Development of a wireless system for auditory neuroscience.

In order to study how the auditory cortex extracts communication sounds in a realistic acoustic environment, a wireless system is being developed that will transmit acoustic as well as neural signals. The miniature transmitter will be capable of transmitting two acoustic signals with 37.5 KHz bandwidths (75 KHz sample rate) and 56 neural signals with bandwidths of 9.375 KHz (18.75 KHz sample rate). These signals will be time-division multiplexed into one high bandwidth signal with a 1.2 MHz sample rate. This high bandwidth signal will then be frequency modulated onto a 2.4 GHz carrier, which resides in the industrial, scientic, and medical (ISM) band that is designed for low-power short-range wireless applications. On the receiver side, the signal will be demodulated from the 2.4 GHz carrier and then digitized by an analog-to-digital (A/D) converter. The acoustic and neural signals will be digitally demultiplexed from the multiplexed signal into their respective channels. Oversampling (20 MHz) will allow the reconstruction of the multiplexing clock by a digital signal processor (DSP) that will perform frame and bit synchronization. A frame is a subset of the signal that contains all the channels and several channels tied high and low will signal the start of a frame. This technological development will bring two benefits to auditory neuroscience. It will allow simultaneous recording of many neurons that will permit studies of population codes. It will also allow neural functions to be determined in higher auditory areas by correlating neural and acoustic signals without apriori knowledge of the necessary stimuli.

Cost-effectiveness of fusion with and without instrumentation for patients with degenerative spondylolisthesis and spinal stenosis.

STUDY DESIGN: A cost-effectiveness study was performed from the societal perspective. OBJECTIVE: To evaluate the costs and benefits of laminectomy alone and laminectomy with concomitant lumbar fusion for patients with degenerative lumbar spondylolisthesis and spinal stenosis. SUMMARY OF BACKGROUND DATA: Costs, probabilities, and utilities were estimated from the literature. Short-term risks considered were perioperative complications, the probability of the fusion healing, and the probability that surgery will relieve symptoms. Long-term risks considered were recurrence of symptoms and reoperation. METHODS: The 10-year costs, quality-adjusted life years, and incremental cost-effectiveness ratios (reported as dollars per quality-adjusted year of life gained) were calculated using a Markov model. Sensitivity analysis was performed on all variables using clinically plausible ranges. RESULTS: Laminectomy with noninstrumented fusion costs $56,500 per quality-adjusted year of life versuslaminectomy without fusion. The cost-effectiveness of laminectomy with noninstrumented fusion was most sensitive to the increase in quality-of-life associated with relief of severe stenosis symptoms. The cost-effectiveness ratio of instrumented fusion compared with noninstrumented fusion was $3,112,800 per quality-adjusted year of life. However, if the proportion of patients experiencing symptom relief after instrumented fusion was 90% as compared with 80% for patients with noninstrumented fusion, then the cost-effectiveness ratio of instrumented fusion compared with noninstrumented fusion would be $82,400 per quality-adjusted year of life. CONCLUSIONS: The cost-effectiveness of laminectomy with noninstrumented fusion compares favorably with other surgical interventions, although it depends greatly on the true effectiveness of these surgeries to alleviatesymptoms and on how patients value the quality-of-life effect of relieving severe stenosis symptoms. Instrumented fusion was very expensive compared with the incremental gain in health outcome. Better data on the effectiveness of these alternative procedures are needed.

Factors affecting lumbar spinal fusion.

There is little information on the effect of nonsurgical factors or postoperative anemia on achieving spinal fusion. In a prospective cohort study of 184 consecutive lumbar spinal fusions, we obtained data on socioeconomic, clinical, radiologic, and traditional surgical factors and analyzed associations between these factors and fusion status at 6 months post surgery. The overall fusion rate was 74%. Among the surgical factors, use of pedicle screw fixation (p = 0.005) predicted fusion success; postoperative anemia (hematocrit < 30%; p = 0.003) and a history of smoking (p = 0.050) predicted fusion failure. However, when the surgical factors were analyzed together with clinical and socioeconomic factors, back pain greater than or equal to leg pain (p < 0.001) and patients working at the initial visit (p = 0.001) predicted fusion success; shoulder pain at the initial visit (p < 0.001) and a family history of back surgery (p = 0.006) predicted fusion failure. These factors were stronger predictors of fusion status than were traditional surgical factors.

Classification of non-stationary neural signals.

Although a number of methods have been proposed for classification of individual action potentials embedded in multi-unit activity, they have been challenged by non-stationarity. The waveform shapes of action potentials can change rapidly over time as a result of shifts in membrane conductances during extended burst firing sequences and more slowly over time due to electrode drift. These changes are typically non-Gaussian. We present an algorithm for waveform identification that makes no assumptions on the distribution of these shapes other than the change in waveform shape for a particular neuron should not be discontinuous. We apply this algorithm to the resolution of multi-unit neural signals recorded in the cat visual cortex and we compare this approach to a spike sorting method that is based on the Bayesian likelihood of a spike fitting a particular model (Lewicki, M. Bayesian modeling and classification of neural signals. Neural Comput 1994;6(5):1005-1030.

Burst firing and modulation of functional connectivity in cat striate cortex.

We studied the influences of the temporal firing patterns of presynaptic cat visual cortical cells on spike generation by postsynaptic cells. Multiunit recordings were dissected into the activity of individual neurons within the recorded group. Cross-correlation analysis was then used to identify directly coupled neuron pairs. The 22 multiunit groups recorded typically showed activity from two to six neurons, each containing between 1 and 15 neuron pairs. From a total of 241 neuron pairs, 91 (38%) had a shifted cross-correlation peak, which indicated a possible direct connection. Only two multiunit groups contained no shifted peaks. Burst activity, defined by groups of two or more spikes with intervals of

Stimulus-dependent modulation of spike burst length in cat striate cortical cells.

Burst activity, defined by groups of two or more spikes with intervals of < or = 8 ms, was analyzed in responses to drifting sinewave gratings elicited from striate cortical neurons in anesthetized cats. Bursting varied broadly across a population of 507 simple and complex cells. Half of this population had > or = 42% of their spikes contained in bursts. The fraction of spikes in bursts did not vary as a function of average firing rate and was stationary over time. Peaks in the interspike interval histograms were found at both 3-5 ms and 10-30 ms. In many cells the locations of these peaks were independent of firing rate, indicating a quantized control of firing behavior at two different time scales. The activity at the shorter time scale most likely results from intrinsic properties of the cell membrane, and that at the longer scale from recurrent network excitation. Burst frequency (bursts per s) and burst length (spikes per burst) both depended on firing rate. Burst frequency was essentially linear with firing rate, whereas burst length was a nonlinear function of firing rate and was also governed by stimulus orientation. At a given firing rate, burst length was greater for optimal orientations than for nonoptimal orientations. No organized orientation dependence was seen in bursts from lateral geniculate nucleus cells. Activation of cortical contrast gain control at low response amplitudes resulted in no burst length modulation, but burst shortening at optimal orientations was found in responses characterized by supersaturation. At a given firing rate, cortical burst length was shortened by microinjection of gamma-aminobutyric acid (GABA), and bursts became longer in the presence of N-methyl-bicuculline, a GABA(A) receptor blocker. These results are consistent with a model in which responses are reduced at nonoptimal orientations, at least in part, by burst shortening that is mediated by GABA. A similar mechanism contributes to response supersaturation at high contrasts via recruitment of inhibitory responses that are tuned to adjacent orientations. Burst length modulation can serve as a form of coding by supporting dynamic, stimulus-dependent reorganization of the effectiveness of individual network connections.

GABAB-receptor-mediated inhibition reduces the orientation selectivity of the sustained response of striate cortical neurons in cats.

Blocking GABAA-receptor-mediated inhibition reduces the selectivity of striate cortical neurons for the orientation of a light bar primarily by reducing the selectivity of their onset transient (initial 200 ms) response. Blocking GABAB-receptor-mediated inhibition with phaclofen, however, is not reported to reduce the orientation selectivity of these neurons when it is measured with a light bar. We hypothesized that blocking GABAB-receptor-mediated inhibition would instead affect the orientation selectivity of cortical neurons by reducing the selectivity of their sustained response to a prolonged stimulus. To test this hypothesis, we stimulated 21 striate cortical neurons with drifting sine-wave gratings and measured their orientation selectivity before, during, and after iontophoretic injection of 2-hydroxy-saclofen (2-OH-S), a selective GABAB-receptor antagonist. 2-OH-S reduced the orientation selectivity of six of eight simple cells by an average of 28.8 (+/- 13.2) % and reduced the orientation selectivity of eight of 13 complex cells by an average of 32.3 (+/- 27.4) %. As predicted, 2-OH-S reduced the orientation selectivity of the neurons' sustained response, but did not reduce the orientation selectivity of their onset transient response. 2-OH-S also increased the length of spike "bursts" (two or more spikes with interspike intervals < or = 8 ms) and eliminated the orientation selectivity of these bursts for six cells. These results are the first demonstration of a functional role for GABAB receptors in visual cortex and support the hypothesis that two GABA-mediated inhibitory mechanisms, one fast and the other slow, operate within the striate cortex to shape the response properties of individual neurons.

Dorso-lumbar spine fractures: recumbent vs. operative treatment.

Internal fixation of fractures of the dorsal-lumbar spine with early ambulation is evaluated in this study of 100 patients with 106 fractures: 34 being treated by recumbency, 13 with Meurig-Williams plates, and 59 with Harrington rods. Fracture reduction in the recumbent group was 14 per cent unsatisfactory, 82 percent satisfactory, and only one case anatomical. Following plating, 38 per cent were unsatisfactory and 61 per cent satisfactory. Harrington rod reduction and internal fixation resulted in 67 per cent anatomical, 31 per cent satisfactory, and 2 per cent unsatisfactory. neurologic improvement in partial lesions was 53 per cent with Harrington rods and 44 per cent with recumbent treatment. For paraplegic patients the time required for wheelchair ambulation was reduced from 10.5 weeks with recumbent treatment to 5.3 weeks with Harrington instrumentation. Ambulatory candidate rehabilitation time was decreased from 7.1 weeks to 2.5 weeks. Complications were reduced from 18 per cent in the recumbent group to 7 per cent in the Harrington rod group. By using the three above-three below, rod long-fuse short approach rather than the two above-two below with fusion over the length of the rods technique, the number of anatomical reductions was increased from 70 per cent to 82 per cent and the length of the fusion decreased from 4.8 levels to 1.4 levels.

Thoracolumbar spinal injuries. A comparative study of recumbent and operative treatment in 100 patients.

Internal fixation of fractures of the thoracolumbar spine with early ambulation is evaluated in this study of 100 patients with 106 fractures, 34 of which were treated by recumbency, 13 with Meurig-Williams plates, and 59 with Harrington rods. Fracture reduction in the recumbent group was 14% unsatisfactory and 82% satisfactory; only one fracture was anatomically reduced. After plating, 38% of fracture reductions were unsatisfactory and 61% satisfactory. Harrington rod reduction and internal fixation resulted in 67% anatomic, 31% satisfactory, and 2% unsatisfactory reductions. Neurologic improvement in partial lesions was 53% with Harrington rods and 44% with recumbent treatment. For paraplegic patients the time between treatment and wheelchair mobilization was reduced from 10.5 weeks with recumbent treatment to 5.3 weeks with Harrington instrumentation. Rehabilitation time for ambulatory candidates was decreased from 7.1 weeks to 2.5 weeks. Complications were reduced from 18% in the recumbent group to 7% in the Harrington rod groups. By using the three above-three below, rod long/fuse short approach rather than the two above-two below with fusion over the length of the rods technique, the number of anatomic reductions was increased from 70% to 82% and the length of the fusion decreased from 4.8 levels to 1.4 levels.