The impact of early musical training on striatal functional connectivity.

Evidence from language, visual and sensorimotor learning suggests that training early in life is more effective. The present work explores the hypothesis that learning during sensitive periods involves distinct brain networks in addition to those involved when learning later in life. Expert pianists were tested who started their musical training early (<7 years of age; n = 21) or late (n = 15), but were matched for total lifetime practice. Motor timing expertise was assessed using a musical scale playing task. Brain activity at rest was measured using fMRI and compared with a control group of nonmusicians (n = 17). Functional connectivity from seeds in the striatum revealed a striatal-cortical-sensorimotor network that was observed only in the early-onset group. In this network, higher connectivity correlated with greater motor timing expertise, which resulted from early/late group differences in motor timing expertise. By contrast, networks that differentiated musicians and nonmusicians, namely a striatal-occipital-frontal-cerebellar network in which connectivity was higher in musicians, tended to not show differences between early and late musicians and not be correlated with motor timing expertise. These results parcel musical sensorimotor neuroplasticity into a set of musicianship-related networks and a distinct set of predominantly early-onset networks. The findings lend support to the possibility that we can learn skills more easily early in development because during sensitive periods we recruit distinct brain networks that are no longer implicated in learning later in life.

Early stages of sensorimotor map acquisition: neurochemical signature in primary motor cortex and its relation to functional connectivity.

The earliest stages of sensorimotor learning involve learning the correspondence between movements and sensory results-a sensorimotor map. The present exploratory study investigated the neurochemical underpinnings of map acquisition by monitoring 25 participants as they acquired a new association between movements and sounds. Functional magnetic resonance spectroscopy was used to measure neurochemical concentrations in the left primary motor cortex during learning. Resting-state functional magnetic resonance imaging data were also collected before and after training to assess learning-related changes in functional connectivity. There were monotonic increases in γ-aminobutyric acid (GABA) and decreases in glucose during training, which extended into the subsequent rest period and, importantly, in the case of GABA correlated with the amount of learning: participants who showed greater behavioral learning showed greater GABA increase. The GABA change was furthermore correlated with changes in functional connectivity between the primary motor cortex and a cluster of voxels in the right intraparietal sulcus: greater increases in GABA were associated with greater strengthening of connectivity. Transiently, there were increases in lactate and reductions in aspartate, which returned to baseline at the end of training, but only lactate showed a statistical trend to correlate with the amount of learning. In summary, during the earliest stages of sensorimotor learning, GABA levels are linked on a subject-level basis to both behavioral learning and a strengthening of functional connections that persists beyond the training period. The findings are consistent with the idea that GABA-mediated inhibition is linked to maintenance of newly learned information.NEW & NOTEWORTHY Learning the mapping between movements and their sensory effects is a necessary step in the early stages of sensorimotor learning. There is evidence showing which brain areas are involved in early motor learning, but their role remains uncertain. Here, we show that GABA, a neurotransmitter linked to inhibitory processing, rises during and after learning and is involved in ongoing changes in resting-state networks.

Early stages of sensorimotor map acquisition: learning with free exploration, without active movement or global structure.

One of the puzzles of learning to talk or play a musical instrument is how we learn which movement produces a particular sound: an audiomotor map. The initial stages of map acquisition can be studied by having participants learn arm movements to auditory targets. The key question is what mechanism drives this early learning. Three learning processes from previous literature were tested: map learning may rely on active motor outflow (target), on error correction, and on the correspondence between sensory and motor distances (i.e., that similar movements map to similar sounds). Alternatively, we hypothesized that map learning can proceed without these. Participants made movements that were mapped to sounds in a number of different conditions that each precluded one of the potential learning processes. We tested whether map learning relies on assumptions about topological continuity by exposing participants to a permuted map that did not preserve distances in auditory and motor space. Further groups were tested who passively experienced the targets, kinematic trajectories produced by a robot arm, and auditory feedback as a yoked active participant (hence without active motor outflow). Another group made movements without receiving targets (thus without experiencing errors). In each case we observed substantial learning, therefore none of the three hypothesized processes is required for learning. Instead early map acquisition can occur with free exploration without target error correction, is based on sensory-to-sensory correspondences, and possible even for discontinuous maps. The findings are consistent with the idea that early sensorimotor map formation can involve instance-specific learning.NEW & NOTEWORTHY This study tested learning of novel sensorimotor maps in a variety of unusual circumstances, including learning a mapping that was permuted in such as way that it fragmented the sensorimotor workspace into discontinuous parts, thus not preserving sensory and motor topology. Participants could learn this mapping, and they could learn without motor outflow or targets. These results point to a robust learning mechanism building on individual instances, inspired from machine learning literature.

The role of auditory feedback in music-supported stroke rehabilitation: A single-blinded randomised controlled intervention.

PURPOSE: Learning to play musical instruments such as piano was previously shown to benefit post-stroke motor rehabilitation. Previous work hypothesised that the mechanism of this rehabilitation is that patients use auditory feedback to correct their movements and therefore show motor learning. We tested this hypothesis by manipulating the auditory feedback timing in a way that should disrupt such error-based learning. METHODS: We contrasted a patient group undergoing music-supported therapy on a piano that emits sounds immediately (as in previous studies) with a group whose sounds are presented after a jittered delay. The delay was not noticeable to patients. Thirty-four patients in early stroke rehabilitation with moderate motor impairment and no previous musical background learned to play the piano using simple finger exercises and familiar children's songs. RESULTS: Rehabilitation outcome was not impaired in the jitter group relative to the normal group. Conversely, some clinical tests suggests the jitter group outperformed the normal group. CONCLUSIONS: Auditory feedback-based motor learning is not the beneficial mechanism of music-supported therapy. Immediate auditory feedback therapy may be suboptimal. Jittered delay may increase efficacy of the proposed therapy and allow patients to fully benefit from motivational factors of music training. Our study shows a novel way to test hypotheses concerning music training in a single-blinded way, which is an important improvement over existing unblinded tests of music interventions.

Musician's dystonia in pianists: long-term evaluation of retraining and other therapies.

OBJECTIVE: Musician's dystonia is characterized by loss of voluntary motor control in extensively trained movements on an instrument. The condition is difficult to treat. This retrospective study reports on the interventions received by a homogeneous cohort of pianists with musician's dystonia and the subjective and objective changes reported in task performance. METHODS: This is a retrospective descriptive study. Fifty four pianists with musician's dystonia who had received care in a Movement Disorders Clinic completed a self report questionnaire regarding type and effectiveness of treatment received over the last 4 years. Pianists' fine motor control was assessed objectively by measuring the temporal regularity of their scale playing. RESULTS: Nearly all patients (98.0%) reported deficits in motor tasks other than musical playing. Half of the patients were taking medications (Botulinum toxin (53%), Trihexyphenidyl (51%)). Subjects reported participating in multiple therapies: retraining (87%), hand therapy (42%), relaxation techniques (38%), physiotherapy (30%), psychotherapy (23%), acupuncture (21%) and body techniques (21%). Self-reported improvements in motor performance were reported by 81.5% of the subjects with 5.6% reporting a complete recovery. Objective gains in task-specific motor performance were documented in 42.9% of the subjects (with deterioration in 4.8%). Retraining therapy, relaxation techniques and change in teacher explained 52% of the variance in subjective outcomes. CONCLUSIONS: Musician's dystonia not only interferes with musical performance but other fine motor tasks. Objectively, approximately 50% of patients improved task performance following participation in a variety of intervention strategies, but subjectively, 80% of subjects reported improvement.

Feline bordetellosis: challenge and vaccine studies.

Four eight-week-old cats, shown to be free from feline calicivirus, feline herpesvirus and Chlamydia psittaci were challenged with an aerosol of Bordetella bronchiseptica. Within five days the cats developed signs of respiratory disease, characterised by nasal discharge, sneezing, spontaneous or induced coughing and dry or wet rales at auscultation. These signs were present for about 10 days, after which they began to resolve. To test the protective capacity of an experimental fimbrial antigen-based subunit vaccine, 10 kittens were vaccinated twice, with two weeks between the vaccinations, and five kittens were left unvaccinated. Two weeks after the booster the 15 kittens were challenged with an aerosol of B bronchiseptica as the sole pathogen. On the day of challenge the vaccinated kittens had a mean bordetella antibody titre of 2(9.5) whereas the control cats remained seronegative (titre < 2(2)). The control cats developed signs of respiratory disease after challenge, whereas the vaccinated cats were almost completely protected. The degrees of protection against rhinitis, sneezing, spontaneous or induced coughing, and dry or wet rales at auscultation were 100 per cent, 95 per cent, 95 per cent and 100 per cent, respectively. Furthermore, the vaccinated kittens cleared the challenge bacteria more quickly than the controls, resulting in a reduction of 80 per cent on days 15 and 18 after challenge and a reduction of 99 per cent on days 22 and 29 after challenge. The results show that B bronchiseptica can act as a primary pathogen in cats and that a vaccine containing the fimbrial antigen induces a protective immune response.

Aspects of ketogenesis: control and mechanism of ketone-body formation in isolated rat-liver mitochondria.

The synthesis of ketone bodies by intact isolated rat-liver mitochondria has been studied at varying rates of acetyl-CoA production and of acetyl-CoA utilization in the Krebs cycle. Factors which enhanced the rate of acetyl-CoA production caused an increase in the fraction of acetyl-CoA which was incorporated into ketone bodies. On the other hand, it was found that factors which stimulated the formation of citrate lowered the relative rate of ketogenesis. It is concluded that acetyl-CoA is preferentially used for citrate synthesis, if the level of oxaloacetate in the mitochondrial matrix space is adequate. The intramitochondrial level of oxaloacetate, which is determined by the malate concentration and the ratio of NADH over NAD+, is the main factor controlling the rate of citrate synthesis. The ATP/ADP ratio per se does not affect the activity of citrate synthase in this in vitro system. Ketogenesis can be described as an overflow of acetyl-groups: Ketone-body formation is stimulated only when the rate of acetyl-CoA production increases beyond the capacity for citrate synthesis. The interaction between fatty acid oxidation and pyruvate metabolism and the effects of long-chain acyl-CoA on mitochondrial metabolism are discussed. Ketone bodies which were generated during the oxidation of [1-14C] fatty acids were preferentially labelled in their carboxyl group. This carboxyl group had the same specific activity as the acetyl-CoA pool, whereas the specific activity of the acetone moiety of acetoacetate was much lower, especially at low rates of ketone-body formation. The activities of acetoacetyl-CoA deacylase and the hydroxymethylglutaryl-CoA (HMG-CoA) pathway were compared in soluble and mitochondrial fractions of rat- and cow-liver in different ketotic states. In rat-liver mitochondria, both pathways of acetoacetate synthesis were stimulated upon starvation or in alloxan diabetes. In cow liver, only the HMG-CoA pathway was increased during ketosis in the mitochondrial as well as in the soluble fraction.

Composition and metabolism of phospholipids of Fasciola hepatics, the common liver fluke.

1. The phospholipid composition of Fasciola hepatica, the common liver fluke, was compared to that of the liver of the host animals (rats and cattle). Considerable differences were found:monoacyl-sn-glycero-3-phosphorylcholine, hardly detectable in the liver, was found in significant amounts in the parasite. On the other hand, sphingomyelin, a normal constituent in the liver, appears to be absent in the liver fluke. Fasciola hepatica isolated from rat and cow liver had a strikingly similar phospholipid composition. 2. Qualitative and quantitative differences were also found between the fatty acyl constituents of the phospholipids of the parasite and the liver. The major difference was the presence of eicosaenoic and eicosadienoic acids in the parasite, whereas these acids were not detected in the liver. 3. In vitro incubations of Fasciola hepatica in the presence of (32P)phosphate and (2-3H)glycerol resulted in the labelling of all phospholipids of the parasite, except that the 3H label did not incorporate into ethanolamine plasmalogen. This is in agreement with the concept that in animals, glycerol is introduced into plasmalogens via dihydroxyacetonephosphate. 4. Homogenates of liver flukes were found to catalyze the synthesis of phosphatidylcholine from 1,2-diacyl-sn-glycerols and CDPcholine. 5. These results strongly suggest that Fasciola hepatica is capable of synthesizing at least part of its fatty acids and phospholipids.