In humans, finely tuned γ synchronization (60–90 Hz) rapidly appears at movement onset in a motor control network involving primary motor cortex, the basal ganglia and motor thalamus. Yet the functional consequences of brief movement-related synchronization are still unclear. Distinct synchronization phenomena have also been linked to different forms of motor inhibition, including relaxing antagonist muscles, rapid movement interruption and stabilizing network dynamics for sustained contractions. Here, I will introduce detailed hypotheses about how intrasite and intersite synchronization could interact with firing rate changes in different parts of the network to enable flexible action control. The here proposed cause-and-effect relationships shine a spotlight on potential key mechanisms of cortico-basal ganglia-thalamo-cortical (CBGTC) communication. Confirming or revising these hypotheses will be critical in understanding the neuronal basis of flexible movement initiation, invigoration and inhibition. Ul...

Voices are arguably among the most relevant sounds in humans’ everyday life, and several studies have suggested the existence of voice-selective regions in the human brain. Despite two decades of research, defining the human brain regions supporting voice recognition remains challenging. Moreover, whether neural selectivity to voices is merely driven by acoustic properties specific to human voices (e.g., spectrogram, harmonicity), or whether it also reflects a higher-level categorization response is still under debate. Here, we objectively measured rapid automatic categorization responses to human voices with fast periodic auditory stimulation (FPAS) combined with electroencephalography (EEG). Participants were tested with stimulation sequences containing heterogeneous non-vocal sounds from different categories presented at 4 Hz (i.e., four stimuli/s), with vocal sounds appearing every three stimuli (1.333 Hz). A few minutes of stimulation are sufficient to elicit robust 1.333 Hz voice-selective focal brai...

Motor behaviors are central to many functions and dysfunctions of the brain, and understanding their neural basis has consequently been a major focus in neuroscience. However, most studies of motor behaviors have been restricted to artificial, repetitive paradigms, far removed from natural movements performed “in the wild.” Here, we leveraged recent advances in machine learning and computer vision to analyze intracranial recordings from 12 human subjects during thousands of spontaneous, unstructured arm reach movements, observed over several days for each subject. These naturalistic movements elicited cortical spectral power patterns consistent with findings from controlled paradigms, but with considerable neural variability across subjects and events. We modeled interevent variability using 10 behavioral and environmental features; the most important features explaining this variability were reach angle and day of recording. Our work is among the first studies connecting behavioral and neural variability ...

The lateral habenula (LHb) is a phylogenetically primitive brain structure that plays a key role in learning to inhibit distinct responses to specific stimuli. This structure is activated by primary aversive stimuli, cues predicting an imminent aversive event, unexpected reward omissions, and cues associated with the omission of an expected reward. The most widely described physiological effect of LHb activation is acutely suppressing midbrain dopaminergic signaling. However, recent studies have identified multiple means by which the LHb promotes this effect as well as other mechanisms of action. These findings reveal the complex nature of LHb circuitry. The present paper reviews the role of this structure in learning from reward omission. We approach this topic from the perspective of computational models of behavioral change that account for inhibitory learning to frame key findings. Such findings are drawn from recent behavioral neuroscience studies that use novel brain imaging, stimulation, ablation, a...

Pediatric traumatic brain injury (TBI) results in heightened risk for social deficits that can emerge during adolescence and adulthood. A moderate TBI in male and female rats on postnatal day 11 (equivalent to children below the age of 4) resulted in impairments in social novelty recognition, defined as the preference for interacting with a novel rat compared with a familiar rat, but not sociability, defined as the preference for interacting with a rat compared with an object in the three-chamber test when tested at four weeks (adolescence) and eight weeks (adulthood) postinjury. The deficits in social recognition were not accompanied by deficits in novel object recognition memory and were associated with a decrease in the frequency of spontaneous inhibitory postsynaptic currents (IPSCs) recorded from pyramidal neurons within Layer II/III of the medial prefrontal cortex (mPFC). Whereas TBI did not affect the expression of oxytocin (OXT) or the OXT receptor (OXTR) mRNAs in the hypothalamus and mPFC, respect...

Prolonged stress induces neural maladaptations in the mesolimbic dopamine (DA) system and produces emotional and behavioral disorders. However, the effects of stress on activity of DA neurons are diverse and complex that hinge on the type, duration, intensity, and controllability of stressors. Here, controlling the duration, intensity, and type of the stressors to be identical, we observed the effects of stressor controllability on the activity of substantia nigra pars compacta (SNc) DA neurons in mice. We found that both lack and loss of control (LOC) over shock enhance the basal activity and intrinsic excitability of SNc DA neurons via modulation of Ih current, but not via corticosterone serum level. Moreover, LOC over shock produces more significant enhancement in the basal activity of SNc DA neurons than that produced by shock per se, and therefore attenuates the response to natural reward. This attenuation can be reversed by control over shock. These results indicate that although chronic stress per s...

Diverse gene products contribute to the pathogenesis of Alzheimer’s disease (AD). Experimental models have helped elucidate their mechanisms and impact on brain functions. Human amyloid precursor protein (hAPP) transgenic mice from line J20 (hAPP-J20 mice) are widely used to simulate key aspects of AD. However, they also carry an insertional mutation in noncoding sequence of one Zbtb20 allele, a gene involved in neural development. We demonstrate that heterozygous hAPP-J20 mice have reduced Zbtb20 expression in some AD-relevant brain regions, but not others, and that Zbtb20 levels are higher in hAPP-J20 mice than heterozygous Zbtb20 knock-out ( Zbtb20 +/–) mice. Whereas hAPP-J20 mice have premature mortality, severe deficits in learning and memory, other behavioral alterations, and prominent nonconvulsive epileptiform activity, Zbtb20 +/– mice do not. Thus, the insertional mutation in hAPP-J20 mice does not ablate the affected Zbtb20 allele and is unlikely to account for the AD-like phenotype of this model.

Although moving sound-sources abound in natural auditory scenes, it is not clear how the human brain processes auditory motion. Previous studies have indicated that, although ocular localization responses to stationary sounds are quite accurate, ocular smooth pursuit of moving sounds is very poor. We here demonstrate that human subjects faithfully track a sound’s unpredictable movements in the horizontal plane with smooth-pursuit responses of the head. Our analysis revealed that the stimulus–response relation was well described by an under-damped passive, second-order low-pass filter in series with an idiosyncratic, fixed, pure delay. The model contained only two free parameters: the system’s damping coefficient, and its central (resonance) frequency. We found that the latter remained constant at ∼0.6 Hz throughout the experiment for all subjects. Interestingly, the damping coefficient systematically increased with trial number, suggesting the presence of an adaptive mechanism in the auditory pursuit syste...

The marmoset has emerged as a promising primate model system, in particular for visual neuroscience. Many common experimental paradigms rely on head fixation and an extended period of eye fixation during the presentation of salient visual stimuli. Both of these behavioral requirements can be challenging for marmosets. Here, we present two methodological developments, each addressing one of these difficulties. First, we show that it is possible to use a standard eye-tracking system without head fixation to assess visual behavior in the marmoset. Eye-tracking quality from head-free animals is sufficient to obtain precise psychometric functions from a visual acuity task. Second, we introduce a novel method for efficient receptive field (RF) mapping that does not rely on moving stimuli but uses fast flashing annuli and wedges. We present data recorded during head-fixation in areas V1 and V6 and show that RF locations are readily obtained within a short period of recording time. Thus, the methodological advance...

The rat oxycodone and cocaine biobanks contain samples that vary by genotypes (by using genetically diverse genotyped HS rats), phenotypes (by measuring addiction-like behaviors in an advanced SA model), timepoints (samples are collected longitudinally before, during, and after SA, and terminally at three different timepoints in the addiction cycle: intoxication, withdrawal, and abstinence or without exposure to drugs through age-matched naive rats), samples collected (organs, cells, biofluids, feces), preservation (paraformaldehyde-fixed, snap-frozen, or cryopreserved) and application (proteomics, transcriptomics, microbiomics, metabolomics, epigenetics, anatomy, circuitry analysis, biomarker discovery, etc. Substance use disorders (SUDs) are pervasive in our society and have substantial personal and socioeconomical costs. A critical hurdle in identifying biomarkers and novel targets for medication development is the lack of resources for obtaining biological samples with a detailed behavioral characteri...