What is the relationship between Aphantasia, Synaesthesia and Autism?

For people with aphantasia, visual imagery is absent or markedly impaired. Here, we investigated the relationship between aphantasia and two other neurodevelopmental conditions also linked to imagery differences: synaesthesia, and autism. In Experiment 1a and 1b, we asked whether aphantasia and synaesthesia can co-occur, an important question given that synaesthesia is linked to strong imagery. Taking grapheme-colour synaesthesia as a test case, we found that synaesthesia can be objectively diagnosed in aphantasics, suggesting visual imagery is not necessary for synaesthesia to occur. However, aphantasia influenced the type of synaesthesia experienced (favouring 'associator' over 'projector' synaesthesia - a distinction tied to the phenomenology of the synaesthetic experience). In Experiment 2, we asked whether aphantasics have traits associated with autism, an important question given that autism - like aphantasia - is linked to weak imagery. We found that aphantasics reported more autistic traits than controls, with weaknesses in imagination and social skills.

Hyperglycaemia-related complications at the time of diagnosis can cause permanent neurological disability in children with neonatal diabetes.

BACKGROUND: Children with neonatal diabetes often present with diabetic ketoacidosis and hence are at risk of cerebral oedema and subsequent long-term neurological deficits. These complications are difficult to identify because neurological features can also occur as a result of the specific genetic aetiology causing neonatal diabetes. CASE REPORTS: We report two cases of neonatal diabetes where ketoacidosis-related cerebral oedema was the major cause of their permanent neurological disability. Case 1 (male, 18 years, compound heterozygous ABCC8 mutation) and case 2 (female, 29 years, heterozygous KCNJ11 mutation) presented with severe diabetic ketoacidosis at 6 and 16 weeks of age. Both had reduced consciousness, seizures and required intensive care for cerebral oedema. They subsequently developed spastic tetraplegia. Neurological examination in adulthood confirmed spastic tetraplegia and severe disability. Case 1 is wheelchair-bound and needs assistance for transfers, washing and dressing, whereas case 2 requires institutional care for all activities of daily living. Both cases have first-degree relatives with the same mutation with diabetes, who did not have ketoacidosis at diagnosis and do not have neurological disability. DISCUSSION: Ketoacidosis-related cerebral oedema at diagnosis in neonatal diabetes can cause long-term severe neurological disability. This will give additional neurological features to those directly caused by the genetic aetiology of the neonatal diabetes. Our cases highlight the need for increased awareness of neonatal diabetes and earlier and better initial treatment of the severe hyperglycaemia and ketoacidosis often seen at diagnosis of these children.

The radiological diagnosis of frontotemporal dementia in everyday practice: an audit of reports, review of diagnostic criteria, and proposal for service improvement.

AIM: To investigate how commonly valuable diagnostic information regarding the frontotemporal dementias (FTDs) may be missed on routine radiological reporting. MATERIALS AND METHODS: The magnetic resonance imaging (MRI) examination results of a series of 39 consecutive patients in whom the diagnosis was initially thought to be a form of FTD were audited. Twenty-two patients satisfied formal diagnostic criteria for subtypes of FTD. The initial non-specialist radiological reports of the MRI examinations were compared with those of a radiologist who specifically examined the images for the possibility of atypical dementia. RESULTS: Six of the 22 original reports provided a full and accurate description of the radiological findings, while two provided a fully accurate interpretation. CONCLUSION: Valuable diagnostic information may be missed unless clinicians and radiologists jointly review and discuss brain imaging in cases of dementia. The use of standardised scales may enhance the reporting of MRI examinations for dementia.

The neural correlates of everyday recognition memory.

We used a novel automatic camera, SenseCam, to create a recognition memory test for real-life events. Adapting a 'Remember/Know' paradigm, we asked healthy undergraduates, who wore SenseCam for 2 days, in their everyday environments, to classify images as strongly or weakly remembered, strongly or weakly familiar or novel, while brain activation was recorded with functional MRI. Overlapping, widely distributed sets of brain regions were activated by recollected and familiar stimuli. Within the medial temporal lobes, 'Remember' responses specifically elicited greater activity in the right anterior and posterior parahippocampal gyrus than 'Know' responses. 'New' responses activated anterior parahippocampal regions. A parametric analysis, across correctly recognised items, revealed increasing activation in the right hippocampus and posterior parahippocampal gyrus (pPHG). This may reflect modulation of these regions by the degree of recollection or, alternatively, by increasing memory strength. Strong recollection elicited greater activity in the left posterior hippocampus/pPHG than weak recollection indicating that this region is specifically modulated by the degree of recollection.

An fMRI study of long-term everyday memory using SenseCam.

We used a novel automatic camera, SenseCam, to investigate recognition memory for real-life events at a 5-month retention interval. Using fMRI we assessed recollection and familiarity memory using the remember/know procedure. Recollection evoked no medial temporal lobe (MTL) activation compared to familiarity and new responses. Instead, recollection activated diverse regions in neocortex including medial prefrontal cortex. We observed decreased activation in anterior hippocampus/ anterior parahippocampal gyrus (aPHG) at 5 months compared to a 36-hour retention interval. Familiarity was associated with greater activation in aPHG and posterior parahippocampal gyrus (pPHG) than recollection and new responses. Familiarity activation decreased over time in anterior hippocampus/aPHG and posterior hippocampus/pPHG. The engagement of neocortical regions such as medial prefrontal cortex at a 5-month delay, together with the reduced MTL activation at 5 months relative to at 36 hours is in line with the assumptions of Consolidation theory. SenseCam provides a valuable technique for assessing the processes that underlie remote everyday recognition memory.

Transient epileptic amnesia: regional brain atrophy and its relationship to memory deficits.

Transient epileptic amnesia (TEA) is a recently recognised form of epilepsy of which the principle manifestation is recurrent, transient episodes of isolated memory loss. In addition to the amnesic episodes, many patients describe significant interictal memory difficulties. Performance on standard neuropsychological tests is often normal. However, two unusual forms of memory deficit have recently been demonstrated in TEA: (i) accelerated long-term forgetting (ALF): the excessively rapid loss of newly acquired memories over a period of days or weeks and (ii) remote autobiographical memory loss: a loss of memories for salient, personally experienced events of the past few decades. The neuroanatomical bases of TEA and its associated memory deficits are unknown. In this study, we first assessed the relationship between subjective and objective memory performance in 41 patients with TEA. We then analysed MRI data from these patients and 20 matched healthy controls, using manual volumetry and voxel-based morphometry (VBM) to correlate regional brain volumes with clinical and neuropsychological data. Subjective memory estimates were unrelated to performance on standard neuropsychological tests but were partially predicted by mood, ALF and remote autobiographical memory. Manual volumetry identified subtle hippocampal volume loss in the patient group. Both manual volumetry and VBM revealed correlations between medial temporal lobe atrophy and standard anterograde memory scores, but no relation between atrophy and ALF or remote autobiographical memory. These results add weight to the hypothesis that TEA is a syndrome of mesial temporal lobe epilepsy. Furthermore, they suggest that although standard anterograde memory test performance is related to the degree of mesial temporal lobe damage, this is not true for ALF and autobiographical amnesia. It is possible that these unusual memory deficits have a more diffuse physiological basis rather than being a consequence of discrete structural damage.

Recent insights into the impairment of memory in epilepsy: transient epileptic amnesia, accelerated long-term forgetting and remote memory impairment.

Complaints of memory difficulties are common among patients with epilepsy, particularly with temporal lobe epilepsy where memory-related brain structures are directly involved by seizure activity. However, the reason for these complaints is often unclear and patients frequently perform normally on standard neuropsychological tests of memory. In this article, we review the literature on three recently described and interrelated forms of memory impairment associated with epilepsy: (i) transient epileptic amnesia, in which the sole or main manifestation of seizures is recurrent episodes of amnesia; (ii) accelerated long-term forgetting, in which newly acquired memories fade over days to weeks and (iii) remote memory impairment, in which there is loss of memories for personal or public facts or events from the distant past. Accelerated long-term forgetting and remote memory impairment are common amongst patients with transient epileptic amnesia, but have been reported in other forms of epilepsy. Their presence goes undetected by standard memory tests and yet they can have a profound impact on patients' lives. They pose challenges to current theoretical models of memory. We discuss the evidence for each of these phenomena, as well as their possible pathophysiological bases, methodological difficulties in their investigation and their theoretical implications.

When a patient with epilepsy complains about poor memory.

Patients with epilepsy often complain of "poor memory". The first step in managing this complaint is a clinical evaluation to define and, if possible, quantify the problem. The memory difficulty may be entirely unconnected to the epilepsy. But if the two appear to be linked, establish whether the memory problem is due to the seizures themselves, the pathology that underlies the seizures, their treatment, or their psychological sequelae such as anxiety or depression. Further management depends on the cause, while practical advice on the amelioration of poor memory can be useful.

Spinocerebellar ataxia type 8 in Scotland: frequency, neurological, neuropsychological and neuropsychiatric findings.

OBJECTIVES: The objectives of this study were to: (i) establish whether the spinocerebellar ataxia type 8 (SCA 8) expansion is associated with ataxia in Scotland; (ii) test the hypothesis that SCA 8 is associated with neuropsychological impairment; and (iii) review neuroradiological findings in SCA 8. METHODS: The methods included: (i) measurement of SCA 8 expansion frequencies in ataxic patients and healthy controls; (ii) comprehensive neuropsychological assessment of patients with SCA 8 and matched controls, neuropsychiatric interview; and (iii) comparison of patient and matched control magnetic resonance imaging (MRI) scans. RESULTS: (i) 10/694 (1.4%) unrelated individuals with ataxia had combined CTA/CTG repeat expansions >100 compared to 1/1190 (0.08%) healthy controls (P < 0.0005); (ii) neuropsychological assessment revealed a dysexecutive syndrome among SCA 8 patients, not readily explained by motor or mood disturbance; neuropsychiatric symptoms occurred commonly; (iii) cerebellar atrophy was the only salient MRI abnormality in the patient group. CONCLUSIONS: The SCA 8 expansion is associated with ataxia in Scotland. The disorder is associated with a dysexecutive syndrome.

Nitrogenase activity in wheat seedlings bearing para-nodules induced by 2,4-dichlorophenoxyacetic acid (2,4-D) and inoculated with Azospirillum.

Nitrogenase activity (C2H2 reduction) was demonstrated in seedlings of wheat roots bearing para-nodules induced by 2,4-dichlorophenoxyacetic acid (2,4-D) and inoculated with Azospirillum brasilense. Increased nitrogenase activity was observed in inoculated para-nodulated seedlings as compared to inoculated roots not treated by 2,4-D under the conditions of assay used. 2,4-D had no stimulating effect on plant ethylene production in the absence of acetylene. When inoculation was performed with a Nif-mutant of A. brasilense, no ethylene production was detected. It was also shown that the energy source required for nitrogenase activity was supplied by the host plant.

Progressive multifocal leucoencephalopathy, sclerosing cholangitis, bronchiectasis and disseminated warts in a patient with primary combined immune deficiency.

A 24 year old man presented with an unusual primary combined immune deficiency syndrome characterised by a profound lymphopenia of CD4 cells, selective serum IgG2 subclass deficiency, poor polysaccharide antibody responses, disseminated warts, recurrent sinopulmonary infection and bronchiectasis. The developed progressive multifocal leucoencephalopathy (PML) in association with sclerosing cholangitis. Progressive multifocal leucoencephalopathy (PML) usually occurs as an opportunistic infection in patients with secondary defects in cellular immunity.

Serum oligoclonal IgG is a common and persistent finding in multiple sclerosis, and has a systemic source.

Synthesis of oligoclonal IgG within the central nervous system is a well established feature of multiple sclerosis. The occurrence of oligoclonal IgG in the serum of patients with multiple sclerosis has received little attention. We detected such a serum response in 20/45 consecutive patients (44%, 95% CI 30-59%) but in only 3/41 age- and sex-matched healthy controls (p < 0.01). We present qualitative and quantitative evidence that this oligoclonal IgG has a systemic origin. The plasma cell clones responsible for the serum response are often also represented in the intrathecal compartment. In a further study of the clinical significance of serum oligoclonal bands, in 80 patients, their presence was associated with elevated levels of intrathecal synthesis, increasing age, later disease onset and the presence of serum autoantibodies. These findings add to the evidence that there is a systemic immune disturbance in multiple sclerosis.

Oxygen increases the steady-state level of nitrate in denitrifying cells of Paracoccus denitrificans.

The levels of nitrate in denitrifying cells of Paracoccus denitrificans were determined by centrifugation through silicone oil into phosphoric acid and ion-exchange HPLC analysis of the cell lysates, using [14C]sucrose to correct for the trapped external medium. Introduction of oxygen brought about a significant upward shift in the intracellular nitrate concentration. This result calls into question the current thinking that oxygen blocks nitrate respiration primarily due to the inhibition of nitrate transport into the cell.

Affinity of antigen-specific IgG distinguishes multiple sclerosis from encephalitis.

The characteristics of antigen-specific IgG in patients with multiple sclerosis and patients with encephalitis have been compared. Both groups of patients showed antigen-specific oligoclonal bands locally synthesised in the CSF. When the affinity distribution of the antigen-specific IgG was measured there was a marked difference between the two groups. Encephalitis patients had high affinity antibody against the causative antigen. This was consistent with the antibody undergoing affinity maturation as a result of the immune system fighting a primary infection. Multiple sclerosis patients lacked high affinity response. This lack of high affinity antibody was also seen in those encephalitis patients when antigens other than the causative antigen were studied.

The role of magnetic stimulation as a quantifier of motor disability in patients with multiple sclerosis.

Magnetic stimulation was used to measure motor conduction time (MCT) between head and neck in a prospective longitudinal study of patients with multiple sclerosis (MS) and normal subjects. MCT measurements showed a high degree of reproducibility in normal subjects and patients with stable MS. In patients with definite MS, there was significant positive correlation between MCT and motor disability. In patients treated with steroids for relapse of MS, there was significant shortening of MCT following treatment in those who clinically improved, but not in those who were clinically unchanged. In a smaller group of patients followed for 3 months, MCT changes tended to mirror the clinical pattern. Magnetic stimulation should prove a useful tool for the quantification of motor disability, and monitoring the response to new treatments in MS.

Haptoglobins as markers of blood-CSF barrier dysfunction: the findings in normal CSF.

Cerebrospinal fluid from 39 healthy individuals showed evidence for increasing blood-CSF barrier permeability with age, and confirmed that haptoglobins are more sensitive but less predictive markers of barrier permeability than total protein. Haptoglobin (Hp) species were identified by polyacrylamide gel electrophoresis followed by immunoblotting. Hp 1-1 (35 A, 85 kDa) was detected in all (9/9) subjects who exhibited this phenotype. Hp 2-1 (42 A, 120 kDa) was detected in 53% (8/15) of subjects in whom Hp 2-1 was the phenotype. Hp 2-2 (54 A, 160 kDa) was detected in only 20% (3/15) of subjects who exhibited this phenotype. The likelihood of detecting any haptoglobin species corresponded to the molecular size and the consequent resistance offered by the barrier. Among younger subjects aged < or =45 years, a significant difference in incidence occurred between the two smaller species Hp 1-1 and Hp 2-1. However, among those aged >45, the significant difference in incidence was between the two larger species Hp 2-1 and Hp 2-2. The incidence of detection among those with Hp 2-1 phenotypes was higher in the older age group. The increased likelihood of detecting haptoglobins with age is in keeping with the notion that barrier function is compromised by age, and also indicates that Hp 2-1 and Hp 2-2 are sensitive markers of barrier function. The appreciable incidence of haptoglobins in normal CSF, even of the larger species, suggests reservation in assuming that their presence signifies barrier damage.

Immunoblotting of transferrin in the identification of cerebrospinal fluid otorrhoea and rhinorrhoea.

Cerebrospinal rhinorrhoea is potentially serious due to the risk from infection. In patients presenting with a nasal discharge of clear fluid it is important to identify the nature of the fluid. Cerebrospinal fluid is readily identified by the presence of asialo-transferrin (tau protein). A method is presented for the identification of tau protein based upon agarose electrophoresis, followed by transfer onto cellulose nitrate membrane and immunochemical detection of transferrin. The method is reliable, sensitive and simple, and requires only basic electrophoresis apparatus.

Atovaquone and proguanil hydrochloride: a review of nonclinical studies.

BACKGROUND: Safe and effective antimalarial drugs are needed for treatment and prophylaxis of malaria. The combination of atovaquone and proguanil hydrochloride is a new antimalarial drug combination that has recently become available in many countries. METHODS: Data were reviewed from nonclinical studies evaluating the microbiology, secondary pharmacology, pharmacokinetics, and toxicology of atovaquone and proguanil hydrochloride. RESULTS: Atovaquone is highly active against asexual erythrocytic stages of Plasmodium falciparum in vitro (IC50 0.7-6 nM) and in animal models. Proguanil per se has only weak antimalarial activity in vitro (IC50 2.4-19 microM), and its effectiveness depends on the active metabolite cycloguanil (IC50 0.5-2.5 nM). The combination of atovaquone and proguanil is synergistic in vitro. Both drugs also have activity against gametocytes and pre-erythrocytic (hepatic) stages of malaria parasites. Atovaquone is a ubiquinone antagonist that inhibits mitochondrial electron transport and collapses mitochondrial membrane potential. The proguanil metabolite cycloguanil is a dihydrofolate reductase inhibitor, but the mode of action of proguanil is unknown. In screening evaluations of secondary pharmacology, neither atovaquone nor proguanil had activity that adversely affected gastrointestinal, cardiovascular, or central or autonomic nervous system functions at clinically relevant concentrations. After oral administration, atovaquone exposure is extensive in rats but limited in dogs, while proguanil and cycloguanil exposure is extensive in dogs but limited in rats. In both species, toxicity was related to proguanil exposure, the principal manifestations being salivation, emesis, and loss of body weight. Neither atovaquone nor proguanil was teratogenic or mutagenic. An increased incidence of hepatic adenomas and adenocarcinomas was seen in mice, but not rats, after lifetime exposure to atovaquone, and appears to be related to species-specific differences in hepatic enzymatic activity. No additional toxicity was evident in animals treated with the combination of atovaquone and proguanil hydrochloride compared to those treated with either drug alone. CONCLUSION: Nonclinical studies of atovaquone and proguanil hydrochloride supported the clinical development of this combination for treatment and prophylaxis of malaria.

A new principle of activation-analysis separations-X Substoichiometric determination of traces of gallium.

A rapid method for the substoichiometric determination of gallium by neutron-activation analysis has been developed. After irradiation and dissolution of the test sample, gallium carrier is added and two preliminary separation steps are performed: the extraction into chloroform of cupferrates from 7N sulphuric acid and of diethyldithiocarbamates from 2-3N sulphuric acid. The pH of the remaining aqueous phase is then adjusted to 5.5, the solution extracted with a substoichiometric amount of 8-hydroxyquinoline in chloroform and the activity of the gallium hydroxyquinolate extract measured. A simultaneously irradiated gallium standard is treated in exactly the same way. From the activities of these two substoichiometric extracts the amount of gallium originally present in the test sample can be calculated. The method has been applied to the determination of 10(-6) to 10(-3)% of gallium in metallic aluminium and transistor-grade silicon.