Gain-control mechanisms adjust neuronal responses to accommodate the wide range of stimulus conditions in the natural environment. Contrast gain control and extraclassical surround suppression are two manifestations of gain control that govern the responses of neurons in the early visual system. Understanding how these two forms of gain control interact has important implications for the detection and discrimination of stimuli across a range of contrast conditions. Here, we report that stimulus contrast affects spatial integration in the lateral geniculate nucleus of alert macaque monkeys (male and female), whereby neurons exhibit a reduction in the strength of extraclassical surround suppression and an expansion in the preferred stimulus size with low-contrast stimuli compared with high-contrast stimuli. Effects were greater for magnocellular neurons than for parvocellular neurons, indicating stream-specific interactions between stimulus contrast and stimulus size. Within the magnocellular pathway, contra...

Maintaining and manipulating sequences online is essential for daily activities such as scheduling a day. In Parkinson's disease (PD), sequential working memory deficits have been associated with altered regional activation and functional connectivity in the basal ganglia. This study demonstrates that the substantia nigra (SN) integrity correlated with basal ganglia function and sequencing performance in 29 patients with PD (17 women) and 29 healthy controls (HCs; 18 women). In neuromelanin-sensitive structural magnetic resonance imaging (MRI), PD patients showed smaller SNs than HCs. In a digit-ordering task with functional MRI (fMRI), participants either recalled sequential digits in the original order (pure recall) or rearranged the digits and recalled the new sequence (reorder and recall). PD patients performed less accurately than HCs, accompanied by the caudate and pallidal hypoactivation, subthalamic hyperactivation, and weakened functional connectivity between the bilateral SN and all three basal g...

Two forms of information, frequency (content) and ordinal position (structure), have to be stored when retaining a sequence of auditory tones in working memory (WM). However, the neural representations and coding characteristics of content and structure, particularly during WM maintenance, remain elusive. Here, in two EEG studies in human participants (both sexes), by transiently perturbing the “activity-silent” WM retention state and decoding the reactivated WM information, we demonstrate that content and structure are stored in a dissociative manner with distinct characteristics throughout WM process. First, each tone in the sequence is associated with two codes in parallel, characterizing its frequency and ordinal position, respectively. Second, during retention, a structural retrocue successfully reactivates structure but not content, whereas a following white noise triggers content but not structure. Third, structure representation remains stable, whereas content code undergoes a dynamic transformatio...

Kisspeptin (Kiss1) neurons provide indispensable excitatory input to GnRH neurons, which is important for the coordinated release of gonadotropins, estrous cyclicity and ovulation. However, Kiss1 neurons also send projections to many other brain regions within and outside the hypothalamus. Two different populations of Kiss1 neurons, one in the arcuate nucleus (Kiss1ARH) and another in the anteroventral periventricular and periventricular nucleus (Kiss1AVPV/PeN) of the hypothalamus are differentially regulated by ovarian steroids, and are believed to form direct contacts with GnRH neurons as well as other neurons. To investigate the projection fields from Kiss1AVPV/PeN and Kiss1ARH neurons in female mice, we used anterograde projection analysis, and channelrhodopsin-assisted circuit mapping (CRACM) to explore their functional input to select target neurons within the paraventricular (PVH) and dorsomedial (DMH) hypothalamus, key pre-autonomic nuclei. Cre-dependent viral (AAV1-DIO-ChR2 mCherry) vectors were i...

The term “memory strength” generally refers to how well one remembers something but more precisely it contains multiple modalities, such as how easily, how accurately, how confidently and how vividly we remember it. In human, these modalities of memory strength are dissociable. In this study, we asked whether we can isolate a behavioral component that is dissociable from others in hippocampus-dependent memory tasks in mice, which potentially reflect a modality of memory strength. Using a virus-mediated inducible method, we ablated immature neurons in the dentate gyrus in mice after we trained the mice with hippocampus-dependent memory tasks normally. In memory retrieval tests, these ablated mice initially show intact performance. However, the ablated mice ceased learned behavior prematurely within a trial compared with control mice. In addition, the ablated mice showed shorter duration of individual episodes of learned behavior. Both affected behavioral measurements point to persistence of learned behavior...

It is widely assumed that we select actions we value the most. While the influence of rewards on decision-making has been extensively studied, evidence regarding the influence of motor costs is scarce. Specifically, how and when motor costs are integrated in the decision process is unclear. Twenty-two right-handed human participants performed a reward-based target selection task by reaching with their right arm toward one of two visual targets. Targets were positioned in different directions according to biomechanical preference, such that one target was systematically associated with a lower motor cost than the other. Only one of the two targets was rewarded, either in a congruent or incongruent manner with respect to the associated motor cost. A timed-response paradigm was used to manipulate participants’ reaction times (RT). Results showed that when the rewarded target carried the highest motor cost, movements produced at short RT (<350ms) were deviated toward the other (i.e., non-rewarded, low-cost) ta...

Pitch is a perceptual attribute enabling perception of melody. There is no consensus regarding the fundamental nature of pitch and its underlying neural code. A stimulus which has received much interest in psychophysical and computational studies is noise with a sharp spectral edge. High- or low-pass noise gives rise to a pitch near the edge frequency (“monaural edge pitch”, MEP). The simplicity of this stimulus, combined with its spectral and autocorrelation properties, make it an interesting stimulus to examine spectral versus temporal cues that could underly its pitch. We recorded responses of single auditory nerve fibers in chinchilla to MEP-stimuli varying in edge frequency. Temporal cues were examined with shuffled autocorrelogram (SAC) analysis. Correspondence between the population’s dominant interspike interval and reported pitch estimates was poor. A fuller analysis of the population interspike interval distribution, which incorporates not only the dominant but all intervals, results in good matc...

Cross-sectional versus longitudinal comparisons of age-related change have often revealed differing results. In the current study, we employed within-subject task-based fMRI to investigate changes in voxel-based activations and behavioral performance across the lifespan in the Reference Ability Neural Network (RANN) cohort, at both baseline and 5-year follow-up. We analyzed fMRI data from between 127 and 159 participants (20-80 years), on a battery of tests relating to each of four cognitive reference abilities (RAs). We applied a Gaussian age kernel to capture continuous change across the lifespan using a 5-year sliding window centered on each age in our participant sample, with a subsequent division into young, middle, and old age brackets. This method was applied separately to both cross-sectional approximations of change and real longitudinal changes adopting a comparative approach. We then focused on longitudinal measurements of neural change to identify regions expressing peak changes and fluctuation...

Primary motor cortex (M1) undergoes protracted development in mammals, functioning initially as a sensory structure. Throughout the first postnatal week in rats, M1 is strongly activated by self-generated forelimb movements—especially by the twitches that occur during active sleep. Here, we quantify the kinematic features of forelimb movements to reveal receptive-field properties of individual units within the forelimb region of M1. At postnatal day (P) 8, nearly all units were strongly modulated by movement amplitude, especially during active sleep. By P12, only a minority of units continued to exhibit amplitude-tuning, regardless of behavioral state. At both ages, movement direction also modulated M1 activity, though to a lesser extent. Finally, at P12, M1 population-level activity became more sparse and decorrelated, along with a substantial alteration in the statistical distribution of M1 responses to limb movements. These findings reveal a transition toward a more complex and informationally rich repr...

Emotional memories are better remembered than neutral ones, but the mechanisms leading to this memory bias are not well understood in humans yet. Based on animal research, it is suggested that the memory enhancing effect of emotion is based on central noradrenergic release, which is triggered by afferent vagal nerve activation. To test the causal link between vagus nerve activation and emotional memory in humans, we applied continuous non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) during exposure to emotional arousing and neutral scenes and tested subsequent, long-term recognition memory after one week. We found that taVNS, compared to sham, increased recollection-based memory performance for emotional, but not neutral, material. These findings were complemented by larger recollection-related brain potentials (parietal ERP Old/New effect) during retrieval of emotional scenes encoded under taVNS, compared to sham. Furthermore, brain potentials recorded during encoding also revealed th...