Biomedical subjects

J R Moeller

Publications and source records attributed to J R Moeller.

At least 37 records · Page 2Linked to original sources

PubMed1997

The metabolic anatomy of Tourette's syndrome.

The functional brain networks underlying the clinical manifestations of Gilles de la Tourette's syndrome (TS) are currently unknown. To identify these networks, we studied TS patients and normal subjects with 18F-fluorodeoxyglucose (FDG) and PET employing a statistical model of regional metabolic covariation. We studied 10 TS patients (mean age, 41.5 +/- 12.7 years) who were either drug naive or medication free for at least 2 years. Ten normal volunteers (mean age, 42.5 +/- 11.5) served as controls. We used quantitative FDG/PET to calculate global, regional, and normalized rates of glucose metabolism (GMR, rCMRGlc, and rCMRGlc/GMR) in all subjects. The Scaled Subprofile Model (SSM) was used to identify specific patterns of regional metabolic covariation associated with TS. We found that global and regional metabolic rates were normal in TS. SSM analysis identified two TS-related brain networks. One pattern (15.8% variance accounted for, VAF) was characterized by covariate bilateral metabolic increases in lateral premotor and supplementary motor association cortices and in the midbrain. Individual patient expression of this pattern (subject score) was abnormally increased in the TS group (p < 0.01). A second pattern (10.5% VAF) was characterized by covariate decreases in caudate and thalamic metabolism associated with smaller reductions in lentiform and hippocampal metabolic activity. Subject scores for this pattern correlated with Tourette Syndrome Global Scale (TSGS) global ratings (r = 0.85, p < 0.005). We conclude that the metabolic landscape of TS is characterized by a nonspecific pattern of increased motor cortical activity identified in other hyperkinetic disorders. TS is also associated with a specific brain network characterized by a reduction in the activity of limbic basal ganglia-thalamocortical projection systems.

Adult↗

PubMed1997

Preoperative indicators of clinical outcome following stereotaxic pallidotomy.

We assessed the utility of preoperative clinical assessment and functional brain imaging with 18F-fluorodeoxyglucose (FDG) and positron emission tomography (PET) in predicting the clinical outcome of stereotaxic pallidotomy for the treatment of advanced Parkinson's disease (PD). Twenty-two PD patients undergoing posteroventral pallidotomy were assessed preoperatively with the Core Assessment Program for Intracerebral Transplantation (CAPIT) ratings measured on and off levodopa; quantitative FDG/PET was also performed before surgery. Preoperative clinical and metabolic measurements were correlated with changes in off-state CAPIT ratings determined 3 months after surgery. Clinical outcome following pallidotomy was also correlated with intraoperative measures of spontaneous pallidal single-unit activity as well as postoperative MRI measurements of lesion volume and location. We found that unilateral pallidotomy resulted in variable clinical improvement in off-state CAPIT scores for the contralateral limbs (mean change 30.9 +/- 15.5%). Postoperative MRI revealed that pallidotomy lesions were comparable in location and volume across the patients. Clinical outcome following surgery correlated significantly with preoperative measures of CAPIT score change with levodopa administration (r = 0.60, p < 0.005) and with preoperative FDG/PET measurements of lentiform glucose metabolism (r = 0.71, p < 0.0005). Operative outcome did not correlate with intraoperative measures of spontaneous pallidal neuronal firing rate. We conclude that preoperative measurements of lentiform glucose metabolism and levodopa responsiveness may be useful indicators of motor improvement following pallidotomy. Both preoperative quantitative measures, either singly or in combination, may be helpful in selecting optimal candidates for surgery.

Aged↗

PubMed1997

Quantifying the speed of symptomatic improvement with electroconvulsive therapy: comparison of alternative statistical methods.

Although electroconvulsive therapy (ECT) is believed to have a rapid onset of antidepressant activity, there has been limited investigation in this area. This study contrasted alternative statistical methods for testing treatment group differences in the rapidity of clinical response to ECT. Patients with major depression were randomly assigned to receive right unilateral or bilateral ECT and low or high electrical dosage relative to seizure threshold. The 24-item Hamilton Rating Scale for Depression (HRSD) was administered by blinded clinical raters twice weekly (non-treatment days). We evaluated four alternative statistical strategies. Two methods considered time to improvement as a dependent variable: (a) time (treatment number) to reach various cutoffs for percentage decrease in HRSD from baseline; and (b) survival analysis using the same cutoffs for percentage decreases as endpoints. Two methods considered time to improvement as an independent variable: (c) the slope of linear regression of HRSD scores against treatment number; and (d) a random regression model using the HRSD scores as repeated measures. The statistical methods differed in whether or not omnibus group differences were observed, the criterion level of improvement associated with group differences, and the results of pairwise comparisons establishing specific therapeutic advantages. Survival analysis generally displayed the greatest sensitivity in detecting treatment group differences.

Analysis of Variance↗

PubMed1996

The effects of electroconvulsive therapy on quantitative electroencephalograms. Relationship to clinical outcome.

BACKGROUND: The efficacy of electroconvulsive therapy (ECT) is determined by stimulus electrical intensity and electrode placement. Three theories offer different accounts for why increasing the stimulus dosage of right unilateral ECT enhances antidepressant effects. This study examined the effects of ECT on interictal quantitative electroencephalograms (EEGs), contrasting these theories in their predictions regarding global, lateralized, and topographic changes in ECT-induced slow-wave activity. The time course of EEG changes and associations with efficacy were also determined. METHODS: Sixty-two inpatients with major depressive disorder were randomized to ECT conditions that differed in stimulus intensity (low vs high dosage) and electrode placement (right unilateral vs bilateral). Resting, eyes closed, 19-lead EEG recordings were obtained at pretreatment, following a single treatment, following an average of 7 treatments, during the week following the ECT course, and after a 2-month follow-up period. RESULTS: Electroconvulsive therapy produced a marked short-term increase in delta and theta power. At a 2-month follow-up, there were no significant alterations in any frequency band. The ECT treatment conditions differed markedly in efficacy. Global and lateralized EEG effects did not distinguish effective and ineffective forms of treatment. Effective forms of ECT resulted in increased delta power in prefrontal regions, and this change was associated with the magnitude of symptomatic improvement. CONCLUSION: The induction of slow-wave activity in prefrontal cortex is linked to the efficacy of ECT.

Delta Rhythm↗

PubMed1996

Regional metabolic correlates of surgical outcome following unilateral pallidotomy for Parkinson's disease.

Stereotaxic ventral pallidotomy has been employed in the symptomatic treatment of patients with advanced Parkinson's disease (PD). To understand the pathophysiology of clinical outcome following this procedure, we studied 10 PD patients (5 men and 5 women; mean age 60.0 +/- 6.1 years; mean Hoehn and Yahr stage 3.8 +/- 1.0) with quantitative 18F-fluorodeoxyglucose (FDG) and positron emission tomography (PET). All patients were scanned preoperatively; 8 of 10 patients were rescanned 6 to 8 months following surgery. Clinical performance was assessed off medications before and after surgery using standardized timed motor tasks. We found that preoperative lentiform metabolism correlated significantly with improvement in contralateral motor tasks at 1 week, 3 months, and 6 months following unilateral pallidotomy (p<0.03). Postoperatively, significant metabolic increases were noted in the primary motor cortex, lateral premotor cortex, and dorsolateral prefrontal cortex (p<0.01) of the hemisphere that underwent surgery. Improvement in contralateral limb motor performance correlated significantly with surgical declines in thalamic metabolism (p<0.01) and increases in lateral frontal metabolism (p<0.05). Principal components analysis disclosed a significant covariance pattern characterized by postoperative declines in ipsilateral lentiform and thalamic metabolism associated with bilateral increase in supplementary motor control metabolism. Subject scores for this pattern correlated significantly with improvements in both contralateral and ipsilateral limb performance (p<0.005). These results suggest that pallidotomy reduced the preoperative overaction of the inhibitory pallidothalamic projection. Clinical improvement may be associated with modulations in regional brain metabolism occurring remote from the lesion site.

Aged↗

PubMed1996

The metabolic topography of normal aging.

Normal aging is associated with the degeneration of specific neural systems. We used [18F] fluorodeoxyglucose (FDG)/positron emission tomography (PET) and a statistical model of regional covariation to explore the metabolic topography of this process. We calculated global and regional metabolic rates for glucose (GMR and rCMRglc) in two groups of normal subjects studied independently on different tomographs: Group 1--130 normal subjects (62 men and 68 women; range 21-90 years); Group 2--20 normal subjects (10 men and 10 women; range 24-78 years). In each of the two groups, the Scaled Subprofile Model (SSM) was applied to rCMRglc data to identify specific age-related profiles. The validity of these profiles as aging markers was assessed by correlating the associated subject scores with chronological age in both normal populations. SSM analysis disclosed two significant topographic profiles associated with aging. The first topographic profile, extracted in an analysis of group 1 normals, was characterized by relative frontal hypometabolism associated with covariate metabolic increases in the parietooccipital association areas, basal ganglia, mid-brain, and cerebellum. Subject scores for this profile correlated significantly with age in both normal groups (R2 = 0.48 and 0.33, p < 0.0001 for groups 1 and 2, respectively). Because of clinical similarities between normal motoric aging and parkinsonism, we explored the possibility of shared elements in the metabolic topography of both processes. We performed a combined group SSM analysis of the 20 group 2 normals and 22 age-matched Parkinson's disease patients, and identified another aging-related topographic profile. This profile was characterized by relative basal ganglia hypermetabolism associated with covariate decreases in frontal premotor cortex. Subject scores for this profile also correlated significantly with age in both normal groups (group 1: R2 = 0.30, p < 0.00001; group 2: R2 = 0.59, p < 0.01). Healthy aging is associated with reproducible topographic covariation profiles associated with specific neural systems. FDG/PET may provide a useful metabolic marker of the normal aging process.

Adult↗

PubMed1995

Regional cerebral blood flow in mood disorders: IV. Comparison of mania and depression.

Cortical regional cerebral blood flow (rCBF) was assessed in minimally medicated, relatively young adults in episodes of either acute mania (n = 11) or major depression (n = 11) and in matched normal control subjects (n = 11), using the 133xenon inhalation method, under eyes-closed, resting conditions. The three groups were equivalent in global CBF. Both patient groups showed significant reductions of rCBF in anterior cortical areas and reduction of the normal anteroposterior gradient. In addition, there was evidence of abnormal, albeit similar, patterns of flow lateralization on a regional basis in both clinical groups compared with normal subjects. An exploratory analysis revealed preliminary evidence of rCBF differences between the clinical groups, localized to the inferior frontal cortex. Otherwise, the evidence in this study suggests that young adult manic and depressed patients are predominantly similar in cortical rCBF parameters.

Administration, Inhalation↗

PubMed1995

The metabolic topography of idiopathic torsion dystonia.

We used [18F]fluorodeoxyglucose (FDG) and PET with a statistical model of regional metabolic covariation to study brain topographic organization in idiopathic torsion dystonia (ITD). We studied 11 patients with predominantly right-sided ITD and 11 age-matched controls, and measured global, regional cerebral and normalized metabolic rates for glucose (GMR, rCMRGlc, rCMRGlc/GMR). The Scaled Subprofile Model was applied to the combined rCMRGlc dataset to identify topographic covariance profiles associated with ITD. We found that global and regional metabolic rates were normal in ITD. The SSM analysis of the combined groups of ITD patients and normals revealed a significant topographic profile characterized by relative bilateral increases in the metabolic activity of the lateral frontal and paracentral cortices, associated with relative covariate hypermetabolism of the contralateral lentiform nucleus, pons and midbrain. Subject scores for this profile correlated significantly with Fahn-Marsden disease severity ratings (r = 0.67, P < 0.02). In contrast to parkinsonism, lentiform and thalamic metabolism were dissociated in dystonia. We conclude that ITD is characterized by relative metabolic overactivity of the lentiform nucleus and premotor cortices. The presence of lentiform thalamic metabolic dissociation suggests that in this disorder hyperkinetic movements may arise through excessive activity of the direct putameno-pallidal inhibitory pathway.

Adult↗

PubMed1995

The reliability of quantitative electroencephalography as an indicator of cerebral ischemia.

The electroencephalogram (EEG) has been used to detect episodes of cerebral ischemia during various surgical procedures. Recently, computerized systems for recording and interpreting the quantitative EEG (QEEG) have been used by anesthesiologists because of their ease of application, clarity of display, and reported ability to identify ischemic EEG changes. However, the extent to which automated techniques of QEEG interpretation reliably differentiate cerebral ischemia from the confounding effects of anesthetics and other sources of "artifact" is not completely established. In this study, EEGs were recorded before and after defibrillator testing in patients undergoing implantable cardioverter defibrillator (ICD) placement and during analogous time periods in control patients undergoing abdominal surgery. EEGs were subjected to standard visual inspection by an experienced electroencephalographer and QEEG analysis with a commercially available system was used for automated EEG interpretation in order to evaluate the reliability of this quantitative technique. The CIMON technique identified episodes which met previously defined criteria for QEEG cerebral dysfunction and ischemic pattern in both groups, despite the presumed absence of cerebral ischemia in the control patients. Since there was no evidence of cerebral ischemia in the raw EEGs of either the ICD patients or the controls, these QEEG changes were not confirmed by conventional techniques of EEG interpretation. Our results suggest that caution is warranted when using automated systems for intraoperative interpretation of EEG.

Adult↗

PubMed1995

Early differential diagnosis of Parkinson's disease with 18F-fluorodeoxyglucose and positron emission tomography.

Early-stage Parkinson's disease (EPD) is often clinically asymmetric. We used 18F-fluorodeoxyglucose (FDG) and PET to assess whether EPD can be detected by a characteristic pattern of regional metabolic asymmetry. To identify this pattern, we studied 10 EPD (Hoehn and Yahr stage I) patients (mean age 61.1 +/- 11.1 years) using 18F-FDG and PET to calculate regional metabolic rates for glucose. The scaled subprofile model (SSM) was applied to metabolic asymmetry measurements for the combined group of EPD patients and normal subjects to identify a specific covariation pattern that discriminated EPD patients from normal subjects. To determine whether this pattern could be used diagnostically, we studied a subsequent group of five presumptive EPD patients (mean age 50.9 +/- 18.3), five normal subjects (mean age 44.6 +/- 15.3), and nine patients with atypical drug-resistant early-stage parkinsonism (APD) (mean age 44.6 +/- 14.0). In each member of this prospective cohort, we calculated the expression of the EPD-related covariation pattern (subject scores) on a case-by-case basis. We also studied 11 of the EPD patients, five patients with APD, and 10 normal subjects with 18F-fluorodopa (FDOPA) and PET to measure presynaptic nigrostriatal dopaminergic function, and we assessed the accuracy of differential diagnosis with both PET methods using discrimination analysis. SSM analysis disclosed a significant topographic contrast profile characterized by covariate basal ganglia and thalamic asymmetries. Subject scores for this profile accurately discriminated EPD patients from normal subjects and APD patients (p < 0.0001). Group assignments into the normal or parkinsonian categories with FDG/PET were comparable to those achieved with FDOPA/PET, although APD and EPD patients were not differentiable by the latter method. Metabolic brain imaging with FDG/PET may be useful in the differential diagnosis of EPD.

Adult↗

PubMed1995

Cerebral metabolic topography in unilateral temporal lobe epilepsy.

OBJECTIVE: Fluorodeoxyglucose positron emission tomography (FDG-PET) studies of temporal lobe epilepsy (TLE) generally report interictal hypometabolism in the vicinity of the seizure focus. Yet, other evidence suggests that interictal metabolic abnormalities might extend to remote brain areas. We used FDG-PET to evaluate metabolism in selected regions distant from the focus in TLE. SUBJECTS: Twenty adult patients with medically intractable TLE were selected by criteria favoring a unilateral mesiobasal temporal focus. Structural imaging in this sample were normal except for medial temporal sclerosis in 13 patients. Twenty normal volunteers were controls. DESIGN: PET imaging was performed interictally. Regional glucose metabolism normalized by global metabolism was analyzed using t tests and correlation analysis. RESULTS: Ipsilateral to the seizure focus, metabolism was depressed compared with normal in the temporal pole (p = 0.001), but relatively elevated in the mesiobasal region (p = 0.005). Contralateral to the focus, metabolism was elevated in lateral temporal cortex (p = 0.0003) and mesiobasal regions (p = 0.0001). Metabolic correlation between ipsilateral and contralateral mesiobasal regions was similar in normal subjects (r = 0.74) and patients (r = 0.68). In contrast, correlations were abnormal between temporal poles and other temporal lobe subregions, both ipsilateral and contralateral to the seizure focus. CONCLUSIONS: Relative to normal values, both elevations and depressions of metabolism exist interictally in TLE. Such abnormalities, and accompanying changes in interregional correlations, may have wide spatial distribution. These findings are atypical among PET studies but are consistent with other physiologic, anatomic, and neuropsychological investigations of TLE.

Adolescent↗

PubMed1995

Assessment of disease severity in parkinsonism with fluorine-18-fluorodeoxyglucose and PET.

UNLABELLED: Fluorine-18-fluorodeoxyglucose (FDG) and PET have been used to identify an abnormal regional metabolic covariance pattern in Parkinson's disease (PD). To examine the potential use of this covariance pattern as a metabolic imaging marker for PD, we describe the Topographic Profile Rating (TPR), which is a method for calculating subject scores for this pattern in individual PD patients. We then assess the relationship between these metabolic measures and objective independent disease severity ratings. METHODS: Two independent groups of PD patients were studied with FDG-PET. Group A consisted of 23 patients (mean age 60.2 +/- 12.2; mean Hoehn and Yahr stages 2.4 +/- 1.3) and Group B had 14 patients (mean age 49.0 +/- 12.1; mean Hoehn and Yahr stage 3.2 +/- 1.2). The regional cerebral metabolic rates for glucose (rCMRGlc) in all patients in each group were measured. TPR was used to calculate subject scores for the disease-related covariance pattern on a patient-by-patient basis. RESULTS: In both PD patient groups, subject scores correlated with Hoehn and Yahr disease severity ratings (Group A: r = 0.59, p < 0.004; Group B: 0.57, p < 0.04), quantitative ratings for bradykinesia (Group A: r = 0.63, p < 0.002; Group B: r = 0.61, p < 0.03), rigidity (Group A: r = 0.59, p < 0.004; Group B: r = 0.59, p < 0.04), but not with tremor. CONCLUSION: These findings indicate that regional metabolic covariance patterns are robust imaging markers of disease severity. FDG-PET may be useful clinically in assessing parkinsonian disability and disease progression.

Adult↗

PubMed1994

Regional cerebral blood flow in mood disorders, III. Treatment and clinical response.

BACKGROUND: Global and regional deficits in cerebral blood flow and glucose metabolism have been reported in major depression, but there is limited information on the effects of somatic treatment and clinical recovery on these abnormalities. METHODS: We assessed cortical blood flow with the xenon 133 technique in depressed patients prior to a course of electroconvulsive therapy (ECT), 30 minutes before and 50 minutes after a single treatment, and during the week following ECT. Acute (preictal and postictal) effects of a single treatment also were studied in manic patients. RESULTS: In the depressed and manic groups, larger blood flow reductions in the acute period, both globally and in particular patterns of brain regions, were associated with a superior clinical outcome following the treatment course. In depressed patients, similar patterns were observed for the blood flow changes over a full treatment course. Blood flow reductions in anterior cortical regions were strongly associated with a positive clinical response in both depression and mania. CONCLUSIONS: The findings indicated that cerebral blood flow abnormalities in major depression were not reversed by successful treatment with ECT. Rather, particularly in responders, ECT resulted in additional perfusion reductions. The therapeutic properties of ECT are related to reduced functional brain activity in specific neural regions.

Adult↗

PubMed1994

The metabolic topography of parkinsonism.

We used [18F]fluorodeoxyglucose/positron emission tomography (18F-FDG/PET) and a statistical model of regional covariation to study brain topographic organization in parkinsonism. We studied 22 patients with Parkinson's disease (PD), 20 age-matched normal volunteers, and 10 age- and severity-matched patients with presumed striatonigral degeneration (SND). We used FDG/PET to calculate global, regional, and normalized metabolic rates for glucose (GMR, rCMRglc, rCMRglc/GMR). Metabolic parameters in the three groups were compared using an analysis of variance, with a correction for multiple comparisons, and discriminant analysis. The scaled subprofile model (SSM) was applied to the combined rCMRglc dataset to identify topographic covariance profiles that distinguish PD patients from SND patients and normals. GMR, rCMRglc, and rCMRglc/GMR were normal in PD; caudate and lentiform rCMRglc/GMR was reduced in the SND group (p < 0.01). SSM analysis of the combined group of patients and normals revealed a significant topographic profile characterized by increased metabolic activity in the lentiform nucleus and thalamus associated with decreased activity in the lateral frontal, paracentral, inferior parietal, and parietooccipital areas. Individual subject scores for this profile were significantly elevated in PD patients compared with normals and SND patients (p < 0.001) and discriminated the three groups. In the PD group, subject scores for this factor correlated with individual subject Hoehn and Yahr (H & Y) scores (p < 0.02), and with quantitative rigidity (p < 0.01) and bradykinesia (p < 0.03) ratings, but not with tremor ratings. SSM analysis of right-left metabolic asymmetries yielded a topographic contrast profile that accurately discriminated mildly affected PD patients (H & Y Stage I) from normals. Our findings demonstrate that abnormal topographic covariance profiles exist in parkinsonism. These profiles have potential clinical application as neuroimaging markers in parkinsonism.

Adult↗

PubMed1994

Physical properties and quantification of the ECT stimulus: I. Basic principles.

The physical properties of the electroconvulsive therapy (ECT) stimulus markedly affect both efficacy and side effects. We review basic principles in characterizing these physical properties and in quantifying the ECT stimulus. The topics discussed include the application of Ohm's law, alternative composite units of ECT dosage (energy and charge), the use of constant-current, constant-voltage, and constant-energy principles in ECT devices, the nature of current shunting in ECT and the determinants of impedance, the relations between impedance and seizure threshold, the seizure-eliciting efficiency of alternative stimulus waveforms and of stimulus parameter configurations, and the role of reactive components (capacitance and inductance) in the ECT circuit. New findings are also presented regarding several of these issues.

Electric Impedance↗

PubMed1993

Striatal hypometabolism distinguishes striatonigral degeneration from Parkinson's disease.

Regional and global metabolic rates for glucose were estimated using 18F-fluorodeoxyglucose and positron emission tomography in 10 patients with a clinical likelihood of striatonigral degeneration (2 men and 8 women; mean age, 61.8 +/- 6.9 years; mean disease duration, 4.7 +/- 2.2 years; mean Hoehn and Yahr score, 3.5 +/- 0.8). Measures of brain glucose metabolism in these patients were compared with those for 10 age-matched normal volunteers, 10 disease severity-matched patients with Parkinson's disease (PD), and 10 disease duration-matched patients with PD. Normalized glucose metabolism was significantly reduced in the caudate (p < 0.03) and putamen (p < 0.003) as compared with that in normal and PD control subjects, and discriminated patients with striatonigral degeneration from control subjects (p < 0.002). Putamenal hypometabolism in patients with striatonigral degeneration correlated significantly with quantitative ratings of motor disability (p < 0.02). These results suggest that quantitative 18F-fluorodeoxyglucose positron emission tomography techniques may be useful in supporting a diagnosis of striatonigral degeneration in life, and in objectively assessing disease severity and potential therapeutic interventions.

Aged↗

PubMed1993

Striatal 18F-dopa uptake: absence of an aging effect.

L-[18F]6-Fluoro-DOPA (L-[18F]6-fluoro-3,4-dihydroxyphenylalanine; FDOPA) has been used with quantitative positron emission tomography (PET) to assess presynaptic nigrostriatal dopaminergic function in life. The relationship of estimated kinetic rate constants for striatal FDOPA uptake [Ki(FDOPA)] to the normal aging process has been the subject of conflicting reports. Resolution of this issue has been hampered by methodological differences in previous FDOPA/PET investigations. We studied 19 healthy normal subjects (aged 27-77 years) and measured striatal Ki-(FDOPA) according to each of the earlier methods. While significant correlations (p < 0.005) existed between Ki(FDOPA) values estimated by the various techniques, none correlated with normal aging. We conclude that normal striatal Ki(FDOPA) values estimated using quantitative FDOPA/PET are uncorrelated with the aging process.

Adult↗

PubMed1993

Regional cerebral blood flow in mood disorders. II. Comparison of major depression and Alzheimer's disease.

We contrasted regional cerebral blood flow in matched groups of 30 patients with major depression, 30 patients with Alzheimer's disease and 30 normal controls using the 133Xe inhalation technique. Whereas both the depressed and Alzheimer's disease groups had markedly reduced global cortical blood flow, the Scaled Subprofile Model, developed to identify abnormalities in regional networks, indicated that they had distinct topographic profiles. Previous findings of an abnormal regional network in major depression were unaltered by the inclusion of Alzheimer's disease patients in the analysis. Alzheimer's disease was associated with a distinct parietotemporal deficit and the degree of this abnormality strongly covaried with cognitive impairment. Alzheimer's disease patients also had abnormal manifestation of three other regional networks. We illustrate a method for distinguishing when a disease imposes a new pattern of interactions among brain regions and when a disease alters the expression of regional patterns characteristic of normal functioning.

Aged↗