Therapeutic potential of computer to cerebral cortex implantable devices

In this article, an overview of some of the latest developments in the field of cerebral cortex to computer interfacing (CCCI) is given. This is posed in the more general context of Brain-Computer Interfaces in order to assess advantages and disadvantages. The emphasis is clearly placed on practical studies that have been undertaken and reported on, as opposed to those speculated, simulated or proposed as future projects. Related areas are discussed briefly only in the context of their contribution to the studies being undertaken. The area of focus is notably the use of invasive implant technology, where a connection is made directly with the cerebral cortex and/or nervous system. Tests and experimentation which do not involve human subjects are invariably carried out a priori to indicate the eventual possibilities before human subjects are themselves involved. Some of the more pertinent animal studies from this area are discussed. The paper goes on to describe human experimentation, in which neural implants have linked the human nervous system bidirectionally with technology and the internet. A view is taken as to the prospects for the future for CCCI, in terms of its broad therapeutic role.

The influence of visual stimuli in ethnobotanical data collection using the listing task method

The listing task, a method used in social and behavioral sciences, is frequently used in ethnobotanical research to constructfolk taxonomies and select relevant itemsfor subsequent research. The objective of the present study was to determine whether visual stimuli are associated with responses to the theme plants or if context influences the answers. Interviews were conducted with 400 women in Rio Claro, São Paulo, Brazil, in four different locations: three with a visible presence of plants (a plant store, a supermarket, and a public plaza) and one with no plants (a street corner in the center of the city). The women were asked to name plants. Analysis indicates that visual stimuli influenced responses and that this is more marked in the plant store than in the other locations. The plants cited most often-roses, orchids, ferns, violets, and daisies-were, with little variation, the same in all the locales studied.

Residual visual processing following real or virtual lesions to primary visual pathways

Lesions to the primary geniculo-striate visual pathway cause blindness in the contralesional visual field. Nevertheless, previous studies have suggested that patients with visual field defects may still be able to implicitly process the affective valence of unseen emotional stimuli (affective blindsight) through alternative visual pathways bypassing the striate cortex. These alternative pathways may also allow exploitation of multisensory (audio-visual) integration mechanisms, such that auditory stimulation can enhance visual detection of stimuli which would otherwise be undetected when presented alone (crossmodal blindsight). The present dissertation investigated implicit emotional processing and multisensory integration when conscious visual processing is prevented by real or virtual lesions to the geniculo-striate pathway, in order to further clarify both the nature of these residual processes and the functional aspects of the underlying neural pathways. The present experimental evidence demonstrates that alternative subcortical visual pathways allow implicit processing of the emotional content of facial expressions in the absence of cortical processing. However, this residual ability is limited to fearful expressions. This finding suggests the existence of a subcortical system specialised in detecting danger signals based on coarse visual cues, therefore allowing the early recruitment of flight-or-fight behavioural responses even before conscious and detailed recognition of potential threats can take place. Moreover, the present dissertation extends the knowledge about crossmodal blindsight phenomena by showing that, unlike with visual detection, sound cannot crossmodally enhance visual orientation discrimination in the absence of functional striate cortex. This finding demonstrates, on the one hand, that the striate cortex plays a causative role in crossmodally enhancing visual orientation sensitivity and, on the other hand, that subcortical visual pathways bypassing the striate cortex, despite affording audio-visual integration processes leading to the improvement of simple visual abilities such as detection, cannot mediate multisensory enhancement of more complex visual functions, such as orientation discrimination.

Extraversion and short-term memory for chromatic stimuli: an event-related potential analysis.

The present study investigated extraversion-related individual differences in visual short-term memory (VSTM) functioning. Event related potentials were recorded from 50 introverts and 50 extraverts while they performed a VSTM task based on a color-change detection paradigm with three different set sizes. Although introverts and extraverts showed almost identical hit rates and reaction times, introverts displayed larger N1 amplitudes than extraverts independent of color change or set size. Extraverts also showed larger P3 amplitudes compared to introverts when there was a color change, whereas no extraversion-related difference in P3 amplitude was found in the no-change condition. Our findings provided the first experimental evidence that introverts' greater reactivity to punctuate physical stimulation, as indicated by larger N1 amplitude, also holds for complex visual stimulus patterns. Furthermore, P3 amplitude in the change condition was larger for extraverts than introverts suggesting higher sensitivity to context change. Finally, there were no extraversion-related differences in P3 amplitude dependent on set size. This latter finding does not support the resource allocation explanation as a source of differences between introverts and extraverts.

Interactions between dorsolateral and ventromedial prefrontal cortex underlie context-dependent stimulus valuation in goal-directed choice.

External circumstances and internal bodily states often change and require organisms to flexibly adapt valuation processes to select the optimal action in a given context. Here, we investigate the neurobiology of context-dependent valuation in 22 human subjects using functional magnetic resonance imaging. Subjects made binary choices between visual stimuli with three attributes (shape, color, and pattern) that were associated with monetary values. Context changes required subjects to deviate from the default shape valuation and to integrate a second attribute in order to comply with the goal to maximize rewards. Critically, this binary choice task did not involve any conflict between opposing monetary, temporal, or social preferences. We tested the hypothesis that interactions between regions of dorsolateral and ventromedial prefrontal cortex (dlPFC; vmPFC) implicated in self-control choices would also underlie the more general function of context-dependent valuation. Consistent with this idea, we found that the degree to which stimulus attributes were reflected in vmPFC activity varied as a function of context. In addition, activity in dlPFC increased when context changes required a reweighting of stimulus attribute values. Moreover, the strength of the functional connectivity between dlPFC and vmPFC was associated with the degree of context-specific attribute valuation in vmPFC at the time of choice. Our findings suggest that functional interactions between dlPFC and vmPFC are a key aspect of context-dependent valuation and that the role of this network during choices that require self-control to adjudicate between competing outcome preferences is a specific application of this more general neural mechanism.

Visual avoidance in phobia: particularities in neural activity, autonomic responding, and cognitive risk evaluations.

We investigated the neural mechanisms and the autonomic and cognitive responses associated with visual avoidance behavior in spider phobia. Spider phobic and control participants imagined visiting different forest locations with the possibility of encountering spiders, snakes, or birds (neutral reference category). In each experimental trial, participants saw a picture of a forest location followed by a picture of a spider, snake, or bird, and then rated their personal risk of encountering these animals in this context, as well as their fear. The greater the visual avoidance of spiders that a phobic participant demonstrated (as measured by eye tracking), the higher were her autonomic arousal and neural activity in the amygdala, orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and precuneus at picture onset. Visual avoidance of spiders in phobics also went hand in hand with subsequently reduced cognitive risk of encounters. Control participants, in contrast, displayed a positive relationship between gaze duration toward spiders, on the one hand, and autonomic responding, as well as OFC, ACC, and precuneus activity, on the other hand. In addition, they showed reduced encounter risk estimates when they looked longer at the animal pictures. Our data are consistent with the idea that one reason for phobics to avoid phobic information may be grounded in heightened activity in the fear circuit, which signals potential threat. Because of the absence of alternative efficient regulation strategies, visual avoidance may then function to down-regulate cognitive risk evaluations for threatening information about the phobic stimuli. Control participants, in contrast, may be characterized by a different coping style, whereby paying visual attention to potentially threatening information may help them to actively down-regulate cognitive evaluations of risk.

Effects of early and late lesion of orbital frontal cortex on visual processing of faces in rhesus macaques (Macaca mulatta)

Many mental disorders disrupt social skills, yet few studies have examined how the brain processes social information. Functional neuroimaging, neuroconnectivity and electrophysiological studies suggest that orbital frontal cortex plays important roles in social cognition, including the analysis of information from faces, which are important cues in social interactions. Studies in humans and non-human primates show that damage to orbital frontal cortex produces social behavior impairments, including abnormal aggression, but these studies have failed to determine whether damage to this area impairs face processing. In addition, it is not known whether damage early in life is more detrimental than damage in adulthood. This study examined whether orbital frontal cortex is necessary for the discrimination of face identity and facial expressions, and for appropriate behavioral responses to aggressive (threatening) facial expressions. Rhesus monkeys (Macaca mulatta) received selective lesions of orbital frontal cortex as newborns or adults. As adults, these animals were compared with sham-operated controls on their ability to discriminate between faces of individual monkeys and between different facial expressions of emotion. A passive visual paired-comparison task with standardized rhesus monkey face stimuli was designed and used to assess discrimination. In addition, looking behavior toward aggressive expressions was assessed and compared with that of normal control animals. The results showed that lesion of orbital frontal cortex (1) may impair discrimination between faces of individual monkeys, (2) does not impair facial expression discrimination, and (3) changes the amount of time spent looking at aggressive (threatening) facial expressions depending on the context. The effects of early and late lesions did not differ. Thus, orbital frontal cortex appears to be part of the neural circuitry for recognizing individuals and for modulating the response to aggression in faces, and the plasticity of the immature brain does not allow for recovery of these functions when the damage occurs early in life. This study opens new avenues for the assessment of rhesus monkey face processing and the neural basis of social cognition, and allows a better understanding of the nature of the neuropathology in patients with mental disorders that disrupt social behavior, such as autism. ^

Neural fate of seen and unseen faces in visuospatial neglect: A combined event-related functional MRI and event-related potential study

To compare neural activity produced by visual events that escape or reach conscious awareness, we used event-related MRI and evoked potentials in a patient who had neglect and extinction after focal right parietal damage, but intact visual fields. This neurological disorder entails a loss of awareness for stimuli in the field contralateral to a brain lesion when stimuli are simultaneously presented on the ipsilateral side, even though early visual areas may be intact, and single contralateral stimuli may still be perceived. Functional MRI and event-related potential study were performed during a task where faces or shapes appeared in the right, left, or both fields. Unilateral stimuli produced normal responses in V1 and extrastriate areas. In bilateral events, left faces that were not perceived still activated right V1 and inferior temporal cortex and evoked nonsignificantly reduced N1 potentials, with preserved face-specific negative potentials at 170 ms. When left faces were perceived, the same stimuli produced greater activity in a distributed network of areas including right V1 and cuneus, bilateral fusiform gyri, and left parietal cortex. Also, effective connectivity between visual, parietal, and frontal areas increased during perception of faces. These results suggest that activity can occur in V1 and ventral temporal cortex without awareness, whereas coupling with dorsal parietal and frontal areas may be critical for such activity to afford conscious perception.

Selective attention to stimulus location modulates the steady-state visual evoked potential.

Steady-state visual evoked potentials (SSVEPs) were recorded from the scalp of human subjects who were cued to attend to a rapid sequence of alphanumeric characters presented to one visual half-field while ignoring a concurrent sequence of characters in the opposite half-field. These two-character sequences were each superimposed upon a small square background that was flickered at a rate of 8.6 Hz in one half-field and 12 Hz in the other half-field. The amplitude of the frequency-coded SSVEP elicited by either of the task-irrelevant flickering backgrounds was significantly enlarged when attention was focused upon the character sequence at the same location. This amplitude enhancement with attention was most prominent over occipital-temporal scalp areas of the right cerebral hemisphere regardless of the visual field of stimulation. These findings indicate that the SSVEP reflects an enhancement of neural responses to all stimuli that fall within the "spotlight" of spatial attention, whether or not the stimuli are task-relevant. Recordings of the SSVEP provide a new approach for studying the neural mechanisms and functional properties of selective attention to multi-element visual displays.

The influence of age on the pattern and flash visual evoked field

We have investigated the effect of ageing on the visual system using the relatively new technique of magentoencephalography (MEG). This technique measures the magnetic signals produced by the visual system using a SQUID magnetometer. The magnetic visual evoked field (VEF) was measured over the occipital cortex to pattern and flash stimuli in 86 normal subjects aged 15 - 86 years. Factors that influenced subject defocussing or defixating the stimulus or selective attention were controlled as far as possible. The latency of the major positive component to the pattern reversal stimulus (P100M) increased with age particularly after the age of 55 years while the amplitude of the P100M decreased over the life span. The latency of the major flash component (P2M) increased much more slowly with age, while its amplitude decreased in only a proportion of elderly subjects. Changes in the P100M with age may reflect senile changes in the eye and optic nerve, e.g. senile miosis or degenerative changes in the retina. The P2M may be more susceptible to senile changes in the retina. The data suggest that the spatial frequency channels deteriorate more rapidly with age than the luminance channels and that MEG may be an effective method of studying ageing in the visual system.

Face context interferes with local part processing in a prosopagnosic patient

We investigated the role of local and global information on perceptual encoding of faces in patient HJA, who shows prosopagnosia and visual agnosia following occipito-temporal damage. HJA and an age-matched control were tested in a simultaneous matching task which focused on detection of local changes in faces: the inversion of central parts (eyes and mouth) relative to their context (as in the Thatcher illusion). Same-different judgements were made to normal, “thatcherised” and mixed type face pairs. Whole faces (Experiment 1), or face parts (Experiment 2), were presented in upright and inverted orientations. Compared to the control, HJA was severely impaired at matching whole faces, but he improved dramatically when face parts were presented in isolation. This suggests an inhibitory influence of face context on HJAs processing of local parts and a relatively intact ability to process part-based information from a face (when context cannot interfere). Face inversion did not affect HJAs performance. A control experiment (Experiment 3) with non-face stimuli (houses) suggested that the inhibitory influence of context on HJAs performance was restricted to faces. These results indicate that contextual information in a face can have an adverse influence on the processing of local part-based information in prosopagnosia.

Automated assessment of visual fields and their inter-relation to evoked potentials in visual disorders

The Octopus Automated Perimeter was validated in a comparative study and found to offer many advantages in the assessment of the visual field. The visual evoked potential was investigated in an extensive study using a variety of stimulus parameters to simulate hemianopia and central visual field defects. The scalp topography was recorded topographically and a technique to compute the source derivation of the scalp potential was developed. This enabled clarification of the expected scalp distribution to half field stimulation using different electrode montages. The visual evoked potential following full field stimulation was found to be asymmetrical around the midline with a bias over the left occiput particularly when the foveal polar projections of the occipital cortex were preferentially stimulated. The half field response reflected the distribution asymmetry. Masking of the central 3° resulted in a response which was approximately symmetrical around the midline but there was no evidence of the PNP-complex. A method for visual field quantification was developed based on the neural representation of visual space (Drasdo and Peaston 1982) in an attempt to relate visual field depravation with the resultant visual evoked potentials. There was no form of simple, diffuse summation between the scalp potential and the cortical generators. It was, however, possible to quantify the degree of scalp potential attenuation for M-scaled full field stimuli. The results obtained from patients exhibiting pre-chiasmal lesions suggested that the PNP-complex is not scotomatous in nature but confirmed that it is most likely to be related to specific diseases (Harding and Crews 1982). There was a strong correlation between the percentage information loss of the visual field and the diagnostic value of the visual evoked potential in patients exhibiting chiasmal lesions.

The investigation of the sensitivity gradient of the visual field, as a function of stimulus dynamic range, in the normal and abnormal eye

The study utilized the advanced technology provided by automated perimeters to investigate the hypothesis that patients with retinitis pigmentosa behave atypically over the dynamic range and to concurrently determine the influence of extraneous factors on the format of the normal perimetric sensitivity profile. The perimetric processing of some patients with retinitis pigmentosa was considered to be abnormal in either the temporal and/or the spatial domain. The standard size III stimulus saturated the central regions and was thus ineffective in detecting early depressions in sensitivity in these areas. When stimulus size was scaled in inverse proportion to the square root of ganglion cell receptive field density (M-scaled), isosensitive profiles did not result, although cortical representation was theoretically equivalent across the visual field. It was conjectured that this was due to variations in the ganglion cell characteristics with increasing peripheral angle, most notably spatial summation. It was concluded that the development of perimetric routines incorporating stimulus sizes adjusted in proportion to the coverage factor of retinal ganglion cells would enhance the diagnostic capacity of perimetry. Good general and local correspondence was found between perimetric sensitivity and the available retinal cell counts. Intraocular light scatter arising both from simulations and media opacities depressed perimetric sensitivity. Attenuation was greater centrally for the smaller LED stimuli, whereas the reverse was true for the larger projected stimuli. Prior perimetric experience and pupil size also demonstrated eccentricity-dependent effect on sensitivity. Practice improved perimetric sensitivity for projected stimuli at eccentricities greater than or equal to 30o; particularly in the superior region. Increase in pupil size for LED stimuli enhanced sensitivity at eccentricities greater than 10o. Conversely, microfluctuation in the accommodative response during perimetric examination and the correction of peripheral refractive error had no significant influence on perimetric sensitivity.

Non-standard techniques for the investigation of the visual field

The study investigated the potential applications and the limitations of non-standard techniques of visual field investigation utilizing automated perimetry. Normal subjects exhibited a greater sensitivity to kinetic stimuli than to static stimuli of identical size. The magnitude of physiological SKD was found to be largely independent of age, stimulus size, meridian and eccentricity. The absence of a dependency on stimulus size indicated that successive lateral spatial summation could not totally account for the underlying mechanism of physiological SKD. The visual field indices MD and LV exhibited a progressive deterioration during the time course of a conventional central visual field examination both for normal subjects and for ocular hypertensive patients. The fatigue effect was more pronounced in the latter stages and for the second eye tested. The confidence limits for the definition of abnormality should reflect the greater effect of fatigue on the second eye. A 330 cdm-2 yellow background was employed for blue-on-yellow perimetry. Instrument measurement range was preserved by positioning a concave mirror behind the stimulus bulb to increase the light output by 60% . The mean magnitude of SWS pathway isolation was approximately 1.4 log units relative to a 460nm stimulus filter. The absorption spectra of the ocular media exhibited an exponential increase with increase in age, whilst that of the macular pigment showed no systematic trend. The magnitude of ocular media absorption was demonstrated to reduce with increase in wavelength. Ocular media absorption was significantly greater in diabetic patients than in normal subjects. Five diabetic patients with either normal or borderline achromatic sensitivity exhibited an abnormal blue-on-yellow sensitivity; two of these patients showed no signs of retinopathy. A greater vulnerability of the SWS pathway to the diabetic disease process was hypothesized.

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.