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Lee Friedman

Publications and source records attributed to Lee Friedman.

16 recordsLinked to original sources
PubMed2006

Reducing interscanner variability of activation in a multicenter fMRI study: controlling for signal-to-fluctuation-noise-ratio (SFNR) differences.

Variation in scanner performance will lead to variation in activation patterns in multicenter fMRI studies. The purpose of this investigation was to evaluate the effect of statistically covarying for scanner differences in signal-to-fluctuation-noise-ratio (SFNR) on reducing scanner differences in activation effect size as part of a multicenter fMRI project (FIRST BIRN). For SFNR, "signal" is typically the mean intensity over time and "fluctuation noise" is the temporal standard deviation. Five subjects were sent to 9 centers (10 scanners) and scanned on two consecutive days using a sensorimotor fMRI protocol. High-field (4 T and 3 T) and low-field (1.5 T) scanners from three vendors (GE, Siemens and Picker) were included. The effect size for the detection of neural activation during a sensorimotor task was evaluated as the percent of temporal variance accounted for by our model (percent of variance accounted for, or PVAF). Marked scanner effects were noted for both PVAF as well as SFNR. After covariate adjustment with one of several measures of SFNR, there were dramatic reductions in scanner-to-scanner variations in activation effect size. Variance components analyses revealed 75%-81% reductions in variance due to scanner with this method. Thus, controlling for scanner variation in SFNR may be an effective method to homogenize activation effect sizes in multicenter studies.

Adult↗
PubMed2006

Reducing inter-scanner variability of activation in a multicenter fMRI study: role of smoothness equalization.

Scanner-to-scanner variability of activation in multicenter fMRI studies is often considered undesirable. The purpose of this investigation was to evaluate the effect of a new procedure, "smoothness equalization", on reducing scanner differences in activation effect size as part of a multicenter fMRI project (FIRST BIRN). Five subjects were sent to 9 centers (10 scanners) and scanned on 2 consecutive days using a sensorimotor fMRI protocol. High-field (4 T and 3 T) and low-field (1.5 T) scanners from three vendors (GE, Siemens, and Picker) were included. The activation effect size of the scanners for the detection of neural activation during a sensorimotor task was evaluated as the percent of temporal variance accounted for by our model (percent of variance accounted for or PVAF). Marked scanner effects were noted for both PVAF as well as the degree of smoothness of the raw and processed images. After smoothness equalization, there was a dramatic (low field) or consistent (high-field) reduction in scanner-to-scanner variation of activation. It was shown that the likely basis of the scanner differences in smoothness was differences in k-space filtering algorithms. This work highlights the need to account for differences in smoothness when comparing scanners on activation effect size in multicenter fMRI studies.

Adult↗
PubMed2006

Report on a multicenter fMRI quality assurance protocol.

Temporal stability during an fMRI acquisition is very important because the blood oxygen level-dependent (BOLD) effects of interest are only a few percent in magnitude. Also, studies involving the collection of groups of subjects over time require stable scanner performance over days, weeks, months, and even years. We describe a protocol designed by one of the authors that has been tested for several years within the context of a large, multicenter collaborative fMRI research project (FIRST-BIRN). A full description of the phantom, the quality assurance (QA) protocol, and the several calculations used to measure performance is provided. The results obtained with this protocol at multiple sites over time are presented. These data can be used as benchmarks for other centers involved in fMRI research. Some issues with the various protocol measures are highlighted and discussed, and possible protocol improvements are also suggested. Overall, we expect that other fMRI centers will find this approach to QA useful and this report may facilitate developing a similar QA protocol locally. Based on the findings reported herein, the authors are convinced that monitoring QA in this way will improve the quality of fMRI data.

Brain Mapping↗
PubMed2006

Measurement of Signal-to-Noise and Contrast-to-Noise in the fBIRN Multicenter Imaging Study.

The ability to analyze and merge data across sites, vendors, and field strengths depends on one's ability to acquire images with the same image quality including image smoothness, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). SNR can be used to compare different magnetic resonance scanners as a measure of comparability between the systems. This study looks at the SNR and CNR ratios in structural fast spin-echo T2-weighted scans acquired in five individuals across ten sites that are part of Functional Imaging Research of Schizophrenia Testbed Biomedical Informatics Research Network (fBIRN). Different manufacturers, field strengths, gradient coils, and RF coils were used at these sites. The SNR of gray matter was fairly uniform (41.3-43.3) across scanners at 1.5 T. The higher field scanners produced images with significantly higher SNR values (44.5-108.7 at 3 T and 50.8 at 4 T). Similar results were obtained for CNR measurements between gray/white matter at 1.5 T (9.5-10.2), again increasing at higher fields (10.1-28.9 at 3 T and 10.9 at 4 T).

Analysis of Variance↗
PubMed2006

Speed, road injury, and public health.

We review milestones in the history of increases in speed limits and travel speeds ("speed creep") and risks for road deaths and injury. Reduced speed limits, speed-camera networks, and speed calming substantially reduce these tolls in absolute numbers-a trend that is apparent in the United Kingdom, Australia, France, and other countries, but not in the United States, which has raised speed limits and does not have speed-camera networks. Newtonian relationships between the fourth power of small increases or reductions in speed and large increases or reductions in deaths state the case for speed control. Speed adaptation and the interaction between speed and other determinants of injury risks, including congestion and countermeasures, enter into these relationships. Speed-camera networks and speed calming lead to large, sustainable, and highly cost-effective drops in road deaths and injuries and should target entire populations, not merely high-risk subgroups or situations. Yet, there are major barriers to preventive strategies based on the discovery that speed kills. Modal shifts from speed on roads to speed on rail, lower maximum vehicle speeds, and speed-camera networks are required for progress toward Vision Zero-the goal of no road deaths-through Killing Speed. The human cost of the delay in killing speed in the United States may be as high as 20,000 lives lost per year.

Acceleration↗
PubMed2004

Cellular changes in the postmortem hippocampus in major depression.

BACKGROUND: Imaging studies report that hippocampal volume is decreased in major depressive disorder (MDD). A cellular basis for reduced hippocampal volume in MDD has not been identified. METHODS: Sections of right hippocampus were collected in 19 subjects with MDD and 21 normal control subjects. The density of pyramidal neurons, dentate granule cell neurons, glia, and the size of the neuronal somal area were measured in systematic, randomly placed three-dimensional optical disector counting boxes. RESULTS: In MDD, cryostat-cut hippocampal sections shrink in depth a significant 18% greater amount than in control subjects. The density of granule cells and glia in the dentate gyrus and pyramidal neurons and glia in all cornv ammonis (CA)/hippocampal subfields is significantly increased by 30%-35% in MDD. The average soma size of pyramidal neurons is significantly decreased in MDD. CONCLUSION: In MDD, the packing density of glia, pyramidal neurons, and granule cell neurons is significantly increased in all hippocampal subfields and the dentate gyrus, and pyramidal neuron soma size is significantly decreased as well. It is suggested that a significant reduction in neuropil in MDD may account for decreased hippocampal volume detected by neuroimaging. In addition, differential shrinkage of frozen sections of the hippocampus suggests differential water content in hippocampus in MDD.

Adult↗
PubMed2004

Genetic and phenotypic analysis of seizure susceptibility in PL/J mice.

Epilepsy is one of the most common but genetically complex neurological disorders in humans. Identifying animal models that recapitulate human epilepsies is important for pharmacological studies of anticonvulsants, dissection of molecular and biochemical pathogenesis of epilepsy, and discovery of epilepsy susceptibility genes. We discovered that the PL/J inbred mouse strain is susceptible to handling- and rhythmic tossing-induced seizure. The tonic-clonic and generalized seizures observed after induction were accompanied by abnormal EEGs, similar to seizures observed in EL and SWXL-4 mice. PL/J mice also had an extremely low threshold to electroconvulsive seizures compared to other strains and showed variable sensitivity to pentylenetetrazole-induced seizures. Gross neurostructural abnormalities were not found in PL/J mice. Crosses with the seizure-resistant C57BL/6 J strain revealed semidominant inheritance of the rhythmic tossing seizure trait with low penetrance. F2 progeny indicated that the genetic inheritance of seizure susceptibility in PL/J is non-Mendelian. We crossed DBA/2 J mice, which are resistant to rhythmic tossing seizure but susceptible to audiogenic seizures, to PL/J. We found that seizure penetrance in (DBA/2 J x PL/J)F1 mice was similar to the penetrance in (C57BL/6 J x PL/J)F1 mice but the severity and frequency of seizure were higher in (DBA/2 J x PL/J)F1 mice. The PL/J strain serves as an interesting new model for studying the genetics, neurobiology, and pharmacology of epilepsy.

Animals↗
PubMed2004

Ventilatory behavior during sleep among A/J and C57BL/6J mouse strains.

The pattern of breathing during sleep could be a heritable trait. Our intent was to test this genetic hypothesis in inbred mouse strains known to vary in breathing patterns during wakefulness (Han F, Subramanian S, Dick TE, Dreshaj IA, and Strohl KP. J Appl Physiol 91: 1962-1970, 2001; Han F, Subramanian S, Price ER, Nadeau J, and Strohl KP, J Appl Physiol 92: 1133-1140, 2002) to determine whether such differences persisted into non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Measures assessed in C57BL/6J (B6; Jackson Laboratory) and two A/J strains (A/J Jackson and A/J Harlan) included ventilatory behavior [respiratory frequency, tidal volume, minute ventilation, mean inspiratory flow, and duty cycle (inspiratory time/total breath time)], and metabolism, as performed by the plethsmography method with animals instrumented to record EEG, electromyogram, and heart rate. In all strains, there were reductions in minute ventilation and CO2 production in NREM compared with wakefulness (P < 0.001) and a further reduction in REM compared with NREM (P < 0.001), but no state-by-stain interactions. Frequency showed strain (P < 0.0001) and state-by-strain interactions (P < 0.0001). The A/J Jackson did not change frequency in REM vs. NREM [141 +/- 15 (SD) vs. 139 +/- 14 breaths/min; P = 0.92], whereas, in the A/J Harlan, it was lower in REM vs. NREM (168 +/- 14 vs. 179 +/- 12 breaths/min; P = 0.0005), and, in the B6, it was higher in REM vs. NREM (209 +/- 12 vs. 188 +/- 13 breaths/min; P < 0.0001). Heart rate exhibited strain (P = 0.003), state (P < 0.0001), and state-by-strain interaction (P = 0.017) and was lower in NREM sleep in the A/J Harlan (P = 0.035) and B6 (P < 0.0001). We conclude that genetic background affects features of breathing during NREM and REM sleep, despite broad changes in state, metabolism, and heart rate.

Animals↗
PubMed2004

Insight and its relationship to violent behavior in patients with schizophrenia.

OBJECTIVE: Lack of insight affects the management of schizophrenia. The interrelationship between lack of insight and illness attributes in patients with schizophrenia who commit violent acts is important and underresearched. METHOD: One hundred fifteen violent patients with schizophrenia in a jail or court psychiatric clinic were evaluated on measures of symptoms, illness severity, insight into illness, and the legal consequences of their illness ("forensic insight"). A sample of nonviolent patients served as a comparison group. RESULTS: Compared with the nonviolent cohort, violent patients were more symptomatic, had poorer functioning, and had a more prominent lack of insight. Deficits of insight into illness coexisted with a lack of forensic insight, which was also associated with psychosis. CONCLUSIONS: Patients with schizophrenia who commit violent acts have insight deficits, including lack of awareness of the legal implications of their behavior. Targeted interventions to improve insight and treatment compliance in this population are warranted.

Adult↗
PubMed2004

Raised speed limits, speed spillover, case-fatality rates, and road deaths in Israel: a 5-year follow-up.

OBJECTIVES: We assessed the 5-year, nationwide impact on road deaths of the raise in the speed limit (November 1, 1993) on 3 major interurban highways in Israel from 90 to 100 kph. METHODS: We compared before-after trends in deaths as well as case fatality-an outcome independent of exposure (defined as vehicle-kilometers traveled). RESULTS: After the raise, speeds rose by 4.5%-9.1%. Over 5 years, there was a sustained increase in deaths (15%) and case fatality rates (38%) on all interurban roads. Corresponding increases in deaths (13%) and case fatality (24%) on urban roads indicated "speed spillover." CONCLUSIONS: Immediate increases in case fatality predicted and tracked the sustained increase in deaths from increased speeds of impact. Newtonian fourth power models predicted the effects of "small" increases in speed on large rises in case fatality rates. Countermeasures and congestion reduced the impact on deaths and case-fatality rates by more than half.

Accidents, Traffic↗
PubMed2004

Respiratory complaints and medication use following cessation of exposure to construction dust and diesel truck emissions (Neve Yakov, Jerusalem).

OBJECTIVES: The aim of the study was to assess respiratory complaints in the residents of Neve Yakov following the closure of a municipal dump, operating in the neighborhood for 3 years. MATERIALS AND METHODS: We carried out a cross sectional survey of 250 adult residents. Exposures to sporadic dust, measurements and estimates of diesel emissions based on traffic load were assessed. RESULTS: Adjusted odds ratios for respiratory symptoms in persons living in the nearest and downwind areas compared to the areas farthest from the dump site were (nearest and downwind respectively): cough OR = 3.7 (95% CI: 1.18-11.4) and OR = 2.9 (95% CI 0.79-10.9); phlegm OR = 1.9 (0.7-5.1) and OR = 2.3 (0.7-7.3); shortness of breath OR = 1.7 (0.6-4.8) and OR = 3.7 (0.9-14.6). After closing the dump, 33% of residents reported improvement in symptoms. Following closure of the dump, residual respiratory illness was observed in many residents. CONCLUSION: A substantial part of the respiratory complaints may have come from diesel emissions in addition to the ambient dust.

Adult↗
PubMed2002

Neurokinin-1 receptors are decreased in major depressive disorder.

Treatment with an antagonist at the neurokinin-1 (NK-1) receptor may alleviate depression, however the brain region(s) in which the NK-1 receptor antagonist exerts its therapeutic effect is unknown. [125I]BH-Substance P was used to measure NK-1 receptors postmortem in cytoarchitectonically defined areas of rostral orbitofrontal cortex (Brodmann's area 47) of subjects with major depressive disorder (n = 12, six females) and psychiatrically normal subjects (n = 11, five females). Six subjects with depression died by suicide. Subjects with depression showed decreased binding to NK-1 receptors across all cortical layers (p = 0.024). The pathophysiology of depression, and the reported therapeutic benefit of NK-1 receptor antagonists, may thus involve NK-1 receptors in prefrontal cortex.

Adult↗
PubMed2002

Head size and schizophrenia.

There is a small but intriguing body of literature which suggests that head size may be reduced in patients with schizophrenia. This literature sits alongside more substantial and compelling evidence that there is a reduction in cerebral volume in schizophrenia. As an extension of earlier work, measures of extracranial head size derived from standard anthropometric approaches were assessed in 44 patients and 46 control subjects. Head size was found to be normal in schizophrenia. The relationship of brain size to head size is elaborated.

Adult↗
PubMed2002

Increased presence of white matter hyperintensities in adolescent patients with bipolar disorder.

Several reports have noted an increase in white matter hyperintensities (WMH) on MRI scans of adult patients with bipolar disorder. We investigated whether this increase was also evident in a group of adolescent patients with bipolar disorder. The sample consisted of 15 bipolar patients, 19 patients with schizophrenia and 16 healthy comparison subjects. All subjects were adolescents. WMH were blindly rated on T2-weighted and PD-weighted MRI scans using our own scale with documented inter-rater reliability. WMH were present in 10 of 15 bipolar patients (67%), seven of 19 patients with schizophrenia (37%) and five of 16 comparison subjects (31%). The bipolar adolescent group had a statistically significant increased presence of WMH compared both with healthy comparison subjects and the schizophrenic group. The association between WMH and bipolar disorder appears to extend to the adolescent years.

Adolescent↗
PubMedDate not supplied

Conflicts of interest and scientific integrity.

The encroachment of conflicts of interest on the peer-review process of scientific journals is discussed, with particular reference to a current example. The authors stress the need for transparency of the connections among authors, reviewers, publishers, editors, and sources of funding to prevent erosion of trust in the scientific integrity of such publications.

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