21 resultados para Hiperostose cortical congênita
em Duke University
Resumo:
During cortical synaptic development, thalamic axons must establish synaptic connections despite the presence of the more abundant intracortical projections. How thalamocortical synapses are formed and maintained in this competitive environment is unknown. Here, we show that astrocyte-secreted protein hevin is required for normal thalamocortical synaptic connectivity in the mouse cortex. Absence of hevin results in a profound, long-lasting reduction in thalamocortical synapses accompanied by a transient increase in intracortical excitatory connections. Three-dimensional reconstructions of cortical neurons from serial section electron microscopy (ssEM) revealed that, during early postnatal development, dendritic spines often receive multiple excitatory inputs. Immuno-EM and confocal analyses revealed that majority of the spines with multiple excitatory contacts (SMECs) receive simultaneous thalamic and cortical inputs. Proportion of SMECs diminishes as the brain develops, but SMECs remain abundant in Hevin-null mice. These findings reveal that, through secretion of hevin, astrocytes control an important developmental synaptic refinement process at dendritic spines.
Resumo:
Recent emergence of human connectome imaging has led to a high demand on angular and spatial resolutions for diffusion magnetic resonance imaging (MRI). While there have been significant growths in high angular resolution diffusion imaging, the improvement in spatial resolution is still limited due to a number of technical challenges, such as the low signal-to-noise ratio and high motion artifacts. As a result, the benefit of a high spatial resolution in the whole-brain connectome imaging has not been fully evaluated in vivo. In this brief report, the impact of spatial resolution was assessed in a newly acquired whole-brain three-dimensional diffusion tensor imaging data set with an isotropic spatial resolution of 0.85 mm. It was found that the delineation of short cortical association fibers is drastically improved as well as the definition of fiber pathway endings into the gray/white matter boundary-both of which will help construct a more accurate structural map of the human brain connectome.
Resumo:
Huntington's disease (HD) is a neurodegenerative disease caused by the expansion of a poly-glutamine (poly-Q) stretch in the huntingtin (Htt) protein. Gain-of-function effects of mutant Htt have been extensively investigated as the major driver of neurodegeneration in HD. However, loss-of-function effects of poly-Q mutations recently emerged as potential drivers of disease pathophysiology. Early synaptic problems in the excitatory cortical and striatal connections have been reported in HD, but the role of Htt protein in synaptic connectivity was unknown. Therefore, we investigated the role of Htt in synaptic connectivity in vivo by conditionally silencing Htt in the developing mouse cortex. When cortical Htt function was silenced, cortical and striatal excitatory synapses formed and matured at an accelerated pace through postnatal day 21 (P21). This exuberant synaptic connectivity was lost over time in the cortex, resulting in the deterioration of synapses by 5 weeks. Synaptic decline in the cortex was accompanied with layer- and region-specific reactive gliosis without cell loss. To determine whether the disease-causing poly-Q mutation in Htt affects synapse development, we next investigated the synaptic connectivity in a full-length knock-in mouse model of HD, the zQ175 mouse. Similar to the cortical conditional knock-outs, we found excessive excitatory synapse formation and maturation in the cortices of P21 zQ175, which was lost by 5 weeks. Together, our findings reveal that cortical Htt is required for the correct establishment of cortical and striatal excitatory circuits, and this function of Htt is lost when the mutant Htt is present.
Resumo:
BACKGROUND: The superior colliculus (SC) has been shown to play a crucial role in the initiation and coordination of eye- and head-movements. The knowledge about the function of this structure is mainly based on single-unit recordings in animals with relatively few neuroimaging studies investigating eye-movement related brain activity in humans. METHODOLOGY/PRINCIPAL FINDINGS: The present study employed high-field (7 Tesla) functional magnetic resonance imaging (fMRI) to investigate SC responses during endogenously cued saccades in humans. In response to centrally presented instructional cues, subjects either performed saccades away from (centrifugal) or towards (centripetal) the center of straight gaze or maintained fixation at the center position. Compared to central fixation, the execution of saccades elicited hemodynamic activity within a network of cortical and subcortical areas that included the SC, lateral geniculate nucleus (LGN), occipital cortex, striatum, and the pulvinar. CONCLUSIONS/SIGNIFICANCE: Activity in the SC was enhanced contralateral to the direction of the saccade (i.e., greater activity in the right as compared to left SC during leftward saccades and vice versa) during both centrifugal and centripetal saccades, thereby demonstrating that the contralateral predominance for saccade execution that has been shown to exist in animals is also present in the human SC. In addition, centrifugal saccades elicited greater activity in the SC than did centripetal saccades, while also being accompanied by an enhanced deactivation within the prefrontal default-mode network. This pattern of brain activity might reflect the reduced processing effort required to move the eyes toward as compared to away from the center of straight gaze, a position that might serve as a spatial baseline in which the retinotopic and craniotopic reference frames are aligned.
Resumo:
Infants' speech perception abilities change through the first year of life, from broad sensitivity to a wide range of speech contrasts to becoming more finely attuned to their native language. What remains unclear, however, is how this perceptual change relates to brain responses to native language contrasts in terms of the functional specialization of the left and right hemispheres. Here, to elucidate the developmental changes in functional lateralization accompanying this perceptual change, we conducted two experiments on Japanese infants using Japanese lexical pitch-accent, which changes word meanings with the pitch pattern within words. In the first behavioral experiment, using visual habituation, we confirmed that infants at both 4 and 10 months have sensitivities to the lexical pitch-accent pattern change embedded in disyllabic words. In the second experiment, near-infrared spectroscopy was used to measure cortical hemodynamic responses in the left and right hemispheres to the same lexical pitch-accent pattern changes and their pure tone counterparts. We found that brain responses to the pitch change within words differed between 4- and 10-month-old infants in terms of functional lateralization: Left hemisphere dominance for the perception of the pitch change embedded in words was seen only in the 10-month-olds. These results suggest that the perceptual change in Japanese lexical pitch-accent may be related to a shift in functional lateralization from bilateral to left hemisphere dominance.
Resumo:
Recently, a number of investigators have examined the neural loci of psychological processes enabling the control of visual spatial attention using cued-attention paradigms in combination with event-related functional magnetic resonance imaging. Findings from these studies have provided strong evidence for the involvement of a fronto-parietal network in attentional control. In the present study, we build upon this previous work to further investigate these attentional control systems. In particular, we employed additional controls for nonattentional sensory and interpretative aspects of cue processing to determine whether distinct regions in the fronto-parietal network are involved in different aspects of cue processing, such as cue-symbol interpretation and attentional orienting. In addition, we used shorter cue-target intervals that were closer to those used in the behavioral and event-related potential cueing literatures. Twenty participants performed a cued spatial attention task while brain activity was recorded with functional magnetic resonance imaging. We found functional specialization for different aspects of cue processing in the lateral and medial subregions of the frontal and parietal cortex. In particular, the medial subregions were more specific to the orienting of visual spatial attention, while the lateral subregions were associated with more general aspects of cue processing, such as cue-symbol interpretation. Additional cue-related effects included differential activations in midline frontal regions and pretarget enhancements in the thalamus and early visual cortical areas.
Resumo:
Humans and song-learning birds communicate acoustically using learned vocalizations. The characteristic features of this social communication behavior include vocal control by forebrain motor areas, a direct cortical projection to brainstem vocal motor neurons, and dependence on auditory feedback to develop and maintain learned vocalizations. These features have so far not been found in closely related primate and avian species that do not learn vocalizations. Male mice produce courtship ultrasonic vocalizations with acoustic features similar to songs of song-learning birds. However, it is assumed that mice lack a forebrain system for vocal modification and that their ultrasonic vocalizations are innate. Here we investigated the mouse song system and discovered that it includes a motor cortex region active during singing, that projects directly to brainstem vocal motor neurons and is necessary for keeping song more stereotyped and on pitch. We also discovered that male mice depend on auditory feedback to maintain some ultrasonic song features, and that sub-strains with differences in their songs can match each other's pitch when cross-housed under competitive social conditions. We conclude that male mice have some limited vocal modification abilities with at least some neuroanatomical features thought to be unique to humans and song-learning birds. To explain our findings, we propose a continuum hypothesis of vocal learning.
Resumo:
The rivalry between the men's basketball teams of Duke University and the University of North Carolina-Chapel Hill (UNC) is one of the most storied traditions in college sports. A subculture of students at each university form social bonds with fellow fans, develop expertise in college basketball rules, team statistics, and individual players, and self-identify as a member of a fan group. The present study capitalized on the high personal investment of these fans and the strong affective tenor of a Duke-UNC basketball game to examine the neural correlates of emotional memory retrieval for a complex sporting event. Male fans watched a competitive, archived game in a social setting. During a subsequent functional magnetic resonance imaging session, participants viewed video clips depicting individual plays of the game that ended with the ball being released toward the basket. For each play, participants recalled whether or not the shot went into the basket. Hemodynamic signal changes time locked to correct memory decisions were analyzed as a function of emotional intensity and valence, according to the fan's perspective. Results showed intensity-modulated retrieval activity in midline cortical structures, sensorimotor cortex, the striatum, and the medial temporal lobe, including the amygdala. Positively valent memories specifically recruited processing in dorsal frontoparietal regions, and additional activity in the insula and medial temporal lobe for positively valent shots recalled with high confidence. This novel paradigm reveals how brain regions implicated in emotion, memory retrieval, visuomotor imagery, and social cognition contribute to the recollection of specific plays in the mind of a sports fan.
Resumo:
The cognitive control of behavior was long considered to be centralized in cerebral cortex. More recently, subcortical structures such as cerebellum and basal ganglia have been implicated in cognitive functions as well. The fact that subcortico-cortical circuits for the control of movement involve the thalamus prompts the notion that activity in movement-related thalamus may also reflect elements of cognitive behavior. Yet this hypothesis has rarely been investigated. Using the pathways linking cerebellum to cerebral cortex via the thalamus as a template, we review evidence that the motor thalamus, together with movement-related central thalamus have the requisite connectivity and activity to mediate cognitive aspects of movement control.
Resumo:
Although it is known that brain regions in one hemisphere may interact very closely with their corresponding contralateral regions (collaboration) or operate relatively independent of them (segregation), the specific brain regions (where) and conditions (how) associated with collaboration or segregation are largely unknown. We investigated these issues using a split field-matching task in which participants matched the meaning of words or the visual features of faces presented to the same (unilateral) or to different (bilateral) visual fields. Matching difficulty was manipulated by varying the semantic similarity of words or the visual similarity of faces. We assessed the white matter using the fractional anisotropy (FA) measure provided by diffusion tensor imaging (DTI) and cross-hemispheric communication in terms of fMRI-based connectivity between homotopic pairs of cortical regions. For both perceptual and semantic matching, bilateral trials became faster than unilateral trials as difficulty increased (bilateral processing advantage, BPA). The study yielded three novel findings. First, whereas FA in anterior corpus callosum (genu) correlated with word-matching BPA, FA in posterior corpus callosum (splenium-occipital) correlated with face-matching BPA. Second, as matching difficulty intensified, cross-hemispheric functional connectivity (CFC) increased in domain-general frontopolar cortex (for both word and face matching) but decreased in domain-specific ventral temporal lobe regions (temporal pole for word matching and fusiform gyrus for face matching). Last, a mediation analysis linking DTI and fMRI data showed that CFC mediated the effect of callosal FA on BPA. These findings clarify the mechanisms by which the hemispheres interact to perform complex cognitive tasks.
Resumo:
The spiking activity of nearby cortical neurons is correlated on both short and long time scales. Understanding this shared variability in firing patterns is critical for appreciating the representation of sensory stimuli in ensembles of neurons, the coincident influences of neurons on common targets, and the functional implications of microcircuitry. Our knowledge about neuronal correlations, however, derives largely from experiments that used different recording methods, analysis techniques, and cortical regions. Here we studied the structure of neuronal correlation in area V4 of alert macaques using recording and analysis procedures designed to match those used previously in primary visual cortex (V1), the major input to V4. We found that the spatial and temporal properties of correlations in V4 were remarkably similar to those of V1, with two notable differences: correlated variability in V4 was approximately one-third the magnitude of that in V1 and synchrony in V4 was less temporally precise than in V1. In both areas, spontaneous activity (measured during fixation while viewing a blank screen) was approximately twice as correlated as visual-evoked activity. The results provide a foundation for understanding how the structure of neuronal correlation differs among brain regions and stages in cortical processing and suggest that it is likely governed by features of neuronal circuits that are shared across the visual cortex.