Anthony Towell

Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant.

Rats exposed chronically (5–9 weeks) to a variety of mild unpredictable stressors showed a reduced consumption of and preference for saccharin or sucrose solutions. Preference deficits took at least 2 weeks to develop and were maintained for more than 2 weeks after termination of the stress regime. Sucrose preference was unaffected by 1 week of treatment with the tricyclic antidepressant DMI but returned to normal after 2–4 weeks of DMI treatment. DMI did not alter sucrose preference in unstressed animals. No significant changes were seen in saline preference either during stress or following drug treatment. DMI reduced blood corticosterone and glucose levels, but stress did not significantly alter either measure. The results are discussed in terms of an animal model of endogenous depression.

Functional Outcome Following Stroke in Children

The aim of this study was to describe the functional consequences of childhood stroke in terms of activity limitation and to explore the relationship between extent of brain damage, impairment, and functional sequelae. A further aim was to describe the health of the parents of these children. Seventeen children and adolescents with cerebral infarction in the territory of the middle cerebral artery were enrolled in the study. A new activity limitation measure with a 4-point Likert scale (the Paediatric Stroke Activity Limitation Measure) was designed to examine the degree of difficulty experienced by the children in daily activities. The relationship between activity limitation scores, standardized health-related quality of life assessment (Child Health Questionnaire), extent of brain damage, and results of a comprehensive neurologic examination (Pediatric Stroke Outcome Measure) were investigated. Parent health was assessed using the Short-Form 36 General Health Survey. Activity limitation was evident in the domains of education, self-care, and motor skills. There was very good interobserver agreement using the new activity limitation scale between the occupational therapist and pediatric neurologist (Cohens kappa = 0.88). In comparison with population norms, the subjects scored below average in both physical and psychologic health. There was a clear relationship between radiologically apparent extent of brain damage, degree of impairment, and functional outcome. Parental health also rated generally lower than expected. This exploratory study suggests that both children who have had a stroke and their parents have significant and wide-ranging health needs. (J Child Neurol 2002;17:429-434).

Changes in dopamine autoreceptor sensitivity in an animal model of depression

Rats exposed for 6 weeks to a variety of mild unpredictable stressors showed reduced consumption of a preferred sucrose solution. The deficit was apparent after 1 week of stress and was maintained for at least 2 weeks after termination of the stress regime. Sucrose preference was unaffected by 2 weeks of treatment with the tricyclic antidepressant DMI but returned to normal after 3 weeks of DMI treatment. Subsensitivity to the anorexic effect of a low dose of apomorphine was seen in vehicle-treated stressed animals, and in unstressed animals following withdrawal from DMI. In both cases, the changes resulted from a failure of apomorphine to reduce eating time (rather than from changes in eating rate); this effect is assumed to represent a subsensitive response to stimulation of dopamine cell body autoreceptors. As the same effect is seen in anhedonic stressed animals and in animals withdrawn from DMI, it is concluded that dopamine autoreceptor desensitization probably does not contribute to clinical improvement following chronic antidepressant treatment.

Intracranial identification of an electric frontal-cortex response to auditory stimulus change: a case study.

The aim of the present study was to clarify whether ERPs recorded directly from the human frontal cortex contributed to the auditory N1 and mismatch negativity (MMN) elicited by changes in non-phonetic and phonetic sounds. We examined the role of prefrontal cortex in the processing of stimulus repetition and change in a 6-year-old child undergoing presurgical evaluation for epilepsy. EEG was recorded from three bilateral sub-dural electrode strips located over lateral prefrontal areas during unattended auditory stimulation. EEG epochs were averaged to obtain event-related potentials (ERPs) to repeating (standard) tones and to infrequent (deviant) shorter duration tones and complex sounds (telephone buzz). In another condition, ERPs were recorded to standard and deviant syllables, /ba/ and /da/, respectively. ERPs to vibration stimuli delivered to the fingertips were not observed at any of the sub-dural electrodes, confirming modality specificity of the auditory responses. Focal auditory ERPs consisting of P100 and N150 deflections were recorded to both tones and phonemes over the right lateral prefrontal cortex. These responses were insensitive to the serial position of the repeating sound in the stimulus train. Deviant tones evoked an MMN peaking at around 128 ms. Deviant complex sounds evoked ERPs with a similar onset latency and morphology but with an approximately two-fold increase in peak-to-peak amplitude. We conclude that right lateral prefrontal cortex (Brodmanns area 45) is involved in early stages of processing repeating sounds and sound changes.

Effects of pimozide on sucrose consumption and preference

The effects of pimozide on sucrose intake were examined, in a two-bottle preference test (sucrose versus water), and in single-bottle tests at five different sucrose concentrations. In the two-bottle test, pimozide dose dependently decreased sucrose intake but increased water intake. In the single-bottle test pimozide decreased sucrose intake at low concentrations but had no effect at high concentrations. The results support a role for dopamine in mediating the rewarding effect of sucrose.

Apomorphine anorexia: A behavioural and neuropharmacological analysis

Anorectic effects of apomorphine were studied in a microstructural analysis paradigm. Low doses of apomorphine (<0.1 mg/kg SC) reduced food intake, by reducting both the rate of eating and eating time. The neuroleptics haloperidol and thioridazine blocked the effect of apomorphine on eating time, but not on eating rate. Anorectic effects elicited by apomorphine administration to the ventral tegmental area and, to a lesser extent, the substantia nigra were mediated by a selective reduction of eating time. Effects of apomorphine on eating time appear to result from an action at presynaptic dopamine receptors; the mechanism of the effect of apomorphine on eating rate is unclear.

Evidence for a neurophysiologic auditory deficit in children with benign epilepsy with centro-temporal spikes

Summary.Benign focal epilepsy in childhood with centro-temporal spikes (BECTS) is one of the most common forms of epilepsy. Recent studies have questioned the benign nature of BECTS, as they have revealed neuropsychological deficits in many domains including language. The aim of this study was to investigate whether the epileptic discharges during the night have long-term effects on auditory processing, as reflected on electrophysiological measures, during the day, which could underline the language deficits. In order to address these questions we recorded base line electroencephalograms (EEG), sleep EEG and auditory event related potentials in 12 children with BECTS and in age- and gender-matched controls. In the children with BECTS, 5 had unilateral and 3 had bilateral spikes. In the 5 patients with unilateral spikes present during sleep, an asymmetry of the auditory event related component (P85-120) was observed contralateral to the side of epileptiform activity compared to the normal symmetrical vertex distribution that was noted in all controls and in 3 the children with bilateral spikes. In all patients the peak to peak amplitude of this event related potential component was statistically greater compared to the controls. Analysis of subtraction waveforms (deviant – standard) revealed no evidence of a mismatch negativity component in any of the children with BECTS. We propose that the abnormality of P85-120 and the absence of mismatch negativity during wake recordings in this group may arise in response to the long-term effects of spikes occurring during sleep, resulting in disruption of the evolution and maintenance of echoic memory traces. These results may indicate that patients with BECTS have abnormal processing of auditory information at a sensory level ipsilateral to the hemisphere evoking spikes during sleep.

Event-related potentials in pediatric cochlear implant patients.

Objective: The main objective of this study was to assess the correlation of auditory event related potential (ERP) measures with behavioral assessment data to identify if ERPs including mismatch negativity (MMN) can be used to categorize cochlear implant patients into good and poor performers. Design: We investigated auditory event–related potentials to standard and deviant speech stimuli presented in a pseudorandom sequence in 35 cochlear implant patients between the ages of 7 and 17 yr. We compared the occurrence, latencies, and amplitudes of P1, N2, and MMN with overall behavioral outcome in these children. Behavioral measures included category of auditory performance scores and speech intelligibility rating scores. Results: Auditory ERPs in response to standard stimuli were identifiable in 30 of 35 patients, demonstrating a major positive component (P1) followed by a negativity (N2) with absence of N1 in all patients. The P1 component in prelingually deaf patients showed a statistically significant reduction in its latency with increasing duration of implant use. MMN was recorded in 80–85% of star performers but in only 15–20% of poor performers. Patients with higher SIR scores demonstrated statistically significant longer duration of MMN compared with those with a lower SIR score. Conclusions: These results indicate that MMN can be used to assess the functional status of the auditory cortex in terms of auditory memory and discrimination in young children with cochlear implants and may provide an objective mechanism for differentiating good from poor performers.

Seasonality, social zeitgebers and mood variability in entrainment of mood: Implications for seasonal affective disorder

BACKGROUND Seasonal variations in mood (seasonality) appear to be entrained to light, a physical zeitgeber. We hypothesised that people high in seasonality may be responsive to a range of zeitgebers, because of greater mood variability. We investigated whether the moods of people high in seasonality were more strongly entrained to the calendar week, a social zeitgeber, and whether any such effect was dependent on variability of mood. METHODS 53 participants (14 male, 39 female; overall mean age=30) completed a daily mood report, over 56 consecutive days. Participants also completed the Seasonality Score Index (SSI) of the Seasonal Pattern Assessment Questionnaire. Each participants time series of daily mood was analysed by spectral analysis to quantify the strength of their weekly mood cycle. RESULTS Participants with high SSI scores (> or =11) had significantly stronger weekly mood cycles than those with low SSI scores (<11), and significantly greater variability in mood. Covarying for mood variability reduced the difference between high and low SSI groups in mean strength of weekly mood cycle to non-significance. LIMITATIONS The time series of moods obtained was relatively short, and moods among high seasonal participants may have been affected by seasonal weather variability. CONCLUSIONS People high in seasonality appear to be more responsive to external zeitgebers, and this could be linked to their greater variability in mood. The integration of research on mood variability with research on SAD appears to be warranted.

Behavioural microanalysis of the role of dopamine in amphetamine anorexia.

A microstructural analysis paradigm was used to study amphetamine anorexia. Doses above 0.40 mg/kg significantly reduced food intake by reducing eating time; in contrast, eating rate was increased at these doses. Examination of the frequency distribution of interresponse times (IRTs) revealed a significant shift to shorter IRTs at doses as low as 0.125 mg/kg. Pimozide blocked amphetamine anorexia at 0.5 and 1.0 mg/kg, suggesting that at both doses amphetamine anorexia has a dopaminergic substrate. However, the atypical neuroleptic thioridazine did not antagonize amphetamine. Furthermore, effects of amphetamine were additive with those of apomorphine, administered at a dose known to suppress feeding by inhibiting mesolimbic DA neurons. These results provide evidence against an involvement of the mesolimbic DA system in amphetamine anorexia.