Targeted detection and repair of a spinal dural defect associated with successful biochemical resolution of subarachnoid bleeding in classical infratentorial superficial siderosis.

BACKGROUND AND IMPORTANCE  : Classical infratentorial superficial siderosis (iSS) is characterised by repeated insidious bleeding into the subarachnoid space, leading to haemosiderin deposition within the subpial layers of the brainstem, cerebellum and spinal cord, sometimes with supratentorial involvement. Although nearly always associated with a dural defect (usually from previous trauma or neurosurgery) there is little evidence to support definitive investigation and management strategies. Here, we present a novel investigation strategy to identify a dural defect and subsequent successful surgical repair with biochemical resolution of subarachnoid bleeding. CLINICAL PRESENTATION: A 55-year-old gentleman presented with a 15-year progressive history of sensorineural deafness, followed by a slowly worsening gait ataxia. He had previously sustained cranio-spinal trauma. On examination there were features of myelopathy and ataxia. MRI demonstrated classical iSS, affecting cerebellum and cerebral cortices, with a cervicothoracic epidural CSF collection. Lumbar puncture (LP) revealed elevated ferritin 413 ng/mL and red cell count of 4160. Reverse CT myelography, a novel technique involving contrast injection into the collection, delineated a dural defect at the T9/T10 level that was not present on conventional myelography. Following surgical repair, repeat LP twelve months later demonstrated biochemical improvement (ferritin 18 ng/mL, red cells < 1). There was no further neurological deterioration in symptoms during eighteen months follow-up. CONCLUSION: We show the value of a rational targeted investigation pathway in identifying a surgically reparable dural defect underlying classical iSS. We also provide proof of concept that surgical repair can facilitate biochemical resolution of subarachnoid bleeding and might prevent progression of neurological disability.

Time to retire 'New daily persistent headache': Mode of onset of chronic migraine and tension-type headache.

New daily persistent headache is described as an enigmatic condition with daily headache from onset. It has posed challenges diagnostically and therapeutically.Methods: We conducted a study of patients referred to headache services based in Central and North-East London, United Kingdom, meeting the International Classificaiton of Headache Disorders - 3 criteria for New daily persistent headache. Information on demographics, phenotype and treatment responses were collected. The syndrome of the daily headache was also classified according any other ICHD-3-defined syndrome.Results: Of 162 patients, females comprised 68.5% with median age of onset 35 years. The daily headache experienced was chronic migraine in 89.7% and tension-type headache in 8.8%. Thunderclap-onset New daily persistent headache occurred in 14.8%. More than one headache syndrome was experienced in 15.4%, including cough, hypnic, sexual and stabbing headache. All aura types were experienced, most commonly brainstem aura in 39%. Prior headache was reported 53.7%. A persisting sub-form was present in 51.2%, relapsing remitting in 12.3% and 14.0% reported improvement; 19.8% were lost to follow-up. Only 11.1% reported an antecedent trigger. The most common premorbid disorders were psychiatric in 35.7%. A fifth improved on preventative medication, most commonly amitriptyline, propranolol and topiramate.Conclusion: Our cohort of New daily persistent headache is consistent with a mode of onset of migraine and tension-type headache which occurs in predisposed individuals.

Vestibulo-perceptual influences upon the vestibulo-spinal reflex.

The vestibular system facilitates gaze and postural stability via the vestibulo-ocular (VOR) and vestibulo-spinal reflexes, respectively. Cortical and perceptual mechanisms can modulate long-duration VOR responses, but little is known about whether high-order neural phenomena can modulate short-latency vestibulo-spinal responses. Here, we investigate this by assessing click-evoked cervical vestibular myogenic-evoked potentials (VEMPS) during visual roll motion that elicited an illusionary sensation of self-motion (i.e. vection). We observed that during vection, the amplitude of the VEMPs was enhanced when compared to baseline measures. This modulation in VEMP amplitude was positively correlated with the subjective reports of vection strength. That is, those subjects reporting greater subjective vection scores exhibited a greater increase in VEMP amplitude. Control experiments showed that simple arousal (cold-induced discomfort) also increased VEMP amplitude but that, unlike vection, it did not modulate VEMP amplitude linearly. In agreement, small-field visual roll motion that did not induce vection failed to increase VEMP amplitude. Taken together, our results demonstrate that vection can modify the response of vestibulo-collic reflexes. Even short-latency brainstem vestibulo-spinal reflexes are influenced by high-order mechanisms, illustrating the functional importance of perceptual mechanisms in human postural control. As VEMPs are inhibitory responses, we argue that the findings may represent a mechanism whereby high-order CNS mechanisms reduce activity levels in vestibulo-collic reflexes, necessary for instance when voluntary head movements need to be performed.

Interhemispheric control of sensory cue integration and self-motion perception.

Spatial orientation necessitates the integration of visual and vestibular sensory cues, in-turn facilitating self-motion perception. However, the neural mechanisms underpinning sensory integration remain unknown. Recently we have illustrated that spatial orientation and vestibular thresholds are influenced by interhemispheric asymmetries associated with the posterior parietal cortices (PPC) that predominantly house the vestibulo-cortical network. Given that sensory integration is a prerequisite to both spatial orientation and motion perception, we hypothesized that sensory integration is similarly subject to interhemispheric influences. Accordingly, we explored the relationship between vestibulo-cortical dominance - assessed using a biomarker, the degree of vestibular-nystagmus suppression following transcranial direct current stimulation over the PPC - with visual dependence measures obtained during performance of a sensory integration task (the rod-and-disk task). We observed that the degree of visual dependence was correlated with vestibulo-cortical dominance. Specifically, individuals with greater right hemispheric vestibulo-cortical dominance had reduced visual dependence. We proceeded to assess the significance of such dominance on behavior by correlating measures of visual dependence with self-motion perception in healthy subjects. We observed that right-handed individuals experienced illusionary self-motion (vection) quicker than left-handers and that the degree of vestibular cortical dominance was correlated with the time taken to experience vection, only during conditions that induced interhemispheric conflict. To conclude, we demonstrate that interhemispheric asymmetries associated with vestibulo-cortical processing in the PPC functionally and mechanistically link sensory integration and self-motion perception, facilitating spatial orientation. Our findings highlight the importance of dynamic interhemispheric competition upon control of vestibular behavior in humans.

Development of a web-based tool for undergraduate engagement in medical research; the ProjectPal experience.

BACKGROUND: We report the development and evaluation of a web-based tool designed to facilitate student extra-curricular engagement in medical research through project matching students with academic supervisors. UK based university students were surveyed to explore their perceptions of undergraduate research, barriers and facilitators to current engagement. Following this, an online web-based intervention ( www.ProjectPal.org ) was developed to support access of students to research projects and supervisors. A pilot intervention was undertaken across a London-based university in January 2013 to February 2016. In March 2016, anonymised data were extracted from the prospective data log for analysis of website engagement and usage. Supervisors were surveyed to evaluate the website and student outputs. RESULTS: Fifty-one students responded to the electronic survey. Twenty-four (47%) reported frustration at a perceived lack of opportunities to carry out extra-curricular academic projects. Major barriers to engaging in undergraduate research reported were difficulties in identifying suitable supervisors (33/51; 65%) and time pressures (36/51; 71%) associated with this. Students reported being opportunistic in their engagement with undergraduate research. Following implementation of the website, 438 students signed up to ProjectPal and the website was accessed 1357 times. Access increased on a yearly basis. Overall, 70 projects were advertised by 35 supervisors. There were 86 applications made by students for these projects. By February 2016, the 70 projects had generated 5 peer-review publications with a further 7 manuscripts under peer-review, 14 national presentations, and 1 national prize. CONCLUSION: The use of an online platform to promote undergraduate engagement with extra-curricular research appears to facilitate extra-curricular engagement with research. Further work to understand the impact compared to normal opportunistic practices in enhancing student engagement is now underway.

Biased numerical cognition impairs economic decision-making in Parkinson's disease.

OBJECTIVE: Previous findings suggest a context-dependent bihemispheric allocation of numerical magnitude. Accordingly, we predicted that lateralized motor symptoms in Parkinson's disease (PD), which reflect hemispheric asymmetries, would induce systematic lateralized biases in numerical cognition and have a subsequent influence on decision-making. METHODS: In 20 PD patients and matched healthy controls we assessed numerical cognition using a number-pair bisection and random number generation task. Decision-making was assessed using both the dictator game and a validated questionnaire. RESULTS: PD patients with predominant right-sided motor symptoms exhibited pathological biases toward smaller numerical magnitudes and formulated less favorable prosocial choices during a neuroeconomics task (i.e., dictator game). Conversely, patients with left-sided motor symptoms exhibited pathological biases toward larger numerical magnitudes and formulated more generous prosocial choices. Our account of context-dependent hemispheric allocation of numerical magnitude in PD was corroborated by applying our data to a pre-existing computational model and observing significant concordance. Notably, both numerical biasing and impaired decision-making were correlated with motor asymmetry. INTERPRETATION: Accordingly, motor asymmetry and functional impairment of cognitive processes in PD can be functionally intertwined. To conclude, our findings demonstrate context-dependent hemispheric allocation and encoding of numerical magnitude in PD and how biases in numerical magnitude allocation in Parkinsonian patients can correspondingly impair economic decision-making.

Influence of biases in numerical magnitude allocation on human prosocial decision making.

Over the past decade neuroscientific research has attempted to probe the neurobiological underpinnings of human prosocial decision making. Such research has almost ubiquitously employed tasks such as the dictator game or similar variations (i.e., ultimatum game). Considering the explicit numerical nature of such tasks, it is surprising that the influence of numerical cognition on decision making during task performance remains unknown. While performing these tasks, participants typically tend to anchor on a 50:50 split that necessitates an explicit numerical judgement (i.e., number-pair bisection). Accordingly, we hypothesize that the decision-making process during the dictator game recruits overlapping cognitive processes to those known to be engaged during number-pair bisection. We observed that biases in numerical magnitude allocation correlated with the formulation of decisions during the dictator game. That is, intrinsic biases toward smaller numerical magnitudes were associated with the formulation of less favorable decisions, whereas biases toward larger magnitudes were associated with more favorable choices. We proceeded to corroborate this relationship by subliminally and systematically inducing biases in numerical magnitude toward either higher or lower numbers using a visuo-vestibular stimulation paradigm. Such subliminal alterations in numerical magnitude allocation led to proportional and corresponding changes to an individual's decision making during the dictator game. Critically, no relationship was observed between neither intrinsic nor induced biases in numerical magnitude on decision making when assessed using a nonnumerical-based prosocial questionnaire. Our findings demonstrate numerical influences on decisions formulated during the dictator game and highlight the necessity to control for confounds associated with numerical cognition in human decision-making paradigms.NEW & NOTEWORTHY We demonstrate that intrinsic biases in numerical magnitude can directly predict the amount of money donated by an individual to an anonymous stranger during the dictator game. Furthermore, subliminally inducing perceptual biases in numerical-magnitude allocation can actively drive prosocial choices in the corresponding direction. Our findings provide evidence for numerical influences on decision making during performance of the dictator game. Accordingly, without the implementation of an adequate control for numerical influences, the dictator game and other tasks with an inherent numerical component (i.e., ultimatum game) should be employed with caution in the assessment of human behavior.

Downregulation of early visual cortex excitability mediates oscillopsia suppression.

OBJECTIVE: To identify in an observational study the neurophysiologic mechanisms that mediate adaptation to oscillopsia in patients with bilateral vestibular failure (BVF). METHODS: We directly probe the hypothesis that adaptive changes that mediate oscillopsia suppression implicate the early visual-cortex (V1/V2). Accordingly, we investigated V1/V2 excitability using transcranial magnetic stimulation (TMS) in 12 avestibular patients and 12 healthy controls. Specifically, we assessed TMS-induced phosphene thresholds at baseline and cortical excitability changes while performing a visual motion adaptation paradigm during the following conditions: baseline measures (i.e., static), during visual motion (i.e., motion before adaptation), and during visual motion after 5 minutes of unidirectional visual motion adaptation (i.e., motion adapted). RESULTS: Patients had significantly higher baseline phosphene thresholds, reflecting an underlying adaptive mechanism. Individual thresholds were correlated with oscillopsia symptom load. During the visual motion adaptation condition, no differences in excitability at baseline were observed, but during both the motion before adaptation and motion adapted conditions, we observed significantly attenuated cortical excitability in patients. Again, this attenuation in excitability was stronger in less symptomatic patients. CONCLUSIONS: Our findings provide neurophysiologic evidence that cortically mediated adaptive mechanisms in V1/V2 play a critical role in suppressing oscillopsia in patients with BVF.