Juan Fernandez-Ruiz

Visual habit formation in monkeys with neurotoxic lesions of the ventrocaudal neostriatum

Visual habit formation in monkeys, assessed by concurrent visual discrimination learning with 24-h intertrial intervals (ITI), was found earlier to be impaired by removal of the inferior temporal visual area (TE) but not by removal of either the medial temporal lobe or inferior prefrontal convexity, two of TEs major projection targets. To assess the role in this form of learning of another pair of structures to which TE projects, namely the rostral portion of the tail of the caudate nucleus and the overlying ventrocaudal putamen, we injected a neurotoxin into this neostriatal region of several monkeys and tested them on the 24-h ITI task as well as on a test of visual recognition memory. Compared with unoperated monkeys, the experimental animals were unaffected on the recognition test but showed an impairment on the 24-h ITI task that was highly correlated with the extent of their neostriatal damage. The findings suggest that TE and its projection areas in the ventrocaudal neostriatum form part of a circuit that selectively mediates visual habit formation.

Prism adaptation in normal aging: slower adaptation rate and larger aftereffect

The effect of aging on prism adaptation, a motor learning paradigm, was evaluated. Different measures were obtained from a task consisting of throwing clay balls to a target in front of the subjects before, during, and after wearing prisms that deviate the visual field by several degrees. When performing the task without wearing the prisms, the aged subjects showed a larger hit variance, whereas the young subjects hit closer to the target. When donning the prisms, the aged group adapted more slowly than the controls, although after throwing all the balls both groups showed the same adaptation levels. After removing the prisms, the aged group showed a larger aftereffect. These findings suggest that the aftereffect requires the involvement of non-cognitive and cognitive processes and indicate that both adaptation and aftereffect are influenced by aging.

Relation between reaction time and reach errors during visuomotor adaptation

Adaptation of reaching movements to visuomotor transformations is generally thought to involve implicit or procedural learning. However, there is evidence that explicit or cognitive processes can also play a role (Redding and Wallace, 2006 [31]). For example, the early phase of adaptation to a visuomotor rotation appears to involve spatial working memory processes linked to mental rotation (Anguera et al., 2010 [11]). Since it is known that cognitive processes like mental rotation lead to larger reaction times (Georgopoulos and Massey, 1987 [12]), here we explored the relation between reaction time (RT) and reach error reduction. Two groups of subjects adapted their reaching movements to a 60° visuomotor rotation either without RT constraints or with RT limited to 350 ms. In the unconstrained group, we found that adaption rate varied widely across subjects and was strongly correlated with RT. Subjects who decreased hand direction error (DE) rapidly exhibited prolonged RTs whereas little RT cost was seen in subjects who decreased DE gradually. RTs were also correlated with after-effects seen when the visuomotor rotation was removed. Subjects with the longest RTs exhibited the smallest after-effects. In the RT constrained group, all subjects exhibited gradual DE adaptation and large after-effects, similar to the fast responders in the free group. These results suggest that adaptation to a visuomotor rotation can involve processes that produce faster error reductions without increasing after-effects, but at an expense of larger reaction times. Possible candidates are processes related to spatial working memory, and more specifically, to mental rotation.

Normal prism adaptation but reduced after-effect in basal ganglia disorders using a throwing task

Prism adaptation is a form of visuomotor learning in which the visual and motor systems need to be adjusted because a visual perturbation is produced by horizontally displacing prisms. Despite being known for over two centuries, the neuronal substrates of this phenomenon are not yet completely understood. In this article the possible role of the basal ganglia in this kind of learning was analysed through a study of Huntingtons and Parkinsons disease patients. A throwing technique requiring the use of open loop feedback was used. The variables analysed were visuomotor performance, adaptation rate and magnitude, and the after‐effect. The results clearly showed that both Huntingtons and Parkinsons disease groups learned at the same rate as control subjects. In addition, despite having a disturbed visuomotor performance, both experimental groups showed the same adaptation magnitude as the control group. Finally, the after‐effect, which is measured after removing the prisms, is reduced in both patients groups. This reduction leads to a disruption in the normal adaptation–after‐effect correlation found in normal volunteers. These results suggest that basal ganglia are not involved in this type of open‐looped visuomotor learning. The large number of patients studied as well as the similarity of the findings between both populations support this hypothesis. By contrast, there is an impairment in the after‐effect on both basal ganglia patient populations. This impairment may be the result of the deterioration of the perceptual recalibration process involved in visuomotor learning.

Spinocerebellar ataxia type 2 olfactory impairment shows a pattern similar to other major neurodegenerative diseases

Olfactory function is affected in different neurodegenerative diseases. Recently, it has been found that some hereditary ataxias are also associated with significant olfactory impairment. However, the initial findings did not examine the nature of the olfactory impairment associated with these ataxias. In the present article the effect of spinocerebellar ataxia type 2 (SCA2) on olfactory function was studied in 53 SCA2 patients and 53 healthy control subjects from Holguín, Cuba. Several tests were applied to evaluate olfactory threshold, description, identification and discrimination. The results show significant impairment in SCA2 patients on all olfactory measurements, and the pattern of olfactory deficits found suggests that they have much in common with those reported for other neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases.

Progression markers of Spinocerebellar Ataxia 2. A twenty years neurophysiological follow up study

Nerve conduction is profoundly affected in Spinocerebellar ataxia 2 (SCA2) even before the onset of the disease, but there is no information regarding its progression to the final stage of SCA2. In order to study the progression patterns of nerve conduction abnormalities in SCA2 we performed a prospective follow up evaluation of sensory and motor conduction in 21 SCA2 mutation carriers-initially presymptomatics- and 19 non-SCA2 mutation carriers during 20years. The earliest electrophysiological alterations were the reduction of sensory amplitudes in median and sural nerves, which could be found 8 to 5years prior disease onset and in the last 4years of the preclinical stage respectively. These abnormalities were followed by the increase of sensory latencies and decrease of conduction velocities. Sensory amplitudes progressively decreased during the follow-up clinical stage, rendering almost all patients with abnormal amplitudes and lack of sensory potentials, with faster progression rates in patients with larger CAG repeat lengths. Peripheral motor nerves showed the later involvement. These findings were used to define three distinct stages that describe the progression of the peripheral neuropathy. We suggest that sensory amplitudes could be useful biomarkers to assess the progression of peripheral nerve involvement and therefore to evaluate future clinical trials of therapeutic agents.

Prism adaptation in spinocerebellar ataxia type 2

Patients with spinocerebellar ataxia type 2 (SCA2), develop severe pontine nuclei, inferior olives, and Purkinje cell degeneration. This form of autosomal dominant cerebellar ataxia is accompanied by progressive ataxia and dysarthria. Although the motor dysfunction is well characterized in these patients, nothing is known about their motor learning capabilities. Here we tested 43 SCA2 patients and their matched controls in prism adaptation, a kind of visuomotor learning task. Our results show that their pattern of brain damage does not entirely disrupt motor learning. Rather, patients had impaired adaptation decrement, but surprisingly a normal aftereffect. Moreover, the mutation degree could discriminate the degree of adaptation. This pattern could reflect the net contribution of two adaptive mechanisms: strategic control and spatial realignment. Accordingly, SCA2 patients show an impaired strategic control that affects the adaptation rate, but a normal spatial realignment measured through the aftereffect. Our results suggest that the neural areas subserving spatial realignment are spared in this form of spinocerebellar ataxia.

Correlation between acetylcholine release and recovery of conditioned taste aversion induced by fetal neocortex grafts

Rats with lesions of the gustatory neocortex (GN) show deficits in the acquisition of taste aversion. Fetal GN grafts to a lesioned animal restore taste aversion learning and establish connections with the host brain. In this work, we examined whether the grafts are biochemically functional and whether this fact can be related to behavioral recovery. Gustatory or occipital cortices from rat fetuses were transplanted to GN-lesioned rats. Two months later, taste aversion recovery was tested and the release of labeled gamma-aminobutyric acid (GABA), acetylcholine (ACh), dopamine and glutamate from the grafted tissue was assayed. Fetal GN grafts promoted recovery of learning and released GABA, ACh and glutamate in response to K+ depolarization. Occipital cortex grafts did not induce behavioral recovery, although they were capable of releasing GABA. In contrast, these grafts did not release ACh. Moreover, GN-grafted rats in which behavioral recovery was not seen also failed to release ACh. These results are in agreement with previous findings that cholinergic transmission is important in the GN and suggest that ACh may play a role in the graft-mediated behavioral recovery observed in this model.

Olfactory dysfunction in hereditary ataxia and basal ganglia disorders.

&NA; In the present study the olfactory system of hereditary ataxia patients was tested using the smell identification test. Two previous findings suggested a possible olfactory impairment in these patients. First, an olfactory dysfunction has been found in different neurodegenerative diseases, and second, human functional imaging has shown cerebellar activation during olfaction. As an initial approach to determine if cerebellar ataxia impairs the olfactory process, cerebellar ataxia patients, along with basal ganglia patients, were tested. The results show an olfactory deficit in both basal ganglia and hereditary ataxia patients. Further exploration of the olfactory capacities in hereditary ataxia is necessary to elucidate the specific nature of the deficits. NeuroReport 14:1339–1341

Long-term cognitive impairment in MPTP-treated rhesus monkeys

Following MPTP administration, monkeys manifest cognitive deficits on tasks known to assess the fronto-striatal system; there are, however, no data regarding long-term cognitive effects. In this study, we examined the cognitive abilities of monkeys 10 years after MPTP administration. MPTP-treated monkeys and age-matched controls performed a spatial delayed response task with fixed and random delays. The MPTP-treated monkeys were impaired in both versions of the task. Both groups performed at the same level at very short delays suggesting that the nature of the impairment is related to a spatial memory deficit that is still apparent 10 years after treatment. These results suggest that, like Parkinsons patients, the MPTP-treated primates display spatial deficits.