Although Galton recognised in 1880 that some individuals lack visual imagery, this phenomenon was largely neglected over the following century. We recently coined the terms ‘aphantasia’ and ‘hyperphantasia’ to describe visual imagery vividness extremes, unlocking a sustained surge of public interest. Aphantasia is associated with subjective impairment of face recognition and autobiographical memory. Here we report the first systematic, wide-ranging neuropsychological and brain imaging study of people with aphantasia (n=24), hyperphantasia (n=25) and mid-range imagery vividness (n=20). Despite equivalent performance on standard memory tests, there were marked group differences on measures of autobiographical memory and imagination, participants with hyperphantasia outperforming controls who outperformed participants with aphantasia. Face recognition difficulties were reported more commonly in aphantasia. The Revised NEO Personality Inventory highlighted reduced extroversion in the aphantasia group and increased openness in the hyperphantasia group. Resting-state fMRI revealed stronger connectivity between prefrontal cortices and the visual network among hyperphantasic than aphantasic participants. In an active fMRI paradigm, there was greater anterior parietal activation among hyperphantasic and control than aphantasic participants when comparing visualisation of famous faces and places with perception. These behavioral and neural signatures of visual imagery vividness extremes validate and illuminate this significant but neglected dimension of individual difference.

Can visual imagining ever be other than a brain-bound, organismically internal process? the practices of artists with aphantasia - the congenital or acquired incapacity to generate visual mental imagery - suggests that it can. Here we report on a qualitative study of ‘aphantasic’ artists and find that imagery lack coincides with a dependence on external, environmental, structures to generate artwork. Indeed, physical manipulations of external media seem to take place in lieu of the ability to generate and manipulate internal, mental images. Cognitive functions that could, for the non-aphantasic, be carried out by mental imagery - such as bringing non-conscious visio-spatial relationships to awareness - can only be carried out for the aphantasic by manipulating their environment. Thus aphantasic art-making constitutes extended visual imagining. As such, it undermines the universality of the ‘hylomorphic’ model of art-making, in which the work is mentally preconceived before being realised in the material world, with the fact of neurocognitive diversity.

Visual imagery typically enables us to see absent items in the mind’s eye. It plays a role in memory, day-dreaming and creativity. Since coining the terms aphantasia and hyperphantasia to describe the absence and abundance of visual imagery, we have been contacted by many thousands of people with extreme imagery abilities. Questionnaire data from 2000 participants with aphantasia and 200 with hyperphantasia indicate that aphantasia is associated with scientific and mathematical occupations, whereas hyperphantasia is associated with ‘creative’ professions. Participants with aphantasia report an elevated rate of difficulty with face recognition and autobiographical memory, whereas participants with hyperphantasia report an elevated rate of synaesthesia. Around half those with aphantasia describe an absence of wakeful imagery in all sense modalities, while a majority dream visually. Aphantasia appears to run within families more often than would be expected by chance. Aphantasia and hyperphantasia appear to be widespread but neglected features of human experience with informative psychological associations.

ObjectiveWe investigated the nature and neural foundations of pathologic tearfulness in a uniquely large cohort of patients who had presented with autoimmune limbic encephalitis (aLE).MethodsWe recruited 38 patients (26 men, 12 women; median age 63.06 years; interquartile range [IQR] 16.06 years) in the postacute phase of aLE who completed questionnaires probing emotion regulation. All patients underwent structural/functional MRI postacutely, along with 67 age- and sex-matched healthy controls (40 men, 27 women; median age 64.70 years; IQR 19.87 years). We investigated correlations of questionnaire scores with demographic, clinical, neuropsychological, and brain imaging data across patients. We also compared patients diagnosed with pathologic tearfulness and those without, along with healthy controls, on gray matter volume, resting-state functional connectivity, and activity.ResultsPathologic tearfulness was reported by 50% of the patients, while no patient reported pathologic laughing. It was not associated with depression, impulsiveness, memory impairment, executive dysfunction in the postacute phase, or amygdalar abnormalities in the acute phase. It correlated with changes in specific emotional brain networks: volume reduction in the right anterior hippocampus, left fusiform gyrus, and cerebellum, abnormal hippocampal resting-state functional connectivity with the posteromedial cortex and right middle frontal gyrus, and abnormal hemodynamic activity in the left fusiform gyrus, right inferior parietal lobule, and ventral pons.ConclusionsPathologic tearfulness is common following aLE, is not a manifestation of other neuropsychiatric features, and reflects abnormalities in networks of emotion regulation beyond the acute hippocampal focus. The condition, which may also be present in other neurologic disorders, provides novel insights into the neural basis of affective control and its dysfunction in disease.

Transient epileptic amnesia (TEA) is an epileptic syndrome characterized by recurrent, brief episodes of amnesia. Patients with TEA often complain of interictal (between attacks) retention deficits, characterised by an ‘evaporation’ of memories for recent events over days to weeks. Clinical tests of anterograde memory often fail to corroborate these complaints as TEA patients commonly perform within the normal range after the standard 10–30-min delay period. Modified laboratory tests that include a 1–3 week delay period frequently reveal clear evidence of ‘accelerated long-term forgetting’ (ALF). However, they are not used routinely and lack ecological validity. In the present study we examined whether ‘real-life’ ALF can be captured via a controlled incidental memory test in TEA patients. To this end, the experimenter told 27 TEA patients and 32 controls a well-rehearsed amusing story, apparently as a way of making light conversation before starting a set of research experiments. Without prior warning, the experimenter subsequently probed the participants' memory of this story via tests of free recall and forced choice recognition after 30 min or 1 week. After 30 min retention was comparable in TEA patients and controls. After 1 week TEA patients retained significantly less story material than controls, and significant ALF was revealed in the TEA patients in the recognition test. Our data show that ALF in a ‘real-life’ situation can occur even when standard memory tests indicate normal memory function. Moreover, our data suggest that incidental memory tests can capture real-life ALF, and that forced-choice recognition tests might be more sensitive than free recall tests for the detection of real-life ALF.

OBJECTIVE: Central nervous system (CNS) features in children with permanent neonatal diabetes (PNDM) due to KCNJ11 mutations have a major impact on affected families. Sulfonylurea therapy achieves outstanding metabolic control but only partial improvement in CNS features. The effects of KCNJ11 mutations on the adult brain and their functional impact are not well understood. We aimed to characterize the CNS features in adults with KCNJ11 PNDM compared with adults with INS PNDM. RESEARCH DESIGN AND METHODS: Adults with PNDM due to KCNJ11 mutations (n = 8) or INS mutations (n = 4) underwent a neurological examination and completed standardized neuropsychological tests/questionnaires about development/behavior. Four individuals in each group underwent a brain MRI scan. Test scores were converted to Z scores using normative data, and outcomes were compared between groups. RESULTS: in individuals with KCNJ11 mutations, neurological examination was abnormal in seven of eight; predominant features were subtle deficits in coordination/motor sequencing. All had delayed developmental milestones and/or required learning support/special schooling. Half had features and/or a clinical diagnosis of autism spectrum disorder. KCNJ11 mutations were also associated with impaired attention, working memory, and perceptual reasoning and reduced intelligence quotient (IQ) (median IQ KCNJ11 vs. INS mutations 76 vs. 111, respectively; P = 0.02). However, no structural brain abnormalities were noted on MRI. The severity of these features was related to the specific mutation, and they were absent in individuals with INS mutations. CONCLUSIONS: KCNJ11 PNDM is associated with specific CNS features that are not due to long-standing diabetes, persist into adulthood despite sulfonylurea therapy, and represent the major burden from KCNJ11 mutations.

The accelerated forgetting of newly learned information is common amongst patients with epilepsy and, in particular, in the syndrome of transient epileptic amnesia (TEA). However, the neural mechanisms underlying accelerated forgetting are poorly understood. It has been hypothesised that interictal epileptiform activity during longer retention intervals disrupts normally established memory traces. Here, we tested a distinct hypothesis-that accelerated forgetting relates to the abnormal encoding of memories. We studied a group of 15 patients with TEA together with matched, healthy control subjects. Despite normal performance on standard anterograde memory tasks, patients showed accelerated forgetting of a word list over one week. We used a subsequent memory paradigm to compare encoding-related brain activity in patients and controls. Participants studied a series of visually presented scenes whilst undergoing functional MRI scanning. Recognition memory for these scenes was then probed outside the scanner after delays of 45 min and of 4 days. Patients showed poorer memory for the scenes compared with controls. In the patients but not the controls, subsequently forgotten stimuli were associated with reduced hippocampal activation at encoding. Furthermore, patients demonstrated reduced deactivation of posteromedial cortex regions upon viewing subsequently remembered stimuli as compared to subsequently forgotten ones. These data suggest that abnormal encoding-related activity in key memory areas of the brain contributes to accelerated forgetting in TEA. We propose that abnormally encoded memory traces may be particularly vulnerable to interference from subsequently encountered material and hence be forgotten more rapidly. Our results shed light on the mechanisms underlying memory impairment in epilepsy, and offer support to the proposal that accelerated forgetting may be a useful marker of subtle dysfunction in memory-related brain systems.

Kufs disease is the major adult form of neuronal ceroid lipofuscinosis, but is rare and difficult to diagnose. Diagnosis was traditionally dependent on the demonstration of characteristic storage material, but distinction from normal age-related accumulation of lipofuscin can be challenging. Mutation of CLN6 has emerged as the most important cause of recessive Kufs disease but, remarkably, is also responsible for variant late infantile ceroid lipofuscinosis. Here we provide a detailed description of Kufs disease due to CLN6 pathogenic variants. We studied 20 cases of Kufs disease with CLN6 pathogenic variants from 13 unrelated families. Mean age of onset was 28 years (range 12-51) with bimodal peaks in teenage and early adult life. The typical presentation was of progressive myoclonus epilepsy with debilitating myoclonic seizures and relatively infrequent tonic-clonic seizures. Patients became wheelchair-bound with a mean 12 years post-onset. Ataxia was the most prominent motor feature. Dementia appeared to be an invariable accompaniment, although it could take a number of years to manifest and occasionally cognitive impairment preceded myoclonic seizures. Patients were usually highly photosensitive on EEG. MRI showed progressive cerebral and cerebellar atrophy. The median survival time was 26 years from disease onset. Ultrastructural examination of the pathology revealed fingerprint profiles as the characteristic inclusions, but they were not reliably seen in tissues other than brain. Curvilinear profiles, which are seen in the late infantile form, were not a feature. of the 13 unrelated families we observed homozygous CLN6 pathogenic variants in four and compound heterozygous variants in nine. Compared to the variant late infantile form, there was a lower proportion of variants that predicted protein truncation. Certain heterozygous missense variants in the same amino acid position were found in both variant late infantile and Kufs disease. There was a predominance of cases from Italy and surrounding regions; this was partially explained by the discovery of three founder pathogenic variants. Clinical distinction of type a (progressive myoclonus epilepsy) and type B (dementia with motor disturbance) Kufs disease was supported by molecular diagnoses. Type a is usually caused by recessive pathogenic variants in CLN6 or dominant variants in DNAJC5. Type B Kufs is usually associated with recessive CTSF pathogenic variants. The diagnosis of Kufs remains challenging but, with the availability of genetic diagnosis, this will largely supersede the use of diagnostic biopsies, particularly as biopsies of peripheral tissues has unsatisfactory sensitivity and specificity.

Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by intractable seizures, abundant epileptiform activity on EEG, and developmental impairment or regression. CACNA1E is highly expressed in the central nervous system and encodes the α1-subunit of the voltage-gated CaV2.3 channel, which conducts high voltage-activated R-type calcium currents that initiate synaptic transmission. Using next-generation sequencing techniques, we identified de novo CACNA1E variants in 30 individuals with DEE, characterized by refractory infantile-onset seizures, severe hypotonia, and profound developmental impairment, often with congenital contractures, macrocephaly, hyperkinetic movement disorders, and early death. Most of the 14, partially recurring, variants cluster within the cytoplasmic ends of all four S6 segments, which form the presumed CaV2.3 channel activation gate. Functional analysis of several S6 variants revealed consistent gain-of-function effects comprising facilitated voltage-dependent activation and slowed inactivation. Another variant located in the domain II S4-S5 linker results in facilitated activation and increased current density. Five participants achieved seizure freedom on the anti-epileptic drug topiramate, which blocks R-type calcium channels. We establish pathogenic variants in CACNA1E as a cause of DEEs and suggest facilitated R-type calcium currents as a disease mechanism for human epilepsy and developmental disorders.

On average, humans sleep for a third of their lives, and sleep disorders are common and treatable. However, services for most sleep disorders are highly variable across the UK, and sleep medicine is neglected in the medical curriculum. We report the findings of an audit of patients with neurological sleep disorders seen in a combined cognitive neurology and sleep disorder clinics over a seven‐year period, 75 with hypersomnias, 67 with parasomnias and 39 with insomnia. Also, the results of a pilot of a cognitive behavioural therapy service for insomnia undertaken in the same population are analysed.

The past 25 years have seen a rapid growth of knowledge about brain mechanisms involved in visual mental imagery. These advances have largely been made independently of the long history of philosophical - and even psychological - reckoning with imagery and its parent concept 'imagination'. We suggest that the view from these empirical findings can be widened by an appreciation of imagination's intellectual history, and we seek to show how that history both created the conditions for - and presents challenges to - the scientific endeavor. We focus on the neuroscientific literature's most commonly used task - imagining a concrete object - and, after sketching what is known of the neurobiological mechanisms involved, we examine the same basic act of imagining from the perspective of several key positions in the history of philosophy and psychology. We present positions that, firstly, contextualize and inform the neuroscientific account, and secondly, pose conceptual and methodological challenges to the scientific analysis of imagery. We conclude by reflecting on the intellectual history of visualization in the light of contemporary science, and the extent to which such science may resolve long-standing theoretical debates.

We investigated whether the benefit of slow wave sleep (SWS) for memory consolidation typically observed in healthy individuals is disrupted in people with accelerated long-term forgetting (ALF) due to epilepsy. SWS is thought to play an active role in declarative memory in healthy individuals and, furthermore, electrographic epileptiform activity is often more prevalent during SWS than during wakefulness or other sleep stages. We studied the relationship between SWS and the benefit of sleep for memory retention using a word-pair associates task. In both the ALF and the healthy control groups, sleep conferred a memory benefit. However, the relationship between the amount of SWS and sleep-related memory benefits differed significantly between the groups. In healthy participants, the amount of SWS correlated positively with sleep-related memory benefits. In stark contrast, the more SWS, the smaller the sleep-related memory benefit in the ALF group. Therefore, contrary to its role in healthy people, SWS-associated brain activity appears to be deleterious for memory in patients with ALF.

OBJECTIVE: Accelerated long-term forgetting (ALF) is typically defined as a memory disorder in which information that is learned and retained normally over standard intervals (∼30 min) is forgotten at an abnormally rapid rate thereafter. ALF has been reported, in particular, among patients with transient epileptic amnesia (TEA). Previous work in TEA has revealed ALF 24 hr - 1 week after initial memory acquisition. It is unclear, however, if ALF observed 24 hr after acquisition reflects (a) an impairment of sleep consolidation processes taking place during the first night's sleep, or (b) an impairment of daytime consolidation processes taking place during the day of acquisition. Here we focus on the daytime-forgetting hypothesis of ALF in TEA by tracking in detail the time course of ALF over the day of acquisition, as well as over 24 hr and 1 week. METHOD: Eleven TEA patients who showed ALF at 1 week and 16 matched controls learned 4 categorical word lists on the morning of the day of acquisition. We subsequently probed word-list retention 30 min, 3 hr, and 8 hr postacquisition (i.e. over the day of acquisition), as well as 24-hr and 1-week post acquisition. RESULTS: ALF became apparent in the TEA group over the course of the day of acquisition 3-8 hr after learning. No further forgetting was observed over the first night in either group. CONCLUSIONS: the results of this study show that ALF in TEA can result from a deficit in memory consolidation occurring within hours of learning without a requirement for intervening sleep.

Transient epileptic amnesia (TEA) is an epileptic syndrome characterized by recurrent, brief episodes of amnesia. Transient epileptic amnesia is often associated with the rapid decline in recall of new information over hours to days (accelerated long-term forgetting - 'ALF'). It remains unknown how recognition memory is affected in TEA over time. Here, we report a systematic study of picture recognition in patients with TEA over the course of one week. Sixteen patients with TEA and 16 matched controls were presented with 300 photos of everyday life scenes. Yes/no picture recognition was tested 5min, 2.5h, 7.5h, 24h, and 1week after picture presentation using a subset of target pictures as well as similar and different foils. Picture recognition was impaired in the patient group at all test times, including the 5-minute test, but it declined normally over the course of 1week. This impairment was associated predominantly with an increased false alarm rate, especially for similar foils. High performance on a control test indicates that this impairment was not associated with perceptual or discrimination deficits. Our findings suggest that, at least in some TEA patients with ALF in verbal recall, picture recognition does not decline more rapidly than in controls over 1week. However, our findings of an early picture recognition deficit suggest that new visual memories are impoverished after minutes in TEA. This could be the result of deficient encoding or impaired early consolidation. The early picture recognition deficit observed could reflect either the early stages of the process that leads to ALF or a separable deficit of anterograde memory in TEA. Lastly, our study suggests that at least some patients with TEA are prone to falsely recognizing new everyday visual information that they have not in fact seen previously. This deficit, alongside their ALF in free recall, likely affects everyday memory performance.

© 2015 the Royal College of Radiologists. 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.

Epilepsy is both a disease of the brain and the mind. Here, we present the first of two papers with extended summaries of selected presentations of the Third International Congress on Epilepsy, Brain and Mind (April 3-5, 2014; Brno, Czech Republic). Epilepsy in history and the arts and its relationships with religion were discussed, as were overviews of epilepsy and relevant aspects of social cognition, handedness, accelerated forgetting and autobiographical amnesia, and large-scale brain networks.

Polyglutamine expansions in the ataxin-2 gene (ATXN2) cause autosomal dominant spinocerebellar ataxia type 2 (SCA2), but have recently also been associated with amyotrophic lateral sclerosis (ALS). We present clinical and pathological features of a family in which a pathological ATXN2 expansion led to frontotemporal lobar degeneration with ALS (FTLD-ALS) in the index case, but typical SCA2 in a son, and compare the neuropathology with a case of typical SCA2. The index case shares the molecular signature of SCA2 with prominent polyglutamine and p62-positive intranuclear neuronal inclusions mainly in the pontine nuclei, while harbouring more pronounced neocortical and spinal TDP-43 pathology. We conclude that ATXN2 mutations can cause not only ALS, but also a neuropathological overlap syndrome of SCA2 and FTLD presenting clinically as pure FTLD-ALS without ataxia. The cause of the phenotypic heterogeneity remains unexplained, but the presence of a CAA-interrupted CAG repeat in the FTLD case in this family suggests that one potential mechanism may be variation in repeat tract composition between members of the same family.

BACKGROUND: Déjà vu can occur as an aura of temporal lobe epilepsy and in some psychiatric conditions but is also common in the general population. It is unclear whether any clinical features distinguish pathological and physiological forms of déjà vu. METHODS: 50 epileptic patients with ictal déjà vu, 50 non-epileptic patients attending general neurology clinics and 50 medical students at Edinburgh University were recruited. Data were collected on demographic factors, the experience of déjà vu using a questionnaire based on Sno's Inventory for Déjà Vu Experiences Assessment, symptoms of anxiety and depression using the Hospital Anxiety and Depression Scale as well as seizure characteristics, anti-epileptic medications, handedness, EEG and neuroimaging findings for epileptic patients. RESULTS: 73.5% of neurology patients, 88% of students and (by definition) all epilepsy patients had experienced déjà vu. The experience of déjà vu itself was similar in the three groups. Epileptic déjà vu occurred more frequently and lasted somewhat longer than physiological déjà vu. Epilepsy patients were more likely to report prior fatigue and concentrated activity, associated derealisation, olfactory and gustatory hallucinations, physical symptoms such as headaches, abdominal sensations and fear. After controlling for study group, anxiety and depression scores were not associated with déjà vu frequency. CONCLUSIONS: Déjà vu is common and qualitatively similar whether it occurs as an epileptic aura or normal phenomenon. However ictal déjà vu occurs more frequently and is accompanied by several distinctive features. It is distinguished primarily by 'the company it keeps'.

This paper explores the relationship between neurology and psychiatry. It marshals evidence that disorders of the brain typically have neurological and psychological-cognitive, affective, behavioural-manifestations, while disorders of the psyche are based in the brain. Given the inseparability of neurological and psychiatric disorders, their disease classifications should eventually fuse, and joint initiatives in training, service and research should be strongly encouraged.

INTRODUCTION: Déjà vu is typically a transient mental state in which a novel experience feels highly familiar. Although extensively studied in relation to temporal lobe epilepsy as part of simple partial seizures, déjà vu has been less studied in other clinical populations. A recent review of temporal lobe epilepsy suggested a possible link between clinical levels of anxiety and debilitating déjà vu, indicating further research is required. Here, for the first time in the literature, we present a case study of a young man with anxiety and depersonalisation who reported experiencing persistent and debilitating déjà vu. This report therefore adds to the limited literature on the relationship between anxiety and déjà vu. CASE PRESENTATION: a 23-year-old White British man presented with a form of persistent déjà vu in 2010, approximately 3 years since symptom onset. He reported a history of anxiety and experiencing feelings of depersonalisation. Neurological assessment (electroencephalogram and magnetic resonance imaging) did not indicate any abnormalities. We assessed his recognition memory with a task used in patients with dementia who report similar experiences but lack awareness of their falseness. CONCLUSIONS: Our case's memory performance was more conservative than controls but did not indicate a memory deficit. Unlike other patients with chronic déjà vu (for example, in dementia), he is fully aware of the false nature of his déjà vu and this presumably leads to his intact recognition memory performance. We suggest that his persistent déjà vu is psychogenic and conclude that déjà vu should be further studied in psychiatric disorders.

Accelerated long-term forgetting (ALF) is a form of memory impairment in which learning and initial retention of information appear normal but subsequent forgetting is excessively rapid. ALF is most commonly associated with epilepsy and, in particular, a form of late-onset epilepsy called transient epileptic amnesia (TEA). ALF provides a novel opportunity to investigate post-encoding memory processes, such as consolidation. Sleep is implicated in the consolidation of memory in healthy people and a deficit in sleep-dependent memory consolidation has been proposed as an explanation for ALF. If this proposal were correct, then sleep would not benefit memory retention in people with ALF as much as in healthy people, and ALF might only be apparent when the retention interval contains sleep. To test this theory, we compared performance on a sleep-sensitive memory task over a night of sleep and a day of wakefulness. We found, contrary to the hypothesis, that sleep benefits memory retention in TEA patients with ALF and that this benefit is no smaller in magnitude than that seen in healthy controls. Indeed, the patients performed significantly more poorly than the controls only in the wake condition and not the sleep condition. Patients were matched to controls on learning rate, initial retention, and the effect of time of day on cognitive performance. These results indicate that ALF is not caused by a disruption of sleep-dependent memory consolidation. Instead, ALF may be due to an encoding abnormality that goes undetected on behavioural assessments of learning, or by a deficit in memory consolidation processes that are not sleep-dependent. © 2014 the Authors.

Accelerated Long-term Forgetting (ALF) is the rapid loss of newly acquired memories over days to weeks despite normal retention at standard (~30 min) intervals. It has recently been described in association with epilepsy, particularly the syndrome of Transient Epileptic Amnesia (TEA). The cognitive mechanisms underlying ALF remain uncertain, but disruption either of memory acquisition or consolidation processes has been postulated. To arbitrate between these accounts, we reanalysed data from an existing word-list recall data set to investigate whether ALF can be observed for words learned under precisely matched conditions in TEA patients and controls. We reanalysed the data of 24 patients with TEA and 24 matched healthy controls who learnt a 15-item word list to a learning criterion of 90% with a minimum of five learning trials. Free recall of the words was probed at delays of 30 min and 1 week and 3 weeks after learning. In addition, a 'yes-no' recognition test was conducted after the 3-week free recall. Forgetting rates across the first 30 min delay and the subsequent 1 week and 3 week delay were compared between patients and controls. To ensure that learning conditions were closely matched between patients and control participants, we excluded exceptionally fast (N(TEA)=1, N(controls)=4) and slow (N(TEA)=6, N(controls)=2) learners. Furthermore, we analysed only words that were presented five or six times during learning and retrieved successfully on four or five occasions during learning. Recall performance on the last learning trial and 30 min after acquisition were indistinguishable between TEA patients and controls. Over the delay interval of 30 min to 1 week, however, accelerated forgetting of this newly learned verbal material was observed in TEA patients. This severe forgetting is also reflected in the three-week recognition test, where TEA patients performed significantly worse than controls. Moreover, whereas recall on the last learning trial correlated significantly with the 30 min delayed recall in both groups, recall on the last learning trial correlated significantly with 1 week and 3 week delayed recall only in the controls. In both groups, the three-week free recall performance correlated with the three-week recognition test. Patients with TEA demonstrate ALF even for verbal material that is learned under precisely matched conditions. These results are consistent with the hypothesis that ALF represents a disruption of memory consolidation rather than an acquisition deficit.

Transient epileptic amnesia (TEA) is a recently described epilepsy syndrome characterized by recurrent episodes of isolated memory loss. It is associated with two unusual forms of interictal memory impairment: accelerated long-term forgetting (ALF) and autobiographical amnesia. We investigated the neural basis of TEA using manual volumetry and automated multi-atlas-based segmentation of whole-brain magnetic resonance imaging data from 40 patients with TEA and 20 healthy controls. Both methods confirmed the presence of subtle, bilateral hippocampal atrophy. Additional atrophy was revealed in perirhinal and orbitofrontal cortices. The volumes of these regions correlated with anterograde memory performance. No structural correlates were found for ALF or autobiographical amnesia. The results support the hypothesis that TEA is a focal medial temporal lobe epilepsy syndrome but reveal additional pathology in connected brain regions. The unusual interictal memory deficits of TEA remain unexplained by structural pathology and may reflect physiological disruption of memory networks by subclinical epileptiform activity.

Transient Epileptic Amnesia (TEA) is a subtype of temporal lobe epilepsy characterised by recurrent episodes of transient amnesia, usually in middle aged people, often occurring on waking, which prove to be due to epilepsy. Attacks are sometimes accompanied by other more familiar manifestations of epilepsy, especially olfactory hallucinations. The epilepsy typically responds very well to anticonvulsant treatment but interictal memory disturbance often persists despite abolition of the seizures, in particular an extensive autobiographical amnesia (AA), and a tendency for memories to fade more rapidly than usual over days to weeks (accelerated long-term forgetting, ALF). The TIME project (The Impairment of Memory in Epilepsy: see http://www.exeter.ac.uk/time/) was established in 2003 to study TEA and its associated interictal memory disturbance. It has since generated around 20 publications describing the clinical, neuropsychological and radiological features of TEA, AA and ALF.(1-4) the British Neurological Surveillance Unit (BNSU) contributed to patient recruitment in 2003-2005 and again recently (2011-present). In 2003-5, 32 patients were referred via the BNSU. 16 were included in the patient cohort described in our 2007 report,(1) nine were excluded as they did not satisfy our diagnostic criteria, seven were potentially suitable but study resources did not allow us to assess them fully. 22 cases have been referred recently. Details are awaited for 13, one refused consent, four have been assessed, three await assessment, one was excluded after assessment. The BNSU has made a major contribution to the success of the TIME project. The recruitment process would work more smoothly if participating neurologists i) asked patients for consent to pass on demographical and clinical details at the time of the clinic visit on which they are identified, ii) communicated these immediately to the researcher or iii) kept a note of patient details if i) and ii) are not feasible. The current system works well, and helps greatly in the recruitment of series of cases of moderately rare disorders, but its efficiency could be improved.

Objective:
to identify the neural basis of autobiographical memory deficits in transient epileptic amnesia (TEA).

Method:
11 people (mean age: 65.91; SD=7.63) diagnosed with transient epileptic amnesia, all of whom complained of extensive autobiographical memory loss, and 17 age and IQ matched controls were recruited. Participants were matched on standard measures of anterograde memory. Participants recalled 32 previously identified autobiographical memories, specific in time and place, from four different time periods (childhood, young adult, middle aged and recent), during fMRI scanning. Activations were analysed using SPM8 software, effective connectivity using dynamic causal modelling (DCM). Post-scan ratings of the subjective vividness, level of detail, pleasantness, personal significance and frequency of retrieval of the memories were recorded.

Results:
Both patients and controls activated core regions of the autobiographical memory network. However, patients had reduced activation in the right posterior parahippocampal gyrus (pPHG), particularly for more recent memories, together with decreased engagement of the right temporoparietal junction and the right cerebellum. In addition, we found reduced effective connectivity in patients between the right pPHG and the right middle temporal gyrus. There were no differences in the subjective ratings of memories between patients and control participants.

Conclusion:
the reduction of activity in the right pPHG is consistent with other evidence that TEA is a disorder of the medial temporal lobes (MTL) and further implicates the pPHG as a key region for contextual information. These MTL differences were most marked for recent and mid-life periods suggesting that, at least at the neural level, remote memories are more robust than recent memories. We also found reduced effective connectivity in patients between the right pPHG and the right middle temporal gyrus. This may reflect persisting effects of the seizures, the continued presence of sub-clinical epileptiform activity or the sequelae of subtle structural changes in the MTL in our patient group.

There are few clues as to the neural basis of selective long-term amnesia. We report group and single-case data to shed light on this issue. In a group study of patients with transient epileptic amnesia, there were no significant correlations between volumetric measures of the hippocampus and indices of accelerated long-term forgetting or longer-term autobiographical memory loss. Post-mortem investigations in a patient with temporal lobe epilepsy who showed accelerated long-term forgetting, together with a degree of autobiographical memory loss, yielded evidence of neuronal loss and gliosis in regions of both the right and the left hippocampus. Neuronal loss and gliosis were more evident in anterior than posterior hippocampus. These results indicate that the unusual forms of long-term forgetting seen in some patients with temporal lobe epilepsy have no gross anatomical correlate. The findings leave open the possibilities that subtle structural damage or subtle functional disturbance, perhaps in the form of subclinical epileptiform activity, underly epilepsy-related long-term amnesia.

Déjà vu (DV) is a widespread, fascinating and mysterious human experience. It occurs both in health and in disease, notably as an aura of temporal lobe epilepsy. This feeling of inappropriate familiarity has attracted interest from psychologists and neuroscientists for over a century, but still there is no widely agreed explanation for the phenomenon of non-pathological DV. Here we investigated differences in brain morphology between healthy subjects with and without DV using a novel multivariate neuroimaging technique, Source-Based Morphometry. The analysis revealed a set of cortical (predominantly mesiotemporal) and subcortical regions in which there was significantly less gray matter in subjects reporting DV. In these regions gray matter volume was inversely correlated with the frequency of DV. Our results demonstrate a structural correlate of DV in healthy individuals for the first time and support a neurological explanation for the phenomenon. We hypothesis that the observed local gray matter decrease in subjects experiencing DV reflects an alteration of hippocampal function and postnatal neurogenesis with resulting changes of volume in remote brain regions.

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 (TEA) is a recently recognised syndrome of epilepsy in which the principle manifestation of seizures is recurrent episodes of isolated memory loss. In this article, we describe the clinical and cognitive profile of this emerging syndrome, and present new data that provide at most weak support for its proposed relationship to cerebrovascular disease. TEA is often associated with two unusual forms of interictal memory impairment: accelerated long-term forgetting and remote memory impairment. We discuss the clinical and theoretical implications of these relatively novel cognitive deficits.

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.

The capacity for imagery, enabling us to visualise absent items and events, is a ubiquitous feature of our experience. This paper describes the case of a patient, MX, who abruptly lost the ability to generate visual images. He rated himself as experiencing almost no imagery on standard questionnaires, yet performed normally on standard tests of perception, visual imagery and visual memory. These unexpected findings were explored using functional MRI scanning (fMRI). Activation patterns while viewing famous faces were not significantly different between MX and controls, including expected activity in the fusiform gyrus. However, during attempted imagery, activation in MX's brain was significantly reduced in a network of posterior regions while activity in frontal regions was increased compared to controls. These findings are interpreted as suggesting that MX adopted a different cognitive strategy from controls when performing the imagery task. Evidence from experimental tasks thought to rely on mental imagery, such as the Brooks' matrices and mental rotation, support this interpretation. Taken together, these results indicate that successful performance in visual imagery and visual memory tasks can be dissociated from the phenomenal experience of visual imagery. (C) 2009 Elsevier Ltd. All rights reserved.

The authors describe and discuss a syndrome of transient psychogenic weakness usually mistaken for cataplexy but which has a close association with a depressive mental state. Four patients were referred to the authors with suspected neurological causes of transient weakness, including cataplexy in three cases, for whom the eventual diagnosis was of a functional or psychogenic motor disorder, related in most cases to depression. This variety of transient functional weakness is related to conditions such as nonepileptic attack disorder, persistent functional weakness, catatonia, and depressive motor retardation. These cases point to the existence of a syndrome of transient motor weakness which resembles cataplexy and has features in common with other forms of mood induced psychogenic weakness such as psychomotor retardation and catatonia. Psychogenic "pseudocataplexy" is a diagnostic consideration in patients with atypical cataplexy, especially in the context of mood disturbance. Despite its close resemblance to cataplexy, pseudocataplexy has a different pathogenesis and requires a different approach to management.

PURPOSE OF REVIEW: Case reports over the past 100 years have raised the possibility that epilepsy can manifest itself in episodes of amnesia. Recent research has established that this is indeed the case, and indicates that characteristic varieties of interictal memory disturbance co-occur with this form of epilepsy. RECENT FINDINGS: Transient epileptic amnesia is a distinctive syndrome of temporal lobe epilepsy principally affecting middle-aged people, giving rise to recurrent, brief attacks of amnesia, often occurring on waking. It is associated with novel forms of interictal memory disturbance: accelerated long-term forgetting, remote memory impairment, especially affecting autobiographical memory, and topographical memory impairment. The seizure focus lies in the medial temporal lobes. The seizures respond promptly to treatment, whereas the interictal impairments generally persist. Further work is required to establish whether the interictal memory impairment is due to physiological or structural disturbance. SUMMARY: Transient epileptic amnesia is an under-recognized but treatable cause of transient memory impairment. Accelerated long-term forgetting and autobiographical amnesia, which are invisible to standard memory tests, help to explain the discrepancy between normal test performance and prominent memory complaints among patients with epilepsy. Further investigation of these forms of memory impairment promises to shed light on processes of human memory.

BACKGROUND: Some patients awaken from coma (that is, open the eyes) but remain unresponsive (that is, only showing reflex movements without response to command). This syndrome has been coined vegetative state. We here present a new name for this challenging neurological condition: unresponsive wakefulness syndrome (abbreviated UWS). DISCUSSION: Many clinicians feel uncomfortable when referring to patients as vegetative. Indeed, to most of the lay public and media vegetative state has a pejorative connotation and seems inappropriately to refer to these patients as being vegetable-like. Some political and religious groups have hence felt the need to emphasize these vulnerable patients' rights as human beings. Moreover, since its first description over 35 years ago, an increasing number of functional neuroimaging and cognitive evoked potential studies have shown that physicians should be cautious to make strong claims about awareness in some patients without behavioral responses to command. Given these concerns regarding the negative associations intrinsic to the term vegetative state as well as the diagnostic errors and their potential effect on the treatment and care for these patients (who sometimes never recover behavioral signs of consciousness but often recover to what was recently coined a minimally conscious state) we here propose to replace the name. CONCLUSION: Since after 35 years the medical community has been unsuccessful in changing the pejorative image associated with the words vegetative state, we think it would be better to change the term itself. We here offer physicians the possibility to refer to this condition as unresponsive wakefulness syndrome or UWS. As this neutral descriptive term indicates, it refers to patients showing a number of clinical signs (hence syndrome) of unresponsiveness (that is, without response to commands) in the presence of wakefulness (that is, eye opening).

The relationship between mind and brain has philosophical, scientific, and practical implications. Two separate but related surveys from the University of Edinburgh (University students, n= 250) and the University of Liège (health-care workers, lay public, n= 1858) were performed to probe attitudes toward the mind-brain relationship and the variables that account for differences in views. Four statements were included, each relating to an aspect of the mind-brain relationship. The Edinburgh survey revealed a predominance of dualistic attitudes emphasizing the separateness of mind and brain. In the Liège survey, younger participants, women, and those with religious beliefs were more likely to agree that the mind and brain are separate, that some spiritual part of us survives death, that each of us has a soul that is separate from the body, and to deny the physicality of mind. Religious belief was found to be the best predictor for dualistic attitudes. Although the majority of health-care workers denied the distinction between consciousness and the soma, more than one-third of medical and paramedical professionals regarded mind and brain as separate entities. The findings of the study are in line with previous studies in developmental psychology and with surveys of scientists' attitudes toward the relationship between mind and brain. We suggest that the results are relevant to clinical practice, to the formulation of scientific questions about the nature of consciousness, and to the reception of scientific theories of consciousness by the general public.

We tend to regard consciousness as a fundamentally subjective phenomenon, yet we can only study it scientifically if it has objective, publicly visible, manifestations. This creates a central, recurring, tension in consciousness science which remains unresolved. On one 'objectivist' view, consciousness is not merely revealed but endowed by the process of reporting which makes it publicly accessible. On a contrasting 'subjectivist' view, consciousness, per se, is independent of the possibility of report, and indeed will always remain beyond the reach of direct observation. I shall explore this tension with examples drawn from clinical neurology, cognitive neuroscience and philosophy. The underlying aim of the paper is to open up the simple but profoundly difficult question that lurks in the background of consciousness science: what is it that are studying?

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.

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.

BACKGROUND: a 54-year-old man presented to a cognitive disorders clinic having experienced recurrent episodes of transient amnesia over a number of years. The attacks often occurred on waking, did not affect other cognitive abilities such as perception, language or judgment, and typically lasted about half an hour. The attacks were sometimes associated with olfactory hallucinations. Between amnestic episodes, the patient noticed a gradual deterioration in his recall of remote events, despite normal performance on standard memory tests. INVESTIGATIONS: Physical examination, laboratory tests, EEG, MRI brain scan, PET imaging, and neuropsychological assessment. DIAGNOSIS: Transient epileptic amnesia. MANAGEMENT: Anticonvulsant medication.

Hydrocephalus is a life-threatening condition presenting with a wide range of symptoms to a variety of specialties. Resulting delays in diagnosis can be hazardous. Doctors in all specialties should be familiar with the protean presentations of hydrocephalus.

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.

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.

Sherrington's late writings are often described as dualistic, yet Sherrington was deeply uneasy with theories that radically separate mind and brain. His questioning, open-minded and historically-informed approach to their relationship eschews dogmatic solutions.

INTRODUCTION: Wernicke's dysphasia and formal thought disorder are regarded as distinct diagnostic entities although both are linked to pathology in the left superior temporal gyrus (STG). We describe a patient with focal pathology in the left STG, giving rise acutely to a fluent dysphasia, which gradually evolved into formal thought disorder. METHOD: Clinical, neuropsychological, neuropsychiatric, and neuroradiological assessment. RESULTS: a right-handed patient, AJ, presented acutely with a fluent dysphasia. His speech output gradually evolved from undifferentiated jargon, through neologistic jargon, to an intelligible but bizarre form of discourse. Comprehension was relatively well preserved. Radiology revealed an arteriovenous malformation in the left middle, and inferior temporal gyri, with reduced perfusion of the left STG. Six months later his overt dysphasia had recovered, but his speech retained some of its previous characteristics, in particular a tendency to a loose association of ideas which now suggested a disorder of thought. CONCLUSIONS: AJ's case illustrates that comprehension may be unexpectedly preserved in jargon aphasia, and that an overtly linguistic impairment can gradually evolve to an apparent disorder of thought. Indistinguishable formal thought disorders can result from "structural" and "functional" pathology in the dominant temporal lobe.

A 67-year-old, right-handed woman became unable to recognize familiar faces following a period of nonconvulsive status epilepticus. Neuropsychological assessment revealed a relatively selective impairment of familiar face recognition in the absence of low-level visual deficits or widespread cognitive impairment. MRI scanning demonstrated an isolated lesion, probably a venous angioma, involving the left fusiform gyrus, mirror-symmetrical to the site typically linked to prosopagnosia. Potential explanations for the patient's prosopagnosia include seizure-related damage to a left fusiform region required for fully competent face recognition and damage to the contralateral fusiform gyrus via interhemispheric connections. Focal neuropsychological deficits in patients with refractory partial epilepsy who develop nonconvulsive status epilepticus may be underdiagnosed.

The concepts of consciousness and awareness are multifaceted, and steeped in cultural and intellectual history. This paper explores their complexities by way of a series of contrasts: (1) states of consciousness, such as wakefulness and sleep are contrasted with awareness, a term that picks out the contents of consciousness: these range across all our psychological capacities; the scientific background of the two concepts is briefly outlined; (2) consciousness is contrasted to self-consciousness, itself a complex term embracing self-detection, self-monitoring, self-recognition, theory of mind and self-knowledge; (3) "narrow" and "broad" senses of consciousness are contrasted, the former requiring mature human awareness capable of guiding action and self-report, the latter involving the much broader capacity to acquire and exploit knowledge; (4) an "inner" conception of consciousness, by which awareness is essentially private and beyond the reach of scientific scrutiny, is contrasted with an "outer" conception which allows that consciousness is intrinsically linked with capacities for intelligent behaviour; (5) finally "easy" and "hard" questions of consciousness are distinguished, the former involving the underlying neurobiology of wakefulness and awareness, the latter the allegedly more mysterious process by which biological processes generate experience: Whether this final distinction is valid is a focus of current debate. Varied interests converge on the study of consciousness from the sciences and the humanities, creating scope for interdisciplinary misunderstandings, but also for a fruitful dialogue. Health professionals treating disorders of consciousness should be aware both of its scientific complexities and of its broad cultural background, which influences the public understanding of these conditions.

BACKGROUND: Recurrent brief isolated episodes of amnesia associated with epileptiform discharges on EEG recordings have been interpreted as a distinct entity termed transient epileptic amnesia (TEA). Patients with TEA often complain of autobiographical amnesia for recent and remote events, but show normal anterograde memory. OBJECTIVE: to investigate (a) accelerated long term forgetting and (b) autobiographical memory in a group of patients with TEA. METHODS: Seven patients with TEA and seven age matched controls were evaluated on a range of anterograde memory tasks in two sessions separated by 6 weeks and by the Galton-Crovitz test of cued autobiographical memory. RESULTS: Patients with TEA showed abnormal long term forgetting of verbal material, with virtually no recall after 6 weeks. In addition, there was impaired recall of autobiographical memories from the time periods 1985-89 and 1990-94 but not from 1995-1999. CONCLUSIONS: TEA is associated with accelerated loss of new information and impaired remote autobiographical memory. There are a number of possible explanations including ongoing subclinical ictal activity, medial temporal lobe damage as a result of seizure, or subtle ischaemic pathology. Future analyses should seek to clarify the relationship between aetiology, seizure frequency, and degree of memory impairment.

A 50-year-old man presented with worsening, virtually lifelong, chorea and progressive behavioural disturbance, involving disinhibition and hoarding, over 10 years. Clinical assessment revealed chorea, dysarthria, areflexia, an inappropriately jovial, impulsive manner and neuropsychological evidence of frontosubcortical dysfunction. Investigation results included an elevated creatine kinase, caudate atrophy and hypoperfusion, acanthocytes in the peripheral blood and the McLeod phenotype. DNA studies demonstrated a single-base deletion at position 172 in exon 1 of the XK gene, giving rise to a premature stop codon at position 129 in exon 2.

In the diagnosis of functional weakness and sensory disturbance, positive physical signs are as important as absence of signs of disease. Motor signs, particularly Hoover's sign, are more reliable than sensory signs, but none should be used in isolation and must be interpreted in the overall context of the presentation. It should be borne in mind that a patient may have both a functional and an organic disorder.

OBJECTIVES: to investigate the roles of visual and tactile information in a dyspraxic patient with corticobasal degeneration (CBD) who showed dramatic facilitation in miming the use of a tool or object when he was given a tool to manipulate; and to study the nature of the praxic and neuropsychological deficits in CBD. METHODS: the subject had clinically diagnosed CBD, and exhibited alien limb behaviour and striking ideomotor dyspraxia. General neuropsychological evaluation focused on constructional and visuospatial abilities, calculation, verbal fluency, episodic and semantic memory, plus spelling and writing because impairments in this domain were presenting complaints. Four experiments assessed the roles of visual and tactile information in the facilitation of motor performance by tools. Experiment 1 evaluated the patient's performance of six limb transitive actions under six conditions: (1) after he described the relevant tool from memory, (2) after he was shown a line drawing of the tool, (3) after he was shown a real exemplar of the tool, (4) after he watched the experimenter perform the action, (5) while he was holding the tool, and (6) immediately after he had performed the action with the tool but with the tool removed from his grasp. Experiment 2 evaluated the use of the same six tools when the patient had tactile but no visual information (while he was blindfolded). Experiments 3 and 4 assessed performance of actions appropriate to the same six tools when the patient had either neutral or inappropriate tactile feedback-that is, while he was holding a non-tool object or a different tool. RESULTS: Miming of tool use was not facilitated by visual input; moreover, lack of visual information in the blindfolded condition did not reduce performance. The principal positive finding was a dramatic facilitation of the patient's ability to demonstrate object use when he was holding either the appropriate tool or a neutral object. Tools inappropriate to the requested action produced involuntary performance of the stimulus relevant action. CONCLUSIONS: Tactile stimulation was paramount in the facilitation of motor performance in tool use by this patient with CBD. This outcome suggests that tactile information should be included in models which hypothesise modality specific inputs to the action production system. Significant impairments in spelling and letter production that have not previously been reported in CBD have also been documented.

OBJECTIVES: to clarify the clinical and neuropsychological aspects of transient epileptic amnesia (TEA) based on 10 personally studied cases as well as review of 21 previously published cases; and to propose tentative diagnostic criteria for the diagnosis of TEA. METHODS: all 10 patients and informants underwent a standardised clinical interview. The radiological and neurophysiological (EEG) data were also reviewed in all cases. The diagnosis of transient epileptic amnesia was made on the basis of the following criteria: (1) there was a history of recurrent witnessed episodes of transient amnesia; (2) cognitive functions other than memory were judged to be intact during typical episodes by a reliable witness; (3) there was evidence for a diagnosis of epilepsy. This evidence was provided by either (a) wake or sleep EEG, or (b) the co-occurrence of other seizure types (if their roughly concurrent onset or close association with episodes of transient amnesia suggested a connection), or (c) a clear cut response to anticonvulsant therapy, or by a combination of these three factors. In addition all patients were administered a comprehensive neuropsychological test battery designed to assess verbal and non-verbal anterograde memory and retrograde memory for famous personalities and personal events. Their results were compared with those of 25 age and IQ matched normal controls. RESULTS: TEA usually begins in later life, with a mean age of 65 years in this series. Episodes are typically brief, lasting less than one hour, and recurrent, with a mean frequency of three a year. Attacks on waking are characteristic. Repetitive questioning occurs commonly during attacks. The anterograde amnesia during episodes is, however, often incomplete so that patients may later be able to "remember not being able to remember". The extent of the retrograde amnesia during attacks varies from days to years. Most patients experience other seizure types compatible with an origin in the temporal lobes, but transient amnesia is the only manifestation of epilepsy in about one third of patients. Epileptiform abnormalities arising from the temporal lobes are most often detected on interictal sleep EEG. Despite normal performance on tests of anterograde memory, many patients complain of persistent interictal disturbance of autobiographical memory, involving a significant but variable loss of recall for salient personal episodes. The epochs affected may predate the onset of epilepsy by many years. CONCLUSIONS: TEA is an identifiable syndrome and comprises episodic transient amnesia with an epileptic basis, without impairment of other aspects of cognitive function. Future studies should consider the question of whether TEA reflects ictal activity or a postictal state, and the mechanism of the persistent autobiographical amnesia. It is hypothesised that the latter may result in part from impairment of very long term memory consolidation as a result of epileptic activity in mesial temporal structures.

Transient global amnesia is an alarming but benign disorder of middle age, which prevents both the formation of new memories, and the retrieval of recently formed ones, for some hours. Research over the last 10 years has shed light on the epidemiology, neuropsychology, functional anatomy and differential diagnosis of this distinctive condition, and clarified its management.

The presence of oligoclonal bands (OCBs) of immunoglobulin G (IgG) in CSF provides evidence for the occurrence of a humoral immune response, but it is not always appreciated that the oligoclonal IgG may have originated in the serum. To determine the diagnostic significance of serum OCBs 146 patients with serum OCBs were identified among 1874 patients with suspected neurological disorders (7.6%). Clear diagnoses had been made in 112 of these patients: in 56 identical CSF and serum bands were present, revealing a systemic immune response, while in 46 additional unique CSF bands indicated that intrathecal IgG synthesis was also occurring. In the first group neoplasia and peripheral neuropathies accounted for over 50% of the diagnoses, infections and systemic inflammatory disorders for 32%, and multiple sclerosis was diagnosed in only one case. These figures contrast considerably with those reported for patients with CSF OCBs alone. Diagnoses in the second group of patients, with unique CSF OCBs in addition to serum OCBs, resembled those among patients with CSF OCBs alone. Examining CSF and serum in parallel for OCBs of IgG provides more diagnostic information than examining CSF alone, and the latter is potentially misleading.