IU Indianapolis ScholarWorks :: Browsing by Author "Sangha, Susan"

Browsing by Author "Sangha, Susan"

Now showing 1 - 10 of 11

Characterization of Biomimetic Spinal Cord Stimulations for Restoration of Sensory Feedback
(2024-05) Zeiser, Sidnee L.; Yadav, Amol; Yoshida, Ken; Berbari, Edward; Sangha, Susan; Surowiec, Rachel
Sensory feedback is a critical component for controlling neuroprosthetic devices and brain-machine interfaces (BMIs). A lack of sensory pathways can result in slow, coarse movements when using either of these technologies and, in addition, the user is unable to fully interact with the environment around them. Spinal cord stimulation (SCS) has shown potential for restoring these pathways, but traditional stimulation patterns with constant parameters fail to reproduce the complex neural firing necessary for conveying sensory information. Recent studies have proposed various biomimetic stimulation patterns as a more effective means of evoking naturalistic neural activity and, in turn, communicating meaningful sensory information to the brain. Unlike conventional patterns, biomimetic waveforms vary in frequency, amplitude, or pulse-width over the duration of the stimulation. To better understand the role of these parameters in sensory perception, this thesis worked to investigate the effects of SCS patterns utilizing stochastic frequency modulation, linear frequency modulation, and linear amplitude modulation. By calculating sensory detection thresholds and just-noticeable differences, the null hypothesis for stochastically-varied frequency and linear amplitude modulation techniques was rejected.
Conditioned Inhibition of Fear and Reward in Male and Female Rats
(Elsevier, 2024) Krueger, Jamie N.; Patel, Nupur N.; Shim, Kevin; Ng, Ka; Sangha, Susan; Psychiatry, School of Medicine
Stimuli in our environment are not always associated with an outcome. Some of these stimuli, depending on how they are presented, may gain inhibitory value or simply be ignored. If experienced in the presence of other cues predictive of appetitive or aversive outcomes, they typically gain inhibitory value and become predictive cues indicating the absence of appetitive or aversive outcomes. In this case, these cues are referred to as conditioned inhibitors. Here, male and female Long Evans rats underwent cue discrimination training where a reward cue was paired with sucrose, a fear cue with footshock, and an inhibitor cue resulted in neither sucrose or footshock. During a subsequent summation test for conditioned inhibition of fear and reward, the inhibitor cue was presented concurrently with the reward and fear cues without any outcome, intermixed with trials of reinforced reward and fear trials. Males showed significant conditioned inhibition of freezing, while females did not, which was not dependent on estrous. Both males and females showed significant conditioned inhibition of reward. During a retardation of fear acquisition test, the inhibitor was paired with footshock and both males and females showed delayed acquisition of fear. During a retardation of reward acquisition test, the inhibitor was paired with sucrose, and females showed delayed acquisition of reward, while males did not. In summary, males and females showed significant reward-fear-inhibitor cue discrimination, conditioned inhibition of reward, and retardation of fear acquisition. The main sex difference, which was not estrous-dependent, was the lack of conditioned inhibition of freezing in females. These data imply that while the inhibitor cue gained some inhibitory value in the females, the strength of this inhibitory value may not have been great enough to effectively downregulate freezing elicited by the fear cue.
Early-life trauma alters hippocampal function during an episodic memory task in adulthood
(2017-05-02) Janetsian-Fritz, Sarine S.; Lapish, Christopher; Sangha, Susan; Goodlett, Charles; Neal-Beliveau, Bethany
Early life trauma is a risk factor for a number of neuropsychiatric disorders, including schizophrenia (SZ) and depression. Animal models have played a critical role in understanding how early-life trauma may evoke changes in behavior and biomarkers of altered brain function that resemble these neuropsychiatric disorders. However, since SZ is a complex condition with multifactorial etiology, it is difficult to model the breadth of this condition in a single animal model. Considering this, it is necessary to develop rodent models with clearly defined subsets of pathologies observed in the human condition and their developmental trajectory. Episodic memory is among the cognitive deficits observed in SZ. Theta (6-10 Hz), low gamma (30-50 Hz), and high gamma (50-100 Hz) frequencies in the hippocampus (HC) are critical for encoding and retrieval of memory. Also, theta-gamma comodulation, defined as correlated fluctuations in power between these frequencies, may provide a mechanism for coding episodic sequences by coordinating neuronal activity at timescales required for memory encoding and retrieval. Given that patients with SZ have impaired recognition memory, the overall objectives of these experiments were to assess local field potential (LFP) recordings in the theta and gamma range from the dorsal HC during a recognition memory task in an animal model that exhibits a subclass of symptoms that resemble SZ. In Aim 1, LFPs were recorded from the HC to assess theta and gamma power to determine whether rats that were maternally deprived (MD) for 24-hrs on postnatal day (PND 9), had altered theta and high/low gamma power compared to sham rats during novel object recognition (NOR). Brain activity was recorded while animals underwent NOR on PND 70, 74, and 78. In Aim 2, the effects of theta-low gamma comodulation and theta-high gamma comodulation in the HC were assessed during NOR between sham and MD animals. Furthermore, measures of maternal care were taken to assess if high or low licking/grooming behaviors influenced recognition memory. It was hypothesized that MD animals would have impaired recognition memory and lower theta and low/high gamma power during interaction with both objects compared to sham animals. Furthermore, it was hypothesized that sham animals would have higher theta-gamma comodulation during novel object exploration compared to the familiar object, which would be higher than the MD group. Measures of weight, locomotor activity, and thigmotaxis were also assessed. MD animals were impaired on the NOR task and had no change in theta or low/high gamma power or theta-gamma comodulation when interacting with the novel or familiar object during trials where they performed unsuccessfully or successfully. However, higher theta and gamma power and theta-gamma comodulation was observed in sham animals depending on the object they were exploring or whether it was a successful or unsuccessful trial. These data indicate altered functioning of the HC following MD and a dissociation between brain activity and behavior in this group, providing support that early life trauma can induce cognitive and physiological impairments that are long-lasting. In conclusion, these data identify a model of early life stress with a translational potential, given that there are points of contact between human studies and the MD model. Furthermore, these data provide a set of tools that could be used to further explore how these altered neural mechanisms may influence cognition and behavior.
Encoding of conditioned inhibitors of fear in the infralimbic cortex
(Oxford University Press, 2023) Ng, Ka H.; Sangha, Susan; Psychiatry, School of Medicine
Cues in the environment signaling the absence of threat, i.e. safety, can influence both fear and reward-seeking behaviors. Heightened and maladaptive fear is associated with reduced activity in the medial prefrontal cortex. We have previously shown in male rats that the infralimbic (IL) prefrontal cortex is necessary for suppressing fear during a safety cue. The objective of the present study was to determine if there was safety cue-specific neural activity within the IL using a Pavlovian conditioning paradigm, where a fear cue was paired with shock, a safety cue was paired with no shock, and a reward cue was paired with sucrose. To investigate how safety cues can suppress fear, the fear and safety cues were presented together as a compound fear + safety cue. Single-unit activity showed a large proportion of neurons with excitatory responses to the fear + safety cue specifically, a separate group of neurons with excitatory responses to both the reward and fear + safety cues, and bidirectional neurons with excitation to the fear + safety cue and inhibition to the fear cue. Neural activity was also found to be negatively correlated with freezing during the fear + safety cue. Together, these data implicate the IL in encoding specific aspects of conditioned inhibitors when fear is being actively suppressed.
Environmental Certainty Influences the Neural Systems Regulating Responses to Threat and Stress
(Elsevier, 2021) Meyer, Heidi C.; Sangha, Susan; Radley, Jason J.; LaLumiere, Ryan T.; Baratta, Michael V.; Psychiatry, School of Medicine
Flexible calibration of threat responding in accordance with the environment is an adaptive process that allows an animal to avoid harm while also maintaining engagement of other goal-directed actions. This calibration process, referred to as threat response regulation, requires an animal to calculate the probability that a given encounter will result in a threat so they can respond accordingly. Here we review the neural correlates of two highly studied forms of threat response suppression: extinction and safety conditioning. We focus on how relative levels of certainty or uncertainty in the surrounding environment alter the acquisition and application of these processes. We also discuss evidence indicating altered threat response regulation following stress exposure, including enhanced fear conditioning, and disrupted extinction and safety conditioning. To conclude, we discuss research using an animal model of coping that examines the impact of stressor controllability on threat responding, highlighting the potential for previous experiences with control, or other forms of coping, to protect against the effects of future adversity.
Interaction of stress and alcohol on discriminating fear from safety and reward in male and female rats
(Springer Nature, 2023) Hackleman, Abigail; Ibrahim, Muhja; Shim, Kevin; Sangha, Susan; Psychiatry, School of Medicine
Rationale: Stressful events can have lasting and impactful effects on behavior, especially in terms of appropriate fear regulation and reward seeking. Our prior work in rats has shown baseline sex differences in fear expression and sucrose seeking in a discriminative reward-fear-safety conditioning task. Objectives: The objectives of the current study were to determine how prior stress may affect alcohol consumption across a reward-fear-safety learning task, and how prior alcohol history may interact with stress to impact learning in this task. Methods: Male and female Long Evans rats were given home cage intermittent 24 h access to both water and alcohol for 5 weeks. A subset of rats then received exposure to stress (15 unsignaled footshocks), while remaining unstressed rats received context exposure without shock. One week later, all rats were trained on the same reward-fear-safety cue task while having continuous home cage access to both water and alcohol. Results: All rats increased consumption (g/kg/24 h) across the 5 weeks of intermittent access, with females showing higher consumption levels. Stress exposure did not alter alcohol consumption in the week following stress, but did increase home cage alcohol consumption during later reward-fear-safety cue learning. Stress in both sexes also elevated freezing levels to the reward cue resulting in decreased sucrose seeking and was positively correlated with home cage alcohol consumption. Conclusions: While stress increased drinking in both males and females, the effects of stress were particularly pronounced in females, indicating our results could be capturing a higher propensity for females to display stress-induced drinking.
Juvenile stress facilitates safety learning in male and female high alcohol preferring mice
(Elsevier, 2021) Müller, Iris; Adams, Demitra D.; Sangha, Susan; Chester, Julia A.; Psychology, School of Science
Adversities during juvenility increase the risk for stress-related disorders, such as post-traumatic stress disorder (PTSD) and alcohol use disorder. However, stress can also induce coping mechanisms beneficial for later stressful experiences. We reported previously that mice selectively bred for high alcohol preference (HAP) exposed to stress during adolescence (but not during adulthood) showed enhanced fear-conditioned responses in adulthood, as measured by fear-potentiated startle (FPS). However, HAP mice also showed enhanced responding to safety cues predicting the absence of foot shocks in adulthood. Here, we pursue these findings in HAP mice by investigating in further detail how juvenile stress impacts the acquisition of safety and fear learning. HAP mice were subjected to three days of juvenile stress (postnatal days 25, 27, 28) and discriminative safety/fear conditioning in adulthood. FPS was used to assess safety versus fear cue discrimination, fear learning, and fear inhibition by the safety cue. Both stressed and unstressed HAP mice were able to discriminate between both cues as well as learn the fear cue-shock association. Interestingly, it was only the previously stressed mice that were able to inhibit their fear response when the fear cue was co-presented with the safety cue, thus demonstrating safety learning. We also report an incidental finding of alopecia in the juvenile stress groups, a phenotype seen in stress-related disorders. These results in HAP mice may be relevant to understanding the influence of juvenile trauma for individual risk and resilience toward developing PTSD and how individuals might benefit from safety cues in behavioral psychotherapy.
On the basis of sex: Differences in safety discrimination vs. conditioned inhibition
(Elsevier, 2021) Krueger, Jamie N.; Sangha, Susan; Psychology, School of Science
Inaccurate discrimination between threat and safety cues is a common symptom of anxiety disorders such as Post-Traumatic Stress Disorder (PTSD). Although females experience higher rates of these disorders than males, the body of literature examining sex differences in safety learning is still growing. Learning to discriminate safety cues from threat cues requires downregulating fear to the safety cue while continuing to express fear to the threat cue. However, successful discrimination between safety and threat cues does not necessarily guarantee that the safety cue can effectively reduce fear to the threat cue when they are presented together. The conditioned inhibitory ability of a safety cue to reduce fear in the presence of both safety and threat is most likely dependent on the ability to discriminate between the two. There are relatively few studies exploring conditioned inhibition as a method of safety learning. Adding to this knowledge gap is the general lack of inclusion of female subjects within these studies. In this review, we provide a qualitative review of our current knowledge of sex differences in safety discrimination versus conditioned inhibition in both humans and rodents. Overall, the literature suggests that while females and males perform similarly in discrimination learning, females show deficits in conditioned inhibition compared to males. Furthermore, while estrogen appears to have a protective effect on safety learning in humans, increased estrogen in female rodents appears to be correlated with impaired safety learning performance.
Psychological and physiological correlates of stimulus discrimination in adults
(Wiley, 2023) Fitzgerald, Jacklynn M.; Webb, E. Kate; Sangha, Susan; Psychiatry, School of Medicine
The discrimination of cues in the environment that signal danger ("fear cue") is important for survival but depends critically on the discernment of such cues from ones that pose no threat ("safety cues"). In rodents, we previously demonstrated the underlying neurobiological mechanisms that support fear versus safety discrimination and documented that these mechanisms extend to the discrimination of reward as well. While learning about reward is equally important for survival, it remains an under-studied area of research, particularly in human studies of conditional discrimination. In the present study, we translated our rodent task of fear reward and neutral discrimination (fear, reward, and neutral discrimination [FRND]) for use in humans. Undergraduate students (N = 53) completed the FRND while electrodermal activity was recorded. Skin conductance response (SCR) amplitude, a marker of arousal response, was derived for fear, reward, and neutral cues that signaled no outcome; critical trials assessed conditional discrimination using combined fear + neutral and reward + neutral cues. Participants provided likeability ratings for each cue type. Results demonstrated that participants rated reward cues the best, fear cues the worst, and neutral cues in between, while SCR amplitude was largest for fear and reward cues and lowest for neutral cues. SCR amplitudes were reduced for fear + neutral (compared to fear) and reward + neutral cues (compared to reward). Results demonstrate that the FRND is a useful paradigm for the assessment of psychological and physiological discrimination of fear and reward. Implications and directions for future work are discussed.
Suppressing fear in the presence of a safety cue requires infralimbic cortical signaling to central amygdala
(Springer Nature, 2024) Ng, Ka; Pollock, Michael; Escobedo, Abraham; Bachman, Brent; Miyazaki, Nanami; Bartlett, Edward L.; Sangha, Susan; Psychiatry, School of Medicine
Stressful events can have lasting and impactful effects on behavior, especially by disrupting normal regulation of fear and reward processing. Accurate discrimination among environmental cues predicting threat, safety or reward adaptively guides behavior. Post-traumatic stress disorder (PTSD) represents a condition in which maladaptive fear persists in response to explicit safety-predictive cues that coincide with previously learned threat cues, but without threat being present. Since both the infralimbic cortex (IL) and amygdala have each been shown to be important for fear regulation to safety cues, we tested the necessity of specific IL projections to the basolateral amygdala (BLA) or central amygdala (CeA) during safety recall. Male Long Evans rats were used since prior work showed female Long Evans rats did not acquire the safety discrimination task used in this study. Here, we show the infralimbic projection to the central amygdala was necessary for suppressing fear cue-induced freezing in the presence of a learned safety cue, and the projection to the basolateral amygdala was not. The loss of discriminative fear regulation seen specifically during IL->CeA inhibition is similar to the behavioral disruption seen in PTSD individuals that fail to regulate fear in the presence of a safety cue.

Browsing by Author "Sangha, Susan"

Results Per Page

Sort Options