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1.
bioRxiv ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39345454

RESUMO

Humans must often keep multiple task goals in mind, at different levels of priority and immediacy, while also interacting with the environment. We might need to remember information for an upcoming task while engaged in more immediate actions. Consequently, actively maintained working memory (WM) content may bleed into ongoing but unrelated motor behavior. Here, we experimentally test the impact of WM maintenance on action execution, and we transcranially stimulate lateral prefrontal cortex (PFC) to parse its functional contributions to WM-motor interactions. We first created a task scenario wherein human participants (both sexes) executed cued hand movements during WM maintenance. We manipulated the compatibility between WM and movement goals at the trial level and the statistical likelihood that the two would be compatible at the block level. We found that remembering directional words (e.g., 'left', 'down') biased the trajectory and speed of hand movements that occurred during the WM delay, but the bias was dampened in blocks when WM content predictably conflicted with movement goals. Then we targeted left lateral PFC with two different transcranial magnetic stimulation (TMS) protocols before participants completed the task. We found that an intermittent theta-burst protocol, which is thought to be excitatory, dampened sensitivity to block-level control demands (i.e., proactive control), while a continuous theta-burst protocol, which is thought to be inhibitory, dampened adaptation to trial-by- trial conflict (i.e., reactive control). Therefore, lateral PFC is involved in controlling the interplay between WM content and manual action, but different PFC mechanisms may support different time-scales of adaptive control. Significance Statement: Working memory (WM) allows us to keep information active in mind to achieve our moment-to-moment goals. However, WM maintenance may sometimes unintentionally shape our externally-geared actions. This study formalizes the everyday "action slips" humans commit when we type out or say the wrong word in conversation because it was held in mind for a different goal. The results show that internally maintained content can influence ongoing hand movements, but this interplay between WM and motor behavior depends on the cortical excitability state of the lateral PFC. Neural perturbation with transcranial magnetic stimulation (TMS) shows that temporarily increasing or decreasing PFC excitability can make participants more or less susceptible to the impact of WM on actions.

2.
bioRxiv ; 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39345422

RESUMO

Both goal-directed and automatic processes shape human behavior. These processes often conflict, and behavioral control is the decision about which determines behavior. Behavioral control, or deciding how to decide, is critical for adaptive behavior. However, the neural mechanisms underlying behavioral control remain unclear. We performed deep phenotyping of individual dopamine system function by combining PET measures of dopamine physiology, functional MRI, and administration of dopaminergic drugs in a within-subject, double-blind, placebo-controlled design. Subjects performed a rule-based response time task in which we operationalized goal-directed and automatic decision-making as model-based and model-free contributions to behavior, respectively. We found convergent and causal evidence that dopamine D2/3 receptors in the striatum regulate behavioral control by enhancing model-based and blunting model-free influences on behavior. In contrast, we found a double dissociation whereby presynaptic dopamine synthesis capacity in the striatum was linked to acquiring model-based knowledge but not behavioral control. Neuroimaging analysis suggested that striatal D2/3 receptors influence behavioral control by adjusting frontostriatal functional connectivity. This multimodal study establishes a specific role of D2/3 receptors in regulating behavioral control and could contribute to an improved understanding of dysregulated behavioral control in clinical disorders affecting dopamine neurotransmission.

3.
J Exp Med ; 221(9)2024 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-39133222

RESUMO

The retinoid nuclear receptor pathway, activated by the vitamin A metabolite retinoic acid, has been extensively investigated for over a century. This study has resulted in conflicting hypotheses about how the pathway regulates health and how it should be pharmaceutically manipulated. These disagreements arise from a fundamental contradiction: retinoid agonists offer clear benefits to select patients with rare bone growth disorders, acute promyelocytic leukemia, and some dermatologic diseases, yet therapeutic retinoid pathway activation frequently causes more harm than good, both through acute metabolic dysregulation and a delayed cancer-promoting effect. In this review, we discuss controlled clinical, mechanistic, and genetic data to suggest several disease settings where inhibition of the retinoid pathway may be a compelling therapeutic strategy, such as solid cancers or metabolic syndromes, and also caution against continued testing of retinoid agonists in cancer patients. Considerable evidence suggests a central role for retinoid regulation of immunity and metabolism, with therapeutic opportunities to antagonize retinoid signaling proposed in cancer, diabetes, and obesity.


Assuntos
Síndrome Metabólica , Neoplasias , Transdução de Sinais , Humanos , Neoplasias/metabolismo , Animais , Síndrome Metabólica/metabolismo , Receptores do Ácido Retinoico/metabolismo , Retinoides/metabolismo
4.
J Cogn Neurosci ; : 1-16, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38579249

RESUMO

Stimulus-response habits benefit behavior by automatizing the selection of rewarding actions. However, this automaticity can come at the cost of reduced flexibility to adapt behavior when circumstances change. The goal-directed system is thought to counteract the habit system by providing the flexibility to pursue context-appropriate behaviors. The dichotomy between habitual action selection and flexible goal-directed behavior has recently been challenged by findings showing that rewards bias both action and goal selection. Here, we test whether reward reinforcement can give rise to habitual goal selection much as it gives rise to habitual action selection. We designed a rewarded, context-based perceptual discrimination task in which performance on one rule was reinforced. Using drift-diffusion models and psychometric analyses, we found that reward facilitates the initiation and execution of rules. Strikingly, we found that these biases persisted in a test phase in which rewards were no longer available. Although this facilitation is consistent with the habitual goal selection hypothesis, we did not find evidence that reward reinforcement reduced cognitive flexibility to implement alternative rules. Together, the findings suggest that reward creates a lasting impact on the selection and execution of goals but may not lead to the inflexibility characteristic of habits. Our findings demonstrate the role of the reward learning system in influencing how the goal-directed system selects and implements goals.

5.
Front Hum Neurosci ; 18: 1353043, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38384333

RESUMO

Human brain imaging research using functional MRI (fMRI) has uncovered flexible variations in the functional connectivity between brain regions. While some of this variability likely arises from the pattern of information flow through circuits, it may also be influenced by rapid changes in effective synaptic strength at the molecular level, a phenomenon called Dynamic Network Connectivity (DNC) discovered in non-human primate circuits. These neuromodulatory molecular mechanisms are found in layer III of the macaque dorsolateral prefrontal cortex (dlPFC), the site of the microcircuits shown by Goldman-Rakic to be critical for working memory. This research has shown that the neuromodulators acetylcholine, norepinephrine, and dopamine can rapidly change the strength of synaptic connections in layer III dlPFC by (1) modifying the depolarization state of the post-synaptic density needed for NMDA receptor neurotransmission and (2) altering the open state of nearby potassium channels to rapidly weaken or strengthen synaptic efficacy and the strength of persistent neuronal firing. Many of these actions involve increased cAMP-calcium signaling in dendritic spines, where varying levels can coordinate the arousal state with the cognitive state. The current review examines the hypothesis that some of the dynamic changes in correlative strength between cortical regions observed in human fMRI studies may arise from these molecular underpinnings, as has been seen when pharmacological agents or genetic alterations alter the functional connectivity of the dlPFC consistent with the macaque physiology. These DNC mechanisms provide essential flexibility but may also confer vulnerability to malfunction when dysregulated in cognitive disorders.

6.
Hum Brain Mapp ; 45(2): e26587, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38339903

RESUMO

Recent years have seen growing interest in characterizing the properties of regional brain dynamics and their relationship to other features of brain structure and function. In particular, multiple studies have observed regional differences in the "timescale" over which activity fluctuates during periods of quiet rest. In the cerebral cortex, these timescales have been associated with both local circuit properties as well as patterns of inter-regional connectivity, including the extent to which each region exhibits widespread connectivity to other brain areas. In the current study, we build on prior observations of an association between connectivity and dynamics in the cerebral cortex by investigating the relationship between BOLD fMRI timescales and the modular organization of structural and functional brain networks. We characterize network community structure across multiple scales and find that longer timescales are associated with greater within-community functional connectivity and diverse structural connectivity. We also replicate prior observations of a positive correlation between timescales and structural connectivity degree. Finally, we find evidence for preferential functional connectivity between cortical areas with similar timescales. We replicate these findings in an independent dataset. These results contribute to our understanding of functional brain organization and structure-function relationships in the human brain, and support the notion that regional differences in cortical dynamics may in part reflect the topological role of each region within macroscale brain networks.


Assuntos
Encéfalo , Córtex Cerebral , Humanos , Encéfalo/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética , Descanso , Rede Nervosa/diagnóstico por imagem
7.
J Cogn Neurosci ; 36(5): 916-935, 2024 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-38319885

RESUMO

Cognitive control allows behavior to be guided according to environmental contexts and internal goals. During cognitive control tasks, fMRI analyses typically reveal increased activation in frontal and parietal networks, and EEG analyses reveal increased amplitude of neural oscillations in the delta/theta band (2-3, 4-7 Hz) in frontal electrodes. Previous studies proposed that theta-band activity reflects the maintenance of rules associating stimuli to appropriate actions (i.e., the rule set), whereas delta synchrony is specifically associated with the control over the context for when to apply a set of rules (i.e., the rule abstraction). We tested these predictions using EEG and fMRI data collected during the performance of a hierarchical cognitive control task that manipulated the level of abstraction of task rules and their set-size. Our results show a clear separation of delta and theta oscillations in the control of rule abstraction and of stimulus-action associations, respectively, in distinct frontoparietal association networks. These findings support a model by which frontoparietal networks operate through dynamic, multiplexed neural processes.


Assuntos
Cognição , Ritmo Teta , Humanos , Cognição/fisiologia , Ritmo Teta/fisiologia , Eletroencefalografia/métodos
8.
bioRxiv ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38328154

RESUMO

The ability to successfully retain and manipulate information in working memory (WM) requires that objects' individual features are bound into cohesive representations; yet, the mechanisms supporting feature binding remain unclear. Binding (or swap) errors, where memorized features are erroneously associated with the wrong object, can provide a window into the intrinsic limits in capacity of WM that represent a key bottleneck in our cognitive ability. We tested the hypothesis that binding in WM is accomplished via neural phase synchrony and that swap errors result from perturbations in this synchrony. Using magnetoencephalography data collected from human subjects in a task designed to induce swap errors, we showed that swaps are characterized by reduced phase-locked oscillatory activity during memory retention, as predicted by an attractor model of spiking neural networks. Further, we found that this reduction arises from increased phase-coding variability in the alpha-band over a distributed network of sensorimotor areas. Our findings demonstrate that feature binding in WM is accomplished through phase-coding dynamics that emerge from the competition between different memories.

9.
Brain Commun ; 6(1): fcad252, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38162898

RESUMO

Stroke alters blood flow to the brain resulting in damaged tissue and cell death. Moreover, the disruption of cerebral blood flow (perfusion) can be observed in areas surrounding and distal to the lesion. These structurally preserved but suboptimally perfused regions may also affect recovery. Thus, to better understand aphasia recovery, the relationship between cerebral perfusion and language needs to be systematically examined. In the current study, we aimed to evaluate (i) how stroke affects perfusion outside of lesioned areas in chronic aphasia and (ii) how perfusion in specific cortical areas and perilesional tissue relates to language outcomes in aphasia. We analysed perfusion data from a large sample of participants with chronic aphasia due to left hemisphere stroke (n = 43) and age-matched healthy controls (n = 25). We used anatomically defined regions of interest that covered the frontal, parietal, and temporal areas of the perisylvian cortex in both hemispheres, areas typically known to support language, along with several control regions not implicated in language processing. For the aphasia group, we also looked at three regions of interest in the perilesional tissue. We compared perfusion levels between the two groups and investigated the relationship between perfusion levels and language subtest scores while controlling for demographic and lesion variables. First, we observed that perfusion levels outside the lesioned areas were significantly reduced in frontal and parietal regions in the left hemisphere in people with aphasia compared to the control group, while no differences were observed for the right hemisphere regions. Second, we found that perfusion in the left temporal lobe (and most strongly in the posterior part of both superior and middle temporal gyri) and inferior parietal areas (supramarginal gyrus) was significantly related to residual expressive and receptive language abilities. In contrast, perfusion in the frontal regions did not show such a relationship; no relationship with language was also observed for perfusion levels in control areas and all right hemisphere regions. Third, perilesional perfusion was only marginally related to language production abilities. Cumulatively, the current findings demonstrate that blood flow is reduced beyond the lesion site in chronic aphasia and that hypoperfused neural tissue in critical temporoparietal language areas has a negative impact on behavioural outcomes. These results, using perfusion imaging, underscore the critical and general role that left hemisphere posterior temporal regions play in various expressive and receptive language abilities. Overall, the study highlights the importance of exploring perfusion measures in stroke.

10.
Cereb Cortex ; 34(2)2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38282457

RESUMO

One of the most important human faculties is the ability to acquire not just new memories but the capacity to perform entirely new tasks. However, little is known about the brain mechanisms underlying the learning of novel tasks. Specifically, it is unclear to what extent learning of different tasks depends on domain-general and/or domain-specific brain mechanisms. Here human subjects (n = 45) learned to perform 6 new tasks while undergoing functional MRI. The different tasks required the engagement of perceptual, motor, and various cognitive processes related to attention, expectation, speed-accuracy tradeoff, and metacognition. We found that a bilateral frontoparietal network was more active during the initial compared with the later stages of task learning, and that this effect was stronger for task variants requiring more new learning. Critically, the same frontoparietal network was engaged by all 6 tasks, demonstrating its domain generality. Finally, although task learning decreased the overall activity in the frontoparietal network, it increased the connectivity strength between the different nodes of that network. These results demonstrate the existence of a domain-general brain network whose activity and connectivity reflect learning for a variety of new tasks, and thus may underlie the human capacity for acquiring new abilities.


Assuntos
Mapeamento Encefálico , Metacognição , Humanos , Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Aprendizagem , Atenção , Imageamento por Ressonância Magnética/métodos
11.
Cereb Cortex ; 34(1)2024 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-37968568

RESUMO

The goal of precision brain health is to accurately predict individuals' longitudinal patterns of brain change. We trained a machine learning model to predict changes in a cognitive index of brain health from neurophysiologic metrics. A total of 48 participants (ages 21-65) completed a sensorimotor task during 2 functional magnetic resonance imaging sessions 6 mo apart. Hemodynamic response functions (HRFs) were parameterized using traditional (amplitude, dispersion, latency) and novel (curvature, canonicality) metrics, serving as inputs to a neural network model that predicted gain on indices of brain health (cognitive factor scores) for each participant. The optimal neural network model successfully predicted substantial gain on the cognitive index of brain health with 90% accuracy (determined by 5-fold cross-validation) from 3 HRF parameters: amplitude change, dispersion change, and similarity to a canonical HRF shape at baseline. For individuals with canonical baseline HRFs, substantial gain in the index is overwhelmingly predicted by decreases in HRF amplitude. For individuals with non-canonical baseline HRFs, substantial gain in the index is predicted by congruent changes in both HRF amplitude and dispersion. Our results illustrate that neuroimaging measures can track cognitive indices in healthy states, and that machine learning approaches using novel metrics take important steps toward precision brain health.


Assuntos
Encéfalo , Hemodinâmica , Humanos , Encéfalo/diagnóstico por imagem , Hemodinâmica/fisiologia , Mapeamento Encefálico , Imageamento por Ressonância Magnética/métodos , Neuroimagem , Cognição
12.
Environ Res ; 242: 117716, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37995999

RESUMO

The textile industry is a major contributor to global waste, with millions of tons of textiles being discarded annually. Material and energy recovery within circular economy offer sustainable solutions to this problem by extending the life cycle of textiles through repurposing, recycling, and upcycling. These initiatives not only reduce waste but also contribute to the reduction of the demand for virgin materials (i.e. cotton, wool), ultimately benefiting the environment and society. The circular economy approach, which aims to recreate environmental, economic, and societal value, is based on three key principles: waste reduction, material circulation, and ecological restoration. Given these difficulties, circularity incorporates the material recovery approach, which is focused on the conversion of waste into secondary raw resources. The goal of this notion is to extract more value from resources by prolonging final disposal as long as feasible. When a textile has outlived its functional life, material recovery is critical for returning the included materials or energy into the manufacturing cycle. The aim of this paper is to examine the material and energy recovery options of main raw materials used in the fashion industry while highlighting the need of close observation of the relation between circularity and material recovery, including the investigation of barriers to the transition towards a truly circular fashion industry. The final results refer to the main barriers of circular economy transition within the industry and a framework is proposed. These insights are useful for academia, engineers, policy makers and other key stakeholders for the clear understanding of the industry from within and highlight beyond circular economy targets, SDGs interactions with energy and material recovery of textile waste (SDG 7, SDG 11, SDG 12 etc.).


Assuntos
Reciclagem , Gerenciamento de Resíduos , Animais , Têxteis , Indústrias , Indústria Têxtil
13.
J Cogn Neurosci ; 36(1): 155-166, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37902578

RESUMO

There is increasing evidence that the left lateral frontal cortex is hierarchically organized such that higher-order regions have an asymmetric top-down influence over lower order regions. However, questions remain about the underlying neuroarchitecture of this hierarchical control organization. Within the frontal cortex, dopamine plays an important role in cognitive control functions, and we hypothesized that dopamine may preferentially influence top-down connections within the lateral frontal hierarchy. Using a randomized, double-blind, within-subject design, we analyzed resting-state fMRI data of 66 healthy young participants who were scanned once each after administration of bromocriptine (a dopamine agonist with preferential affinity for D2 receptor), tolcapone (an inhibitor of catechol-O-methyltransferase), and placebo, to determine whether dopaminergic stimulation modulated effective functional connectivity between hierarchically organized frontal regions in the left hemisphere. We found that dopaminergic drugs modulated connections from the caudal middle frontal gyrus and the inferior frontal sulcus to both rostral and caudal frontal areas. In dorsal frontal regions, effectivity connectivity strength was increased, whereas in ventral frontal regions, effective connectivity strength was decreased. These findings suggest that connections within frontal cortex are differentially modulated by dopamine, which may bias the influence that frontal regions exert over each other.


Assuntos
Catecol O-Metiltransferase , Dopamina , Humanos , Lobo Frontal/fisiologia , Córtex Pré-Frontal/fisiologia , Agonistas de Dopamina/farmacologia , Imageamento por Ressonância Magnética
14.
bioRxiv ; 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37502887

RESUMO

Recent years have seen growing interest in characterizing the properties of regional brain dynamics and their relationship to other features of brain structure and function. In particular, multiple studies have observed regional differences in the "timescale" over which activity fluctuates during periods of quiet rest. In the cerebral cortex, these timescales have been associated with both local circuit properties as well as patterns of inter-regional connectivity, including the extent to which each region exhibits widespread connectivity to other brain areas. In the current study, we build on prior observations of an association between connectivity and dynamics in the cerebral cortex by investigating the relationship between BOLD fMRI timescales and the modular organization of structural and functional brain networks. We characterize network community structure across multiple scales and find that longer timescales are associated with greater within-community functional connectivity and diverse structural connectivity. We also replicate prior observations of a positive correlation between timescales and structural connectivity degree. Finally, we find evidence for preferential functional connectivity between cortical areas with similar timescales. We replicate these findings in an independent dataset. These results contribute to our understanding of functional brain organization and structure-function relationships in the human brain, and support the notion that regional differences in cortical dynamics may in part reflect the topological role of each region within macroscale brain networks.

15.
Mol Psychiatry ; 28(10): 4390-4398, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37460847

RESUMO

The dorsal raphe nucleus (DRN) is one of the earliest targets of Alzheimer's disease-related tau pathology and is a major source of brain serotonin. We used [18F]Fluoro-m-tyrosine ([18F]FMT) PET imaging to measure serotonin synthesis capacity in the DRN in 111 healthy adults (18-85 years-old). Similar to reports in catecholamine systems, we found elevated serotonin synthesis capacity in older adults relative to young. To establish the structural and functional context within which serotonin synthesis capacity is elevated in aging, we examined relationships among DRN [18F]FMT net tracer influx (Ki) and longitudinal changes in cortical thickness using magnetic resonance imaging, longitudinal changes in self-reported depression symptoms, and AD-related tau and ß-amyloid (Aß) pathology using cross-sectional [18F]Flortaucipir and [11C]Pittsburgh compound-B PET respectively. Together, our findings point to elevated DRN [18F]FMT Ki as a marker of poorer aging trajectories. Older adults with highest serotonin synthesis capacity showed greatest temporal lobe cortical atrophy. Cortical atrophy was associated with increasing depression symptoms over time, and these effects appeared to be strongest in individuals with highest serotonin synthesis capacity. We did not find direct relationships between serotonin synthesis capacity and AD-related pathology. Exploratory analyses revealed nuanced effects of sex within the older adult group. Older adult females showed the highest DRN synthesis capacity and exhibited the strongest relationships between entorhinal cortex tau pathology and increasing depression symptoms. Together these findings reveal PET measurement of the serotonin system to be a promising marker of aging trajectories relevant to both AD and affective changes in older age.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Feminino , Humanos , Idoso , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Serotonina , Proteínas tau , Estudos Transversais , Doença de Alzheimer/psicologia , Envelhecimento , Peptídeos beta-Amiloides , Atrofia , Tomografia por Emissão de Pósitrons , Imageamento por Ressonância Magnética
16.
J Vis ; 23(7): 1, 2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-37395704

RESUMO

Serial dependence is an attractive pull that recent perceptual history exerts on current judgments. Theory suggests that this bias is due to a form of short-term plasticity prevalent specifically in the frontal lobe. We sought to test the importance of the frontal lobe to serial dependence by disrupting neural activity along its lateral surface during two tasks with distinct perceptual and motor demands. In our first experiment, stimulation of the lateral prefrontal cortex (LPFC) during an oculomotor delayed response task decreased serial dependence only in the first saccade to the target, whereas stimulation posterior to the LPFC decreased serial dependence only in adjustments to eye position after the first saccade. In our second experiment, which used an orientation discrimination task, stimulation anterior to, in, and posterior to the LPFC all caused equivalent decreases in serial dependence. In this experiment, serial dependence occurred only between stimuli at the same location; an alternation bias was observed across hemifields. Frontal stimulation had no effect on the alternation bias. Transcranial magnetic stimulation to parietal cortex had no effect on serial dependence in either experiment. In summary, our experiments provide evidence for both functional differentiation (Experiment 1) and redundancy (Experiment 2) in frontal cortex with respect to serial dependence.


Assuntos
Lobo Frontal , Córtex Pré-Frontal , Humanos , Lobo Frontal/fisiologia , Córtex Pré-Frontal/fisiologia , Movimentos Oculares , Movimentos Sacádicos , Lobo Parietal/fisiologia , Estimulação Luminosa/métodos
17.
J Cogn Neurosci ; 35(9): 1423-1431, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37315335
18.
Front Pain Res (Lausanne) ; 4: 1156108, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37363755

RESUMO

Precision neuromodulation of central brain circuits is a promising emerging therapeutic modality for a variety of neuropsychiatric disorders. Reliably identifying in whom, where, and in what context to provide brain stimulation for optimal pain relief are fundamental challenges limiting the widespread implementation of central neuromodulation treatments for chronic pain. Current approaches to brain stimulation target empirically derived regions of interest to the disorder or targets with strong connections to these regions. However, complex, multidimensional experiences like chronic pain are more closely linked to patterns of coordinated activity across distributed large-scale functional networks. Recent advances in precision network neuroscience indicate that these networks are highly variable in their neuroanatomical organization across individuals. Here we review accumulating evidence that variable central representations of pain will likely pose a major barrier to implementation of population-derived analgesic brain stimulation targets. We propose network-level estimates as a more valid, robust, and reliable way to stratify personalized candidate regions. Finally, we review key background, methods, and implications for developing network topology-informed brain stimulation targets for chronic pain.

19.
Front Behav Neurosci ; 17: 1128610, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37138661

RESUMO

Introduction: Top-down control underlies our ability to attend relevant stimuli while ignoring irrelevant, distracting stimuli and is a critical process for prioritizing information in working memory (WM). Prior work has demonstrated that top-down biasing signals modulate sensory-selective cortical areas during WM, and that the large-scale organization of the brain reconfigures due to WM demands alone; however, it is not yet understood how brain networks reconfigure between the processing of relevant versus irrelevant information in the service of WM. Methods: Here, we investigated the effects of task goals on brain network organization while participants performed a WM task that required participants to detect repetitions (e.g., 0-back or 1-back) and had varying levels of visual interference (e.g., distracting, irrelevant stimuli). We quantified changes in network modularity-a measure of brain sub-network segregation-that occurred depending on overall WM task difficulty as well as trial-level task goals for each stimulus during the task conditions (e.g., relevant or irrelevant). Results: First, we replicated prior work and found that whole-brain modularity was lower during the more demanding WM task conditions compared to a baseline condition. Further, during the WM conditions with varying task goals, brain modularity was selectively lower during goal-directed processing of task-relevant stimuli to be remembered for WM performance compared to processing of distracting, irrelevant stimuli. Follow-up analyses indicated that this effect of task goals was most pronounced in default mode and visual sub-networks. Finally, we examined the behavioral relevance of these changes in modularity and found that individuals with lower modularity for relevant trials had faster WM task performance. Discussion: These results suggest that brain networks can dynamically reconfigure to adopt a more integrated organization with greater communication between sub-networks that supports the goal-directed processing of relevant information and guides WM.

20.
J Cogn Neurosci ; 35(7): 1144-1153, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37159230

RESUMO

Decades of evidence across taxa have established the importance of dopamine (DA) signaling in the pFC for successful working memory performance. Genetic and hormonal factors can shape individual differences in prefrontal DA tone. The catechol-o-methyltransferase (COMT) gene regulates basal prefrontal DA, and the sex hormone 17ß-estradiol potentiates DA release. E. Jacobs and M. D'Esposito [Estrogen shapes dopamine-dependent cognitive processes: Implications for women's health. Journal of Neuroscience, 31, 5286-5293, 2011] investigated the moderating role of estradiol on cognition using the COMT gene and COMT enzymatic activity as a proxy for pFC DA tone. They found that increases in 17ß-estradiol within women at two time points during the menstrual cycle influenced working memory performance in a COMT-dependent manner. Here, we aimed to replicate and extend the behavioral findings of Jacobs and D'Esposito by employing an intensive repeated-measures design across a full menstrual cycle. Our results replicated the original investigation. Within-person increases in estradiol were associated with improved performance on 2-back lure trials for participants with low basal levels of DA (Val/Val carriers). The association was in the opposite direction for participants with higher basal levels of DA (Met/Met carriers). Our findings support the role of estrogen in DA-related cognitive functions and further highlight the need to consider gonadal hormones in cognitive science research.


Assuntos
Catecol O-Metiltransferase , Memória de Curto Prazo , Humanos , Feminino , Memória de Curto Prazo/fisiologia , Catecol O-Metiltransferase/genética , Estradiol , Dopamina , Estrogênios , Genótipo , Córtex Pré-Frontal/fisiologia
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