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Clinical neurology uses conversation, detailed questioning, and discussion, observation, structured examination, and selective investigation to formulate the patients’ problems into an anatomical and pathological framework. The competent neurologist identifies and probes relevant components of the history, reliably elicits the physical signs, knows which investigations are necessary and relevant, appreciates the most likely underlying diagnosis and mechanism of disease, and communicates relevant information to the patient accurately, intelligibly, and sensitively. This system has evolved over several centuries, during which much knowledge has accumulated on structure and function in health and disease, the reliability of physical signs and laboratory investigations, and the nosology of disease.

This chapter investigates visual disturbances, which may be caused by diseases of the optic disc, optic nerve, optic chiasm, optic tract, lateral geniculate nucleus, optic radiations, and occipital lobe of the brain, as well as other brain areas involved in complex visual processing. Diagnosis of disturbances of the visual pathways requires both knowledge of their anatomy and physiology, and the ability to carry out a thorough neuro-ophthalmological examination which should enable (1) documentation of the character and extent of the visual disturbance, and (2) topographic localization of the lesion, so that the relevant investigative techniques, such as radiological imaging, can be appropriately requested.

Visual perceptual learning describes the improvement of visual perception with repeated practice. Previous research has established that the learning effects of perceptual training may be transferable to untrained stimulus attributes such as spatial location under certain circumstances. However, the mechanisms involved in transfer have not yet been fully elucidated. Here, we investigated the effect of altering training time course on the transferability of learning effects. Participants were trained on a motion direction discrimination task or a sinusoidal grating orientation discrimination task in a single visual hemifield. The 4000 training trials were either condensed into one day, or spread evenly across five training days. When participants were trained over a five-day period, there was transfer of learning to both the untrained visual hemifield and the untrained task. In contrast, when the same amount of training was condensed into a single day, participants did not show any transfer of learning. Thus, learning time course may influence the transferability of perceptual learning effects.

Neocortical-hippocampal interactions support new episodic (event) memories, but there is conflicting evidence about the dependence of remote episodic memories on the hippocampus. In line with systems consolidation and computational theories of episodic memory, evidence from model organisms suggests that the cornu ammonis 3 (CA3) hippocampal subfield supports recent, but not remote, episodic retrieval. In this study, we demonstrated that recent and remote memories were susceptible to a loss of episodic detail in human participants with focal bilateral damage to CA3. Graph theoretic analyses of 7.0-Tesla resting-state fMRI data revealed that CA3 damage disrupted functional integration across the medial temporal lobe (MTL) subsystem of the default network. The loss of functional integration in MTL subsystem regions was predictive of autobiographical episodic retrieval performance. We conclude that human CA3 is necessary for the retrieval of episodic memories long after their initial acquisition and functional integration of the default network is important for autobiographical episodic memory performance.

Objectives The evaluation of novel disease modifying drugs requires biomarkers that are simultaneously sensitive to disease state but resistant to the effects of background symptomatic treatment. Saccadic eye movement parameters have been proposed as a neurophysiological biomarker for Parkinson's disease (PD) and so it is important to know how they are affected by dopaminergic medication. Studies to date are conflicting: some have concluded that medication prolongs saccadic latencies while others suggest they are shortened. We aimed to characterise the effects of antiparkinsonian medication on prosaccadic and antisaccadic parameters in a large cohort of PD patients and age matched healthy controls and to survey the current literature in comparison to the study findings. Methods We studied saccades both off and on medication in 38 PD patients and 34 healthy controls (HC). Latencies, amplitudes, velocities, and directional errors were evaluated, using a published standardised protocol. We then combined this study and previously published literature in a meta-analysis of the effects of antiparkinsonian medication on prosaccadic latency (PSL). Results PSL is significantly prolonged by dopaminergic medication in PD, from a mean of 222.7 ms in the OFF medication state to a mean of 236.0 ms in the ON medication state (p = 0.028). This effect size is comparable to the difference between PD OFF medication and healthy control values. There was no statistically significant change in any other saccadic parameter with medication. Of particular note, antisaccadic latency was almost exactly the same on and off medication (means of 414.9 ms and 417.2 ms respectively, p = 0.97), while being almost 20% longer in PD patients compared to healthy controls (HC mean 357.2 ms; PD ON vs HC p = 0.015; PD OFF vs HC p = 0.0066). Conclusion PSL is significantly affected by dopaminergic medication which may complicate its use as a biomarker in drug trials. Antisaccadic latency is particularly interesting in this regard because it shows a large disease effect with no medication effect.

The cortico–basal–ganglia circuit plays a critical role in decision making on the basis of probabilistic information. Computational models have suggested how this circuit could compute the probabilities of actions being appropriate according to Bayes' theorem. These models predict that the subthalamic nucleus (STN) provides feedback that normalizes the neural representation of probabilities, such that if the probability of one action increases, the probabilities of all other available actions decrease. Here we report the results of an experiment testing a prediction of this theory that disrupting information processing in the STN with deep brain stimulation should abolish the normalization of the neural representation of probabilities. In our experiment, we asked patients with Parkinson's disease to saccade to a target that could appear in one of two locations, and the probability of the target appearing in each location was periodically changed. When the stimulator was switched off, the target probability affected the reaction times (RT) of patients in a similar way to healthy participants. Specifically, the RTs were shorter for more probable targets and, importantly, they were longer for the unlikely targets. When the stimulator was switched on, the patients were still faster for more probable targets, but critically they did not increase RTs as the target was becoming less likely. This pattern of results is consistent with the prediction of the model that the patients on DBS no longer normalized their neural representation of prior probabilities. We discuss alternative explanations for the data in the context of other published results.

Vertigo is one of the most common complaints in medicine. Despite its high prevalence, patients with vertigo often receive either inappropriate or inadequate treatment. The most important reasons for this deplorable situation are insufficient interdisciplinary cooperation, nonexistent standards in diagnostics and therapy, the relatively rare translations of basic science findings to clinical applications, and the scarcity of prospective controlled multicenter clinical trials. To overcome these problems, the German Center for Vertigo and Balance Disorders (DSGZ) started an initiative to establish a European Network for Vertigo and Balance Research called DIZZYNET. The central aim is to create a platform for collaboration and exchange among scientists, physicians, technicians, and physiotherapists in the fields of basic and translational research, clinical management, clinical trials, rehabilitation, and epidemiology. The network will also promote public awareness and help establish educational standards in the field. The DIZZYNET has the following objectives as regards structure and content: to focus on multidisciplinary translational research in vertigo and balance disorders, to develop interdisciplinary longitudinal and transversal networks for patient care by standardizing and personalizing the management of patients, to increase methodological competence by implementing common standards of practice and quality management, to internationalize the infrastructure for prospective multicenter clinical trials, to increase recruitment capacity for clinical trials, to create a common data base for patients with vertigo and balance disorders, to offer and promote attractive educational and career paths in a network of cooperating institutions. In the long term, the DIZZYNET should serve as an internationally visible network for interdisciplinary and multiprofessional research on vertigo and balance disorders. It ideally should equally attract the afflicted patients and those managing their disorders. DIZZYNET will not compete with the traditional national or international societies active in the field, but will function as an additional structure that addresses some of the above problems.

BackgroundHuman visual cortical area hMT+, like its homologue MT in the macaque monkey, has been shown to be particularly selective to visual motion. After damage to the primary visual cortex (V1), patients often exhibit preserved ability to detect moving stimuli, which is associated with neural activity in area hMT+. As an anatomical substrate underlying residual function in the absence of V1, promoting functional plasticity in hMT+ could potentially boost visual performance despite cortical damage.ObjectiveTo establish in healthy participants whether it is possible to use transcranial direct current stimulation (tDCS) over hMT+ to potentiate learning of visual motion direction discrimination.MethodsParticipants were trained daily for five days on a visual motion direction discrimination task. Task difficulty was increased as performance improved, by decreasing the proportion of coherently moving dots, such that participants were always performing at psychophysical threshold. tDCS, either anodal or sham, was applied daily during the 20-minute training session. Task performance was assessed at baseline and at the end of the training period.ResultsAll participants showed improved task performance both during and after training. Contrary to our hypothesis, anodal tDCS did not further improve performance compared to sham stimulation. Bayesian statistics indicated significant evidence in favour of the null hypothesis.ConclusionAnodal tDCS to hMT+ does not enhance visual motion direction discrimination learning in the young healthy visual system.

In his paper on page 518 of this issue, Dr Eric Nieman describes his medical journey of a progressive visual deterioration due to glaucoma, accompanied by the gradual development of increasingly distressing visual hallucinations - the Charles Bonnet syndrome. The eponym was coined by de Morsier in the 1930s, in recognition of Charles Bonnet (1720–1793), a renowned Genoese naturalist, philosopher and biologist, who in 1769 described the hallucinatory experiences of his grandfather Charles Lullin, a 89-year-old magistrate. Lullin described his subjective perception of visions of people, animals, and buildings of various shapes and sizes, associated with visual deterioration after bilateral cataract surgery. He had normal cognition and realised his visions were ‘fictions’ of his brain.1 Charles Bonnet syndrome occurs predominantly in elderly, visually impaired people. Around 11%–15% experience complex visual hallucinations, whereas a significantly greater number, between 41%–59%, experience elementary visual phenomena. Such individuals do not have psychological or cognitive …

Visual neglect is considerably exacerbated by increases in visual attentional load. These detrimental effects of attentional load are hypothesised to be dependent on an interplay between dysfunctional inter-hemispheric inhibitory dynamics and load-related modulation of activity in cortical areas such as the posterior parietal cortex (PPC). Continuous Theta Burst Stimulation (cTBS) over the contralesional PPC reduces neglect severity. It is unknown, however, whether such positive effects also operate in the presence of the detrimental effects of heightened attentional load. Here, we examined the effects of cTBS on neglect severity in overt visual search (i.e., with eye movements), as a function of high and low visual attentional load conditions. Performance was assessed on the basis of target detection rates and eye movements, in a computerised visual search task and in two paper-pencil tasks. cTBS significantly ameliorated target detection performance, independently of attentional load. These ameliorative effects were significantly larger in the high than the low load condition, thereby equating target detection across both conditions. Eye movement analyses revealed that the improvements were mediated by a redeployment of visual fixations to the contralesional visual field. These findings represent a substantive advance, because cTBS led to an unprecedented amelioration of overt search efficiency that was independent of visual attentional load.

Change blindness is a phenomenon of visual perception that occurs when a stimulus undergoes a change without this being noticed by its observer. Since it was first described in the 1990s, change blindness has provided a unique means to investigate the role of attention in visual processing. To date, the effect has been produced by changing images displayed on screen as well as changing people and objects in an individual’s environment. In this study, we combine these two approaches to directly compare the levels of change blindness produced in real-world and on-screen scenarios. We use a single series of museum artefacts and two groups of participants to simultaneously produce saccade-contingent change blindness in a real-world scenario, and camera pan-contingent change blindness in an on-screen scenario. We present the results in two parts. First, we find no significant difference between the mean levels of change blindness produced in on-screen and real-world scenarios by the same visual stimuli. Second, we identify a group of artefacts that were associated with a high level of change blindness in both scenarios and a group that were associated with a low level of change blindness in both scenarios. We suggest that the difference in change blindness levels results from bottom-up influences including the visible area and contrast of changes. We discuss the relation of these findings to our understanding of change detection as a part of visual processing, as well as the insights they offer to our understanding of the experience of viewing objects within a museum setting.

Background Cognitive impairment is well recognized in Parkinson's disease (PD), but when it begins to develop is unclear. The aim of this study was to identify early signs of cognitive impairment along with abnormalities in saccadic behavior in newly diagnosed unmedicated PD patients. Methods Nineteen drug-naive PD patients and 20 controls were examined using a battery of tests, including an antisaccade task, phonemic and semantic verbal fluencies, and a switching and rule finding task. Results With simple tasks, no differences were found between the two groups. However, cognitive performance of the two groups diverged with more complex tasks, occurring independently of PD-related motor impairment. Patients exhibited higher antisaccadic error rates and switch costs in the task switching test, and performed significantly worse in the rule finding task. Conclusions Certain cognitive domains and saccadic parameters are already significantly impoverished in newly diagnosed Parkinson's patients, even before the initiation of medication. © 2015 International Parkinson and Movement Disorder Society

Background: Recent basic and clinical evidence suggests amiloride may be neuroprotective in multiple sclerosis (MS) through the blockade of the acid sensing ion channel (ASIC). Objective: To examine the neuroprotective efficacy of amiloride in acute optic neuritis (ON). Methods: A total of 48 patients were recruited to a phase 2, double blind, single site, randomised controlled trial. Scanning laser polarimetry (GDx) at 6 months was the primary outcome measure and optical coherence tomography (OCT) and visual and electrophysiological measures were secondary outcome measures. Participants aged 18–55 years, ≤28 days of onset of first episode unilateral ON, were randomised to amiloride (10 mg daily for 5 months) or placebo ( clinicaltrials.gov , NCT 01802489). Results: Intention-to-treat (ITT) cohort consisted of 43 patients; 23 placebo and 20 amiloride. No significant drug-related adverse events occurred. No significant differences were found in GDx ( p = 0.840). Visual evoked potentials (VEP) were significantly prolonged in the amiloride group compared to placebo ( p = 0.004). All other secondary outcome measures showed no significant difference. Baseline analysis of OCT data demonstrated a significant pre-randomisation thinning of ganglion cell layer. Conclusion: Amiloride has not demonstrated any neuroprotective benefit within this trial paradigm, but future neuroprotective trials in ON should target the window of opportunity to maximise potential neuroprotective benefit.

Making robust inferences about the functional neuroanatomy of the brain is critically dependent on experimental techniques that examine the consequences of focal loss of brain function. Unfortunately, the use of the most comprehensive such technique-lesion-function mapping-is complicated by the need for time-consuming and subjective manual delineation of the lesions, greatly limiting the practicability of the approach. Here we exploit a recently-described general measure of statistical anomaly, zeta, to devise a fully-automated, high-dimensional algorithm for identifying the parameters of lesions within a brain image given a reference set of normal brain images. We proceed to evaluate such an algorithm in the context of diffusion-weighted imaging of the commonest type of lesion used in neuroanatomical research: ischaemic damage. Summary performance metrics exceed those previously published for diffusion-weighted imaging and approach the current gold standard-manual segmentation-sufficiently closely for fully-automated lesion-mapping studies to become a possibility. We apply the new method to 435 unselected images of patients with ischaemic stroke to derive a probabilistic map of the pattern of damage in lesions involving the occipital lobe, demonstrating the variation of anatomical resolvability of occipital areas so as to guide future lesion-function studies of the region. © 2012 Elsevier Ltd.

The effects of 4-aminopyridine (4-AP) on downbeat nystagmus (DBN) were analysed in terms of slow-phase velocity (SPV), stance, locomotion, visual acuity (VA), patient satisfaction and side effects using standardised questionnaires.Twenty-seven patients with DBN received 5 mg 4-AP four times a day or placebo for 3 days and 10 mg 4-AP four times a day or placebo for 4 days. Recordings were done before the first, 60 min after the first and 60 min after the last drug administration.SPV decreased from 2.42 deg/s at baseline to 1.38 deg/s with 5 mg 4-AP and to 2.03 deg/s with 10 mg 4-AP (p0.05; post hoc: 5 mg 4-AP: p=0.04). The rate of responders was 57%. Increasing age correlated with a 4-AP-related decrease in SPV (p0.05). Patients improved in the 'get-up-and-go test' with 4-AP (p0.001; post hoc: 5 mg: p=0.025; 10 mg: p0.001). Tandem-walk time (both p0.01) and tandem-walk error (4-AP: p=0.054; placebo: p=0.059) improved under 4-AP and placebo. Posturography showed that some patients improved with the 5 mg 4-AP dose, particularly older patients. Near VA increased from 0.59 at baseline to 0.66 with 5 mg 4-AP (p0.05). Patients with idiopathic DBN had the greatest benefit from 4-AP. There were no differences between 4-AP and placebo regarding patient satisfaction and side effects.4-AP reduced SPV of DBN, improved near VA and some locomotor parameters. 4-AP is a useful medication for DBN syndrome, older patients in particular benefit from the effects of 5 mg 4-AP on nystagmus and postural stability.

Making flexible associations between what we see and what we do is important for many everyday tasks. Previous work in patients with focal lesions has shown that the control of saccadic eye movements in such contexts relies on a network of areas in the frontal cerebral cortex. These regions are reciprocally connected with structures in the basal ganglia although the contribution of these sub-cortical structures to oculomotor control in complex tasks is not well understood. We report the performance of patients with idiopathic Parkinsons disease (PDs) in a test which required learning and switching between arbitrary cue-saccade rules. In Experiment 1 feedback was given following each response which reliably indicated which of the two possible rules was correct. PDs were slower to learn the first cue-saccade association presented, but did not show increased error or reaction time switch costs when switching between two rules within blocks. In a follow up experiment the feedback given by the computer was adjusted to be probabilistic such that executing a response based upon the “correct” rule only resulted in positive feedback on 80% of trials. Under these conditions patients were impaired in terms of response latencies and number of errors. In all conditions PDs showed multi-stepping/hypometria of saccades consistent with a motoric deficit in executing actions based on cognitive cues. The findings are consistent with a role for the nigrostriatal dopamine system in the reinforcement of saccade-response-outcome associations. Intact performance of PDs when associations are not stochastically reinforced suggests that striatal learning systems are complemented by cognitive representations of task rules which are unaffected in the early stages of PD., Highlights • We examine how People with Parkinsons learn rules linking visual cues and saccades. • Patients were slower to learn single colour-saccade direction rule mappings. • Patients made increased errors but no increase in rule “switch costs”. • The deficits related to dopamine and cortico-striatal circuitry. • The findings have relevance for understanding deficits in everyday tasks.

The analysis of saccades offers an opportunity to study a number of different cognitive processes, such as visuospatial attention, working memory, and volitional conflict. A study of saccades in patients with visuospatial hemineglect, who performed a visual search task, showed repeated fixations on targets previously discovered, yet they often failed to retain the information that a particular target had previously been discovered. High-resolution structural brain scanning showed that this abnormality was due either to a lesion in the right intraparietal sulcus or the right inferior frontal lobe. Detailed analysis of the scanpaths suggested that the former location was associated with an accumulating impairment in remapping target locations across saccades or impaired memory of previously inspected target locations, whereas the latter location was more consistent with a failure to inhibit responses to rightward locations. When combined with a spatial bias to the right, such deficits might explain why many neglect patients often reexamine rightward targets, at the expense of items to their left. The functions of the supplementary eye field (SEF), in the medial frontal lobe, in relation to saccade generation are controversial. A series of studies in a patient with a focal lesion of the right SEF has indicated an important role for the SEF in the rapid self-control of saccadic eye movements and in set-switching (i.e., implementing control in situations of response conflict when ongoing saccadic plans have to be changed rapidly), rather than monitoring errors. In a recent fMRI study of normal subjects, it was shown that the SEF is involved in implementing the resolution of any volitional conflict, whereas other presupplementary motor areas are involved in the generation of volitional plans and processing volitional conflict.

We review the latest literature on the neuropharmacological treatments for acquired nystagmus.Nystagmus may have a significant [corrected] impact on health, yet there is little scientific evidence on which to make firm recommendations for treatment. Acquired pendular nystagmus may respond to gabapentin or memantine; downbeat and upbeat nystagmus to aminopyridines; and periodic alternating nystagmus to baclofen. To improve treatment we need multi-centre, randomised controlled trials using standardised techniques in reporting objective outcomes, with good follow-up duration and careful reporting of side effects.

The Functional Rating Scale Taskforce for pre-Huntington Disease (FuRST-pHD) is a multinational, multidisciplinary initiative with the goal of developing a data-driven, comprehensive, psychometrically sound, rating scale for assessing symptoms and functional ability in prodromal and early Huntington disease (HD) gene expansion carriers. The process involves input from numerous sources to identify relevant symptom domains, including HD individuals, caregivers, and experts from a variety of fields, as well as knowledge gained from the analysis of data from ongoing large-scale studies in HD using existing clinical scales. This is an iterative process in which an ongoing series of field tests in prodromal (prHD) and early HD individuals provides the team with data on which to make decisions regarding which questions should undergo further development or testing and which should be excluded. We report here the development and assessment of the first iteration of interview questions aimed to assess functional impact of motor manifestations in prHD and early HD individuals.

Measuring the rate of finger tapping is a technique commonly used as an indicator of impairment in degenerative neurological conditions, such as Huntington's disease. The information it provides can be greatly enhanced by analysing not simply the overall tapping rate, but also the statistical characteristics of the individual times between each successive response. Recent technological improvements in the recording equipment allow the responses to be analysed extremely quickly, and permit modification of the task in the interest of greater clinical specificity. Here we illustrate its use with some pilot data from a group of manifest HD patients and age-matched controls. Even in this small cohort, differences in the responses are apparent that appear to relate to the severity of the disease as measured by conventional behavioural tests.

A patient with a lesion confined largely to the right inferior frontal gyrus was found to be impaired on tests of spatial working memory and executive functioning. By contrast, his pattern recognition was good. The patient's selective impairments are consistent with the view that prefrontal cortex contributes to processes involved in spatial working memory. The patient was also tested on a range of oculomotor paradigms, some of which required the temporary suppression of a saccadic response. He was unable to suppress making contra- or ipsilesional reflexive glances to peripheral stimuli on the "anti-saccade" paradigm, but his performance improved on delayed saccade, memory-guided saccade and fixation tasks. Although reflexive glances were observed under these conditions they occurred more frequently in response to contralesional stimuli than ipsilesional ones. Furthermore, the patient had no difficulty in performing anti-point movements with his ipsilesional hand. Thus, his inability to suppress reflexive glances on the anti-saccade task is not due to a generalised problem of "distractibility". The patient's deficits are discussed in terms of models of anti-saccade generation and are related to recent findings regarding the role of prefrontal cortex in working memory and visual attention.

When briefly presented with pairs of words, skilled readers can sometimes report words with migrated letters (e.g., they report hunt when presented with the words hint and hurt). This and other letter migration phenomena have been often used to investigate factors that influence reading such as letter position coding. However, the neural basis of letter migration is poorly understood. Previous evidence has implicated the right posterior parietal cortex (PPC) in processing visuospatial attributes and lexical properties during word reading. The aim of this study was to assess this putative role by combining an inhibitory TMS protocol with a letter migration paradigm, which was designed to examine the contributions of visuospatial attributes and lexical factors. Temporary interference with the right PPC led to three specific effects on letter migration. First, the number of letter migrations was significantly increased only in the group with active stimulation (vs. a sham stimulation group or a control group without stimulation), and there was no significant effect on other error types. Second, this effect occurred only when letter migration could result in a meaningful word (migration vs. control context). Third, the effect of active stimulation on the number of letter migrations was lateralized to target words presented on the left. Our study thus demonstrates that the right PPC plays a specific and causal role in the phenomenon of letter migration. The nature of this role cannot be explained solely in terms of visuospatial attention, rather it involves an interplay between visuospatial attentional and word reading-specific factors.

The brain regions that are critically associated with visual neglect have become intensely disputed. In particular, one study of middle cerebral artery (MCA) stroke patients has claimed that the key brain region associated with neglect is the mid portion of the superior temporal gyrus (STG), on the lateral surface of the right hemisphere, rather than the posterior parietal lobe. Such a result has wide-ranging implications for both our understanding of the normal function these cortical areas and the potential mechanisms underlying neglect. Here, we use novel high resolution MRI protocols to map the lesions of 35 right-hemisphere patients who had suffered either MCA or posterior cerebral artery (PCA) territory stroke. For patients with MCA territory strokes, the critical area involved in all neglect patients was the angular gyrus of the inferior parietal lobe (IPL). Although the STG was damaged in half of our MCA neglect patients, it was spared in the rest. For PCA territory strokes, all patients with neglect had lesions involving the parahippocampal region, on the medial surface of the temporal lobe. PCA patients without neglect did not have damage to this area. We conclude that damage to two posterior regions, one in the IPL and the other in the medial temporal lobe, is associated with neglect. Although some neglect patients do have damage to the STG, our findings challenge the recent influential proposal that lesions of this area are critically associated with neglect. Instead, our results implicate the angular gyrus and parahippocampal region in this role.

Although regions within the medial frontal cortex are known to be active during voluntary movements their precise role remains unclear. Here we combine functional imaging localisation with psychophysics to demonstrate a strikingly selective contralesional impairment in the ability to inhibit ongoing movement plans in a patient with a rare lesion involving the right pre-supplementary motor area (pre-SMA), but sparing the supplementary motor area (SMA). We find no corresponding delay in simple reaction times, and show that the inhibitory deficit is sensitive to the presence of competition between responses. The findings demonstrate that the pre-SMA plays a critical role in exerting control over voluntary actions in situations of response conflict. We discuss these findings in the context of a unified framework of pre-SMA function, and explore the degree to which extant data on this region can be explained by this function alone.

A 29-year-old right handed lady presented with a right one and a half syndrome secondary to ipsilateral pontine haemorrhage. Eight months later she complained of oscillopsia and developed vertical plane predominant ∼2 Hz pendular nystagmus. There was no pharyngeal, facial or diaphragmatic involvement, however, she had a subtle, synchronous palatal tremor and de novo features of inferior olivary nucleus hypertrophic degeneration were seen on repeat MRI. Oculopalatal tremor (OPT) is often misdiagnosed as acquired pendular nystagmus (APN) as palatal tremor may be subtle and asymptomatic. The pathogenesis of OPT is distinct from other causes of APN with implications for optimal treatment.

Aims To outine the use of Optic Neuritis as a model for neuroprotective trials To present baseline clinical data on the first 14 participants within the ACTION trial. Methods ACTION is a phase II randomised controlled trial of amiloride vs placebo in patients with acute optic neuritis, recruited within 28 days of onset. The primary outcome measure is comparison of 6 month retinal nerve fibre layer thickness between the affected and unaffected eye. Participants undergo OCT and GDx, high and low contrast visual acuity, colour vision, Humphrey visual fields, PERG, VEP, and MRI brain. Results 14 patients have been recruited from 47 referrals. Mean time from onset of symptoms to commencing the study drug is 14.7 days, median 13. Mean visual acuity in the affected eye is 50 letters (6/60), median 64 (6/30). 7 patients had T2 white matter lesions on baseline MRI imaging. One patient had a pre-existing diagnosis of multiple sclerosis. Conclusions Recruiting to clinical trials in acute optic neuritis is challenging but feasible. Ongoing and future neuroprotective trials in optic neuritis require a robust and motivated network of clinicians and researchers recognising the “window of opportunity” to facilitate timely referral.

Background One of the most promising categories of clinical biomarker in Parkinson9s disease is eye movement abnormalities, in particular visually guided horizontal saccades. Methods odern equipment permits the rapid acquisition of large datasets enabling highly accurate quantification and statistical analysis of saccadic abnormalities. We examined a cohort of 50 PD patients and 50 age and sex matched healthy controls using a portable non invasive infra-red oculometer to record horizontal (a) prosaccades and (b) antisaccades (a saccade in the opposite direction of an abruptly appearing visual stimulus). 420 trials were obtained per patient in less than 30 min. The latency distributions were analyzed using the LATER model and analysis of variance was used to compare the groups. Saccadic tasks were performed in single–task blocks (either blocks of prosaccades or blocks of antisaccades) and in a conflict task in mixed-task blocks (blocks of randomly interleaved pro- and antisaccades). Results PD patients displayed deficits in the antisaccadic task, with normal latencies in performing the prosaccades but higher error rates in performing an antisaccade than in controls. Conclusion Measurement of antisaccades may provide unique insights into the mechanisms of oculomotor control and its dysfunction in early Parkinson9s disease patients.

When we identify a visual object such as a word or letter, our ability to detect a second object is impaired if it appears within 400ms of the first. This phenomenon has been termed the attentional blink or dwell time and is a measure of our ability to allocate attention over time (temporal attention). Patients with unilateral visual neglect are unaware of people or objects contralateral to their lesion. They are considered to have a disorder of attending to a particular location in space (spatial attention). Here we examined the non-spatial temporal dynamics of attention in patients, using a protocol for assessing the attentional blink. Neglect patients with right parietal, frontal or basal ganglia strokes had an abnormally severe and protracted attentional blink When they identified a letter, their awareness of a subsequent letter was significantly diminished for a length of time that was three times as long as for individuals without neglect. Our results demonstrate for the first time that visual neglect is a disorder of directing attention in time, as well as space.

In the paper by Thurtell and colleagues,1 two patients with epilepsy are described in whom in one stimulation over the frontal eye field (FEF) resulted in dysconjugate contraversive horizontal eye movements and in the other similar eye movements were observed as a result of focal seizures (see page 683) . The neural system controlling eye movements, particularly rapid conjugate versive movements, called saccades, is one of the most thoroughly understood neural circuits in the brain. It contains a number of cortical centres, …

A cellular model of the primate retina has been developed. Unlike existing models, it incorporates spatial non-uniformities, such as the random arrangement of L and M cones, and the radial dilation with eccentricity. Based on a population of ganglion cell activities, colour-image representation is modelled with the luminance and the R–G opponent channels. The developed model reproduces experimentally known properties in temporal and spatial vision. Furthermore, spatio-temporally coupled properties such as transition from positive to negative phases in an afterimage, are recapped. In colour vision, the model can explain the insensitivity in our colour perception to the L/M cone ratio.

Visual prostheses for the restoration of functional vision are currently under development. To guide prosthesis research and allow for an accurate prognosis of functional gain, simulating the experience of a retinal prosthesis in healthy individuals is desirable. Current simulation paradigms lack crucial aspects of the prosthetic experience such as realistic head- and eye-position-dependent image presentation. We developed a simulation paradigm that used a head-mounted camera and eye tracker to lock the simulation to the point of fixation. We evaluated visual acuity, object recognition and manipulation, and wayfinding under simulated prosthetic vision. We explored three ways of optimizing the information content of the prosthetic visual image: Full-Field representation (wide visual angle, low sampling frequency), Region of Interest (ROI; narrow visible angle, high sampling frequency), and Fisheye (high sampling frequency in the center, progressively lower resolution toward the edges). Full-Field representation facilitated visual search and navigation, whereas ROI improved visual acuity. The Fisheye representation, designed to incorporate the benefits of both Full-Field representation and ROI, performed similarly to ROI with subjects unable to capitalize on the peripheral data. The observation that different image representation conditions prove advantageous for different tasks should be taken into account in the process of designing and testing new visual prosthesis prototypes.

Summary Human primary visual cortex (V1) has long been associated with learning simple low-level visual discriminations [1] and is classically considered outside of neural systems that support high-level cognitive behavior in contexts that differ from the original conditions of learning, such as recognition memory [2, 3]. Here, we used a novel fMRI-based dichoptic masking protocol—designed to induce activity in V1, without modulation from visual awareness—to test whether human V1 is implicated in human observers rapidly learning and then later (15–20 min) recognizing a non-conscious and complex (second-order) visuospatial sequence. Learning was associated with a change in V1 activity, as part of a temporo-occipital and basal ganglia network, which is at variance with the cortico-cerebellar network identified in prior studies of “implicit” sequence learning that involved motor responses and visible stimuli (e.g., [4]). Recognition memory was associated with V1 activity, as part of a temporo-occipital network involving the hippocampus, under conditions that were not imputable to mechanisms associated with conscious retrieval. Notably, the V1 responses during learning and recognition separately predicted non-conscious recognition memory, and functional coupling between V1 and the hippocampus was enhanced for old retrieval cues. The results provide a basis for novel hypotheses about the signals that can drive recognition memory, because these data (1) identify human V1 with a memory network that can code complex associative serial visuospatial information and support later non-conscious recognition memory-guided behavior (cf. [5]) and (2) align with mouse models of experience-dependent V1 plasticity in learning and memory [6]., Highlights • Sequence learning and recognition memory can operate without visual awareness • V1, hippocampus, and basal ganglia support learning of a non-conscious sequence • Old/new status of non-conscious recognition probes modulates V1-hippocampal coupling • V1 activity predicts non-conscious recognition memory performance, Rosenthal et al. demonstrate that responses in human primary visual cortex (V1) support perceptual learning and recognition of a complex and non-conscious visuospatial sequence, and predict high-level, non-conscious recognition memory performance. These results elaborate on V1’s established role in simple, low-level perceptual learning.

Homonymous visual field loss is a common consequence of stroke and traumatic brain injury. It is associated with an adverse functional prognosis and has implications on day-to-day activities such as driving, reading, and safe navigation. Early recovery is expected in around half of cases, and may be associated with a return in V1 activity. In stable disease, recovery is unlikely beyond 3 and certainly 6 months. Rehabilitative approaches generally target three main areas, encompassing a range of techniques with variable success: visual aids aim to expand or relocate the affected visual field; eye movement training builds upon compensatory strategies to improve explorative saccades; visual field restitution aims to improve visual processing within the damaged field itself. All these approaches seem to offer modest improvements with repeated practice, with none clearly superior to the rest. However, a number of areas are demonstrating particular promise currently, including simple web-based training initiatives, and work on neuroimaging and learning. The research interest in this area is encouraging, and it is to be hoped that future trials can better untangle and control for the number of complicated confounds, so that we will be in a much better position to evaluate and select the most appropriate therapy for patients. © 2012 Elsevier Masson SAS.

The role of the primary visual cortex in visual mental imagery has provided significant debate in the imagery literature. Functional neuroimaging studies show considerable variation depending on task and technique. Patient studies can be difficult to interpret due to the diverse nature of cortical damage. The type of cortical damage in patient SBR is exceedingly rare as it is restricted to the gray matter of the calcarine sulcus. In this study, we show that in spite of his near-complete cortical blindness, SBR exhibits vivid visual mental imagery both behaviorally and when measured with functional magnetic resonance imaging. The pattern of cortical activation to visual mental imagery in SBR is indistinguishable from individual sighted subjects, in contrast to the visual perceptual responses, which are greatly attenuated. Electronic supplementary material The online version of this article (doi:10.1007/s00415-011-6299-z) contains supplementary material, which is available to authorized users.