Hemispherical differences in the pattern onset visual evoked magnetic response

Recently, hemispherical asymmetries have been demonstrated for primary visual processing suggesting that basic spatiotemporal features of the stimulus may play a role in the lateralisation effects that have been observed in the human brain. However, to our knowledge no studies have reported hemispheric differences using magnetoencephalography (MEG). Hence, the objective of this study was to determine whether MEG could detect hemispherical asymmetry to the onset of a checkerboard pattern.

Influence of blur on the visual evoked magnetic response to a pattern reversal stimulus

Blurring a pattern reversal stimulus increases the latency and decreases the amplitude of the visual evoked potential (VEP) P100 peak. Recording the visual evoked magnetic response (VEMR) is some subjects may therefore be difficult because their spectacles create excessive magnetic noise. Hence, the effect of varying degrees of blur (-5 to +5 D) on the VEMR was investigated in three subjects with 6/6 vision to determine whether refraction with non-magnetic frames and lenses was necessary before magnetic recording. Small (32') and larger (70') checks were studied since there is evidence that blurring small checks has a more significant effect on the VEP compared with large checks. The VEMR was recorded using a single channel dc-SQUID, second order gradiometer in an unshielded laboratory. The latency (ms) and amplitude (fT) of the most prominant positive peak within the first 130 ms (P100M) were measured. Blurring the 32' checks significantly increased latency aand reduced the amplitude of the P100M peak. The resulting response curves were parabolic with minimum latency and maximum amplitude recorded at 0 D. Blurring the 70' check had no significant effect on latency or amplitude. Hence, the magnetic P100M responds similarly to the electrical P100 in response to blur. It would be essential when recording the VEMR that vision is corrected with non-magnetic spectacles especially when small checks are used.

Development and application of magnetoencephalographic methods in the investigation of the human visual system

This thesis is an exploration of the organisation and functioning of the human visual system using the non-invasive functional imaging modality magnetoencephalography (MEG). Chapters one and two provide an introduction to the ‘human visual system and magnetoencephalographic methodologies. These chapters subsequently describe the methods by which MEG can be used to measure neuronal activity from the visual cortex. Chapter three describes the development and implementation of novel analytical tools; including beamforming based analyses, spectrographic movies and an optimisation of group imaging methods. Chapter four focuses on the use of established and contemporary analytical tools in the investigation of visual function. This is initiated with an investigation of visually evoked and induced responses; covering visual evoked potentials (VEPs) and event related synchronisation/desynchronisation (ERS/ERD). Chapter five describes the employment of novel methods in the investigation of cortical contrast response and demonstrates distinct contrast response functions in striate and extra-striate regions of visual cortex. Chapter six use synthetic aperture magnetometry (SAM) to investigate the phenomena of visual cortical gamma oscillations in response to various visual stimuli; concluding that pattern is central to its generation and that it increases in amplitude linearly as a function of stimulus contrast, consistent with results from invasive electrode studies in the macaque monkey. Chapter seven describes the use of driven visual stimuli and tuned SAM methods in a pilot study of retinotopic mapping using MEG; finding that activity in the primary visual cortex can be distinguished in four quadrants and two eccentricities of the visual field. Chapter eight is a novel implementation of the SAM beamforming method in the investigation of a subject with migraine visual aura; the method reveals desynchronisation of the alpha and gamma frequency bands in occipital and temporal regions contralateral to observed visual abnormalities. The final chapter is a summary of main conclusions and suggested further work.

Electrophysiological studies of the visual pathways in Alzheimer's and Parkinson's disease

It is known that parallel pathways exist within the visual system. These have been described as magnocellular and parvocellular as a result of the layered organisation of the lateral geniculate nucleus and extend from the retina to the cortex. Dopamine (DA) and acetylcholine (ACH) are neurotransmitters that are present in the visual pathway. DA is present in the retina and is associated with the interplexiform cells and horizontal cells. ACH is also present in the retina and is associated with displaced amacrine cells; it is also present in the superior colliculus. DA is found to be significantly depleted in the brain of Parkinson's disease (PD) patients and ACH in Alzheimer's disease (AD) patients. For this reason these diseases were used to assess the function of DA and ACH in the electrophysiology of the visual pathway. Experiments were conducted on young normals to design stimuli that would preferentially activate the magnocellular or parvocellular pathway. These stimuli were then used to evoke visual evoked potentials (VEP) in patients with PD and AD, in order to assess the function of DA and ACH in the visual pathway. Electroretinograms (ERGs) were also measured in PD patients to assess the role of DA in the retina. In addition, peripheral ACH function was assessed by measuring VEPs, ERGs and contrast sensitivity (CS) in young normals following the topical instillation of hyoscine hydrobromide (an anticholinergic drug). The results indicate that the magnocellular pathway can be divided into two: a cholinergic tectal-association area pathway carrying luminance information, and a non-cholinergic geniculo-cortical pathway carrying spatial information. It was also found that depletion of DA had very little effect on the VEPs or ERGs, confirming a general regulatory function for this neurotransmitter.

The clinical utility of the middle latency and 40Hz auditory evoked potentials in audiological electrodiagnosis

The two elcctrophysiological tests currently favoured in the clinical measurement of hearing threshold arc the brainstorm evoked potential (BAEP) and the slow vertex response (SVR). However, both tests possess disadvantages. The BAEP is the test of choice in younger patients as it is stable at all levels of arousal, but little information has been obtained to date at a range of frequencies. The SVR is frequency specific but is unreliable in certain adult subjects and is unstable during sleep or in young children. These deficiencies have prompted research into a third group of potentials, the middle latency response (MLR) and the 40HZ responses. This research has compared the SVR and 40HZ response in waking adults and reports that the 40HZ test can provide a viable alternative to the SVR provided that a high degree of subject relaxation is ensured. A second study examined the morphology of the MLR and 40HZ during sleep. This work suggested that these potentials arc markedly different during sleep and that methodological factors have been responsible for masking these changes in previous studies. The clinical possibilities of tone pip BAEPs were then examined as these components were proved to be the only stable responses present in sleep. It was found that threshold estimates to 5OOHz, lOOOHz and 4000Hz stimuli could be made to within 15dBSL in most cases. A final study looked more closely at methods of obtaining frequency specific information in sleeping subjects. Threshold estimates were made using established BAEP parameters and this was compared to a 40HZ procedure which recorded a series of BAEPs over a 100msec. time sweep. Results indicated that the 40mHz procedure was superior to existing techniques in estimating threshold to low frequency stimuli. This research has confirmed a role for the MLR and 40Hz response as alternative measures of hearing capability in waking subjects and proposes that the 40Hz technique is useful in measuring frequency specific thresholds although the responses recorded derive primarily from the brainstem.

Objective and psychophysical studies of infant visual development

Distortion or deprivation of vision during an early `critical' period of visual development can result in permanent visual impairment which indicates the need to identify and treat visually at-risk individuals early. A significant difficulty in this respect is that conventional, subjective methods of visual acuity determination are ineffective before approximately three years of age. In laboratory studies, infant visual function has been quantified precisely, using objective methods based on visual evoked potentials (VEP), preferential looking (PL) and optokinetic nystagmus (OKN) but clinical assessment of infant vision has presented a particular difficulty. An initial aim of this study was to evaluate the relative clinical merits of the three techniques. Clinical derivatives were devised, the OKN method proved unsuitable but the PL and VEP methods were evaluated in a pilot study. Most infants participating in the study had known ocular and/or neurological abnormalities but a few normals were included for comparison. The study suggested that the PL method was more clinically appropriate for the objective assessment of infant acuity. A study of normal visual development from birth to one year was subsequently conducted. Observations included cycloplegic refraction, ophthalmoscopy and preferential looking visual acuity assessment using horizontally and vertically oriented square wave gratings. The aims of the work were to investigate the efficiency and sensitivity of the technique and to study possible correlates of visual development. The success rate of the PL method varied with age; 87% of newborns and 98% of infants attending follow-up successfully completed at least one acuity test. Below two months monocular acuities were difficult to secure; infants were most testable around six months. The results produced were similar to published data using the acuity card procedure and slightly lower than, but comparable with acuity data derived using extended PL methods. Acuity development was not impaired in infants found to have retinal haemorrhages as newborns. A significant relationship was found between newborn binocular acuity and anisometropia but not with other refractive findings. No strong or consistent correlations between grating acuity and refraction were found for three, six or twelve months olds. Improvements in acuity and decreases in levels of hyperopia over the first week of life were suggestive of recovery from minor birth trauma. The refractive data was analysed separately to investigate the natural history of refraction in normal infants. Most newborns (80%) were hyperopic, significant astigmatism was found in 86% and significant anisometropia in 22%. No significant alteration in spherical equivalent refraction was noted between birth and three months, a significant reduction in hyperopia was evident by six months and this trend continued until one year. Observations on the astigmatic component of the refractive error revealed a rather erratic series of changes which would be worthy of further investigation since a repeat refraction study suggested difficulties in obtaining stable measurements in newborns. Astigmatism tended to decrease between birth and three months, increased significantly from three to six months and decreased significantly from six to twelve months. A constant decrease in the degree of anisometropia was evident throughout the first year. These findings have implications for the correction of infantile refractive error.

The effect of stimulus location on the major components of the visual evoked response

The topographical distribution of the pattern reversal Visual Evoked Response (VER) was recorded from a localised montage of 20 electrodes over the visual cortex. The response was recorded after stimulation with a black and white checkerboard stimulus. The effect of field location on the major components was investigated in 11 subjects (age range (23-55). The major components of the half field response were; a negative around 75ms (N75) followed by a positivity around 80ms (P80), then a positivity around 100ms (P100) followed by another positivity at around 120ms (P120) and a negativity at approximately 145ms (N145). No effect of field size could be demonstrated on either the amplitude or latency of the late negativity, N145. No significant effect of field size or location was shown on the latency of the P100 response. A delay previously shown in the upper half field response was therefore not substantiated. In contrast the amplitude of the major positivity, P100 was significantly affected by the field size and location. The amplitude of both P100 and N145 were significantly reduced following upper field stimulation when compared with the lower field response. No significant amplitude difference between the upper and lower field responses was demonstrated using electroretinography, the amplitude may therefore be reduced as a result of the ventral position of the upper field representation on the visual cortex. The lateral half field VEP was compared with the distribution of the visual evoked magnetic response (VEMR). The distribution of the VEMR supported the proposal that the paradoxical lateralisation of the VEP half field response is the result of the source being directed ipsilaterally. The morphology of the VEP following octant and double octant stimulation suggests that the response is generated in the striate cortex, with a reversal in response distribution following stimulation of the upper vertical and horizontal meridia.

Development of visual evoked responses to tritan,red-green and luminance stimuli in human infants

The principal aim of this work was to investigate the development of the S-cone colour-opponent pathway in human infants aged 4 weeks to 6 months. This was achieved by recording transient visual evoked responses to pattern-onset stimuli along a tritanopic confusion axis (tritan stimuli) at and around the adult isoluminant match. For comparison, visual evoked responses to red-green and luminance-modulated stimuli were recorded from the same infants at the same ages. Evoked responses were also recorded from colour-normal adults for comparison with those of the infants. The transient VEP allowed observation of response morphology as luminance differences were introduced to the chromatic stimuli. In this way, an estimate of isoluminance was possible in infants. Estimated isoluminant points for a group of six infants aged 6 to 10 weeks closely approximated the adult isoluminant match. This finding has implications for the use of photometric isoluminance in infant work, and suggests that photopic spectral sensitivity is similar in infants and adults. Abnormalities of the visual evoked responses to tritan, red-green and luminance-modulated stimuli in an infant with cystic fibrosis are reported. The results suggest abnormal function of the retino-striate visual pathway in this infant, and it is argued that these may be secondary to his illness, although data from more infants with cystic fibrosis are needed to clarify this further. A group of nine healthy infants demonstrated evoked responses to tritan stimuli by 4 to 10 weeks and to red-green stimuli by 6 to 11 weeks post-term age. Responses to luminance-modulated stimuli were present in all nine infants at the earliest age tested, namely 4 weeks post-term. The slightly earlier age of onset of evoked responses to tritan stimuli than for red-green may be explained by the relatively lower cone contrast afforded by red-green stimuli. Latency of the evoked response to both types of chromatic stimuli and to luminance-modulated stimuli decreased with age at a similar rate, suggesting that the visual pathways transmitting luminance and chromatic information mature at similar rates in young infants.

The visual cortex in Alzheimer disease:laminar distribution of the pathological changes in visual areas V1 and V2

Alzheimer’s disease (AD) is an important neurodegenerative disorder causing visual problems in the elderly population. The pathology of AD includes the deposition in the brain of abnormal aggregates of ?-amyloid (A?) in the form of senile plaques (SP) and abnormally phosphorylated tau in the form of neurofibrillary tangles (NFT). A variety of visual problems have been reported in patients with AD including loss of visual acuity (VA), colour vision and visual fields; changes in pupillary responses to mydriatics, defects in fixation and in smooth and saccadic eye movements; changes in contrast sensitivity and in visual evoked potentials (VEP); and disturbances in complex visual tasks such as reading, visuospatial function, and in the naming and identification of objects. In addition, pathological changes have been observed to affect the eye, visual pathway, and visual cortex in AD. To better understand degeneration of the visual cortex in AD, the laminar distribution of the SP and NFT was studied in visual areas V1 and V2 in 18 cases of AD which varied in disease onset and duration. In area V1, the mean density of SP and NFT reached a maximum in lamina III and in laminae II and III respectively. In V2, mean SP density was maximal in laminae III and IV and NFT density in laminae II and III. The densities of SP in laminae I of V1 and NFT in lamina IV of V2 were negatively correlated with patient age. No significant correlations were observed in any cortical lamina between the density of NFT and disease onset or duration. However, in area V2, the densities of SP in lamina II and lamina V were negatively correlated with disease duration and disease onset respectively. In addition, there were several positive correlations between the densities of SP and NFT in V1 with those in area V2. The data suggest: (1) NFT pathology is greater in area V2 than V1, (2) laminae II/III of V1 and V2 are most affected by the pathology, (3) the formation of SP and NFT in V1 and V2 are interconnected, and (4) the pathology may spread between visual areas via the feed-forward short cortico-cortical connections.

Evaluation of hemifield sector analysis protocol in multifocal visual evoked potential (MFVEP) objective perimetry for the diagnosis and early detection of glaucomatous field defects

Visual field assessment is a core component of glaucoma diagnosis and monitoring, and the Standard Automated Perimetry (SAP) test is considered up until this moment, the gold standard of visual field assessment. Although SAP is a subjective assessment and has many pitfalls, it is being constantly used in the diagnosis of visual field loss in glaucoma. Multifocal visual evoked potential (mfVEP) is a newly introduced method used for visual field assessment objectively. Several analysis protocols have been tested to identify early visual field losses in glaucoma patients using the mfVEP technique, some were successful in detection of field defects, which were comparable to the standard SAP visual field assessment, and others were not very informative and needed more adjustment and research work. In this study, we implemented a novel analysis approach and evaluated its validity and whether it could be used effectively for early detection of visual field defects in glaucoma. OBJECTIVES: The purpose of this study is to examine the effectiveness of a new analysis method in the Multi-Focal Visual Evoked Potential (mfVEP) when it is used for the objective assessment of the visual field in glaucoma patients, compared to the gold standard technique. METHODS: 3 groups were tested in this study; normal controls (38 eyes), glaucoma patients (36 eyes) and glaucoma suspect patients (38 eyes). All subjects had a two standard Humphrey visual field HFA test 24-2 and a single mfVEP test undertaken in one session. Analysis of the mfVEP results was done using the new analysis protocol; the Hemifield Sector Analysis HSA protocol. Analysis of the HFA was done using the standard grading system. RESULTS: Analysis of mfVEP results showed that there was a statistically significant difference between the 3 groups in the mean signal to noise ratio SNR (ANOVA p<0.001 with a 95% CI). The difference between superior and inferior hemispheres in all subjects were all statistically significant in the glaucoma patient group 11/11 sectors (t-test p<0.001), partially significant 5/11 (t-test p<0.01) and no statistical difference between most sectors in normal group (only 1/11 was significant) (t-test p<0.9). sensitivity and specificity of the HAS protocol in detecting glaucoma was 97% and 86% respectively, while for glaucoma suspect were 89% and 79%. DISCUSSION: The results showed that the new analysis protocol was able to confirm already existing field defects detected by standard HFA, was able to differentiate between the 3 study groups with a clear distinction between normal and patients with suspected glaucoma; however the distinction between normal and glaucoma patients was especially clear and significant. CONCLUSION: The new HSA protocol used in the mfVEP testing can be used to detect glaucomatous visual field defects in both glaucoma and glaucoma suspect patient. Using this protocol can provide information about focal visual field differences across the horizontal midline, which can be utilized to differentiate between glaucoma and normal subjects. Sensitivity and specificity of the mfVEP test showed very promising results and correlated with other anatomical changes in glaucoma field loss.

The role of hemifield sector analysis in multifocal visual evoked potential objective perimetry in the early detection of glaucomatous visual field defects

Objective: The purpose of this study was to examine the effectiveness of a new analysis method of mfVEP objective perimetry in the early detection of glaucomatous visual field defects compared to the gold standard technique. Methods and patients: Three groups were tested in this study; normal controls (38 eyes), glaucoma patients (36 eyes), and glaucoma suspect patients (38 eyes). All subjects underwent two standard 24-2 visual field tests: one with the Humphrey Field Analyzer and a single mfVEP test in one session. Analysis of the mfVEP results was carried out using the new analysis protocol: the hemifield sector analysis protocol. Results: Analysis of the mfVEP showed that the signal to noise ratio (SNR) difference between superior and inferior hemifields was statistically significant between the three groups (analysis of variance, P<0.001 with a 95% confidence interval, 2.82, 2.89 for normal group; 2.25, 2.29 for glaucoma suspect group; 1.67, 1.73 for glaucoma group). The difference between superior and inferior hemifield sectors and hemi-rings was statistically significant in 11/11 pair of sectors and hemi-rings in the glaucoma patients group (t-test P<0.001), statistically significant in 5/11 pairs of sectors and hemi-rings in the glaucoma suspect group (t-test P<0.01), and only 1/11 pair was statistically significant (t-test P<0.9). The sensitivity and specificity of the hemifield sector analysis protocol in detecting glaucoma was 97% and 86% respectively and 89% and 79% in glaucoma suspects. These results showed that the new analysis protocol was able to confirm existing visual field defects detected by standard perimetry, was able to differentiate between the three study groups with a clear distinction between normal patients and those with suspected glaucoma, and was able to detect early visual field changes not detected by standard perimetry. In addition, the distinction between normal and glaucoma patients was especially clear and significant using this analysis. Conclusion: The new hemifield sector analysis protocol used in mfVEP testing can be used to detect glaucomatous visual field defects in both glaucoma and glaucoma suspect patients. Using this protocol, it can provide information about focal visual field differences across the horizontal midline, which can be utilized to differentiate between glaucoma and normal subjects. The sensitivity and specificity of the mfVEP test showed very promising results and correlated with other anatomical changes in glaucomatous visual field loss. The intersector analysis protocol can detect early field changes not detected by the standard Humphrey Field Analyzer test. © 2013 Mousa et al, publisher and licensee Dove Medical Press Ltd.

An assessment of the technique and clinical application of visual evoked response measurements

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT

Evaluation of hemifield sector analysis protocol in multifocal visual evoked potential objective perimetry for the diagnosis and early detection of glaucomatous field defects

CONCLUSIONS: The new HSA protocol used in the mfVEP testing can be applied to detect glaucomatous visual field defects in both glaucoma and glaucoma suspect patients. Using this protocol can provide information about focal visual field differences across the horizontal midline, which can be utilized to differentiate between glaucoma and normal subjects. Sensitivity and specificity of the mfVEP test showed very promising results and correlated with other anatomical changes in glaucoma field loss. PURPOSE: Multifocal visual evoked potential (mfVEP) is a newly introduced method used for objective visual field assessment. Several analysis protocols have been tested to identify early visual field losses in glaucoma patients using the mfVEP technique, some were successful in detection of field defects, which were comparable to the standard automated perimetry (SAP) visual field assessment, and others were not very informative and needed more adjustment and research work. In this study we implemented a novel analysis approach and evaluated its validity and whether it could be used effectively for early detection of visual field defects in glaucoma. METHODS: Three groups were tested in this study; normal controls (38 eyes), glaucoma patients (36 eyes) and glaucoma suspect patients (38 eyes). All subjects had a two standard Humphrey field analyzer (HFA) test 24-2 and a single mfVEP test undertaken in one session. Analysis of the mfVEP results was done using the new analysis protocol; the hemifield sector analysis (HSA) protocol. Analysis of the HFA was done using the standard grading system. RESULTS: Analysis of mfVEP results showed that there was a statistically significant difference between the three groups in the mean signal to noise ratio (ANOVA test, p < 0.001 with a 95% confidence interval). The difference between superior and inferior hemispheres in all subjects were statistically significant in the glaucoma patient group in all 11 sectors (t-test, p < 0.001), partially significant in 5 / 11 (t-test, p < 0.01), and no statistical difference in most sectors of the normal group (1 / 11 sectors was significant, t-test, p < 0.9). Sensitivity and specificity of the HSA protocol in detecting glaucoma was 97% and 86%, respectively, and for glaucoma suspect patients the values were 89% and 79%, respectively.