Self-observation reinstates motor awareness in anosognosia for hemiplegia

We report a patient with severe anosognosia for hemiplegia, who recovered instantly and permanently when viewing herself in a video replay. We believe the observed dramatic reinstatement of the patient's awareness related to her self-observation ‘from the outside’ (3rd person perspective) and ‘off-line’ (at a time later than the actual attempt to execute a movement); her anosognosia had been unaltered when she observed her plegic arm in her ipsilateral visual field (self-observation from a 1st-person perspective and ‘on-line’). To our knowledge, the role of self-observation in videos or mirrors has not being assessed in AHP to date. Our study provides preliminary evidence that, when right hemisphere damage impairs the ability to update one's body representation, judgements relying on 3rd-person and off-line self-observation may be spared in some patients and may facilitate 1st person awareness.     

Imagining the impossible: motor representations in anosognosia for hemiplegia

Anosognosia for hemiplegia (AHP) is characterised by poor insight or underestimation of hemiplegia after brain injury. Recent explanations of AHP have used an established ‘forward model’, which proposes that normal motor awareness involves comparing the predicted and actual sensory consequences of movements. These accounts propose that AHP patients may be able to form representations of their intended movements (i.e., motor representations), but fail to register discrepancy between intended and actual movements. A prediction arising from this proposal is that AHP patients are able to generate motor representations involving their hemiplegic limb(s). Our study provides the first direct examination of this prediction in patients with AHP. We used an existing ‘grip selection task’, which investigates motor representations by comparing how patients would grasp an object and how they actually grasp the same object. Eight right hemisphere stroke patients with AHP, 10 control patients (non-AHP), and 22 age-matched healthy volunteers (HVs) completed the task. Results showed that HVs outperformed both AHP and non-AHP patients in their motor representations for the hemiplegic limb; however, the performance of AHP and non-AHP patients did not differ significantly. Motor representations for the intact limb were lower than normal in AHP patients, whereas performance in non-AHP patients was midway between the AHP and HV groups. Findings suggested that the ability to form motor representations lie on a continuum, but that impaired motor representations for the paralysed limb cannot account for AHP. Distorted motor representations, in combination with other deficits, might contribute to the pathogenesis of AHP.     

Phenomenology and neural correlates of implicit and emergent motor awareness in patients with anosognosia for hemiplegia

Anosognosia for hemiplegia (AH) is characterized by a lack of awareness of motor disorders and appears associated with fronto-temporal-parietal damage. Neuropsychological evidence indicates that behavioral indices of residual forms of motor awareness may co-exist with explicit denial of impairment. Here we explore whether the attempt by AH patients to perform an action may disclose residual forms of motor awareness and whether such forms are underpinned by different neural structures. Twelve hemiplegic patients affected by AH were tested in tasks assessing: (i) implicit awareness (IA), indexed by discrepancies between verbal reports and actual motor behavior; (ii) emergent awareness (EA), indexed by increased verbal awareness induced by the attempt to perform actions. IA and EA were found in five and three patients, respectively. Lesion analysis indicates that while the lack of IA is associated with damage to subcortical white matter anterior to the basal ganglia, lack of EA is linked to damage to cortical regions including insulo-frontal, temporal and parietal structures. Our results indicate that deficits in explicit and implicit awareness are associated with lesions involving different cortico-subcortical structures. Moreover, the results show that the attempt to perform an action may ameliorate body awareness deficits and have implications for rehabilitation.     

Error-based training and emergent awareness in anosognosia for hemiplegia

Residual forms of awareness have recently been demonstrated in subjects affected by anosognosia for hemiplegia, but their potential effects in recovery of awareness remain to date unexplored. Emergent awareness refers to a specific facet of motor unawareness in which anosognosic subjects recognise their motor deficits only when they have been requested to perform an action and they realise their errors. Four participants in the chronic phase after a stroke with anosognosia for hemiplegia were recruited. They took part in an “error-full” or “analysis of error-based” rehabilitative training programme. They were asked to attempt to execute specific actions, analyse their own strategies and errors and discuss the reasons for their failures. Pre- and post-training and follow-up assessments showed that motor unawareness improved in all four patients. These results indicate that unsuccessful action attempts with concomitant error analysis may facilitate the recovery of emergent awareness and, sometimes, of more general aspects of awareness.     

Anosognosia for hemiplegia as a global deficit in motor awareness: Evidence from the non-paralysed limb

The current study adds to the growing empirical research into the mechanisms underlying unawareness of paralysis following stroke (anosognosia for hemiplegia or AHP) by investigating action awareness for the non-paralysed limb in a single AHP patient. Visual feedback representing patient GG's goal-directed reaching movements was either modified by a computer or left unperturbed. Unlike healthy and brain-damaged controls, GG was unable to detect computer-generated visual perturbations as large as 20°. GG also failed to report awareness of the large on-line corrective movements that he made when compensating (often unsuccessfully) for the visual perturbations. These results suggest that the motor comparators implicated in AHP are functioning, but not at optimum levels. Moreover, because the current findings reveal a deficit in awareness for reaches with the unimpaired limb, it is suggestive of common right hemisphere networks for motor awareness in both limbs and that AHP may be a global deficit in motor awareness as opposed to a specific lack of awareness for a particular motor deficit.     

Belief and awareness: reflections on a case of persistent anosognosia

Persisting anosognosia after acute lesions is relatively rare, and no case studies to date have reported functional scanning investigation of this disorder. This is a case report of an 85-year-old right-handed Scottish woman, EN, who showed persistent anosognosia for hemiplegia following a haemorrhagic stroke. Extensive damage in the right hemisphere caused left upper and lower limb flaccid hemiplegia and severe left-sided neglect. Lack of awareness for her deficits was still present 2 years after the stroke, when neurological, neuropsychological, and SPECT examinations were performed. Testing revealed severe left unilateral neglect and poor performance on verbal fluency tasks. EN had age normal memory performance, and her object recognition and praxic abilities were preserved. She showed no global reasoning or language problems apart from her abnormal beliefs. EN believed that she was able to walk and carry out several activities, in a context of other disorders of belief. SPECT scan showed marked hypoperfusion in the right parietotemporal cortex and this extended to the associative cortex in the right frontal regions. The persistence of anosognosia in this patient cannot be explained by memory impairments or global cognitive decline. A possible account might be that alteration in awareness was maintained by contingent right frontal and/or parietal dysfunction causing a suspension or change in the ability to monitor and check the 'real' and especially to assess the veracity of mental contents.     

Individualized exergame training improves postural control in advanced degenerative spinocerebellar ataxia: A rater-blinded,intra-individually controlled trial

BackgroundTreatment options are rare in degenerative ataxias, especially in advanced, multisystemic disease. Exergame training might offer a novel treatment strategy, but its effectiveness has not been investigated in advanced stages.MethodsWe examined the effectiveness of a 12-week home-based training with body-controlled videogames in 10 young subjects with advanced degenerative ataxia unable or barely able to stand. Training was structured in two 6-weeks phases, allowing to adapt the training according to individual training progress. Rater-blinded clinical assessment (Scale for the Assessment and Rating of Ataxia; SARA), individual goal-attainment scoring (GAS), and quantitative movement analysis were performed two weeks before training, immediately prior to training, and after training phases 1 and 2 (intra-individual control design). This study is registered with ClinicalTrials.gov, NCT02874911).ResultsAfter intervention, ataxia symptoms were reduced (SARA -2.5 points, p < 0.01), with benefits correlating to the amount of training (p = 0.04). Goal attainment during daily living was higher than expected (GAS: 0.45). Movement analysis revealed reduced body sway while sitting (p < 0.01), which correlated with improvements in SARA posture and gait (p = 0.005), indicating training-induced improvements in posture control mechanisms.ConclusionThis study provides first evidence that, even in advanced stages, subjects with degenerative ataxia may benefit from individualized training, with effects translating into daily living and improving underlying control mechanisms. The proposed training strategy can be performed at home, is motivating and facilitates patient self-empowerment.     

The peer's point of view: Observing a peer performing an action enhances third-person perspective in adolescents

Adolescents are particularly prone to peer influence. Since group membership modulates the person's tendency to take someone else's viewpoint, here we decided to investigate whether adolescents are influenced by the presence of a peer when taking another person's perspective. A group of adolescents from upper secondary schools in Naples (Italy) had to observe scenes of an actor (an adolescent or an adult) gazing, grasping, gazing/grasping an object or staying still. When required to judge the spatial location of the object, the adolescent participants adopted the actor's viewpoint (third-person perspective) more frequently when the actor was an adolescent rather than when he was an adult and when the adolescent actor grasped the object. Thus, adolescents seem particularly prone to mentally simulate someone else's actions when the other person is a peer. These findings suggest that modulating motor simulation processes via social environmental factors could influence adolescents' perspective taking.     

Awareness of deficits during intracarotid anesthetic procedures in epilepsy: Comparisons of motor, naming, and comprehension awareness under amobarbital versus under etomidate

Awareness of deficits is often impaired following disruption of the right hemisphere. Intracarotid anesthetic procedures (IAPs) represent a unique method by which we can assess functioning of each hemisphere in isolation. We used this technique to explore deficits of awareness of specific functions-motor ability, naming, and comprehension-in patients with temporal lobe epilepsy. Some patients were injected with amobarbital, whereas others were injected with etomidate. We found that injection into the right hemisphere, or epileptogenic focus in the right hemisphere following injection in the left, resulted in the lowest levels of motor awareness. We also found a higher level of awareness for expressive language deficits and less awareness for receptive language deficits. Comparison of etomidate and amobarbital suggested more awareness following injection of etomidate. We discuss how these findings contribute to our understanding of the right hemisphere's special role in awareness, and how research in other disorders and in comparative neurology has shaped our conceptualization of the neuroanatomy of insight.     

Growth hormone combined with child-specific motor training improves motor development in infants with Prader-Willi syndrome: A randomized controlled trial

Although severe motor problems in infants with Prader-Willi syndrome (PWS) are striking, motor development has never been studied longitudinally and the results of growth hormone (GH) treatment on motor development are contradictory. The authors studied whether GH treatment can enhance the effect of physical training on motor development in infants with PWS. Twenty-two infants were followed for two years during a randomized controlled trial. The treatment and control groups began GH after baseline or following a control period, respectively. Both groups followed a child-specific physical training program. Motor performance was measured every three months. Multi-level regression analysis revealed that motor development differed significantly between infants (p < .001), and this could be partially explained by baseline motor developmental level (p < .01). GH treatment enhanced the effects of child-specific physical training on both motor developmental rate and motor developmental potential. Moreover, this effect was more pronounced when GH treatment was initiated at a younger age.     

Rotational field TMS: Comparison with conventional TMS based on motor evoked potentials and thresholds in the hand and leg motor cortices

BackgroundTranscranial magnetic stimulation (TMS) is a rapidly expanding technology utilized in research and neuropsychiatric treatments. Yet, conventional TMS configurations affect primarily neurons that are aligned parallel to the induced electric field by a fixed coil, making the activation orientation-specific. A novel method termed rotational field TMS (rfTMS), where two orthogonal coils are operated with a 90° phase shift, produces rotation of the electric field vector over almost a complete cycle, and may stimulate larger portion of the neuronal population within a given brain area.ObjectiveTo compare the physiological effects of rfTMS and conventional unidirectional TMS (udTMS) in the motor cortex.MethodsHand and leg resting motor thresholds (rMT), and motor evoked potential (MEP) amplitudes and latencies (at 120% of rMT), were measured using a dual-coil array based on the H7-coil, in 8 healthy volunteers following stimulation at different orientations of either udTMS or rfTMS.ResultsFor both target areas rfTMS produced significantly lower rMTs and much higher MEPs than those induced by udTMS, for comparable induced electric field amplitude. Both hand and leg rMTs were orientation-dependent.ConclusionsrfTMS induces stronger physiologic effects in targeted brain regions at significantly lower intensities. Importantly, given the activation of a much larger population of neurons within a certain brain area, repeated application of rfTMS may induce different neuroplastic effects in neural networks, opening novel research and clinical opportunities.     

Early surgery improves peripheral motor axonal dysfunction in acute traumatic central cord syndrome: A prospective cohort study

ObjectiveTo investigate the impact of early vs. delayed surgical decompression on peripheral motor axonal dysfunction following acute traumatic central cord syndrome (ATCCS).MethodsBoth axonal excitability testing and motor unit number estimation (MUNE) were performed in 30 ATCCS patients (early- vs. delayed-surgical treatment: 12 vs. 18) before operation and 28 healthy subjects. Axonal excitability testing was repeated 3–5 days and 1-year after operation, and MUNE was re-evaluated 1-year after operation.ResultsPreoperatively, an obvious modification in membrane potentials was observed in ATCCS patients that mostly coincided with depolarization-like features, and MUNE further revealed reduced motor units in tested muscles (P < 0.05). Unlike delayed-surgical cases, early-surgical cases showed recoveries of most measurements of axonal excitabilities soon after operation (P < 0.05). Postoperative one-year follow-up demonstrated that greater motor unit numbers in tested muscles were obtained in early-surgical cases than in delayed-surgical cases (P < 0.05).ConclusionsATCCS has adverse downstream effects on peripheral nervous system, even in the early stage of ATCCS. Early surgical treatment can ameliorate both excitability abnormalities and motor unit loss in distal motor axons.SignificanceOptimizing axonal excitability in the early phases of ATCCS may alleviate peripheral nerve injury secondary to lesions of upper motor neuron and improve clinical outcomes.     

Therapeutic effects of complex motor training on motor performance deficits induced by neonatal binge-like alcohol exposure in rats: I. Behavioral results

The effects of complex motor task learning on subsequent motor performance of adult rats exposed to alcohol on postnatal days 4 through 9 were studied. Male and female Long–Evans rats were assigned to one of three treatments: (1) alcohol exposure (AE) via artificial rearing to 4.5.g kg⁻¹ day⁻¹ of ethanol in a binge-like manner (two consecutive feedings), (2) gastrostomy control (GC) fed isocaloric milk formula via artificial rearing, and (3) suckling control (SC), where pups remained with lactating dams. After completion of the treatments, the pups were fostered back to lactating dams, and after weaning they were raised in standard cages (two–three animals per cage) until they were 6 months old. Rats from each of the postnatal treatments then spent 20 days in one of three conditions: (1) inactive condition (IC), (2) motor control condition (MC) (running on a flat oval track), or (3) rehabilitation condition (RC) (learning to traverse a set of 10 elevated obstacles). After that all the animals were tested on three tasks, sensitive to balance and coordination deficits (parallel bars, rope climbing and traversing a rotating rod). On parallel bars, both male and female rats demonstrated the same pattern of outcomes: AE-IC rats made significantly more mistakes (slips and falls) than IC rats from both control groups. After 20 days of training in the RC condition, there were no differences between AE and both SC and GC animals in their ability to perform on the parallel bars test. On rope climbing, female animals showed a similar pattern of abilities: AE-IC rats were the worst group; exercising did not significantly improve the AE rats' ability to climb, whereas the RC groups (SC, GC and AE) all performed near asymptote and there were no significant differences among three neonatal treatment groups. There was a substantial effect of the male rats' heavier body weight on climbing ability, and this may have prevented the deficits in AE rats behavior from being detected. Nevertheless, male animals from all three postnatal treatments (SC, GC and AE) were significantly better on this task after RC. Female and male rats from all three postnatal groups demonstrated significantly better performance on the rotarod task after 20 days of ‘rehabilitation'. These results suggest that complex motor skill learning improves some of the motor performance deficits produced by postnatal exposure to alcohol and can potentially serve as a model for rehabilitative intervention.     

Magnetic transcranial stimulation in healthy humans: influence on the behavior of upper limb motor units

Aim of the study was to analyze the characteristics of motor action potentials recruitment during magnetic trans-cranial stimulation (TCS) of the brain. Coaxial needle recordings from hand and upper limb musculature, as well as surface electrodes were employed in 20 healthy controls during magnetic TCS with regular and figure-of-8 coil in different experimental protocols including: (a) simple reaction time paradigm during which TCS at subthreshold intensity for eliciting MEPs in relaxation was delivered at various intervals between the signal to move and the onset of the voluntary EMG burst; (b) suprathreshold TCS was randomly delivered while the subject was voluntarily firing at a regular rate one ‘low’ and/or ‘high threshold’ motor unit action potential (MUAP). The pre- and post-TCS MUAPs recruitment as well as their firing rates were compared; (c) recordings with two separate needles picking up individual MUAPs from the same or from two different muscles were obtained in order to test ‘synchrony’ of MUAP's discharge before and after TCS; (d) the influence of the time-interval separating the last discharged MUAP from ICS was evaluated. (e) differences between simultaneous surface and depth recordings were examined. The following results were obtained. (a) The same low-amplitude MUAP which is first voluntarily recruited at the onset of the EMG burst is the one initially fired by TCS in the pre-movement period. Latency shortenings and amplitude enlargement of surface MEPs were observed with faster reaction times. Such changes were coupled to the recruitment of high-threshold MUAPs being larger in amplitude and briefer in latency than the initial one. (b) When using suprathreshold TCS, MEPs followed by silent periods were found. The SP was followed by a rebound acceleration of the MUAPs firing rate compared with pre-TCS levels. Besides rebound acceleration, new MUAPs of larger amplitude than the original (=pre-stimulus) ones were recruited beyond the voluntary control. This phenomenon-together with longer SPs- was progressively more pronounced with stronger stimuli. (c) TCS was affecting the ‘synchrony’ of MUAPs. (d) If the latency difference between the last pre-stimulus spike and the TCS was exceeding the half-cycle of the MUAP ‘natural’ firing, the SP was longer in duration. (e) SPs not preceded by MEPs were clearly present in depth recordings. Surface recordings mainly reflected the behavior of high-threshold and large MUAPs.     

A hospital-based study: risk factors in development of motor complications in 555 Parkinson's patients on levodopa therapy

OBJECTIVES: Although levodopa (LD) is the gold standard therapy for symptomatic treatment of Parkinson's disease (PD), the chronic use of LD leads to the development of motor complications in almost all patients. PATIENTS AND METHODS: We assessed the presence and risk factors for motor complications in PD patients on LD therapy. We examined 555 PD patients on LD for the presence or absence of wearing-off (WO+/-) and dyskinesia (DK+/-). RESULTS: WO was present in 46.3%, and DK in 30.1% of patients. The mean age at onset of symptoms were earlier in WO(+)/DK(+) groups (p<0.001). The duration of PD was longer in WO(+)/DK(+) groups (p<0.001). The time between the first symptom and the occurrence of WO/DK, or LD initiation were not significantly different. The initial LD dose was significantly higher in WO(+) compared to WO(-) (300.1mg/d versus 232.5mg/d, p<0.001), and DK(+) compared to DK(-) groups (291.4 mg/d versus 251.9 mg/d, p=0.001). The time until dopamine agonist (DA) initiation was longer in WO(+)/DK(+) groups (p<0.001). WO (p<0.001) and DK (p=0.002) were more common in patients with H&Y stages 3+4. UPDRS scores were higher in WO(+) and DK(+) patients (p<0.001 and p=0.027). CONCLUSION: Our study showed that the development of motor complications was associated with early onset PD, longer disease duration, advanced disease, higher initial LD dose, longer LD use, and late DA initiation, but not with the timing of LD initiation.     

The movement assessment battery in Greek preschoolers: the impact of age, gender, birth order, and physical activity on motor outcome

Early identification of possible risk factors that could impair the motor development is crucial, since poor motor performance may have long-term negative consequences for a child's overall development. The aim of the current study was the examination of disorders in motor coordination in Greek pre-school aged children and the detection of differences in motor performance with regards to age, gender, participation in sports and order of birth in the family. Performance profiles on the movement ABC were used to classify 412 Greek children aged 4-6 years old. It appears from the results that the occurrence rate of probable developmental coordination disorders (DCD) was 5.4%. Significant differences were observed in all independent variables except the order of birth in the family. The findings reinforce the need for the evaluation of motor performance in preschool-aged children, in order specific individual motor profiles to be established for optimizing and adapting early intervention programs.     

Therapeutic effects of complex motor training on motor performance deficits induced by neonatal binge-like alcohol exposure in rats: II. A quantitative stereological study of synaptic plasticity in female rat cerebellum

Twenty days of complex motor skill training in adult rats was previously demonstrated to rehabilitate motor performance deficits induced by binge alcohol exposure in neonatal rats. This follow-up study evaluated morphological plasticity in the paramedian lobule of the cerebellum (PML) using the same treatment and training regimens. On postnatal days (PD) 4-9, female Long-Evans rats were given either alcohol (Alcohol Exposure - AE, 4.5 g/kg/day via artificial rearing), exposure to gastrostomy control (GC) artificial rearing procedures, or reared normally as suckle controls (SC). After weaning, all rats were housed two to three per cage. At 180 days old, rats were randomly assigned either to a rehabilitation condition (RC: given 20 days of complex motor skill training), or to an inactive condition (IC: remained in their home cage). The AE rats were delayed in acquiring the training, but there were no group differences in performance over the last 2 weeks of training. Unbiased stereological techniques were used to evaluate PML volume, Purkinje cell and parallel fiber synapse density. Although total volume of PML was significantly reduced in the AE rats, complex motor skill training resulted in a significant increase in the PML molecular layer in all three postnatal treatment groups. The RC animals from the SC and AE groups had more parallel fiber synapses per Purkinje cell than corresponding IC animals. These data support the hypothesis that 'rehabilitative' motor training stimulates synaptogenesis in the PML, and that Purkinje neurons that survive the early postnatal alcohol insult are capable of substantial experience-induced plasticity.     

Differential gene expression profiling in the mouse brain during motor skill learning: focus on the striatum structure

Much research has implicated the striatum in motor learning, but the underlying mechanism is still under extensive investigation. In this study, genome-wide analysis of gene expression was conducted in mice that have learned a complex motor task. It is well recognized that successful learning requires repetitive training and is learned slowly over several training sessions. We therefore used mice that have fully learned the accelerating rotarod task that discriminates the faster and slower phases of motor learning. As important modulators of movement behavior, the striatum was the target of this analysis along with the cerebellum and anterior cortex. To identify potential genes implicated in long memorization process, we compared the lists of genes modulated in the striatum to those modulated in the cerebellum and cortex. As a second approach, we also determined which gene ontology categories were enriched in modulated striatal genes and identified genes with the highest numbers of annotation throughout categories. Although only some of these changes were further confirmed by RT-PCR, these two complementary analyses allowed the identification of highly relevant genes like calcium/calmodulin-dependent protein kinase 2, protein kinase C zeta and N-methyl-d-aspartate receptors. Notably, these genes are all associated with synaptic plasticity, suggesting that stabilized neuronal connections in the striatum are the foundation of durable motor memory. Our study provides the first report of a whole genome analysis of gene expression in mice that have memorized a new complex motor task, and expands our knowledge on striatal gene expression changes associated with motor skill learning.