Jon F. DeFrance

Topographical Analyses of Attention Disorders of Childhood

Cognitive ERPs and EEG spectral differences were compared in three groups of children: nonreferred controls, those with a dominant hyperactivity/impulsivity factor (ADHD-Im), and those with a dominant inattentive factor (ADHD-Ia). The results from the ERP analyses indicated that the P250, P350, and P500 components differed between the groups. The most marked differences were seen with respect to the amplitude of the P500 components. In addition, the topographic foci of the P500 components for the CON and ADHD-Im groups were symmetrical, but the ADHD-Ia group featured P250 and P350 components that were biased away from the right hemisphere. Nevertheless, the P500 was found to be an effective discriminator between the groups. The combined spectral and ERP results suggest that the attention disordered children have difficulty adjusting their level of physiological arousal, and are defective with respect to controlled (or effortful) processing.

Effects of CCK-8 in the nucleus accumbens

The electrophysiological effects of CCK-8 were studied in the rabbit nucleus accumbens. CCK-8 was found to influence neurotransmitter (modulator) systems so as to enhance their action. For example, CCK-8 enhanced the effects of stimulation of the glutaminergic pathways, the fimbria. In addition, when CCK-8 was co-administered with dopamine and acetylcholine, their suppressive effect on the fimbria evoked response was enhanced. Therefore, CCK-8 appears to be capable of enhancing the influence of multiple neurotransmitter (modulator) systems.

Regional Distribution of Catecholamines in Nucleus Accumbens of the Rabbit

Abstract: The nucleus accumbens is an important telencephalic region, which is the target limbic and mesolimbic pathways. Because of an ongoing physiological study of the effects of dopamine, we wanted to determine regional differences of dopamine and norepinephrine concentrations in the nucleus. As determined by radioenzymatic assays, dopamine levels were not significantly different in the anterior‐posterior dimension, averaging approximately 187 ng dopamine/mg protein. Substantial amounts of norepinephrine were found throughout the nucleus, but the levels were significantly higher in the caudal portions of the nucleus, being approximately 4.5 times higher than in the anterior portions.

Origin of cingulate cortex cholinergic innervation in the rat.

The relative contribution of the n. diagonal band and thalamic nuclei to the cholinergic innervation of the cingulate cortex was examined. Lesions were placed in the n. diagonal band, anterior thalamus, and medial thalamus of rats, and changes in choline acetyltransferase in discrete regions of the cingulate cortex were determined. The n. diagonal band lesion produced a large decrease in choline acetyltransferase activity while the thalamic lesions produced no significant change in activity.

Evidence for cholinergic muscarinic receptors on mediodorsal thalamic projections to the anterior cingulate cortex

Cholinergic muscarinic receptor binding was analyzed in the rat brain anterior cingulate cortex following lesions of the mediodorsal or anterior thalamic nuclei, or the diagonal band of Broca. A significant change in receptor binding was noted only after lesions of the mediodorsal projection, suggesting that cholinergic muscarinic receptors are located on these terminals. These findings suggest that the projection from the diagonal band of Broca which is cholinergic may act as a modulator of the mediodorsal thalamic projection.

Frequency specific effects of dopamine in the nucleus accumbens

Abstract The action of dopamine was evaluated in the nucleus accumbens of acutely prepared rabbits. It was found that the effect of iontophoretically applied dopamine depended upon the frequency of stimulation of an afferent pathway; in this case the ipsilateral fimbria. Dopamine had a marked suppressive effect on field responses evoked by fimbria stimulation at 0.5 Hz, but not those responses evoked at 6.0 Hz. Dopamine was also effective in activating adenylate cyclase. Both the physiological and the biochemical effects of dopamine could be blocked by appropriate antagonists, suggesting that the phenomena observed were receptor mediated. It is suggested that dopamine serves to enhance information arriving from the hippocampal formation within the theta range by the suppression of competing non-theta activity.

Age-related changes in cognitive ERPs of attenuation.

SummaryThis investigation explored developmental changes in passive and effortful components of ERPs associated with a visual attention task in children, adolescents, and adults. The task was a ‘go-go’ version of a continuous performance task, coupled with a passive attending phase in which the subjects merely watched the stimuli of the task. The three age groups featured a constellation of ERP components that shared the same general morphological appearance and distribution, but differences were seen with respect to latencies and amplitudes. Consistent with other studies, there was an inverse relationship with respect to age and peak latencies of the major passive and effortful components. With respect to peak amplitudes, however, the most impressive changes with age were observed in the passive processing components. For example, the P150 and P250 components presented greater amplitudes in children, whereas the N200 component presented its greatest amplitude in adults. While passive in the sense that their appearances were independent of the ‘decision-making’ process, these components were found to be upwardly adjustable by effort. The late positive component was found to be a combination of a passive P350 and an effortful P450.The P350 component was judged to be largely passive in character as it was well developed in subjects of all age groups when passively attending to the visual stimuli. There was no marked amplitude difference between the child and adult P450 components, but the components peaked in amplitude later in the children. Finally, the childrens ERPs featured a distinct frontal negativity (FN) that was present in the Passive phase, but greatly enhanced during the Effortful phase. This study, as have many others, showed that there are reliable developmental changes in the components of visual ERPs. Therefore, the characteristics of the various components of cognitive ERPs may be effective markers of neurodevelopmental status, especially of those neuronal systems vital to attentional processing and effort regulation.

Effect of morphine on the excitability of rabbit hippocampus

Abstract The effects of morphine with respect to the excitability of hippocampal pyramidal cells were studied in acutely prepared rabbits. Microelectrode techniques were used for stimulation, recording, and iontophoresis of morphine and naloxone. Field potential responses were recorded before, during, and after drug delivery in different hippocampal layers. The data indicate that morphine administration results in a naloxone-reversible enhancement in pyramidal cell excitability. “Supersensitivity” was seen with repeated, but short-term, administration of morphine.

Energy metabolism in rat hippocampus during and following seizure activity.

The hippocampus exhibits a post-ictal phenomenon in which it is unresponsive to further stimulation. It has been suggested that this loss of excitability is the basis of post-seizure amnesia. The biochemical events associated with this phenomenon are unclear. In the present study, energy metabolites were measured in the stratum oriens, stratum pyramidale and stratum radiatum in rat hippocampus, and correlated with field potential recordings. Wistar rats were anesthetized and the calvarium removed. Following removal of the cortex by aspiration, the hippocampus was covered with oil, and stimulating and recording electrodes were placed. Stimulation consisted of a train of stimuli at 100 Hz (10–20 m Amps). This stimulation was found to be effective in evoking self-sustaining after-discharges and post-ictal depression. Tissues for metabolite analysis were taken from a series of controls, from animals during active self-sustaining seizures, and from animals which were totally unresponsive to further electrical stimulation. Hippocampal tissue for metabolite analysis was obtained by pouring liquid N2 on the exposed tissue, then removing the frozen tissue. Glucose, ATP, and phosphocreatine were measured in hippocampal layers of CA1 using fluorescence techniques and enzymatic cycling. Results showed that during seizure activity, glucose, ATP, and phosphocreatine were all decreased from 40–80% in the three layers of the hippocampus, whereas from 60 seconds after the onset of hippocampal shutdown, energy metabolites had returned toward normal. Thus, at a time when the hippocampus was unresponsive, energy metabolites were at control levels. These data suggest that the shutdown phenomenon occurs in the presence of adequate energy stores.

The effect of muscimol on hippocampal pyramidal cells

The effects of muscimol on rabbit hippocampal pyramidal cell firing were studied and compared after iontophoretic, topical, and intravenous administration of the drug. All modes of application resulted in a bicuculline-sensitive, strychnine-insensitive, depression of the monosynaptically activated population spike evoked by micro-stimulation of the contralateral hippocampal field. These findings indicate that systemically administered muscimol selectively activates hippocampal GABA receptors suggesting that this compound may be useful for studying limbic system physiology.