Sharon C. Kowalik

Persistent QEEG Abnormality in Crack Cocaine Users at 6 Months of Drug Abstinence

The major objective of this study was to examine the persistence of abnormal quantitative EEG (qEEG) measures over a six month time interval in subjects in strictly supervised drug free residential treatment for crack cocaine dependence. Seventeen subjects were assessed with qEEG at five to 10 days, one month and six months following their last use of cocaine. No significant changes were noted over time in abnormal qEEG measures, which included deficits of absolute and relative power in the delta band and increased relative alpha power. The persistence of qEEG abnormality in crack cocaine withdrawal suggests a persistent neurobiologic alteration resulting from chronic cocaine exposure. The specificity of the qEEG findings is discussed, and an interpretation is suggested with reference to the hypothesis of neural sensitization in cocaine dependence.

Quantitative electroencephalographic characteristics of crack cocaine dependence

This study replicates preliminary findings reporting a quantitative electroencephalographic (QEEG) profile of crack cocaine dependence in abstinence. All subjects (n = 52) met criteria for DMS-III-R cocaine dependence (in the form of crack), and were residing in a drug-free therapeutic community. Baseline QEEG evaluations were conducted at intake (5-10 days after last use of crack, and at follow-up (1 month after last reported use). Previous findings of significant excess of relative alpha power and deficit of absolute and relative delta and theta power were replicated in this expanded group. Abnormalities were greater in anterior than posterior regions, and disturbances in interhemispheric relationships were also observed. Further, QEEG showed little change in the interval between the first and second evaluations. This QEEG profile may reflect persistent alterations in neurotransmission as a possible consequence of chronic cocaine exposure.

Outcome Related Electrophysiological Subtypes of Cocaine Dependence

We previously described the existence of two quantitative EEG (QEEG) subtypes of cocaine dependent males, identified at baseline, displaying differential pronenessto relapse. The current study expands the population to include females and enhances the measure set to include both QEEG and somatosensory EP (SEP) features. Fifty-seven cocaine dependent adults (16 F, 41 M) were evaluated 5–14 days after last cocaine use, while in residence at a drug-free therapeutic community. The median length of stay in treatment (continued abstinence) was 25 weeks. Using a small subset of QEEG and SEP baseline features, three subtypes (CLUS) were identified. CLUS 2 (n=25) and CLUS 3 (n=23) replicated the published subtypes, while CLUS 1 (n=9) was previously undescribed. Cluster membership was significantly associated with length of stay in treatment (χ2=13.789, P<0.001), but not with length of exposure to crack cocaine or to any demographic or clinical features. Seventy-eight percent of CLUS 1 and 65% of CLUS 3 left treatment ≤ 25 weeks, whereas 80% of CLUS 2 remained in treatment > 25 weeks. The existence of outcome related subtypes may reflect: [1] differential neurophysiological vulnerability, “traits,” predisposing individuals to cocaine addiction; or [2] differential neurosensitivity, “states,” due to the effects of chronic cocaine exposure, and associated differences in treatment outcome. Using Variable Resolution Electrical Tomographic Analysis (VARETA), the mathematically most probable neuroanatomical source of the scalp recorded EEG data was localized. Computation of VARETA on the baseline Cluster profiles suggest significant differences in the underlying pathophysiology of these subtypes.

Prediction of treatment outcome in cocaine dependent males using quantitative EEG

This study investigates the existence of outcome related neurophysiological subtypes within a population of abstinent cocaine dependent adults. We have previously reported and replicated the existence of a distinctive quantitative EEG (QEEG) profile in such a population, and demonstrated the persistence of this pattern at one and six month follow-up evaluations. This profile is characterized by significant deficits of absolute and relative delta and theta power, and excess of relative alpha power, as compared with age expected normal values. Abnormalities were greater in anterior than posterior regions, and disturbances in interhemispheric relationships were also observed. In the current study, 35 adult males with DSM-III-R cocaine dependence, were evaluated while residents of a drug-free residential therapeutic community, 5-15 days after last use of crack cocaine. Using multivariate cluster analysis, two neurophysiological subtypes were identified from the baseline QEEGs; Cluster 1 characterized by significant deficits of delta and theta activity, significant excess of alpha activity and more normal amounts of beta activity (alpha CLUS) and Cluster 2 characterized by deficits of delta, more normal amounts of theta and anterior excess of alpha and beta activity beta CLUS). No significant relationships were found between QEEG subtype membership and length of exposure to cocaine, time since last use of cocaine or any demographic characteristics. Further, no significant relationships were found between the commonly reported comorbid clinical features of depression and anxiety and subtype membership. However, a significant relationship was found between QEEG subtype membership and length of stay in treatment, with members of the alpha CLUS retained in treatment significantly longer than members of the beta CLUS.

Quantitative EEG Characteristics of Children Exposed in Utero to Cocaine

Quantitative EEGs (QEEGs) were evaluated in a group of 6 school age children with in utero cocaine exposure. Their QEEGs showed significant deviations from age expected normal values. Further, the QEEG profile of brain dysfunction seen in these children was extremely similar to that previously reported in a large population of crack cocaine dependent adults. These abnormalities were characterized by significant excess of relative power in the alpha frequency band, and deficits of absolute and relative power in the delta and theta bands. Characteristic disturbances in interhemispheric relationships were also present. The similarities between the QEEG profiles of those adults with chronic exposure and children with prenatal exposure suggests that the brain dysfunction reflected in the QEEG is not a result of a transient change in neurotransmission, but a more profound alteration which persists in these children at school age. Further study is required to extend these findings to a larger group of children, and to investigate the potential relationship between these neurophysiological abnormalities and the developmental, behavioral and co-morbid features observed in such children.

Dexmethylphenidate extended-release capsules for the treatment of attention deficit hyperactivity disorder.

Dexmethylphenidate is a chirally pure d-isomer of the racemic mixture of methylphenidate. The extended-release form of this compound was developed using proprietary Spheroidal Oral Drug Absorption System technology. The product is approved for the treatment of attention deficit hyperactivity disorder in individuals as young as 6 years old. It represents the first methylphenidate product approved for use in adults. The agent’s delivery system is designed to provide an initial release of medication immediately after dosing, with a second release ~ 4 h later. Blood levels first peak at ~ 1.5 h, and the second peak is noted at an average of 6.5 h post-dose. Laboratory classroom studies have demonstrated clinically and statistically meaningful efficacy throughout a 12-h day. Pharmacokinetics, safety and efficacy data are reviewed.

Electrophysiologic Evidence of Neural Injury or Adaptation in Cocaine Dependence

The electroencephalogram (EEG) is an emergent phenomenon of neural activity, which suggests that the EEG might reflect the apparently abnormal neurobiology observed in cocaine dependence. The EEG is noninvasive, inexpensive, and quantitative analysis of the EEG (QEEG) is based on information processing technology that is constantly growing with respect to analytic power and accessibility. Clinically, QEEG has been shown to be sensitive to psychiatric conditions, such as depression or attention deficit hyperactivity disorder (ADHD) that are often comorbid with cocaine dependence (1–3). Pretreatment QEEG has been shown to be predictive of subsequent psychotropic drug response in patients with a variety of psychiatric disorders evaluated prospectively (4,5). Neural injury or adaptation in cocaine dependence resulting in changes in the underlying sources of the EEG and reflected quantitatively in the QEEG, could be relevant to “staging” the disorder with respect to the identification of reversible vs irreversible components, and could potentially provide an approach to the development or selection of treatment. This chapter focuses on data obtained from a large population of cocaine-dependent subjects in our ongoing National Institute on Drug Abuse (NIDA) funded work on cocaine dependence. The chapter first provides a brief overview of structural and metabolic imaging studies in cocaine dependence, then reviews studies of EEG power spectral findings in chronic cocaine exposure in animals and humans, and our work on persistence of QEEG abnormality and evidence of electrophysiologic heterogeneity and its clinical correlates in cocaine dependence. Lastly, we attempt an interpretation of our QEEG findings will be considered in the context of hypothetical mechanisms of neural injury or adaptation.