Eena L. Kosik’s research while affiliated with University of California, San Diego and other places

Undergraduate research programs improve career outcomes for historically marginalized students in the US, but low retention rates in postgraduate research persist. As graduate students and postdocs, we present a combination of trainee-informed approaches for tailoring summer research programs to these students’ needs and share key materials to facilitate adoption of these approaches at other institutions.

In March 2014, a team of cosmologists made headlines around the world when they reported possible evidence for cosmic inflation – an extremely short period during which the universe rapidly expanded immediately after the Big Bang (Ade et al., 2014). However, it later emerged that some of the signal this result was based on had been produced by something seemingly quite insignificant: cosmic dust (Cowen, 2015). This episode underscored how small, apparently innocuous factors can have colossal implications when studying the universe. The same is true in neuroscience, with perhaps even higher stakes.

The human face plays a central role in emotions and social communication. The emotional and somatic motor networks generate facial behaviors, but whether facial behaviors have representations in the structural anatomy of the human brain is unknown. We coded 16 facial behaviors in 55 healthy older adults who viewed five videos that elicited emotions and examined whether individual differences in facial behavior related to regional variation in gray matter volume. Voxel-based morphometry analyses revealed that greater emotional facial behavior during the disgust trial (i.e., greater brow furrowing and eye tightening as well as nose wrinkling and upper lip raising) and the amusement trial (i.e., greater smiling and eye tightening) was associated with larger gray matter volume in midcingulate cortex, supplementary motor area, and precentral gyrus, areas spanning both the emotional and somatic motor networks. When measured across trials, however, these facial behaviors (and others) only related to gray matter volume in the precentral gyrus, a somatic motor network hub. These findings suggest that the emotional and somatic motor networks store structural representations of facial behavior, and that the midcingulate cortex is critical for generating the predictable movements in the face that arise during emotions.

BACKGROUND Sleep-disordered breathing (SDB) is common and associated with worse cardiovascular and brain health. Hispanic/Latino individuals are at increased risk for SDB. OSA is the most studied SDB; it is characterized by apnea-hypopnea events and has been linked to adverse vascular health and cognitive sequelae. Less is known about upstream factors such as parameters of breathing. Breathing dynamics such as breathing rate and breathing rate variability have been linked to changes in mood and oscillatory brain activity. Their relationships with cognitive performance, particularly in diverse and understudied Hispanic/Latino communities, are unknown. RESEARCH QUESTION What is the association between parameters of breathing and cognitive outcomes? STUDY DESIGN AND METHODS The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a prospective study of diverse Hispanic/Latino subjects. Individuals were given an ARES monitor for in-home sleep testing. Breathing information was extracted from the cannula channel, and parameters of breathing were calculated by using bycycle, a novel tool for time series analysis. A total of 6,737 individuals were included in the study. RESULTS Faster breathing rate was linked with worse domain-specific and global cognitive performance (bglobal = −0.011; P < .01), and breathing rate variability was associated with worse global cognitive performance (βglobal = −0.022; P < .05). In interaction models, breathing rate variability was found to be significantly associated with worse verbal fluency and global cognitive performance in women but not in men. INTERPRETATION Parameters of breathing are novel methods for understanding SDB and cognitive function. These results also suggest that faster breathing rate variability in women, but not in men, is related to worse cognitive function.

Background Sleep disorders are common in patients with Alzheimer’s Disease (AD). Obstructive sleep apnea (OSA), characterized by intermittent cessation of breathing and hypoxemia, has been associated with increased risk of AD and worse cognitive function. However, the interacting effects of neurocognitive function with sleep breathing patterns, independent of the apnea‐hypopnea index, (a measure of OSA severity) have not been carefully studied. We use a novel approach to analyzing home sleep apnea data to examine breathing patterns and their relationships with neurocognitive function. Method The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a prospective multicenter study of diverse Latinos. Around 16,000 diverse Hispanic/Latinos were recruited from four major metropolitan cities. Participants used an ARES unirecorder device for a single night of unsupervised at home recording. We used python package “bycycle” to cannula data (sampled at 10Hz). Bycycle uses a time domain approach to parameterizing rhythmic time‐series data. We extracted breathing rate (breaths per minute), breathing variability (interquartile range of breathing rate) and time spent in inhalation phase (percent time). Participants ages ≥45 (unweighted n = 5,957) were tested in their preferred language using a brief battery including: B‐SEVLT (3‐trials sum) and Delayed Recall (memory), World Fluency (verbal fluency), and Digit Symbol Substitution (executive function). Covariates used in our models are described in Table 1. All presented estimates were weighted for appropriate generalization to the HCHS/SOL target population. Result In unadjusted models, all breathing measures were negatively associated with cognitive function, but only breathing rate remained significant after full covariate adjustment (Figure 1). We found significant interactions between breathing rate and sex, as well as age for verbal fluency models. Being female and older age were associated with steeper slopes of cognitive under‐performance for both breathing rate and breathing variability (Figure 2). Conclusion These results suggest that breathing patterns outside apneas‐hypopneas may be as critical in understanding sleep related changes and cognitive function in an aging population. Given cessation of breathing during an apnea‐hypopnea event, breathing variability may add more precision to account for varying oxygen demands. Further studies should examine whether breathing instability is also associated with cognitive decline, impairment, and dementia.

Major depressive disorder (MDD) is a leading cause of disability worldwide. One of the most efficacious treatments for treatment-resistant MDD is electroconvulsive therapy (ECT). Recently, magnetic seizure therapy (MST) was developed as an alternative to ECT due to its more favorable side effect profile. While these approaches have been very successful clinically, the neural mechanisms underlying their therapeutic effects are unknown. For example, clinical “slowing” of the electroencephalogram beginning in the postictal state and extending days to weeks post-treatment has been observed in both treatment modalities. However, a recent longitudinal study of a small cohort of ECT patients revealed that, rather than delta oscillations, clinical slowing was better explained by increases in aperiodic activity, an emerging EEG signal linked to neural inhibition. Here we investigate the role of aperiodic activity in a cohort of patients who received ECT and a cohort of patients who received MST treatment. We find that aperiodic neural activity increases significantly in patients receiving either ECT or MST. Although not directly related to clinical efficacy in this dataset, increased aperiodic activity is linked to greater amounts of neural inhibition, which is suggestive of a potential shared neural mechanism of action across ECT and MST.

In semantic dementia (SD), asymmetric degeneration of the anterior temporal lobes is associated with loss of semantic knowledge and alterations in socioemotional behavior. There are two clinical variants of SD: semantic variant primary progressive aphasia (svPPA), which is characterized by predominant atrophy in the anterior temporal lobe and insula in the left hemisphere, and semantic behavioral variant frontotemporal dementia (sbvFTD), which is characterized by predominant atrophy in those structures in the right hemisphere. Previous studies of behavioral variant frontotemporal dementia, an associated clinical syndrome that targets the frontal lobes and anterior insula, have found impairments in baseline autonomic nervous system activity that correlate with left-lateralized frontotemporal atrophy patterns and disruptions in socioemotional functioning. Here, we evaluated whether there are similar impairments in resting autonomic nervous system activity in SD that also reflect left-lateralized atrophy and relate to diminished affiliative behavior. A total of 82 participants including 33 people with SD (20 svPPA and 13 sbvFTD) and 49 healthy older controls completed a laboratory-based assessment of respiratory sinus arrhythmia (RSA; a parasympathetic measure) and skin conductance level (SCL; a sympathetic measure) during a two-minute resting baseline period. Participants also underwent structural magnetic resonance imaging, and informants rated their current affiliative behavior on the Interpersonal Adjective Scale. Results indicated that baseline RSA and SCL were lower in SD than in healthy controls, with significant impairments present in both svPPA and sbvFTD. Voxel-based morphometry analyses revealed left-greater-than-right atrophy related to diminished parasympathetic and sympathetic outflow in SD. While left-lateralized atrophy in the mid-to-posterior insula correlated with lower RSA, left-lateralized atrophy in the ventral anterior insula correlated with lower SCL. In SD, lower baseline RSA, but not lower SCL, was associated with lower gregariousness/extraversion. Neither autonomic measure related to warmth/agreeableness, however. Through the assessment of baseline autonomic nervous system physiology, the present study contributes to expanding conceptualizations of the biological basis of socioemotional alterations in svPPA and sbvFTD.

Individuals with high emotional granularity make fine-grained distinctions between their emotional experiences. To have greater emotional granularity, one must acquire rich conceptual knowledge of emotions and use this knowledge in a controlled and nuanced way. In the brain, the neural correlates of emotional granularity are not well understood. While the anterior temporal lobes, angular gyri, and connected systems represent conceptual knowledge of emotions, inhibitory networks with hubs in the inferior frontal cortex (i.e., posterior inferior frontal gyrus, lateral orbitofrontal cortex, and dorsal anterior insula) guide the selection of this knowledge during emotions. We investigated the structural neuroanatomical correlates of emotional granularity in 58 healthy, older adults (ages 62–84 years), who have had a lifetime to accrue and deploy their conceptual knowledge of emotions. Participants reported on their daily experience of 13 emotions for 8 weeks and underwent structural magnetic resonance imaging. We computed intraclass correlation coefficients across daily emotional experience surveys (45 surveys on average per participant) to quantify each participant’s overall emotional granularity. Surface-based morphometry analyses revealed higher overall emotional granularity related to greater cortical thickness in inferior frontal cortex ( p FWE < 0.05) in bilateral clusters in the lateral orbitofrontal cortex and extending into the left dorsal anterior insula. Overall emotional granularity was not associated with cortical thickness in the anterior temporal lobes or angular gyri. These findings suggest individual differences in emotional granularity relate to variability in the structural neuroanatomy of the inferior frontal cortex, an area that supports the controlled selection of conceptual knowledge during emotional experiences.

Introduction Obesity and or obstructive sleep apnea (OSA) can impact awake breathing patterns, such as increments in the breathing rate. However, little is known about their associations with breathing dysregulations during sleep beyond the apnea-hypopnea events. Understanding this could help elucidate treatment mechanisms or different pathways for disease. Furthermore, there is a strong connection between breathing patterns and cardiovascular disease, thus it is also critical to understand the links between cardiovascular risk factors and disease (CVD) and sleep breathing patterns. Methods The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a prospective multicenter study of diverse Latinos. A total of N=16,415 participants from four major metropolitan areas and six different Hispanic/Latino backgrounds were sampled for appropriate generalization to the target population. Participants were given an ARES unirecorder device (Carlsbad, San Diego) for a single night of unsupervised at home recording (N=12,022). Raw data from cannula channel (sampled at 10Hz) was processed using the python Bycycle package. Bycycle is a cycle-by-cycle approach to analyzing time series data. Bycycle finds all peaks and throughs in cycles and allows users to extract time dependent information of cycles. We extracted breathing rate (breaths per minute), breathing variability (interquartile range of breathing rate) and time spent in inhalation phase (percent time). Results In multivariable models (N=10,175), age was linked to decreased breathing rate, breathing variability, and time spent in inhalation phase. Compared to females, males had higher breathing variability and spent more time in the inhalation phase. Compared to Mexicans and? Central Americans, Cubans, Dominicans, and Puerto Ricans had less time spent in inhalation phase. Dominicans and Puerto Ricans also had increased breathing rate compared to Mexicans. Smoking, body mass index, and moderate to severe OSA were associated with increased breathing rate and variability. Systolic, but not diastolic blood pressure, was associated with increased breathing rate. We found no significant associations with cardiovascular disease. Conclusion Factors commonly linked to OSA were associated with increased breathing rate, a compensatory mechanism for optimal oxygenation, and breathing variability. Given cessation or reduced breathing during an apnea-hypopnea event, breathing variability may add more precision to account for varying oxygen demands. Support (if any)

Major depressive disorder (MDD) is a leading cause of disability worldwide. One of the most efficacious treatments for treatment-resistant MDD is electroconvulsive therapy (ECT). Recently, magnetic seizure therapy (MST) was developed as an alternative to ECT due to its more favorable side effect profile. While these approaches have been very successful clinically, the neural mechanisms underlying their therapeutic effects are unknown. For example, clinical slowing of the electroencephalogram has been observed in both treatment modalities. A recent longitudinal study of a small cohort of ECT patients revealed that observed clinical slowing was better explained by increases in frontal aperiodic activity, an emerging EEG signal linked to neural inhibition. Here we investigate the role of aperiodic activity in a cohort of patients who received ECT and a cohort of patients who received MST treatment. We find that across treatments, frontal aperiodic activity better explains increases in delta band power associated with clinical slowing, compared to delta oscillations. Increased aperiodic activity is also linked to therapeutic efficacy, which is suggestive of a potential shared neural mechanism of action across ECT and MST: an increase in frontal inhibitory activity.