Preference Reversals in Delay of Gratification

Intertemporal choices are decisions between outcomes occurring at different times. For example, people may choose to quit smoking cigarettes for the delayed health-related benefits associated with abstention, or they may continue to smoke for the immediate gratification associated with smoking now. Importantly, patterns of intertemporal choices among people are associated with a number of maladaptive behaviors (e.g., cigarette smoking). In the present set of studies, I examine a facet of intertemporal choice: preference reversals. Although there are multiple forms of preference reversal, I focus on those characterized by shifts in preference from a larger-later reward to a smallerimmediate reward after a choice of that larger-later reward. Little research has been dedicated to examining these preference reversals despite their potential role in some maladaptive behaviors (e.g., relapse). To address this gap, I first developed a procedure to examine these preference reversals in a preclinical rat model (Chapter II). After developing this procedure, I used it to examine the effect of delay pre-exposure training on preference reversals in rats, allowing me to investigate a potential process (i.e., changes in temporal expectations) contributing to these preference reversals (Chapter III). Importantly, identifying the processes that contribute to these preference reversals may provide the means for developing interventions to avoid such reversals as they relate to human health. Thus, the goal of these studies was to provide an important step in progressing our understanding of preference reversals so that interventions can be developed to prevent them in people

Complex Independent Component Analysis of Frequency-Domain Electroencephalographic Data

Independent component analysis (ICA) has proven useful for modeling brain and electroencephalographic (EEG) data. Here, we present a new, generalized method to better capture the dynamics of brain signals than previous ICA algorithms. We regard EEG sources as eliciting spatio-temporal activity patterns, corresponding to, e.g., trajectories of activation propagating across cortex. This leads to a model of convolutive signal superposition, in contrast with the commonly used instantaneous mixing model. In the frequency-domain, convolutive mixing is equivalent to multiplicative mixing of complex signal sources within distinct spectral bands. We decompose the recorded spectral-domain signals into independent components by a complex infomax ICA algorithm. First results from a visual attention EEG experiment exhibit (1) sources of spatio-temporal dynamics in the data, (2) links to subject behavior, (3) sources with a limited spectral extent, and (4) a higher degree of independence compared to sources derived by standard ICA.Comment: 21 pages, 11 figures. Added final journal reference, fixed minor typo

Validation of the 40 Hz Auditory Steady State Response as a Pharmacodynamic Biomarker of Evoked Neural Synchrony

Schizophrenia is a troubling and severe mental illness that is only incompletely treated by currently available drugs. New drug development is hindered by a scarcity of functionally relevant pharmacodynamic biomarkers that are translatable across preclinical and human subjects. Although psychosis is a major feature of schizophrenia, cognitive and negative symptoms determine the long-term functional outcomes for patients. Stimulus-evoked neural synchrony at gamma (~ 40 Hz) frequency plays an important role in the processing and integration of sensory information. Not surprisingly, schizophrenia patients show deficits in gamma oscillations. NMDA receptor (NMDAR) activation on fast-spiking parvalbumin-positive interneurons is deemed important for the generation of gamma oscillations. NMDA hypofunction has been proposed as an alternative hypothesis to the well-known dopamine dysregulation to explain the neurochemical abnormalities associated with schizophrenia. For this dissertation, we validated a preclinical model to pharmacologically probe NMDA-mediated gamma oscillations by further characterizing the auditory-steady state response (ASSR) in female Sprague Dawley rats. The ASSR is a measure of cortical neural synchrony evoked in response to periodic auditory stimuli. ASSR at 40 Hz is consistently disrupted in patients. First, we established the reliability of click train-evoked 40 Hz ASSR and tone-evoked gamma oscillations in 6 separate sessions, spread over a 3-week period. Then we established the sensitivity of these neural synchrony measures to acute NMDAR blockade using the high affinity NMDA channel blocker MK-801, using a repeated measures design. Next, we compared the reliability and sensitivity of the 40 Hz ASSR from two distinct recording sites. Results from this study showed that as compared to vertex, temporal recording showed a greater gamma synchrony. However, the temporal recording had poor test-retest reliability and lower sensitivity to MK-801-induced disruption. Lastly, we characterized the dose-response profiles of an NMDA co-agonist D-serine, an atypical (clozapine) and a typical (haloperidol) antipsychotic, on the 40 Hz ASSR. Results from these studies showed that only clozapine was effective in robustly augmenting 40 Hz ASSR. Furthermore, only clozapine pretreatment had partial protective effect against MK-801 induced ASSR disruption. Overall, this work establishes that vertex recorded 40 Hz ASSR is a reliable neural synchrony biomarker in female SD rats that is amenable for bidirectional pharmacodynamic modulation

Altered Cortical Oscillations: Investigations into a Putative Neural Correlate of Tinnitus

Abnormal cortical oscillations have been implicated in tinnitus generation. To gain further insight into this relationship, we performed two Experimental Series, both employing behavioural, pharmacological, and in vivo electrophysiological techniques in an animal model. To that end, we revealed three novel findings: (1) While exposure to 250 mg/kg sodium salicylate or transient loud noise induced behavioural evidence of tinnitus, these insults caused dissimilar effects on spontaneous cortical oscillations; (2) Despite these dissimilar effects, sodium salicylate and loud noise exposure caused similar deficits in the evoked oscillatory activity elicited by the auditory steady state response; and (3) Manipulation of medial geniculate body GABAergic inhibition is sufficient to alter spontaneous cortical oscillations, but does not induce tinnitus-like behaviour. Collectively, these findings suggest that there is no clear link between altered cortical oscillations and tinnitus, and the 40 Hz ASSR might be a useful tool for assessing the presence of tinnitus in animals

Reward-related activity in the medial prefrontal cortex is driven by consumption

An emerging literature suggests that the medial prefrontal cortex (mPFC) is crucial for the ability to track behavioral outcomes over time and has a critical role in successful foraging. Here, we examine this issue by analyzing changes in neuronal spike activity and local field potentials in the rat mPFC in relation to the consumption of rewarding stimuli. Using multi-electrode recording methods, we simultaneously recorded from ensembles of neurons and field potentials in the mPFC during the performance of an operant-delayed alternation task and a variable-interval licking procedure. In both tasks, we found that consummatory behavior (licking) activates many mPFC neurons and is associated with theta-band phase locking by mPFC field potentials. Many neurons that were modulated by the delivery of reward were also modulated when rats emitted bouts of licks during the period of consumption. The majority of these licking-modulated neurons were found in the rostral part of the prelimbic cortex, a region that is heavily interconnected with the gustatory insular cortex and projects to subcortical feeding-related centers. Based on the tight coupling between spike activity, theta-band phase locking, and licking behavior, we suggest that reward-related activity in the mPFC is driven by consummatory behavior

Representation of Multiple, Independent Categories in the Primate Prefrontal Cortex

Neural correlates of visual categories have been previously identified in the prefrontal cortex (PFC). However, whether individual neurons can represent multiple categories is unknown. Varying degrees of generalization versus specialization of neurons in the PFC have been theorized. We recorded from lateral PFC neural activity while monkeys switched between two different and independent categorical distinctions (Cats versus Dogs, Sports Cars versus Sedans). We found that many PFC neurons reflected both categorical distinctions. In fact, these multitasking neurons had the strongest category effects. This stands in contrast to our lab's recent report that monkeys switching between competing categorical distinctions (applied to the same stimulus set) showed independent representations. We suggest that cognitive demands determine whether PFC neurons function as category “multitaskers.”National Institute of Mental Health (U.S.) (Grant 2R01MH065252-06