Search PubMed⌕ Search

Biomedical subjects

R D Oades

Publications and source records attributed to R D Oades.

At least 37 records · Page 2Linked to original sources
PubMed1996

Event-related potentials during an auditory discrimination with prepulse inhibition in patients with schizophrenia, obsessive-compulsive disorder and healthy subjects.

Prepulse inhibition (PPI) is a measure of the influence of a stimulus (S1) on the response elicited by a second stimulus (S2) occurring shortly afterwards. Most S1/S2 measures of gating have used behavioural startle and the P50 event-related potential (ERP) amplitudes to detect PPI in a simple paired stimulus paradigm. We report on two behavioural (reaction time, RT, and the electromyographically recorded response of the musculus orbicularis oculi, EMG) and 5 ERP measures of PPI where S2 was the target in an auditory two-tone discrimination. Subjects were 21 healthy controls (CON), 11 obsessive-compulsive (OCD) and 9 schizophrenic patients (SCH). The prepulse 100 ms before S2 induced more omission errors and longer RTs compared to 500ms S1-S2 interval in all subjects. PPI was also evident in EMG, P50, N1, P3 but not P2 or N2 amplitudes of CON subjects. SCH patients showed attenuation of PPI on the same measures. OCD patients were characterized only by their slow RT and a marginal attenuation of PPI of the EMG response. A correlational analysis implied separate relationships of ERP indices of PPI to the cognitive and psychomotor consequences of the prepulse on behavioural and discrimination responses. However, SCH patients showed a general rather than a specific impairment of these indices.

Acoustic Stimulation↗
PubMed1995

Mismatch negativity (MMN) is altered by directing attention.

MMN is a negative component resulting from the difference in event-related potential (ERP) waveforms elicited by a standard and a deviant stimulus. It is usually studied in the absence of attentional requirements. We compared this measure of perceptual comparison in a non-task situation (three tones presented) with that obtained in a task requiring focused attention and response to the third tone. MMN (comparison of standard and deviant irrelevant tones) increased with focused attention to the third (target) tone and frontal maxima shifted slightly posteriorly. The succeeding P3 in the difference waveform increased more posteriorly than frontally confirming continued differential processing of irrelevant stimuli under active conditions. This demonstrates that not only attending to stimuli, but the active processing of irrelevant stimuli (vs passive perception) involves small changes in the amount and distribution of neural activity.

Acoustic Stimulation↗
PubMed1995

The topography of event-related potentials in passive and active conditions of a 3-tone auditory oddball test.

Normalized event-related potential (ERP) data were analysed for topographical differences of ERP amplitude or latency in two conditions of a 3-tone oddball paradigm. The aim was to compare perception-related features relating to tone-type (passive non-task condition) with focussed attention-related features (active discrimination of target from non-target) in 5 ERP components from 23 young healthy subjects. The tones used were a common standard (70%, 0.8 KHz), a deviant standard (15%, 2 KHz) and a 1.4 KHz tone (15%, t) also used as the target (T). A site x tone interaction was obtained for P1 amplitude (augmenting with pitch anterior to posterior). The opposite tendency was seen for P2 to the right of midline maxima. No interaction was obtained for N1 amplitude. Condition became relevant for the N2-P3 complex. Frontal N2 amplitude increased after rare tones in the active condition. Posterior P3 peak size distinguished between tone (more widespread response to the common tone) and condition (more right-sided in the passive condition). The common tone elicited more widespread shift to the right than the rare tones. Latency was affected by condition from the P2 onwards and confirmed many of the amplitude interactions. This report extends and qualifies well-known main effects of tone and condition through main site effects to lateral sites. It supports claims of multiple sources of ERP components, except for N1 and P2. The contributions of these sources are influenced by tone-features (from P1) and the presence or absence of focussed attention (from the N2-P3 complex).

Adult↗
PubMed1995

The topography of 4 subtraction ERP-waveforms derived from a 3-tone auditory oddball task in healthy young adults.

Five components were studied in 4 subtraction waveforms derived from ERPs obtained in passive and active conditions of a 3-tone oddball task (common = 70%, C, 0.8 KHz; deviant = 15%, D, 2 KHz; 1.4 KHz = 15%, t, also used as a target (T)). These waveforms reflect different stimulus-mismatch processes and thus their topography could be revealing of different brain regions mediating them. The following mismatches were studied: stimulus-mismatch (deviant--common, D/C, rarity and pitch confounded), pitch-mismatch (T--deviant, T/D, rarity not target features controlled), attention-mismatch (T-t), T/t, controlled for pitch and rarity to show the influence of target features). These are compared with Goodin's procedure [G-wv, (T--common (active))--(t--common (passive))]. There were main site effects in normalized data in all cases (not P2 and N2 latency). There were separate frontal and posterior contributions to P1, with the former emphasized where target comparisons were involved. Frontal N1 peaks, largest in D/C, spread posterior and to the right where target matching was involved. P2 posterior maxima were also less localized where target features were involved in the comparison. N2 topography was similar between waveforms but spread slightly more to each side in the T/t comparison. Onset was earlier in the D/C comparison. Parietal P3 peaks in waves based on target-ERPs showed a left temporal shift (vs D/C), though in T/D P3 was in fact maximal on the right. Thus an attentional effect is evident as early as 60 ms. Target features modify the anteroposterior distribution of positivity and negativity for the early components and in the lateralization of P3-like positivity. A comparison of waveforms by latency of potential shift (running t-test) vs peak identification (MANOVA) is illustrated and discussed. D/C and T/t (rather than T/D or G-wv) waveforms are recommended for distinguishing comparator mechanisms for stimulus- and task-relevant features.

Attention↗
PubMed1994

Monoamine activity reflected in urine of young patients with obsessive compulsive disorder, psychosis with and without reality distortion and healthy subjects: an explorative analysis.

Positive psychotic symptoms are reported to be associated with high, negative symptoms with low dopamine (DA) activity and serotonin (5HT) activity may be altered in obsessive-compulsive disorder (OCD). We analysed 24 h urine samples in these patient groups and in healthy controls for supportive evidence. Young unmedicated OCD subjects excreted more adrenaline (AD) and homovanillic acid (HVA) and showed a higher HVA/MHPG ratio and metabolic rate than healthy controls. Independent of general metabolic rate they showed higher HVA concentrations which suggests that the relative activity of catecholamine systems in OCD (HVA/MHPG) is due more to high DA than to low noradrenergic (NA) activity. Concentrations of 5HT were also high in OCD patients. In psychotic patients low levels of DA, HVA, NA and MHPG probably resulted from neuroleptic medication. Patients diagnosed with paranoid psychosis showed higher DA utilization than controls and those with few paranoid symptoms showed high 5HT utilization. These results support studies suggesting that paranoid psychosis is associated more with increased DA activity (discussed in the context of neuroleptic reactivity), that non-paranoid forms are associated more with increased 5HT activity and that OCD patients are unusually aroused with high levels of Ad, 5HT and HVA.

Adolescent↗
PubMed1994

Serum gonadal steroid hormones in young schizophrenic patients.

Psychosis is reported to show a later age of onset in women than in men and its nature and course in women may also differ. The purpose of this study was to determine if levels of four steroid hormones at the start of early onset psychosis differ from the levels of other groups of young people and if predicted low levels of estrogen (E2) are a feature of female psychosis. Two blood samples from 22 young psychotic patients were analysed by radioimmunoassay for E2, progesterone (PROG), testosterone (TE), and dehydroepiandrosterone sulphate (DHEAS). Female psychotic patients showed E2 levels lower than matched healthy cycling controls but higher than those on a contraceptive pill; they also showed higher TE levels than controls. Male psychotic patients had higher DHEAS levels than healthy or obsessive compulsive disorder (OCD) subjects. We suggest that illness-related changes of steroids can be measured superimposed on medication-induced changes and that lower E2 levels in psychotic women may increase their vulnerability to psychosis. Changes of TE in female and DHEAS in male psychotics may be more a consequence of the illness.

Adolescent↗
PubMed1994

Negative difference (Nd), an ERP marker of stimulus relevance: different lateral asymmetries for paranoid and nonparanoid schizophrenics.

We studied Nd in psychotic patients with varying degrees of paranoid symptoms. Nd is an ERP measurement of the difference in the way a nonattended tone is registered and the way the same tone is registered when used later as a discrimination target. In a three-tone oddball paradigm with passive-tone presentation and active discrimination, we recorded from 19 sites in 22 young healthy subjects and 28 schizophrenics. Nd (200-260 ms) was bilaterally symmetrical in healthy subjects. Paranoid patients showed a left frontal/right temporoparietal amplitude reduction which was reversed in nonparanoid subjects (reduced at right frontal/left posterior sites). These asymmetries were clearer when the groups were separated according to active paranoid symptoms rather than by diagnosis. There would therefore seem to be functional asymmetries mediating stimulus relevance in schizophrenics which differ from controls and differ between patients with and without active paranoid symptoms.

Acoustic Stimulation↗
PubMed1992

Paranoid schizophrenics may not use irrelevant signals. The use of measures of blocking and of urinary dopamine.

Conditioned blocking tests for the use of superfluous (irrelevant) information in task-solving. Paranoid psychotic, obsessive-compulsive and healthy subjects usually showed normal blocking, but non-paranoid subjects tended to learn about the superfluous stimulus. Attenuated blocking was usually associated with increased dopamine utilization measured in 24h urine samples. This may reflect poor stabilization of response to neuroleptic medication.

Adolescent↗
PubMed1990

Event-related potentials and monoamines in autistic children on a clinical trial of fenfluramine.

In a double blind, crossover study of the response of autistic subjects to fenfluramine, event-related potentials (ERPs) were recorded from 7 subjects on an attention-demanding auditory choice reaction time task (ACRT). ACRT, IQ and biochemical measures were taken after 5 months placebo and 5 months fenfluramine treatment. After fenfluramine treatment blood serotonin levels fell, urinary catecholamine levels fell and the HVA/DA ratio rose. IQ and ACRT performance improved. On the ACRT subjects were asked to press a button to a rare target (500 Hz, P = 0.14) and to ignore higher pitched rare (2,000 Hz, P = 0.14) and frequent non-targets (1,000 Hz). After fenfluramine treatment N1 latencies increased. The scalp distribution of ERP maxima changes slightly with treatment. P3 maxima elicited by rare non-targets were recorded more rostrally after fenfluramine treatment. After rare non-targets N1 amplitudes at Fz decreased but P3 amplitudes at Pz increased. Early negativity after the rare non-target (particularly on the right side) was negatively correlated with the HVA/DA ratio. Subtraction of the P3 component elicited in a passive condition where no response was required from the active condition showed that P3 positivity to targets was halved with treatment. (In contrast Nd increased on fenfluramine treatment). Overall, N1 and P3 components showed greatest responsiveness to rare non-targets on fenfluramine. N1 but not P3 changes may represent slight improvement of attention-related function with treatment. Small changes in ERP latency and distribution, associated with the neuroleptic action of fenfluramine may be partly responsible for a mild improvement of IQ and ACRT performance on medication.

Adolescent↗
PubMed1990

A controlled crossover trial of fenfluramine in autism.

We report a 12 month double-blind randomized crossover trial of fenfluramine in 20 children with the syndrome of autism. On active drug most of the children lost weight and blood serotonin levels fell by an average of 60%. There was a fall in urinary dopamine (DA) and noradrenaline (NA) levels and increased excretion of homovanillic acid (HVA). Some of the children showed improvement in tests of cognitive and language function, although the results did not achieve overall statistical significance. Event-related brain potentials (ERPs) were obtained in seven subjects on an auditory choice reaction time task. Side effects of the drug included irritability and lethargy. Fenfluramine may have a limited place in the management of some patients with autistic disorder.

Adolescent↗
PubMed1988

Event-related potentials in autistic and healthy children on an auditory choice reaction time task.

Event-related potentials (ERPs) were recorded from midline (Fz, Cz, Pz) and lateral sites (F3, F4, P3, P4) in autistic children (n = 7) and age-matched controls (n = 9) on an auditory choice reaction time task. Subjects were asked to press a button to an infrequent target (500 Hz, P = 0.14) and to ignore higher pitched infrequent (2000 Hz, P = 0.14) and frequent (1000 Hz) non-targets. Autistic subjects made twice as many errors of omission as controls and showed a higher criterion (beta) for targets. Maximum ERP peak amplitudes showed a more varied scalp distribution in the autistic group. N1 latencies were consistently shorter in the autistic group and in 3 subjects the target P3 latencies were markedly longer than for the controls. Compared to controls, the N1 amplitude of the autistic response was larger to the rare stimuli (particularly to non-targets). The amplitude of the P3 component was smaller in the autistic group (particularly to the target). The stimuli were also presented in a passive condition requiring no response. After subtraction of the waveform obtained in the passive condition from that obtained in the active condition or subtraction of the waveform elicited by the rare non-target from that elicited by the target, N1 target amplitude was larger in control than in autistic children. Autistic subjects showed more early negativity to the rare non-target at left frontal and a larger P3 to the target at right parietal sites. ERPs of autistic children are more responsive to stimulus features (e.g. high/rare non-target tone) and less responsive to their associations or meaningfulness (e.g. target P3). Attention-related ERPs of autistic children show signs of precocious (right dominance for P3) and delayed development (P3 not maximal at parietal sites).

Adolescent↗
PubMed1987

Catecholamines and conditioned blocking: effects of ventral tegmental, septal and frontal 6-hydroxydopamine lesions in rats.

The performance of rats on the conditioned blocking test of learned inattention was measured in a two-way shuttle avoidance task after sham and dopamine (DA)-depleting lesions of the frontal cortex, septum and ventral tegmental area (VTA). Animals were trained on two sessions with tone and/or light as conditioned stimuli. One group was trained with both stimuli on both sessions. A second group was trained on the first session with one stimulus and on the second with both stimuli. The blocking of conditioning to the added stimulus (b) was tested by presenting the stimuli (a and b) separately and measuring the blocking ratio (avoidance to b/a + b) and response latencies. No deficits were recorded on tests of sensory and motor ability. The VTA group alone showed a hyperlocomotor response to apomorphine treatment and did not acquire the avoidance response. The appearance of blocking in the septal group was delayed until the end of the test session. Blocking was mildly attenuated in the frontal group. DA levels were depleted by about 80% and noradrenaline (NA) levels by, respectively, 20 and 50% in frontal and septal areas. This suggests that the level of DA activity or the balance between the activity of DA and NA in frontal and limbic regions can contribute to efficient associative conditioning and/or the normal ability of rats not to attend to a redundant stimulus.

Animals↗
PubMed1987

Ventral tegmental (A10) system: neurobiology. 1. Anatomy and connectivity.

The VTA contains the A10 group of DA containing neurons. These neurons have been grouped into nuclei to be found on the floor of the midbrain tegmentum--Npn, Nif, Npbp and Nln rostralis and caudalis. The VTA is traversed by many blood vessels and nerve fibers. Close to its poorly defined borders are found DA (A8, A9, A11) and 5-HT containing neurons (B8). Efferent projections of the VTA can be divided into 5 subsystems. The mesorhombencephalic projects to other monoaminergic nuclei, the cerebellum and a fine projection descends to other tegmental nuclei as far as the inferior olive. Fibers to the spinal cord have not been demonstrated. The mesodiencephalic path projects to several thalamic and hypothalamic nuclei and possibly the median eminence. Functionally important examples are the anterior hypothalamic-preoptic area, N. medialis dorsalis and reuniens thalami. These two subsystems are largely non-dopaminergic. A minor mesostriatal projection is overshadowed by the large mesolimbic projection to the accumbens, tuberculum olfactorium, septum lateralis and n. interstitialis stria terminalis. There are also mesolimbic connections with several amygdaloid nuclei (especially centralis and basolateralis), the olfactory nuclei and entorhinal cortex. A minor projection to the hippocampus has been detected. The mesocortical pathway projects to sensory (e.g. visual), motor, limbic (e.g. retrosplenial) and polysensory association cortices (e.g. prefrontal). Prefrontal, orbitofrontal (insular) and cingulate cortices receive the most marked innervation from the VTA. A more widespread presence of DA in other cortices of rodents becomes progressively more evident in carnivores and primates. Most but not all projections are unilateral. Some neurons project to more than one area in mesodiencephalic, limbic and cortical systems. The majority of these fibers ascend in the MFB. Most areas receiving a projection from the VTA (DA or non-DA) project back to the VTA. The septohippocampal complex in particular and the limbic system in general provide quantitatively much less feedback than other areas. The role of the VTA as a mediator of dialogue with the frontostriatal and limbic/extrapyramidal system is discussed under the theme of circuit systems. The large convergence of afferents to certain VTA projection areas (prefrontal, entorhinal cortices, lateral septum, central amygdala, habenula and accumbens) is discussed under the theme of convergence systems.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Attention deficit disorder with hyperactivity (ADDH): the contribution of catecholaminergic activity.

An attention deficit disorder with hyperactivity in children (ADDH) is now recognized in most countries although diagnostic practices differ. Evidence is presented to show that the two cardinal symptoms of poor attentional performance and high motor activity may be functionally and causally separate. Both are temporarily relieved in a proportion of subjects that respond to psychostimulants. Beneficial treatment decreases nonadrenergic metabolism and normalizes variable levels of dopaminergic metabolism. Parallels are drawn with other clinical syndromes arising from changed catecholaminergic activity and with behavioral interpretations of the result of damage to the dorsal noradrenergic bundle and dopaminergic A10 nucleus. Prognosis of ADDH subjects after treatment remains poor. There may be a further defect of neurotransmitter metabolism in the ADDH syndrome. Research strategies are suggested based on the neurobiological correlates of the cognitive style of ADDH subjects and septal function in the animal model of the hypertensive rat.

Animals↗
PubMed1986

Locomotor activity in relation to dopamine and noradrenaline in the nucleus accumbens, septal and frontal areas: a 6-hydroxydopamine study.

Locomotor activity was automatically recorded in a circular corridor in rats treated with 6-hydroxydopamine in the ventral tegmental area (VTA), septum and frontal cortex. Control and experimental groups showed similar hyperlocomotor responses in the novel apparatus lasting 3 h. Circadian changes are described. VTA lesions resulted in increased dark activity and a large response to apomorphine compared to other lesion and control groups. Septal lesions did not affect locomotion. The frontal group showed a small increase of locomotion after apomorphine treatment that might reflect increased receptor sensitivity in cortical or subcortical areas. Together with correlations between motor activity and cortical levels of dopamine and noradrenaline these results are interpreted to support a role for dopamine, noradrenaline and the frontal cortex in modulating locomotion which is primarily mediated by VTA-accumbens-dopamine activity.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

The role of noradrenaline in tuning and dopamine in switching between signals in the CNS.

Neuronal catecholaminergic activity modulates central nervous function. Specifically noradrenaline can exert a tuning or biassing function whereby the signal to noise ratio is altered. Dopamine activity may promote switching between inputs and outputs of information to specific brain regions. It has been ten years since evidence for a tuning function was advanced for noradrenaline and in the last 5 years the switching hypothesis for dopamine has been tentatively put forward. Recent studies are reviewed to show that while catecholamine activity contributes to neural interactions in separate brain regions that give rise to the organization of different functions, their working principles may be common between species and independent of the nucleus of origin. Behavioral examples are discussed and an attempt is made to integrate this with evidence from intracellular recording studies. It is suggested that the tuning principle in noradrenergic systems is particularly important for the formation of associations and neural plasticity (interference control) and that the switching principle of dopaminergic systems modulates the timing, time-sharing and initiation of responses (program-control).

Adrenergic Fibers↗