Faculty Bibliography

The thalamus is a key crossroad structure in the brain and is recognized as a major contributor to sensory perception, attention, sleep and arousal and memory. For all senses except olfaction, the information from the sensory neurons necessarily passes through a thalamic nucleus before reaching the primary sensory cortex. However, an olfactory thalamic nucleus exists: the mediodorsal thalamic nucleus (MDT) receives direct input from different olfactory structures including the piriform cortex (PCX), and in turn has bi-directional projections with the orbitofrontal cortex (OFC). Functionally, we have shown that, in urethane-anesthetized rats, MDT units respond to a wide variety of odorants and that odor stimuli induce a conjoint emergence of beta frequency oscillations in both the MDT and the PCX. Beyond this odor responsiveness, the precise role of the MDT in olfaction remains unclear. In fact, lesion studies in both humans and animal models suggest a role for the MDT in olfactory perception, odor discrimination, learning and attention. To investigate precisely the role of the MDT in olfactory processing, we recorded MDT single unit activity, using a multi-tetrode drive, in 8 rats performing a two alternative odor discrimination task. Our preliminary analyses demonstrate that a majority of MDT units modulate their firing rate during the task window. The MDT units seem to encode a variety of information. For example, a subset of MDT units modulate their firing rate before the nose poke/ trial initiation, others show modulation during the sampling period as a function of the odorant, while others are modulated during sampling termination/decision making. Our initial analyzes thus reveal the involvement and the complex role of the MDT in olfactory processing

Episodic memory decline, olfactory identification deficits and the ApoE-e4 allele constitute risk factors for incident Alzheimers' Disease (AD). However, the relationships among these three risk factors are poorly understood, in part due to the paucity of large longitudinal datasets that involve such assessments. The present study used data from the Betula study (n=1225), which involves memory testing every five years. Participants completed an odor identification test, were genotyped for the ApoE gene, and had completed episodic memory testing for a 10-year period (3 testing occasions) leading up to the olfactory assessment. The episodic memory measure was a composite of five tasks, and decline was defined as an estimated change >1SD below the age norm. Participants were thus classified as "decliners" (n=125) or "non-decliners" (n=1100). Results showed that decliners had a poorer olfactory identification than nondecliners. However, when ApoE-e4 was taken into consideration, the association between memory decline and odor identification deficit was only present in ApoE-e4 carriers, whereas odor identification in memory decliners without e4 reached the same level as that of non-decliners. Future research on the role of olfaction in age-related memory impairment and dementia should consider the mediating role played by the ApoE-e4

The rodent piriform cortex (PCX) is a paleocortical structure known to support olfactory perception toward learned behavior. While the anterior PCX is used in associative odor object information decoding, the posterior PCX receives more descending input fibers from brain structures such as the amygdala that are thought to provide a qualitative relevance to raw odor percepts. Here we investigate the influence of top-down influence of specific brain regions on spontaneous and odor-induced activity in the posterior PCX at the single unit level. Using optogenetic techniques, we artificially stimulated descending fibers in the posterior PCX that were virally transduced from one of two interconnected brain regions. Specifically, the lateral and basolateral amygdala (LA/BLA) and the lateral entorhinal cortex (LEC) were independently targeted to express Channelrhodopsin in pyramidal neurons that also express CaMKII. Photostimulation at 473nm and 1mW near infected axon terminals in the posterior piriform was sufficient to drive temporally coincident responses of unit activity and local field potential, as recorded in anaesthetized animals injected at any one of the two target regions. Odorpaired photostimulation of descending fibers at the posterior PCX modulated local single unit response patterns compared to odor only. Photo-induced effects on unit odor responses ranged from suppressive to stimulatory, which often varied depending on the combinatorial timing of odor and light stimulation. These results demonstrate the importance of top-down inputs to piriform cortex in odor coding, and highlight that cortical odor processing takes place in a rich milieu of sensory, emotional and contextual information

Two studies explored the role of the amygdala in response modulation by an aversive conditioned stimulus (CS) in rats. Experiment 1 investigated the role of amygdala circuitry in conditioned suppression using a paradigm in which licking for sucrose was inhibited by a tone CS that had been previously paired with footshock. Electrolytic lesions of the lateral amygdala (LA) impaired suppression relative to sham-operated animals, and produced the same pattern of results when applied to central amygdala. In addition, disconnection of the lateral and central amygdala, by unilateral lesion of each on opposite sides of the brain, also impaired suppression relative to control subjects that received lesions of both areas on the same side. In each case, lesions were placed following Pavlovian conditioning and instrumental training, but before testing. This procedure produced within-subjects measures of the effects of lesion on freezing and between-group comparisons for the effects on suppression. Experiment 2 extended this analysis to a task where an aversive CS suppressed shuttling responses that had been previously food reinforced and also found effects of bilateral lesions of the central amygdala in a pre-post design. Together, these studies demonstrate that connections between the lateral and central amygdala constitute a serial circuit involved in processing aversive Pavlovian stimuli, and add to a growing body of findings implicating central amygdala in the modulation of instrumental behavior.

The Patient Protection and Affordable Care Act focuses on improving consumer engagement and patient-centered care. This article describes the design and rationale of a study targeting family engagement in pediatric mental health services. The study is a 90-day randomized trial of a telephone-delivered Family Navigator services versus usual care for parents of Medicaid-insured youth younger than 13 years with serious mental illness. Youth are identified through a pediatric antipsychotic medication preauthorization program. Family Navigators offer peer support to empower and engage parents in their child's recovery. Outcomes include parent report of empowerment, social support, satisfaction with child mental health services, and child functioning as well as claims-based measures of psychotherapy service utilization and antipsychotic medication dosage. The focus on "family-centered" care in this study is strongly supported by the active role of consumers in study design and implementation.

PURPOSE: Untreated parent mental health problems have deleterious effects upon the family, yet caregivers are unlikely to receive services for their emotional health. We conducted a review of treatments and services for children and adolescents that also offered services to parents. METHODS: Child treatment and service studies were included in the present study if they analyzed parent symptoms or diagnoses over time, and the intervention contained a parent component. RESULTS: Of 200 studies reviewed, 20 contained a component for the parent and assessed the parent's emotional health at multiple time points. Depression and anxiety were the most commonly studied parental mental health problem; most parent components consisted of behavioral strategies in service of the child's psychological health. CONCLUSION: Major shifts in health care policy affecting mental health services provide an opportunity to create integrated and coordinated health and behavioral health systems. Attention must be given to ensure that the workforce of providers, the administrative structures, and the reimbursement strategies are strengthened and connected to serve the needs of parents/caregivers and children in order to enhance family outcomes.