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Vasilev, D.

Publications and source records attributed to Vasilev, D..

6 recordsLinked to original sources

Long-term Humoral Immune Dynamics After SARS-CoV-2 Vaccination and Infection in Healthcare Workers: The VaCoMRI Study

ObjectivesThe VaCoMRI study tracked a healthcare worker cohort from 2020 through June 2024 to characterize the long-term sustainability of vaccine- and infection-induced SARS-CoV-2 immunity. MethodsFollowing an initial anti-nucleocapsid (N) IgG screening of 4,554 employees in early 2020, participants were monitored regularly from the BNT162b2 rollout (December 2020). Serum collected at predefined intervals after vaccination and breakthrough infection (BTI) was analyzed for anti-N, quantitative anti-spike (anti-S) IgG, and surrogate viral neutralizing antibody (sVNT) titers. ResultsOver a median follow-up of 1,180 days, 142 healthcare workers contributed longitudinal samples; 66.2% experienced one BTI and 14.1% a second. In previously seronegative individuals, anti-N titers decreased 2.3-fold between 3 and 6 months post-first BTI, with seropositivity dropping from 82% to 40.4% (median time to seronegativity: 179 days). Conversely, prior anti-N seropositivity was associated with 4.5-fold higher anti-N IgG levels during follow-up, and a second BTI led to 3-fold higher titers at 3 months. Before BTI, the third vaccine dose significantly enhanced antibody persistence versus the second dose; at 9 months, titers remained 7.2-fold higher for sVNT and 3.9-fold higher for anti-S IgG. Initial seropositivity also predicted 2.9-fold higher sVNT levels during follow-up. ConclusionsRepeated vaccination and infection synergistically induced robust, durable spike-directed hybrid immunity. Conversely, rapid anti-N IgG waning severely limits its reliability for the retrospective serosurveillance of SARS-CoV-2 exposure in occupational settings.

microbiology↗

Volitional stopping is preceded by a transient beta oscillation

Human motor cortex EEG beta (15-30 Hz) oscillations undergo transient power modulations (bursts) during volitional control of movements. They are a potential control signal for brain-machine interfaces and are a therapeutic target in Parkinsons disease. The prevailing view is that EEG beta bursts increase during stopping and immobility, but do not precede stopping. In contrast to prior work in humans and animals that used a latent and unobservable stopping time in the stop-signal task, we developed a translational animal model to align EEG with overt action stopping. We recorded 32-electrode EEG along with the angular velocity of a treadmill while head-fixed rats stopped in-progress running on a freely-rotating, non-motorized treadmill. Contrasting prior work, motor cortex beta bursts increased before stopping and not during stopping or immobility. Using information theoretic measures, we show that beta power was informative about treadmill velocity 200 msec in the future, but only during planning to stop. By introducing artificial temporal jitter to mimic the estimation of stopping time used in prior work, we show that this predictive brain-action relationship fails with even small jitter. Finally, we use a variety of machine learning methods to show that, despite EEG beta oscillations being a clear neural correlate preceding stopping, it has limited utility for real-time action decoding. Our work suggests a new conceptual model for neural control of action stopping.

neuroscience↗

Aberrant prefrontal activity and arousal level correlate with action initiation and response vigor

Orchestrating learned Stimulus-Response (S-R) mappings has been suggested as one of the central functions of the prefrontal cortex (PFC). While S-R selective activity has been demonstrated, it remains unclear whether the strength of such activity is related to the vigor of the subsequent response. Here, we trained male rats to perform a Go/NoGo response task while head-fixed on a treadmill. This allowed us to record PFC (cingulate, area 24) single unit spiking, as well as running speed as a proxy for response vigor. We show that aberrant activation of the "wrong" S-R mapping is correlated with initiation of the incorrect response. The vigor of the incorrect response was directly related to the strength of the aberrant stimulus-evoked activity. A similar relationship was observed for pre-trial arousal state and response vigor. Our findings confirm the long-standing concept, established in psychology and cognitive neuroscience, that S-R mappings are directly related to response vigor. Moreover, we provide evidence for the often suggested but rarely tested relationship between arousal and response vigor and a potential underlying neuronal mechanism involving neuromodulation of S-R mapping activity. Significance statementThe concept of stimulus-response (S-R) mappings is fundamental in psychology and has been widely documented as a key function of the prefrontal cortex. Here, the authors directly link prefrontal single neuron mapping-selective activity to the vigor of responses. Moreover, they link a physiological measure of arousal to response vigor and suggest that neuromodulatory systems invigorate responses by potentially modulating PFC S-R mapping-selective activity.

neuroscience↗

Brightness illusions evoke pupil constriction and a visual cortex response in rats

The mind affects the body via central nervous system (CNS) control of the autonomic nervous system (ANS). In humans, one striking illustration of the mind-body connection is that illusions, subjectively perceived as bright, drive constriction of the eyes pupil by activating the sympathetic arm of the ANS. How the CNS is involved in this pupil response is unknown and requires an animal model for intracerebral investigation of potential regions, cell types, and neuronal projections. However, the physiological response to this illusion has long been thought to occur only in humans. Here, we report that the same brightness illusion that evokes pupil constriction in humans also does so in rats. Cortex-wide EEG recordings revealed that, compared to a luminance-matched control stimulus, the illusion (which appears subjectively brighter to humans) evoked a larger response only in primary visual cortex (V1). This cortical response preceded pupil constriction by ~335 msec suggesting a potential causal role for V1 on the pupil. Our results establish a new animal model of importance for studying how the CNS response involved in sensing a brightness illusion drives a physiological reaction in the body. We provide objective evidence that complex mind-body connections are not confined to humans and that V1 may be part of a shared, mammalian, neural network for bodily reactions to illusions.

neuroscience↗

Focusing perceptual attention in one modality constrains subsequent learning in another modality

Contemporary neuroscience and psychiatry suggest that attention to decision outcomes guides rule learning by adjusting stimulus-outcome associations. Separately, sensory neurophysiology conceptualizes attention as a filter that improves perception. Here, we show that the contemporary view is incomplete by demonstrating an unconventional and novel effect of perceptual attention on subsequent outcome-based rule learning. Moreover, we show for the first time in rodents that, like in primates, this attentional process involves tuning of modality specific cortico-cortical interactions. We designed a novel head-fixed rat-on-a-treadmill apparatus and used it to train rats to discriminate auditory-visual stimuli using one modality and then reduced stimulus discriminability in that modality. We observed perceptual learning suggesting engagement of perceptual attention. Moreover, engaging visual perceptual attention resulted in more saccades and increased frontal-visual cortex EEG Granger causality relative to engaging auditory perceptual attention. We then presented novel and easily discriminable stimuli in both modalities and measured outcome-driven learning in the other modality. Learning was slower after engaging perceptual attention. Our work suggests that a more complete description of learning requires integrating these previously siloed concepts of attention. Moreover, treating impaired set-shifting as a trans-diagnostic symptom may require targeting different neural circuits for perceptual attention or outcome-based attention depending on which type of attention is impaired in each neuro-psychiatric disorder.

neuroscience↗

Three water restriction schedules used in rodent behavioral tasks transiently impair growth and differentially evoke a stress hormone response without causing dehydration

Water restriction is commonly used to motivate rodents to perform behavioral tasks; however, its on hydration and stress hormone levels are unknown. Here, we report daily body weight and bi-weekly packed red blood cell volume and corticosterone in adult male rats across 80 days for three commonly used water restriction schedules. We also assessed renal adaptation to water restriction using post-mortem histological evaluation of renal medulla. A control group received ad libitum water. After one week of water restriction, rats on all restriction schedules resumed similar levels of growth relative to the control group. Nominal hydration was observed, and water restriction did not drive renal adaptation. An intermittent restriction schedule was associated with an increase in corticosterone relative to the control group. Our results suggest that the water restriction schedules used here will maintain welfare in rats. However, intermittent restriction evokes a stress response which could affect behavioral and neurobiological results. Our results also suggest that stable motivation in behavioral tasks may only be achieved after one week of restriction.

neuroscience↗