Karl Syndulko

D2 dopamine receptor gene and obesity

The prevalence of Taql A D2 dopamine receptor (DRD2) alleles was determined in 73 obese women and men. In this sample with a mean body mass index of 35.1, the A1 (minor) allele of the DRD2 gene was present in 45.2% of these nonalcohol, nondrug abusing subjects. The DRD2 A1 allele was not associated with a number of cardiovascular risk factors examined, including blood lipids (cholesterol, high-density lipoprotein [HDL]- and low-density lipoprotein [LDL]-cholesterol, and triglycerides). However, phenotypic factors characterized by the presence of parental history and postpuberty onset of obesity as well as carbohydrate preference were associated with obese subjects carrying the A1 allele. The cumulative number of these three factors was positively and significantly (p < .0002) related to A1 allelic prevalence. The data showing an association of the minor allele of the DRD2 gene with phenotypic characteristics suggest that this gene, located on q22-q23 region of chromosome 11, confers susceptibility to a subtype of this disorder.

Cortical slow negative waves following non-paired stimuli: effects of task factors.

Abstract Negative afterwaves were recorded in response to single (unpaired) tone pips under a variety of task conditions. In all cases the waves reached their maximum peak at frontal sites, where they attained amplitudes up to 15μV or more within the first seconds and persisted as long as 2 sec. Compared to no-task conditions, instructions simply to count stimuli produced a several-fold increase in amplitude. Further enhancement was obtained by requiring a difficult pitch discrimination, or by embedding the counted target stimuli in a train of more frequent non-targets. Separate conditions using simultaneous trains of visual and auditory stimuli (each train having both rare and frequent stimuli) established that the enhancement occurred only for stimuli in the designated target modality. Whereas some of these conditions led also to a prominent P300 component at posterior sites, the P300 component and the frontal negative afterwave could be experimentally dissociated from one another. Little or no P300 was recorded in a simple stimulus counting condition, which yielded a sizeable negative afterwave. Conversely, a prominent P300, but little or no negative afterwave, accompanied the infrequent omission of a tone pip from a regular train. When analyzed by principal components analysis, the negative afterwave was shown to comprise two separate factors. The first accounts for the early negative peak of the wave at frontal sites, and incorporates in some conditions also the positive P300 component. The second factor reflects late negativity distributed widely over the scalp. The negative afterwave was similar in appearance to the early wave that is recorded often in long-interval CNV paradigms, suggesting that an appreciable portion of the CNV may reflect processes associated solely with the warning stimulus.

Cortical slow negative waves following non-paired stimuli: Effects of modality, intensity and rate of stimulation ☆

Using a simple stimulus counting task, negative after-waves following single (unpaired) stimuli were investigated under a variety of stimulus conditions. Responses were obtained to tones at 3 intensities, to light flashes at 3 intensities, and to tones at 3 rates of presentation. The acoustic stimuli led to a negative after-wave that peaked at frontal sites around 500 or 600 msec, and then trailed off to a more central scalp representation. This negative after-wave was increased in amplitude by slowing the rate of stimulus presentation. In comparison, no appreciable or sustained after-wave was elicited by visual stimuli. No significant effects in the negative after-wave were associated with intensity, either for visual or for acoustic stimuli. When analyzed by Principal Components Analysis, the negative after-waves were shown to comprise in all cases two underlying factors, although the factors contributed less to the total wave form for visual stimuli than for acoustic stimuli. Two interpretations for the negative after-wave were contrasted, one considering it to be an integral feature of the auditory evoked potential. A second interpretation, more compatible with the data obtained here, links the negative after-wave with non-specific activation processes.

Psychophysiology of sociopathy: Electrocortical measures

The CNV, visual AEP and resting EEG were analyzed in sociopaths and controls matched for age and sex. Twenty-seven male sociopaths were selected by psychiatric interview and special rating scale, restricted to Shipley-Hartford IQs of 115-145 and separated into young (x = 20.5 yr) and older (x = 35.3 yr) age groups. Subjects participated in forewarned reaction-time tasks in which the imperative stimulus was either an innocuous or noxious tone that the subject escaped by pressing a response key. Sociopaths and controls did not differ in reaction time, vertex and occipital AEP amplitude or latency, and power spectral density of the EEG. Contrary to previous findings, there also were no significant differences between sociopaths and controls in overall CNV amplitude or topography. However, while most controls showed increased CNV amplitude in the noxious tone condition as compared to the innocuous tone condition, older sociopaths showed no change, or decreased amplitudes.

Aversive conditioning in the sociopath

Results of two experiments on differential conditioning of the skin conductance (SCR) in sociopaths and normal control subjects are described. In the first experiment it was found that an equal number of sociopaths and control subjects were aware of the conditioning contingency. However, only the normal subjects displayed reliable differential SCR conditioning. Sociopaths showed a dissociation between verbal learning and conditioning of a physiological change. The second experiment examined the differential conditioning of normal subjects and sociopaths in partial remission. The number of aware subjects in the two groups did not differ. Aware subjects in both groups showed differential SCR conditioning. Differential conditioning in sociopaths did not persist over trials as it did in control subjects. A deficiency in ACTH 4–10 as well as neurological dysfunctions were considered possible factors in the etiology of sociopathy. Further research on the relation of neuropeptides to the etiology and treatment of sociopathy is suggested.

An event-related potential analysis of coding processes in human memory.

Publisher Summary This chapter discusses an event-related potential (ERP) analysis of coding processes in human memory. The endogenous ERPs have been shown to vary in the context of learning and memory tasks. For example, several lines of evidence indicate that the contingent negative variation (CNV) and P300 components reflect the processes of acquisition and retention in short term memory situations. One question to emerge from these results is the extent to which ERP changes can be related to retention over the longer term, i.e., in situations where memory is not tested immediately on every trial. It would be of interest to observe the extent to which ERPs reflect the level of perceptual processing at acquisition, and how such processing manifests itself in memory performance. Phonemic encodings yield intermediate performance. An ancillary finding is that words yielding a “yes” response to a query are better remembered than those yielding a “no” response in phonemic and semantic levels of processing. These effects have been obtained in a number of other experiments and represent a robust behavioral phenomenon with which to test the utility of ERPs as indices of learning and memory.

Trans-blood-brain-barrier albumin leakage and comparisons of intrathecal IgG synthesis calculations in multiple sclerosis patients

We compared four equations for estimating intrathecal IgG synthesis (Tibbling and Link IgG index (T/L), Schuller and Sagar (S/S), Reiber and Felgenhauer (R/F), and Tourtellotte (T) equations) using data from chronic progressive MS patients. For normal albumin leakage (AL) (< 75 mg/day-intact BBB), T (r = 0.15) and R/F (r = 0.10) showed comparable positive correlations with trans-BBB AL, T/L (r = -0.10) was negative and S/S was uncorrelated (r = 0.05). For abnormal AL (> or = 75 mg/day), the R/F (r = -0.24), S/S (r = -0.37) and the T/L (r = -0.22) equations overcorrected, whereas the T (r = 0.07) equation values did not correlate with AL. The albumin index and trans-BBB albumin leakage rate formulae gave essentially identical estimates of BBB leakage (r = 0.99, P = 0.0001). We conclude that in chronic progressive MS patients the R/F, T/L and S/S formulae overcompensate for large abnormal T-BBB albumin leakage rates. The T formula corrected best for IgG transudate at high AL rate values in MS.

Multiple Sclerosis De Novo Central Nervous System IgG Synthesis: Measurement, Antibody Profile, Significance, Eradication, and Problems

Three independent means may be used to detect and measure de novo central nervous system (CNS) IgG synthesis: the application of an empirical formula, the results of an IgG isotopic test, and the analysis of cerebrospinal fluid (CSF) for IgG oligoclones. The empirical formula and the isotope test provide a quantitative measure of the synthesis rate in mg per day. In contrast, the detection of CSF IgG oligoclones, presently a qualitative test, supports the presence of de novo CNS IgG synthesis, providing the serum does not contain IgG oligoclones and the blood-brain barrier (BBB) to protein is not excessively damaged.

Use of P300 and a dementia rating scale in the evaluation of cognitive dysfunction in MS

The assessment of mental dysfunction in multiple sclerosis and discrimination from the secondary effects of sensory and motor deficits has comparability to similar work done on dementia in Alzheimers disease and Parkinson disease. Two approaches to testing might include adaptation of the Alzheimer Disease Assessment Scale and inclusion of the P300 component of the event‐related auditory evoked potential.

Multiple Sclerosis Clinical Trials: A Comprehensive System for the Measurement and Evaluation of Neurologic Function

Although many systems have been developed to measure the cognitive, sensory, and motor functions of multiple sclerosis (MS) patients, few are as comprehensive as the Neurofunction Laboratory. Under development since 1960, the Neurofunction Laboratory presently consists of six different qualitative and quantitative evaluation systems for measuring and evaluating neurologic function. The Neurofunction Laboratory includes: (1) a quantitative neuropsychological examination; (2) an instrumented clinical quantitative neurologic examination; (3) a quantitative simulated activities of daily living examination; (4) a cerebral evoked response examination; (5) a video-neurologic assessment; and (6) a neurologist’s qualitative examination of neurologic function. In addition, a battery of clinical laboratory tests is included to evaluate organ systems and adversities. The instrumented tests have been evaluated for reliability and validity when administered by trained technicians, and for effects of motivation, learning, handedness, age, and sex. The Neurofunction Laboratory has been used in MS clinical trials to evaluate putative therapies. Methods have been developed to reduce data from clinical trials into composite neurologic functions vs time to facilitate the neurologist’s task of determining how near normal function a treatment brings a MS patient. In these ways, the Neurofunction Laboratory offers the neurologist a quantification of the nervous system that is not available with ordinal scale data and hence enables the clinician to assess more objectively the value of a therapeutic treatment.