Glioblastoma (GBM) is the most common aggressive primary malignant brain tumorin adults with a median age of onset of 65 years of age. Although advanced age is often associated with worse GBM patient survival, the predominant source(s) of maladaptive aging
effects remains to be established. Here we studied intra-tumoral and...
Each neuron in the primary motor cortex (M1) is like a musician in an orchestra, contributing to a larger harmony under the constraint of a “neural manifold”—a geometric score describing the correlated signals produced by the neural musicians that drive movement. Despite the widespread recognition of the importance of M1...
Chronic stress is a significant risk factor for the development of numerous psychiatric disorders, including major depressive disorder (MDD). Individuals with MDD exhibit impairments in reward processing and decreased motivation to engage in previously-rewarding activities. Importantly, there is a large sex disparity in MDD diagnosis, such that it affects nearly...
Conversation is an important part of human life. Given globalization and the numerous languages around the world, it is increasingly likely that we will be communicating with others speaking in their second language (L2) rather than their first language (L1). In these situations, communication may require more effort. However, people...
Breast cancer patients have reported nonspecific neurologic symptoms such as fatigue, depression, and cognitive concerns while undergoing adjuvant therapy. Few neuroimaging studies have examined hormone therapy, an adjuvant therapy, and more research is needed to determine possible neurologic and cognitive effects. Previous estrogen research has found alterations in gray matter...
Temperature affects all biological processes, from the rate of cellular growth and metabolism to the stability of proteins that make up the machinery of life itself. Thus, all organisms must have the capacity to detect and respond to external temperature. Thermosensation endows animals with the ability to sense and respond...
Visual information plays a critical role in controlling movement. People use visual information to plan future actions and correct current actions through feedforward and feedback processes, respectively. We can gain insights into these visually guided motor control processes by quantifying where people look during movement and measuring how much they...
Parkinson’s disease (PD) is the second most common neurodegenerative disorder, causing devastating disabilities in both motor and non-motor domains following the degeneration of dopamine (DA) producing neurons of the substantia nigra pars compacta (SNc). Current treatments are highly limited in efficacy, and no established treatments currently exist to alter disease...
Genetic studies have found variants in the protein-degrading autophagy-lysosomal pathway (ALP) to be among the most common risk factors for developing Parkinson’s disease (PD). Macroautophagy (MA) is the arm of this pathway which delivers cytosolic components to lysosomes for degradation and is essential for neuronal health. The defining pathological protein...
As of 2020, there are currently 5.8 million people in the United States suffering from Alzheimer’s Disease (AD), a debilitating and progressive neurodegenerative disorder. Of these nearly six million people, two-thirds are women. While it has been suggested that women’s longer lifespan accounts for this disparity, the overall lifetime risk...
Voltage-gated potassium (KV) currents play a crucial role in shaping and controlling the firing patterns that serve as the fundamental basis for the differential signal processing from the ear to the auditory cortex, with distinct firing patterns observed with high- and low-frequency phenotypes. This is an interesting phenomenon, in the...
SCN2A encodes the NaV1.2 voltage-gated sodium channel, which is thought to contribute to the development of the central nervous system. Pathogenic variants in SCN2A have been associated with neurodevelopmental disorders (NDD), including developmental and epileptic encephalopathies (DEE), intellectual disability (ID), and autism spectrum disorder (ASD). These disorders represent a significant...
The basal ganglia operate largely in closed parallel loops, including an associative circuit for goal-directed behavior originating from the dorsomedial striatum (DMS) and a somatosensory circuit important for habit formation originating from the dorsolateral striatum (DLS). An exception to this parallel circuit organization was proposed to explain how information is...
Simple sensorimotor tasks, such as lifting a cup or balancing a tray, requires not only controlled motor output, but also the ability to accurately perceive sensory information. After a hemiparetic stroke, individuals often experience sensory deficits in addition to motor impairments. However, research on the extent of changes in sensory...
Different features of the visual world are conveyed to the retino-recipient regions of the brain by more than 40 types of retinal ganglion cells (RGCS). Feature detection by RGCs depends on a combination of intrinsic and morphological properties where the interplay of excitatory and inhibitory inputs occurs through local retinal...
Autism spectrum disorder (ASD) and intellectual disability (ID) are two of the most highly prevalent neurodevelopmental disorders (NDDs), each affecting roughly 2% of the population. Despite the need for therapies, few exist due to a myriad of challenges, such as the complex underlying genetic etiology and historic inaccessibility of neural...
Vertebrate brains evolved to facilitate a diverse array of behaviors and internal cognitive processes. Theories of neural function have proposed that neural computation is organized within populations or ensembles of neurons. Here, we identify ensembles of neurons in the striatum, the main input nucleus of the basal ganglia, in which...
Human olfactory function is important for a myriad of behaviors, including food seeking, social cognition, memory, emotional regulation, and detecting environmental threats. In animal models, particularly dense olfactory inputs have been shown to target orbitofrontal cortex (OFC), a region involved in multimodal sensory integration, reward coding, and flexibly guiding our...
The retina detects light, processes the visual signal, and sends a complex set of parallel information channels to the brain via a functionally diverse set of retinal ganglion cells types. This manuscript examines these retinal ganglion cell types, the visual features they encode, and the computational mechanisms leading to their...
Involuntary motor activities such as spasms arise from hyperreflexia in about 70% of individuals with spinal cord injuries (SCI). Despite this prevalence and the negative impact on health and safety, it is unclear what determines the severity of the spasms that develop. This study investigated the impact of injury severity...
Our sense of smell, or olfaction, is one of our most evolutionarily ancient senses. In vertebrates, olfaction plays a crucial role in many functions, such as detecting and evaluating food, avoiding predators, regulating appetite, spatial navigation, and selecting mating partners. In addition, the olfactory system is highly dynamic and exhibits...
Findings in both humans and animal models have associated the hippocampal theta oscillation with hippocampal memory function. In animal models, previous research supports that the theta oscillation contributes to memory via phase-dependent changes in hippocampal network connectivity, wherein memory encoding versus retrieval are optimized at different phases of the theta...
Aging is the greatest known risk factor for Alzheimer’s Disease (AD); however, the molecular mechanisms underlying aging and how it can initiate and or exacerbate AD, is still unknown. Epigenetic regulation has been widely accepted to play an essential role in aging or AD-related processes; however, whether dysregulations of histone...
Simple sensorimotor tasks, such as lifting a cup or balancing a tray, requires not only controlled motor output, but also the ability to accurately perceive sensory information. After a hemiparetic stroke, individuals often experience sensory deficits in addition to motor impairments. However, research on the extent of changes in sensory...
Voltage-gated potassium (KV) currents play a crucial role in shaping and controlling the firing patterns that serve as the fundamental basis for the differential signal processing from the ear to the auditory cortex, with distinct firing patterns observed with high- and low-frequency phenotypes. This is an interesting phenomenon, in the...
Aging is the greatest known risk factor for Alzheimer’s Disease (AD); however, the molecular mechanisms underlying aging and how it can initiate and or exacerbate AD, is still unknown. Epigenetic regulation has been widely accepted to play an essential role in aging or AD-related processes; however, whether dysregulations of histone...
The retina detects light, processes the visual signal, and sends a complex set of parallel information channels to the brain via a functionally diverse set of retinal ganglion cells types. This manuscript examines these retinal ganglion cell types, the visual features they encode, and the computational mechanisms leading to their...
Human olfactory function is important for a myriad of behaviors, including food seeking, social cognition, memory, emotional regulation, and detecting environmental threats. In animal models, particularly dense olfactory inputs have been shown to target orbitofrontal cortex (OFC), a region involved in multimodal sensory integration, reward coding, and flexibly guiding our...
Findings in both humans and animal models have associated the hippocampal theta oscillation with hippocampal memory function. In animal models, previous research supports that the theta oscillation contributes to memory via phase-dependent changes in hippocampal network connectivity, wherein memory encoding versus retrieval are optimized at different phases of the theta...
Dopamine neurons are characterized by their response to unexpected rewards, but some also fire during movement and in response to aversive stimuli. Dopamine neuron diversity has also been observed based on their genetic expression profiles, suggesting that different functions might map onto such genetic subtypes. However, this has not been...
Electrical spinal cord stimulation is an emerging treatment for spinal cord injury that can improve walking and bladder control, among many other functions. While the anatomical location of the motor pools for muscles involved in locomotion in the lumbosacral cord has been identified, the map of the functional output of...
The current view in neuroscience holds that the brain, together with its sensory and motor structures and the environment, form a closed-loop system – a sensorimotor loop – in which the brain receives information from the environment and converts it into a motor response while simultaneously making predictions about future...
Affect represents a major domain of human consciousness, consisting of a complex group of psychophysiological processes to drive human behavior. Many genetic and environmental factors may cause dysregulation of affective states, resulting in disorders that severely disrupt normal cognitive function and diminish the quality of life. Transitions among affective states...
Cholinergic modulation of the brain cortex is critical for cognitive processes, and altered cholinergic modulation of the prefrontal cortex is emerging as an important mechanism of neuropathic pain. Despite the known sex differences in pain prevalence and perception, the precise nature of the mechanisms responsible for sexual dimorphism in chronic...
Persons with spinal cord injuries can use state-of-the-art brain-computer interfaces to control robotic arms. Despite this high-tech solution, their movements are slow and imprecise, much like those made by individuals who have lost proprioception, the sense of body position and movement. Intracortical microstimulation (ICMS) used to reactivate neural circuits in...
The answer to the question “Why do we sleep?” lies in understanding the biological underpinnings of homeostatic drive to sleep. Wakefulness is correlated with numerous changes in brain activity, structure and gene/protein expression that re-normalize following sleep however which of these elements is sufficient to cause sleep drive and how...
Research over the past several decades has revealed that memory reactivation in sleep contributes to the formation of long-lasting memories. Among the most recent developments in this field is the widespread use of the technique of targeted memory reactivation (TMR), which allows researchers to induce reactivation of specific memories during...
Over the course of disease progression, half of adults with type II diabetes also develop diabetic peripheral neuropathy (DPN), peripheral nerve damage precipitated by the downstream metabolic effects of hyperglycemia, insulin resistance, and dyslipidemia. This multifactorial pathogenesis of DPN leads to various structural and physiological changes within the nerve, ultimately...
Perturbations to the physiology or impairments in the formation of synapses within the cochlea, specifically the ribbon synapses, result in decreased sensitivity to auditory stimuli. In example, prolonged exposure to moderately intense auditory stimuli, like power tools, can result in the swelling of nerve terminals, retraction of the postsynaptic membrane,...
In the adult hippocampus of many mammalian species, populations of newborn dentate granule cells (DGCs) are continuously generated and undergo subsequent activity-dependent neuronal maturation and incorporation into the preexisting hippocampal circuitry. Increasing evidence has demonstrated that these young adult-born DGCs (abDGCs) participate in numerous cognitive and affective processes such as...
My research at northwestern with Dr. Christina Zelano focused on the human amygdala subnucleithat receive monosynaptic input from the olfactory bulb. Surprisingly little is known
about these brain regions, including their potential roles in olfactory and nonolfactory
processing. During my PhD, I completed three projects aimed at furthering our understanding...
Anxiety and depression are highly prevalent, recurrent, and major public health problems. Decades of research has uncovered associations between symptom dimensions of anxiety and depression and abnormal neural activation across executive control-, threat-, and reward-related networks. Recent studies have developed a hierarchical symptom structure of anxiety and depression termed the...
Background: The way in which one perceives their visual world (i.e., bottom-up visual perception) and what one pays attention to in their surroundings (i.e., top-down attention), are critical to uncovering underlying thoughts and cognitions, and impact how one operates in the social world. Individuals with autism spectrum disorder (ASD), a...
Herpes simplex virus (HSV) encephalitis (HSE) is the most common cause of sporadic fatal encephalitis, and despite targeted antiviral therapy, outcomes remain poor. While rare in adults, neonates are significantly more susceptible to severe HSV disease. Understanding both the host and viral factors that contribute to pathogenesis is critical to...
The retina does not act as a simple camera, rather visual information goes through multiple layers of processing before it reaches the brain. Retinal ganglion cells (RGCs) are the output neurons of the retina and process visual information in the retina and then project into the brain. There are over...
All animals purposefully navigate feature-rich environments: while exploring, in search of vital resources of food and water, finding mates, and patrolling and marking habitats. During these complex behaviors, continuous analogue input information from peripheral sensory organs guides discrete and digital sequential motor output; accordingly, each action is informed, modulated, or...
The cerebellar cortical system is an extensively studied circuit which is critical for motor learning. While multiple monoamines, such as norepinephrine and serotonin, modulate cerebellar cortical output, the mechanistic details of dopaminergic signaling in the cerebellum remain poorly understood. Additionally, neuronal cell types residing within the cerebellum remain relatively under-characterized....
Glioblastoma multiforme (GBM) is the most prevalent primary central nervous system tumor, characterized by resistance to therapeutic intervention, inevitable recurrence, and ultimately patient death. The dismal prognosis is due in part to underlying molecular factors that promote an intratumoral cellular state heterogeneity and protect tumor cells from cell death pathways....
Numerous insights into the sensorimotor systems that guide the control of voice have been garnered by observing how the system responds to manipulations of its auditory feedback. However, current approaches may be limited in the exploration of more complex parameters of volitional and adaptive voice control due to their limited...
Sensorimotor integration is a general term to describe how task-specific motor output is generated from the selective and rapid processing of sensory and motor information. The rodent vibrissal (whisker) system is an important model for the study of sensorimotor integration and active tactile sensing. This research uses the rodent vibrissal...