Seizure prediction is the grand challenge of epileptology. However, effort was devoted to prediction of focal seizures, while generalized seizures were regarded as stochastic events. Long-lasting local field potential (LFP) recordings containing several hundred generalized spike and wave discharges (SWDs), acquired at eight locations in the cortico-thalamic system of absence epileptic rats, were iteratively analyzed in all possible combinations of either two or three recording sites, by a wavelet-based algorithm, calculating the product of the wavelet-energy signaling increases in synchronicity. Sensitivity and false alarm rate of prediction were compared between various combinations, and wavelet spectra of true and false positive predictions were fed to a random forest machine learning algorithm to further differentiate between them. Wavelet analysis of intracortical and cortico-thalamic LFP traces showed a significantly smaller number of false alarms compared with intrathalamic combinations, while predic...

Noise introduced in the human nervous system from cellular to systems levels can have a major impact on signal processing. Using transcranial stimulation, electrical noise can be added to cortical circuits to modulate neuronal activity and enhance function in the healthy brain and in neurologic patients. Transcranial random noise stimulation (tRNS) is a promising technique that is less well understood than other non-invasive neuromodulatory methods. The aim of the present scoping review is to collate published evidence on the effects of electrical noise at the cellular, systems, and behavioral levels, and discuss how this emerging method might be harnessed to augment perceptual and motor functioning of the human nervous system. Online databases were used to identify papers published in 2008–2021 using tRNS in humans, from which we identified 70 publications focusing on sensory and motor function. Additionally, we interpret the existing evidence by referring to articles investigating the effects of noise st...

The human amygdala and hippocampus are critically involved in various processes in face perception. However, it remains unclear how task demands or evaluative contexts modulate processes underlying face perception. In this study, we employed two task instructions when participants viewed the same faces and recorded single-neuron activity from the human amygdala and hippocampus. We comprehensively analyzed task modulation for three key aspects of face processing and we found that neurons in the amygdala and hippocampus (1) encoded high-level social traits such as perceived facial trustworthiness and dominance and this response was modulated by task instructions; (2) encoded low-level facial features and demonstrated region-based feature coding, which was not modulated by task instructions; and (3) encoded fixations on salient face parts such as the eyes and mouth, which was not modulated by task instructions. Together, our results provide a comprehensive survey of task modulation of neural processes underly...

There is consensus that primary auditory cortex (A1) utilizes a combination of rate codes and temporally precise population codes to represent discreet auditory objects. During the response to auditory streams, forward suppression constrains cortical rate coding strategies, but it may also be well positioned to enhance temporal coding strategies that rely on synchronized firing across neural ensembles. Here, we exploited the rapid temporal dynamics of bat echolocation to investigate how forward suppression modulates the cortical ensemble representation of complex acoustic signals embedded in echo streams. We recorded from auditory cortex of anesthetized free-tailed bats while stimulating the auditory system with naturalistic biosonar pulse-echo sequences covering a range of pulse emission rates. As expected, increasing pulse repetition rate significantly reduced the number of spikes per echo stimulus, but it also increased spike timing precision and doubled the information gain. This increased spike-timing...

Employing postsynaptically tethered calcium sensor GCaMP, we investigated spontaneous synaptic transmission at individual active zones (AZs) at the Drosophila (both sexes) neuromuscular junction. Optical monitoring of GCaMP events coupled with focal electrical recordings of synaptic currents revealed “hot spots” of spontaneous transmission, which corresponded to transient states of elevated activity at selected AZs. The elevated spontaneous activity had two temporal components, one at a timescale of minutes and the other at a sub-second timescale. We developed a three-state model of AZ preparedness for spontaneous transmission and performed Monte-Carlo simulations of the release process, which produced an accurate quantitative description of the variability and time-course of spontaneous transmission at individual AZs. To investigate the mechanisms of elevated activity, we first focused on the protein complexin, which binds the SNARE protein complex and serves to clamp spontaneous fusion. Overexpression of...

A main characteristic of dyslexia is poor use of sound categories. We now studied within-session learning of new sound categories in dyslexia – behaviorally and neurally, using fMRI. Human participants (males and females) with and without dyslexia were asked to discriminate which of two serially-presented tones had a higher pitch. The task was administered in two protocols, with and without a repeated reference frequency. The reference condition introduces regularity, and enhances frequency sensitivity in typically developing (TD) individuals. Enhanced sensitivity facilitates the formation of “high” and “low” pitch categories above and below this reference, respectively. We found that in TDs, learning was paralleled by a gradual decrease in activation of the primary auditory cortex, and reduced activation of the superior temporal gyrus and left posterior parietal cortex, which are important for utilizing sensory history. No such sensitivity was found among individuals with dyslexia (IDDs). Rather, IDDs sho...

Emotional states provide an ever-present source of contextual information that should inform behavioral goals. Despite the ubiquity of emotional signals in our environment, the neural mechanisms underlying their influence on goal-directed action remains unclear. Prior work suggests that the lateral frontal pole (FPl) is uniquely positioned to integrate affective information into cognitive control representations. We used pattern similarity analysis to examine the content of representations in FPl and interconnected mid-lateral prefrontal and amygdala circuitry. Healthy participants (n=37; n=21 females) were scanned while undergoing an event-related Affective Go/No-Go task, which requires goal-oriented action selection during emotional processing. We found that FPl contained conjunctive emotion-action goal representations that were related to successful cognitive control during emotional processing. These representations differed from conjunctive emotion-action goal representations found in the basolateral ...

Mechanisms underlying the initial accumulation of tau pathology across the human brain are largely unknown. We examined whether baseline factors including age, amyloid-β, and neural activity predicted longitudinal tau accumulation in temporal lobe regions that reflect distinct stages of tau pathogenesis. Seventy cognitively normal human older adults (77±6 years, 59% female) received ≥2 18F-Flortaucipir (FTP) and 11C-Pittsburgh Compound B (PiB) PET scans (2.5±1.1 years follow-up) to quantify tau and amyloid-β. Linear mixed effects models were used to calculate slopes of FTP change in entorhinal cortex (EC), parahippocampal cortex (PHC), and inferior temporal gyrus (IT), and slopes of global PiB change. Thirty-seven participants received functional MRI to measure baseline activation. Older age predicted EC tau accumulation, and baseline EC tau predicted subsequent tau accumulation in EC and PHC. In IT, however, baseline EC tau interacted with Aβ to predict IT tau accumulation. Higher baseline local activatio...

In the mammalian brain perivascular astrocytes (PAs) closely juxtapose blood vessels and are postulated to have important roles in the control of vascular physiology, including regulation of the blood-brain barrier (BBB). Deciphering specific functions for PAs in BBB biology, however, has been limited by the ability to distinguish these cells from other astrocyte populations. In order to characterize selective roles for PAs in vivo, a new mouse model has been generated in which the endogenous megalencephalic leukoencephalopathy with subcortical cysts 1 (Mlc1) gene drives expression of Cre fused to a mutated estrogen ligand-binding domain (Mlc1-T2A-CreERT2). This knock-in mouse model, which we term MLCT, allows for selective identification and tracking of PAs in the post-natal brain. We also demonstrate that MLCT-mediated ablation of PAs causes severe defects in BBB integrity, resulting in premature death. PA loss results in aberrant localization of Claudin 5 and VE-Cadherin in endothelial cell junctions as...

While opioids produce both analgesia and side-effects by action at mu-opioid receptors (MOR), at spinal and supraspinal sites, potency of different opioids to produce these effects vary. While it has been suggested that these differences might be due to bias for signaling via β-arrestin versus G protein alpha (Gα), recent studies suggest that G protein biased MOR agonists still produce clinically important side-effects. Since bias also exists in the role of Gα subunits, we evaluated the role of Gαi/o subunits in analgesia, hyperalgesia, and hyperalgesic priming produced by fentanyl and morphine, in male rats. We found that intrathecal treatment with oligodeoxynucleotides antisense (AS-ODN) for Gαi2, Gαi3 and Gαo markedly attenuated hyperalgesia induced by sub-analgesic dose (sub-AD) fentanyl, while AS-ODN for Gαi1, as well as Gαi2 and Gαi3, but not Gαo, prevented hyperalgesia induced by sub-AD morphine. AS-ODN for Gαi1 and Gαi2 unexpectedly enhanced analgesia induced by analgesic dose (AD) fentanyl, while ...