Journal of Neuroscience最新文献

Young children strongly depend on others, and learning to understand their mental states (referred to as Theory of Mind, ToM) is a key challenge of early cognitive development. Traditionally, ToM is thought to emerge around the age of 4 years. Yet, in non-verbal tasks, preverbal infants already seem to consider others' mental states when predicting their actions. These early non-verbal capacities, however, seem fragile and distinct from later-developing verbal ToM. So far, little is known about the nature of these early capacities and the neural networks supporting them. To identify these networks, we investigated the maturation of nerve fiber connections associated with children's correct non-verbal action prediction and compared them with connections supporting verbal ToM reasoning in 3- to 4-year-old children of both sexes, that is, before and after their breakthrough in verbal ToM. This revealed a ventral network for non-verbal action prediction versus a dorsal network for verbal ToM. Non-verbal capacities were associated with maturational indices in ventral fiber tracts connecting regions of the salience network, involved in bottom-up social attention processes. In contrast, verbal ToM performance correlated with maturational indices of the arcuate fascicle and cingulum, which dorsally connect regions of the default network, involved in higher-order social cognitive processes including ToM in adults. As non-verbal tasks were linked to connections of the salience network, young children may make use of salient perceptual social cues to predict others' actions, questioning theories of mature ToM before 4 years.Significance Statement As highly social beings, humans frequently reason about other people's thoughts, termed Theory of Mind (ToM). While ToM is traditionally assumed not to emerge before 4 years, preverbal infants already seem to consider others' thoughts when predicting their actions non-verbally. This raises the question of when ToM develops and what explains this discrepancy. We show that young children's success in non-verbal tasks is related to different neural networks than those involved in mature verbal ToM. While verbal ToM was linked to ToM network connections, younger children's non-verbal capacities were associated with the maturation of connections of the salience network. This indicates that, instead of mature ToM, young children might utilize salient social cues to predict others' actions.

Communication from secondary (M2, premotor) to primary (M1) motor cortex is implicated in forelimb motor control. We investigated the underlying synaptic circuits in this corticocortical pathway in male and female mice using cell-type-specific optogenetic-electrophysiology methods, focusing on identifying the cell-type-specific synaptic connections in the excitatory and feedforward inhibitory circuits impinging on cervically projecting M1 corticospinal neurons. In forelimb M1 brain slices, recordings from layer (L)5B corticospinal neurons during brief photostimulation of M2 axons showed strong monosynaptic excitatory currents that, although accompanied by potent feedforward inhibitory currents, were capable of evoking action potentials (APs) in most neurons. In contrast, responses in L2/3 pyramidal neurons were generally much weaker. Parvalbumin (PV)-expressing neurons, particularly in deeper layers, showed direct excitation from M2 axons without feedforward inhibition and could fire APs robustly. Somatostatin (SST) neurons received generally weak inputs, whereas vasoactive intestinal protein (VIP) and neuron-derived neurotrophic factor (Ndnf) neurons received stronger excitation and inhibition from M2 axons. Corticospinal neurons received little or no local inhibition from Ndnf and VIP interneurons but relatively strong soma-targeting PV and dendrite-targeting SST inhibitory inputs, as functionally imaged by laser-scanning synaptic input mapping ("sCRACM"). The domains of PV and SST inputs were partly overlapping around the corticospinal somata but broader for PV and more vertical for SST inputs. Collectively, the results provide a working model for the cell-type-specific synaptic circuits of this "top-down" corticocortical pathway, organized around direct M2 excitation and PV-mediated inhibition of M1 corticospinal neurons.

In Alzheimer's disease (AD) models, ventral tegmental area (VTA) dopamine neurons are intrinsically hyperexcitable yet release less dopamine and exhibit dysfunctional downstream signaling. Synaptic transmission is broadly disrupted in AD, but it is not known to what extent excitatory and inhibitory inputs to the VTA are altered. Here we describe enhanced synaptic excitation in dopamine neurons from male and female 3xTg-AD mice (an amyloid + tau-driven model). AMPAR-mediated excitatory input was enhanced in a subset of connections, while GABA_AR-mediated inhibition decreased as a function of dendritic atrophy. Protein phosphorylation analysis and pharmacology suggested that strengthened excitation depends on both presynaptic protein kinase C activity and postsynaptic enhancement of perisomatic AMPA receptor currents. Biophysical modeling predicted that enhanced excitatory synaptic input in 3xTg-AD dopamine neurons, combined with altered dendritic morphology and intrinsic hypersensitivity, produces increased firing and a steeper input-output relationship. These results suggest that AD pathology is associated with increased sensitivity of single dopamine neurons, which may serve to maintain phasic dopamine signaling in early stages of degeneration.

Flexible prioritization in working memory (WM) is supported by neural oscillations in frontal and sensory brain areas, but the roles of different oscillations remain poorly understood. Recordings in humans suggest an interplay between prefrontal slow frequency (2-8 Hz) and posterior alpha-band (10 Hz) oscillations regulating top-down control and retrieval of WM representations, respectively. Complementary work, primarily in nonhuman primates, suggests an additional role for beta (15-30 Hz) oscillations in clearing or inhibiting stimuli from entering WM. Here we investigated the role of neural oscillations in prioritizing WM content using electroencephalography (EEG) as participants (humans of any sex) performed a task requiring frequent priority switches between two memorized oriented bars. Behavioral performance revealed switch costs, which scaled with the angular distance between the two items, suggesting that priority shifts are modulated by shift magnitude. Time-frequency analyses revealed increased frontal theta (4-8 Hz) and decreased central-parietal beta (15-25 Hz) power during switches. Crucially, only beta power scaled with the magnitude of the priority shift and predicted the fidelity of neural decoding of the newly prioritized item during subsequent recall. Theta power, in contrast, was elevated on switch trials but did not vary with update magnitude or decoding strength, suggesting a more general role in signaling control demands. Our findings highlight a particular and previously overlooked role for beta-band oscillations in the flexible prioritization of WM content.

Sudden environmental changes can render planned hand movements suboptimal or even counterproductive. To prevent the execution of outdated motor plans, the motor system may transiently inhibit actions following salient changes, allowing time to evaluate alternatives. While such a mechanism is well established for eye movements, its applicability to hand movements remains unclear. Here, we present findings from three online behavioral experiments and two lab-based replications designed to probe key features of this mechanism in manual responses: reflexive inhibition, temporal precedence, complete movement updating, and sensitivity to saliency. Participants of either sex performed rapid sequential tapping movements toward onscreen targets. At an unpredictable time, either a relevant change (a target displacement) or an irrelevant change (a brief luminance flash) occurred. We measured movement initiation rates following these changes and compared them with a no-change baseline. A significant transient inhibition of movement initiation followed both relevant and irrelevant changes. This inhibition preceded observable updates to the movement plan. At the time of inhibition release, the update to a movement plan was complete. Across experiments, we observed stronger inhibitory effects for more salient changes. The lab-based replication confirmed that the latency of this inhibitory response aligns with visuomotor reaction times. These results support the existence of a general-purpose, rapid inhibitory mechanism in hand movements analogous to inhibition in the oculomotor system. We propose that such inhibition provides a reflexive, domain-general safeguard against obsolete actions following unexpected changes.

To navigate the world, we store knowledge about relationships between concepts and retrieve this information flexibly to suit our goals. The semantic control network, comprising left inferior frontal gyrus (IFG) and posterior middle temporal gyrus (pMTG), is thought to orchestrate this flexible retrieval by modulating sensory inputs. However, interactions between semantic control and input regions are not sufficiently understood. Moreover, pMTG's well-formed structural connections to IFG and visual cortex suggest it as a candidate region to integrate control and input processes. We used magnetoencephalography to investigate oscillatory dynamics during semantic decisions to pairs of words, when participants (both sexes) did or did not know the type of semantic relation between them. IFG showed increases and decreases in oscillatory activity to prior task knowledge, while pMTG only showed positive task knowledge effects. Furthermore, IFG provided sustained feedback to pMTG when task goals were known, while in the absence of goals this feedback was delayed until receiving bottom-up input from the second word. This goal-dependent feedback coincided with an earlier onset of feedforward signaling from visual cortex to pMTG, indicating rapid retrieval of task-relevant features. This pattern supports a model of semantic cognition in which pMTG integrates top-down control from IFG with bottom-up input from visual cortex to activate task-relevant semantic representations. Our findings elucidate the separate roles of anterior and posterior components of the semantic control network and reveal the spectro-temporal cascade of interactions between semantic and visual regions that underlie our ability to flexibly adapt cognition to the current goals.