The multifocal visual evoked cortical potential in visual field mapping: a methodological study.

The application of multifocal techniques to the visual evoked cortical potential permits objective electrophysiological mapping of the visual field. The multifocal visual evoked cortical potential (mfVECP) presents several technical challenges. Signals are small, are influenced by a number of sources of noise and waveforms vary both across the visual field and between subjects due to the complex geometry of the visual cortex. Together these factors hamper the ability to distinguish between a mfVECP response from the healthy visual pathway, and a response that is reduced or absent and is therefore representative of pathology. This thesis presents a series of methodological investigations with the aim of maximising the information available in the recorded electrophysiological response, thereby improving the performance of the mfVECP. A novel method of calculating the signal to noise ratio (SNR) of mfVECP waveform responses is introduced. A noise estimate unrelated to the response of the visual cortex to the visual stimulus is created. This is achieved by cross-correlating m-sequences which are created when the orthogonal set of m-sequences are created but are not used to control a stimulus region, with the physiological record. This metric is compared to the approach of defining noise within a delayed time window and shows good correlation. ROC analysis indicates a small improvement in the ability to distinguish between physiological waveform responses and noise. Defining the signal window as 45-250ms is recommended. Signal quality is improved by post-acquisition bandwidth filtering. A wide range of bandwidths are compared and the greatest gains are seen with a bandpass of 3 to 20Hz applied after cross-correlation. Responses evoked when stimulation is delivered using a cathode ray tube (CRT) and a liquid crystal display (LCD) projector system are compared. The mode of stimulus delivery affects the waveshape of responses. A significantly higher SNR is seen in waveforms is shown in waveforms evoked by an m=16 bit m-sequence delivered by a CRT monitor. Differences for shorter m-sequences were not statistically significant. The area of the visual field which can usefully be tested is investigated by increasing the field of view of stimulation from 20° to 40° of radius in 10° increments. A field of view of 30° of radius is shown to provide stimulation of as much of the visual field as possible without losing signal quality. Stimulation rates of 12.5 to 75Hz are compared. Slowing the stimulation rate produced increases waveform amplitudes, latencies and SNR values. The best performance was achieved with 25Hz stimulation. It is shown that a six-minute recording stimulated at 25Hz is superior to an eight-minute, 75Hz acquisition. An electrophysiology system capable of providing multifocal stimulation, synchronising with the acquisition of data from a large number of electrodes and performing cross-correlation has been created. This is a powerful system which permits the interrogation of the dipoles evoked within the complex geometry of the visual cortex from a very large number of orientations, which will improve detection ability. The system has been used to compare the performance of 16 monopolar recording channels in detecting responses to stimulation throughout the visual field. A selection of four electrodes which maximise the available information throughout the visual field has been made. It is shown that a several combinations of four electrodes provide good responses throughout the visual field, but that it is important to have them distributed on either hemisphere and above and below Oz. A series of investigations have indicated methods of maximising the available information in mfVECP recordings and progress the technique towards becoming a robust clinical tool. A powerful multichannel multifocal electrophysiology system has been created, with the ability to simultaneously acquire data from a very large number of bipolar recording channels and thereby detect many small dipole responses to stimulation of many small areas of the visual field. This will be an invaluable tool in future investigations. Performance has been shown to improve when the presence or absence of a waveform is determined by a novel SNR metric, when data is filtered post-acquisition through a 3-20Hz bandpass after cross-correlation and when a CRT is used to deliver the stimulus. The field of view of stimulation can usefully be extended to a radius of 30° when a 60-region dartboard pattern is employed. Performance can be enhanced at the same time as acquisition time is reduced by 25%, by the use of a 25Hz rate of stimulation instead of the frequently employed rate of 75Hz

Proprioceptive contribution to oculomotor control in humans

This work was supported by an award from the Wellcome Trust Institutional Strategic Support Fund at the University of St Andrews, grant code 204821/Z/16/Z (DB).Stretch receptors in the extraocular muscles (EOMs) inform the central nervous system about the rotation of one's own eyes in the orbits. Whereas fine control of the skeletal muscles hinges critically on proprioceptive feedback, the role of proprioception in oculomotor control remains unclear. Human behavioural studies provide evidence for EOM proprioception in oculomotor control, however, behavioural and electrophysiological studies in the macaque do not. Unlike macaques, humans possess numerous muscle spindles in their EOMs. To find out whether the human oculomotor nuclei respond to proprioceptive feedback we used functional magnetic resonance imaging (fMRI). With their eyes closed, participants placed their right index finger on the eyelid at the outer corner of the right eye. When prompted by a sound, they pushed the eyeball gently and briefly towards the nose. Control conditions separated out motor and tactile task components. The stretch of the right lateral rectus muscle was associated with activation of the left oculomotor nucleus and subthreshold activation of the left abducens nucleus. Because these nuclei control the horizontal movements of the left eye, we hypothesized that proprioceptive stimulation of the right EOM triggered left eye movement. To test this, we followed up with an eye-tracking experiment in complete darkness using the same behavioural task as in the fMRI study. The left eye moved actively in the direction of the passive displacement of the right eye, albeit with a smaller amplitude. Eye tracking corroborated neuroimaging findings to suggest a proprioceptive contribution to ocular alignment.Publisher PDFPeer reviewe

fMRI evidence supporting the role of memory conflict in the déjà vu experience

This research was funded by an anonymous donation to the School of Psychology and Neuroscience at the University of St Andrews.Attempts to generate déjà vu experimentally have largely focused on engineering partial familiarity for stimuli, relying on an ensuing, but unprompted evaluation of conflict to generate the experience. Without verification that experimentally-generated familiarity is accompanied by the awareness of stimulus novelty, these experimental procedures potentially provide an incomplete déjà vu analogue. We used a modified version of the Deese-Roediger-McDermott (DRM) false memory procedure to generate both familiarity and novelty within a déjà vu analogue—we coupled experimentally-generated familiarity with cues indicating that the familiarity was erroneous, using this additional source of mnemonic information to generate cognitive conflict in our participants. We collected fMRI and behavioural data from 21 participants, 16 of whom reported déjà vu. Using univariate contrasts we identified brain regions associated with mnemonic conflict, including the anterior cingulate cortex, medial prefrontal cortex and parietal cortex. This is the first experiment to image an analogue of the déjà vu experience in healthy volunteers. The increased likelihood of déjà vu reports to DRM critical lures correctly identified as “new”, and the activation of neural substrates supporting the experience of cognitive conflict during déjà vu, suggest that the resolution of memory conflict may play an integral role in déjà vu.PostprintPeer reviewe

Epidemiology of chronic pain in children and adolescents : a protocol for a systematic review update

Funding This work was supported by an operating grant from the Canadian Institutes of Health Research (FRN167902) awarded to CTC and funding from the Dalhousie Medical Research Foundation (DMRF). CTC is the senior author and is supported by a Tier 1 Canada Research Chair with infrastructure support from the Canada Foundation for Innovation. CLL is supported by an IWK Health Centre Summer Studentship (1025420). PRT is supported by a Research Nova Scotia Scholars Award, a Nova Scotia Graduate Scholarship and an IWK Graduate Studentship Award, and is a trainee member of Pain Child Health (PICH).Peer reviewedPublisher PD

Incidence of community-acquired lower respiratory tract infections and pneumonia among older adults in the United Kingdom: a population-based study.

Community-acquired lower respiratory tract infections (LRTI) and pneumonia (CAP) are common causes of morbidity and mortality among those aged ≥65 years; a growing population in many countries. Detailed incidence estimates for these infections among older adults in the United Kingdom (UK) are lacking. We used electronic general practice records from the Clinical Practice Research Data link, linked to Hospital Episode Statistics inpatient data, to estimate incidence of community-acquired LRTI and CAP among UK older adults between April 1997-March 2011, by age, sex, region and deprivation quintile. Levels of antibiotic prescribing were also assessed. LRTI incidence increased with fluctuations over time, was higher in men than women aged ≥70 and increased with age from 92.21 episodes/1000 person-years (65-69 years) to 187.91/1000 (85-89 years). CAP incidence increased more markedly with age, from 2.81 to 21.81 episodes/1000 person-years respectively, and was higher among men. For both infection groups, increases over time were attenuated after age-standardisation, indicating that these rises were largely due to population aging. Rates among those in the most deprived quintile were around 70% higher than the least deprived and were generally higher in the North of England. GP antibiotic prescribing rates were high for LRTI but lower for CAP (mostly due to immediate hospitalisation). This is the first study to provide long-term detailed incidence estimates of community-acquired LRTI and CAP in UK older individuals, taking person-time at risk into account. The summary incidence commonly presented for the ≥65 age group considerably underestimates LRTI/CAP rates, particularly among older individuals within this group. Our methodology and findings are likely to be highly relevant to health planners and researchers in other countries with aging populations

Disrupted limbic-prefrontal effective connectivity in response to fearful faces in lifetime depression

Background: Multiple brain imaging studies of negative emotional bias in major depressive disorder (MDD) have used images of fearful facial expressions and focused on the amygdala and the prefrontal cortex. The results have, however, been inconsistent, potentially due to small sample sizes (typically N < 50 ). It remains unclear if any alterations are a characteristic of current depression or of past experience of depression, and whether there are MDD-related changes in effective connectivity between the two brain regions.Methods: Activations and effective connectivity between the amygdala and dorsolateral prefrontal cortex (DLPFC) in response to fearful face stimuli were studied in a large population-based sample from Generation Scotland. Participants either had no history of MDD ( N = 664 in activation analyses, N = 474 in connectivity analyses) or had a diagnosis of MDD during their lifetime (LMDD, N = 290 in activation analyses, N = 214 in connectivity analyses). The within-scanner task involved implicit facial emotion processing of neutral and fearful faces.Results: Compared to controls, LMDD was associated with increased activations in left amygdala ( PFWE = 0.031 , k E = 4 ) and left DLPFC ( PFWE = 0.002 , k E = 33 ), increased mean bilateral amygdala activation ( β = 0.0715, P = 0.0314 ), and increased inhibition from left amygdala to left DLPFC, all in response to fearful faces contrasted to baseline. Results did not appear to be attributable to depressive illness severity or antidepressant medication status at scan time.Limitations: Most studied participants had past rather than current depression, average severity of ongoing depression symptoms was low, and a substantial proportion of participants were receiving medication. The study was not longitudinal and the participants were only assessed a single time.Conclusions: LMDD is associated with hyperactivity of the amygdala and DLPFC, and with stronger amygdala to DLPFC inhibitory connectivity, all in response to fearful faces, unrelated to depression severity at scan time. These results help reduce inconsistency in past literature and suggest disruption of ‘bottom-up’ limbic-prefrontal effective connectivity in depression