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For decades, the external globus pallidus (GPe) has been viewed as a passive way-station in the indirect pathway of the cortico-basal ganglia-thalamic (CBGT) circuit, sandwiched between striatal inputs and basal ganglia outputs. According to this model, one-way descending striatal signals in the indirect pathway amplify the suppression of downstream thalamic nuclei by inhibiting GPe activity. Here, we revisit this assumption, in light of new and emerging work on the cellular complexity, connectivity and functional role of the GPe in behaviour. We show how, according to this new circuit-level logic, the GPe is ideally positioned for relaying ascending and descending control signals within the basal ganglia. Focusing on the problem of inhibitory control, we illustrate how this bidirectional flow of information allows for the integration of reactive and proactive control mechanisms during action selection. Taken together, this new evidence points to the GPe as being a central hub in the CBGT circuit, participating in bidirectional information flow and linking multifaceted control signals to regulate behaviour.
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Resting heart rate may confer risk for cardiovascular disease (CVD) and other adverse cardiovascular events. While the brainstem's autonomic control over heart rate is well established, less is known about the regulatory role of higher level cortical and subcortical brain regions, especially in humans. This study sought to characterize the brain networks that predict variation in prevailing heart rate in otherwise healthy adults. We used machine learning approaches designed for complex, high-dimensional data sets, to predict variation in instantaneous heart period (the inter-heartbeat-interval) from whole-brain hemodynamic signals measured by fMRI. Task-based and resting-state fMRI, as well as peripheral physiological recordings, were taken from two data sets that included extensive repeated measurements within individuals. Our models reliably predicted instantaneous heart period from whole-brain fMRI data both within and across individuals, with prediction accuracies being highest when measured within-participants. We found that a network of cortical and subcortical brain regions, many linked to visceral motor and visceral sensory processes, were reliable predictors of variation in heart period. This adds to evidence on brain-heart interactions and constitutes an incremental step toward developing clinically applicable biomarkers of brain contributions to CVD risk.
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In situations featuring uncertainty about action-reward contingencies, mammals can flexibly adopt strategies for decision-making that are tuned in response to environmental changes. Although the cortico-basal ganglia thalamic (CBGT) network has been identified as contributing to the decision-making process, it features a complex synaptic architecture, comprised of multiple feed-forward, reciprocal, and feedback pathways, that complicate efforts to elucidate the roles of specific CBGT populations in the process by which evidence is accumulated and influences behavior. In this paper we apply a strategic sampling approach, based on Latin hypercube sampling, to explore how variations in CBGT network properties, including subpopulation firing rates and synaptic weights, map to variability of parameters in a normative drift diffusion model (DDM), representing algorithmic aspects of information processing during decision-making. Through the application of canonical correlation analysis, we find that this relationship can be characterized in terms of three low-dimensional control ensembles within the CBGT network that impact specific qualities of the emergent decision policy: responsiveness (a measure of how quickly evidence evaluation gets underway, associated with overall activity in corticothalamic and direct pathways), pliancy (a measure of the standard of evidence needed to commit to a decision, associated largely with overall activity in components of the indirect pathway of the basal ganglia), and choice (a measure of commitment toward one available option, associated with differences in direct and indirect pathways across action channels). These analyses provide mechanistic predictions about the roles of specific CBGT network elements in tuning the way that information is accumulated and translated into decision-related behavior.
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Ganglios Basales , Tálamo , Animales , Ganglios Basales/fisiología , Cognición , Mamíferos , Vías Nerviosas/fisiología , Recompensa , Tálamo/fisiología , IncertidumbreRESUMEN
Repetition of specific movement biases subsequent actions towards the practiced movement, a phenomenon known as use-dependent learning (UDL). Recent experiments that impose strict constraints on planning time have revealed two sources of use-dependent biases, one arising from dynamic changes occurring during motor planning and another reflecting a stable shift in motor execution. Here, we used a distributional analysis to examine the contribution of these biases in reaching. To create the conditions for UDL, the target appeared at a designated 'frequent' location on most trials, and at one of six 'rare' locations on other trials. Strikingly, the heading angles were bimodally distributed, with peaks at both frequent and rare target locations. Despite having no constraints on planning time, participants exhibited a robust bias towards the frequent target when movements were self-initiated quickly, the signature of a planning bias; notably, the peak near the rare target was shifted in the frequently practiced direction, the signature of an execution bias. Furthermore, these execution biases were not only replicated in a delayed-response task but were also insensitive to reward. Taken together, these results extend our understanding of how volitional movements are influenced by recent experience.
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Objetivos , Desempeño Psicomotor , Sesgo , Humanos , Movimiento/fisiología , Desempeño Psicomotor/fisiología , RecompensaRESUMEN
Variation in cognitive ability arises from subtle differences in underlying neural architecture. Understanding and predicting individual variability in cognition from the differences in brain networks requires harnessing the unique variance captured by different neuroimaging modalities. Here we adopted a multi-level machine learning approach that combines diffusion, functional, and structural MRI data from the Human Connectome Project (N = 1050) to provide unitary prediction models of various cognitive abilities: global cognitive function, fluid intelligence, crystallized intelligence, impulsivity, spatial orientation, verbal episodic memory and sustained attention. Out-of-sample predictions of each cognitive score were first generated using a sparsity-constrained principal component regression on individual neuroimaging modalities. These individual predictions were then aggregated and submitted to a LASSO estimator that removed redundant variability across channels. This stacked prediction led to a significant improvement in accuracy, relative to the best single modality predictions (approximately 1% to more than 3% boost in variance explained), across a majority of the cognitive abilities tested. Further analysis found that diffusion and brain surface properties contribute the most to the predictive power. Our findings establish a lower bound to predict individual differences in cognition using multiple neuroimaging measures of brain architecture, both structural and functional, quantify the relative predictive power of the different imaging modalities, and reveal how each modality provides unique and complementary information about individual differences in cognitive function.
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Cognición , Neuroimagen/métodos , Conectoma/métodos , Humanos , Aprendizaje Automático , Imagen por Resonancia Magnética/métodosRESUMEN
The question of how cortico-basal ganglia-thalamic (CBGT) pathways use dopaminergic feedback signals to modify future decisions has challenged computational neuroscientists for decades. Reviewing the literature on computational representations of dopaminergic corticostriatal plasticity, we show how the field is converging on a normative, synaptic-level learning algorithm that elegantly captures both neurophysiological properties of CBGT circuits and behavioral dynamics during reinforcement learning. Unfortunately, the computational studies that have led to this normative algorithmic model have all relied on simplified circuits that use abstracted action-selection rules. As a result, the application of this corticostriatal plasticity algorithm to a full model of the CBGT pathways immediately fails because the spatiotemporal distance between integration (corticostriatal circuits), action selection (thalamocortical loops) and learning (nigrostriatal circuits) means that the network does not know which synapses should be reinforced to favor previously rewarding actions. We show how observations from neurophysiology, in particular the sustained activation of selected action representations, can provide a simple means of resolving this credit assignment problem in models of CBGT learning. Using a biologically realistic spiking model of the full CBGT circuit, we demonstrate how this solution can allow a network to learn to select optimal targets and to relearn action-outcome contingencies when the environment changes. This simple illustration highlights how the normative framework for corticostriatal plasticity can be expanded to capture macroscopic network dynamics during learning and decision-making.
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Ganglios Basales , Modelos Neurológicos , Refuerzo en Psicología , Sinapsis , TálamoRESUMEN
While stress may be a potential mechanism by which childhood threat and deprivation influence mental health, few studies have considered specific stress-related white matter pathways, such as the stria terminalis (ST) and medial forebrain bundle (MFB). Our goal was to examine the relationships between childhood adversity and ST and MFB structural integrity and whether these pathways may provide a link between childhood adversity and affective symptoms and disorders. Participants were young adults (n = 100) with a full distribution of maltreatment history and affective symptom severity. Threat was determined by measures of childhood abuse and repeated traumatic events. Socioeconomic deprivation (SED) was determined by a measure of childhood socioeconomic status (parental education). Participants underwent diffusion spectrum imaging. Human Connectome Project data was used to perform ST and MFB tractography; these tracts were used as ROIs to extract generalized fractional anisotropy (gFA) from each participant. Childhood threat was associated with ST gFA, such that greater threat was associated with less ST gFA. SED was also associated with ST gFA, however, conversely to threat, greater SED was associated with greater ST gFA. Additionally, threat was negatively associated with MFB gFA, and MFB gFA was negatively associated with post-traumatic stress symptoms. Our results suggest that childhood threat and deprivation have opposing influences on ST structural integrity, providing new evidence that the context of childhood adversity may have an important influence on its neurobiological effects, even on the same structure. Further, the MFB may provide a novel link between childhood threat and affective symptoms.
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Experiencias Adversas de la Infancia , Síntomas Afectivos/patología , Haz Prosencefálico Medial/patología , Estrés Psicológico/patología , Sustancia Blanca/patología , Adulto , Adultos Sobrevivientes del Maltrato a los Niños , Síntomas Afectivos/diagnóstico por imagen , Imagen de Difusión Tensora , Femenino , Fórnix/diagnóstico por imagen , Fórnix/patología , Humanos , Masculino , Haz Prosencefálico Medial/diagnóstico por imagen , Carencia Psicosocial , Núcleos Septales/diagnóstico por imagen , Núcleos Septales/patología , Factores Socioeconómicos , Estrés Psicológico/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Adulto JovenRESUMEN
Goal-directed behavior requires integrating action selection processes with learning systems that adapt control using environmental feedback. These functions are known to intersect at a common neural substrate with multiple known targets of plasticity (the cortico-basal ganglia-thalamic network), suggesting that feedback signals have a multifaceted impact on future decisions. Using a hybrid of accumulation-to-bound decision models and reinforcement learning, we modeled the performance of humans in a stop signal task where participants (N 75: 37 males, 38 females) learned the prior distribution of the timing of a stop signal through trial-and-error feedback. Changes in the drift rate of the action execution process were driven by errors in action timing, whereas adaptation in the boundary height served to increase caution following failed stops. These findings highlight two interactive learning mechanisms for adapting the control of goal-directed actions based on dissociable dimensions of feedback error.SIGNIFICANCE STATEMENT Many complex behavioral goals rely on the ability to regulate the timing of action execution while also maintaining enough control to cancel actions in response to "Stop" cues in the environment. Here we examined how these fundamental components of behavior become tuned to the control demands of the environment by combining principles of reinforcement learning with accumulation-to-bound models. Model fits to behavioral data in an adaptive stop signal task revealed two adaptive mechanisms: (1) timing error-related changes in the rate of the execution signal; and (2) an increase in the execution boundary after failed stops. These findings demonstrate unique effects of timing and control errors on the underlying mechanisms of control, the rate and threshold of accumulating action signals.
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Toma de Decisiones , Inhibición Psicológica , Aprendizaje , Desempeño Psicomotor , Adulto , Femenino , Humanos , Masculino , Modelos Psicológicos , Tiempo de Reacción , Refuerzo en Psicología , Adulto JovenRESUMEN
As a sequence of movements is learned, serially ordered actions get bound together into sets to reduce computational complexity during planning and execution. Here, we investigated how actions become naturally bound over the course of learning and how this learning affects cortical representations of individual actions. Across 5 weeks of practice, neurologically healthy human subjects learned either a complex 32-item sequence of finger movements (trained group, n = 9; 3 female) or randomly ordered actions (control group, n = 9; 3 female). Over the course of practice, responses during sequence production in the trained group became temporally correlated, consistent with responses being bound together under a common command. These behavioral changes, however, did not coincide with plasticity in the multivariate representations of individual finger movements, assessed using fMRI, at any level of the cortical motor hierarchy. This suggests that the representations of individual actions remain stable, even as the execution of those same actions become bound together in the context of producing a well learned sequence.SIGNIFICANCE STATEMENT Extended practice on motor sequences results in highly stereotyped movement patterns that bind successive movements together. This binding is critical for skilled motor performance, yet it is not currently understood how it is achieved in the brain. We examined how binding altered the patterns of activity associated with individual movements that make up the sequence. We found that fine finger control during sequence production involved correlated activity throughout multiple motor regions; however, we found no evidence for plasticity of the representations of elementary movements. This suggests that binding is associated with plasticity at a more abstract level of the motor hierarchy.
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Corteza Motora/fisiología , Neuronas/fisiología , Desempeño Psicomotor/fisiología , Aprendizaje Seriado/fisiología , Adulto , Femenino , Dedos/fisiología , Humanos , Imagen por Resonancia Magnética , Masculino , Corteza Motora/diagnóstico por imagen , Destreza Motora/fisiología , Movimiento/fisiología , Adulto JovenRESUMEN
Cortico-basal-ganglia-thalamic (CBGT) networks are critical for adaptive decision-making, yet how changes to circuit-level properties impact cognitive algorithms remains unclear. Here we explore how dopaminergic plasticity at corticostriatal synapses alters competition between striatal pathways, impacting the evidence accumulation process during decision-making. Spike-timing dependent plasticity simulations showed that dopaminergic feedback based on rewards modified the ratio of direct and indirect corticostriatal weights within opposing action channels. Using the learned weight ratios in a full spiking CBGT network model, we simulated neural dynamics and decision outcomes in a reward-driven decision task and fit them with a drift diffusion model. Fits revealed that the rate of evidence accumulation varied with inter-channel differences in direct pathway activity while boundary height varied with overall indirect pathway activity. This multi-level modeling approach demonstrates how complementary learning and decision computations can emerge from corticostriatal plasticity.
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Toma de Decisiones/fisiología , Neuronas Dopaminérgicas/fisiología , Red Nerviosa/fisiología , Animales , Ganglios Basales , Cuerpo Estriado , Retroalimentación , Humanos , Aprendizaje , Modelos Neurológicos , Vías Nerviosas/fisiología , Plasticidad Neuronal/fisiología , Neuronas/fisiología , Refuerzo en Psicología , Recompensa , Sinapsis/fisiología , TálamoRESUMEN
The relative influence of affective and cognitive processes on behavior is increasingly understood to transform through development, from adolescence into adulthood, but the neuroanatomical mechanisms underlying this change are not well understood. We analyzed diffusion magnetic resonance imaging in 115 10- to 28-year-old participants to identify convergent corticostriatal projections from cortical systems involved in affect and cognitive control and determined the age-related differences in their relative structural integrity. Results indicate that the relative integrity of affective projections, in relation to projections from cognitive control systems, decreases with age and is positively associated with reward-driven task performance. Together, these findings provide new evidence that developmental differences in the integration of corticostriatal networks involved in affect and cognitive control underlie known developmental decreases in the propensity for reward-driven behavior into adulthood.
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Afecto/fisiología , Corteza Cerebral/crecimiento & desarrollo , Cognición/fisiología , Cuerpo Estriado/crecimiento & desarrollo , Vías Nerviosas/fisiología , Recompensa , Adolescente , Adulto , Factores de Edad , Anisotropía , Atención/fisiología , Mapeo Encefálico , Corteza Cerebral/diagnóstico por imagen , Niño , Cuerpo Estriado/diagnóstico por imagen , Femenino , Lateralidad Funcional , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Vías Nerviosas/diagnóstico por imagen , Oxígeno/sangre , Análisis de Regresión , Caracteres Sexuales , Adulto JovenRESUMEN
A comprehensive map of the structural connectome in the human brain has been a coveted resource for understanding macroscopic brain networks. Here we report an expert-vetted, population-averaged atlas of the structural connectome derived from diffusion MRI data (Nâ¯=â¯842). This was achieved by creating a high-resolution template of diffusion patterns averaged across individual subjects and using tractography to generate 550,000 trajectories of representative white matter fascicles annotated by 80 anatomical labels. The trajectories were subsequently clustered and labeled by a team of experienced neuroanatomists in order to conform to prior neuroanatomical knowledge. A multi-level network topology was then described using whole-brain connectograms, with subdivisions of the association pathways showing small-worldness in intra-hemisphere connections, projection pathways showing hub structures at thalamus, putamen, and brainstem, and commissural pathways showing bridges connecting cerebral hemispheres to provide global efficiency. This atlas of the structural connectome provides representative organization of human brain white matter, complementary to traditional histologically-derived and voxel-based white matter atlases, allowing for better modeling and simulation of brain connectivity for future connectome studies.
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Atlas como Asunto , Conectoma/métodos , Imagen de Difusión Tensora/métodos , Red Nerviosa/anatomía & histología , Sustancia Blanca/anatomía & histología , Adulto , Femenino , Humanos , Masculino , Red Nerviosa/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Adulto JovenRESUMEN
When making risky spatial decisions, humans incorporate estimates of sensorimotor variability and costs on outcomes to bias their spatial selections away from regions that incur feedback penalties. Since selection variability depends on the reliability of sensory signals, increasing the spatial variance of targets during visually guided actions should increase the degree of this avoidance. Healthy adult participants (N = 20) used a computer mouse to indicate their selection of the mean of a target, represented as a 2D Gaussian distribution of dots presented on a computer display. Reward feedback on each trial corresponded to the estimation error of the selection. Either increasing or decreasing the spatial variance of the dots modulated the spatial uncertainty of the target. A non-target distractor cue was presented as an adjacent distribution of dots. On a subset of trials, feedback scores were penalized with increased proximity to the distractor mean. As expected, increasing the spatial variance of the target distribution increased selection variability. More importantly, on trials where proximity to the distractor cue incurred a penalty, increasing variance of the target increased selection bias away from the distractor cue and prolonged reaction times. These results confirm predictions that increased sensory uncertainty increases avoidance during risky spatial decisions.
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Toma de Decisiones , Desempeño Psicomotor/fisiología , Incertidumbre , Percepción Visual/fisiología , Adolescente , Femenino , Humanos , Masculino , Estimulación Luminosa , Tiempo de Reacción/fisiología , Adulto JovenRESUMEN
The dual-system model of sequence learning posits that during early learning there is an advantage for encoding sequences in sensory frames; however, it remains unclear whether this advantage extends to long-term consolidation. Using the serial RT task, we set out to distinguish the dynamics of learning sequential orders of visual cues from learning sequential responses. On each day, most participants learned a new mapping between a set of symbolic cues and responses made with one of four fingers, after which they were exposed to trial blocks of either randomly ordered cues or deterministic ordered cues (12-item sequence). Participants were randomly assigned to one of four groups (n = 15 per group): Visual sequences (same sequence of visual cues across training days), Response sequences (same order of key presses across training days), Combined (same serial order of cues and responses on all training days), and a Control group (a novel sequence each training day). Across 5 days of training, sequence-specific measures of response speed and accuracy improved faster in the Visual group than any of the other three groups, despite no group differences in explicit awareness of the sequence. The two groups that were exposed to the same visual sequence across days showed a marginal improvement in response binding that was not found in the other groups. These results indicate that there is an advantage, in terms of rate of consolidation across multiple days of training, for learning sequences of actions in a sensory representational space, rather than as motoric representations.
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Aprendizaje , Destreza Motora , Percepción Visual , Concienciación , Señales (Psicología) , Humanos , Pruebas Neuropsicológicas , Distribución Aleatoria , Tiempo de ReacciónRESUMEN
Quantifying differences or similarities in connectomes has been a challenge due to the immense complexity of global brain networks. Here we introduce a noninvasive method that uses diffusion MRI to characterize whole-brain white matter architecture as a single local connectome fingerprint that allows for a direct comparison between structural connectomes. In four independently acquired data sets with repeated scans (total N = 213), we show that the local connectome fingerprint is highly specific to an individual, allowing for an accurate self-versus-others classification that achieved 100% accuracy across 17,398 identification tests. The estimated classification error was approximately one thousand times smaller than fingerprints derived from diffusivity-based measures or region-to-region connectivity patterns for repeat scans acquired within 3 months. The local connectome fingerprint also revealed neuroplasticity within an individual reflected as a decreasing trend in self-similarity across time, whereas this change was not observed in the diffusivity measures. Moreover, the local connectome fingerprint can be used as a phenotypic marker, revealing 12.51% similarity between monozygotic twins, 5.14% between dizygotic twins, and 4.51% between none-twin siblings, relative to differences between unrelated subjects. This novel approach opens a new door for probing the influence of pathological, genetic, social, or environmental factors on the unique configuration of the human connectome.
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Encéfalo/anatomía & histología , Conectoma/métodos , Imagen de Difusión Tensora/métodos , Interpretación de Imagen Asistida por Computador/métodos , Técnica de Sustracción , Sustancia Blanca/anatomía & histología , Adulto , Algoritmos , Femenino , Humanos , Aumento de la Imagen/métodos , Masculino , Reconocimiento de Normas Patrones Automatizadas/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
In the last few decades, non-invasive neuroimaging has revealed macro-scale brain dynamics that underlie perception, cognition and action. Advances in non-invasive neuroimaging target two capabilities; 1) increased spatial and temporal resolution of measured neural activity, and 2) innovative methodologies to extract brain-behavior relationships from evolving neuroimaging technology. We target the second. Our novel methodology integrated three neuroimaging methodologies and elucidated expertise-dependent differences in functional (fused EEG-fMRI) and structural (dMRI) brain networks for a perception-action coupling task. A set of baseball players and controls performed a Go/No-Go task designed to mimic the situation of hitting a baseball. In the functional analysis, our novel fusion methodology identifies 50ms windows with predictive EEG neural correlates of expertise and fuses these temporal windows with fMRI activity in a whole-brain 2mm voxel analysis, revealing time-localized correlations of expertise at a spatial scale of millimeters. The spatiotemporal cascade of brain activity reflecting expertise differences begins as early as 200ms after the pitch starts and lasting up to 700ms afterwards. Network differences are spatially localized to include motor and visual processing areas, providing evidence for differences in perception-action coupling between the groups. Furthermore, an analysis of structural connectivity revealed that the players have significantly more connections between cerebellar and left frontal/motor regions, and many of the functional activation differences between the groups are located within structurally defined network modules that differentiate expertise. In short, our novel method illustrates how multimodal neuroimaging can provide specific macro-scale insights into the functional and structural correlates of expertise development.
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Modification of spatial attention via reinforcement learning (Lee and Shomstein, 2013) requires the integration of reward, attention, and executive processes. Corticostriatal pathways are an ideal neural substrate for this integration because these projections exhibit a globally parallel (Alexander et al., 1986), but locally overlapping (Haber, 2003), topographical organization. Here we explore whether there are unique striatal regions that exhibit convergent anatomical connections from orbitofrontal cortex, dorsolateral prefrontal cortex, and posterior parietal cortex. Deterministic fiber tractography on diffusion spectrum imaging data from neurologically healthy adults (N = 60) was used to map frontostriatal and parietostriatal projections. In general, projections from cortex were organized according to both a medial-lateral and a rostral-caudal gradient along the striatal nuclei. Within rostral aspects of the striatum, we identified two bilateral convergence zones (one in the caudate nucleus and another in the putamen) that consisted of voxels with unique projections from orbitofrontal cortex, dorsolateral prefrontal cortex, and parietal regions. The distributed cortical connectivity of these striatal convergence zones was confirmed with follow-up functional connectivity analysis from resting state fMRI data, in which a high percentage of structurally connected voxels also showed significant functional connectivity. The specificity of this convergent architecture to these regions of the rostral striatum was validated against control analysis of connectivity within the motor putamen. These results delineate a neurologically plausible network of converging corticostriatal projections that may support the integration of reward, executive control, and spatial attention that occurs during spatial reinforcement learning.
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Corteza Cerebral/fisiología , Cuerpo Estriado/fisiología , Vías Nerviosas/fisiología , Adolescente , Adulto , Núcleo Caudado/fisiología , Imagen de Difusión por Resonancia Magnética , Femenino , Lóbulo Frontal/fisiología , Humanos , Imagen por Resonancia Magnética , Masculino , Lóbulo Parietal/fisiología , Corteza Prefrontal/fisiología , Putamen/fisiología , Adulto JovenRESUMEN
Here we introduce the concept of the local connectome: the degree of connectivity between adjacent voxels within a white matter fascicle defined by the density of the diffusing spins. While most human structural connectomic analyses can be summarized as finding global connectivity patterns at either end of anatomical pathways, the analysis of local connectomes, termed connectometry, tracks the local connectivity patterns along the fiber pathways themselves in order to identify the subcomponents of the pathways that express significant associations with a study variable. This bottom-up analytical approach is made possible by reconstructing diffusion MRI data into a common stereotaxic space that allows for associating local connectomes across subjects. The substantial associations can then be tracked along the white matter pathways, and statistical inference is obtained using permutation tests on the length of coherent associations and corrected for multiple comparisons. Using two separate samples, with different acquisition parameters, we show how connectometry can capture variability within core white matter pathways in a statistically efficient manner and extract meaningful variability from white matter pathways, complements graph-theoretic connectomic measures, and is more sensitive than region-of-interest approaches.
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Encéfalo/fisiología , Conectoma/métodos , Modelos Neurológicos , Sustancia Blanca/fisiología , Imagen de Difusión por Resonancia Magnética , Humanos , Procesamiento de Imagen Asistido por Computador , Vías Nerviosas/fisiologíaRESUMEN
White matter structure declines with advancing age and has been associated with a decline in memory and executive processes in older adulthood. Yet, recent research suggests that higher physical activity and fitness levels may be associated with less white matter degeneration in late life, although the tract-specificity of this relationship is not well understood. In addition, these prior studies infrequently associate measures of white matter microstructure to cognitive outcomes, so the behavioral importance of higher levels of white matter microstructural organization with greater fitness levels remains a matter of speculation. Here we tested whether cardiorespiratory fitness (VO2max) levels were associated with white matter microstructure and whether this relationship constituted an indirect pathway between cardiorespiratory fitness and spatial working memory in two large, cognitively and neurologically healthy older adult samples. Diffusion tensor imaging was used to determine white matter microstructure in two separate groups: Experiment 1, N=113 (mean age=66.61) and Experiment 2, N=154 (mean age=65.66). Using a voxel-based regression approach, we found that higher VO2max was associated with higher fractional anisotropy (FA), a measure of white matter microstructure, in a diverse network of white matter tracts, including the anterior corona radiata, anterior internal capsule, fornix, cingulum, and corpus callosum (PFDR-corrected<.05). This effect was consistent across both samples even after controlling for age, gender, and education. Further, a statistical mediation analysis revealed that white matter microstructure within these regions, among others, constituted a significant indirect path between VO2max and spatial working memory performance. These results suggest that greater aerobic fitness levels are associated with higher levels of white matter microstructural organization, which may, in turn, preserve spatial memory performance in older adulthood.
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Envejecimiento/patología , Envejecimiento/fisiología , Encéfalo/citología , Capacidad Cardiovascular/fisiología , Memoria a Corto Plazo/fisiología , Memoria Espacial/fisiología , Sustancia Blanca/citología , Anciano , Anciano de 80 o más Años , Encéfalo/fisiología , Mapeo Encefálico , Imagen de Difusión Tensora/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Red Nerviosa/citología , Red Nerviosa/fisiología , Plasticidad Neuronal/fisiología , Consumo de Oxígeno/fisiología , Sustancia Blanca/fisiologíaRESUMEN
Functional magnetic resonance imaging (fMRI) evidence indicates that different subregions of ventrolateral prefrontal cortex (VLPFC) participate in distinct cortical networks. These networks have been shown to support separable cognitive functions: anterior VLPFC [inferior frontal gyrus (IFG) pars orbitalis] functionally correlates with a ventral fronto-temporal network associated with top-down influences on memory retrieval, while mid-VLPFC (IFG pars triangularis) functionally correlates with a dorsal fronto-parietal network associated with postretrieval control processes. However, it is not known to what extent subregional differences in network affiliation and function are driven by differences in the organization of underlying white matter pathways. We used high-angular-resolution diffusion spectrum imaging and functional connectivity analysis in unanesthetized humans to address whether the organization of white matter connectivity differs between subregions of VLPFC. Our results demonstrate a ventral-dorsal division within IFG. Ventral IFG as a whole connects broadly to lateral temporal cortex. Although several different individual white matter tracts form connections between ventral IFG and lateral temporal cortex, functional connectivity analysis of fMRI data indicates that these are part of the same ventral functional network. By contrast, across subdivisions, dorsal IFG was connected with the midfrontal gyrus and correlated as a separate dorsal functional network. These qualitative differences in white matter organization within larger macroanatomical subregions of VLPFC support prior functional distinctions among these regions observed in task-based and functional connectivity fMRI studies. These results are consistent with the proposal that anatomical connectivity is a crucial determinant of systems-level functional organization of frontal cortex and the brain in general.