Faculty Bibliography

OBJECTIVE: To determine the source localization(s) of the midlatency auditory magnetic response M50, the equivalent of the P50 potential, a sleep state-dependent waveform known to habituate to repetitive stimulation. METHODS: We used a paired stimulus paradigm at interstimulus intervals of 250, 500 and 1000 ms, and magnetoencephalographic (MEG) recordings were subjected to computational methods for current density reconstruction, blind source separation, time-frequency analysis, and data visualization to characterize evoked dynamics. RESULTS: Each subject showed localization of a source for primary auditory evoked responses in the region of the auditory cortex, usually at a 20-30 ms latency. However, responses at 40-70 ms latency that also decreased following the second stimulus of a pair were not localizable to the auditory cortex, rather showing multiple sources usually including the frontal lobes. CONCLUSIONS: The M50 response, which shows habituation to repetitive stimulation, was not localized to the auditory cortex, but showed multiple sources including frontal lobes. SIGNIFICANCE: These MEG results suggest that sources for the M50 response may represent non-auditory, perhaps arousal-related, diffuse projections to the cortex

PRIMARY OBJECTIVE: To explore whether baseline diffusion tensor imaging (DTI) metrics are predictive of cognitive functioning 6 months post-injury in patients with mild traumatic brain injury (MTBI). RESEARCH DESIGN: Seventeen patients with MTBI and 29 sex- and age-matched healthy controls were studied. METHODS AND PROCEDURES: Participants underwent an MRI protocol including DTI, at an average of 4.0 (range: 1-10) days post-injury. Mean diffusivity (MD) and fractional anisotropy (FA) were measured in the following white matter (WM) regions: centra semiovale, the genu and the splenium of the corpus callosum and the posterior limb of the internal capsule. Participants underwent neuropsychological (NP) testing at baseline and at 6-month follow-up. Least squares regression analysis was used to evaluate the association of MD and FA with each NP test score at baseline and follow-up. MAIN OUTCOMES AND RESULTS: Compared to controls, average MD was significantly higher (p = 0.02) and average FA significantly lower (p = 0.0001) in MTBI patients. At the follow-up, there was a trend toward a significant association between baseline MD and response speed (r = -0.53, p = 0.087) and a positive correlation between baseline FA and Prioritization form B (r = 0.72, p = 0.003). CONCLUSIONS: DTI may provide short-term non-invasive predictive markers of cognitive functioning in patients with MTBI

Mutations in the lamin A/C (LMNA) gene, which encodes nuclear membrane proteins, cause a variety of human conditions including dilated cardiomyopathy (DCM) with associated cardiac conduction system disease. To investigate mechanisms responsible for electrophysiologic and myocardial phenotypes caused by dominant human LMNA mutations, we performed longitudinal evaluations in heterozygous Lmna(+/-) mice. Despite one normal allele, Lmna(+/-) mice had 50% of normal cardiac lamin A/C levels and developed cardiac abnormalities. Conduction system function was normal in neonatal Lmna(+/-) mice but, by 4 weeks of age, atrioventricular (AV) nodal myocytes had abnormally shaped nuclei and active apoptosis. Telemetric and in vivo electrophysiologic studies in 10-week-old Lmna(+/-) mice showed AV conduction defects and both atrial and ventricular arrhythmias, analogous to those observed in humans with heterozygous LMNA mutations. Isolated myocytes from 12-month-old Lmna(+/-) mice exhibited impaired contractility. In vivo cardiac studies of aged Lmna(+/-) mice revealed DCM; in some mice this occurred without overt conduction system disease. However, neither histopathology nor serum CK levels indicated skeletal muscle pathology. These data demonstrate cardiac pathology due to heterozygous Lmna mutations reflecting a 50% reduction in lamin protein levels. Lamin haploinsufficiency caused early-onset programmed cell death of AV nodal myocytes and progressive electrophysiologic disease. While lamin haploinsufficiency was better tolerated by non-conducting myocytes, ultimately, these too succumbed to diminished lamin levels leading to dilated cardiomyopathy, which presumably arose independently from conduction system disease

Whether ocular orientation to gravity is produced solely by linear acceleration in the horizontal plane of the head or depends on both horizontal and vertical components of the acceleration of gravity is controversial. Here, we compared orienting eye movements of rabbits during head tilt to those produced by centrifugation that generated centripetal acceleration along the naso-occipital (X-), bitemporal (Y-) and vertical (Z-) axes in a constant gravitational field. Sensitivities of ocular counter-pitch and vergence during pitch tilts were approximately 25 degrees /g and approximately 26 degrees /g, respectively, and of ocular counter-roll during roll tilts was approximately 20 degrees /g. During X-axis centripetal acceleration with 1 g of gravity along the Z-axis, pitch and vergence sensitivities were reduced to approximately 13 degrees /g and approximately 16 degrees /g. Similarly, Y-axis acceleration with 1g along the Z-axis reduced the roll sensitivity to approximately 16 degrees /g. Modulation of Z-axis centripetal acceleration caused sensitivities to drop by approximately 6 degrees /g in pitch, approximately 2 degrees /g in vergence, and approximately 5 degrees /g in roll. Thus, the constant 1g acceleration along the Z-axis reduced the sensitivity of ocular orientation to linear accelerations in the horizontal plane. Orienting responses were also modulated by varying the head Z-axis acceleration; the sensitivity of response to Z-axis acceleration was linearly related to the response to static tilt. Although the sign of the Z-axis modulation is opposite in the lateral-eyed rabbit from that in frontal-eyed species, these data provide evidence that the brain uses both the horizontal and the vertical components of acceleration from the otolith organs to determine the magnitude of ocular orientation in response to linear acceleration

Though many neuronal cell fate decisions result in reproducible outcomes, stochastic choices often lead to spatial randomization of cell subtypes. This is often the case in sensory systems where expression of a specific sensory receptor gene is selected randomly from a set of possible outcomes. Here, we describe recent findings elucidating the mechanisms controlling color photoreceptor subtypes in flies and olfactory receptor subtypes in worms and mice. Although well-known biological concepts such as lateral signaling and promoter selection play roles in these cases, fundamental questions concerning these choice mechanisms remain.

OBJECTIVE: To assess word recognition and pitch-scaling abilities of cochlear implant users first implanted with a Nucleus 10-mm Hybrid electrode array and then reimplanted with a full length Nucleus Freedom array after loss of residual hearing. BACKGROUND: Although electroacoustic stimulation is a promising treatment for patients with residual low-frequency hearing,a small subset of them lose that residual hearing. It is not clear whether these patients would be better served by leaving in the 10-mm array and providing electric stimulation through it, or by replacing it with a standard full-length array. METHODS: Word recognition and pitch-scaling abilities were measured in 2 users of hybrid cochlear implants who lost their residual hearing in the implanted ear after a few months. Tests were repeated over several months, first with a 10-mm array, and after, these patients were reimplanted with a full array. The word recognition task consisted of 2 50-word consonant nucleus consonant (CNC) lists. In the pitch-scaling task, 6 electrodes were stimulated in pseudorandom order, and patients assigned a pitch value to the sensation elicited by each electrode. RESULTS: Shortly after reimplantation with the full electrode array, speech understanding was much better than with the 10-mm array. Patients improved their ability to perform the pitch-scaling task over time with the full array, although their performance on that task was variable, and the improvements were often small. CONCLUSION: 1) Short electrode arrays may help preserve residual hearing but may also provide less benefit than traditional cochlear implants for some patients. 2) Pitch percepts in response to electric stimulation may be modified by experience