T.M. Hyde, M.E. Stacey, R. Coppola, S.F. Handel, K.C. Rickler, and D.R. Weinberger
Neurology 1995; 45:1176-82.
Although the pathologic substrate of Tourette's syndrome (TS) is unknown, studies have implicated subtle changes in the basal ganglia. To further investigate structural basal ganglia pathology in TS, we performed morphometric analyses of MRIs of 10 monozygotic twin pairs discordant for severity of TS but concordant for the presence of tic disorders (mean age, 16.3 years; range, 9 to 31 years). Right caudate volume was slightly but significantly reduced in the relatively more severely affected twins as a group compared with the less affected twins (mean difference = 6%, p < 0.01). Most of this difference was attributable to volume reduction in the anterior right caudate (p < 0.02), which was smaller in the more severely affected twin in nine of 10 twin sets. The mean volume of the left lateral ventricle was 16% smaller in the more severely affected twins than in the less severely affected twins (p < 0.01). The normal asymmetry of the lateral ventricles (left greater than right) was not present in the more severely affected twins, who had a trend toward a larger right lateral ventricle. Moreover, the difference within a pair in the degree of loss of the normal ventricular asymmetry correlated with the difference within a pair in the severity of the tic disorder (r = 0.75, p < 0.02). There were no other basal ganglia, ventricular volumetric, or asymmetry abnormalities. These findings partially replicate other MRI studies and suggest that subtle structural abnormalities in the CNS, particularly in the caudate, may play a role in the pathophysiology of TS.(ABSTRACT TRUNCATED AT 250 WORDS)
M.B. Knable, D.W. Jones, R. Coppola, T.M. Hyde, K.S. Lee, J. Gorey, et al.
J Nucl Med 1995; 36:1216-25.
We used equilibrium analysis of SPECT data from patients with asymmetric Parkinson's disease to determine if lateralized differences in the striatal uptake of [123I]IBZM correlate with asymmetry in clinical findings and, by inference, with lateralized differences in the concentration of extracellular dopamine. METHODS: Twelve patients with asymmetric clinical signs of idiopathic Parkinson's disease were injected with a bolus of [123I]IBZM, and multiple SPECT scans recorded the time course of radioligand uptake. The time integral method was used to estimate peak specific binding, so that a ratio of specific-to-nonspecific binding in the left and right striatum of each subject at equilibrium could be determined. Nine patients also had 99mTc-HMPAO SPECT scans which were examined for evidence of blood flow asymmetries. RESULTS: Paired t-tests comparing [123I]IBZM uptake revealed significantly greater (mean = 7.3%) availability of dopamine-D2 receptors in the basal ganglia contralateral to maximal clinical signs. Differences in receptor availability correlated significantly with differences in every measure of the clinical assessment. No significant differences in regional cerebral blood flow between the two sides were observed with 99mTc-HMPAO. CONCLUSION: These results demonstrate the ability of [123I]IBZM SPECT to reveal clinically meaningful variations in striatal dopamine receptor availability in patients with asymmetric Parkinson's disease. The equilibrium analysis technique used to determine these findings is a simple and robust method of measuring relative receptor availability and may be useful in studying other illnesses where dysfunction of dopaminergic neurotransmission is suspected.
M.A. Kling, D.L. Gardner, A.E. Calogero, R. Coppola, J. Trettau, C.H. Kellner, et al.
J Pharmacol Exp Ther 1994; 268:1548-64.
Local anesthetics, given i.v. to treat cardiac arrhythmias and for regional anesthesia, exert prominent central nervous system side effects, such as sensory distortions and mood changes. In experimental animals, these drugs activate limbic structures, such as the amygdala, that may coordinately regulate sensory processing, mood and pituitary hormone secretion during stress. Clinically relevant i.v. doses of the short-acting local anesthetic procaine were administered to 17 healthy volunteers and topographic electroencephalographic (EEG) spectra, stress- responsive neuroendocrine and cardiovascular parameters and sensory- cognitive and mood changes were examined. Because corticotropin-releasing hormone (CRH) mimics the behavioral and physiologic responses to stress and activates limbic structures in experimental animals, the effects of procaine and lidocaine on immunoreactive CRH release from rat hypothalami in vitro were also explored. Procaine administration produced a dose-related increase in fast (21-50 Hz) EEG activity, a significant decrease in alpha EEG activity and dose- dependent increases in heart rate, systolic blood pressure and plasma adrenocorticotropic hormone, cortisol and prolactin secretion. Dose-dependent increases in sensory distortions involved virtually all modalities, particularly auditory, visual and somatosensory. Mood changes occurred in most subjects, including anxiety, euphoria and arousal. In vitro, procaine and lidocaine both produced significant dose-related increases in immunoreactive CRH release from rat hypothalami, maximal at 10(-6) M, that were blocked by carbamazepine, a limbic anticonvulsant used in the management of mood disorders. The electrophysiologic effects of procaine in these volunteers were analogous to local anesthetic effects in experimental animals and consistent with the activation of subcortical structures localized within the temporal lobe, such as the amygdala. The effects of procaine on stress-responsive neurohormones were similar to those of amygdala stimulation both in experimental animals and human subjects. The in vitro data suggested that procaine-induced pituitary-adrenal activation involves stimulation of hypothalamic CRH, although additional (e.g., limbic-hypothalamic) mechanisms may contribute in vivo. These data were compatible with a direct action of local anesthetics on limbic structures that might account for many of the central effects seen with the systemic use of these agents in clinical practice.
S.L. Bressler, R. Coppola, and R. Nakamura
Nature 1993; 366:153-6.
The way in which the brain integrates fragmentary neural events at multiple locations to produce unified perceptual experience and behaviour is called the binding problem. Binding has been proposed to involve correlated activity at different cortical sites during perceptuomotor behaviour, particularly by synchronization of narrow-band oscillations in the gamma-frequency range (30-80 Hz). In the rabbit olfactory system, inhalation induces increased gamma-correlation between sites in olfactory bulb and cortex. In the cat visual system, coherent visual stimuli increase gamma- correlation between sites in both the same and different visual cortical areas. In monkeys, some groups have found that gamma-oscillations transiently synchronize within striate cortex, superior temporal sulcus and somatosensorimotor cortex. Others have reported that visual stimuli produce increased broad-band power, but not gamma-oscillations, in several visual cortical areas. But the absence of narrow-band oscillations in itself does not disprove interregional synchronization, which may be a broad-band phenomenon. We now describe episodes of increased broad-band coherence among local field potentials from sensory, motor and higher-order cortical sites of macaque monkeys performing a visual discrimination task. Widely distributed sites become coherent without involving other intervening sites. Spatially selective multiregional cortical binding, in the form of broad-band synchronization, may thus play a role in primate perceptuomotor behaviour.
R. Coppola
J Clin Neurophysiol 1993; 10:537.
R. Coppola, R. Masetti, M.E. Riccioni, S. Ciletti, A. De Franco, M. Detweiler, et al.
Endoscopy 1993; 25:255-6.
E.M. Kahn, R.D. Weiner, R. Coppola, H.S. Kudler, and K. Schultz
Biol Psychiatry 1993; 33:284-90.
The authors performed spectral analysis of electroencephalograms (EEG), recorded awake, with eyes closed, in 13 patients with schizophrenia and 9 age-matched individuals without psychiatric diagnosis. We tested several possible parameterizations of the data, and two data-reduction strategies; these yielded similar results. Comparison of the two groups revealed a relative increase in alpha frequency activity in the frontal regions in the patient group. The authors believe that this finding is consistent with data from neuropsychologic tests, metabolic imaging studies, and evoked potential studies that suggest impaired activation of frontal brain areas in patients with schizophrenia.
S. Marenco, R. Coppola, D.G. Daniel, J.R. Zigun, and D.R. Weinberger
Psychiatry Res 1993; 50:177-92.
We studied regional cerebral blood flow (rCBF) by xenon-133 dynamic single photon emission computed tomography (SPECT) in 17 normal volunteers who were performing the Wisconsin Card Sorting Test (WCST), a task that is particularly sensitive to disturbance of the prefrontal cortex, and a simple matching-to-sample task (BAR) as a sensorimotor control. Three methods for statistical analysis of regional subtraction data were used: absolute rCBF values, percent distribution values, and means adjusted for global CBF changes (covariance analysis). The absolute values had high variance, due to the combination of interindividual differences in global flow and intra-individual variation, and showed no statistically significant regional changes. This variation was greatly reduced by percent values and covariance analysis, which had quite similar outcomes. With both methods, significant increases of rCBF during the WCST as compared with the BAR were seen in the right anterior dorsolateral prefrontal and left occipital cortices, and reduction of rCBF in the left pararolandic region. Moreover, significant correlations with performance were found in the medial regions of the frontal lobes, with opposite trends for the right and left hemisphere. The posterior dorsolateral prefrontal region showed a negative correlation with sensory-motor frequency, an index related to the task's difficulty. These results are consistent with previous findings using other rCBF techniques and confirm the statistical advantage of normalization and covariance methods, which yield practically identical results, at least in this analysis based on regions of interest.
R.T. Pivik, R.J. Broughton, R. Coppola, R.J. Davidson, N. Fox, and M.R. Nuwer
Psychophysiology 1993; 30:547-58.
Developments in technologic and analytical procedures applied to the study of brain electrical activity have intensified interest in this modality as a means of examining brain function. The impact of these new developments on traditional methods of acquiring and analyzing electroencephalographic activity requires evaluation. Ultimately, the integration of the old with the new must result in an accepted standardized methodology to be used in these investigations. In this paper, basic procedures and recent developments involved in the recording and analysis of brain electrical activity are discussed and recommendations are made, with emphasis on psychophysiological applications of these procedures.
O.M. Wolkowitz, R. Coppola, A. Breier, A.R. Doran, D.R. Rubinow, W.H. Berrettini, et al.
Neuropsychobiology 1993; 27:224-30.
Elevated levels of circulating corticosteroids are frequently associated with behavioral alterations in man, although the mechanisms by which corticosteroids may affect behavior are poorly understood. To evaluate possible effects of exogenous corticosteroids on brain electrophysiological functioning and the relationship of such effects to behavioral and biochemical changes, we administered prednisone (80 mg p.o. daily for 5 days) in a double-blind manner to 11 medically healthy volunteers. Quantitative electroencephalogram analysis was performed following 4 days of prednisone administration and during the preceding and ensuing placebo administration periods. Central theta wave brain electrical activity significantly increased following prednisone administration and returned to baseline following prednisone withdrawal. This effect was directly correlated with prednisone-induced increases in subjective sadness ratings and with decreases in self-rated energy and well-being. Prednisone-induced reductions in peak alpha wave activity were also directly correlated with increases in subjective sadness and Symptom Checklist-90 ratings and with decreases in self-rated 'hypomanic' symptoms. Further, prednisone-induced increases in theta activity were significantly correlated with prednisone-induced decreases in CSF levels of somatostatin-like immunoreactivity, and prednisone-induced decreases in peak alpha activity were significantly correlated with decreases in CSF levels of norepinephrine and with relative increases (or lesser decreases) in CSF levels of beta- endorphin and beta-lipotropic hormone. This preliminary report of the concomitant development of prednisone-induced changes in brain electrical activity, neurochemistry and behavior highlights areas for future exploration in the study of corticosteroid effects on behavior in man.
R. Coppola, S. Marenco, D.W. Jones, K.F. Berman, and D.R. Weinberger
Psychiatry Res 1992; 45:187-200.
Phantom studies and cerebral blood flow (CBF) measurements in 11 normal subjects at rest were performed by single photon emission tomography (SPECT) with Xe-133 (16 mm full-width at half-maximum [FWHM] collimation) and Xe-127 (16 mm, 12 mm, and 9 mm FWHM collimation). The phantom results clearly illustrated the feasibility of Xe-127 studies and the advantage of Xe-127 over Xe-133 for equivalent patient dose exposures. CBF values obtained with Xe-127 were comparable to those of Xe-133 for the 16 mm collimator, although higher flow values were found with the better resolution, probably because of reduced partial volume effects. The correlations between the various groups of examinations were high, except for the Xe-133 and Xe- 127 16 mm collimator groups. Xe-127 allows a considerable increase in the resolution of the images, while exposing the patient to a lower radiation dose. Potential limitations because of higher energy penetrating photons from Xe-127 were not observed in this specially shielded equipment.
J.M. Gold, C. Randolph, R. Coppola, C.J. Carpenter, T.E. Goldberg, and D.R. Weinberger
Schizophr Res 1992; 7:203-9.
Patients with schizophrenia demonstrate a variety of attentional impairments which have proven difficult to relate to specific neural systems. Posner et al. (1988) reported an asymmetric slowing of right visual field orienting in schizophrenia similar to that observed in patients with parietal lesions. We examined the visual orienting performance of 19 patients and controls using two different versions of the Posner paradigm. In overall ANOVAs we found main effects of group, cue condition, and delay interval. However, we did not observe any main effect of visual field or interactions involving visual field. There was some evidence of an asymmetric cost of invalid cues similar to those reported by Posner et al. The bulk of data suggests bilateral attentional deficits.
F. Newman, M.B. Stein, J.R. Trettau, R. Coppola, and T.W. Uhde
Psychiatry Res 1992; 45:105-13.
It has been demonstrated that patients with panic disorder are more sensitive than normal control subjects to the anxiogenic effects of caffeine. The underlying physiologic basis for this difference is unclear. We examined the electroencephalographic (EEG) activity of seven patients with panic disorder and seven normal control subjects during the randomized double-blind, placebo-controlled administration of oral caffeine (7 mg/kg). EEG data were collected on-line from 28 electrodes; artifact-free epochs were selected manually for off-line Fourier transformation. Caffeine was associated with a significant increase in peak occipital alpha frequency and significant decreases in occipital alpha amplitude, central beta amplitude, and central theta amplitude. Despite the observation that caffeine increased anxiety more in the patients with panic disorder than in the normal control subjects, the two groups did not differ in their EEG responses to caffeine.
D.R. Weinberger, D. Jones, R.C. Reba, U. Mann, R. Coppola, R. Gibson, et al.
J Neuropsychiatry Clin Neurosci 1992; 4:239-48.
Prior studies of patients with dementia have found similar qualitative patterns of cerebral glucose utilization with [18F]2-fluoro-2-deoxyglucose (FDG) PET and of putative muscarinic receptor activity with [123I]3-quinuclidinyl-4- iodobenzilate (IQNB). This raised doubts about whether receptor binding determines IQNB distribution and whether clinical information in IQNB scans is unique. To compare the methods directly, 4 normal volunteers and 7 patients with dementia underwent FDG PET and high-resolution IQNB SPECT scans. In normal subjects, relative regional activity from the paired scans was only weakly correlated (r = 0.29). Some regions (e.g., thalamus, frontal cortex) showed a clear disassociation of activity. In demented patients, IQNB scans tended to show larger defects than FDG scans, although one focal defect appeared only with PET. Results suggest that IQNB SPECT data are not primarily related to general physiological activity or regional cerebral blood flow and are not explained by attenuation or volume-averaging artifacts. Further studies should investigate whether IQNB scanning is a more sensitive in vivo measure of the extent of Alzheimer's disease than is FDG PET.
R. Coppola
Brain Topogr 1991; 4:81-3.
D.G. Daniel, D.R. Weinberger, D.W. Jones, J.R. Zigun, R. Coppola, S. Handel, et al.
J Neurosci 1991; 11:1907-17.
To explore the role of monoamines on cerebral function during specific prefrontal cognitive activation, we conducted a double-blind placebo-controlled crossover study of the effects of 0.25 mg/kg oral dextroamphetamine on regional cerebral blood flow (rCBF) as determined by 133Xe dynamic single-photon emission- computed tomography (SPECT) during performance of the Wisconsin Card Sorting Test (WCST) and a sensorimotor control task. Ten patients with chronic schizophrenia who had been stabilized for at least 6 weeks on 0.4 mg/kg haloperidol participated. Amphetamine produced a modest, nonsignificant, task-independent, global reduction in rCBF. However, the effect of amphetamine on task-dependent activation of rCBF (i.e., WCST minus control task) was striking. Whereas on placebo no significant activation of rCBF was seen during the WCST compared with the control task, on amphetamine significant activation of the left dorsolateral prefrontal cortex (DLPFC) occurred (p = 0.0006). Both the mean number of correct responses and the mean conceptual level increased (p less than 0.05) with amphetamine relative to placebo. In addition, with amphetamine, but not with placebo, a significant correlation (p = -0.71; p less than 0.05) emerged between activation of DLPFC rCBF and performance of the WCST task. These findings are consistent with animal models in which mesocortical catecholaminergic activity modulates and enhances the signal-to-noise ratio of evoked cortical activity.
M.S. Myslobodsky, R. Coppola, and D.R. Weinberger
Brain Topogr 1991; 3:381-90.
Bilateral EEG recording is a common practice when brain laterality needs to be assessed in cognitive neurophysiology and psychiatry research. Its precision and validity remain uncertain. With structural brain imaging methods, it is possible to examine EEG electrode placements according to the 10-20 system and the validity of inferences made on derived data. Frequent sources of placement errors are examined along with important factors that contribute to EEG imbalance. Examples are mentioned where asymmetries of EEG/ERP caused by cranial and parenchymal brain asymmetries may be mistaken for cognition- related laterality changes. Because external skull landmarks are not reliable predictors of cranial and parenchymal brain asymmetries, laterality assessment cannot be guaranteed by the 10-20 system. Consequently, a return, on a case- to-case basis, to nonstandard montages, assisted by structural brain imaging is seen as an acceptable alternative.
M.S. Myslobodsky, J. Glicksohn, R. Coppola, and D.R. Weinberger
Vision Res 1991; 31:1677-85.
The topography of visual evoked potentials (VEP) is dependent on occipital lobe morphology. Using magnetic resonance imaging we examine the sulcal pattern (the calcarine and parieto-occipital sulci), and assess the size of the cuneus and the asymmetry of the occipital lobes, computed separately for its ventral and dorsal segments. No differences were found for either the cuneus or the sulci pattern. In contrast, hemispheric asymmetry values appeared to be substantial. The predominance of the left occipital area was seen distinctly in the ventro-caudal portion of the occipital lobe. It was frequently reversed in the dorsal aspect of the lobe, notably in more rostral cuts. Such complexities may lead to ambiguities in interpreting VEP asymmetries.
G. Rodriguez, R. Coppola, F. De Carli, S. Francione, S. Marenco, F. Nobili, et al.
Brain Topogr 1991; 4:57-63.
Regional cerebral blood flow (rCBF) asymmetries were studied in 189 subjects (96 males and 93 females) at rest with the 133Xenon inhalation method using a fixed detector system. rCBF asymmetries in the resting condition were very small, nevertheless a significant (p less than 0.001) effect for their topographical distribution was present, reflecting higher rCBF in the right fronto-temporal and left parieto-occipital regions. rCBF asymmetries were not correlated with age, and there were no significant differences between males and females. Asymmetries are therefore useful from a statistical point of view in detecting rCBF abnormalities in the resting condition: they are more stable than absolute values in normal subjects and no matching according to age or sex is required when statistical comparisons are performed.
D.R. Weinberger, R. Gibson, R. Coppola, D.W. Jones, S. Molchan, T. Sunderland, et al.
Arch Neurol 1991; 48:169-76.
A high-affinity muscarinic receptor antagonist, 123IQNB (3- quinuclidinyl-4-iodobenzilate labeled with iodine 123), was used with single photon emission computed tomography to image muscarinic acetylcholine receptors in 14 patients with dementia and in 11 healthy controls. High- resolution single photon emission computed tomographic scanning was performed 21 hours after the intravenous administration of approximately 5 mCi of IQNB. In normal subjects, the images of retained ligand showed a consistent regional pattern that correlated with postmortem studies of the relative distribution of muscarinic receptors in the normal human brain, having high radioactivity counts in the basal ganglia, occipital cortex, and insular cortex, low counts in the thalamus, and virtually no counts in the cerebellum. Eight of 12 patients with a clinical diagnosis of Alzheimer's disease had obvious focal cortical defects in either frontal or posterior temporal cortex. Both patients with a clinical diagnosis of Pick's disease had obvious frontal and anterior temporal defects. A region of interest statistical analysis of relative regional activity revealed a significant reduction bilaterally in the posterior temporal cortex of the patients with Alzheimer's disease compared with controls. This study demonstrates the practicability of acetylcholine receptor imaging with 123IQNB and single photon emission computed tomography. The data suggest that focal abnormalities in muscarinic binding in vivo may characterize some patients with Alzheimer's disease and Pick's disease, but further studies are needed to address questions about partial volume artifacts and receptor quantification.
R. Coppola, and J. Gold
Arch Gen Psychiatry 1990; 47:291-2.
R. Coppola, and J. Gold
Arch Gen Psychiatry 1990; 47:393-5.
M.S. Myslobodsky, R. Coppola, J. Bar-Ziv, and D.R. Weinberger
J Clin Neurophysiol 1990; 7:507-18.
The adequacy of the International 10-20 System is reviewed in light of demands imposed on the accuracy of lead placement by improvements in spatiotemporal brain electrical activity mapping technology. Computed tomography (CT) and magnetic resonance imaging (MRI) studies reveal that the most frequent sources of inaccuracy of electrode locations are difficulties in defining the inion, variance in the anatomy of the occipital bone, inconspicuous sagittal deformities, variance of sulcal pattern, and brain width asymmetries. Owing to these factors, electrodes placed bilaterally and equidistant from the nasion-inion line may not be homotopically located. Therefore, the authors suggest that practitioners who employ the 10-20 System in order to gain precise and more individualized laterality information do so with extreme caution until the range of placement and interpretative errors is more precisely determined using CT/MRI-assisted EEG.
D.R. Weinberger, U. Mann, R.E. Gibson, R. Coppola, D.W. Jones, A.R. Braun, et al.
Adv Neurol 1990; 51:147-50.
D.G. Daniel, M.S. Myslobodsky, L.J. Ingraham, R. Coppola, and D.R. Weinberger
Schizophr Res 1989; 2:465-72.
It has long been hypothesized, but never proven that an organic brain injury early in life predisposes to schizophrenia. Since brain and cranial development are closely linked, if such an event occurred early enough in the premorbid course of schizophrenia, it could conceivably effect skull architecture. To approach this question, the occipital bone depth and the occipitomedian angle were measured in 50 patients with chronic schizophrenia and in 35 medical controls. Strong correlations emerged between the skull asymmetry indices and the occipital and temporal lobe parenchymal asymmetry indices. There were no statistically significant differences in cranial asymmetry measures between the patients with schizophrenia and the medical controls. However, when the comparison was limited to right handed individuals with homolateral sighting dominance, a weak, but statistically significant trend was observed for more symmetrical slanting along the sagittal suture in the schizophrenic patients. In addition, cranial asymmetry was weakly predictive of increased prefrontal markings in the schizophrenic patients. The congruence of skull findings with parenchymal variables suggests that certain aspects of skull and parenchymal architecture are co-determined.
M.S. Myslobodsky, R. Coppola, J. Bar-Ziv, C. Karson, D. Daniel, H. van Praag, et al.
Brain Topogr 1989; 1:221-8.
The plagiocephaly index, an index that reflects an underlying anatomic asymmetry of the brain, was assessed in ten schizophrenic patients and its values were correlated with the lateral distribution of quantitatively evaluated EEG. The correlations between the index and alpha power at F7 were significant, positive for frontal asymmetry (frontal bulging) and negative for occipital flattening. We then studied ten normal subjects in an attempt to illuminate the contribution of several cephalic and cranial variables to the imbalance of alpha-afterdischarges (AD) of VEP recorded at O1-O2. The asymmetry index of AD was computed and correlated with asymmetries of CT-derived measures of occipital bone thickness, occipital lobe width, mastoid area, and sulcal asymmetry (the asymmetry of intraparietal sulcus location from the longitudinal fissure). With the exception of the sulcal variable all measures significantly covaried with alpha AD. These findings caution that it may be important to determine cranial and brain parenchymal asymmetries where brain laterality is pertinent to studies of EEG.
J.M. Rumsey, R. Coppola, M.B. Denckla, S.D. Hamburger, and M.J. Kruesi
Electroencephalogr Clin Neurophysiol 1989; 73:30-40.
To identify and localize differences in brain functioning, electrical activity was recorded with a full complement of scalp electrodes in 14 healthy, severely dyslexic men (mean age = 22 years, S.D. = 3) and 15 matched controls during rest and during word and design recognition. The electroencephalograms were spectrum analyzed, and the mean amplitude in each of 5 bands--delta, theta, alpha, slow beta and fast beta--compared topographically between conditions and groups. The two tasks did not elicit differentially lateralized patterns of electrical activity, but produced anteroposterior differences in alpha and theta. The Designs task, more difficult for both groups, was associated with less posterior alpha than was the Words task. The strongest group difference was likewise seen along an anteroposterior axis on the Designs task. With performance equal to that of controls, the dyslexics showed relatively greater fronto-central theta and less posterior theta (a more activated state), suggesting that dyslexics were compensating for less efficient information processing. There were no group differences in overall amplitude in any band for any condition. The differences in the topographic distribution of theta may reflect subtle differences in brain organization or compensatory recruitment of widely distributed neuronal networks.
M.J. Eckardt, J.W. Rohrbaugh, D. Rio, R.R. Rawlings, and R. Coppola
Adv Alcohol Subst Abuse 1988; 7:59-71.
Imaging in vivo aspects of brain structure and function hold great promise for the study of alcoholism. Computerized axial tomography and magnetic resonance imaging have been used successfully to demonstrate structural abnormalities in alcoholic patients. Positron emission tomography and topographic images of electrical and magnetic activity are useful measures of brain function that could be applied more rigorously to the study of alcoholism. Interrelating various types of imaging data is an important area that is still in the developmental stage.
E.M. Kahn, R.D. Weiner, R.P. Brenner, and R. Coppola
Biol Psychiatry 1988; 23:628-36.
Topographic mapping of brain electrical activity is a popular, powerful, and potentially misleading technique. The map lies at the end of a long chain of physiological, technical, electronic, and mathematical processes and is vulnerable to artifact, error, and distortion at many points. Close attention must be paid to data collection parameters, subject cooperation, minimization of artifact, limitations of resolutions, selection, and transformation of parameters for display, and map generation strategy to yield an accurate, physiologically interpretable map. Review of the data at each step of analysis, from the paper electroencephalogram (EEG) to sets of maps on video display, may be necessary for optimum understanding. Development of more sophisticated qualitative and quantitative concepts of normal physiology is needed. These improvements in electrophysiological data analysis demand, rather than obviate, sophistication on the part of the user.
C.N. Karson, R. Coppola, and D.G. Daniel
Am J Psychiatry 1988; 145:861-4.
Low alpha frequency (less than 10.2 Hz) occurred more frequently in medication-free schizophrenic patients than in normal control subjects, as determined by quantitative EEG analysis. Furthermore, those patients with low alpha frequency had significantly larger lateral ventricles, as measured by CT scan, than did other schizophrenic patients (mean +/- SD ventricle-brain ratios = 9.8 +/- 1.9 versus 5.0 +/- 2.4; p less than 0.01). This finding suggests the existence of a relationship between cerebral structural pathology and the alpha rhythm that may be based on involvement of alpha- generating structures which border the cerebral ventricles. Future EEG studies of schizophrenia may resolve these questions in the context of other brain findings.
C.N. Karson, R. Coppola, D.G. Daniel, and D.R. Weinberger
Schizophr Bull 1988; 14:193-7.
Despite advances in the processing and display of electroencephalographic (EEG) data, the utility of this inexpensive and noninvasive technique in the investigation of schizophrenia has not been well established. We studied the resting EEG in 19 medication- free patients with chronic schizophrenia and 21 normal controls. Patients with schizophrenia had increased delta activity which was not specific to the frontal regions. Schizophrenic patients also had increased fast activity, and this increase was left sided for the fast beta frequency. Alpha frequency was reduced (less than 10.2 Hz) in 7 of 16 schizophrenic patients. Moreover, those patients with an alpha frequency reduction had a significantly larger mean cerebral ventricular size. These results indicate that the EEG does detect neurophysiological changes in schizophrenia. Our understanding of these changes may be enhanced by other neuroimaging techniques such as computed tomography.
C.N. Karson, T.E. Goldberg, and R. Coppola
Schizophr Res 1988; 1:399-403.
Patients with chronic schizophrenia had their EEGs recorded during medication withdrawal. Neuropsychological testing was done on the same patients during a period of 'optimum' functioning during neuroleptic treatment. Correlations between alpha activity, verbal IQ and Halsted-Reitan battery performance were evident over the entire scalp. This led us to examine whether these correlations were related to the inability of a substantial proportion of these patients to generate significant alpha activity. Patients unable to generate significant alpha activity tended to have neuropsychological impairment. These preliminary results suggest that this measure of brain physiology may relate to functional impairment in schizophrenia.
O.M. Wolkowitz, A. Breier, A. Doran, D. Rubinow, W. Berrettini, R. Coppola, et al.
Psychopharmacol Bull 1988; 24:492-4.
R. Coppola, and W.M. Herrmann
Neuropsychobiology 1987; 18:97-104.
In a double-blind fourfold crossover design, 11 subjects were randomly assigned to placebo, 10 mg diazepam, 75 mg amitriptyline, and 75 mg chlorpromazine. During a simple vigilance task, 12 midline and left hemisphere leads were recorded before and 3 h after drug administration. The EEG was quantified by spectrum analysis, the topographic structure displayed by brain mapping techniques, and the results compared with earlier studies which used the same design and drugs. Diazepam showed the expected increase in beta; however, fast beta was increased as much as slow beta. Amitriptyline showed an increase of slow wave power and a reduction of alpha. In contrast to earlier studies, a decrease of fast beta was found. In addition, the spatial pattern of alpha changed from an occipital to a parietal maximum. Chlorpromazine showed an increase in the theta band. In occipital regions, there was a small decrease of fast beta; however, centrally there was an increase of both slow and fast beta. These results were confirmed by a multivariate analysis of variance.
R. Coppola, and N.T. Morgan
Electroencephalogr Clin Neurophysiol 1987; 67:191-3.
Topographic analysis of EEG and evoked potentials requires the computer processing of data from multi-lead recording. The use of 20 or more channels is now quite common, straining the resources of the usual EEG machine. We present a design for a high gain, low noise, 32-channel amplifier matched to computer data acquisition requirements. Low cost and small size are additional benefits to the design.
C.N. Karson, R. Coppola, J.M. Morihisa, and D.R. Weinberger
Arch Gen Psychiatry 1987; 44:514-7.
Several topographic mapping studies of electroencephalographic (EEG) power spectra have reported increased slow (delta) activity in the frontal regions of schizophrenic patients. Using supraorbital and lateral canthus electrodes to detect eye movement, we deleted EEG epochs during eye movement in 15 medication- free patients with schizophrenia and in 13 normal control subjects. Power spectral analysis of the 28-channel EEG demonstrated a diffuse mild increase in delta activity in schizophrenic patients compared with normal control subjects but no tendency for frontal localization of this slow activity. There were no differences between schizophrenic patients and normal control subjects in other frequency bands. These results, which replicate earlier findings of increased delta activity in schizophrenia, emphasize the importance of excluding the slow activity due to eye movement in the comparisons of summed EEG spectra. This emphasis can best be ensured by equating the summed spectra from extraocular movement channels of experimental and control groups.
C.H. Kellner, R.M. Post, F. Putnam, R. Cowdry, D. Gardner, M.A. Kling, et al.
Biol Psychiatry 1987; 22:1107-26.
Evidence from animal and human studies suggests that procaine hydrochloride may selectively activate limbic system structures and suppress neocortical structures. We administered a series of intravenous bolus doses of procaine hydrochloride to 31 subjects (7 with affective disorders, 17 with borderline personality disorder, and 7 healthy normal volunteers). Dose-related cognitive and sensory distortions and illusions were observed; affective experiences ranged widely from euphoric to dysphoric. Topographic electroencephalogram (EEG) analysis indicated selective increases in fast activity (26-45 Hz) over the temporal lobes; the degree of increase in this activity correlated with degree of dysphoria experienced. Procaine was associated with increases in secretion of cortisol, adrenocorticotrophic hormone (ACTH), and prolactin, but not with growth hormone. These preliminary data are consistent with the possibility that procaine might serve as a clinically useful probe of psychosensory, affective, electrophysiological, and endocrine effects referable to the limbic system.
M.A. Kling, C.H. Kellner, R.M. Post, R.W. Cowdry, D.L. Gardner, R. Coppola, et al.
Prog Neuropsychopharmacol Biol Psychiatry 1987; 11:459-81.
1. Literature is reviewed that implicates various limbic structures (particularly amygdala and hippocampus) in the modulation of stress- associated neuroendocrine systems. 2. Procaine and related local anesthetics may show a selective proclivity for activating limbic structures. 3. Procaine stimulates ACTH-cortisol and prolactin, but not growth hormone secretion. This pattern is most comparable to that elicited by stimuli which act bilaterally on temporal lobe and limbic areas. 4. Procaine may be a useful agent for helping to elucidate the anatomic and physiologic basis for mood, endocrine, and cognitive dysregulation associated with stress and affective disorders. 5. The endocrine concomitants of limbic activation may have relevance to the course and symptom complex of affective disorders and related psychiatric conditions.
R.K. Nakamura, M.S. Myslobodsky, R. Coppola, J. Johannesen-Conway, and A.F. Mirsky
Behav Brain Res 1987; 26:19-27.
It has been suggested that monkeys, administered gamma- hydroxybutyrate (GHB), manifest a state resembling petit mal status. This implies that an animal would produce erroneous responses immediately prior to, and discontinue behaviors requiring any cognitive effort concurrently with, an episode of GHB-induced generalized 3 cps wave-spike bursts in the EEG. This prediction was not confirmed in the present study. Rhesus macaques (Macaca mulatta) were trained to perform in a visual discrimination Go/No-go test. Thereafter bipolar transcortical electrodes were implanted in the hemisphere contralateral to the preferred hand. All monkeys discontinued to lever-press for water reward when administered GHB (125 or 250 mg/kg, esophageal intubation) and exhibited signs of reduced postural control and somnolence punctuated by episodes of hypermotility about 40-50 min after GHB. However, the monkey's difficulties in completing the program were not associated with the development of generalized hypersynchronous EEG activity. While occasional wave-spike bursts did occur, they were poorly regulated, often 'focal' (i.e. developed only in isolated areas), and had a frequency of 1.5-2 cps. In this state, animals could be easily roused by sensory stimuli. All of them reacted with a characteristic aversive-aggressive display when confronted by a direct gaze. These effects are interpreted to be more consistent with characterization of GHB activity as that of a potent hypnotic rather than a convulsant agent.
R. Coppola, and R.H. Gracely
Pain 1983; 17:257-66.
Many applications of sensory decision theory (SDT) to pain research have used discrimination as a measure of pain or sensory sensitivity. This belief is based on the classical SDT assumption that discrimination and criterion represent separation of sensory and decision processes. This assumed separation stems from a model where all noise or variability is part of the sensory transduction mechanism. We present an alternative formulation that allows for decision variability as well as variability in sensory transduction. This formulation documented by computer simulation shows that decision variability and sensory variability are indistinguishable and that any measure of discriminability is degraded by both. Thus discriminability is influenced by both sensory and non-sensory factors. There is no way of knowing if a drug-induced change in discriminability represents an analgesic effect or a change of the observer's ability to make consistent judgments.
M.S. Buchsbaum, W.B. Mendelson, W.C. Duncan, R. Coppola, J. Kelsoe, and J.C. Gillin
Sleep 1982; 5:248-55.
Computer-generated cortical maps of power spectral estimates derived from 16 leads were drawn based on daytime sleep recordings in four normal volunteers. These data were compiled from nine 10-s artifact-free, EEG epochs from awake, stages 1-4 and REM sleep in each volunteer. EEG leads were placed on the left hemisphere and midline according to the 10-20 system with four additional interpolated posterior locations. Magnitude spectral estimates with 1 Hz resolution and adjacent frequencies (delta 2-4, alpha 8-12, beta 13-18) were analyzed with two-way ANOVA (lead by sleep stage). Delta activity was relatively uniform and of low amplitude in awake, eyes-closed subjects, and REM. Delta power increased at the vertex in stage 1. With progressing, non-REM sleep stages, it increased in power and enlarged radially to the intraparietal sulcus posteriorly, and the superior frontal gyrus anteriorly. Comparison of maps with ear and a computed average reference yielded similar topographic patterns. Alpha activity was expectedly maximal occipitally in awake subjects, but surprisingly a frontal area appeared in slow wave sleep. Beta activity in awake subjects was low and maximal parietally; stages 1 and REM showed even lower and more uniform distribution. Stage 2 showed the greatest power, concentrated at the vertex, with stages 3 and 4 diminishing. These data suggest that sleep stages are not completely uniform electrophysiologically across the cortex. This opens the possibility for a new method for the diagnosis of sleep disorders and alternatives in sleep staging.
M.S. Buchsbaum, F. Rigal, R. Coppola, J. Cappelletti, C. King, and J. Johnson
Electroencephalogr Clin Neurophysiol 1982; 53:237-42.
This report describes an integrated anatomical, electrophysiological and data management system for presenting cortical surface distribution maps. Approximately equal area projections (lateral and top) were constructed from a cross-sectional whole head atlas. Anatomical landmarks (major sulcus and gyrus locations) were also located on the outline. The outline and weights for interpolation are stored in the computer, with software for map generation directly from multilead EEG or evoked potential data. Electrode position and number can be easily varied and mapped onto any shaped space using the same program. Data derived from other sources such as xenon blood flow, brain scans or positron emission tomography can similarly be presented. The program uses a laboratory computer and emphasizes simplicity of data management and a mapping algorithm which is applicable to many forms of data.
R. Coppola, M.S. Buchsbaum, and F. Rigal
Comput Biol Med 1982; 12:191-9.
A laboratory computer system in described which will rapidly generate gray-scale maps showing the distribution of measures derived from the electrical activity of the brain, such as the electroencephalogram (EEG) or other biological measures. The system allows flexible description of electrode number and placement, mapping onto any shaped space and rapid generation of maps by integration with the data collection software.
M.S. Buchsbaum, G.C. Davis, R. Coppola, and D. Naber
Pain 1981; 10:367-77.
Somatosensory evoked potentials (EPs) to stimuli ranging from barely perceptible to painful were recorded in 153 normal adults. Reliability of amplitude and amplitude/intensity slopes were demonstrated in 29 individuals tested twice, two or more weeks apart. In randomized, double-blind placebo controlled trials, both aspirin and morphine significantly diminished N120 component at high stimulus intensities. Age, sex and pharmacological effects paralleled those found with psychophysical techniques in part I of this study.
M.S. Buchsbaum, G.C. Davis, R. Coppola, and D. Naber
Pain 1981; 10:357-66.
A new electric stimulation pain assessment technique using the Tursky electrode and a non-parametric analysis of subjects ratings was found sensitive to aspirin, morphine and opiate antagonists in a series of double-blind cross-over trials in normal adults. Stable individual differences in pain sensitivity (off medication) were maintained on two testing sessions 7 months apart. Older individuals were less pain sensitive than younger individuals. Men were more insensitive than women under age 30. Together, these results suggest the empiric usefulness of this pain measurement technique.
M. Dubois, R. Coppola, M.S. Buchsbaum, and D.E. Lees
Electroencephalogr Clin Neurophysiol 1981; 52:157-62.
Somatosensory evoked potentials (SEPs) and body temperature were recorded in patients subjected to induced total hyperthermia for treatment of advanced neoplasms. Elevation of body temperature up to 42 degrees C for 2 h was achieved using a computer- controlled external heating system. SEPs were recorded continuously on-line during the treatment using finger shock stimulation. Evoked potential components later than 160 msec disappeared in the early part of the treatment, but reappeared quickly during cooling. P50 and P50-N70 amplitudes decreased regularly and significantly over the whole duration of the heating period. During the plateau period, no evoked potential peaks could be detected but short latency peaks reappeared as soon as cooling started. The disappearance of SEPs to finger stimulation during sustained hyperthermia at 42 degrees C confirms the findings obtained by EEG recording that a major neuronal dysfunction occurs under these circumstances which subsides quickly as temperature is dropped.
R. Coppola
Electroencephalogr Clin Neurophysiol 1979; 46:224-6.
A method for isolating and removing very slow activity from EEG records prior to spectrum computation is presented. This is accomplished by an autoregressive filter whose frequency transfer characteristic can be easily controlled. Examples of spectra computed for various filter parameter values are shown.
R. Coppola, R. Tabor, and M.S. Buchsbaum
Electroencephalogr Clin Neurophysiol 1978; 44:214-22.
Techniques were developed for measurement of signal to noise ratio and response variability in single trial evoked potentials. These techniques were extended and verified using a digital computer simulation of signal plus noise trials. When applied to real data the measures appear to have high reliability and to demonstrate that human evoked potentials are more variable than would be expected from background noise variation alone. Empirical equations are presented which can be applied to existing single trial EP data to estimate both signal-to-noise ratio and its expected variance.
M. Buchsbaum, R. Coppola, and T.E. Bittker
Neuropsychologia 1974; 12:533-44.
S.G. Landau, M.S. Buchsbaum, R. Coppola, and M. Sihvonen
Percept Mot Skills 1974; 39:239-46.