Adrian Williams

Task-related changes in cortical synchronization are spatially coincident with the hemodynamic response.

Using group functional Magnetic Resonance Imaging (fMRI) and group Magnetoencephalography (MEG) we studied two cognitive paradigms: A language task involving covert letter fluency and a visual task involving biological motion direction discrimination. The MEG data were analyzed using an adaptive beam-former technique known as Synthetic Aperture Magnetometry (SAM), which provides continuous 3-D images of cortical power changes. These images were spatially normalized and averaged across subjects to provide a group SAM image in the same template space as the group fMRI data. The results show that frequency-specific, task-related changes in cortical synchronization, detected using MEG, match those areas of the brain showing an evoked cortical hemodynamic response with fMRI. The majority of these changes were event-related desynchronizations (ERDs) in the 5-10 Hz and 15-25 Hz frequency ranges. Our study demonstrates how SAM, spatial normalization, and intersubject averaging enable group MEG studies to be performed. SAM analysis also allows the MEG experiment to have exactly the same task design as the corresponding fMRI experiment. This new analysis framework represents an important advance in the use of MEG as a cognitive neuroimaging technique and also allows mutual cross-validation with fMRI.

Sensitivity to optic flow in human cortical areas MT and MST

The macaque V5/MT complex comprises several sub‐regions but little is known of their human homologues. We examined human V5/MT with fMRI in terms of specificity to optic flow stimuli, a key characteristic of macaque MST. Stimuli were large fields of moving dots, forming coherent global flow patterns. Random motion was used as a control. Retinotopic mapping was also conducted. The previously suggested existence of at least two distinct sub‐regions, MT and MST, within the V5/MT complex was confirmed. Human MT is activated about equally by all moving dot patterns, including random motion, suggesting that it has little sensitivity to global flow structure. As previously described, this region shows strong signs of retinotopic organization and is only weakly activated by stimuli confined to the ipsilateral hemifield. In human MST, located immediately anterior to MT and strongly driven by ipsilateral stimuli, activation varies markedly with optic flow structure. The strongest activation is produced by complex flow that contains multiple flow components (expansion, contraction and rotation). Single components produce rather less response, while rigid translation and random motion produce less still. The results suggest that human MST is strongly specialized for encoding global flow properties, while human MT is less so.

Negative BOLD in the visual cortex: Evidence against blood stealing

The positive BOLD (blood oxygen level‐dependent) response elicited in human visual cortex by a localized visual stimulus is accompanied by a reduction in the BOLD response in regions of the visual cortex that represent unstimulated locations in the visual field. We have suggested previously that this negative BOLD reflects attention‐related suppression of neural activity, but it might also be explained in terms of “blood stealing,” i.e., hemodynamic changes that have no neural correlate. We distinguish two possible hemodynamic effects of this type: (1) blood flow reduction caused by locally reduced pressure in vessels that share their blood supply with nearby dilated vessels; and (2) blood flow reduction caused by active constriction of vessels under neural control. The first is ruled out as an explanation of negative BOLD by showing that a visual stimulus that stimulates primary visual cortex in one hemisphere can cause extensive suppression in the other hemisphere i.e., it is not a local phenomenon. Negative BOLD most likely reflects suppression of neural activity, but could also reflect an active blood flow control system. Hum. Brain Mapping 21:213–220, 2004.

The confounding effect of response amplitude on MVPA performance measures

Multi-voxel pattern analysis (MVPA) is proving very powerful in the analysis of fMRI timeseries data, yielding surprising sensitivity, in many different contexts, to the response characteristics of neurons in a given brain region. However, MVPA yields a metric (classification performance) that does not readily lend itself to quantitative comparisons across experimental conditions, brain regions or people. This is because performance is influenced by a number of factors other than the sensitivity of neurons to the experimental manipulation. One such factor that varies widely but has been largely ignored in MVPA studies is the amplitude of the response being decoded. In a noisy system, it is expected that measured classification performance will decline with declining response amplitude, even if the underlying neuronal specificity is constant. We document the relationship between response amplitude and classification performance in the context of orientation decoding in the visual cortex. Flickering sine gratings were presented at each of two orthogonal orientations in a block design (multivariate experiment) or an event-related design (univariate experiment). Response amplitude was manipulated by varying stimulus contrast. Orientation classification performance in retinotopically defined occipital area V1 increased approximately linearly with the logarithm of stimulus contrast. As expected, univariate response amplitude also increased with contrast. Similar results were obtained in V2, V3 and V3A. Plotting classification performance against response amplitude gave a function with a compressive non-linearity that was well fit by a power function. Knowledge of this function potentially allows adjustment of classification performance to take account of the effect of response size, making comparisons across brain areas, categories or people more meaningful.

Demonstration of CSF gamma‐globulin banding in presenile dementia

An improved agarose gel electrophoretic technique was used to fractionate serum and cerebrospinal fluid (CSF) proteins in patients with presenile dementia. The CSF electrophoretic patterns demonstrated three abnormal bands in the gamma-globulin region in five out of eight of these patients.

Is abnormal retinal development in albinism only a mammalian problem? Normality of a hypopigmented avian retina

The central retina in hypopigmented mammals is underdeveloped. In the outer retina this deficit is confined to rods. Also, many ganglion cells in temporal regions project inappropriately to the contralateral hemisphere. This study addresses the question of whether pigment-related abnormalities occur in the central retina of a non-mammal, the bird. Birds have a highly developed central retina, but unlike most mammals they do not have a significant uncrossed retinal projection. Consequently, examination of the retinae of hypopigmented birds will reveal whether there is a relationship between the two abnormalities. Also if one of the primary effects of albinism is centred on rods, then albino birds may not show a deficit, because their retinae are cone dominated. Retinae from normally pigmented and two forms of hypopigmented budgerigars (Melopsittacus undulatus) were studied. Measurements of layer thickness, cell density and cell size were made at a range of locations in the ganglion cell layer and in the inner and the outer nuclear layers. Estimates of cone numbers were also made. Each strain of bird had an area of increased retinal layer thickness in dorso-temporal regions, but not a fovea. Although there were variations in the measurements undertaken between the strains, none were pigment related or consistent with the abnormality found in the central retina in albino mammals. Consequently, the underdevelopment of the central retina seen in hypopigmented mammals does not occur in this bird. There are two possible explanations for this result. First, normal mammalian retinal development may depend partly on time-dependent interactions in the maturation of the retinal pigment epithelium and the neural retina. Although there is a common time table for the development of the mammalian visual system when expressed in terms of the caecal period, which is between conception and eye opening, the pace of retinal development in birds is accelerated, which may alter interactions between these regions. Second, as the bird retina is cone dominated, any deficits in albino strains may be relatively minor.

Representation of Eye Position in the Human Parietal Cortex

Neurons that signal eye position are thought to make a vital contribution to distinguishing real world motion from retinal motion caused by eye movements, but relatively little is known about such neurons in the human brain. Here we present data from functional MRI experiments that are consistent with the existence of neurons sensitive to eye position in darkness in the human posterior parietal cortex. We used the enhanced sensitivity of multivoxel pattern analysis (MVPA) techniques, combined with a searchlight paradigm, to isolate brain regions sensitive to direction of gaze. During data acquisition, participants were cued to direct their gaze to the left or right for sustained periods as part of a block-design paradigm. Following the exclusion of saccade-related activity from the data, the multivariate analysis showed sensitivity to tonic eye position in two localized posterior parietal regions, namely the dorsal precuneus and, more weakly, the posterior aspect of the intraparietal sulcus. Sensitivity to eye position was also seen in anterior portions of the occipital cortex. The observed sensitivity of visual cortical neurons to eye position, even in the total absence of visual stimulation, is possibly a result of feedback from posterior parietal regions that receive eye position signals and explicitly encode direction of gaze.

Aging and CSF hydroxylase cofactor

The level of cerebrospinal fluid (CSF) hydroxylase cofactor activity was measured in 34 neurologically normal patients and analyzed according to age. Levels declined by approximately one-third over a 40-year span, probably reflecting loss of aminergic neurons. Fourteen patients with Parkinson disease all tended to have lower values than age-matched controls. Among Parkinson patients with the same order of disability, younger cases had higher CSF concentrations of hydroxylase cofactor than older patients.

Attentional modulation in the human visual cortex: The time-course of the BOLD response and its implications

Throughout the visual areas of the brain, the sensory response to a stimulus is enhanced by attending to the stimulus. Neurophysiological studies in primates show that such enhancement is marked in posterior parietal cortex and some anterior occipital areas, but much more modest in the earliest processing stages, such as the primary visual cortex (V1). In contrast, human fMRI studies show large and robust attentional modulation in all visual areas, including V1. We investigate the possibility that, in the case of fMRI, the BOLD (blood oxygen level dependent) response may be increased not only by local attention-related increases in neural activity, but also by local blood-flow increases caused by remote control systems that anticipate an impending need for oxygen at the attended location. Such changes could be much more rapid than the rather slow response to oxygenation change that typifies the BOLD response. We have employed a paradigm that isolates the component of the BOLD response due to attentional modulation and the component due to the mere presence of a visual stimulus. The results show that the temporal profiles of the BOLD responses in human V1 to the onset of a stimulus and to the onset of attention are extremely similar. The time-course of the attention-related BOLD response is not consistent with the action of remote, anticipatory control mechanisms and suggests that the modulatory effect of attention seen in human V1 with fMRI probably reflects genuine changes in local neural activity that are considerably larger than in non-human primates.

Growth dynamics of the developing lateral geniculate nucleus

Segregated binocular maps in the lateral geniculate nucleus (LGN) develop from stages where they initially completely overlap. Here, we show that segregation occurs at different rates across the depth of the nucleus and that the volume of the ipsilateral projection does not decrease significantly during this period, rather LGN volume expands markedly and its shape changes. Hence, we have examined the differential growth of the ferret LGN during the process of segregation by using novel shape modelling techniques. These have facilitated quantification of its three‐dimensional structure at successive developmental stages as well as the definition of growth vectors which illustrate shape change. This has been undertaken in direct representations of the LGN and those normalised for size and orientation. Spatiotemporal aspects of shape change have then been compared with different measurements of its cellular population. Initial stages of segregation are associated with a large expansion of the rostrocaudal axis of the nucleus along which segregation takes place, and an expansion of caudal regions that will eventually contain the binocular representation. Later stages are associated with dorsoventral expansions and a consolidation of the rostrocaudal axis. The pace of shape change peaks toward the end of the period of segregation when the nucleus has adopted ∼50% of its adult shape. After segregation, nuclear growth is mainly isotropic. The mature shape of the nucleus is achieved before it reaches its full size and while cell density and cell sizes are still changing. J. Comp. Neurol. 430:332–342, 2001.