Of the many types of devastating spinal cord injuries, incomplete injuries of the cervical spinal cord are the most common among patients. For these individuals, the highest treatment priority is restoration of hand and arm function; much more important than any other symptom of paralysis. The goal of our project is to restore hand and arm function by recording movement intention in the brain and using it in real time to control spinal cord stimulation. We use single unit activity encoding movement intention in the rat motor cortex, and intra-spinal microstimulation (ISMS) for movement induction. ISMS may be superior to direct muscle stimulation (FES), since it causes little fatigue and a more natural recruitment of motor pools. ISMS in the cervical and lumbar regions of the spinal cord can also be utilized to produce a wide array of functional limb movements. By using rats that I have trained to perform a lever-pressing task, I can quantify the functional relevance of movements evoked by varying ISMS parameters. By combining both recorded cortical data and ISMS, we have created a brain-machine spinal interface (BMSI). This BMSI can deliver brain-controlled, functionally useful stimulation directly to the spinal cord and caudal to a contusion injury in order to restore some movements to the animal’s injured forelimb. Our long-term goal is to translate this device to a clinical setting, where it could be used to restore hand and arm function to patients with complete spinal cord injuries.

The human brain is rapidly growing during the last trimester and there is evidence that premature birth is related to adverse neurological events. Magnetic resonance (MR) imaging of premature neonates and subsequent automated segmentation allows us to quantify subtle disruptions in cortical growth and folding in large population based studies. We use an age-specific automated tissue segmentation technique combined with an age-specific parcellation scheme to study regional patterns of tissue growth in a large study of brain development in premature neonates. We aimed to investigate the additional information provided by regional analysis of MR scans when determining risks for delayed neurocognitive outcomes. Our image analysis framework incorporates a spatiotemporal reference atlas that covers the age range of 27.43 to 46.43 gestational weeks (GW), and consisted of manually segmented brain tissues and 8 hemispheric lobe regions. The tissue atlas was used to automatically segment all 269 MR scans, age range from 27.29 to 47.00 GW, using a hybrid framework that combines an age-specific atlas-based EM segmentation with a patch-based prior. This tissue segmentation was then used to re-align the subject anatomy with an age-specific tissue template and the region parcellation of each subject was carried out by template probability propagation into the subject anatomy from the spatiotemporal parcellation model. Multiple linear regression models of the parcellation volumes, divided into gray matter and white matter tissues, showed a significant correlation between regional volume and Bayley’s Scale of Infant and Toddler Development scores, beyond gestational age at birth. Parietal and occipital lobes were clear markers for language and motor abilities, while the temporal lobe volumes were correlated with cognitive abilities. These findings support a more anatomically-specific analysis of brain structure after premature birth and may provide the possibility of earlier and more specific clinical diagnostics and timely developmental interventions.

In order to communicate, patients with total loss of muscle control including eye movement can rely on brain computer interfaces (BCI) that utilize evoked related potentials (ERP) which are voltage deflection of the brain following stimulus presentation recorded using EEG. Typically, ERP spellers rely on visual input. However, due to the auditory system's acute ability to selectively attend an auditory stream in what's known as the "cocktail effect", new speller paradigms that aid listeners' ability to selectively attend may increase the maximum bitrate of communication. The focus of this project was to create a unique auditory ERP-based speller that allows users to successfully use tone, spatial location, and informational cues to aid in auditory streaming while still increasing the total amount of selections of auditory streams. The research project can be separated into two phases: 1) a proof of concept psychophysics experiment assessing users ability to discriminate different auditory cues used in an auditory BCI environment and 2) an application of psychophysics findings from the previous phase to an online analysis of bitrate using EEG recording which will be conducted in the summer of 2014. This presentation will focus on analyzing and applying the experimental findings from the first phase to explore how can we modify parameters of the experiment design to maximize the bitrate (i.e. either through maximizing the ERP response amplitude, improving accuracy, lowering trial time, etc.). This project offers future possibilities for auditory systems to help not only improve the ease of use and practicality for the community of individuals who rely on speller systems but in other areas for the BCI community as a whole.

In natural environments, animals seeking resources face potential perils associated with foraging behavior, namely predation. Thus, animals must balance their needs with risks by utilizing adaptive behavioral strategies, such as adapting foraging behavior in the presence of environmental threats. The periaqueductal gray (PAG) has been implicated in the generation of defensive behaviors as part of this fear system. Specifically, the dorsal PAG (dPAG) is involved in escape when a threat is imminent (proximal), while the ventral PAG (vPAG) is involved in freezing when a threat is relatively remote (distal). Previous research has shown that the stimulation of the dPAG is an effective unconditioned stimulus (US) in fear conditioning because it transmits aversive US information to the amygdala, a crucial component of the fear conditioning system. Electrolytic lesions of the dPAG have shown to enhance defensive freezing in fear conditioning paradigms, supporting the view that the dPAG is involved in a circa-strike adaptive response to escape a predatory attack. In order to investigate the role of the dPAG in a risky foraging paradigm, I trained two groups of rats, sham controls (n=2) and dPAG lesions (n=4), to venture into a foraging area in which a remotely controlled robot surges and snaps as the animal approaches the food pellets placed at varying distances from the safe nest zone. The sham control animals learned quickly that the robot could not physically harm them as it always surged a fixed distance, successfully retrieving the pellets at all distances after the first two trials. The dPAG lesioned animals had a lower success rate of retrieving the pellets due to compromised escape behavior. These results suggest that the dPAG mediates threat detection and defensive responses in semi-naturalistic environments, shedding more light on the fear system to better understand anxiety disorders.

The balance between neuronal birth and death is a fundamental process of adult neural plasticity that mediates the maintenance and production of behavior. Aberration in this balance often coincides with neurodegenerative diseases including Parkinson’s, chronic depression, and stroke. Songbirds are an excellent model for exploring the dynamics of neuronal turnover, i.e. the balance between neuronal birth and death, and its effects on behavior, as seasonal production of song is under the control of a well-defined plastic neural circuit. This circuit includes the song control nucleus HVC (proper name) and its target, the robust nucleus of the arcopallium. Seasonal plasticity of HVC in Gambel’s white-crowned sparrows (Zonotrichia leucophrys gambelli) involves pronounced changes in neuron number; HVC neuron number changes 25% (>68,000 neurons) between breeding and nonbreeding seasons. The dramatic differences in neuron number between breeding and nonbreeding conditions suggest that dynamics between neuronal birth and death also differ between seasons. To determine if there are seasonal differences in neuronal turnover, I labeled two cohorts of new HVC neurons separated by one, two, and four months with two thymidine analogs, BrdU and Edu, in both breeding and nonbreeding condition birds. I determined turnover rate by quantifying the number of new neurons from each cohort that were present in HVC at the different intervals. Preliminary data indicates that in breeding birds more new neurons belonged to the first cohort, whereas in nonbreeding birds more new neurons belonged to the second cohort. The replacement of first cohort neurons by the second cohort neurons increases with time in non-breeding birds. This suggests that testosterone in breeding birds promotes survival of the first wave of new neurons entering HVC. This study demonstrates that the seasonal changes in HVC neuron number results from a dynamic shifting balance between neuronal birth and death.

The broad association of neurological disorders, epileptic symptoms, and dysfunctional bone regulation in both animal and human studies support the hypothesis that neurological activity in the brain affects the formation and remodeling of bone throughout the body. In mice, brain-specific deletion of the PTEN gene has been shown to induce an overactive P13K-Akt-mTOR pathway, resulting in macrocephaly, hypertrophic neurons, and epileptic symptoms with persistent seizures. In this study, we present evidence that brain-specific knockout of the PTEN gene induces abnormal skeletal activity in mice. Total volume was significantly increased in knockout mice in the proximal tibia (p<0.01) and mid diaphysis (p<0.01) compared to wildtype controls, while tissue mineral density was significantly lower in knockout mice for both tibia locations (p<0.01). Effects of PTEN deletion were highly localized and compartment specific, as evidenced by the significantly lower trabecular bone volume in the proximal tibia (p<0.05) but significantly higher bone volume in the mid-diaphysis (p<0.05). Given the association of brain-specific PTEN deletion with seizure-like cortical activity, as well as the known influence of skeletal nerves on bone cell function, these studies provide an essential first step toward understanding the role of cortical brain activity in regulating bone metabolism. Further research into the brain’s role in bone homeostasis could be fundamental in treating bone diseases such as osteoporosis.