Sebastian Uijtdehaage

ASSESSING THE ACCURACY OF TOPOGRAPHIC EEG MAPPING FOR DETERMINING LOCAL BRAIN FUNCTION

OBJECTIVE There has been considerable discussion regarding the accuracy of topographic electroencephalographic (EEG) maps for assessing local cerebral function. We performed this study to test the accuracy of EEG mapping by examining the association between electrical activity and the perfusion under each electrode as another measure of local cerebral function. METHODS EEG mapping was performed simultaneously with (H15)2O positron emission tomography (PET) scanning in 6 normal adult subjects, both at rest and during a simple motor task. EEG data were processed using 3 different montages; two EEG power measures (absolute and relative power) were examined. RESULTS Relative power had much stronger associations with perfusion than did absolute power. In addition, calculating power for bipolar electrode pairs and averaging power over electrode pairs sharing a common electrode yielded stronger associations with perfusion than data from referential or single source montages. CONCLUSIONS These findings indicate (1) that topographic EEG mapping can accurately reflect local brain function in a way that is comparable to other methods, and (2) that the choice of EEG measure and montage have a significant influence on the degree with which maps reflect this local activity and function.

Early changes in prefrontal activity characterize clinical responders to antidepressants.

Previous studies have shown that changes in brain function precede clinical response to antidepressant medications. Here we examined quantitative EEG (QEEG) absolute and relative power and a new measure, cordance, for detecting regional changes associated with treatment response. Fifty-one adults with unipolar depression completed treatment trials using either fluoxetine or venlafaxine vs. placebo. Data were recorded at baseline and after 48 h and 1 week on drug or placebo. Baseline and change from baseline values were examined for specific brain regions in four subject groups (medication and placebo responders and nonresponders). No regional baseline QEEG differences were found among the groups; there also were no significant changes in theta power over time. In contrast, medication responders uniquely showed significant decreases in prefrontal cordance at 48 h and 1 week. Clinical differences did not emerge until after four weeks. Subjects with greater changes in cordance had the most complete 8-week responses. These findings implicate the prefrontal region in mediating response to antidepressant medications. Cordance may have clinical applicability as a leading indicator of individual response.

Relationship between brain electrical activity and cortical perfusion in normal subjects

Cerebral glucose uptake and perfusion are accepted as tightly coupled measures of energy utilization in both normal and diseased brain. The coupling of brain electrical activity to perfusion has been demonstrated, however, only in the presence of chronic brain disease. Very few studies have examined the relationship between cerebral electrical activity and energy utilization in normal brain tissue. To clarify this relationship, we performed 33 H2(15)O-positron emission tomography (PET) scans in six normal subjects both at rest and during a simple motor task, and acquired surface-recorded quantitative electroencephalogram (QEEG) data simultaneously with isotope injection. We examined the associations between cerebral perfusion directly underlying each recording electrode and three QEEG measures (absolute power, relative power, and cordance). All EEG measures had moderately strong coupling with perfusion at most frequency bands, although the directions of the associations differed from those previously reported in subjects with stroke or dementia. Of the three QEEG measures examined, cordance had the strongest relationship with perfusion (multiple R2 = 0.58). Cordance and PET were equally effective in detecting lateralized activation associated with the motor task, while EEG power did not detect this activation. Electrodes in the concordant state had a significantly higher mean perfusion than those in the discordant state. These results indicate that normal brain electrical activity has a moderately strong association with cerebral perfusion. Cordance may be the most useful QEEG measure for monitoring cerebral perfusion in subjects without chronic brain disease.

Prevalence and Predictors of Posttraumatic Stress Disorder in Adult Survivors of Childhood Cancer

OBJECTIVE: This study compared the prevalence of symptoms of posttraumatic stress disorder (PTSD), with functional impairment and/or clinical distress, among very long-term survivors of childhood cancer and a group of healthy siblings. METHODS: A total of 6542 childhood cancer survivors >18 years of age who received diagnoses between 1970 and 1986 and 368 siblings of cancer survivors completed a comprehensive demographic and health survey. RESULTS: A total of 589 survivors (9%) and 8 siblings (2%) reported functional impairment and/or clinical distress in addition to the set of symptoms consistent with a full diagnosis of PTSD. Survivors had more than fourfold greater risk of PTSD, compared with siblings (odds ratio [OR]: 4.14 [95% confidence interval [CI]: 2.08–8.25]). With controlling for demographic and treatment variables, increased risk of PTSD was associated with educational level of high school or less (OR: 1.51 [95% CI: 1.16–1.98]), being unmarried (OR: 1.99 [95% CI: 1.58–2.50]), having annual income below

Accentuated antagonism in the control of human heart rate

20000 (OR: 1.63 [95% CI: 1.21–2.20]), and being unemployed (OR: 2.01 [95% CI: 1.62–2.51]). Intensive treatment also was associated with increased risk of full PTSD (OR: 1.36 [95% CI: 1.06–1.74]). CONCLUSIONS: PTSD was reported significantly more often by survivors of childhood cancer than by sibling control subjects. Although most survivors apparently are faring well, a subset reported significant impairment that may warrant targeted intervention.

Eradicating Medical Student Mistreatment: A Longitudinal Study of One Institution’s Efforts

Invasive animal models indicate that the accelerative effects of the sympathetic nervous system on heart rate are highly dependent on the background level of vagal activity. A noninvasive, parasympathetic chronotropic index (respiratory sinus arrhythmia) and a sympathetic chronotropic index (left ventricular ejection time) were used to evaluate autonomic control of human heart rate. A strong interaction, previously called accentuated antagonism, was found. Sympathetic heart rate effects were substantially smaller with high levels of vagal tone than with low vagal background activity. Furthermore, vagal effects became progressively stronger with increasing sympathetic background activity, demonstrating the predominance of parasympathetic control of human heart rate. This finding implies that changes in cardiac activity resulting from changes in sympathetic control cannot be interpreted accurately unless concurrent vagal activity is taken into account, as well.

Neurophysiologic predictors of treatment response to fluoxetine in major depression

Purpose Since 1995, the David Geffen School of Medicine at UCLA (DGSOM) has created policies to prevent medical student mistreatment, instituted safe mechanisms for reporting mistreatment, provided resources for discussion and resolution, and educated faculty and residents. In this study, the authors examined the incidence, severity, and sources of perceived mistreatment over the 13-year period during which these measures were implemented. Method From 1996 to 2008, medical students at DGSOM completed an anonymous survey after their third-year clerkships and reported how often they experienced physical, verbal, sexual harassment, ethnic, and power mistreatment, and who committed it. The authors analyzed these data using descriptive statistics and the students’ descriptions of these incidents qualitatively, categorizing them as “mild,” “moderate,” or “severe.” They compared the data across four periods, delineated by milestone institutional measures to eradicate mistreatment. Results Of 2,151 eligible students, 1,946 (90%) completed the survey. More than half (1,166/1,946) experienced some form of mistreatment. Verbal and power mistreatment were most common, but 5% of students (104/1,930) reported physical mistreatment. The pattern of incidents categorized as “mild,” “moderate,” or “severe” remained across the four study periods. Students most frequently identified residents and clinical faculty as the sources of mistreatment. Conclusions Despite a multipronged approach at DGSOM across a 13-year period to eradicate medical student mistreatment, it persists. Aspects of the hidden curriculum may be undermining these efforts. Thus, eliminating mistreatment requires an aggressive approach both locally at the institution level and nationally across institutions.

Introducing HEAL: the Health Education Assets Library.

Treatment with antidepressants is marked by heterogeneity of response; predicting individual response to any given agent remains problematic. Neuroimaging studies suggest that response is accompanied by physiologic changes in cerebral energy utilization, but have not provided useful markers at pretreatment baseline. Using quantitative EEG (QEEG) techniques, we investigated pretreatment neurophysiologic features to identify responders and non-responders to fluoxetine. In a double-masked study, 24 adult subjects with current major depression of the unipolar type were studied over 8 weeks while receiving fluoxetine (20 mg QD) or placebo. Neurophysiology was assessed with QEEG cordance, a measure reflecting cerebral energy utilization. Response was determined with rating scales and clinical interview. Subjects were divided into discordant and concordant groups based upon the number of electrodes exhibiting discordance. The concordant group had a more robust response than the discordant group, judged by lower final Hamilton Depression (HAM-D) mean score (8.0+/-7.5 vs. 19.6+/-4.7, P = 0.01) and final Beck Depression Inventory (BDI) mean score (14.0+/-9.4 vs. 27.8+/-3.7, P = 0.015), and by faster reduction in symptoms (HAM-D: 14.0+/-5.0 vs. 23.8+/-4.1, P = 0.004 at 1 week). Groups did not differ on pretreatment clinical or historical features. Response to placebo was not predicted by this physiologic measure. We conclude that cordance distinguishes depressed adults who will respond to treatment with fluoxetine from those who will not. This measure detects a propensity to respond to fluoxetine and may indicate a more general responsiveness to antidepressants.

Increasing the pool of educational leaders for UCLA.

Digital multimedia, such as images and videos, are playing an increasingly important role in health sciences education. Educators, however, often do not have the time or resources to create high-quality materials. The authors describe the development of a new Health Education Assets Library (HEAL), a freely accessible, national library of high-quality digital multimedia to support all levels of health sciences education. HEALs primary mission is to provide educators with high-quality and free multimedia materials (such as images and videos) to augment health science education. In addition, HEAL is working with other organizations to establish a network of distributed databases of high-quality teaching resources. By using state-of-the-art Internet technologies HEAL enables educators across the country to efficiently search and retrieve teaching materials from a variety of sources.

Altered cerebral energy utilization in late life depression

The dual goals of the faculty Fellowship in Medical Education (MEF) program at the David Geffen School of Medicine at UCLA, established in 1992, are to prepare excellent teachers to serve as clerkship chairs, course chairs, or residency program directors while strengthening their dossiers for promotion based on a scholarly approach to curriculum development, implementation, and evaluation. Fellows are nominated from their departments and must demonstrate a strong interest in assuming educational leadership in their respective specialties. A total of eight fellows are accommodated each year based on interviews with the MEF faculty. The two-year program consists of two seminars and two projects focused on four objectives: to critique teaching and testing practices in medical education in light of current theories of learning; to develop and implement curricula that reflect these theories; to improve personal teaching skills through reflection and feedback; and to design and conduct an educational research or program evaluation study. An analysis of the curricula vitae of faculty members who have completed the fellowship suggest that this program continues to provide educational leaders for the school as originally intended. Of the 71 medical school faculty members who completed the MEF between 1993 and 2004 and have remained at the university, 43 (61%) have assumed new leadership roles in medical education. The evaluation data strongly suggest that the MEF has had a major role since its inception in creating a pool of faculty members with the confidence to manage the tasks of educational planning and implementation.