Growing access to large-scale longitudinal structural neuroimaging data has fundamentally altered our understanding of cortical development en route to human adulthood, with consequences for basic science, medicine, and public policy. In striking contrast, basic anatomical development of subcortical structures such as the striatum, pallidum, and thalamus has remained poorly describeddespite these evolutionarily ancient structures being both intimate working partners of the cortical sheet and critical to diverse developmentally emergent skills and disorders. Here, to begin addressing this disparity, we apply methods for the measurement of subcortical volume and shape to 1,171 longitudinally acquired structural magnetic resonance imaging brain scans from 618 typically developing males and females aged 5-25 y. We show that the striatum, pallidum, and thalamus each follow curvilinear trajectories of volume change, which, for the striatum and thalamus, peak after cortical volume has already begun to decline and show a relative delay in males. Four-dimensional mapping of subcortical shape reveals that (i) striatal, pallidal, and thalamic domains linked to specific fronto-parietal association cortices contract with age whereas other subcortical territories expand, and (ii) each structure harbors hotspots of sexually dimorphic change over adolescence-with relevance for sex-biased mental disorders emerging in youth. By establishing the developmental dynamism, spatial heterochonicity, and sexual dimorphism of human subcortical maturation, these data bring our spatiotemporal understanding of subcortical development closer to that of the cortex-allowing evolutionary, basic, and clinical neuroscience to be conducted within a more comprehensive developmental framework.O ur understanding of human brain maturation has been rapidly advanced over the past decade by increased availability of large longitudinal in vivo structural magnetic resonance imaging (sMRI) datasets of pediatric brain development (1). However, to date, large-scale longitudinal sMRI studies have focused on the cortical sheet at the expense of subcortical structures such as the striatum, pallidum, and thalamus. Through the analysis of such data, we now know that cortical volume does not undergo a spatially homogenous linear change with development, but rather follows a highly dynamic and regionally heterogenous "inverted-U" trajectory (2-5). These basic aspects of anatomical maturation-the timing of overall growth and regional differences in the tempo of structural maturation-have yet to be longitudinally resolved in the human subcortex (6-9).Access to spatiotemporally fine-grained maps of human cortical development has had major scientific and societal consequences. These maps have impacted the study of brain evolution (10), cognitive-behavioral variation in health (11), and mechanisms of neurodevelopmental disease (12, 13). However, evolution, function, and dysfunction of the cortical sheet occur in the context of its rich structural and functional connectedn...

Neurophysiological studies in non-human primates have identified saccade-related neuronal activity in cortical regions including frontal (FEF), supplementary (SEF) and parietal eye fields. Lesion and neuroimaging studies suggest a generally homologous mapping of the oculomotor system in humans; however, a detailed mapping of the precise anatomical location of these functional regions has not yet been achieved. We investigated dorsal frontal and parietal cortex during a saccade task vs. central fixation in 10 adult subjects using functional magnetic resonance imaging (fMRI). The FEF were restricted to the precentral sulcus, and did not extend anteriorly into Brodmann area 8, which has traditionally been viewed as their location in humans. The SEF were located in cortex along the interhemispheric fissure and extended minimally onto the dorsal cortical surface. Parietal activation was seen in precuneus and along the intraparietal sulcus, extending into both superior and inferior parietal lobules. These findings localize areas in frontal and parietal cortex involved in saccade generation in humans, and indicate significant differences from the macaque monkey in both frontal and parietal cortex. These differences may have functional implications for the roles these areas play in visuomotor processes.

High-field (3 Tesla) functional magnetic resonance imaging (MRI) was used to investigate the cortical circuitry subserving pursuit tracking in humans and compare it to that for saccadic eye movements. Pursuit performance, relative to visual fixation, elicited activation in three areas known to contribute to eye movements in humans and in nonhuman primates: the frontal eye field, supplementary eye field, and intraparietal sulcus. It also activated three medial regions not previously identified in human neuroimaging studies of pursuit: the precuneus and the anterior and posterior cingulate cortices. All six areas were also activated during saccades. The spatial extent of activation was similar for saccades and pursuit in all but two regions: spatial extent was greater for saccades in the superior branch of the frontal eye field and greater for pursuit in posterior cingulate cortex. This set of activations for smooth pursuit parallels the network of oculomotor areas characterized in nonhuman primates and complements recent studies showing that common cortical networks subserve oculomotor functions and spatial attention in humans.

No abstract

No abstract

How our vision remains stable in spite of the interruptions produced by saccadic eye movements has been a repeatedly revisited perceptual puzzle. The major hypothesis is that a corollary discharge (CD) or efference copy signal provides information that the eye has moved, and this information is used to compensate for the motion. There has been progress in the search for neuronal correlates of such a CD in the monkey brain, the best animal model of the human visual system. In this article, we briefly summarize the evidence for a CD pathway to frontal cortex, and then consider four questions on the relation of neuronal mechanisms in the monkey brain to stable visual perception. First, how can we determine whether the neuronal activity is related to stable visual perception? Second, is the activity a possible neuronal correlate of the proposed transsaccadic memory hypothesis of visual stability? Third, are the neuronal mechanisms modified by visual attention and does our perceived visual stability actually result from neuronal mechanisms related primarily to the central visual field? Fourth, does the pathway from superior colliculus through the pulvinar nucleus to visual cortex contribute to visual stability through suppression of the visual blur produced by saccades?

SUMMARY A critical technique for understanding how neuronal activity contributes to behavior is determining whether perturbing it changes behavior. The advent of optogenetic techniques allows the immediately reversible alteration of neuronal activity in contrast to chemical approaches lasting minutes to hours. Modification of behavior using optogenetics has had substantial success in rodents, but has not been as successful in monkeys. Here we show how optogenetic inactivation of superior colliculus neurons in awake monkeys leads to clear and repeatable behavioral deficits in the metrics of saccadic eye movements. We used our observations to evaluate principles governing the use of optogenetic techniques in the study of the neuronal bases of behavior in monkeys, particularly how experimental design must address relevant parameters, such as the application of light to subcortical structures, the spread of viral injections, and the extent of neuronal inactivation with light.

The idea of a second visual pathway, in which visual signals travel from brainstem to cortex via the pulvinar thalamus, has had considerable influence as an alternative to the primary geniculo-striate pathway. Existence of this second pathway in primates, however, is not well established. A major question centers on whether the pulvinar acts as a relay, particularly in the path from the superior colliculus (SC) to the motion area in middle temporal cortex (MT). We used physiological microstimulation to identify pulvinar neurons belonging to the path from SC to MT in the macaque. We made three salient observations. First, we identified many neurons in the visual pulvinar that received input from SC or projected to MT, as well as a largely separate set of neurons that received input from MT. Second, and more importantly, we identified a subset of neurons as relay neurons that both received SC input and projected to MT. The identification of these relay neurons demonstrates a continuous functional path from SC to MT through the pulvinar in primates. Third, we histologically localized a subset of SC-MT relay neurons to the subdivision of inferior pulvinar known to project densely to MT but also localized SC-MT relay neurons to an adjacent subdivision. This pattern indicates that the pulvinar pathway is not limited to a single anatomically defined region. These findings bring new perspective to the functional organization of the pulvinar and its role in conveying signals to the cerebral cortex.