Kenneth L. Grieve

Separate body- and world-referenced representations of visual space in parietal cortex

In order to direct a movement towards a visual stimulus, visualspatial information must be combined with postural information. For example, directing gaze (eye plus head) towards a visible target requires the combination of retinal image location with eye and head position to determine the location of the target relative to the body. Similarly, world-referenced postural information is required to determine where something lies in the world. Posterior parietal neurons recorded in monkeys combine visual information with eye and head position. A population of such cells could make up a distributed representation of target location in an extraretinal frame of reference. However, previous studies have not distinguished between world-referenced and body-referenced signals,. Here we report that modulations of visual signals (gain fields) in two adjacent cortical fields, LIP and 7a, are referenced to the body and to the world, respectively. This segregation of spatial information is consistent with a streaming of information, with one path carrying body-referenced information for the control of gaze, and the other carrying world-referenced information for navigation and other tasks that require an absolute frame of reference.

The primate pulvinar nuclei: vision and action

The pulvinar nuclei of the thalamus are proportionately larger in higher mammals, particularly in primates, and account for a quarter of the total mass. Traditionally, these nuclei have been divided into oral (somatosensory), superior and inferior (both visual) and medial (visual, multi-sensory) divisions. With reciprocal connections to vast areas of cerebral cortex, and input from the colliculus and retina, they occupy an analogous position in the extra-striate visual system to the lateral geniculate nucleus in the primary visual pathway, but deal with higher-order visual and visuomotor transduction. With a renewed recent interest in this thalamic nuclear collection, and growth in our knowledge of the cortex with which it communicates, perhaps the time is right to look to new dimensions in the pulvinar code.

Functional magnetic resonance imaging in macaque cortex.

THE ability to use fMRI in a monkey model would bridge the gap between the fMRI demonstration of cerebral activation in humans and the cumulative wealth of monkey data on the functional organization of the brain from single electrode mapping, radioisotope and histology studies. We report a new technique for fMRI in an awake co-operative rhesus macaque (Macaca mulatta) in a conventional clinical 1.5T MR scanner and present the first fMRI images from a macaque. Good resolution, signal-to-noise ratio and BOLD response (2.6–4.6%) have been achieved using the manufacturers standard volume knee coil. T1 values of macaque gray and white matter (1490 ms, 1010 ms respectively) are higher than human brain, whereas T2 values are lower (55 ms, 48 ms respectively). An MR-compatible design for restraining the monkey is also described, along with a suitable EPI sequence for BOLD images, optimized for monkey T2, with voxel sizes from 29 to 61 μl, and MPRAGE sequence for anatomical studies with 0.8 mm isotropic resolution, optimized for monkey T1.

A re-appraisal of the role of layer VI of the visual cortex in the generation of cortical end inhibition

SummaryThese experiments examine the effect of blockade of layer VI of the cat striate cortex on the length tuning of hypercomplex cells in the overlying layers II, III and IV. It has previously been suggested that local inactivation of layer VI results in the complete loss of length selectivity in all hypercomplex cells in layers II, III and IV above the blocked region, by removal of an inhibitory mechanism within layer IV, driven from layer VI. However, we have found that, using iontophoretic application of the inhibitory substance GABA to block the activity of layer VI, 29% of hypercomplex cells were unaffected by blockade of the underlying layer VI. The predominant effect on hypercomplex cells was a reduction in visual responsiveness, seen in 71% of cells, with responses reduced on average by 43%. In 50% of these cells (35% of the population) this reduction was apparently specific to responses to the optimum bar length; responses to longer stimuli were unaffected. Iontophoretic application of the potent GABAA analogue muscimol in layer VI showed a similar spectrum of effects on hypercomplex cells. In these cases, however, the cortical blockade was slowly increased to encompass the recorded cell. In each case, any decreases in length selectivity were also the result of a decreased visual responsiveness. Thus, decreases in length selectivity seen when using either GABA or muscimol were almost exclusively the result of decreased responsiveness to the optimal length of bar stimulus, rather than an increase in response to non-optimal, long stimuli. This suggests the loss of a facilitatory influence from layer VI to layer IV, rather than the loss of inhibition.

The length summation properties of layer VI cells in the visual cortex and hypercomplex cell end zone inhibition

SummaryLayer VI of the visual cortex has been considered to be dominated by cells with very long receptive fields, typically summing to 8° or more. We have re-examined this issue in a series of experiments in which the length tuning profiles of layer VI cells in the cat visual cortex have been quantitatively determined. Responses were assessed to optimally oriented bars of light of varying length drifted over the receptive field. The lengths were varied on a randomised interleaved sequence. Although our data confirm the presence of long field cells in layer VI, only 24% of a population of 119 cells had fields greater than 6° in length. Fields greater than 8° were only seen in 17% of cells. 61% of the population of cells had fields showing summation to 4° or less with a mean length of 2.8° (+ / -0.15 sem). In this “short field” group, 18% had fields of 1° or less. We observed 7 cells with rapid initial spatial summation up to 1°, followed by clear end zone inhibition. It has been recently suggested on the basis of localised inactivation experiments, that layer VI cells with long (> 8°) fields may provide the drive to inhibitory interneurones in layer IV generating hypercomplex cell end zone inhibition. This observation is difficult to equate with evidence indicating that hypercomplex cell end zone inhibition reflects a mechanism showing maximal summation at lengths in the region of 2.8°. The present data show layer VI to possess cells capable of providing the drive for hypercomplex cell end zone inhibition in layer IV.

Further observations on the role of nitric oxide in the feline lateral geniculate nucleus

We have examined the responses of a population of 77 cells in the dorsal lateral geniculate nucleus (dLGN) of the anaesthetized, paralysed cat. Here the synthetic enzyme for the production of nitric oxide, nitric oxide synthase, is found only in the presynaptic terminals of the cholinergic input from the brainstem. In our hands, iontophoretic application of inhibitors of this enzyme resulted both in significant decreases in visual responses and decreased responses to exogenous application of NMDA, effects which were reversed by coapplication of the natural substrate for nitric oxide synthase, L‐arginine, but not the biologically inactive isomer, D‐arginine. Nitroprusside and S‐nitroso‐N‐acetylpenicillamine (SNAP), nitric oxide donors, but not L‐arginine, were able to increase markedly both spontaneous activity and the responsiveness to NMDA application. Furthermore, SNAP application facilitated visual responses. Responses of cells in animals without retinal, cortical and parabrachial input to the LGN suggest a postsynaptic site of action of nitric oxide. This modulation of the gain of visual signals transmitted to the cortex suggests a completely novel pathway for nitric oxide regulation of function, as yet described only in primary sensory thalamus of the mammalian central nervous system.

Actions of compounds manipulating the nitric oxide system in the cat primary visual cortex

1 We iontophoretically applied NG‐nitro‐L‐arginine (l‐NOArg), an inhibitor of nitric oxide synthase (NOS), to cells (n= 77) in area 17 of anaesthetized and paralysed cats while recording single‐unit activity extracellularly. In twenty‐nine out of seventy‐seven cells (38%), compounds altering NO levels affected visual responses. 2 In twenty‐five out of twenty‐nine cells, l‐NOArg non‐selectively reduced visually elicited responses and spontaneous activity. These effects were reversed by co‐application of l‐arginine (l‐Arg), which was without effect when applied alone. Application of the NO donor diethylamine‐nitric oxide (DEA‐NO) produced excitation in three out of eleven cells, all three cells showing suppression by l‐NOArg. In ten cells the effect of the soluble analogue of cGMP, 8‐bromo‐cGMP, was tested. In three of those in which l‐NOArg application reduced firing, 8‐bromo‐cGMP had an excitatory effect. In six out of fifteen cells tested, L‐NOArg non‐selectively reduced responses to NMDA and α‐amino‐3‐hydroxy‐5‐methylisoxasole‐4‐propionic acid (AMPA). Again, co‐application of l‐Arg reversed this effect, without enhancing activity beyond control values. 3 In a further subpopulation of ten cells, l‐NOArg decreased responses to ACh in five. 4 In four out of twenty‐nine cells l‐NOArg produced the opposite effect and increased visual responses. This was reversed by co‐application of l‐Arg. Some cells were also affected by 8‐bromo‐cGMP and DEA‐NO in ways opposite to those described above. It is possible that the variety of effects seen here could also reflect trans‐synaptic activation, or changes in local circuit activity. However, the most parsimonious explanation for our data is that NO differentially affects the activity of two populations of cortical cells, in the main causing a non‐specific excitation.

Controlled Trial on the Effect of 10 Days Low-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) on Motor Signs in Parkinson's Disease

We evaluated the effect of low‐frequency rTMS on motor signs in Parkinsons disease (PD), under a double‐blind placebo‐controlled trial design. PD patients were randomly assigned to received either real (n = 9) or sham (n = 9) rTMS for 10 days. Each session comprises two trains of 50 stimuli each delivered at 1 Hz and at 90% of daily rest motor threshold using a large circular coil over the vertex. The effect of the stimulation, delivered during the ON‐period, was evaluated during both ON and OFF periods. Tests were carried out before and after the stimulation period, and again 1 week after. The effect of the stimulation was evaluated through several gait variables (cadence, step amplitude, velocity, the CVstride‐time, and the turn time), hand dexterity, and also the total and motor sections of the UPDRS. Only the total and motor section of the UPDRS and the turn time during gait were affected by the stimulation, the effect appearing during either ON or OFF evaluation, and most importantly, equally displayed in both real and sham group. The rest of the variables were not influenced. We conclude the protocol of stimulation used, different from most protocols that apply larger amount of stimuli, but very similar to some previously reported to have excellent results, has no therapeutic value and should be abandoned. This contrasts with the positive reported effects using higher frequency and focal coils. Our work also reinforces the need for sham stimulation when evaluating the therapeutic effect of rTMS.

Receptive field structure of burst and tonic firing in feline lateral geniculate nucleus

There are two recognised modes of firing activity in thalamic cells, burst and tonic. A low‐threshold (LT) burst (referred to from now on as ‘burst’) comprises a small number of high‐frequency action potentials riding the peak of a LT Ca2+ spike which is preceded by a silent hyperpolarised state > 50 ms. This is traditionally viewed as a sleep‐like phenomenon, with a shift to tonic mode at wake‐up. However, bursts have also been seen in the wake state and may be a significant feature for full activation of recipient cortical cells. Here we show that for visual stimulation of anaesthetised cats, burst firing is restricted to a reduced area within the receptive field centre of lateral geniculate nucleus cells. Consistently, the receptive field size of all the recorded neurons decreased in size proportionally to the percentage of spikes in bursts versus tonic spikes, an effect that is further demonstrated with pharmacological manipulation. The role of this shrinkage may be distinct from that also seen in sleep‐like states and we suggest that this is a mechanism that trades spatial resolution for security of information transfer.

Non-length-tuned cells in layers II/III and IV of the visual cortex: the effect of blockade of layer VI on responses to stimuli of different lengths

We have previously shown, using a local inactivation technique, that layer VI provides a facilitatory input to the majority of hypercomplex cells located in layer IV above, and hence to layers II/III, which in many cases enhances length selectivity. However, many cells in these layers are not tuned for stimulus length, being equally responsive to long and short stimuli. Thus it is important to know whether layer VI can influence the responses of these cells. We have now used a similar paradigm of iontophoretic application of GABA to examine the effect of blockade of layer VI on the length tuning profiles of these cells in layers II–IV. During the blockade of layer VI, the most common effect, seen in 41% of the cells, was inhibition of visual responses, (i.e. commensurate with loss of a facilitatory input). An increase in response magnitude was found in 21% of the population, and responses were unaffected in 36% of cells tested. This suggests that the predominant influence of local regions of layer VI on this cell type, located in layers II/III and IV, is facilitatory, with a smaller proportion of cells receiving an inhibitory input. Such effects were seen even with the shortest lengths tested, suggesting once more that elements of layer VI are responsive to stimuli much shorter than was previously accepted. Thus these data suggest that layer VI plays a role in the generation of the response dynamics of non-length-tuned cells in overlying layers II/III and IV.