Biomedical subjects

Steven B Lowen

Publications and source records attributed to Steven B Lowen.

7 recordsLinked to original sources

PubMed2006

Emotional task-dependent low-frequency fluctuations and methylphenidate: Wavelet scaling analysis of 1/f-type fluctuations in fMRI of the cerebellar vermis.

UNLABELLED: Ion channel currents, neural firing patterns, and brain BOLD signals display 1/f-type fluctuations or fractal properties in time. By design, fMRI methods attempt to minimize the contribution of variance from low-frequency physiological 1/f-noise. New fMRI methods are described to visualize and measure 1/f-type BOLD fluctuations in volunteers recalling affectively neutral or emotional memories or meditating (i.e., attending to breathing) then retrospectively rating emotional content. A wavelet scaling exponent (alpha) was used to characterize signals from 0.015625 to 0.5Hz in cerebellar lobules VIII to X of the vermis (posterior inferior vermis; PIV), a region coordinating balance, eye tracking, locomotion, and vascular tone, and a possible site of pathology in attention deficit hyperactivity disorder (ADHD). RESULTS: Changes in alpha and emotional measures were correlated in PIV voxels (r = 0.622, d.f .= 14, P < 0.0005), but not other regions examined. In contrast, conventional means and standard deviations of PIV voxels were unchanged. Methylphenidate, shown to decrease slow oscillations in rodent basal ganglia [Ruskin DN, Bergstrom DA, Shenker A, Freeman LE, Baek D, Walters JR. Drugs used in the treatment of attention-deficit/hyperactivity disorder affect postsynaptic firing rate and oscillation without preferential dopamine autoreceptor action. Biol Psychiatry 2001;49:340-50.], abolished task-dependent alpha changes in the PIV of an adult with ADHD. Wavelet analysis of long BOLD time series appears well suited to fractal physiology and studies of pharmacologically modulated cerebellar-thalamic-cortical function in ADHD or other psychiatric disorders.

Adult↗

PubMed2006

A low-cost, MR-compatible olfactometer.

We present a design for an olfactometer, suitable for fMRI experiments, that can be constructed at extremely low cost. The olfactometer presents odors directly to the nose via a nasal cannula at unobtrusively low flow velocities, with no large assemblies required on or near the subject's face. The olfactometer can be controlled manually, or by computer via a serial interface. A validation study verified that the olfactometer reliably presents odors to test subjects. Errors and response latency times decreased with increased flow rate in an orderly manner, as expected.

Adult↗

PubMed2005

Dynamics of sleep-wake cyclicity in developing rats.

Adult mammals cycle between periods of sleep and wakefulness. Recent assessments of these cycles in humans and other mammals indicate that sleep bout durations exhibit an exponential distribution, whereas wake bout durations exhibit a power-law distribution. Moreover, it was found that wake bout distributions, but not sleep bout distributions, exhibit scale invariance across mammals of different body sizes. Here we test the generalizability of these findings by examining the distributions of sleep and wake bout durations in infant rats between 2 and 21 days of age. In agreement with Lo et al., we find that sleep bout durations exhibit exponential distributions at all ages examined. In contrast, however, wake bout durations also exhibit exponential distributions at the younger ages, with a clear power-law distribution only emerging at the older ages. Further analyses failed to find substantial evidence either of short- or long-term correlations in the data, thus suggesting that the durations of current sleep and wake bouts evolve through time without memory of the durations of preceding bouts. These findings further support the notion that bouts of sleep and wakefulness are regulated independently. Moreover, in light of recent evidence that developmental changes in sleep and wake bouts can be attributed in part to increasing forebrain influences, these findings suggest the possibility of identifying specific neural circuits that modulate the changing complexity of sleep and wake dynamics during development.

Age Factors↗

PubMed2005

Intrinsic oscillations in spike trains indicate non-renewal statistics due to convergence of inputs in dorsal cochlear nucleus neurons.

The occurrence of intrinsic oscillations (IOs) in a unit's discharge is reflected by a prominent peak in the power spectrum (i.e., Fourier transform of the autocorrelation function) of spike trains obtained from single-unit discharge, at a frequency independent of stimulus spectral characteristics. IOs have been reported by researchers in the dorsal cochlear nucleus (DCN) of both the cat and the Mongolian gerbil. It has been hypothesized that IOs are related to inter-spike interval (ISI) regularity (e.g., [Hear. Res. 58 (1992) 153]). This hypothesis is tested in this paper. Responses to multiple presentations of 50-300 ms duration tone bursts, at and near the unit's best frequency (BF) at 20-60 dB re threshold were recorded from DCN units of barbiturate-anesthetized (30 units), as well as decerebrate (53 units) Mongolian gerbils. IOs in the recordings were then compared with the IOs in simulations of spiking-neuron models. The models were selected because: (1) their ISI regularity characteristics follow those of experimental data and (2) their IO properties are completely determined by their ISI regularity. Such comparison reveals that Ghoshal's hypothesis fails for a fraction of the units. These results suggest a re-evaluation of the purported relationship between IOs, ISI regularity, and SAM response. Alternate hypotheses are proposed here using computational models that are based on convergence of multiple neural inputs onto the unit under study. These models produce non-renewal statistics that resemble those of the experimental data, as is evident from IO-based analysis.

Action Potentials↗

PubMed2004

Novel strategy for the analysis of CPT data provides new insight into the effects of methylphenidate on attentional states in children with ADHD.

Continuous performance tasks (CPTs) provide a method for studying some components of attention, but do not take into account that attention fluctuates from moment to moment. To address this issue, CPT performance was classified into one of four states (on-task, impulsive, distracted, or randomly responding) every 30 seconds, based on commission and omission error rates. We evaluated this method on 60 boys (10.6 +/- 1.1 years) with attention-deficit hyperactivity disorder (ADHD)-Combined subtype, tested before and after a dose of methylphenidate (MPH, 0.4 mg/kg), and 8 unmedicated healthy control boys (11.3 +/- 2.0 years of age). Healthy controls were on-task during 82.4% of the 30-second epochs, and made an average of 5.4 attention shifts. In contrast, children with ADHD were only on-task during 42.6% of the epochs (p = 0.0006), and they made an average of 12.8 attention shifts (p = 0.00004). These state measures provided more robust indicators of the difference between children with ADHD and controls than did traditional CPT measures of error rates, latency, and variability. The new state measures were also more significantly affected by MPH. MPH produced a 77% increase in the percent of time children with ADHD spent on-task (p < 10(12)). Conversely, MPH reduced time spent in the distracted, impulsive, and random response states by 79%, 44.5%, and 69.2%, respectively (all p values < 0.0002). Unlike errors of omission and commission, which are highly correlated (r = 0.722, n = 60, p < 10(-11)), the percent of epochs spent in impulsive, distracted, and random response states were uncorrelated, and loaded onto discrete independent factors on principal component analysis. The level of activity during the CPT correlated with the degree of distraction, but not with the degree of impulsivity. Children with ADHD could be subtyped according to the nature of their attention performance problems, and these subtypes differed in levels of hyperactivity and degrees of response to MPH.

Attention↗

PubMed2003

Rate dependency revisited: understanding the effects of methylphenidate in children with attention deficit hyperactivity disorder.

Although stimulants are widely prescribed for the treatment of attention deficit hyperactivity disorder (ADHD), their calming effects are not easily understood. One hypothesis derived from preclinical studies is that stimulants exert "rate-dependent" effects that are inversely related in magnitude and direction to the baseline rate of activity or distraction. Previously, compelling support for this hypothesis has been lacking. We provide preliminary evidence that methylphenidate exerts rate-dependent behavioral effects in children with ADHD. Activity and attention were quantified in children with ADHD tested on placebo and different doses of methylphenidate using objective measures. Higher doses altered activity and attentiveness in a rate-dependent manner after correction for regression-to-the-mean artifacts. These findings illustrate a clear inverse association between symptom severity and degree of therapeutic response that is crucial for our understanding of stimulant effects and effective clinical treatment of ADHD.

Attention↗

PubMed2002

Effects of methylphenidate on functional magnetic resonance relaxometry of the cerebellar vermis in boys with ADHD.

OBJECTIVE: The authors used functional magnetic resonance imaging (fMRI) to test the effects of methylphenidate on steady-state blood volume in the midline vermis of the cerebellum in boys with attention deficit hyperactivity disorder (ADHD). This region was selected as it has been observed to be significantly smaller in children with ADHD. Also, in preclinical studies, the vermis has been shown to modulate forebrain dopamine systems, to influence locomotor activity, and to contain a significant density of dopamine transporters. METHOD: T(2) relaxometry was used to indirectly assess blood volume in the cerebellum (hemispheres and midline vermis) of 10 boys with ADHD who were administered placebo or one of three different doses of methylphenidate continuously for 1 week. T(2) relaxation time values are inversely proportional to local cerebral blood volume. After each week of treatment, and within 1-3 hours of the boys' afternoon dose, testing for drug efficacy was performed by using objective measures of activity. RESULTS: Moderate and high doses of methylphenidate increased T(2) relaxation time in a rate-dependent manner-increasing T(2) relaxation time in the most active children with ADHD and reducing T(2) relaxation time in subjects with ADHD who were not objectively hyperactive. CONCLUSIONS: This preliminary study supports a role for the vermis in ADHD and suggests that further research is needed to clarify the relationship between vermal size, vermal blood flow, stimulant response, and the developmental pathophysiology of ADHD.

Attention↗