Selective depression of serum growth hormone during maternal deprivation in rat pups.

Maternal deprivation was associated with a decline in immunoreactive growth hormone in the serum of rat pups. Pups that were returned to the mother showed a rapid reversal in this deprivation-induced decrease. The change in growth hormone concentration was not accompanied by changes in the concentrations of prolactin, thyrotropin, or corticosterone in the serum, but were correlated with alteration in the activity of ornithine decarboxylase in the brain. Treatment of neonatal rat pups with cyprohepatadine, a serotonin antagonist that suppresses growth hormone secretion, resulted in a significant decline in both serum growth hormone concentration and brain ornithine decarboxylase activity. These findings suggest that maternal deprivation elicits a specific suppression of growth hormone release which mediates the decrease in ornithine decarboxylase activity. The study is consistent with clinical findings of impaired growth hormone "responsitivity" in human maternal deprivation syndrome.

Maternal behavior as a regulator of polyamine biosynthesis in brain and heart of the developing rat pup.

Rat pups removed from the mother and placed in a warm incubator for 1 hour or more show a 50 percent reduction in ornithine decarboxylase activity in the brain and heart. The decline is not caused by lack of nutrition. Instead, these studies suggest that active maternal behavior is necessary to maintain normal polyamine metabolism in brain and heart of the pup during development.

Visual search in Alzheimer's disease: a deficiency in processing conjunctions of features.

Human vision often needs to encode multiple characteristics of many elements of the visual field, for example their lightness and orientation. The paradigm of visual search allows a quantitative assessment of the function of the underlying mechanisms. It measures the ability to detect a target element among a set of distractor elements. We asked whether Alzheimer's disease (AD) patients are particularly affected in one type of search, where the target is defined by a conjunction of features (orientation and lightness) and where performance depends on some shifting of attention. Two non-conjunction control conditions were employed. The first was a pre-attentive, single-feature, "pop-out" task, detecting a vertical target among horizontal distractors. The second was a single-feature, partly attentive task in which the target element was slightly larger than the distractors-a "size" task. This was chosen to have a similar level of attentional load as the conjunction task (for the control group), but lacked the conjunction of two features. In an experiment, 15 AD patients were compared to age-matched controls. The results suggested that AD patients have a particular impairment in the conjunction task but not in the single-feature size or pre-attentive tasks. This may imply that AD particularly affects those mechanisms which compare across more than one feature type, and spares the other systems and is not therefore simply an 'attention-related' impairment. Additionally, these findings show a double dissociation with previous data on visual search in Parkinson's disease (PD), suggesting a different effect of these diseases on the visual pathway.

Event-related potentials--neurophysiological tools for predicting emergence and early outcome from traumatic coma.

OBJECTIVE: To determine the prognostic value of multimodal evoked potentials (EPs) and event-related (ERPs) potentials in coma (Glasgow Coma Score <8), after severe traumatic brain injury (TBI). DESIGN: Prospective, longitudinal study of neurophysiological responses recorded during traumatic coma. SETTING: Intensive Care Unit, Frenchay Hospital, Bristol, UK. PARTICIPANTS: Fifty-four comatose TBI patients (age range 1-80 years, mean 36.4). METHODS: Neurophysiological responses were recorded from 11 scalp electrodes with earlobe reference. Conduction times were measured for brainstem auditory, flash visual and somatosensory, short-latency EPs. Peak latencies and amplitudes were determined for long-latency components of visual and auditory ERPs, generated by passive "oddball" paradigms. These neurophysiological and various clinical parameters were correlated with patient outcome using Pearson's coefficient. MAIN OUTCOME MEASURE: Three month Glasgow Outcome Scale (GOS). RESULTS AND CONCLUSION: Highly significant (P <0.001) correlations exist between long-latency ERP components and 3-month outcome. Short-latency EPs, brainstem (wave I-V) and somatosensory conduction times also correlate significantly with the GOS (P <0.01). Of the clinical measurements, pupillary response patterns, APACHE II and Glasgow Coma Scores (GCS) correlate significantly with outcome, as do the retrospective measures of duration of coma and post-traumatic amnesia (PTA) in survivors. Unfortunately, due to variance of long-latency responses, even in controls, absolute values cannot be relied upon as prognosticators. The presence of "mismatch negativity" predicted the return of consciousness (89.7% sensitivity and 100% specificity) and preceded changes in GCS. Its latency was the single best indicator of 90-day outcome from coma (r = -0.641).

Age-related changes in the preattentional detection of visual change.

The ability to detect changes in the environment which occur outside the focus of current awareness is essential if the individual is to be able to divert attention to biologically salient stimuli. The preattentional mechanism underlying the automatic detection of stimulus change in the auditory modality has been extensively studied by recording an event-related potential known as the mismatch negativity. Recently a homologous response from the visual cortex has also been described. Ageing has been shown to affect the efficiency of preattentional processing in the auditory modality, a factor which may contribute to cognitive changes in the elderly. It is unclear whether a similar effect occurs in the visual system. To investigate this issue the visual mismatch negativity was recorded from 12 older adults and 24 younger adults. Whereas the younger adults displayed a robust visual MMN, that evoked in the older adults was significantly reduced in amplitude. The results are indicative of age-related deficits in automatic visual processing.

Does amnesia after transection of the fornix in monkeys reflect abnormal sensitivity to proactive interference?

Monkeys in whom the fornix had been transected and controls were tested in two versions of delayed non-matching to sample (DNMS). On DNMS-LSS both of the stimuli for each trial were selected from a large set of junk objects that were already familiar to the subjects. On DNMS-CSN the new stimulus at the retention test of each trial was one which the animals had never encountered before. Memory for the sample was assessed with retention intervals of 10, 70 and 130 s. In DNMS-LSS the lesioned animals were impaired, being more susceptible than controls to increases in the retention interval. However, no impairment in DNMS-CSN was observed. The abnormally fast forgetting by lesioned animals in DNMS-LSS seems therefore to reflect abnormal sensitivity to proactive interference. The results are compared with similar findings from amnesic humans and their implications for theoretical accounts of the effects of hippocampal disruption are discussed.

Amnesia after transection of the fornix in monkeys: long-term memory impaired, short-term memory intact.

Monkeys in whom the fornix had been transected and controls were trained on two versions of delayed non-matching to sample (DNMS). On DNMS-LSS the stimulus pair for each trial was selected from a large set of junk objects so that the animals saw particular stimuli infrequently. On DNMS-RS the same two stimuli were presented repeatedly. Memory for the sample was assessed with retention intervals of 10, 70 and 130 sec spent either in the dark or with levels of illumination designed to promote interference effects. On DNMS-LSS the lesioned animals were impaired, being more susceptible than controls to increases in the retention interval. However, neither group was particularly sensitive to interference. In contrast, on DNMS-RS the lesioned monkeys were unimpaired, both groups showing a marked decrement in performance with increasing retention interval and a high sensitivity to the effects of interference. These data suggest that monkeys possess a short-term memory which is intact after transection of the fornix and a long-term memory which is not.

The effects of visual cortex lesions on the perception of rotated shapes.

Monkeys with inferior temporal cortex lesions cannot discriminate between different shapes (e.g., + vs. O) but can discriminate between shapes that differ only in orientation (e.g., 6 vs 9). Lesions of the parietal cortex, on the other hand, impair the discrimination of rotated shapes but spare the ability to discriminate between different shapes. A similar dissociation is found between some visual agnosics who can match but not identify rotated views of objects and other patients who can identify and discriminate objects only if the view is conventional; any change in orientation disrupts performance. In this paper we argue that two mechanisms may be available for the perception of rotated shapes. Which mechanism is used depends on the degree of rotation. It is suggested that the different effects of parietal and temporal lesions reflect the relative contributions of the two areas to the task and disrupt different stages of the two strategies used. A framework for the cortical processing of rotated shapes in the non-human primate is presented.

The effects of lesions of area V4 on the visual abilities of macaques: colour categorization.

Monkeys with V4 lesions and unoperated controls were tested behaviourally for their perception of the colour categories red, green, blue and yellow. As expected, the monkeys with V4 lesions took longer to acquire the colour discriminations. However, the pattern of learning was the same in the two groups of animals. Both the lesioned and the control animals made more errors when the stimuli to be discriminated belonged to the same colour category than when they belonged to different categories and thus showed normal colour categorization. The results suggest that monkeys with V4 lesions perceive the colour spectrum according to the same fundamental perceptual categories as normal monkeys and humans, and thus support the view that, in the colour domain, the four basic perceptual categories are constructed by chromatic mechanisms operating earlier than visual area V4.

The effects of V4 lesions on the visual abilities of macaques: shape discrimination.

Monkeys with bilateral ablation of cortical visual area V4 were compared with unoperated controls for their ability to relearn postoperatively a series of preoperatively acquired two-choice visual discrimination problems. The animals with V4 lesions were impaired on relearning to discriminate between different shapes, and discrimination between identical shapes presented at different orientations was also impaired. Some of the deficits were consistent with disrupting the input to inferotemporal cortex, but discrimination of a subset of the stimuli is known to be unaffected by inferotemporal cortex lesions and could not be explained in the same way. To clarify the nature of the deficit, and to test the hypothesis that shapes differing in orientation are analyzed in the occipitoparietal processing pathway, animals with V4 lesions were also compared to normals on their ability to acquire a version of the landmark task. The V4 animals performed as well as the control animals on this task. The results suggest that V4 is important for the shape discrimination abilities that survive inferotemporal cortex lesions. The role of V4 in shape analysis is discussed in the light of recent evidence that V4 neurones are modulated by visual attention.

The effects of V4 lesions on the visual abilities of macaques: hue discrimination and colour constancy.

Monkeys with lesions of cortical visual area V4 were compared with unoperated monkeys in three experiments. In Expt. 1 they were tested for the reacquisition of a pre-operatively learned hue discrimination task. In Expt. 2, as a test of colour constancy, the monkeys were required to perform previously overlearned colour discrimination tasks when the amounts of red, green and blue light in the illuminant were changed. In Expt. 3 the animals were compared on the post-operative acquisition of hue, greyness and saturation discrimination tasks. The results of Expt. 1 showed that monkeys with V4 lesions can regain their pre-operative levels of performance on hue discrimination tasks. Expt. 2 showed that monkeys with V4 lesions have a colour constancy deficit. Expt. 3 reinforced the finding that the animals with V4 lesions could learn to perform fine hue discriminations but that their final, asymptotic performance was not as reliable as that of normal animals. The wavelength discrimination data are discussed within the context of recent electrophysiological findings that V4 is involved in selective attention to visual stimuli and the constancy data are interpreted as evidence that V4 is important for defining colour constancy thresholds but not for constructing the perceptual categories underlying constant colour perception.

The electrophysiological basis of colour processing in macaques with V4 lesions.

Monkeys with lesions of visual area V4 have deficits in colour constancy, but are able to discriminate hues and segment the spectrum in a categorical manner. To investigate the nature of the processing mechanisms subserving the spared functions we recorded occipital visual evoked potentials (VEPs) of normal monkeys and monkeys with bilateral lesions of area V4. The stimuli used to elicit the potentials were chromatic and achromatic gratings of low spatial frequency. The waveforms from the two groups of animals were similar in all respects. VEPs for the onset of a chromatic grating were negative-going, indicative of the activity of sustained units, as opposed to those elicited by offset or reversal of the grating which were positive-going. The amplitude of the chromatic, 12.5 Hz reversal VEP went through a minimum at isoluminance, in accord with low temporal resolution of colour processing. The VEP waveforms were identical in character from three weeks to approximately four years post-operatively. These data indicate that chromatic processing in areas V1 and V2 is normal after V4 lesions and, together with the behavioural evidence, that these areas are sufficient for some basic aspects of colour perception.

Alpha EEG asymmetry and speed of left hemisphere thinking.

Mental activity which engages one half of the brain is usually accompanied by a suppression of alpha rhythm that is greater over the active hemisphere. When the left hemisphere is active, as during mental arithmetic, the magnitude of the asymmetry in the alpha rhythm is proportional to the rate at which subjects perform their calculations.

Hemispheric asymmetry of EEG alpha activation: effects of gender and familial handedness.

Twenty-four male and twenty-four female undergraduates took part in an experiment to investigate the effects of gender and familial handedness on hemispheric activation during numeric and visuospatial thinking. Each gender group was divided into twelve subjects with close left handed relatives and twelve subjects without. All subjects were overtly right handed. EEG alpha activity was recorded from left and right occipital and parietal regions with respect to mastoid references while the subjects performed numeric tasks with eyes open and with eyes closed, a face-recognition and a tactile-discrimination (figural-unification) task. EEG alpha power was quantified during these conditions and during relaxed wakefulness with eyes open and eyes closed. Relative activation, (suppression of alpha activity from rest) of left and right parietal regions during numeric and spatial tasks was found to depend upon gender and familial handedness. Males, not females, tended to switch from left hemisphere activation during face recognition. Irrespective of gender and to some extent of task, a tendency towards greater activation of the right hemisphere was associated with the possession of left handers among close relatives.

Asymmetries of the contingent negative variation (CNV) and its after positive wave (APW) related to differential hemispheric involvement in verbal and non-verbal tasks.

The CNV and the subsequent positive wave (including both the P300 wave and the slow positivity following it) were recorded at left and right frontal and central electrodes during the performance of tasks in which nine right-handed subjects (male and female) had to determine whether S1 and S2 were the same or different. In one task, works had to be matched for meaning while in a second, faces had to be matched for identity. Words elicited CNVs which were more negative over left than right frontal regions. This effect was reversed when the stimuli were faces. Since the CNV is presumed to reflect processes of anticipation rather than stimulus processing, the asymmetry cannot be explained in terms of the lateralisation of neural mechanisms specialised for the analysis of verbal or visuospatial stimuli. Instead the observation is regarded as evidence for mechanisms of lateral activation of a more general nature than would be necessary for the facultative selection of cognitive mode. The amplitude of the CNV relative to baseline was affected by the amplitude of P300 response to S1. This was larger to faces than words in both hemispheres. A small asymmetry in the positive wave following S2 was observed, the amplitude being greater over the right hemisphere for words and over the left for faces. This is interpreted in terms of the subjective probability of the two types of stimulus for a hemisphere ill-equipped to receive them.

Reading program-Remedial, integrated, and innovative.

An innovative integrated remedial reading program has been developed based on recent research findings. My longitudinal studies have revealed that poor reading compounds itself over the years. The majority of children with reading disabilities currently remain in regular classrooms with varying techniques being used depending upon individual school directives and current educational theory.Despite current remedial techniques, the poorer reader tends to remain so throughout the school years. Innovative techniques must be developed in the hope of altering this pattern.This paper presents one alternative strategy which can be used to upgrade reading skills and break the cycle of reading failure. The Reading Assistance Tutorial Pack (R.A.T. Pack) is a carefully sequenced series of activities that enables the learner to experience the motivating and reinforcing properties of success through all stages of phonetic and reading skills development.It is a systematic, multidisciplinary remedial reading program based on sound behavior, psycholinguistic and cognitive theories of learning-incorporating listening, speaking, seeing, writing, thinking, and comprehension skills. The R.A.T. Pack demands a high percentage of on-task behavior and trains phonological processing strategies. Functional language use is promoted through enjoyable activities involving sentence construction, cloze passages, puzzles, games, and other creative manipulations of the surface features of languages. The program has proven successful in schools, homes, and clinics.

Functional outcome in patients after excision of extracanalicular acoustic neuromas using the suboccipital approach.

An audit of surgery for acoustic neuroma was carried out to determine the frequency and nature of postoperative symptoms and their impact upon the patient's quality of life and vocation. Fifty-six patients were interviewed between 6 months and 5 years (mean 26 months) after surgical excision of an acoustic neuroma. The objective surgical results in these patients are good, with normal or near normal functional preservation rates of 80% for the facial nerve (House-Brackmann grade I/II), and 27.3% for a previously functioning acoustic nerve. Despite this there was no significant overall reduction in the reported occurrence of balance problems, tinnitus, headache and other neurological sequelae of the tumour after surgical excision. In 20% of the patients persistent symptoms, including deafness and facial weakness, had prevented the resumption of former social activities. As a result of these symptoms 8.6% of the patients were certified medically unfit for work, but of those employed preoperatively over 70% had returned to their jobs. The success of neuro-otological surgical management of acoustic neuroma is offset by some degree of chronic morbidity. Our patients expressed the need to know whether their symptoms would resolve, but were often too afraid to ask. Patients can be reassured that the majority resume their former social and vocational activities, but should be advised that some symptoms can persist or occur de novo after surgery. Our data suggest that early intervention would reduce the incidence of these troublesome sequelae.

Consultants workload due to alcohol related conditions in acute medical receiving gastroenterology and endocrinology.

A four-week survey was performed into the incidence of alcohol related problems in the acute medical receiving unit, and the prevalence of alcohol related cases in a ward shared between two gastroenterologists and an endocrinologist. Alcohol related conditions were the commonest reason for acute admission (19%). Gastroenterologists, in contrast to their colleagues have a substantial workload related to alcohol, especially chronic liver disease. These patients have longer lengths of stay with higher morbidity and mortality than those without alcohol related conditions. The reason for these differences and the implications for service planning are discussed.

Safety and feasibility of autologous bone marrow cellular therapy in relapsing-progressive multiple sclerosis.

In this phase I study, we assessed the safety and feasibility of intravenous, autologous bone marrow (BM) cell therapy, without immunosuppressive preconditioning, in six patients with clinically definite, relapsing-progressive multiple sclerosis (MS). Assessment of efficacy was a secondary objective and employed clinical disability rating scales, multimodal evoked potential (MMEP) recordings, and magnetic resonance imaging (MRI) scans. Cells were harvested, filtered and infused intravenously in a day-case procedure that was well tolerated by patients and was not associated with any serious adverse events (AEs). Over a period of 12 months after the therapy, clinical disability scores showed either no change (Extended Disability Status Score, EDSS) or improvement (MS impact scale-29, MSIS-29), and MMEPs showed neurophysiological improvement. MRI scans did not show any significant changes over a post-therapy period of 3 months. The lack of serious adverse effects and the suggestion of a beneficial effect in this small sample of patients with progressive disease justify conducting a larger phase II/III study to make a fuller assessment of the efficacy of mobilization of autologous BM in patients with MS.