Cortical excitability and the shape of the haemodynamic response.

Individual differences in the temporal dynamics of the haemodynamic response can reflect cortical excitation and can reveal underlying cortical physiology. Here, we show differences in the shape of the haemodynamic response that are dependent on stimulus parameters. Two sets of visual stimuli were used varying in parameters that are known to manipulate the haemodynamic response in the visual cortex. We measured the oxyhaemoglobin response using near infrared spectroscopy. The first set of stimuli comprised chromatic square-wave gratings that varied with respect to the separation in the CIE UCS chromaticities of the alternating bars. The gratings with large separations in chromaticity evoked an oxyhaemoglobin response with greater amplitude, consistent with greater activation of the visual cortex. The second set of stimuli comprised horizontal achromatic gratings that (1) were static, (2) drifted at a constant velocity towards fixation, or (3) reversed direction every half spatial cycle to create a vertical vibrating motion. Although the three types of grating had a similar effect on the amplitude of the oxyhaemoglobin response, the moving gratings (2 and 3) evoked a steeper decrease in oxyhaemoglobin concentration after stimulus-offset. The steeper slope appears to reflect the post-stimulus undershoot and the slope may provide a correlate of cortical excitability when the amplitude of the haemodynamic response has saturated.

The possible use of precision tinted lenses to improve social cognition in children with autism spectrum disorders.

A masked randomised control design compared the effectiveness of precision ophthalmic tints in improving the recognition of emotion in Autism Spectrum Disorders (ASD). Fourteen children aged 10-14 with ASD and 14 control children matched on verbal and non-verbal IQ, wore spectacles with coloured lenses to complete two tasks that involved the observation of coloured video sequences in which social interactions were depicted. On one occasion (randomly first or second) the coloured lenses provided light of a colour that the child had one month previously selected as optimal for the clarity of text. On the other occasion the lenses differed in CIE UCS chromaticity by 0.077. Performance in the ASD group was superior in both social interaction tasks with the lenses that provided the optimal colour of light.

Chromaticity separation and the alpha response.

Chromatic gratings can be uncomfortable to view and can evoke a large haemodynamic response. Both the discomfort and the amplitude of the haemodynamic response increase monotonically with the perceptual difference in the colour of the component bars of the grating, as registered by the separation in their chromaticity in the CIE 1976 UCS diagram. Individuals with photosensitive epilepsy exhibit epileptiform EEG activity in response to flickering light of alternate colours. The probability of the epileptiform response again increases monotonically with the separation of the colours in the CIE UCS diagram. We investigated whether alpha power, which is known to reflect the excitation of large populations of neurons, is similarly affected by the separation in chromaticity. Chromatic square-wave gratings with bars that differed in CIE UCS chromaticity were presented, together with a central fixation cross. In 18 non-clinical participants, alpha responses were recorded over the visual cortex (O1, Oz, O2, PO3, POz, PO4, P1, P2) and compared to responses in prefrontal cortex (F1, F2). Gratings comprised bars of two alternate colours that either had a small difference in chromaticity (mean CIE UCS separation of 0.03), a medium difference (mean separation of 0.19), or a large difference (mean separation of 0.43). The colour pairs had chromaticities that lay on the red-green, red-blue, or blue-green borders of the screen gamut. Regardless of the hue, the larger the separation in chromaticity, the greater the alpha desynchronization and the lower the alpha power (p = 0.004), but only in posterior electrodes (p < 0.001). Together this indicates that differences in colour evoke a cortical excitation that increases monotonically with the colour difference. In this respect the alpha response resembles the haemodynamic response.

Spectral filters can improve reading and visual search in patients with multiple sclerosis.

We investigated the possible benefit for 26 patients with multiple sclerosis of placing Intuitive Overlays (spectral filters) over the page during reading and visual search. Initially all patients were allowed to select an overlay of a colour that reduced perceptual distortion and were tested with and without that overlay. With the coloured overlay, 25/26 patients reported fewer symptoms of visual stress, 50% read at least 20% more quickly and 50% omitted at least 57% fewer targets during visual search. Subsequently, under double-masked conditions 13 randomly-selected patients were given grey overlays,while the remaining 13 gender- and agematched patients were each given an overlay of their individually selected colour. Patients were permitted to use their overlays as and when they wished during the next 2 weeks. The reading and visual search performance of those patients who had received a grey overlay did not change,whereas the performance of those who received an overlay of their selected colour subsequently improved, both when using the overlays and also when not. After testing, the 13 patients who had received a grey overlay returned it prior to subsequent testing. The 13 patients were then each given an overlay of their selected colour and their performance subsequently improved.A large proportion of patients with multiple sclerosis may benefit from the use of spectral overlays.

Frontal lesions and sustained attention.

Neurological patients were presented with a succession of 2-11 stimuli which they were required to count, reporting the number in the series when it finished. The stimuli were binaural clicks, or pulses on the right or on the left index finger. Regardless of stimulus modality or lateralization, patients with lesions involving the right frontal lobe were impaired when the presentation rate was 1/sec. There was no corresponding impairment when the presentation rate was increased to 7/sec. It is argued that at slow rates when the task was monotonous patients with right-frontal lesions were less able than others to sustain attention voluntarily.

Spatiotemporal visual function in tinted lens wearers.

PURPOSE: Tinted lenses have been widely publicized as a successful new treatment for reading disorders and visual stress in children. The present study was designed to investigate a variety of visual deficits reported by children who experience high levels of visual stress and perceptual distortions when reading (Meares-Irlen syndrome; MIS) and to assess the improvements in visual comfort they report when tinted lenses are worn. METHODS: Twenty children (13.1 +/- 0.9 years of age) were recruited who had successfully worn tinted lenses for at least 6 months and were compared with an age-matched control group (12.6 +/- 2.2 years of age) of 21 children who were not lens wearers. A range of psychophysical tasks was adapted to identify specific anomalous visual perceptions. Spatiotemporal contrast sensitivity and contrast increment thresholds were used to investigate subjective reports of dazzle and hypercontrast, and a minimum motion perception (D(min)) and a motion-coherence task were used to assess subjective reports of visual instability and motion. RESULTS: In all viewing conditions (with versus without lens), no selective functional visual loss was demonstrated with any of the tasks used. Psychometric functions also revealed no significant difference between subject groups (control versus MIS). CONCLUSIONS: Under thorough psychophysical investigation, these results revealed no significant difference in visual function between subject group, and this finding is consistent with the absence of any effect of the tinted lenses in the group with MIS.

Prostacyclin analogues reduce ADP-ribosylation of the alpha-subunit of the regulatory Gs-protein and diminish adenosine (A2) responsiveness of platelets.

Prostacyclin and adenosine activate adenylate cyclase in human platelet membranes and inhibit platelet aggregation. Results are presented which show that prolonged incubation of platelets with iloprost (a stable prostacyclin analogue) results in a reduction in the capacity for adenylate cyclase activation by the adenosine analogue 5'-(N-ethyl)-carboxamidoadenosine (NECA), NaF, guanyl-5'-yl imidodiphosphate or GTP. However, iloprost pretreatment resulted in no change in the binding of [3H]-NECA to platelet membranes. These results contrast with those obtained after pretreatment with 2-chloroadenosine which revealed no change in NaF or guanyl-5'-yl imidodiphosphate sensitivity of adenylate cyclase. Pretreatment with 2-chloroadenosine resulted in reduced NECA-dependent adenylate cyclase activation, and loss of [3H]-NECA binding sites. The heterologous desensitization of adenosine A2-receptors by iloprost is accompanied by a loss (greater than 80%) of a 45 kDa protein from the plasma membrane, as revealed by [32P]-ADP-ribosylation in the presence of cholera toxin. It is proposed that this example of heterologous desensitization is mediated by elimination of Gs alpha, a subunit of the stimulatory guanyl nucleotide-binding regulatory protein.

Efficacy of clonidine in treatment of alcohol withdrawal state.

Clonidine hydrochloride 5 micrograms/kg and placebo were given orally to 11 patients experiencing well-developed alcohol withdrawal states. Active drug and placebo were given in a randomised, cross-over double blind fashion 2 h apart. Clonidine significantly suppressed heart rate (P = 0.002), arterial blood pressure (P = 0.006), and an accumulated score of withdrawal symptoms and signs (P = 0.004). These data suggest that clonidine may be useful in the management of alcohol withdrawal states, and that the underlying pathophysiology of at least some of these manifestations may be sympathetic nervous system hyperactivity.

Neuropsychological correlates of sustained attention in schizophrenia.

We employed a simple and relatively undemanding task of monotone counting for the assessment of sustained attention in schizophrenic patients. The monotone counting task has been validated neuropsychologically and is particularly sensitive to right prefrontal lesions. We compared the performance of schizophrenic patients with age- and education-matched controls. We then explored the extent to which a range of commonly employed neuropsychological tasks in schizophrenia research are related to attentional impairment as measured in this way. Monotone counting performance was found to be correlated with digit span (WAIS-R-HK), information (WAIS-R-HK), comprehension (WAIS-R-HK), logical memory (immediate recall) (Weschler Memory Scale, WMS), and visual reproduction (WMS). Multiple regression analysis also identified visual reproduction, digit span and comprehension as significant predictors of attention performance. In contrast, logical memory (delay recall) (WMS), similarity (WAIS-R-HK), semantic fluency, and Wisconsin Card Sorting Test (perseverative errors) were not correlated with attention. In addition, no significant correlation between sustained attention and symptoms was found. These findings are discussed in the context of a weakly modular cognitive system where attentional impairment may contribute selectively to a range of other cognitive deficits.

The putative prostacyclin receptor antagonist (FCE-22176) is a full agonist on human platelets and NCB-20 cells.

The action of FCE-22176 on prostacyclin receptors of human platelets and the NCB-20 cell line have been examined. FCE-22176 is a full agonist in both systems, mediating activation of adenylate cyclase. The concentration required for half-maximum enzyme activation was 174 nM in platelet membranes and 193 nM in homogenates of NCB-20 cells. The binding of [3H]iloprost to human platelet or NCB-20 cell membranes was inhibited by FCE-22176, and Ki values of 400 and 280 nM were obtained.

Interactions of epileptiform EEG discharges and cognition.

Interactions of subclinical epileptiform EEG discharges and cognitive functioning were studied in 91 patients with epilepsy, under video monitoring, to exclude overt clinical ictal phenomena during the investigations. A short-term memory test was presented as an engaging television game, in two versions, using spatial, or verbal material. Transitory cognitive impairment (TCI) was demonstrated during EEG discharges, either generalised or focal, in half the patients. Right-sided discharges were associated with impairment of the spatial task and left-sided with errors on the verbal version. TCI was demonstrable only when the discharge occurred during presentation of the material to be recalled. Increasing task difficulty, up to the patients' limit of performance, was associated with increasing susceptibility to TCI. Sixteen patients showed a significant effect of task on discharge rate, but in some this increased during the stimulus and in others while responding. There are thus complex interactions of epileptiform EEG activity on cognitive function and vice versa.

The influence of tinted lenses upon ocular accommodation.

We determined the effect upon accommodative responses of tinted lenses prescribed for the relief of visual discomfort in a group of five long term lens wearers. Static and dynamic responses were measured under four viewing conditions (1) prescribed tinted lens (2) neutral density filter (3) tinted lens of complementary colour and (4) no absorptive lens. While similarity and normality of the mean stimulus-response functions between the four viewing conditions were evident, the low frequency component of the accommodation microfluctuations was significantly greater while viewing the target in the 'no lens' viewing condition. These increases in the low frequency components (LFC) of the accommodation may be a subtle indicator of visual stress in these patients. Colour specificity is not supported by this finding.

Impaired contrast sensitivity in diabetic patients with and without retinopathy: a new technique for rapid assessment.

A simple technique is described for assessing the sensitivity of the human visual system to gratings at threshold contrast. The technique has advantages for clinical use in that it is (1) inexpensive, (2) quick to administer, (3) portable, and (4) relatively free from bias. Forty-two diabetic patients and 84 normal controls have been tested. Fifteen diabetic patients (6/20 with retinopathy and 9/22 without) had test scores more than two standard deviations below the norm for age-matched controls.

Treatment of photosensitive epilepsy using coloured glasses.

A recently introduced optometric technique, colorimetry, enables the perceptual effects of ophthalmic tints to be evaluated subjectively, optimized, and then prescribed in tinted spectacles. The new technique is beneficial in reducing visual stress in patients with dyslexia and migraine. We describe an open trial designed to ascertain: (1) whether the colorimetry assessment, as it is now given, is safe for the investigation of photosensitive patients in optometry clinics where colorimetry equipment is most readily available, but where EEG control is not practical; (2) what proportion of patients with photosensitive epilepsy is likely to benefit to the extent already described in individual cases; (3) whether a tint selected by colorimetry could be shown to reduce the incidence of paroxysmal epileptiform EEG activity in response to flicker and patterns, thereby validating the subjective methods and corroborating the reported seizure reduction. Twenty-four females and nine males (aged 12-43 years) took part. All the patients had suffered visually-provoked seizures, had exhibited a photoparoxysmal response on at least one previous EEG recording, and had received a diagnosis of photosensitive epilepsy. Twenty-two were currently experiencing seizures. A further EEG was recorded in all except seven cases: a routine resting record, followed by hyperventilation. Colorimetry was performed after hyperventilation and before photic stimulation. Twenty-three (70%) reported beneficial effects during colorimetry and were prescribed glasses. There was a preponderance of lenses with a rose or purple colour, in contrast to patients with dyslexia. Seventeen of the 23 patients were available at follow-up, an average of 2.4 years later. Thirteen (57%) reported benefits, and said they were still using the lenses. In six of the 13 the benefits were pronounced, including a reduction of dizziness from fluorescent lighting, elimination of aura when using computer screens etc. Only in three cases was there a reduction in seizures that could reasonably be attributed to the use of lenses; in two of these cases no medications were prescribed, and in the third the medications remained unchanged for four years, two before and two after the introduction of the glasses. In an additional four cases a reduction in seizures was observed but medication had been changed. There was a modest reduction in EEG photosensitivity with the coloured lenses but also to an equivalent or lesser extent with grey in all of the eight patients examined in this way. One patient had seizures during colorimetry, but the seizures were not accompanied by scalp EEG changes.

Attempted infanticide.

The offence of attempted infanticide has hitherto been unknown in English Law. A case is here described in which a woman was convicted of infanticide, and attempted infanticide, having been charged with murder and attempted murder. The relevance of this is discussed, together with an aspect of infanticide previously unreported in the English literature, i.e. repetition of the offence.