Speech listening entails neural encoding of invisible articulatory features.

Speech processing entails a complex interplay between bottom-up and top-down computations. The former is reflected in the neural entrainment to the quasi-rhythmic properties of speech acoustics while the latter is supposed to guide the selection of the most relevant input subspace. Top-down signals are believed to originate mainly from motor regions, yet similar activities have been shown to tune attentional cycles also for simpler, non-speech stimuli. Here we examined whether, during speech listening, the brain reconstructs articulatory patterns associated to speech production. We measured electroencephalographic (EEG) data while participants listened to sentences during the production of which articulatory kinematics of lips, jaws and tongue were also recorded (via Electro-Magnetic Articulography, EMA). We captured the patterns of articulatory coordination through Principal Component Analysis (PCA) and used Partial Information Decomposition (PID) to identify whether the speech envelope and each of the kinematic components provided unique, synergistic and/or redundant information regarding the EEG signals. Interestingly, tongue movements contain both unique as well as synergistic information with the envelope that are encoded in the listener's brain activity. This demonstrates that during speech listening the brain retrieves highly specific and unique motor information that is never accessible through vision, thus leveraging audio-motor maps that arise most likely from the acquisition of speech production during development.

Motor synergies: Evidence for a novel motor signature in autism spectrum disorder.

In autism spectrum disorder (ASD), socio-communicative impairments and stereotypical behaviours are paralleled by sensorimotor deficits. Individuals with ASD show an altered selection of motor parameters, resulting in clumsy and fragmented actions. Here, we investigated inter-joint coordination and motor synergies as a potential substrate of motor control problems in ASD. Synergies enable co-controlling redundant motor degrees of freedom (DoF, e.g. joint angles, muscles) by mapping behavioural goals into a flexible and low-dimensional set of variables. This mechanism simplifies motor control and helps to find unambiguous solutions for motor tasks. In a reaching-grasping paradigm, children with ASD showed reduced coupling between DoF, which correlated with socio-communicative symptoms severity. Impaired synergies may help to frame well-established motor problems in ASD, including impaired motor sequencing and abnormal trial-to-trial motor variability. On the other hand, synergies also provide an effective and compact coding system of observed actions. Impaired synergies may thus jeopardize motor interaction by initiating bottom-up cascade effects, leading to pervasive impairments of social behaviour. Finally, we trained an automatic classification algorithm to distinguish between ASD and typically developing (TD) participants based on reaching-grasping kinematics. Classification accuracy reached up to 0.947. This result corroborates and expands previous accounts claiming that motor-based early recognition is feasible and effective in ASD.

Motor Recruitment during Action Observation: Effect of Interindividual Differences in Action Strategy.

Visual processing of other's actions is supported by sensorimotor brain activations. Access to sensorimotor representations may, in principle, provide the top-down signal required to bias search and selection of critical visual features. For this to happen, it is necessary that a stable one-to-one mapping exists between observed kinematics and underlying motor commands. However, due to the inherent redundancy of the human musculoskeletal system, this is hardly the case for multijoint actions where everyone has his own moving style (individual motor signature-IMS). Here, we investigated the influence of subject's IMS on subjects' motor excitability during the observation of an actor achieving the same goal by adopting two different IMSs. Despite a clear dissociation in kinematic and electromyographic patterns between the two actions, we found no group-level modulation of corticospinal excitability (CSE) in observers. Rather, we found a negative relationship between CSE and actor-observer IMS distance, already at the single-subject level. Thus, sensorimotor activity during action observation does not slavishly replicate the motor plan implemented by the actor, but rather reflects the distance between what is canonical according to one's own motor template and the observed movements performed by other individuals.

Publisher Correction: Anticipatory postural adjustments during joint action coordination.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Anticipatory postural adjustments during joint action coordination.

There is a current claim that humans are able to effortlessly detect others' hidden mental state by simply observing their movements and transforming the visual input into motor knowledge to predict behaviour. Using a classical paradigm quantifying motor predictions, we tested the role of vision feedback during a reach and load-lifting task performed either alone or with the help of a partner. Wrist flexor and extensor muscle activities were recorded on the supporting hand. Early muscle changes preventing limb instabilities when participants performed the task by themselves revealed the contribution of the visual input in postural anticipation. When the partner performed the unloading, a condition mimicking a split-brain situation, motor prediction followed a pattern evolving along the task course and changing with the integration of successive somatosensory feedback. Our findings demonstrate that during social behaviour, in addition to self-motor representations, individuals cooperate by continuously integrating sensory signals from various sources.

X-linked hypophosphatemic rickets: an Italian experts' opinion survey.

BACKGROUND: X-linked hypophosphatemic rickets (XLH) is the first cause of inherited hypophosphatemia and is caused by mutation in the PHEX gene, resulting in excessive expression of the phosphaturic factor FGF23. Symptoms are mainly related to rickets in children and osteomalacia in adults and cause several complications that can be highly invalidating. Due to its rarity, XLH is poorly known and diagnosis is frequently delayed. Conventional treatment is based on oral phosphate salts supplementation and activated vitamin D analogs, which however, cannot cure the disease in most cases. OBJECTIVE: Due to the low prevalence of XLH, an experts' opinion survey was conducted across Italian centers to collect data on XLH and on its management. METHODS: A questionnaire was developed by a group of experts to collect data on XLH epidemiology, diagnosis and treatment in Italy. RESULTS: Data from 10 Italian centers (nine of which pediatric) on 175 patients, followed between 1998 and 2017, were included in the survey. Most patients were followed since childhood and 63 children became adults during the investigated period. The diagnosis was made before the age of 1 and between 1 and 5 years in 11 and 50% of cases, respectively. Clinically apparent bone deformities were present in 95% of patients. These were ranked moderate/severe in 75% of subjects and caused growth stunting in 67% of patients. Other frequent complications included bone pain (40%), dental abscesses (33%), and dental malpositions (53%). Treatment protocols varied substantially among centers. Nephrocalcinosis was observed in 34% of patients. Tertiary hyperparathyroidism developed in 6% of patients. CONCLUSIONS: XLH remains a severe condition with significant morbidities.

Cost-effectiveness analysis of late prophylaxis vs. on-demand treatment for severe haemophilia A in Italy.

INTRODUCTION: Long-term regular administrations of factor VIII (FVIII) concentrate (prophylaxis) initiated at an early age prevents bleeding in patients with severe haemophilia A (HA). The 5-year prospective Italian POTTER study provided evidence of benefits in adolescents and adults of late prophylaxis (LP) vs. on-demand therapy (OD) in reducing bleeding episodes and joint morbidity and improving quality of life; however, costs were increased. AIM: The aim of this study was to determine the cost-effectiveness of LP vs. OD with sucrose-formulated recombinant FVIII in adolescents and adults with severe HA in Italy. METHODS: A Markov model evaluated lifetime cost-effectiveness of LP vs. OD in patients with severe HA in Italy, from both the healthcare and societal perspectives. Clinical input parameters were taken from the POTTER study and published literature. Health utility values were assigned to each health state as measured by the joint disease severity Pettersson score. Costs were expressed in Euro (€) 2014, including drug and other medical costs. Sensitivity analyses were performed considering societal perspective (including productivity lost) and varying relative risk of bleeding episodes between regimens. Clinical outcomes and costs were discounted at 6% according to previous studies. RESULTS: Lifetime incremental discounted quality-adjusted life-years (QALYs) were +4.26, whereas incremental discounted costs were +€229,694 from a healthcare perspective, with estimated incremental cost-effectiveness ratios (ICERs) equal to €53,978/QALY. Sensitivity analyses confirmed the base-case results showing lower ICERs with the societal perspective. CONCLUSION: Late prophylaxis vs. on-demand therapy results in a cost-effective approach with ICERs falling below the threshold considered acceptable in Italy.

Distinct brain signatures of content and structure violation during action observation.

Sentences, musical phrases and goal-directed actions are composed of elements that are linked by specific rules to form meaningful outcomes. In goal-directed actions including a non-canonical element or scrambling the order of the elements alters the action's content and structure, respectively. In the present study we investigated event-related potentials of the electroencephalographic (EEG) activity recorded during observation of both alterations of the action content (obtained by violating the semantic components of an action, e.g. making coffee with cola) and alterations of the action structure (obtained by inverting the order of two temporally adjacent pictures of sequences depicting daily life actions) interfering with the normal flow of the motor acts that compose an action. Action content alterations elicited a bilateral posterior distributed EEG negativity, peaking at around 400 ms after stimulus onset similar to the ERPs evoked by semantic violations in language studies. Alteration of the action structure elicited an early left anterior negativity followed by a late left anterior positivity, which closely resembles the ERP pattern found in language syntax violation studies. Our results suggest a functional dissociation between the processing of action content and structure, reminiscent of a similar dissociation found in the language or music domains. Importantly, this study provides further support to the hypothesis that some basic mechanisms, such as the rule-based structuring of sequential events, are shared between different cognitive domains.

Listening to speech recruits specific tongue motor synergies as revealed by transcranial magnetic stimulation and tissue-Doppler ultrasound imaging.

The activation of listener's motor system during speech processing was first demonstrated by the enhancement of electromyographic tongue potentials as evoked by single-pulse transcranial magnetic stimulation (TMS) over tongue motor cortex. This technique is, however, technically challenging and enables only a rather coarse measurement of this motor mirroring. Here, we applied TMS to listeners' tongue motor area in association with ultrasound tissue Doppler imaging to describe fine-grained tongue kinematic synergies evoked by passive listening to speech. Subjects listened to syllables requiring different patterns of dorso-ventral and antero-posterior movements (/ki/, /ko/, /ti/, /to/). Results show that passive listening to speech sounds evokes a pattern of motor synergies mirroring those occurring during speech production. Moreover, mirror motor synergies were more evident in those subjects showing good performances in discriminating speech in noise demonstrating a role of the speech-related mirror system in feed-forward processing the speaker's ongoing motor plan.

Lexicality drives audio-motor transformations in Broca's area.

Broca's area is classically associated with speech production. Recently, Broca's area has also been implicated in speech perception and non-linguistic information processing. With respect to the latter function, Broca's area is considered to be a central area in a network constituting the human mirror system, which maps observed or heard actions onto motor programs to execute analogous actions. These mechanisms share some similarities with Liberman's motor theory, where objects of speech perception correspond to listener's intended articulatory gestures. The aim of the current series of behavioral, TMS and fMRI studies was to test if Broca's area is indeed implicated in such audio-motor transformations. More specifically, using a classical phonological rhyme priming paradigm, we investigated whether the role of Broca's area could be purely phonological or rather, is lexical in nature. In the behavioral baseline study, we found a large priming effect in word prime/target pairs (W-W) and no effect for pseudo-words (PW-PW). Online TMS interference of Broca's area canceled the priming difference between W-W and PW-PW by enhancing the effects for PW-PW. Finally, the fMRI study showed activation of Broca's area for W-W pairs, but not for PW-PW pairs. Our data show that Broca's area plays a significant role in speech perception strongly linked to the lexicality of a stimulus.

An fMRI investigation on image generation in different sensory modalities: the influence of vividness.

In the present fMRI study the issue of the specific cortices activation during imagery generation in different sensory modalities is addressed. In particular, we tested whether the vividness variability of imagery was reflected in the BOLD signal within specific sensory cortices. Subjects were asked to generate a mental image for each auditory presented sentence. Each imagery modality was contrasted with an abstract sentence condition. In addition, subjects were asked to fill the Italian version of the Questionnaire Upon Mental Imagery (QMI) prior to each neuroimaging session. In general, greater involvement of sensory specific cortices in high-vivid versus low-vivid subjects was found for visual (occipital), gustatory (anterior insula), kinaesthetic (pre-motor), and tactile and for somatic (post-central parietal) imagery modalities. These results support the hypothesis that vividness is related to image format: high-vivid subjects would create more analogical representations relying on the same specific neural substrates active during perception with respect to low-vivid subjects. Results are also discussed according to the simulation perspective.

Brain network for passive word listening as evaluated with ICA and Granger causality.

Brain network modeling is probably the biggest challenge in fMRI data analysis. Higher cognitive processes in fact, rely on complex dynamics of temporally and spatially segregated brain activities. A number of different techniques, mostly derived from paradigmatic hypothesis-driven methods, have been successfully applied for such purpose. This paper instead, presents a new data-driven analysis approach that applies both independent components analysis (ICA) and the Granger causality (GC). The method includes two steps: (1) ICA is used to extract the independent functional activities; (2) the GC is applied to the independent component (IC) most correlated with the stimuli, to indicate its functional relation with other ICs. This new method is applied to the analysis of fMRI study of listening to high-frequency trisyllabic words, non-words and reversed words. As expected, activity was found in the primary and secondary auditory cortices. Additionally, a parieto-frontal network of activations, supported by temporal and causality relationships, was found. This network is modulated by experimental conditions in agreement with the most recent models presented for word perception. The results have confirmed the validity of the proposed method, and seem promising for the detection of cognitive causal relationships in neuroimaging data.

Cost effectiveness of olanzapine in prevention of affective episodes in bipolar disorder in the United Kingdom.

This study evaluated the cost effectiveness of olanzapine compared with lithium as maintenance therapy for patients with bipolar I disorder (BP1) in the UK. A Markov model was developed to assess costs and outcomes from the perspective of the UK National Health Service over a 1-year period. Patients enter the model after stabilization of a manic episode and are then treated with olanzapine or lithium. Using the findings of a recent randomized clinical trial, the model considers the monthly risk of manic or depressive episodes and of dropping out from allocated therapy. health care resources associated with acute episodes were derived primarily from a recent UK chart review. Costs of maintenance therapy and monitoring were also considered. Key factors influencing cost effectiveness were identified and included in a stochastic sensitivity analysis. The model estimated that, compared to lithium, olanzapine significantly reduced the annual number of acute mood episodes per patient from 0.81 to 0.58 (difference -0.23; 95% CI: -0.34, -0.12). Per patient average annual care costs fell by 799 UK pounds (95% CI: - 1,824 UK pounds, 59 UK pounds) driven by reduced inpatient days--but the cost difference was not statistically significant. Sensitivity analysis found the results to be robust to plausible variation in the model's parameters. The model estimated that using olanzapine instead of lithium as maintenance therapy for BP1 would significantly reduce the rate of acute mood events resulting in reduced hospital costs. Based on available evidence, there is a high likelihood that olanzapine would reduce costs of care compared to lithium.

Cross-modal plasticity of the motor cortex while listening to a rehearsed musical piece.

Learning a musical piece requires the development of a strong linkage between sensory and motor representations. Audition plays a central role and a tight cortical auditory-motor corepresentation is a characteristic feature of music processing. Recent works have indicated the establishment of a functional connection between auditory and motor cortices during the learning of a novel piece, although no causal relation has yet been demonstrated. Here transcranial magnetic stimulation of the cortical motor representation involved in musical performance was used to test excitability changes in piano players during auditory presentation of a rehearsed and a non-rehearsed piece. Results showed an increased motor excitability for the rehearsed but not for the non-rehearsed piece. Moreover, we observed an increase of excitability over time as intracortical facilitation was already present after 30 min of training whereas cortico-spinal facilitation increased after a longer training period (5 days).