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Abstract We investigated whether prestimulus alpha-band oscillatory activity and stimulus-elicited recurrent processing interact to facilitate conscious visual perception. Participants tried to perceive a visual stimulus that was perceptually masked through object substitution masking (OSM). We showed that attenuated prestimulus alpha power was associated with greater negative-polarity stimulus-evoked ERP activity that resembled the visual awareness negativity (VAN), previously argued to reflect recurrent processing related to conscious perception. This effect, however, was not associated with better perception. Instead, when prestimulus alpha power was elevated, a preferred prestimulus alpha phase was associated with a greater VAN-like negativity, which was then associated with better cue perception. Cue perception was worse when prestimulus alpha power was elevated but the stimulus occurred at a nonoptimal prestimulus alpha phase and the VAN-like negativity was low. Our findings suggest that prestimulus alpha activity at a specific phase enables temporally selective recurrent processing that facilitates conscious perception in OSM.

The most common complication in older surgical patients is postoperative delirium (POD). POD is associated with preoperative cognitive impairment and longer durations of intraoperative burst suppression (BSup) – electroencephalography (EEG) with repeated periods of suppression (very low-voltage brain activity). However, BSup has modest sensitivity for predicting POD. We hypothesized that a brain state of lowered EEG power immediately precedes BSup, which we have termed “pre-burst suppression” (preBSup). Further, we hypothesized that even patients without BSup experience these preBSup transient reductions in EEG power, and that preBSup (like BSup) would be associated with preoperative cognitive function and delirium risk. Data included 83 32-channel intraoperative EEG recordings of the first hour of surgery from 2 prospective cohort studies of patients ≥age 60 scheduled for ≥2-h non-cardiac, non-neurologic surgery under general anesthesia (maintained with a potent inhaled anesthetic or a propofol infusion). Among patients with BSup, we defined preBSup as the difference in 3–35 Hz power (dB) during the 1-s preceding BSup relative to the average 3–35 Hz power of their intraoperative EEG recording. We then recorded the percentage of time that each patient spent in preBSup, including those without BSup. Next, we characterized the association between percentage of time in preBSup and (1) percentage of time in BSup, (2) preoperative cognitive function, and (3) POD incidence. The percentage of time in preBSup and BSup were correlated (Spearman’s ρ [95% CI]: 0.52 [0.34, 0.66], p < 0.001). The percentage of time in BSup, preBSup, or their combination were each inversely associated with preoperative cognitive function (β [95% CI]: −0.10 [−0.19, −0.01], p = 0.024; −0.04 [−0.06, −0.01], p = 0.009; −0.04 [−0.06, −0.01], p = 0.003, respectively). Consistent with prior literature, BSup was significantly associated with POD (odds ratio [95% CI]: 1.34 [1.01, 1.78], p = 0.043), though this association did not hold for preBSup (odds ratio [95% CI]: 1.04 [0.95, 1.14], p = 0.421). While all patients had ≥1 preBSup instance, only 20.5% of patients had ≥1 BSup instance. These exploratory findings suggest that future studies are warranted to further study the extent to which preBSup, even in the absence of BSup, can identify patients with impaired preoperative cognition and/or POD risk.

Physiologic signals such as the electroencephalogram (EEG) demonstrate irregular behaviors due to the interaction of multiple control processes operating over different time scales. The complexity of this behavior can be quantified using multi-scale entropy (MSE). High physiologic complexity denotes health, and a loss of complexity can predict adverse outcomes. Since postoperative delirium is particularly hard to predict, we investigated whether the complexity of preoperative and intraoperative frontal EEG signals could predict postoperative delirium and its endophenotype, inattention. To calculate MSE, the sample entropy of EEG recordings was computed at different time scales, then plotted against scale; complexity is the total area under the curve. MSE of frontal EEG recordings was computed in 50 patients ≥ age 60 before and during surgery. Average MSE was higher intra-operatively than pre-operatively (p = 0.0003). However, intraoperative EEG MSE was lower than preoperative MSE at smaller scales, but higher at larger scales (interaction p < 0.001), creating a crossover point where, by definition, preoperative, and intraoperative MSE curves met. Overall, EEG complexity was not associated with delirium or attention. In 42/50 patients with single crossover points, the scale at which the intraoperative and preoperative entropy curves crossed showed an inverse relationship with delirium-severity score change (Spearman ρ = −0.31, p = 0.054). Thus, average EEG complexity increases intra-operatively in older adults, but is scale dependent. The scale at which preoperative and intraoperative complexity is equal (i.e., the crossover point) may predict delirium. Future studies should assess whether the crossover point represents changes in neural control mechanisms that predispose patients to postoperative delirium.

Attention can be involuntarily biased toward reward-associated distractors (value-driven attentional capture, VDAC). Yet past work has primarily demonstrated this distraction phenomenon during a particular set of circumstances: transient attentional orienting to potentially relevant stimuli occurring in our visual environment. Consequently, it is not well-understood if reward-based attentional capture can occur under other circumstances, such as during sustained visuospatial attention. Using EEG, we investigated whether associating transient distractors with reward value would increase their distractibility and lead to greater decrements in concurrent sustained spatial attention directed elsewhere. Human participants learned to associate three differently colored, laterally presented squares with rewards of varying magnitude (zero, small, and large). These colored squares were then periodically reintroduced as distractors at the same lateral locations during a demanding sustained-attention rapid-serial-visual-presentation (RSVP) task at the midline. Behavioral and neural evidence indicated that participants had successfully learned and maintained the reward associations to the distractors. During the RSVP task, consistent with prior work, we found that the distractors generated dips in the instantaneous amplitude of the steady-state visual evoked potentials (SSVEPs) elicited by the midline RSVP stimuli, indicating that the distractors were indeed transiently disrupting sustained spatial attention. Contrary to our hypotheses, however, the magnitude of this dip did not differ by the magnitude of the distractor’s reward associations. These results indicate that while sustained spatial attention can be impaired by the introduction of distractors at another location, the main distraction process is resistant to the distractors’ reward associations, thus providing evidence of an important boundary condition to value-driven attentional capture.

In our daily lives, we continuously evaluate feedback information, update our knowledge, and adapt our behavior in order to reach desired goals. This ability to learn from feedback information, however, declines with age. Previous research has indicated that certain higher-level learning processes, such as feedback evaluation, integration of feedback information, and updating of knowledge, seem to be affected by age, and recent studies have shown how the adaption of choice behavior following feedback can differ with age. The neural mechanisms underlying this age-related change in choice behavior during learning, however, remain unclear. The aim of this study is therefore to investigate the relation between learning-related neural processes and choice behavior during feedback learning in two age groups. Behavioral and fMRI data were collected, while a group of young (age 18–30) and older (age 60–75) adults performed a probabilistic learning task consisting of 10 blocks of 20 trials each. On each trial, the participants chose between a house and a face, after which they received visual feedback (loss vs. gain). In each block, either the house or the face image had a higher probability of yielding a reward (62.5 vs. 37.5%). Participants were instructed to try to maximize their gains. Our results showed that less successful learning in older adults, as indicated by a lower learning rate, corresponded with a higher tendency to switch to the other stimulus option, and with a reduced adaptation of this switch choice behavior following positive feedback. At the neural level, activation following positive and negative feedback was found to be less distinctive in the older adults, due to a smaller feedback-evaluation response to positive feedback in this group. Furthermore, whereas young adults displayed increased levels of knowledge updating prior to adapting choice behavior, we did not find this effect in older adults. Together, our results suggest that diminished learning performance with age corresponds with diminished evaluation of positive feedback and reduced knowledge updating related to changes in choice behavior, indicating how such differences in feedback processing at the trial level in older adults might lead to reduced learning performance across trials.

While parietal cortex is thought to be critical for representing numerical magnitudes, we recently reported an event-related potential (ERP) study demonstrating selective neural sensitivity to numerosity over midline occipital sites very early in the time course, suggesting the involvement of early visual cortex in numerosity processing. However, which specific brain area underlies such early activation is not known. Here, we tested whether numerosity-sensitive neural signatures arise specifically from the initial stages of visual cortex, aiming to localize the generator of these signals by taking advantage of the distinctive folding pattern of early occipital cortices around the calcarine sulcus, which predicts an inversion of polarity of ERPs arising from these areas when stimuli are presented in the upper versus lower visual field. Dot arrays, including 8–32 dots constructed systematically across various numerical and non-numerical visual attributes, were presented randomly in either the upper or lower visual hemifields. Our results show that neural responses at about 90 ms post-stimulus were robustly sensitive to numerosity. Moreover, the peculiar pattern of polarity inversion of numerosity-sensitive activity at this stage suggested its generation primarily in V2 and V3. In contrast, numerosity-sensitive ERP activity at occipito-parietal channels later in the time course (210–230 ms) did not show polarity inversion, indicating a subsequent processing stage in the dorsal stream. Overall, these results demonstrate that numerosity processing begins in one of the earliest stages of the cortical visual stream.

Each year over 16 million older Americans undergo general anesthesia for surgery, and up to 40% develop postoperative delirium and/or cognitive dysfunction (POCD). Delirium and POCD are each associated with decreased quality of life, early retirement, increased 1-year mortality, and long-term cognitive decline. Multiple investigators have thus suggested that anesthesia and surgery place severe stress on the aging brain, and that patients with less ability to withstand this stress will be at increased risk for developing postoperative delirium and POCD. Delirium and POCD risk are increased in patients with lower preoperative cognitive function, yet preoperative cognitive function is not routinely assessed, and no intraoperative physiological predictors have been found that correlate with lower preoperative cognitive function. Since general anesthesia causes alpha-band (8–12 Hz) electroencephalogram (EEG) power to decrease occipitally and increase frontally (known as “anteriorization”), and anesthetic-induced frontal alpha power is reduced in older adults, we hypothesized that lower intraoperative frontal alpha power might correlate with lower preoperative cognitive function. Here, we provide evidence that such a correlation exists, suggesting that lower intraoperative frontal alpha power could be used as a physiological marker to identify older adults with lower preoperative cognitive function. Lower intraoperative frontal alpha power could thus be used to target these at-risk patients for possible therapeutic interventions to help prevent postoperative delirium and POCD, or for increased postoperative monitoring and follow-up. More generally, these results suggest that understanding interindividual differences in how the brain responds to anesthetic drugs can be used as a probe of neurocognitive function (and dysfunction), and might be a useful measure of neurocognitive function in older adults.

OBJECTIVES/SPECIFIC AIMS: The objective of this project is to determine whether HRV, collected peri-operatively, is predictive of cognitive decline among older adults who undergo elective surgery/anesthesia. METHODS/STUDY POPULATION: This project is a part of the ongoing INTUIT/PRIME study, which is collecting pre- and post-operative cognitive testing, fMRI imaging, CSF samples, and EEG recordings from 200 older adults (age ≥ 60) undergoing elective non-cardiac/non-neurologic surgery scheduled to last > 2 hours at Duke University Medical Center and Duke Regional Hospital. This project utilizes data from the first 60 INTUIT participants who contributed continuous heart rate data before and during surgery. Participants undergo cognitive testing prior to surgery (baseline) and at 6 weeks after surgery. Our primary dependent variable is the change in the composite score from baseline to 6-weeks. Delirium is assessed in the hospital with the twice daily 3D-CAM tool, so we will report the proportion of individuals with 6-week cognitive decline who exhibited delirium in the days following surgery. Participants’ echocardiogram (ECG) recordings are extracted pre- and intraoperatively from B650/B850 patient monitors with VSCapture software. HRV is defined as the variability between successive R-spikes or inter-beat-intervals on ECG. RESULTS/ANTICIPATED RESULTS: We anticipate that lower intraoperative HRV is associated with worse cognitive decline at 6 weeks after surgery. As secondary objectives, we will determine whether pre-operative HRV or change in HRV (from pre-operative to intra-operative measures) are predictive of cognitive decline after surgery. We expect that in-hospital delirium will be detected in a higher proportion of those with 6-week cognitive decline, compared to those with stable or improved cognition at 6 weeks. DISCUSSION/SIGNIFICANCE OF IMPACT: HRV may address the present need for pre- and intra-operative cognitive risk stratification in the elderly. Physiological indices like HRV have the potential to dramatically change our understanding of CI in older adults undergoing surgery, as they offer an accessible, cost-effective, and non-invasive means whereby clinicians, particularly those unfamiliar with the nuances of geriatric and CI/dementia-related care, can monitor patients and refer those at high-risk of CI after surgery for early intervention.

In a previous functional magnetic resonance (fMRI) study, a subdivision of the human auditory cortex into four distinct territories was achieved. One territory (T1a) exhibited functional specialization in terms of a foreground-background decomposition task involving matching-to-sample monitoring on tone sequences. The present study more specifically determined whether memory-guided analysis of tone sequences is part of the T1a specialization. During the encoding periods, an arbitrary and unfamiliar four-tone-sequence (melody) played by one instrument was presented. The melody-instrument-combination was different in each period. During subsequent retrieval periods, learned and additional combinations were presented, and the tasks were either to detect the target melodies (experiment I) or the target instruments (experiment II). T1a showed larger activation during the melody retrieval. The results generally suggest that (1) activation of T1a during retrieval is determined less by the sound material than by the executed task, and (2) more specifically, that memory-guided sequential analysis in T1a is dominant over recognition of characteristic complex sounds.