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Development [Editorial]

Luo, LQ; Fishell, G
ISI:000257621700001
ISSN: 0959-4388
CID: 86848

Vertical (Z-axis) acceleration alters the ocular response to linear acceleration in the rabbit

Maruta, Jun; Raphan, Theodore; Simpson, John I; Cohen, Bernard
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
PMID: 17926026
ISSN: 1432-1106
CID: 94734

Exploring opportunities for collaboration between the corporate sector and the dental education community

Alexander, D; Clarkson, J; Buchanan, R; Chadwick, G; Chesters, R; Drisko, C L; Douglass, C W; Farrell, L; Fletcher, K; Makoni, F; Monaco, M; Nordquist, B; Park, N I; Riggs, S; Schou, L; Smales, F C; Stamm, J W; Toh, C G; Volpe, T; Ward, P; Warren, P
The ultimate purpose of both dental industry and dental education is to improve the oral health of the public. This report provides background information on the different roles and objectives of the dental industry and dental education communities, the different operating environment of each sector and also areas of common interest where collaboration will be of mutual benefit. The report addresses five areas for potential collaboration between the dental industry and the dental education communities: 1. Contribution to joint activities. 2. Effectiveness and efficiency. 3. Workforce needs. 4. Middle- and low-income countries. 5. The future of International Federation of Dental Educators and Associations (IFDEA). The traditional areas of support and their limitations that have been provided by industry are outlined in the report and some new approaches for collaboration are considered. Industry-based research has been an important factor in developing new products and technologies and in promoting oral health. However there is a need to facilitate the introduction of these developments at an early stage in the education process. Industry has to operate in an efficient manner to remain competitive and maximise its returns and therefore survive. The academic sector operates in a different environment and under different governance structures; although some trends are noted towards adoption of greater efficiency and financial accountability similar to industry. Opportunities to jointly develop best business practices should be explored. Industry has responded well to the oral health needs of the public through the development of new products and technologies. The education community needs to respond in a similar way by examining different healthcare delivery models worldwide and developing programmes to train members of the dental team to cater for future needs and demands of communities in different regions of the world. The reputation of industry-based scientists and clinicians is high, and their role in contributing to the dental education process in practical ways needs to be explored and further developed. Closer relationships between industry scientists and faculty and students could assist industrys need and desire to develop new technologies for the broader dental care system. The corporate sector can play a key role in the future success of IFDEA by providing support and expertise in developing areas such as regional leadership institutes, a Global Faculty and Network and in collaborating in developing continuing education programmes as well as involvement in its governance. Thirteen recommendations are made in the report. These are considered to be important initial steps in developing the already strong relationship between the education and corporate sectors. Partnership and collaborating more effectively along the lines suggested should, almost certainly, generate mutually beneficial outcomes, whilst serving over the long term to elevate the publics oral health status on a global basis.
PMID: 18289269
ISSN: 1396-5883
CID: 3629782

Reimplantation of hybrid cochlear implant users with a full-length electrode after loss of residual hearing [Case Report]

Fitzgerald, Matthew B; Sagi, Elad; Jackson, Michael; Shapiro, William H; Roland, J Thomas Jr; Waltzman, Susan B; Svirsky, Mario A
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
PMID: 18165793
ISSN: 1531-7129
CID: 76765

Magnetic sources of the M50 response are localized to frontal cortex

Garcia-Rill, E; Moran, K; Garcia, J; Findley, W M; Walton, K; Strotman, B; Llinas, R R
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
PMCID:2272533
PMID: 18078782
ISSN: 1388-2457
CID: 78727

Lamin A/C haploinsufficiency causes dilated cardiomyopathy and apoptosis-triggered cardiac conduction system disease

Wolf, Cordula M; Wang, Libin; Alcalai, Ronny; Pizard, Anne; Burgon, Patrick G; Ahmad, Ferhaan; Sherwood, Megan; Branco, Dorothy M; Wakimoto, Hiroko; Fishman, Glenn I; See, Vincent; Stewart, Colin L; Conner, David A; Berul, Charles I; Seidman, Christine E; Seidman, J G
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
PMCID:3011813
PMID: 18182166
ISSN: 1095-8584
CID: 96064

Predicting grade of cerebral glioma using vascular-space occupancy MR imaging

Lu, H; Pollack, E; Young, R; Babb, J S; Johnson, G; Zagzag, D; Carson, R; Jensen, J H; Helpern, J A; Law, M
BACKGROUND AND PURPOSE: MR imaging can measure tissue perfusion and the integrity of the blood-brain barrier. We hypothesize that a combined measure of cerebral blood volume and vascular permeability using vascular-space occupancy (VASO) MR imaging, a recently developed imaging technique, is of diagnostic value for predicting tumor grade. MATERIALS AND METHODS: Thirty-nine patients (9 World Health Organization [WHO] grade II, 20 grade III, and 10 grade IV as determined by histopathologic assessment) were examined using VASO MR imaging, and regions-of-interest analysis was performed in tumoral regions, as well as in regions contralateral to the tumor. A Mann-Whitney test was conducted on the resulting VASO indices for a pairwise comparison across tumor grades. Nominal logistic regression was used to evaluate the use of VASO parameters for predicting group membership (by the percentage of correct classifications). RESULTS: The ratio between tumor side and contralateral side, VASO(Ratio), showed significant differences in all 3 of the pairwise comparisons (P < .01). VASO values in the tumoral regions, VASO(Tumor), showed significant difference between grade II and III and between II and IV but not between III and IV. Both VASO(Tumor) and VASO(Ratio) were found to be significant predictors of tumor grade, giving diagnostic accuracies of 66.7% and 71.8%, respectively. When testing to discriminate grade II tumors from higher grade tumors, the areas under the receiver operating characteristic curve were found to be 0.974 and 0.985 for VASO(Tumor) and VASO(Ratio), respectively. CONCLUSION: VASO MR imaging can be used for noninvasive tumor grade prediction based on cerebral blood volume and vascular permeability. VASO is more effective in separating WHO grade II from higher grades than in separating grade III from grade IV
PMID: 17974612
ISSN: 1936-959x
CID: 78348

Type III neuregulin-1 promotes oligodendrocyte myelination

Taveggia, Carla; Thaker, Pratik; Petrylak, Ashley; Caporaso, Gregg L; Toews, Arrel; Falls, Douglas L; Einheber, Steven; Salzer, James L
The axonal signals that regulate oligodendrocyte myelination during development of the central nervous system (CNS) have not been established. In this study, we have examined the regulation of oligodendrocyte myelination by the type III isoform of neuregulin-1 (NRG1), a neuronal signal essential for Schwann cell differentiation and myelination. In contrast to Schwann cells, primary oligodendrocytes differentiate normally when cocultured with dorsal root ganglia (DRG) neurons deficient in type III NRG1. However, they myelinate type III NRG1-deficient neurites poorly in comparison to wild type cultures. Type III NRG1 is not sufficient to drive oligodendrocyte myelination as sympathetic neurons are not myelinated even with lentiviral-mediated expression of NRG1. Mice haploinsufficient for type III NRG1 are hypomyelinated in the brain, as evidenced by reduced amounts of myelin proteins and lipids and thinner myelin sheaths. In contrast, the optic nerve and spinal cord of heterozygotes are myelinated normally. Together, these results implicate type III NRG1 as a significant determinant of the extent of myelination in the brain and demonstrate important regional differences in the control of CNS myelination. They also indicate that oligodendrocyte myelination, but not differentiation, is promoted by axonal NRG1, underscoring important differences in the control of myelination in the CNS and peripheral nervous system (PNS)
PMID: 18080294
ISSN: 0894-1491
CID: 76859

Development of a disease severity scoring system for patients with Pompe disease [Meeting Abstract]

Marsden, D; Berger, K; van der Ploeg, A; Case, L; Dandrea, C; Kishnani, P; Giannini, E
ISI:000253358500083
ISSN: 1096-7192
CID: 87127

Decoding spatiotemporal spike sequences via the finite state automata dynamics of spiking neural networks

Jin, Dezhe Z.
Temporally complex stimuli are encoded into spatiotemporal spike sequences of neurons in many sensory areas. Here, we describe how downstream neurons with dendritic bistable plateau potentials can be connected to decode such spike sequences. Driven by feedforward inputs from the sensory neurons and controlled by feedforward inhibition and lateral excitation, the neurons transit between UP and DOWN states of the membrane potentials. The neurons spike only in the UP states. A decoding neuron spikes at the end of an input to signal the recognition of specific spike sequences. The transition dynamics is equivalent to that of a finite state automaton. A connection rule for the networks guarantees that any finite state automaton can be mapped into the transition dynamics, demonstrating the equivalence in computational power between the networks and finite state automata. The decoding mechanism is capable of recognizing an arbitrary number of spatiotemporal spike sequences, and is insensitive to the variations of the spike timings in the sequences.
ISI:000253085300008
ISSN: 1367-2630
CID: 3332002