Humans rapidly update the control of an ongoing movement following changes in contextual parameters. This involves adjusting the controller to exploit redundancy in the movement goal, such as when reaching for a narrow or wide target, and adapting to dynamic changes such as velocity-dependent force fields (FFs). Although flexible control and motor adaptation are computationally distinct, the fact that both unfold within the same movement suggests that they interact functionally to support task-specific adjustments. To test this hypothesis, we conducted a series of experiments combining changes in the target structure and a force field presented separately or in combination. Seventy-six human participants (both sexes) took part in this study, with each experiment involving different participants. They were asked to reach for a target that could change from a narrow square to a wide rectangle between or during trials. Step loads were used to assess whether participants exploited target redundancy. In a separ...

This study aims to examine the changes in AQP4 polarity and pericyte vascularity during temporal lobe epilepsy (TLE) progression, with the goal of identifying potential drug targets or strategies to delay the onset and progression of TLE. Chronic TLE was induced in male rats using pilocarpine. AQP4 polarity and pericyte vascular coverage were assessed by immunofluorescence. The effects of modulating AQP4 polarity on PTZ-induced TLE model using male mice were studied. Molecular mechanisms of AQP4 polarity were explored using transwell coculture and transcriptomics, validated at the protein level. ELISA was used to measure PDGF-BB levels in serum and cerebrospinal fluid. Following pilocarpine-induced chronic TLE model establishment, AQP4 polarity and pericyte vascular coverage rapidly increased but later declined, reaching the lowest levels in epileptic animals. Trifluoperazine prevented AQP4 redistribution, reduced seizure duration, and alleviated brain edema in PTZ-induced TLE mouse model. Transcriptomic a...

Alzheimer's disease (AD) has traditionally been associated with amyloid-β plaques, but growing evidence underscores the role of neuroinflammation in disease progression. The autoinflammatory hypothesis of AD suggests chronic immune dysfunction contributes to neuronal damage, making immune modulation a promising therapeutic strategy. Cannabidiol (CBD), a phytocannabinoid with anti-inflammatory properties, may offer therapeutic potential. This study investigates how CBD independently influences two key neuroinflammatory regulators in AD: the indoleamine 2,3-dioxygenase (IDO) pathway and the cyclic GMP-AMP synthase (cGAS) pathway. Though mechanistically distinct, both shape CNS immune responses. Targeting these immune-metabolic axes provides a mechanistic alternative to amyloid- or tau-based approaches by addressing upstream drivers of neuroinflammation and immune dysregulation. Using the male 5XFAD transgenic AD mouse model, we administered CBD via inhalation and assessed IDO and cGAS expression using flow c...

Aberrant dopamine transmission is a hallmark of several psychiatric disorders. Dopamine neurons in the ventral tegmental area (VTA) display distinct activity states that are regulated by discrete afferent inputs. For example, burst firing requires excitatory input from the mesopontine tegmentum, while dopamine neuron population activity, defined as the number of spontaneously active dopamine neurons, is thought to be dependent on inhibitory drive from the ventral pallidum (VP). Rodent models used to study psychiatric disorders, such as psychosis, consistently exhibit elevated dopamine neuron population activity, due to decreased tonic inhibition from the VP. However, it remains unclear whether the VP can modulate all dopamine neurons or if only a specific subset of VTA dopamine neurons receive innervation from the VP to be recruited as required. This knowledge is critical for understanding dopamine regulation in normal and pathological conditions. Here, we used in vivo electrophysiology in male and female ...

Despite various histological, electrophysiological, and imaging studies, the topographic organization of saccade-related activity in the posterior parietal cortex (PPC) has been notoriously difficult to characterize. In part, this is because areas of interest in PPC are often embedded deep in sulci in macaques and humans. Understanding the extent of topographic organization in PPC can provide insights into the computation contributions of PPC. The lissencephalic cortex of the common marmoset offers a unique opportunity to investigate fine-scale topographic organization in PPC. Recordings were obtained from the PPC of two male marmosets performing a visually guided center-out saccade task with 8 or 36 peripheral targets using multichannel electrode arrays with 100 μm spacing. By plotting the pattern of saccade direction tuning preferences across all penetrations and cortical depths, we uncovered topographic organizational features within the PPC. Like other primates, multiunits in marmoset PPC tend to prefe...

Recent investigations have revealed that selective attention to lateralized speech increases ipsilateral tonic electromyographic activity in the vestigial human auriculomotor system. However, it has yet to be determined whether this modulation depends upon predictive cues that are inherent in continuous speech or whether it is a general concomitant of selective attention to sounds in the auditory periphery. The present study addressed this question by replacing speech with randomized, unpredictable sequences of brief tonal stimuli in a dichotic listening task that necessitated a sustained anticipatory focus of attention. Participants (8 female, 23 male) were presented with sequences of brief tone bursts in one ear and frequency-modulated “chirps” in the other ear and were instructed to focus on sounds in one ear and report attenuated deviant stimuli in that ear. Posterior auricular muscle (PAM) activity was recorded behind both ears, and non-rectified stimulus-locked responses were assessed to ensure the r...

Perception is shaped by both the physical properties of stimuli and their contextual presentation, often leading to systematic biases such as the central tendency effect, where perceptual judgments shift toward the average of the stimulus set. This study explored the central tendency bias in vibrotactile perception, an area that has received limited attention while also replicating its well-documented occurrence in color perception to validate previous findings. Using a within-subject design, participants (5 males, 15 females) completed color and vibrotactile discrimination tasks, each consisting of three blocks, which comprised systematically shifted stimulus sets. In an established virtual reality color task, stimuli ranged from yellow–green to blue–green, while in the vibrotactile task, stimuli varied in vibration intensity around a baseline distribution. As predicted, the point of subjective equality shifted toward the mean of the stimulus sets in both tasks, confirming the presence of a central tenden...

Sleep–wake states bidirectionally interact with epilepsy and seizures, but the mechanisms are unknown. A barrier to comprehensive characterization and the study of mechanisms has been the difficulty of annotating large chronic recording datasets. To overcome this barrier, we sought to develop an automated method of classifying sleep–wake states, seizures, and the postictal state in mice ranging from controls to mice with severe epilepsy with accompanying background electroencephalographic (EEG) abnormalities. We utilized a large dataset of recordings, including electromyogram, EEG, and hippocampal local field potentials, from control and intra-amygdala kainic acid-treated mice. We found that an existing sleep–wake classifier performed poorly, even after retraining. A support vector machine, relying on typically used scoring parameters, also performed below our benchmark. We then trained and evaluated several multilayer neural network architectures and found that a bidirectional long short-term memory–based...

Thirst is a strongly motivated internal state that is represented in central brain circuits that are only partially understood. Water seeking is a discrete step of the thirst behavioral sequence that is amenable to uncovering the mechanisms for motivational properties such as goal-oriented behavior, value encoding, and behavioral competition. In Drosophila , water seeking is regulated by the NPY-like neuropeptide NPF; however, the circuitry for NPF-dependent water seeking is unknown. To uncover the downstream circuitry, we identified the NPF receptor NPFR and the neurons it is expressed in as being acutely critical for thirsty water seeking in males. Refinement of the NPFR pattern uncovered a role for a single neuron, the L1-l, in promoting thirsty water seeking. The L1-l neuron increases its activity in thirsty flies and is involved in the regulation of dopaminergic neurons in long-term memory formation. Thus, NPFR and its ligand NPF, already known for its role in feeding behavior, are also important for ...

Although clinical and experimental evidence highlight the role of the thalamus in voluntary movement production, the involvement of the thalamus in complex motor tasks such as speech production remains to be elucidated. The present study examined neural activity within the bilateral thalamus in 13 participants (seven females) with essential tremor undergoing awake deep brain stimulation implantation surgery, using three speech tasks of varied complexity [vowel vocalization, a diadochokinetic task (DDK), and sentence repetition]. Low-frequency neural activity (delta/theta band) activity was significantly increased during sentence and DDK compared with vowel vocalization in the bilateral motor thalamus and, to a lesser extent, increased for sentence repetition compared with DDK. Moreover, there was prominent prespeech beta band activity, with a greater decrease in the power of beta activity for sentence compared with DDK and vowel vocalization. The greater low-frequency activity in more complex speech tasks ...