Browsing by Subject "Psychobiology"

The goal of this dissertation is to characterize goal directed proactive behavioral responses to threat as well as reactive responses to threat exposure, and to identify the neural and personality correlates of individual differences in these responses. Three specific studies are reported wherein participants completed a novel shock avoidance paradigm while concurrent measures of behavioral, muscular, and sympathetic autonomic activity were collected; self-report was used to measure mood and trait personality; and blood oxygen-level dependent functional magnetic resonance imaging (BOLD fMRI) was used to measure individual differences in threat-related amygdala reactivity and intrinsic connectivity within the corticolimbic circuit.

Results from Study 1 demonstrate that during threat exposure, participants exhibit increased avoidance behavior, faster reaction times, and increased muscular and sympathetic activity. Moreover, results demonstrate that two broad patterns characterize individual differences in how participants respond during avoidance: 1) a generalized tendency to exhibit magnified threat responses across domains; and 2) a tendency to respond either with proactive behavioral responses or reactive autonomic responses. Heightened state anxiety during the shock avoidance paradigm, and increased trait anxiety were both associated with the generalized tendency to exhibit magnified threat responses. However, gender moderated the relationship between trait anxiety and generalized increases in threat responses during avoidance, such that only male participants exhibited a positive relationship between these two factors. Study 2 demonstrates that intrinsic connectivity between the dorsomedial prefrontal cortex and centromedial region of the amygdala prospectively predicts whether participants will respond proactively or reactively during active avoidance. Finally, Study 3 provides evidence that responses to threat-related facial expressions within the centromedial region of the amygdala are associated with more reactive and less proactive responses during avoidance.

These results demonstrate that patterns observed in animal models of avoidance, specifically the competition between proactive and reactive responses to threat cues, extend to human participants. Moreover, our results suggest that while anxious mood during performance and heightened trait anxiety are associated with a generalized facilitation of threat responses across domains, measures of neural circuit function within the corticolimbic system predict whether individuals will exhibit increased proactive or reactive responses during active avoidance. In addition to facilitating the search for the neural processes underlying how the brain responds dynamically to threat, these results have the potential to aide researchers in characterizing the symptoms and neural processes underlying anxiety disorders.

Smooth pursuit eye movements are movements of the eyes that are used to foveate moving objects. Their precision and adaptation is believed to depend on a constellation of sites across the cerebellum, but only one region’s contribution is well characterized, the floccular complex. Here, I characterize the response properties of neurons in the oculomotor vermis, another major division of the oculomotor cerebellum whose role in pursuit remains unknown. I recorded Purkinje cells, the output neurons of this region, in two monkeys as they executed pursuit eye movements in response to step ramp target motion. The responses of these Purkinje cells in the oculomotor vermis were very different from responses that have been documented in the floccular complex. The simple spikes of these cells encoded movement direction in retinal, as opposed to muscle coordinates. They were less related to movement kinematics, and had smaller values of trial-by-trial correlations with pursuit speed, latency, and direction than their floccular complex counterparts. Unlike Purkinje cells in the floccular complex, simple spike firing rates in the oculomotor vermis remained unchanged over the course of pursuit adaptation, likely excluding the oculomotor vermis as a site of directional plasticity. Complex spikes of these Purkinje cells were only partially responsive to target motion, and did not fall into any clear opponent directional organization with simple spikes, as has been found in the floccular complex. In general, Purkinje cells in the oculomotor vermis were responsive to both pursuit and to saccadic eye movements, but maintained tuning for the direction of these movements along separate directions at a population level. Predictions of caudal fastigial nucleus activity, generated on the basis of our population of oculomotor vermal Purkinje cells, faithfully tracked moment-by-movement changes in pursuit kinematics. By contrast, these responses did not faithfully track moment-by-moments changes in saccade kinematics. These results suggest that the oculomotor vermis is likely to play a smaller role in influencing pursuit eye movements by comparison to the floccular complex.

Humans make decisions in highly complex physical, economic and social environments. In order to adaptively choose, the human brain has to learn about- and attend to- sensory cues that provide information about the potential outcome of different courses of action. Here I present three event-related potential (ERP) studies, in which I evaluated the role of the interactions between attention and reward learning in economic decision-making. I focused my analyses on three ERP components (Chap. 1): (1) the N2pc, an early lateralized ERP response reflecting the lateralized focus of visual; (2) the feedback-related negativity (FRN), which reflects the process by which the brain extracts utility from feedback; and (3) the P300 (P3), which reflects the amount of attention devoted to feedback-processing. I found that learned stimulus-reward associations can influence the rapid allocation of attention (N2pc) towards outcome-predicting cues, and that differences in this attention allocation process are associated with individual differences in economic decision performance (Chap. 2). Such individual differences were also linked to differences in neural responses reflecting the amount of attention devoted to processing monetary outcomes (P3) (Chap. 3). Finally, the relative amount of attention devoted to processing rewards for oneself versus others (as reflected by the P3) predicted both charitable giving and self-reported engagement in real-life altruistic behaviors across individuals (Chap. 4). Overall, these findings indicate that attention and reward processing interact and can influence each other in the brain. Moreover, they indicate that individual differences in economic choice behavior are associated both with biases in the manner in which attention is drawn towards sensory cues that inform subsequent choices, and with biases in the way that attention is allocated to learn from the outcomes of recent choices.

In the present study, we examined the predictions of an attentional-associative model (Schmajuk, Lam, & Gray Journal of Experimental Psychology: Animal Behavior Processes, 22, 321-349, 1996) regarding the effect of attentional manipulations on both discrete and contextual conditioned inhibitors.

The SLG model assumes that non-reinforced presentations of an inhibitory conditioned stimulus (CS) do not decrease its inhibitory associations. However, the model predicts that extended presentations will decrease attention to the inhibitor, thereby, decreasing both the expression of its inhibitory power in a summation test and the rate of acquisition in a retardation test. The model also predicts that subsequent presentations of the inhibitory CS with a novel CS will increase both its inhibitory power in a summation test and the rate of acquisition in a retardation test. Using a predictive learning design in humans, Experiment 1 examined the predictions involving the summation tests, whereas Experiments 2 and 3 examined the predictions involving the retardation tests. Experimental results were in agreement with the predictions of the model.

The SLG model also predicts that a salient extinction context (CX) becomes inhibitory and prevents extinction of the excitatory CS-unconditioned stimulus (US) association. Although some data seem to contradict that prediction (e.g., Bouton and King, 1983, Bouton and Swartzentruber, 1986, 1989), Larrauri and Schmajuk (2008) indicated that the CX might not appear inhibitory in a summation test because attention to the CX decreases with many but not few extinction trials. In a human predictive learning experiment, we confirmed the model's predictions that the inhibitory power of the extinction CX can be detected after a few extinction trials when attention to the CX is still high, but not after many extinction trials once attention to the CX has decreased (Experiment 4), and even after many extinction trials by presenting novel CSs to increase attention to the unattended CX (Experiment 5). Furthermore, using an eye-tracker, we confirmed the model's explanation of Experiment 4 results by showing decreased overt attention to the CX after many but not after few extinction trials (Experiment 6).

Importantly, the view that the extinction CX becomes inhibitory allows the model to explain spontaneous recovery (because attention to the excitatory CS increases before attention to the inhibitory CX), renewal (because the inhibition provided by the extinction CX disappears), and reinstatement (the inhibitory CX becomes neutral or excitatory), as well as a very large number of other experimental results related to extinction. Based on the prediction of the SLG, model the implications of our results for the treatments of anxiety disorders were discussed.

Obsessive-compulsive disorder (OCD) is a devastating illness that afflicts around 2% of the world's population with recurrent distressing thoughts (obsessions) and repetitive ritualistic behaviors (compulsions). While dysfunction at excitatory glutaminergic excitatory synapses leading to hyperactivity of the orbitofrontal cortex and head of the caudate - brain regions involved in reinforcement learning - are implicated in the pathology of OCD, clinical studies involving patients are unable to dissect the molecular mechanisms underlying this cortico-striatal circuitry defect. Since OCD is highly heritable, recent studies using mutant mouse models have shed light on the cellular pathology mediating OCD symptoms. These studies point toward a crucial role for deltaFosB, a persistent transcription factor that accumulates with chronic neuronal activity and is involved in various diseases of the striatum. Furthermore, elevated deltaFosB levels results in the transcriptional upregulation of Grin2b, which codes GluN2B, an N-methyl-D-aspartate glutamate receptor (NMDAR) subunit required for the formation and maintenance of silent synapses. Taken together, the current evidence indicates that deltaFosB-mediated expression of aberrant silent synapses in caudate medium spiny neurons (MSNs), in particular D1 dopamine-receptor expressing MSNs (D1 MSNs), mediates the defective cortico-striatal synaptic transmission that underlies compulsive behavior in OCD.

In most aspects of music--e.g., tempo, intensity, and rhythm--the emotional coloring of a melody is due at least in part to physical imitation of the characteristics of emotional expression in human behavior. Thus excited, happy melodies are fast and loud, with syncopated rhythms, whereas subdued sad melodies are slow and quiet, with more even rhythms. The tonality of a melody (e.g. major or minor) also conveys emotion, but unlike other aspects of music, the basis for its affective impact is not clear. This thesis examines the hypothesis that different collections of musical tones are associated with specific emotions because they mimic the natural relationship between emotion and tonality present in the human voice. To evaluate this possibility, I have conducted acoustical analyses on databases of music and speech drawn from a variety of cultures, and compared the tonal characteristics of emotional expression between these two forms of social communication. I find that: (1) the melodic characteristics of music and the prosodic characteristics of speech co-vary when examined across cultures; (2) the principal tonal characteristics of melodies composed in tonalities associated with positive/excited emotion and negative/subdued emotion are much the same in different cultures; (3) cross-cultural tonal similarities in music parallel cross-cultural tonal similarities in vocal expression; and (4) the tonal characteristics of emotional expression in the voice convey distinct emotions, thereby accounting for the specificity of emotional association in musical tonality. These findings, and the implausibility of alternative explanations that could account for them, suggest that the affective impact of musical tonality derives from mimicry of the tonal characteristics of vocalization in different emotional states.

Locomotion is an essential component of all animal behavior. It is highly conserved across species. Locomotion is defined as movement from one place to another. Studies of locomotion focus on two aspects: (1) the motor program including footfalls and rhythmic swings including maintaining stance under continuous environmental disturbance, which are largely regulated by the spinal cord; (2) the volitional aspect of locomotion including adjusting posture of trunk and leaning to achieve goal-directed locomotion, which require top-down control from the brain. Decades of research on locomotion has revealed the function of central pattern generator and motor programs in regulating the motor synergy during locomotion, but little is known about the circuit that provides top-down control of locomotion direction and initiation.

The mesencephalic locomotor region (MLR) has long been identified as a key region for locomotion initiation. Number of studies have shown that stimulation of the MLR can initiate various speed of gait, and it is considered as the central node for integration of top-down control of locomotion. However, limited research has been done investigating how MLR regulate locomotion direction, which is essential in any goal-directed locomotion. Two reasons for this are (1) firstly, the MLR is not an anatomically well-defined region with diverse neuronal populations and connectivity. Technology for identification and manipulation of specific neural population has been extremely challenging. (2) Secondly, monitoring and quantifying locomotion requires high temporal and spatial resolution during free-moving behavior, which has not been approachable without advanced computational image processing tools. Although locomotion is intuitively reflected by rhythmic limb lift-off and footfalls, the MLR does not generate rhythmic activity in limb muscles. Instead, MLR likely coordinates whole-body locomotion. Since any goal-directed locomotion requires direction-specific regulation, it remains unclear how MLR regulate locomotion direction during locomotion initiation.

This paper is to examine the role of MLR in controlling goal-directed locomotion. The first experiment investigates the relationship of MLR neural activity and locomotion direction in a goal-directed behavioral task. It shows that MLR glutamatergic neural activity is predominantly modulated by movement direction during target pursuit. There are two types of glutamatergic neurons in MLR. One type responds to forward and backward movement, and the other type responds to steering(left and right) movement. Neurons shows modulatory response to steering prone to positively correlate with ipsilateral direction. Activity of these neurons is modulated by the center of mass movement even in absence of gaits.

The second experiment investigates the MLR glutamatergic neurons function in controlling locomotion direction. The function of MLR glutamatergic neurons show heterogenous effect on generating locomotion. Steering and forward-backward locomotion are elicited by separate populations of the MLR glutamatergic neurons. Additionally, the spatial distribution these functional distinct populations follows a topographical map inside the MLR. The rostral and ventral portion is prone to generate steering (left and right movement) locomotion and the dorso-caudal portion is more likely to generate symmetrical forward locomotion.

The third experiment examines whether MLR control of steering is achieved through frontal-cortical-pyramidal-to-MLR tract. Results shows that neural activity of motor cortex is bidirectionally modulated by steering velocity. Stimulation of pyramidal cells in supplementary motor cortex elicits similar steering movement as stimulations to MLR glutamatergic neurons. However, stimulation of cortical-MLR tract cannot elicit steering locomotion in free-moving animals.

Taken together, our results demonstrate that the MLR are important in controlling locomotion direction by regulating the center of mass movement. And the control of steering movement of MLR is independent of frontal cortex pyramidal tract.