Javier Cudeiro

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.

Always returning: feedback and sensory processing in visual cortex and thalamus

Feedback projections are an integral part of the mammalian visual system. Although it is tempting to relegate them to a subsidiary role in visual processing, because their supposed latency and lag might appear to be unfavourable for an involvement in fast processing, this is a dangerous simplification. Certainly for the world in motion, feedback from higher motion areas can influence the transfer of ascending input when, or even before, the input arrives. Here, we consider the circuit formed by layer 6 feedback cells in the visual cortex and how this straddles the retinothalamic and thalamocortical transfer of visual input. We discuss its links to feedback from the cortical motion area MT (V5), and suggest that motion perception involves a dynamic interplay between MT, V1 and the thalamus. This review is part of the TINS special issue on The Neural Substrates of Cognition.

Effects of rhythmic sensory stimulation (auditory, visual) on gait in Parkinson’s disease patients

This study has focused on how sensory stimulation affects gait in Parkinson’s disease (PD). The kinematic parameters of gait [cadence, step amplitude, velocity, coefficient of variation of stride time (CVstride-time), and the coefficient of variation of the step amplitude (CVstep-amplitude)] were analysed in 25 PD patients and 10 control subjects. Step amplitude, velocity and CVstride-time were altered in the patients with PD. However, when kinematic parameters were analysed as a function of disease severity, none of the parameters differed between early PD (I–II Hoehn and Yahr) and the controls. Nevertheless, more severely affected PD patients (III–IV Hoehn and Yahr) walked with a reduced step amplitude, lower velocity, higher CVstride-time, and higher CVstep-amplitude than the controls. The administration of auditory stimulation at a frequency matching the preferred walking cadence led to a decrease in the CVstride-time in PDIII–IV patients, and to an increase in step amplitude in PDIII–IV and controls. Visual stimulation at the same frequency did not modify any of the altered kinematic parameters in PDIII–IV patients. When different stimulation frequencies were utilised, auditory stimulation significantly changed some of the altered walking parameters in Parkinson patients. Frequencies matching preferred walking cadence or above this, up to the fastest walking, were those that seem to interact most effectively with the abnormal kinematic parameters in PDIII–IV patients. Visual stimulation negatively modulated cadence in PDIII–IV in the frequency range used. Sensory stimulation facilitates gait in PD. Studies using sensory stimulation as a tool to facilitate walking should take into account the grade of disability of the patients.

Looking back: corticothalamic feedback and early visual processing

Although once regarded as a simple sensory relay on the way to the cortex, it is increasingly apparent that the thalamus has a role in the ongoing moment-by-moment processing of sensory input and in cognition. This involves extensive corticofugal feedback connections and the interplay of these with the local thalamic circuitry and the other converging inputs. Here, using the feline visual system as the primary model, some of the latest developments in this field are reviewed and placed in the perspective of an integrated view of system function. Cortical feedback mediated by ionotropic and metabotropic glutamate receptors, and effects mediated by the neuromodulator nitric oxide, all have a role in integrating the thalamic mechanism into the cortical circuit. The essential point is that the perspective of higher-level sensory mechanisms shifts and modulates the thalamic circuitry in ways that optimize abstraction of a meaningful representation of the external world. This review is part of the TINS special issue on The Neural Substrates of Cognition.

Effect of Rhythmic Auditory Stimulation on Gait in Parkinsonian Patients with and without Freezing of Gait

Freezing of gait (FOG) in Parkinsons disease (PD) rises in prevalence when the effect of medications decays. It is known that auditory rhythmic stimulation improves gait in patients without FOG (PD-FOG), but its putative effect on patients with FOG (PD+FOG) at the end of dose has not been evaluated yet. This work evaluates the effect of auditory rhythmic stimulation on PD+FOG at the end of dose. 10 PD+FOG and 9 PD-FOG patients both at the end of dose periods, and 10 healthy controls were asked to perform several walking tasks. Tasks were performed in the presence and absence of auditory sensory stimulation. All PD+FOG suffered FOG during the task. The presence of auditory rhythmic stimulation (10% above preferred walking cadence) led PD+FOG to significantly reduce FOG. Velocity and cadence were increased, and turn time reduced in all groups. We conclude that auditory stimulation at the frequency proposed may be useful to avoid freezing episodes in PD+FOG.

Aquatic therapy versus conventional land-based therapy for Parkinson's disease: an open-label pilot study

OBJECTIVES To assess and compare 2 different protocols of physiotherapy (land or water therapy) for people with Parkinsons disease (PD) focused on postural stability and self-movement, and to provide methodological information regarding progression within the program for a future larger trial. DESIGN Randomized, controlled, open-label pilot trial. SETTING Outpatients, Parkinsons disease Center of Ferrol-Galicia (Spain). PARTICIPANTS Individuals (N=11) with idiopathic PD in stages 2 or 3 according to the Hoehn and Yahr Scale completed the investigation (intervention period plus follow-up). INTERVENTIONS After baseline evaluations, participants were randomly assigned to a land-based therapy (active control group) or a water-based therapy (experimental group). Participants underwent individual sessions for 4 weeks, twice a week, for 45 minutes per session. Both interventions were matched in terms of exercise features, which were structured in stages with clear objectives and progression criteria to pass to the next phase. MAIN OUTCOME MEASURES Participants underwent a first baseline assessment, a posttest immediately after 4 weeks of intervention, and a follow-up assessment after 17 days. Evaluations were performed OFF-dose after withholding medication for 12 hours. Functional assessments included the Functional Reach Test (FRT), the Berg Balance Scale (BBS), the UPDRS, the 5-m walk test, and the Timed Up and Go test. RESULTS A main effect of both therapies was seen for the FRT. Only the aquatic therapy group improved in the BBS and the UPDRS. CONCLUSIONS In this pilot study, physiotherapy protocols produced improvement in postural stability in PD that was significantly larger after aquatic therapy. The intervention protocols are shown to be feasible and seem to be of value in amelioration of postural stability-related impairments in PD. Some of the methodological aspects detailed here can be used to design larger controlled trials.

Effect of whole body vibration in Parkinson's disease: a controlled study

In the search of new strategies to improve the quality of life of Parkinsons disease patients, recent work has reported an amelioration of Parkinsonian symptoms using Whole Body Vibration (WBV). A double‐blinded, placebo controlled design was used to evaluate the effect of a 12 WBV sessions‐programme on a number of motor and clinical tests in 23 Parkinsons disease patients. Patients were assigned to one of two groups, one receiving WBV and the other a placebo group. At the end of the programme as well as during intra‐session evaluation, there was no difference between the experimental (vibration) and placebo groups in any outcomes. These results suggest that reported benefits of vibration are due to a placebo response.

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.

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.