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Alesha Usuki - PhD Candidate, Neuroscience PhD Program

Advisor: Dr. Mark Noble

 Dec 20, 2021 @ 1:00 p.m.

Host: The University of Rochester Neuroscience Graduate Program

Michael Duhain - PhD Candidate, Thesis Proposal - Advisers: Manuel Gomex-Ramirez & Kuan Wang

Object sensing and manipulation (i.e. haptics) requires discriminating a myriad of tactile features through the sense of touch. Key to this process are mechanisms of feature-based attention, which provide preferential processing of attended sensory features, while filtering out sensory information encoding non-relevant features. A previous study showed that selection of behaviorally relevant features is represented in the synchronized spiking between neurons tuned for the attended feature. The study further showed that increases in synchronized spiking were associated with enhanced performance. Yet, although this study showed how the brain enables selection of neural signals encoding the relevant features in the somatosensory system, the underlying circuit mechanism generating this feature-specific spike synchrony effect is yet to be elucidated. Fast scale coordinated spiking in neuronal populations is thought to be mediated by the activity of parvalbumin (PV) expressing inhibitory interneurons. Furthermore, in visual cortex, PV neurons are known to selectively respond to visual features (e.g., orientation and spatial frequency). Based on these findings, I propose that feature-specific spike synchrony in the somatosensory system is generated by a parvalbumin (PV) and pyramidal microcircuit (PvPy), whose cells are tuned for the same tactile feature. In this circuit, feature tuned PV interneurons generate inhibition of similarly tuned excitatory cells that is followed by a short window of high spiking probability between feature tuned pyramidal ensembles. I hypothesize that feature selection controls the coordinated spiking dynamics within a PvPy circuit to enhance representations of selected features in local neuronal populations, and facilitate interareal communication between functional subgroups in primary (S1) and secondary (S2) somatosensory cortex. To test the validity of this circuit and its dynamics, I trained mice to perform a 2-alternative forced-choice task that requires a response to a change in vibration frequency of a tactile stimulus delivered to the forepaws. Animals are visually cued to discriminate stimuli at one paw, while ignoring all stimuli at the uncued paw. In aim 1 of this project, I systematically test that the proposed PvPy circuit generates feature-specific spike synchrony effects in S1. In aim 2, I test how feature-specific spike synchrony drives interareal communication between functional subgroups of neurons. These aims will be accomplished in behaving animals through a series of experiments consisting of electrophysiological recordings with multi-laminar electrode arrays, in vivo 2-photon calcium imaging of specific neuronal populations, and optogenetics. Overall, this project aims to critically evaluate the presence of a novel functional circuit (PvPy) within somatosensory cortex that implements feature-based attention to enable preferential processing of selected features within local and across cortical areas.

 Sep 29, 2021 @ 2:00 p.m.

Host: Neuroscience Graduate Program

Johanna Fritzinger - PhD Candidate, Thesis Proposal - Advisor: Laurel Carney, PhD

Timbre, the quality that allows sounds to be distinguished when they are identical in pitch, level, and duration, is a critical aspect of speech comprehension and music enjoyment. My proposal will fill a gap in neural studies of timbre by investigating how underlying mechanisms of encoding lead to robust representations of suprathreshold synthetic and natural instrument timbre in the inferior colliculus (IC). To test our hypotheses, we will record single-unit IC responses from awake Dutch-belted rabbits. We will also develop a new computational IC model based on physiological responses.
The spectral envelope of a harmonic sound is correlated with the timbral perception of “brightness”. We propose two mechanisms that contribute to spectral envelope encoding in the IC: capture and off-characteristic frequency (CF) inhibition. The first mechanism, capture, refers to a reduction of neural fluctuations, or the low-frequency changes in firing rate, of auditory-nerve fibers. Capture occurs when inner-hair-cell responses saturate due to a tone presented near their CF. IC neurons are sensitive to neural fluctuations, as characterized by modulation transfer functions in response to amplitude-modulated sounds. Preliminary results indicate that spectral peaks of synthetic timbre stimuli capture peripheral responses, leading to a rate representation of salient spectral features in the midbrain. The second mechanism is off-CF inhibition, which has been proposed to explain frequency-sweep sensitivity and psychophysical forward masking. Exciting preliminary responses to wideband tone-in-noise stimuli show inhibitory sidebands consistent with off-CF inhibition. A computational model that features capture, but not off-CF inhibition, was not able to predict responses to wideband tone-in-noise, indicating the need to add complexity to the model.
We have designed a set of experiments to test the hypothesis that the timbre of synthetic and instrument sounds is robustly encoded in the midbrain via capture and off-CF inhibition. In Aim 1, we hypothesize that the influences of capture and off-CF inhibition can be teased apart by recording single-unit responses to binaural or contralateral wideband tone-in-noise stimuli. We will update our computational model of the IC by adding off-CF inhibition and fitting the model to physiological responses. Aim 2 will test the hypothesis that the spectral peak of a shaped harmonic complex, synthetic timbre, is robustly encoded in the inferior colliculus over a range of suprathreshold levels. Aim 3 bridges the gap between synthetic and natural timbre by recording physiological responses to real instrument sounds. Responses from Aim 1 and Aim 2 will be used to further test the accuracy of the off-CF inhibition model. This project will provide insight on suprathreshold encoding of timbre, and the computational models created can be used for further research into hearing loss. Currently hearing aids and cochlear implants are not able to convey timbre well, and this research could lead to the improvement of these devices.

 Sep 29, 2021 @ 11:00 a.m.

Host: Neuroscience Graduate Program

Matthew Adusei - PhD Candidate

Thesis Proposal - Advisor: Farran Briggs, PhD

In the visual system, geniculocortical projection neurons in the visual thalamus, the dorsal lateral geniculate nucleus (LGN), convey distinct visual information coming from the retina mainly to the primary visual cortex (V1) (Callaway 2005, Kaplan 2004, Sherman & Guillery 2006). From V1, visual information is passed on to extrastriate cortical areas along the visual cortical hierarchy (Felleman & Van Essen 1991). However, there are sparse V1-bypassing projections from the LGN to extrastriate visual cortical areas which are thought to originate primarily from cells within the koniocellular and C layers of the LGN (Dell et al 2018, Lyon & Rabideau 2012, Lysakowski et al 1988, Sherk 1986, Sincich et al 2004, Tong et al 1982). Visual perception likely involves reciprocal feedback circuits connecting the cortex with the LGN, which complement the feedforward geniculocortical projections. Using virus-mediated retrograde tracing techniques, we have identified and characterized multiple morphologically distinct corticogeniculate subtypes, predominantly in area 17 (V1) and area 18 (V2) (Briggs et al 2016, Hasse et al 2019), as well as in extrastriate visual cortical areas V4, MT and MST in macaques, and area 21a, PMLS, and PLLS, in ferrets. Physiological evidence based on axon conduction latencies and visual responses properties suggests that distinct V1 corticogeniculate subtypes align with the feedforward parallel processing streams (Briggs & Usrey 2005, Briggs & Usrey 2007, Briggs & Usrey 2009). Whether extrastriate corticogeniculate neurons are similarly functionally distinct and stream-specific is not known. Importantly, the presence of complementary, reciprocal, V1-independent connections between the LGN and extrastriate visual cortex, in ferrets and macaques, could provide a substrate for residual vision following V1 damage.
For my thesis project, I will investigate the functional role of the corticogeniculate feedback circuits that connect extrastriate visual areas with the LGN. I will investigate this by pursuing two aims using ferrets as an animal model. The first aim will investigate the functional role of extrastriate corticogeniculate neurons in regulating the activity of LGN neurons in the intact animal using a combination of virus-mediated gene delivery, optogenetics and electrophysiology. I hypothesize that extrastriate corticogeniculate neurons connect to LGN neurons in a stream-specific manner, consistent with our morphological data. I hypothesize that optogenetic activation of extrastriate corticogeniculate neurons will reduce response latencies and increase spike-timing precision among LGN neurons to which they connect. After shorter (~1 week, acute) and longer (~1 month, chronic) durations following V1 lesions, I hypothesize that there will be a progressive increase in the activity of extrastriate corticogeniculate neurons aligned with the W stream (similar to koniocellular stream) compared to intact animals. This hypothesis is supported by results from Schmid et al. (2009) suggesting that the koniocellular V1-bypassing pathway may be strengthened from a modulatory to a driving role post V1-damage. In the second aim, we will explore physiological changes among LGN, PMLS, PLLS, and area 21a neurons over time following V1 lesions. We will train ferrets to discriminate contrast, temporal frequency, spatial frequency, and direction changes among moving visual stimuli. We hypothesize that physiological changes in each area may depend on the type of visual discrimination tasks performed by the animals. Furthermore, we predict that changes in physiological properties of extrastriate corticogeniculate neurons following V1 lesions (observed in Aim 1) may dictate the changes we observe in the LGN and extrastriate areas. Altogether, these results will help us assess the functional significance of sparse extrastriate corticogeniculate projections, and

 Sep 24, 2021 @ 1:00 p.m.

Host: Univ. Rochester Med. Center: The Neuroscience Graduate Program

MaKenna Cealie - PhD Candidate

Thesis Proposal - Advisor: Ania Majewska, PhD

Fetal alcohol spectrum disorders (FASD) are the most common cause of non-heritable, preventable mental disability. It occurs in almost 5% of births in the U.S., leading to a wide range of cognitive, behavioral, and physical impairments. There is no known cure for FASD, and its mechanisms remain unclear.
I will be investigating the cerebellum, as this unique structure is affected in FASD. Deficits in behaviors related to the cerebellum, such as impaired motor coordination and learning, have been discovered after developmental ethanol exposure (Servais et al., 2007; Topper et al., 2015). The changes in behavior may arise from ethanol’s effects on the cellular level. Studies in rodents have found reductions in the number of the neurons that are the sole output of the cerebellum, Purkinje cells, as well as microglia, the immune cells of the Central Nervous System, after developmental ethanol exposure (Goodlett et al., 1990; Kane et al., 2011; Topper et al., 2015). Additionally, ethanol has been shown to alter Purkinje cell excitability and firing (Servais et al., 2007; Zamudio-Bulcock et al., 2014). Microglia, on the other hand, display a phenotype associated with immune activation and release pro-inflammatory factors after developmental ethanol exposure (Topper et al., 2015). Blocking this immune activation with peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists has been shown to attenuate some of the inflammatory responses in microglia and reduce Purkinje cell loss in rodents (Drew et al., 2015; Kane et al., 2011), suggesting that microglia may be a therapeutic target in FASD.
While it is clear that ethanol affects both cerebellar neurons and microglia, it is not yet known when these changes occur and how they are maintained or progressively altered into adulthood. Additionally, while each cell type has been studied individually, how microglia and Purkinje cells interact is also unclear. Microglia are known to shape neuronal circuit development and connectivity in the cerebellum through phagocytosis, synaptic refinement, and modulation of neuronal activity. Elucidating how ethanol-induced changes in microglia mediate some of the pathological changes in cerebellar Purkinje cells may be critical for understanding the onset of FASD pathology. Furthermore, modulating microglial survival and activity during ethanol exposure through PPAR-γ agonists may provide some answers and potential therapies for this disease.
I hypothesize that ethanol induces neuroimmune changes in cerebellar microglia that alter their interactions with Purkinje cells, and reducing microglia-mediated inflammation through PPAR-γ agonists mitigate the pathological effects of ethanol. To test this hypothesis, I will pursue two aims using a mouse model of FASD. The first will investigate how developmental ethanol and a PPAR-γ agonist affects microglial phenotype over time using immunohistochemistry, quantitative real time PCR, and in vivo two-photon imaging of microglial dynamics. This will further our knowledge of the role of microglia and microglia-mediated neuro-immune responses in the onset and propagation of FASD pathology. The second will determine if Purkinje cell and microglia interactions are affected throughout life by developmental ethanol exposure and PPAR-γ agonist administration with immunohistochemistry, electron microscopy, and two-photon imaging. These experiments will elucidate the effects of cerebellar microglia on Purkinje cells in the cerebellum after developmental ethanol exposure and assess microglia as a potential target to mitigate disease pathology in a mouse model of FASD.

 Sep 08, 2021 @ 11:30 a.m.

Host: Univ. Rochester School of Medicine and Dentistry - The Neuroscience Graduate Program

Kathryn-Mary Wakim-Takaki - PhD Candidate, Neuroscience Graduate Program

PhD Thesis Defense
Advisor: John Foxe, PhD

Cocaine use is associated with high-risk sexual practices that accelerate the spread of human immunodeficiency virus (HIV) infection. Substantial literature has demonstrated that active substance use leads to impairment on assessments of executive function. Inhibitory control--the ability to withhold a thought, feeling, or action--is a central construct involved in the minimization of risk-taking behaviors and is frequently blunted both by active substance use and by neurocognitive impairment. While the effects of HIV on the brain are largely progressive, performance in many of the cognitive domains affected by active substance use normalize following drug abstinence. It is unknown whether this same abstinence-related neurocognitive recovery trajectory persists in former users with comorbid HIV. Converging findings from the three studies comprising the current work indicate that HIV+ individuals with a history of cocaine dependence (CD) experience persistent deficits in both inhibitory control capabilities and their underlying neural substrates despite current cocaine-abstinence. These deficits exceed those observed in age-matched HIV+ individuals with no history of substance dependence, as well as age-matched HIV- individuals in recovery from CD. In Chapter 2, I used diffusion tensor imaging (DTI) to understand the effect of combined HIV+ serostatus and former cocaine dependence on cerebral white matter integrity. I observed widespread decreases in diffusion measures across major white-matter tracts in the brain relative to healthy control participants, indicating an extensive neuropathological effect of HIV and former CD on white matter. In Chapters 3 and 4, I investigate the neural substrates of inhibitory control using electroencephalography (EEG) (Chapter 3) and functional magnetic resonance imaging (fMRI) (Chapter 4) as individuals perform a “Go-NoGo” response inhibition task requiring participants to exercise inhibitory control in the presence of drug and non-drug cues. Results from Chapters 3 and 4 indicate complex and interactive alterations in neural activation during response inhibition and highlight the importance of examining the neurocognitive effects of co-morbid conditions. Taken together, these results suggest that abstinence-related recovery of inhibitory control is attenuated in patients with comorbid HIV, suggesting that further or more targeted interventions may be needed to facilitate positive health outcomes in this population.

 Sep 08, 2021 @ 9:30 a.m.

Host: Univ. Rochester School of Medicine and Dentistry - The Neuroscience Graduate Program

Brendan Whitelaw - PhD Candidate
Advisor: Ania Majewska, PhD

Microglia are dynamic cells whose extensive interactions with neurons and glia allow them to regulate neuronal development and function. One way microglia and neurons communicate is through extracellular nucleotides, namely ATP. The microglial P2Y12 receptor is crucial for microglial responsiveness to extracellular ATP and mediates numerous microglial functions, including ATP-dependent directional motility, microglia-neuron interactions, and experience dependent synaptic plasticity. However, little is known about the downstream signaling effectors that mediate these diverse actions of P2Y12. Here, we investigated the intracellular signaling downstream of P2Y12 that drives directed microglial motility. Phosphoinositide-3-kinase gamma (PI3K?), a lipid kinase activated downstream of Gi protein-coupled receptors such as P2Y12, could translate localized extracellular ATP signals into directed microglial action and serve as a broad effector of P2Y12-dependent signaling. While pan-inhibition of all PI3K activity substantially affected P2Y12-dependent microglial responses, our results suggest that PI3K? specifically was only a minor part of the P2Y12 signaling pathway. Loss or inhibition of PI3K? had subtle effects on microglial response to ATP, but did not affect baseline microglial dynamics or P2Y12-dependent synaptic plasticity. We then tested alternative signaling pathways that could bridge P2Y12 activation and directed microglial motility. Inhibition phospholipase C, activated in parallel to PI3K? by Gi signaling, had no effect. Many aspects of cellular motility are controlled by the Rho-family GTPases, RhoA, Rac, and Cdc42, considered master regulators of cytoskeletal dynamics. However, inhibition of each of these proteins, separately or in combination, had no effect on directed microglial motility. Targeting additional fundamental regulators of actin dynamics, Arp2/3, formin, and myosin, had little effect either. Overall, the directed microglial process response to focal ATP was remarkably insensitive to pharmacological inhibitors of several common signaling pathways associated with cellular motility, including those required for ATP-mediated microglial chemotaxis in vitro. To better understand the structure of microglial processes while moving towards an ATP source, we developed a method to take a ‘snapshot’ of microglia responding to a focal injury in vivo. These new methods will help target future physiological studies. Overall, we found that microglial process dynamics are governed by a complex intracellular pathway that cannot be extrapolated from in vitro microglial experiments or studies performed in other immune cells.

 May 20, 2021 @ 10:00 a.m.

Linh Le - PhD Candidate
Advisors: Ania Majewska, PhD and Kerry O'Banion, MD, PhD

 May 07, 2021 @ 1:00 p.m.

Holly Beaulac - PhD Candidate
Advisor: Pat White, PhD

Approximately 16% of global cases of adult-onset hearing loss are attributable to excessive, occupational noise exposure. The prevalence of noise-induced hearing loss (NIHL) continues to increase with limited therapeutic options available. By studying the underlying pathology of NIHL using genetic loss-of-function models, it is possible to identify genes that contribute to hearing loss susceptibility. FOXO3 is a forkhead transcription factor involved in several cellular processes including growth, survival, stress resistance, apoptosis, and longevity. My lab has previously established a role for FOXO3 in preserving outer hair cells (OHCs) and hearing thresholds following a mild noise exposure in mice. I hypothesized that in the absence of FOXO3, reactive oxygen species would accumulate in response to noise exposure and lead to OHC apoptosis. I analyzed the immediate effect of mild noise exposure on wild-type, Foxo3 heterozygous (Foxo+/KO), and Foxo3 knock-out (Foxo3KO/KO) FVB mice. Well-characterized components of noise-induced damage including calcium regulation, oxidative stress, inflammation, apoptosis, necrosis, and parthanatos were examined. In the Foxo3KO/KO mouse, dynamic immunoreactive modulation of the calcium buffer oncomodulin was correlated with OHC loss beginning 4 hours post-noise exposure. Parthanatos was identified as the main cell death pathway for OHCs. In opposition to my hypothesis, oxidative stress response pathways were not significantly altered. Using RNA sequencing I identified differentially expressed genes and examined one whose role in the cochlea has not been described. Glycerophosphodiester Phosphodiesterase Domain Containing 3 (GDPD3) is a possible source of Lysophosphatidic acid (LPA). LPA has been demonstrated to prevent OHC loss after severe noise exposure. When I treated noise-exposed animals with LPA, immediate OHC damage was reduced but no long-term prevention of cell death and hearing loss was observed. These data suggest that FOXO3 acts prior to acoustic insult to maintain cochlear resilience, in part through interaction with GDPD3 to help sustain endogenous LPA levels. Continuing work includes examining FOXO3’s cell-specific importance and recapitulating the NIHL susceptibility linked to human single nucleotide polymorphisms (SNPs) associated with increased FOXO3 levels.

 Apr 26, 2021 @ 10:00 a.m.

Host: Univ. Rochester School of Medicine and Dentistry
The Neuroscience Graduate Program

Humberto Mestre - PhD Candidate
Advisor: Maiken Nedergaard, M.D., D.M.Sc.

Water is the principal component of all biological tissues. The brain is not an exception to this rule and has one of the highest water contents of any tissue type. Normal brain function depends on the precise balance within all the different fluid compartments that include intracellular and extracellular fluid, cerebrospinal fluid (CSF), and cerebral blood volume. When any one of these compartments becomes deranged, such as in cerebral edema, any abnormal accumulation of fluid can lead to herniation and death. The mammalian brain has evolved a global network of fluid conduits surrounding the blood vessels that perfuse it to allow for the rapid exchange of brain fluids. These perivascular spaces serve a multitude of roles in central nervous system physiology and form the basis for the glymphatic system. The flow of CSF through the glymphatic system aids in the clearance of metabolic waste from the parenchyma serving the role of the brain’s lymphatic system. This thesis aimed to understand the mechanisms that regulate flow within the brain. Chapter two of this thesis aimed to determine the anatomical structure and geometry of perivascular spaces in the murine brain. We developed a novel imaging modality to quantify flow within perivascular spaces for the first time. This technique demonstrated that perivascular fluid flow is pumped by arterial pulsations driven by the cardiac cycle and that arterial hypertension disrupts effective pumping slowing the flow. In chapter three, we developed a mesoscopic imaging platform to show that perivascular fluid enters the brain secondary to changes in plasma osmolarity. We then exploited this finding to improve the delivery of a monoclonal antibody targeted against amyloid plaques used in the treatment of Alzheimer’s disease. Astrocytes ensheathe virtually all cerebral blood vessels, forming the outside wall of the perivascular spaces. Their endfeet express high levels of the water channel aquaporin-4 (AQP4) and this unique, polarized distribution increases the influx of CSF to the brain. In chapter four we evaluated the dependence of perivascular transport on AQP4 expression uniting efforts with four independent research groups and using five different AQP4 knockout rodent lines to confirm the dependence of brain fluid transport on AQP4. In chapter five, we leveraged the newly developed imaging modalities from chapter two and three to evaluate how acute cerebrovascular diseases contribute to abnormal fluid flow within the brain. Mainly, we tested how acute ischemic stroke enhanced perivascular inflow of CSF to the brain. This abnormal state of fluid inflow caused the detrimental accumulation of CSF and triggered the onset of edema formation. More importantly, we identified that knocking out AQP4 reduced this effect and protected against edema fluid accumulation after stroke. The results of the present thesis provide novel insights into the principles governing fluid transport in the mammalian brain and developed innovative imaging techniques to further evaluate them. The goal of gaining further insight into these processes is to ultimately use our newly gained understanding to develop novel therapeutic interventions.

 Apr 12, 2021 @ 9:00 a.m.

Host: University of Rochester School of Medicine and Dentistry
The Neuroscience Graduate Program

Colin Lockwood - PhD Candidate
Advisor: Charles Duffy, MD, PhD

Self-movement creates a radial pattern of optic flow that tells us where we are going. Navigation-related optic flow perceptual deficits in aging and Alzheimer’s Disease (AD) suggest a combination of visual perceptual deficits and loss of attentional control of visual processing. We have examined these deficits using human evoked potentials to elucidate these deficits and tried to replicate and expand on these mechanisms through recorded monkey evoked potentials.
In our studies of aging and AD, we combined optic flow discrimination with cued spatial attention to assess the effects of shifting attention on optic flow perceptual deficits. We find diminished attentional effects in aging and loss of attentional effects in AD coupled with delayed responses in aging and increased failures of navigation in AD. In addition, aging leads to a loss of coherence in late evoked potentials and an increase in power in early perceptual evoked potentials. However, in AD there is no increase in early evoked potentials leading to decreased responses throughout the task. Thus, aging is associated with increased visual processing and decreased attentional control, while AD is associated with a loss of attentional control and diminished optic flow responses.
Monkeys trained in the same visuo-spatial attentional optic flow discrimination task evoke homologous responses to humans. However, differences in monkey behavior may shed light into different attentional strategies used to complete the task. The monkey that exhibits behavior similar to young people in the task has correspondingly strong attentional evoked potentials. Another monkey who exhibits behavior that suggests a more perceptual strategy has neurophysiological responses similar to those seen in aging. While monkey neurophysiology closely resembles humans, differences between monkeys provide insight into the mechanisms of optic flow deficits in aging and AD.
Despite the differences in species, evoked potentials recorded in both humans and monkeys clearly demonstrate early sensory signals followed closely by cognitive signals that modulate self-movement perception. In aging and in a monkey with a perceptual strategy we see a decrease in the cognitive signals coupled with an increase in the power of sensory signals. In AD the loss of cognitive signals is accompanied by a decrease in the power of the sensory signals, leading to increased failure of optic flow discrimination and navigation.

 Mar 29, 2021 @ 9:00 a.m.

Host: Univ. Rochester School of Medicine and Dentistry
The Neuroscience Graduate Program

Emily Przysinda - PhD Candidate
Advisors: Ed Lalor, PhD and David Dodell-Feder, PhD

Schizophrenia is a chronic and complex disorder with many symptoms, including the hallmark symptoms of hallucinations and delusions that can distort perception of reality. Medications primarily address these positive symptoms, and thus negative symptoms such as anhedonia and social difficulties can cause significant functional impairment for these patients. More research examining how these social difficulties manifest in the brain is needed, especially research utilizing naturalistic stimuli that can mimic real life. Here we use naturalistic paradigms, episodes of TV show, The Office, as our stimuli, because it captures a rich variety of social interactions including some that may be violating social norms. In addition, this experimental design is rich with potential stimulus parameters that we can quantify and relate to the neural signals, including lower-level of perceptual domains such as language and vision. Given that patients with schizophrenia are known to have lower-level perceptual deficits, it will be important to explore how these deficits may impact measures of social cognition. Here, we will use two complementary neuroimaging imaging modalities to examine social brain network differences in patients with schizophrenia and how more basic perceptual deficits may be influencing these measures. Aim 1 will use functional magnetic resonance imaging (fMRI) techniques to characterize neural dynamics of social processing deficits in schizophrenia. We will first explore various lower level perceptual processes during these stimuli utilizing a general linear model approach (GLM). Next, we will utilize GLMs involving social parameters and effective connectivity determined by dynamic causal modeling (DCM) that will allow us to characterize social neural dynamics and explore how these measures may be influenced by lower level sensory processing deficits. Aim 2 will characterize neural dynamics of social processing deficits in schizophrenia using electroencephalography (EEG) across multiple episodes of The Office with various social tasks. We will explore how lower-level features of the stimulus are related to the neural signals using a temporal response function approach. Using the spatially informed models from structural MRI, we will examine social neural dynamics in an analogous way to fMRI with TRFs and DCM analyses. We aim to recruit the same participants for aim one and two, so we can capitalize on the strengths of both methods and examine how these measures may be providing both converging and diverging information about social processing deficits in schizophrenia. We hope that this research can be used to inform future research for biomarkers of mental illness and ultimately improve healthcare outcomes for patients with schizophrenia.

 Mar 04, 2021 @ 9:00 a.m.

Host: Neuroscience Graduate Program