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Biomedical subjects

Perry F Renshaw

Publications and source records attributed to Perry F Renshaw.

At least 55 records · Page 3Linked to original sources

Frontal glucose hypometabolism in abstinent methamphetamine users.

Changes in relative regional cerebral glucose metabolism (rCMRglc) and their potential gender differences in abstinent methamphetamine (MA) users were explored. Relative rCMRglc, as measured by (18)F-fluorodeoxyglucose positron emission tomography, and frontal executive functions, as assessed by Wisconsin card sorting test (WCST), were compared between 35 abstinent MA users and 21 healthy comparison subjects. In addition, male and female MA users and their gender-matched comparison subjects were compared to investigate potential gender differences. MA users had lower rCMRglc levels in the right superior frontal white matter and more perseveration and nonperseveration errors in the WCST, relative to healthy comparison subjects. Relative rCMRglc in the frontal white matter correlated with number of errors in the WCST in MA users. In the subanalysis for gender differences, lower rCMRglc in the frontal white matter and more errors in the WCST were found only in male MA users, not in female MA users, relative to their gender-matched comparison subjects. The current findings suggest that MA use causes persistent hypometabolism in the frontal white matter and impairment in frontal executive function. Our findings also suggest that the neurotoxic effect of MA on frontal lobes of the brain might be more prominent in men than in women.

Adult↗

A comparison of brain and serum pharmacokinetics of R-fluoxetine and racemic fluoxetine: A 19-F MRS study.

Racemic fluoxetine consists of R- and S-fluoxetine, which are metabolized to R- and S-norfluoxetine, respectively. This study was designed to compare brain levels achieved with R-fluoxetine to those achieved with racemic fluoxetine in healthy subjects using fluorine-19 (19-F) magnetic resonance spectroscopy (MRS). In all, 13 healthy volunteers received study drug for 5 weeks using a dosing schedule designed to achieve steady state for 20 mg/day racemic fluoxetine, 80 mg/day R-fluoxetine, or 120 mg/day R-fluoxetine. The resulting brain drug levels were measured using 19-F MRS. At 5 weeks, the racemate, 80 and 120 mg/day R-fluoxetine groups had mean brain levels of 25.5, 34.9, and 41.4 microM, respectively. In the serum, R-norfluoxetine, which is thought to be an inactive metabolite, accounted for 17, 71, and 63% of the fluoxetine/norfluoxetine concentration, respectively. When the relative proportion of active to total species in serum are taken into account, the data suggest that doses of R-fluoxetine greater than 120 mg/day would be needed to achieve brain levels of active drug comparable to 20 mg/day of racemate. The 120 mg/day R-fluoxetine group experienced a mean increase in QTc interval of 44 ms, with one individual having an increase of 89 ms, which suggests that higher doses may not be tolerable. While these data support the use of MRS to aid in defining the therapeutic dose range for drug development, they also highlight the need for additional studies with concurrent animal models to establish the validity of using serum drug/metabolite ratios to interpret MRS determined brain drug levels.

Brain↗

Oral methylphenidate challenge selectively decreases putaminal T2 in healthy subjects.

Despite the recent rise in oral methylphenidate (MPH) abuse, few studies have characterized the time course of oral MPH brain effects in human subjects. Accordingly, this study assessed the hemodynamic effects of oral MPH effects in 11 healthy young adults (six women), by measuring brain transverse relaxation times (T2). T2 can be interpreted as a surrogate marker for, and inversely correlated with, steady-state cerebral blood volume (CBV). Data were acquired from the caudate nucleus, putamen, and thalamus, using a 1.5 T MRI scanner at baseline and serially for 2 h following oral MPH administration (0.5 mg/kg). Physiological and subjective measures and plasma MPH levels also were examined. MPH induced a selective T2 decrease (-1.65+/-0.53 ms) in the putamen (F(6,54)=2.68, P<0.03). Heartrate, blood pressure and plasma MPH levels increased significantly after drug administration, as well as subjective ratings of "feeling drug effect". T2 decreases may reflect MPH-induced increases in putaminal blood volume. These data suggest that T2 relaxometry can be used to study the time course of regional cerebral blood volume responses to MPH and perhaps to other stimulant drugs.

Administration, Oral↗

Cerebral phosphorus metabolite and transverse relaxation time abnormalities in heroin-dependent subjects at onset of methadone maintenance treatment.

Cerebral bioenergetic and phospholipid abnormalities have been reported in heroin-dependent subjects. The goal of the present study was to characterize the neurochemical profile of subjects voluntarily enrolled in a methadone maintenance (MM) treatment program to overcome their heroin addiction. Participants included 43 heroin-dependent subjects during their first month of MM and 15 age-matched healthy individuals. Phosphorus magnetic resonance spectroscopy ((31)P MRS) and transverse relaxation times (T2-RT), which can reflect steady state cerebral perfusion and metabolism, were acquired at 1.5 T from an axial slice prescribed through the orbitofrontal and occipital cortices, including basal ganglia and frontal cortex. MM subjects exhibited reduced phosphocreatine (PCr) levels (-15.3%), elevated phosphodiesters (+ 12.9%, PDE) and significantly longer T2-RT ((+) 2.1%) compared with healthy comparison subjects. When MM subjects were stratified into subgroups based on treatment duration, we found a treatment duration effect on metabolite values but not T2-RT; reduced PCr was observed only after 8+ days of MM, and phosphomonoesters (PME) were elevated in the 15-28 day MM group. Taken together, these cross-sectional data suggest that the first month of MM treatment may be associated with altered cerebral bioenergetics and phospholipid metabolite levels.

Adenosine Triphosphate↗

Lithium and valproic acid treatment effects on brain chemistry in bipolar disorder.

BACKGROUND: Prior work reported elevated gray matter (GM) lactate and Glx (glutamate + glutamine + GABA) concentrations in unmedicated patients with bipolar disorder (BP) compared with healthy controls (HC). This study examined whether lithium (Li) and valproic acid (VPA) treatment modulated these chemicals. METHODS: A subset of previously reported BP patients were treated with Li (n = 12, 3.6 +/- 1.9 months) or VPA (n = 9, 1.4 +/- 1.7 months) and compared untreated HC subjects (n = 12, 2.9 +/- 2.4 months) using proton echo-planar spectroscopic imaging. Regression analyses (voxel gray/white composition by chemistry) were performed at each time point, and change scores computed. Metabolite relaxation and regions of interest (ROI) were also examined. RESULTS: Across treatment, Li-treated BP subjects demonstrated GM Glx decreases (Li-HC, p =.08; Li-VPA p =.04) and GM myo-inositol increases (Li-HC p =.07; Li-VPA p =.12). Other measures were not significant. Serum Li levels were positively correlated with Glx decreases at the trend level. CONCLUSIONS: Li treatment of BP was associated with specific GM Glx decreases and myo-inositol increases. Findings are discussed in the context of cellular mechanisms postulated to underlie Li and VPA therapeutic efficacy.

Adult↗

White matter hyperintensities in subjects with cocaine and opiate dependence and healthy comparison subjects.

The prevalence, severity, and location of white matter signal hyperintensities (WMH) on brain magnetic resonance images were compared in patients with cocaine or opiate dependence and healthy subjects. Patients with cocaine (n=32) and opiate dependence (n=32), whose diagnoses were confirmed with the Structured Clinical Interview for DSM-IV, and age- and sex-matched healthy subjects (n=32) were scanned using a 1.5 T whole body GE magnetic resonance scanner. Axial proton-density and T2-weighted images were obtained as well as fluid-attenuated inversion recovery axial images. The severity of WMH was assessed separately for deep (and insular) and periventricular WMH, using a modified composite version of the rating scales of Fazekas and Coffey. The cocaine-dependent group had greater severity of WMH than the opiate-dependent group, which in turn had greater severity of WMH than the healthy comparison group (odds ratios=2.54 and 2.90, respectively). The cocaine-dependent group had greater lesion severity of deep and insular WMH than the opiate-dependent group and the healthy comparison group (odds ratio>3.25 for deep WMH; odds ratio>4.38 for insular WMH). For periventricular WMH, there were no significant differences between the three groups. The frontal lobes were the predominant locations of WMH in both substance-dependent groups. The greater prevalence and severity of WMH in cocaine-dependent subjects than in opiate-dependent subjects may reflect the fact that cocaine induces more ischemia via vasoconstriction than opiates. Also, there was a trend for lower WMH severity in substance-dependent women relative to the healthy comparison group, possibly due to estrogen's protective effect against cerebrovascular accidents.

Adult↗

Functional MRI study of working memory in MDMA users.

RATIONALE: Methylene-dioxymethamphetamine (MDMA) is known to cause degeneration of serotonin nerve terminals after acute doses in animals. Similarly, behavioral studies in human MDMA users regularly find abnormalities in memory, mood, and impulse control. However, studies of brain function using brain imaging in MDMA users have been less consistent. OBJECTIVES: The purpose of this study was to determine, using functional magnetic resonance imaging (fMRI), whether individuals with a self-reported history of MDMA use would differ from non-MDMA using controls on activation while performing a working memory task. METHODS: Fifteen MDMA using subjects and 19 non-MDMA using controls underwent fMRI scanning while performing the immediate and delayed memory task (IMT/DMT). The study was based on a block design in which the delayed memory task (DMT) alternated with the immediate memory task (IMT), which served as a control condition. FMRI scans were acquired on a 1.5 T scanner, using a gradient echo echoplanar pulse sequence. RESULTS: Random effects SPM99 analysis showed significantly greater activation (whole volume corrected cluster P<0.05) during the DMT relative to the IMT in the MDMA subjects compared with the control subjects in the medial superior frontal gyrus, in the thalamus extending into putamen, and in the hippocampus. CONCLUSIONS: Although these effects could be due to other drugs used by MDMA users, these results are consistent with behavioral problems that are associated with MDMA use, and with animal studies on the effects of MDMA on brain function.

Adult↗

Lateral visual field stimulation reveals extrastriate cortical activation in the contralateral hemisphere: an fMRI study.

We examined whether lateral visual field stimulation (LSTM) could activate contralateral extrastriate cortical areas as predicted by a large experimental literature. We asked seven unscreened, control subjects to wear glasses designed to allow vision out of either the left (LVF) or right lateral visual field (RVF) depending upon which side the subject looked toward. Each subject participated in a block design functional magnetic resonance imaging (fMRI) study with alternating 30-s epochs in which he was asked to look to one side and then the other for a total of five epochs. On each side of the bore of the scanner, we taped a photograph for the subject to view in the LVF and RVF. The data were analyzed with SPM99 using a fixed effect, box-car design with contrasts for the LVF and the RVF conditions. Both LVF and RVF conditions produced the strongest fMRI activation in the contralateral occipitotemporal and posterior parietal areas as well as the contralateral dorsolateral prefrontal cortex. LSTM appears to increase contralateral fMRI activation in striate and extrastriate cortical areas as predicted by earlier studies reporting differential cognitive and/or emotional effects from unilateral sensory or motor stimulation.

Adult↗

Frontal lobe GABA levels in cocaine dependence: a two-dimensional, J-resolved magnetic resonance spectroscopy study.

Non-invasive measures of brain gamma-aminobutyric acid (GABA) concentrations may be especially useful in the identification of cocaine-related changes in brain chemistry that can be used to guide the development of future treatments for cocaine-dependent persons. This study assessed whether brain GABA levels in cocaine-dependent subjects with and without an alcohol disorder differ from GABA levels in healthy comparison subjects. Two-dimensional, proton magnetic resonance spectroscopy was used to determine GABA levels in the left prefrontal lobe of cocaine-dependent subjects (N=35) recruited from a National Institute on Drug Abuse (NIDA)-sponsored treatment trial of cocaine dependence and a comparison group (N=20). At treatment baseline, mean GABA concentrations were 0.93+/-0.27 mM/kg in cocaine-dependent subjects and 1.32+/-0.44 mM/kg in the comparison sample (t [d.f.=53]=3.65, P<0.001). Cocaine-dependent subjects with a history of a co-morbid alcohol disorder (N=23) had significantly lower baseline GABA levels (0.87 mM/kg) (t [d.f.=41]=4.31, P<0.001) than the comparison group. However, cocaine-dependent subjects without an alcohol disorder (N=12) also had lower GABA levels (1.04 mM/kg) than the comparison subjects (t [d.f.=30]=2.09, P=0.045), suggesting that cocaine dependence alone can decrease GABA levels.

Adult↗

Frontal lobe gray matter density decreases in bipolar I disorder.

BACKGROUND: This study was conducted to explore differences in gray and white matter density between bipolar and healthy comparison groups using voxel-based morphometry (VBM). METHODS: Brain magnetic resonance imaging was performed for 39 subjects with bipolar I disorder and 43 comparison subjects. Images were registered into a proportional stereotaxic space and segmented into gray matter, white mater, and cerebrospinal fluid. Statistical parametric mapping was used to calculate differences in gray and white matter density between groups. RESULTS: Bipolar subjects had decreased gray matter density in left anterior cingulate gyrus (Brodmann's area [BA] 32, 7.3% decrease), an adjacent left medial frontal gyrus (BA 10, 6.9% decrease), right inferior frontal gyrus (BA 47, 9.2% decrease), and right precentral gyrus (BA 44, 6.2% decrease), relative to comparison subjects. CONCLUSIONS: The observation of a gray matter density decrease in the left anterior cingulate, which processes emotions, in bipolar subjects is consistent with prior reports that used region-of-interest analytic methods. Decreased gray matter density in the right inferior frontal gyrus, which processes nonverbal and intrinsic functions, supports nondominant hemisphere dysfunction as a component of bipolar disorder.

Adolescent↗

Ethanolamine and phosphoethanolamine inhibit mitochondrial function in vitro: implications for mitochondrial dysfunction hypothesis in depression and bipolar disorder.

BACKGROUND: A growing body of experimental evidence suggests that mitochondrial dysfunction, including alterations in phospholipid metabolism, might be involved in the pathophysiology of affective illnesses, such as depression and bipolar disorder. The purpose of this study was to determine whether the phosphomonoester phosphoethanolamine (PE) and the lipid metabolite choline (Cho), which are known to be altered in depression and bipolar disorder, and/or their precursors/metabolites, might directly affect mitochondrial bioenergetic function in vitro. METHODS: To this end, rates of oxygen consumption in freshly isolated, intact mitochondria were determined polarographically in the presence and absence of PE, Cho, ethanolamine (Etn), glycerophosphoethanolamine (GPE), and glycerophosphocholine (GPC). RESULTS: The data demonstrate that PE and Etn inhibit mitochondrial respiratory activity in a dose-dependent manner, whereas Cho, GPC, and GPE have no measurable effect on bioenergetic function. CONCLUSIONS: This reflects a specific inhibition by Etn and PE on mitochondrial function rather than a more generalized phenomenon induced by similarities in structure between the lipid metabolites. These results also suggest a possible relationship between mitochondrial dysfunction and altered phospholipid metabolism in the brains of patients with depression and bipolar disorder.

Animals↗

Oral choline increases choline metabolites in human brain.

Choline, a precursor of acetylcholine and phosphatidylcholine, is largely obtained from the diet. Animal studies demonstrate increased choline metabolites in brain following oral administration. Several proton magnetic resonance spectroscopy ((1)H-MRS) reports differ as to whether similar increases are observable in human subjects. This study was designed to minimize intra-subject variance and thereby maximize the ability to determine if a significant increase in brain choline can be detected after choline ingestion. (1)H-MRS was performed continuously for 2.5 h on 11 healthy young males following choline ingestion. Nine of the original subjects returned for identical scans without choline ingestion. Following oral choline, there was a statistically significant increase in the choline signal (Cho) measured from the left putamen, representing choline-containing compounds, as measured against creatine (Cr) or N-acetylaspartate (NAA). The mean increase in Curve maxima (C(max)) is 6.2% for Cho/Cr and 3.0% for Cho/NAA. The Mean Time to C(max) (T(max)) was approximately 2 h after ingestion. A 3-6% increase in Cho by MRS likely corresponds to a 10-22% increase in phosphocholine, similar to findings in animal studies. In conclusion, a significant increase in choline-containing compounds in human brain can be detected by (1)H-MRS after choline ingestion in young subjects.

Administration, Oral↗

Brain metabolic alterations in medication-free patients with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) has substantial morbidity and incompletely understood neurobiological underpinnings. OBJECTIVE: To investigate brain chemistry in medication-free individuals with BD. DESIGN: Two-dimensional proton echo-planar spectroscopic imaging (PEPSI) (32 x 32, 1-cm(3) voxel matrix) acquired axially through the cingulate gyrus was used to quantify regional brain chemistry. SETTING: The Center for Anxiety and Depression at the University of Washington in Seattle and the Bipolar Research Programs at McLean Hospital and the Massachusetts General Hospital in Boston. PARTICIPANTS: Thirty-two medication-free outpatients with a diagnosis of BD type I (BDI) or BD type II (BDII), predominantly in a depressed or mixed-mood state, were compared with 26 age- and sex-matched healthy controls. MAIN OUTCOME MEASURES: Tissue type (white and gray) and regional analyses were performed to evaluate distribution of lactate; glutamate, glutamine, and gamma-aminobutyric acid (Glx); creatine and phosphocreatine (Cre); choline-containing compounds (Cho); N-acetyl aspartate; and myo-inositol. Chemical relationships for diagnosis and mood state were evaluated. RESULTS: Patients with BD exhibited elevated gray matter lactate (P =.005) and Glx (P =.007) levels; other gray and white matter chemical measures were not significantly different between diagnostic groups. Isolated regional chemical alterations were found. An inverse correlation between 17-item Hamilton Depression Rating Scale scores and white matter Cre levels was observed for BD patients. CONCLUSIONS: Gray matter lactate and Glx elevations in medication-free BD patients suggest a shift in energy redox state from oxidative phosphorylation toward glycolysis. The possibility of mitochondrial alterations underlying these findings is discussed and may provide a theoretical framework for future targeted treatment interventions.

Adult↗

In vivo proton magnetic resonance spectroscopy of the temporal lobe in Alzheimer's disease.

PURPOSE: Prior proton magnetic resonance spectroscopy (MRS) studies have consistently reported decreased brain n-acetyl aspartate (NAA) levels and increased myo-inositol (mI) levels in subjects with Alzheimer's disease (AD) relative to healthy comparison subjects. These studies have usually been conducted in small and homogeneous populations of patients with established Alzheimer's disease. Few studies have tested the usefulness of this finding in a general population seeking evaluation for memory loss and other cognitive declines. We designed a study to evaluate the significance of single-voxel proton MRS findings in these patients with memory loss and other cognitive declines. GENERAL METHOD: Thirty-five subjects with a primary complaint of memory loss and other cognitive declines were consecutively referred over a period of 13 months to a specialty clinic. Patients with a diagnosis of mild to moderate probable Alzheimer's disease (N = 22), non-Alzheimer's dementia (depression, multiinfarct dementia, Parkinson's Disease, Korsakoff's Psychosis, and bipolar disorder; N = 13), and healthy comparison subjects (N = 18) were examined with respect to possible differences in metabolites using proton MRS in a 3.4-ml anterior temporal lobe voxel. FINDINGS: The Alzheimer's disease group had 10.7% lower NAA/creatine (Cr) ratios relative to the healthy comparison group and 9.4% lower NAA/creatine relative to the non-Alzheimer's dementia group (15.0% lower NAA/creatine relative to the depression subgroup of the non-Alzheimer's dementia group). There were no significant differences in choline (Cho) or myo-inositol ratios among the groups. There were significant correlations between NAA/creatine ratios and mini-mental status exam (MMSE) scores in subjects with Alzheimer's disease (t = 2.41, p = 0.032) but not in subjects with non-Alzheimer's dementia or in its depression subgroup. CONCLUSIONS: This study found a reduction in the neuronal marker NAA in the anterior temporal lobe of patients diagnosed with probable Alzheimer's disease, using a short add-on proton MRS exam. This change was not observed in patients whose memory loss and other cognitive declines were not attributed to Alzheimer's disease, suggesting that it may aid in the diagnosis or detection of Alzheimer's disease.

Aged↗

White matter hyperintensities and their associations with suicidality in psychiatrically hospitalized children and adolescents.

OBJECTIVE: Increasingly, researchers and clinicians are recognizing that there may be biological markers associated with increased risk of suicide. The objective of this study was to compare white matter hyperintensities in psychiatrically hospitalized children and youth with and without a history of suicide attempt while controlling for other variables. METHOD: White matter hyperintensities of 153 child and adolescent psychiatry inpatients were rated on T2-weighted magnetic resonance imaging scans using a modified Coffey scale. DSM-IV diagnosis, history of suicide attempt, and control variables such as gender, age, comorbid medical illnesses, developmental disorder, substance abuse, severity of mental illness, head injury, and possible cerebral hypoxia were obtained from discharge medical records. RESULTS: Within the unipolar depression group (n = 48), white matter hyperintensities were significantly associated with a higher prevalence of past suicide attempts (Fisher exact test, p =.03). Logistic regression analysis confirmed this relationship, indicating that none of the control variables confounded our results and suggesting a specificity of 0.94. CONCLUSIONS: This is the first report of an increased prevalence of white matter hyperintensities in children and youth with unipolar depression and a history of suicide attempt. Replication and expansion of our preliminary findings could be of great clinical interest.

Adolescent↗

White matter hyperintensities in subjects with bipolar disorder.

There have been divergent reports on the prevalence and severity of white matter hyperintensities (WMH) on brain magnetic resonance (MR) images in subjects with bipolar disorder. In the present study, evaluations were made on the prevalence and severity of WMH in subjects with bipolar disorder using contiguous 3-mm thick MR slices as well as fluid attenuated inversion recovery (FLAIR) images. A detailed WMH rating system was employed to assess these WMH. A total of 43 bipolar patients, as diagnosed by the Structured Clinical Interview from the Diagnostic and Statistical Manual-IV (SCID-IV), and 39 healthy comparison subjects were scanned using a 1.5-T whole body GE magnetic resonance scanner. WMH were assessed with a modified composite version of the Fazekas' and Coffey's rating scales to detect less severe WMH. Periventricular and subcortical WMH were coded separately. Subjects with bipolar disorder had greater prevalence of WMH abnormalities than comparison subjects (Bipolar, grade 1 = 11.6%, grade 2 = 9.3%, grade 3 = 7.0%; Comparison, grade 1 = 5.1%, grade 2 = 2.6%, grade 3 = 0%). This difference is mainly due to the differences in deep WMH (Bipolar, grade 1 = 14.0%, grade 2 = 14.0%; Comparison, grade 1 = 7.7%, grade 2 = 0%). The current study confirms the higher prevalence of WMH in subjects with bipolar disorder. Differences of small-sized WMH abnormalities between groups were successfully detected using a large number of bipolar subjects and thinner sliced MR images with FLAIR.

Adult↗

Omega-3 fatty acid treatment and T(2) whole brain relaxation times in bipolar disorder.

OBJECTIVE: The authors hypothesized that changes in brain membrane composition resulting from omega-3 fatty acid administration in patients with bipolar disorder would result in greater membrane fluidity, as detected by reductions in T(2) values. METHOD: Women with bipolar disorder (N=12) received omega-3 fatty acids for 4 weeks. A cohort of bipolar subjects (N=9) and a group without bipolar disorder (N=12) did not receive omega-3 fatty acids. T(2) values were acquired at baseline and after 4 weeks. RESULTS: Bipolar subjects who received omega-3 fatty acids had significant decreases in T(2). There was a dose-dependent effect when the bipolar omega-3 fatty acid group was subdivided into high- and low-dose cohorts. CONCLUSIONS: Omega-3 fatty acids lowered T(2) values, consistent with the hypothesis that the fluidity of cell membranes was altered. Further studies are needed to clarify the significance of alterations in brain physiology induced by omega-3 fatty acids, as reflected in T(2) values.

Adult↗

Low-field magnetic stimulation in bipolar depression using an MRI-based stimulator.

OBJECTIVE: Anecdotal reports have suggested mood improvement in patients with bipolar disorder immediately after they underwent an echo-planar magnetic resonance spectroscopic imaging (EP-MRSI) procedure that can be performed within clinical MR system limits. This study evaluated possible mood improvement associated with this procedure. METHOD: The mood states of subjects in an ongoing EP-MRSI study of bipolar disorder were assessed by using the Brief Affect Scale, a structured mood rating scale, immediately before and after an EP-MRSI session. Sham EP-MRSI was administered to a comparison group of subjects with bipolar disorder, and actual EP-MRSI was administered to a comparison group of healthy subjects. The characteristics of the electric fields generated by the EP-MRSI scan were analyzed. RESULTS: Mood improvement was reported by 23 of 30 bipolar disorder subjects who received the actual EP-MRSI examination, by three of 10 bipolar disorder subjects who received sham EP-MRSI, and by four of 14 healthy comparison subjects who received actual EP-MRSI. Significant differences in mood improvement were found between the bipolar disorder subjects who received actual EP-MRSI and those who received sham EP-MRSI, and, among subjects who received actual EP-MRSI, between the healthy subjects and the bipolar disorder subjects and to a lesser extent between the unmedicated bipolar disorder subjects and the bipolar disorder subjects who were taking medication. The electric fields generated by the EP-MRSI scan were smaller (0.7 V/m) than fields used in repetitive transcranial magnetic stimulation (rTMS) treatment of depression (1-500 V/m) and also extended uniformly throughout the head, unlike the highly nonuniform fields used in rTMS. The EP-MRSI waveform, a 1-kHz train of monophasic trapezoidal gradient pulses, differed from that used in rTMS. CONCLUSIONS: These preliminary data suggest that the EP-MRSI scan induces electric fields that are associated with reported mood improvement in subjects with bipolar disorder. The findings are similar to those for rTMS depression treatments, although the waveform used in EP-MRSI differs from that used in rTMS. Further investigation of the mechanism of EP-MRSI is warranted.

Adolescent↗