of dynamic brain networks.

The role of alpha oscillations in free- and goal-directed semantic associations.

Alpha oscillations are known to play a central role in several higher-order cognitive functions, especially selective attention, working memory, semantic memory, and creative thinking. Nonetheless, we still know very little about the role of alpha in the generation of more remote semantic associations, which is key to creative and semantic cognition. Furthermore, it remains unclear how these oscillations are shaped by the intention to "be creative," which is the case in most creativity tasks. We aimed to address these gaps in two experiments. In Experiment 1, we compared alpha oscillatory activity (using a method which distinguishes genuine oscillatory activity from transient events) during the generation of free associations which were more vs. less distant from a given concept. In Experiment 2, we replicated these findings and also compared alpha oscillatory activity when people were generating free associations versus associations with the instruction to be creative (i.e. goal-directed). We found that alpha was consistently higher during the generation of more distant semantic associations, in both experiments. This effect was widespread, involving areas in both left and right hemispheres. Importantly, the instruction to be creative seems to increase alpha phase synchronisation from left to right temporal brain areas, suggesting that intention to be creative changed the flux of information in the brain, likely reflecting an increase in top-down control of semantic search processes. We conclude that goal-directed generation of remote associations relies on top-down mechanisms compared to when associations are freely generated.

The role of alpha oscillations in free- and goal-directed semantic associations.

Alpha oscillations are known to play a central role in several higher-order cognitive functions, especially selective attention, working memory, semantic memory, and creative thinking. Nonetheless, we still know very little about the role of alpha in the generation of more remote semantic associations, which is key to creative and semantic cognition. Furthermore, it remains unclear how these oscillations are shaped by the intention to "be creative," which is the case in most creativity tasks. We aimed to address these gaps in two experiments. In Experiment 1, we compared alpha oscillatory activity (using a method which distinguishes genuine oscillatory activity from transient events) during the generation of free associations which were more vs. less distant from a given concept. In Experiment 2, we replicated these findings and also compared alpha oscillatory activity when people were generating free associations versus associations with the instruction to be creative (i.e. goal-directed). We found that alpha was consistently higher during the generation of more distant semantic associations, in both experiments. This effect was widespread, involving areas in both left and right hemispheres. Importantly, the instruction to be creative seems to increase alpha phase synchronisation from left to right temporal brain areas, suggesting that intention to be creative changed the flux of information in the brain, likely reflecting an increase in top-down control of semantic search processes. We conclude that goal-directed generation of remote associations relies on top-down mechanisms compared to when associations are freely generated.

The Effects of Musicality on Brain Network Topology in the Context of Alzheimer’s Disease and Memory Decline

Abstract Music's role in modulating brain structure, particularly in neurodegenerative contexts such as Alzheimer's Disease (AD), has been increasingly recognized. While previous studies have hinted at the potential neuroplastic benefits of musical engagement and training, the mechanisms through which music impacts structural connectivity in neurodegenerative pathways remain under explored. We aimed to examine the impact of music perception skills, active musical engagement, and musical training on structural connectivity in areas relating to memory, emotion, and learning in individuals with worsening memory impairment, investigating the potential neuroplastic effects of music. Employing diffusion tensor imaging (DTI) based structural connectivity and graph theoretical analysis, we investigated brain topological features in 78 participants aged 42 to 85 with a range of memory impairments. Participants were assessed for musical training, engagement, and perception skills. The study analyzed regional and local network topological metrics to examine the influence of musical activities on graph metrics, while controlling for stages of objective memory impairment (SOMI) and diagnosis, separately. This study aimed to elucidate the effects of musical perception skills, active musical engagement, and musical training on structural connectivity within memory, emotion, and learning-related brain areas in individuals with varying degrees of memory impairment. We found enhanced structural connectivity of the right hippocampus and the right posterior cingulate cortex was associated with stronger local network metrics, such as clustering coefficient and betweenness centrality, with increased music perception skills like melody and beat perception. Musical training specifically impacted the clustering coefficient of the right hippocampus and the node degree of the right mid cingulate gyrus. Active musical engagement influenced the eigenvector centrality of the right hippocampus. Furthermore, musical training was associated with enhanced global metrics, such as global efficiency and characteristic path length. Our study integrates diffusion MRI and graph theoretical analysis to reveal significant effects of musical activities on structural connectivity in key brain regions. The results highlight the potential of musical activities to serve as a non-invasive modulatory tool for cognitive resilience, especially in memory impairment and neurodegeneration contexts. These insights contribute to the understanding of delaying AD onset and aiding early-stage patients through music-based interventions, emphasizing the importance of musical engagement in maintaining cognitive and brain health.