Changes in local and network brain activity after stereotactic thermocoagulation in patients with drug-resistant epilepsy

Objective

Stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) aims to reduce seizure frequency by modifying epileptogenic networks through local thermocoagulative lesions. Although RF-TC is hypothesized to functionally modify brain networks, reports of changes in functional connectivity (FC) following the procedure are missing. We evaluated, by means of SEEG recordings, whether variation in brain activity after RF-TC is related to clinical outcome.

Methods

Interictal SEEG recordings from 33 patients with drug-resistant epilepsy (DRE) were analyzed. Therapeutic response was defined as a >50% reduction in seizure frequency for at least 1 month following RF-TC. Local (power spectral density [PSD]) and FC changes were evaluated in 3-min segments recorded shortly before (baseline), shortly after, and 15 min after RF-TC. The PSD and FC strength values after thermocoagulation were compared with baseline as well as between the responder and nonresponder groups.

Results

In responders, we found a significant reduction in PSD after RF-TC in channels that were thermocoagulated for all frequency bands (p = .007 for broad, delta and theta, p <.001 for alpha and beta bands). However, we did not observe such PSD decrease in nonresponders. At the network level, nonresponders displayed a significant FC increase in all frequency bands except theta (broad, delta, beta band: p <.001; alpha band: p <.01), although responders showed a significant FC decrease in delta (p <.001) and alpha bands (p <.05). Nonresponders showed stronger FC changes with respect to responders exclusively in TC channels (broad, alpha, theta, beta: p >.05; delta: p = .001).

Significance

Thermocoagulation induces both local and network-related (FC) changes in electrical brain activity of patients with DRE lasting for at least 15 min. This study demonstrates that the observed short-term modifications in brain network and local activity significantly differ between responders and nonresponders and opens new perspectives for studying the longer-lasting FC changes after RF-TC.     

EEG development in Attention Deficit Hyperactivity Disorder: From child to adult

ObjectiveAttention Deficit Hyperactivity Disorder (ADHD) is one of the most common psychiatric disorders found in children. While an extensive literature has documented the EEG in this clinical population, few studies have investigated EEG throughout the lifespan in ADHD. This study aimed to investigate EEG maturational changes, in subjects with ADHD combined type, that spanned from childhood into adulthood.MethodTwenty five male adults with ADHD were assessed between the ages of 8–12 years and again as adults. At both ages, an EEG was recorded during an eyes-closed resting period, and power estimates were calculated for relative delta, theta, alpha and beta.ResultsAt the childhood assessment, the ADHD subjects had elevated posterior delta. Relative theta was elevated, with diminished alpha activity across all sites. Significant maturational changes were observed, with reductions in the delta and theta bands, and increases in the alpha and beta bands across all electrodes. In adulthood, relative to controls, diminished frontal delta and elevated global theta activity were apparent.ConclusionsSubstantial developmental changes occurred in the EEG of these subjects. These results identify important issues when using EEG as part of the diagnosis for ADHD.SignificanceThis study is the first to explore EEG changes from childhood to adulthood over an 11 year period in the same subjects with ADHD.     

Responder characteristics to a single oral dose of cholinesterase inhibitor: a double-blind placebo-controlled study with tacrine in Alzheimer patients

A proportion of Alzheimer's disease (AD) patients treated for several months with cholinesterase (ChE) inhibitors have shown some favorable response on cognition, but the characteristics of the responders are still unclear. This study attempts to identify the characteristics of individuals with a positive behavioral response after a double-blind randomized administration of a single oral dose of tacrine (40 mg) and placebo to AD patients. Furthermore, the relationship between single-dose and long-term responders are examined. Twenty-four mildly to very mildly demented AD patients participated in the study. They all fulfilled the diagnosis of probable AD according to NINCDS-ADRDA criteria. Active treatment (tacrine 40 mg) and placebo was administered in random order on 2 consecutive days, and the effects were evaluated within 2 h using neuropsychological tests (assessing visuospatial ability, episodic memory and attention), registration of EEG activity and measurement of red blood cells (RBC) acetylcholinesterase (AChE), ChE activity and concentrations of tacrine and its metabolites in plasma. Results demonstrated significant improvement, tacrine compared to placebo, in measures of attention, but not in episodic memory or visuospatial ability. A single-dose response was therefore defined in terms of improvement in attention. The tacrine plasma concentration (pcTHA) showed a positively skewed distribution (mean +/- SD: 10.5 +/- 11.8, range: 1.0-51.8 ng/ml). There were no significant differences between single-dose responders compared to nonresponders in pcTHA, metabolites of tacrine, inhibition of AChE in RBC, tau levels in CSF, AChE activity in CSF or plasma and demographic variables. However, single-dose responders showed a higher right frontal alpha/theta ratio on EEG and had lower glucose metabolism in the parietal-temporal association cortex at baseline. In addition, the frequency of apolipoprotein E (APOE) epsilon 4 alleles was higher in responders. Interestingly, the single-dose response was related to the long-term response, although not significantly, which probably was due to lack of power. To conclude, the present study identified single-dose responders in terms of improved attentional performance associated with a relatively higher alpha/theta activity in the right frontal regions of the brain measured on EEG and predominance of APOE epsilon 4 allele.     

EEG differences between good and poor responders to methylphenidate in boys with the inattentive type of attention-deficit/hyperactivity disorder.

OBJECTIVES: This study investigated electroencephalographic (EEG) differences between good and poor responders to methylphenidate in boys with the Inattentive type of Attention-Deficit/Hyperactivity Disorder (ADHD).METHODS: Twenty good and 15 poor responders to methylphenidate, based on the results of a continuous performance task, and 35 age- and sex-matched control subjects, participated in this study. EEG was recorded from 21 sites during an eyes-closed resting condition and Fourier transformed to provide estimates for total power, and absolute and relative power in the delta, theta, alpha and beta bands, and for the theta/alpha and theta/beta ratios.RESULTS: EEG differences were found between the ADHD children and controls which were compatible with previous literature on the Inattentive type. Differences were also found between the good and poor responders to methylphenidate.CONCLUSIONS: Good responders had EEG profiles that suggested that they were more cortically hypoaroused than poor responders.     

Changes in EEG order in neuroleptically treated normal volunteers during a voluntary movement task

Summary 15 normal volunteers were treated over three weeks with haloperidol (HAL) and in the third week additionally with biperidene (BIP). The order of the EEG spectra at different topographical locations and in different frequency bands during a movement task was analyzed using uncertainty analysis (UA), a multivariate analysis technique based on informationtheoretical methods. Different patterns of drug-induced changes were found. HAL decreases the theta and alpha band order at the fronto-central lateral areas but increases it at the fronto-central midline in the theta band and at the parietal areas in the alpha band. With the exception of the fronto-central midline locations, BIP more or less counterbalances the effect of HAL. Volunteers felt unwell and had motor disturbances during HAL and felt well again during HAL + BIP. Reaction time values were increased during HAL and normalized during HAL + BIP.     

EEG differences between good and poor responders to methylphenidate and dexamphetamine in children with attention-deficit/hyperactivity disorder.

OBJECTIVES: This series of studies investigated (1) electroencephalographic (EEG) differences between good and poor responders to methylphenidate, (2) EEG differences between good and poor responders to dexamphetamine, and (3) differences in the EEGs of good responders to methylphenidate versus dexamphetamine, within samples of children with the combined type of attention-deficit/hyperactivity disorder (ADHD). METHODS: Twenty good and 20 poor responders to each of methylphenidate and dexamphetamine, based on the results of a continuous performance task, and 20 age-matched control subjects, participated in this study. EEG was recorded from 21 sites during an eyes-closed resting condition and Fourier transformed to provide estimates for total power, and absolute and relative power in the delta, theta, alpha and beta bands, and for the theta/alpha and theta/beta ratios. RESULTS: EEG differences were found between the good and poor responders to each medication. Good responders to methylphenidate had EEG profiles that suggested that they were more cortically hypoaroused than poor responders. In contrast, the good responders to dexamphetamine appeared to be more maturationally lagged than the poor responders. The two good-responder groups had EEG profiles which suggested that there were two different underlying central nervous system (CNS) dysfunctions. CONCLUSIONS: Children with the combined type of ADHD do not constitute a homogeneous clinical group, as different types of CNS dysfunction are present within this population. These results also indicate the need for medication testing to be undertaken before a child is prescribed stimulant medication for ADHD.     

Changes in QEEG prefrontal cordance as a predictor of response to antidepressants in patients with treatment resistant depressive disorder: a pilot study

INTRODUCTION: Previous studies of patients with unipolar depression have shown that early decreases of EEG cordance (a new quantitative EEG method) can predict clinical response. We examined whether early QEEG decrease represents a phenomenon associated with response to treatment with different antidepressants in patients with treatment resistant depression. METHOD: The subjects were 17 inpatients with treatment resistant depression. EEG data and response to treatment were monitored at baseline and after 1 and 4 weeks on an antidepressant treatment. QEEG cordance was computed at three frontal electrodes in theta frequency band. The prefrontal cordance combines complementary information from absolute and relative power of EEG spectra. Recent studies have shown that cordance correlates with cortical perfusion. Depressive symptoms were assessed using Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: All 17 patients completed the 4-week study. All five responders showed decreases in prefrontal cordance after the first week of treatment. Only 2 of the 12 nonresponders showed early prefrontal cordance decrease. The decrease of prefrontal QEEG cordance after week 1 in responders as well as the increase in nonresponders were both statistically significant (p-value 0.03 and 0.01, respectively) and the changes of prefrontal cordance values were different between both groups (p-value 0.001). CONCLUSION: Our results suggest that decrease in prefrontal cordance may indicate early changes of prefrontal activity in responders to antidepressants. QEEG cordance may become a useful tool in the prediction of response to antidepressants.     

Individual analysis of EEG band power and clinical drug response in schizophrenia

The main purpose of this study was to investigate the relationship between short-term clinical outcome and changes in electroencephalogram (EEG) power after drug treatment in patients with schizophrenia, and also to compare two different methods for quantitative EEG analysis. EEG power analysis was performed by both conventional fixed frequency band and adjusted frequency band based on individual alpha frequency (IAF) in 16 drug-naive patients before and after drug administration. In the theta bands determined by both conventional fixed band and IAF methods, the EEG power after treatment was larger than that before treatment. In addition, there was a correlation between EEG power and clinical drug response evaluated by changes in BPRS score. With regard to this correlation, IAF methods showed no apparent advantage over methods using conventional fixed frequency bands. Conventional quantitative EEG analysis can still serve as a useful tool for the assessment of short-term outcome of drug treatment.     

EEG changes in patients during the introduction of carbamazepine.

This study evaluates the EEG changes during the standardized introduction of carbamazepine in 16 previously untreated neurological patients and their relationship to serum levels of carbamazepine and carbamazepine-10,11-epoxide. Therapy was started with a dosage of 400 mg carbamazepine b.i.d. and remained unchanged during the whole study period of 35 days. Frequency analysis of serial EEG records was performed by Fast Fourier Transformation. In comparison to the pretreatment period (1) the mean values of the total power and relative powers of the theta and delta bands increased and (2) the mean values of the relative power of the alpha band and the center frequency decreased. These changes were already established 3 days after the beginning of the treatment and remained constant during the observation period. There were marked interindividual differences. (3) There was no statistically significant correlation between serum levels of carbamazepine or carbamazepine-10,11-epoxide and the EEG parameters. Our results demonstrate that the degree of EEG change primarily reflects individual susceptibility to carbamazepine and its metabolite during the early stage of carbamazepine exposure and is not dose related.     

EEG changes in patients during the introduction of carbamazepine

This study evaluates the EEG changes during the standardized introduction of carbamazepine in 16 previously untreated neurological patients and their relationship to serum levels of carbamazepine and carbamazepine-10,11-epoxide. Therapy was started with a dosage of 400 mg carbamazepine b.i.d. and remained unchanged during the whole study period of 35 days. Frequency analysis of serial EEG records was performed by Fast Fourier Transformation. In comparison to the pretreatment period (1) the mean values of the total power and relative powers of the theta and delta bands increased and (2) the mean values of the relative power of the alpha band and the center frequency decreased. These changes were already established 3 days after the beginning of the treatment and remained constant during the observation period. There were marked interindividual differences. (3) There was no statistically significant correlation between serum levels of carbamazepine or carbamazepine-10,11-epoxide and the EEG parameters. Our results demonstrate that the degree of EEG change primarily reflects individual susceptibility to carbamazepine and its metabolite during the early stage of carbamazepine exposure and is not dose related.     

Changes in plasma GABA concentration during vigabatrin treatment of epilepsy: a prospective study

The aim of the present prospective study was to evaluate changes in plasma GABA concentration in relation to clinical response during vigabatrin treatment of epilepsy. We studied 29 patients with uncontrolled partial-onset seizures during open add-on vigabatrin treatment and measured plasma GABA and vigabatrin concentrations by a sensitive HPLC method. Following short-term treatment 17 out of 28 patients had a seizure reduction of > 50% (responders). After long-term treatment 16 out of 22 patients were responders. There was no difference between responders and nonresponders regarding pretreatment seizure frequency, treatment duration, vigabatrin dose, or plasma vigabatrin concentration. Responders had a significant (p < 0.001) increase in mean plasma GABA both after short-term (from 0.380 to 0.530 nmol/ml; mean increase: 48%) and after long-term (from 0.392 to 0.618 nmol/ml; mean increase: 71%) vigabatrin treatment, whilst nonresponders had no significant changes in GABA levels. However, since plasma GABA increased in a subgroup of nonresponders, mean plasma GABA levels did not differ between responders and nonresponders. Although plasma GABA increased significantly in the responder but not in the nonresponder group during vigabatrin treatment of patients with epilepsy, it does not seem to be a reliable marker of individual clinical response to vigabatrin treatment.     

Valproate decreases EEG synchronization in a use-dependent manner in idiopathic generalized epilepsy.

INTRODUCTION: In order to explore the mechanism of action of valproate (VPA) in idiopathic generalized epilepsy (IGE), the effect of VPA on cortical EEG activity was investigated. Hypothesis: VPA decreases EEG synchronization in the delta and theta frequency bands in a use-dependent manner in IGE patients. METHODS: First setting: EEG records of 17 untreated IGE patients (NAE group) were analyzed and compared to those of 15 healthy controls (NC group). Second setting: EEG recorded in the untreated condition (NAE) was compared to the EEG recorded in the treated condition (VPA) of the patient group. Technique and analysis: 2 min of eyes-closed, waking EEG background activity (without epileptiform potentials and artifacts) were analyzed. Absolute power (AP) and mean frequency (MF) were computed for 19 electrodes and four frequency bands (delta=1.5-3.5 Hz, theta=3.5-7.5 Hz, alpha=7.5-12.5 Hz, beta=12.5-25.0 Hz). Log-transformed data entered further analysis. Group differences were computed by means of parametric statistics including correction for multiple comparisons. The VPA-related changes (APvpa-APnae) were correlated with the degree of the baseline abnormality (APnae) and the daily dose/serum levels of VPA. MAIN RESULTS: Statistically significant (p<0.05, corrected) changes in the first setting: diffuse delta, theta, alpha AP increase, mainly right hemispheric beta AP increase was found in the NAE group, as compared to the NC group. Second setting: VPA decreased delta and theta AP. Strong correlation was demonstrated between the degree of the initial AP abnormality and the VPA-related AP decrease. AP decrease did not correlate with the daily dose and the serum level of the drug. CONCLUSION: The hypothesis that VPA decreased EEG synchronization in the delta and theta frequency bands in a use-dependent manner was supported. The findings contribute to the understanding of the action of VPA at the network level.     

The quantitative analysis of electroencephalography in primary hypothyroidism

The EEG topography was recorded in the patients with primary hypothyroidism, and the relationship between equivalent potential and blood thyroid hormonal levels were investigated. To determine the relationship between the % equivalent potential fraction (%EPF) and the levels of blood free T3, free T4, and TSH in each patient, regression lines were drawn in respective EEG spectral bands. The %EPF of each patient showed a tendency to have a negative correlation with the values of blood free T3 and free T4 in slow frequency spectral bands such as delta, theta, and alpha 1 waves, whereas a positive correlation in fast frequency bands such as alpha 2, beta 1, and beta 2 waves. In particular %EPF had a significant relationship with blood free T3 levels in alpha 1 and beta 2 spectral bands. These results suggest that the thyroid hormones may have influence on the mechanisms of EEG rhythm formation in primary pypothyroidism.     

EEG coherence in attention-deficit/hyperactivity disorder: a comparative study of two DSM-IV types.

OBJECTIVES: This study investigated differences in intrahemispheric and interhemispheric electroencephalographic (EEG) coherences between attention-deficit/hyperactivity disorder (ADHD) and control children, and between children with the Combined (ADHDcom) and Inattentive (ADHDin) types of ADHD. METHODS: Three age- and sex-matched groups of 40 children, aged 8-12 years, diagnosed with ADHDcom, ADHDin, and normal control children, participated in this study. EEG was recorded from 21 sites during an eyes-closed resting condition and Fourier transformed. Wave-shape coherence was calculated for 8 intrahemispheric electrode pairs (4 in each hemisphere), and 8 interhemispheric electrode pairs, within each of the delta, theta, alpha and beta bands. RESULTS: At shorter inter-electrode distances, ADHD children had elevated intrahemispheric coherences in the theta band and reduced lateral differences in the theta and alpha bands. At longer inter-electrode distances, ADHD children had lower intrahemispheric alpha coherences than controls. Frontally, ADHD children had interhemispheric coherences elevated in the delta and theta bands, and reduced in the alpha band. An alpha coherence reduction in temporal regions, and a theta coherence enhancement in central/parietal/occipital regions, were also apparent. ADHDcom had greater intrahemispheric theta and beta coherences than ADHDin. Frontally, ADHDcom had higher levels of interhemispheric coherences than ADHDin for the delta and theta bands. In central/parietal/occipital regions, beta coherences were elevated in ADHDcom. CONCLUSIONS: EEG coherences suggest reduced cortical differentiation and specialisation in ADHD, particularly in cortico-cortical circuits involving theta activity. Generally, ADHDcom children displayed greater anomalies than ADHDin children.     

Increased EEG power density in alpha and theta bands in adult ADHD patients

This study examined EEG abnormalities in adults with attention deficit hyperactivity disorder (ADHD). We investigated EEG frequencies in 34 adults with ADHD and 34 control subjects. Two EEG readings were taken over 5 min intervals during an eyes-closed resting period with 21 electrodes placed in accordance with the international 10–20 system. Fourier transformation was performed to obtain absolute power density in delta, theta, alpha and beta frequency bands. The ADHD patients showed a significant increase of absolute power density in alpha and theta bands. No differences were found for beta activity. Our findings indicate that abnormalities in the EEG power spectrum of adults with ADHD are different than those described in children. Reliable discriminators between patients and healthy subjects in adulthood could be alpha and theta power density. Based on our results, we suggest further research involving longitudinal studies in ADHD patients to investigate the changes of EEG abnormalities with age.     

Effect of donepezil on EEG spectral analysis in Alzheimer's disease

EEG spectral analysis allows a quantitative analysis of changes in the frequency bands during disease progression in Alzheimer's disease (AD) and could be used to monitor treatment and disease progression. Eighteen patients with probable AD were evaluated by Folstein Mini Mental State Examination (MMSE) and EEG spectral analysis before donepezil treatment, 2 months after 5 mg/day and 4 months after the dose was raised to 10 mg/day. EEG evaluations were done in 4 derivations (T3-T5, T4-T6, C3-P3, C4-P4). Six months after treatment there was a significant reduction in the temporal delta amplitudes and an increase in the amplitudes of all the other frequency ranges including theta amplitudes both in the temporal and centroparietal derivations. MMSE scores increased during treatment but the change was not significant. These findings show that donepezil exerts a positive effect on EEG in AD by decreasing delta activity and increasing alpha and beta activity. The increase in theta activity after treatment may reflect a therapeutic shift of delta activity to theta activity.     

Enhanced signal transduction by adenylate cyclase in platelet membranes of patients showing antidepressant responses to alprazolam: preliminary data

The triazolobenzodiazepine, alprazolam, was administered to 11 depressed patients over a period of six weeks, and six patients showed a favorable antidepressant response. There were no significant differences between responders and nonresponders in age, pretreatment Hamilton Depression Rating Scores, 4 p.m. postdexamethasone plasma cortisol levels, or platelet monoamine oxidase activities. Blood levels of alprazolam were not meaningfully different in responders and nonresponders when measured on treatment day 8. However, on treatment day 8, significantly enhanced prostaglandin D2-stimulated platelet adenylate cyclase activity, greater suppression of prostaglandin D2-stimulated platelet adenylate cyclase activity by epinephrine, and enhanced sodium fluoride-stimulated platelet adenylate cyclase activity were seen in the six patients who went on to respond to alprazolam, but not in the five nonresponders. In contrast, there were no significant changes in prostaglandin D2, (-)-isoproterenol, or fluoride ion-stimulated leukocyte adenylate cyclase activity in responders or nonresponders. No meaningful changes were observed in the mean densities of either the high-affinity platelet alpha 2-adrenergic receptor (for 3H-p-aminoclonidine) or the leukocyte beta-adrenergic receptor (for 3H-dihydroalprenolol) in responders or nonresponders. The present findings, taken in conjunction with findings from other recent studies, suggest that enhanced coupling between certain neurotransmitter or hormone receptors and adenylate cyclase through the guanine nucleotide regulatory proteins may help explain the antidepressant effects of alprazolam and possibly other forms of antidepressant treatment.     

Lamotrigine decreases EEG synchronization in a use-dependent manner in patients with idiopathic generalized epilepsy.

OBJECTIVE: To investigate the quantitative EEG effects of lamotrigine (LTG) monotherapy. Hypothesis: LTG was predicted to decrease thalamo-cortical neuronal synchronization in idiopathic generalized epilepsy (IGE). METHODS: Waking EEG background activity of 19 IGE patients was investigated before treatment and in the course of LTG monotherapy. Raw absolute power (RAP), raw percent power (RRP), and raw mean frequency (RMF) were computed for 19 electrodes and four frequency bands (delta=1.5-3.5Hz, theta=3.5-7.5Hz, alpha=7.5-12.5Hz, and beta=12.5-25.0Hz). Inter- and intrahemispheric coherence was computed for eight electrode pairs and the four frequency bands. In addition, scalp-averages were calculated for each variable. Group differences were computed by means of nonparametric statistics including correction for multiple comparisons. RESULTS: Main results were decreased delta and theta RAP (p<0.05 for scalp-averages). LTG compressed the delta, theta, and alpha RAP datasets, reducing the upper limit of the scatter in particular. Spearman r-values indicated marked correlation between the starting values (RAPuntreated) and the LTG-related decrease (RAPtreated-RAPuntreated) in three bands: delta (r=-0.72; p=0.0005), theta (r=-0.59; p=0.007), and alpha (r=-0.61; p=0.006). Thus, the greater the baseline neuronal synchronization, the marked the dampening effect of LTG on it. The remaining findings were decreased theta RRP, theta RMF, and increased alpha RMF (p<0.05 for scalp-averages). The electrode-related changes were small but topographically consistent across the 19 electrode sites. LTG did not affect coherence. CONCLUSIONS: 1. LTG partially normalized the spectral composition of EEG background activity. LTG decreased pathological thalamo-cortical synchronization in use-dependent manner. 2. LTG did not cause quantitative EEG alterations suggesting worsening of the physiological brain functions. Instead, its profile suggested a mild psychostimulant effect. SIGNIFICANCE: The results contribute to the understanding of the effect of LTG at the network level.     

EEG differences between eyes-closed and eyes-open resting conditions

OBJECTIVE: Recent work has attempted to clarify the energetics of physiological responding and behaviour by refining and separating the operational definitions of "arousal" and "activation", which have different effects on physiological responding and behaviour. At the EEG level, we relate the former to widespread activity, and the latter to task-specific topographically-focussed activity reflecting regional processing. This study aimed to investigate this further in terms of differences in EEG activity between eyes-closed and eyes-open resting conditions. METHODS: EEG activity was recorded from 28 university students during both eyes-closed and eyes-open resting conditions, Fourier transformed to provide estimates for absolute power in the delta, theta, alpha and beta bands, and analysed in 9 regions across the scalp. Skin conductance level was also measured as an indicator of arousal level. RESULTS: Across the eyes-closed conditions, skin conductance levels were negatively correlated with mean alpha levels. Skin conductance levels increased significantly from eyes-closed to eyes-open conditions. Reductions were found in across-scalp mean absolute delta, theta, alpha and beta from the eyes-closed to eyes-open condition. Topographic changes were also evident in all bands except for alpha, with reduced lateral frontal delta and posterior theta, and decreased posterior/increased frontal beta in the eyes-open condition. In particular, the topographic beta effects indicate that the across-scalp reduction arose from focal reductions rather than global changes. CONCLUSIONS: The obtained results confirm the use of mean alpha level as a measure of resting-state arousal under eyes-closed and eyes-open conditions. The focal nature of EEG effects in the other bands suggests that these reflect cortical processing of visual input, producing differences in activation between eyes-closed and eyes-open resting conditions, rather than just the simple increase in arousal level shown in alpha. SIGNIFICANCE: This study demonstrates that the eyes-closed and eyes-open conditions provide EEG measures differing in topography as well as power levels. These differences should be recognised when evaluating EEG research, and considered when choosing eyes-open or eyes-closed baseline conditions for different paradigms.     

Computerized EEG profiles of haloperidol, chlorpromazine, clozapine and placebo in treatment resistant schizophrenia

In this paper we have described early applications of computerized EEG techniques in psychopharmacology. Perhaps our most remarkable finding was there were practically no differences between very chronic drug free schizophrenic patients and normals, which contradicts much of the EEG imaging literature. To us, the most likely explanation is that most of the anterior slowing observed in other studies was due to contamination from orbital artifacts, which we took exceptional pains to remove. Lingering effects of neuroleptic medications may also have contributed. Alternatively, EEG deviations in schizophrenia may recede when the illness reaches a very chronic stage, although this hypothesis is less tenable. There were significant differences between placebo and the three neuroleptics in terms of increased amplitudes in the delta and theta frequency bands in the anterior head regions, which is compatible with data from other studies. These changes were most pronounced with clozapine and least prominent with haloperidol, with chlorpromazine occupying an intermediate position. This order happens to parallel their relative antiserotonergic, antihistaminic and anticholinergic properties. The latter may have been partially obscured by the addition of benztropine. In a subgroup of patients who were recorded under each of the treatment conditions, there were more fast frequencies with clozapine than with the other neuroleptics agreeing with Roubicek and Major. This could be a function of clozapine's increased adrenergic activity as reported by Ackenheil. An unexpected finding was that patients who responded to clozapine had higher amplitudes in the alpha spectrum, most pronounced in the left anterior quadrant, than did the nonresponders. These differences between responders and nonresponders obtained whether patients were on placebo, haloperidol or clozapine. Curiously, Buchsbaum et al. found that anxious patients who responded to benzodiazepines also had higher alpha amplitudes in the same brain regions, which differentiated them from nonresponders. These findings clearly warrant future scientific investigation. In this regard, the generalizability of our data is limited by the extremely chronic, treatment-resistant population studied. However, promising directions for further research in EEG and psychopharmacology have been identified.