Determining the presence of bias error using statistical methods.

Current techniques in image-guided surgery rely on the use of localizers for the measurement of position in physical space. These measurements are prone to error due to intrinsic properties of the localizer used. The error and thus accuracy of a localizer can be determined using various techniques, many of which assume that the error is isotropic and free of bias. A bias error adds an orientation dependence to the error of measured points. Determination of the presence of a bias error is an important component in the characterization of a localizer's performance. Statistical analysis of localized points on a rigid phantom can be used to detect the presence of a bias error. In this paper, we will examine the use of statistical techniques in the characterization of a series of localizers and how that information is useful in determining localizer efficacy.

Wavelet methods for spike detection in mouse renal sympathetic nerve activity.

Abnormal autonomic nerve traffic has been associated with a number of peripheral neuropathies and cardiovascular disorders prompting the development of genetically altered mice to study the genetic and molecular components of these diseases. Autonomic function in mice can be assessed by directly recording sympathetic nerve activity. However, murine sympathetic spikes are typically detected using a manually adjusted voltage threshold and no unsupervised detection methods have been developed for the mouse. Therefore, we tested the performance of several unsupervised spike detection algorithms on simulated murine renal sympathetic nerve recordings, including an automated amplitude discriminator and wavelet-based detection methods which used both the discrete wavelet transform (DWT) and the stationary wavelet transform (SWT) and several wavelet threshold rules. The parameters of the wavelet methods were optimized by comparing basal sympathetic activity to postmortem recordings and recordings made during pharmacological suppression and enhancement of sympathetic activity. In general, SWT methods were found to outperform amplitude discriminators and DWT methods with similar wavelet coefficient thresholding algorithms when presented with simulations with varied mean spike rates and signal-to-noise ratios. A SWT method which estimates the noise level using a "noise-only" wavelet scale and then selectively thresholds scales containing the physiologically important signal information was found to have the most robust spike detection. The proposed noise-level estimation method was also successfully validated during pharmacological interventions.

Treatment enhances ultradian rhythms of CSF monoamine metabolites in patients with major depressive episodes.

Unipolar and bipolar depressions show abnormal behavioral manifestations of ultradian (less than 24 h) rhythms, but abnormal rhythms of the central neurotransmitters thought to be important for depression pathophysiology (eg dopamine (DA) and serotonin (5-HT)) have not been shown in this time frame. Since antidepressant treatments normalize disrupted rhythms in depression (eg rapid-eye-movement sleep and hormonal rhythms), we hypothesized that depression-related changes in ultradian oscillations of DA and 5-HT might be revealed during antidepressant treatment. Cerebrospinal fluid (CSF) samples collected q10 min for 24 h in 13 patients experiencing major depressive episodes (MDE) before and after treatment for 5 weeks with sertraline or bupropion were assayed for levels of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), and their ratio was calculated. Data were analyzed in the frequency domain using Fourier transforms and multivariate permutation testing. Antidepressant treatments were associated with decreased variance for 5-HIAA, increased variance for HVA, and markedly increased variance for the HVA : 5-HIAA ratio (p<0.05, p<0.02, and p<0.003, respectively). With treatment, the correlations between 5-HIAA and HVA weakened (p=0.06). Power spectral density (PSD-the Fourier magnitude squared) of the 5-HIAA signals at periods of 1.75 and 3.7 h (both p<0.05) decreased, while circadian cycling of HVA levels (p<0.05) and of the ratio (p<0.005) increased after treatment. The PSD of the full-length HVA : 5-HIAA ratio series after treatment increased in rapid variability (20-103 min periods, p<0.05). Spectrographic windowing demonstrated a focal span of enhanced HVA : 5-HIAA ratio variability following antidepressant treatment, in an approximately 84-min period through the evening (p<0.05). Periodic neurotransmitter relationships in depressed patients were altered by treatment in this analysis of a small data set. This may represent a baseline abnormality in the regulation of periodic functions involved in the depression pathophysiology, but it could also be due to an unrelated antidepressant effect. Further studies including comparisons with healthy subject data are in progress.

Investigation of vocal jitter and glottal flow spectrum as possible cues for depression and near-term suicidal risk.

Among the many clinical decisions that psychiatrists must make, assessment of a patient's risk of committing suicide is definitely among the most important, complex, and demanding. When reviewing his clinical experience, one of the authors observed that successful predictions of suicidality were often based on the patient's voice independent of content. The voices of suicidal patients judged to be high-risk near-term exhibited unique qualities, which distinguished them from nonsuicidal patients. We investigated the discriminating power of two excitation-based speech parameters, vocal jitter and glottal flow spectrum, for distinguishing among high-risk near-term suicidal, major depressed, and nonsuicidal patients. Our sample consisted of ten high-risk near-term suicidal patients, ten major depressed patients, and ten nondepressed control subjects. As a result of two sample statistical analyses, mean vocal jitter was found to be a significant discriminator only between suicidal and nondepressed control groups (p < 0.05). The slope of the glottal flow spectrum, on the other hand, was a significant discriminator between all three groups (p < 0.05). A maximum likelihood classifier, developed by combining the a posteriori probabilities of these two features, yielded correct classification scores of 85% between near-term suicidal patients and nondepressed controls, 90% between depressed patients and nondepressed controls, and 75% between near-term suicidal patients and depressed patients. These preliminary classification results support the hypothesized link between phonation and near-term suicidal risk. However, validation of the proposed measures on a larger sample size is necessary.

Six degrees-of-freedom kinematics of ACL deficient knees during locomotion-compensatory mechanism.

The purpose of the study was to investigate six degrees-of-freedom (DOF) kinematic changes in anterior cruciate ligament ACL-deficient knees during locomotion and the possible compensatory mechanism involved. Compared with healthy subjects, ACL-deficient patients walked with increased tibial external rotation throughout most of the stride and increased tibial abduction at the heel contact, and the tibia was more anterior during swing phase (P<0.05). Considering tibial external rotation and abduction unload the ACL, the kinematic changes indicated compensatory mechanism developed by patients to avoid unstable knee positions due to the loss of the ACL or to avoid stretching a partially torn ACL.

Serial cerebrospinal fluid tryptophan and 5-hydroxy indoleacetic acid concentrations in healthy human subjects.

The role of the serotonergic system in the pathogenesis of behavioral disorders such as depression, alcoholism, obsessive-compulsive disorder, and violence is not completely understood. Measurement of the concentration of neurotransmitters and their metabolites in cerebrospinal fluid (CSF) is considered among the most valid, albeit indirect, methods of assessing central nervous system function in man. However, most studies in humans have measured lumbar CSF concentrations only at single time points, thus not taking into account rhythmic or episodic variations in levels of neurotransmitters, precursors, or metabolites. We have continuously sampled lumbar CSF via subarachnoid catheter in 12 healthy volunteers, aged 20-65 years. One ml (every 10 min) CSF samples were collected at a rate of 0.1ml/min for 24-hour (h), and the levels of tryptophan (TRP) and 5-hydroxy indoleacetic acid (5-HIAA) were measured. Variability across all 12 subjects was significantly greater (P < 0.0001) than the variability seen in repeated analysis of a reference CSF sample for both 5-HIAA (32.0% vs 7.9%) and TRP (25.4% vs 7.0%), confirming the presence of significant biological variability during the 24-hr period examined. This variability could not be explained solely by meal related effects. Cosinor analysis of the 24-hr TRP concentrations from all subjects revealed a significant diurnal pattern in CSF TRP levels, whereas the 5-HIAA data were less consistent. These studies indicate that long-term serial CSF sampling reveals diurnal and biological variability not evident in studies based on single CSF samples.