Repetitive subconcussive head impacts in sports and their impact on brain anatomy and function.

Repetitive subconcussive head impacts occur regularly in sports. However, the exact relationship between the biomechanical properties of repetitive subconcussive head impacts in sports and their consequences on brain structure and function has not been clarified yet. We therefore reviewed prospective cohort studies that objectively reported the biomechanical characteristics of repetitive subconcussive head impacts and their impact on brain anatomy and function. Only studies with a pre- to post measurement design were included. Twenty-four studies met the inclusion criteria. Structural white matter alterations, such as reduced fractional anisotropy and an increase in mean diffusivity values, seem to be evident in athletes exposed to repetitive subconcussive head impacts exceeding 10 g. Such changes are observable after only one season of play. Furthermore, it exists a dose-response relationship between white matter abnormalities and the total number of subconcussive head impacts. However, functional changes after repetitive subconcussive head impacts remain inconclusive. We therefore conclude that repetitive subconcussive head impacts induce structural changes, but thus far without overt functional changes.

Limb Apraxias: The Influence of Higher Order Perceptual and Semantic Deficits in Motor Recovery After Stroke.

Stroke is a leading cause of disability worldwide. Limb apraxia is a group of higher order motor disorders associated with greater disability and dependence after stroke. Original neuropsychology studies distinguished separate brain pathways involved in perception and action, known as the dual stream hypothesis. This framework has allowed a better understanding of the deficits identified in Limb Apraxia. In this review, we propose a hierarchical organization of this disorder, in which a distinction can be made between several visuomotor pathways that lead to purposeful actions. Based on this, executive apraxias (such as limb kinetic apraxia) cause deficits in executing fine motor hand skills, and intermediate apraxias (such as optic ataxia and tactile apraxia) cause deficits in reaching to grasp and manipulating objects in space. These disorders usually affect the contralesional limb. A further set of disorders collectively known as limb apraxias include deficits in gesture imitation, pantomime, gesture recognition, and object use. These deficits are due to deficits in integrating perceptual and semantic information to generate complex movements. Limb apraxias are usually caused by left-hemisphere lesions in right-handed stroke patients, affecting both limbs. The anterior- to posterior-axis of brain areas are disrupted depending on the increasing involvement of perceptual and semantic processes with each condition. Lower-level executive apraxias are linked to lesions in the frontal lobe and the basal ganglia, while intermediate apraxias are linked to lesions in dorso-dorsal subdivisions of the dorsal fronto-parietal networks. Limb apraxias can be caused by lesions in both dorsal and ventral subdivisions including the ventro-dorsal stream and a third visuomotor pathway, involved in body schema and social cognition. Rehabilitation of these disorders with behavioral therapies has aimed to either restore perceptuo-semantic deficits or compensate to overcome these deficits. Further studies are required to better stratify patients, using modern neurophysiology and neuroimaging techniques, to provide targeted and personalized therapies for these disorders in the future.

Neural correlates of virtual reality-based attention training: An fMRI study.

THEORETICAL BACKGROUND: Virtual Reality technology is increasingly used in attention rehabilitation for functional training purposes. However, the neural mechanisms by which Virtual Reality can affect attentional functioning are still unclear. The current study's objective is to examine the effects of stereoscopic vs. monoscopic presentation on neural processing during a visual attention task. METHOD: Thirty-two healthy participants performed a visual attention task in an immersive virtual environment that was displayed via MR-compatible video goggles in an MRI scanner. The paradigm altered between trials that required active engagement with the task and mere observation trials. Furthermore, the form of binocular presentation switched between monoscopic and stereoscopic presentation. RESULTS: Analyses yielded evidence for increased activation in stereoscopic compared to monoscopic trials in the tertiary visual cortex area V3A as well as elevated activation in the dorsal attention network when engaging in the attention task. An additional ROI analysis of area V3A revealed significantly lower attentional engagement costs in stereoscopic conditions. DISCUSSION: Results support previous findings suggesting that V3A is involved in binocular depth perception. Furthermore, heightened activation in V3A following stereoscopic presentation seemed to facilitate attentional engagement with the task. Considering that V3A is the origin of the dorso-dorsal, ventro-dorsal, and ventral visual processing pathways, we regard it as a gating area that decides which kind of visual perception is processed.

Neural Correlates of Oral Stereognosis-An fMRI Study.

Oral stereognosis is the ability to recognize, discriminate and localize a bolus in the oral cavity. Clinical observation indicates deficits in oral stereognosis in patients with vascular or neurodegenerative diseases particularly affecting the parietal lobes. However, the precise neural representation of oral stereognosis remains unclear whereas the neural network of manual stereognosis has already been identified. We hypothesize that oral and manual stereognosis share common neuronal substrates whilst also showing somatotopic distribution. Functional magnetic resonance images (fMRI; Siemens Prisma 3 T) from 20 healthy right-handed participants (11 female; mean age 25.7 years) using a cross-modal task of oral and manual spatial object manipulation were acquired. Data were analyzed using FSL software using a block design and standard analytical and statistical procedures. A conjunction analysis targeted the common neuronal substrate for stereognosis. Activations associated with manual and oral stereognosis were found in partially overlapping fronto-parietal networks in a somatotopic fashion, where oral stereognosis is located caudally from manual stereognosis. A significant overlap was seen in the left anterior intraparietal sulcus. Additionally, cerebellar activations were shown particularly for the oral condition. Spatial arrangement of shaped boli in the oral cavity is associated with neuronal activity in fronto-parietal networks and the cerebellum. These findings have significant implications for clinical diagnostics and management of patients with lesions or atrophy in parietal lobule (e.g. Alzheimer's disease, stroke). More studies are required to investigate the clinical effect of damage to these areas, such as loss of oral stereognosis or an impaired oral phase.

Magnetic resonance spectroscopy with transcranial direct current stimulation to explore the underlying biochemical and physiological mechanism of the human brain: A systematic review.

A large body of molecular and neurophysiological evidence connects synaptic plasticity to specific functions and energy metabolism in particular areas of the brain. Furthermore, altered plasticity and energy regulation has been associated with a number of neuropsychiatric disorders. A favourable approach enabling the modulation of neuronal excitability and energy in humans is to stimulate the brain using transcranial direct current stimulation (tDCS) and then to observe the effect on neurometabolites using magnetic resonance spectroscopy (MRS). In this way, a well-defined modulation of brain energy and excitability can be achieved using a dedicated tDCS protocol to a predetermined brain region. This systematic review was guided by the preferred reporting items for systematic reviews and meta-analysis and summarises recent literature studying the effect of tDCS on neurometabolites in the human brain as measured by proton or phosphorus MRS. Limitations and recommendations are discussed for future research. The findings of this review provide clear evidence for the potential of using tDCS and MRS to examine and understand the effect of neurometabolites in the in vivo human brain.

The prominent role of perceptual salience in object discrimination: overt discrimination of graspable side does not activate grasping affordances.

Responses to object stimuli are often faster when jutting handles are aligned with responding hands, than when they are not: handle-to-hand correspondence effects. According to a location coding account, locations of visually salient jutting parts determine the spatial coding of objects. This asymmetry then facilitates same-sided responses compared to responses on the opposite side. Alternatively, this effect has been attributed to grasping actions of the left or the right hand afforded by the handle orientation and independent of its salience (affordance activation account). Our experiments were designed to disentangle the effects of pure salience from those of affordance activations. We selected pictures of tools with one salient and non-graspable side, and one graspable and non-salient side (non-jutting handle). Two experiments were run. Each experiment had two groups of participants: one group discriminated the location of the salient side of the object stimuli; the other group discriminated the location of the graspable side of them. In Experiment 1, responses were left and right button presses; in Experiment 2, they were left and right button presses plus reach-and-grasp actions. When visual salience was removed from graspable sides, no correspondence effect was observed between their orientation and the responding hands in both the experiments. Conversely, when salience depended on non-graspable portions, a correspondence effect was produced between their orientation and the responding hand. Overt attention to graspable sides did not potentiate any grasping affordance even when participants executed grasping responses in addition to button presses. Results support the location coding account: performance was influenced by the spatial coding of visually salient properties of objects.

Asymmetric tumor-related alterations of network-specific intrinsic functional connectivity in glioma patients.

Resting-state functional MRI (rs-fMRI) allows mapping temporally coherent brain networks, and intra- and inter-network alterations have been described in different diseases. This prospective study investigated hemispheric resting-state functional connectivity (RSFC) differences in the default-mode network (DMN) and fronto-parietal network (FPN) between patients with left- and right-hemispheric gliomas (LH PAT, RH PAT), addressing asymmetry effects the tumor might have on network-specific intrinsic functional connectivity under consideration of the prognostically relevant isocitrate-dehydrogenase (IDH) mutation status. Twenty-seven patients (16 LH PAT, 12 IDH-wildtype) and 27 healthy controls underwent anatomical and rs-fMRI as well as neuropsychological assessment. Independent component analyses were performed to identify the DMN and FPN. Hemispheric DMN- and FPN-RSFC were computed, compared across groups, and correlated with cognitive performance. Patient groups did not differ in tumor volume, grade or location. RH PAT showed higher contra-tumoral DMN-RSFC than controls and LH PAT. With regard to the FPN, contra-tumoral RSFC was increased in both patient groups as compared to controls. Higher contra-tumoral RSFC was associated with worse cognitive performance in patients, which, however, seemed to apply mainly to IDH-wildtype patients. The benefit of RSFC alterations for cognitive performance varied depending on the affected hemisphere, cognitive demand, and seemed to be altered by IDH-mutation status. At the time of study initiation, a clinical trial registration was not mandatory at our faculty, but it can be applied for if requested.

Correspondence effect driven by salient visual asymmetries in integral object stimuli.

The handle-to-hand correspondence effect consists of faster and more accurate responses when the responding hand is aligned with the handle side of an object tool, compared to when they lay on opposite sides. This effect has been attributed to the activation of affordances. Recent studies, however, claimed that it may depend on the spatial coding of the object on the basis of its visual asymmetry (location-coding account). Affordances are namely direct and meaningful relations between recognized objects and the observers' action system. Therefore, any manipulation that disrupts the body structure of object tools could potentially affect their identification and prevent the activation of affordances. The present study investigated the nature of the handle-to-hand correspondence effects by manipulating structural asymmetry and visual salience of object tools, while preserving their integrity that is, leaving unaltered the original possibilities to activate grasping affordances. Three experiments were run. Results were consistent with the location-coding account and claim for accurate control of visual asymmetries in object stimuli during investigation of affordance effects.

The unimanual handle-to-hand correspondence effect: evidence for a location coding account.

The handle-to-hand correspondence effect refers to faster and more accurate responses when the responding hand is aligned with the graspable part of an object tool, compared to when they lay on opposite sides. We performed four behavioral experiments to investigate whether this effect depends on the activation of grasping affordances (affordance activation account) or is to be traced back to a Simon effect, resulting from the spatial coding of stimuli and responses and from their dimensional overlap (location coding account). We manipulated the availability of a response alternative by requiring participants to perform either a unimanual go/no-go task (absence of a response alternative) or a joint go/no-go task (available response alternative) and the type of response required (button-press or grasping response). We found no handle-to-hand correspondence effect in the individual go/no-go task either when a button-press (Experiment 1A) or a grasping (Experiment 2A) response was required, whereas a significant effect emerged in the joint go/no-go task, irrespective of response modality (Experiments1B and 2B). These results do not support the idea that complex motor affordances are activated for meaningful objects, but are rather consistent with the more parsimonious location coding account.

Cerebral Activation During Initial Motor Learning Forecasts Subsequent Sleep-Facilitated Memory Consolidation in Older Adults.

Older adults exhibit deficits in motor memory consolidation; however, little is known about the cerebral correlates of this impairment. We thus employed fMRI to investigate the neural substrates underlying motor sequence memory consolidation, and the modulatory influence of post-learning sleep, in healthy older adults. Participants were trained on a motor sequence and retested following an 8-h interval including wake or diurnal sleep as well as a 22-h interval including a night of sleep. Results demonstrated that a post-learning nap improved offline consolidation across same- and next-day retests. This enhanced consolidation was reflected by increased activity in the putamen and the medial temporal lobe, including the hippocampus, regions that have previously been implicated in sleep-dependent neural plasticity in young adults. Moreover, for the first time in older adults, the neural substrates subserving initial motor learning, including the putamen, cerebellum, and parietal cortex, were shown to forecast subsequent consolidation depending on whether a post-learning nap was afforded. Specifically, sufficient activation in a motor-related network appears to be necessary to trigger sleep-facilitated consolidation in older adults. Our findings not only demonstrate that post-learning sleep can enhance motor memory consolidation in older adults, but also provide the system-level neural correlates of this beneficial effect.

An ultrasound investigation of tongue shape in stroke patients with lingual hemiparalysis.

BACKGROUND: Stroke can cause hemilateral paresis of the tongue. The present study investigated the functional consequences of a lingual hemiparalysis on the symmetry and the grooving of the tongue in the coronal plane during the production of vowel-consonant-vowel sequences. The hypotheses were that, because of the lingual hemiparalysis, the stroke patients' tongue shapes would be (1) more asymmetrical and (2) less grooved than the tongues of the control speakers. METHODS: The participants in this prospective data collection were 9 stroke patients with lingual hemiparalysis and 6 control speakers. All participants produced vowel-consonant-vowel sequences with the vowels [a, i, and u] and the target consonants [k, t, ∫, s, and r]. The tongue shape in the coronal plane was traced and measured. The outcome measures were asymmetry and midlingual concavity. The participants and controls were compared using repeated measures analyses of variance with post hoc Scheffé tests. RESULTS: There were no significant differences in asymmetry. There was significantly reduced midlingual concavity for the stroke patients (F[1, 13] = 8.78; P < .05). There was also a within-subjects effect for consonant (F[4, 50] = 14.26; P < .01). Post hoc testing with Scheffé tests indicated that the consonant [k] had significantly lower grooving than the other consonant sounds (P < .05). CONCLUSIONS: The hemilateral paresis affected not the symmetry but the midlingual grooving. Residual ipsilateral innervation in the hemiparalyzed tongue may help patients compensate. More research is needed to assess the impact of the intrinsic deformation of the tongue on speech acceptability and intelligibility in patients with a lingual hemiparalysis.

Perception of robotic actions and the influence of gender.

In our society interaction with robots is becoming more and more frequent since robots are not only used in the industry, but increasingly often in assistance and in health system. Perception of robots and their movements is crucial for their acceptance. Here we shortly review basic mechanisms of perception of actions, and then of perception of robotic and human movements. The literature demonstrates that there are commonalities, but also differences in the perception of human and robotic movements. Especially interesting are biologic gender differences in the perception of robotic movements. The results show that males seem to be more sensitive to the differences between robotic and anthropomorphic movements, whereas females seem not to perceive such differences. However, females transfer more anthropomorphic features to robotic movements. While looking at the brain activation during perception of humanoid and robotic movements in different genders one can conclude that different strategies are used; female seem to analyse robotic movements online, while male seem to use previous knowledge from interaction with robots. Further research is needed to specify more such gender differences.

Characteristic functional connectome related to Post-COVID-19 syndrome.

Post-COVID-19 syndrome is a serious complication following SARS-CoV-2 infection, characterized primarily by fatigue and cognitive complaints. Although first metabolic and structural imaging alterations in Post-COVID-19 syndrome have been identified, their functional consequences remain unknown. Thus, we explored the impact of Post-COVID-19 syndrome on the functional connectome of the brain providing a deeper understanding of pathophysiological mechanisms. In a cross-sectional observational study, resting-state functional magnetic resonance imaging data of 66 patients with Post-COVID-19 syndrome after mild infection (mean age 42.3 years, 57 female) and 57 healthy controls (mean age 42.1 years, 38 female) with a mean time of seven months after acute COVID-19 were analysed using a graph theoretical approach. Network features were quantified using measures including mean distance, nodal degree, betweenness and Katz centrality, and compared between both groups. Graph measures were correlated with clinical measures quantifying fatigue, cognitive function, affective symptoms and sleep disturbances. Alterations were mainly found in the brainstem, olfactory cortex, cingulate cortex, thalamus and cerebellum on average seven months after SARS-CoV-2 infection. Additionally, strong correlations between fatigue severity, cognitive functioning and daytime sleepiness from clinical scales and graph measures were observed. Our study confirms functional relevance of brain imaging changes in Post-COVID-19 syndrome as mediating factors for persistent symptoms and improves our pathophysiological understanding.

Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation.

The inverse effects of creatine supplementation and sleep deprivation on high energy phosphates, neural creatine, and cognitive performances suggest that creatine is a suitable candidate for reducing the negative effects of sleep deprivation. With this, the main obstacle is the limited exogenous uptake by the central nervous system (CNS), making creatine only effective over a long-term diet of weeks. Thus far, only repeated dosing of creatine over weeks has been studied, yielding detectable changes in CNS levels. Based on the hypothesis that a high extracellular creatine availability and increased intracellular energy consumption will temporarily increase the central creatine uptake, subjects were orally administered a high single dose of creatinemonohydrate (0.35 g/kg) while performing cognitive tests during sleep deprivation. Two consecutive 31P-MRS scans, 1H-MRS, and cognitive tests were performed each at evening baseline, 3, 5.5, and 7.5 h after single dose creatine (0.35 g/kg) or placebo during sub-total 21 h sleep deprivation (SD). Our results show that creatine induces changes in PCr/Pi, ATP, tCr/tNAA, prevents a drop in pH level, and improves cognitive performance and processing speed. These outcomes suggest that a high single dose of creatine can partially reverse metabolic alterations and fatigue-related cognitive deterioration.

Success rates of intensive aphasia therapy: real-world data from 448 patients between 2003 and 2020.

BACKGROUND: Aphasia is a devastating consequence after stroke, affecting millions of patients each year. Studies have shown that intensive speech and language therapy (SLT) is effective in the chronic phase of aphasia. Leveraging a large single-center cohort of persons with aphasia (PWA) including patients also in the subacute phase, we assessed treatment effects of intensive aphasia therapy in a real-world setting. METHODS: Data were collected at the Aachen aphasia ward in Germany between 2003 and 2020. Immediate treatment responses across different language domains were assessed with the Aachen Aphasia Test (AAT) using single-case psychometrics, conducted before and after 6-7 weeks of intensive SLT (10 h per week, median (IQR) dosage = 68 (61-76)). We adjusted for spontaneous recovery in subacute patients. Differential treatment effects between subgroups of chronicity and predictors of therapy response were investigated. RESULTS: A total of 448 PWA were included (29% female, median (IQR) age = 54 (46-62) years, median (IQR) time post-onset = 11 (6-20) months) with 12% in the early subacute, 15% in the late subacute and 74% in the chronic phase of aphasia. The immediate responder rate was 59%. Significant improvements in all AAT subtests und subscales were observed hinting at broad effectiveness across language domains. The degree of therapy-induced improvement did not differ between the chronicity groups. Time post-onset, dosage of therapy and aphasia severity at the beginning of treatment were predictors of immediate treatment response. DISCUSSION: Intensive therapy protocols for aphasia after stroke are yielding substantial responder rates in a routine clinical setting including a wide range of patients.

Compensatory premotor activity during affective face processing in subclinical carriers of a single mutant Parkin allele.

Patients with Parkinson's disease suffer from significant motor impairments and accompanying cognitive and affective dysfunction due to progressive disturbances of basal ganglia-cortical gating loops. Parkinson's disease has a long presymptomatic stage, which indicates a substantial capacity of the human brain to compensate for dopaminergic nerve degeneration before clinical manifestation of the disease. Neuroimaging studies provide evidence that increased motor-related cortical activity can compensate for progressive dopaminergic nerve degeneration in carriers of a single mutant Parkin or PINK1 gene, who show a mild but significant reduction of dopamine metabolism in the basal ganglia in the complete absence of clinical motor signs. However, it is currently unknown whether similar compensatory mechanisms are effective in non-motor basal ganglia-cortical gating loops. Here, we ask whether asymptomatic Parkin mutation carriers show altered patterns of brain activity during processing of facial gestures, and whether this might compensate for latent facial emotion recognition deficits. Current theories in social neuroscience assume that execution and perception of facial gestures are linked by a special class of visuomotor neurons ('mirror neurons') in the ventrolateral premotor cortex/pars opercularis of the inferior frontal gyrus (Brodmann area 44/6). We hypothesized that asymptomatic Parkin mutation carriers would show increased activity in this area during processing of affective facial gestures, replicating the compensatory motor effects that have previously been observed in these individuals. Additionally, Parkin mutation carriers might show altered activity in other basal ganglia-cortical gating loops. Eight asymptomatic heterozygous Parkin mutation carriers and eight matched controls underwent functional magnetic resonance imaging and a subsequent facial emotion recognition task. As predicted, Parkin mutation carriers showed significantly stronger activity in the right ventrolateral premotor cortex during execution and perception of affective facial gestures than healthy controls. Furthermore, Parkin mutation carriers showed a slightly reduced ability to recognize facial emotions that was least severe in individuals who showed the strongest increase of ventrolateral premotor activity. In addition, Parkin mutation carriers showed a significantly weaker than normal increase of activity in the left lateral orbitofrontal cortex (inferior frontal gyrus pars orbitalis, Brodmann area 47), which was unrelated to facial emotion recognition ability. These findings are consistent with the hypothesis that compensatory activity in the ventrolateral premotor cortex during processing of affective facial gestures can reduce impairments in facial emotion recognition in subclinical Parkin mutation carriers. A breakdown of this compensatory mechanism might lead to the impairment of facial expressivity and facial emotion recognition observed in manifest Parkinson's disease.

Parietal control of hand movement.

The parietal lobe has been implicated in the sensorimotor control and integration that supports the skillful use of our hands to reach for, grasp, and manipulate objects in the environment. This area is involved in several circuits within the classic subdivisions of the dorsal stream. Recently, the dorsal stream has been further divided into a "dorso-dorsal" and a "ventro-dorsal" streams. The ventro-dorsal stream is regarded as functionally linked to object manipulation. The dorso-dorsal stream is proposed to subserve reaching and online control of actions. Affordances indicate action possibilities characterized by object properties the environment provides. Affordances are likely represented by the dorsal stream. They code structural object properties that can elicit actions. A further subdivision of affordances into "stable" and "variable" allows an understanding of the neuronal mechanisms underlying object manipulation. Whereas stable affordances emerge from slow processing of visual information based on knowledge of object properties from previous experiences and object interaction, variable affordances emerge from fast online processing of visual information during actual object interaction, within a changing environment. The relevance of the dorsal stream subdivisions in this context is that the dorso-dorsal stream is associated with coding of variable affordances, while that of the dorso-ventral stream is implicated in action representations elicited by stable affordances. A greater interaction between these and ventral stream perceptual and semantic representations allows the parietal control of hand movement. An understanding of these networks is likely to underlie recovery from complex deficits described in limb apraxias.

Increasing striatal dopamine release through repeated bouts of theta burst transcranial magnetic stimulation of the left dorsolateral prefrontal cortex. A 18F-desmethoxyfallypride positron emission tomography study.

Introduction: Transcranial Magnetic Stimulation (TMS) can modulate fronto-striatal connectivity in the human brain. Here Positron Emission Tomography (PET) and neuro-navigated TMS were combined to investigate the dynamics of the fronto-striatal connectivity in the human brain. Employing 18F-DesmethoxyFallypride (DMFP) - a Dopamine receptor-antagonist - the release of endogenous dopamine in the striatum in response to time-spaced repeated bouts of excitatory, intermittent theta burst stimulation (iTBS) of the Left-Dorsolateral Prefrontal Cortex (L-DLPFC) was measured. Methods: 23 healthy participants underwent two PET sessions, each one with four blocks of iTBS separated by 30 minutes: sham (control) and verum (90% of individual resting motor threshold). Receptor Binding Ratios were collected for sham and verum sessions across 37 time frames (about 130 minutes) in striatal sub-regions (Caudate nucleus and Putamen). Results: Verum iTBS increased the dopamine release in striatal sub-regions, relative to sham iTBS. Dopamine levels in the verum session increased progressively across the time frames until frame number 28 (approximately 85 minutes after the start of the session and after three iTBS bouts) and then essentially remained unchanged until the end of the session. Conclusion: Results suggest that the short-timed iTBS protocol performed in time-spaced blocks can effectively induce a dynamic dose dependent increase in dopaminergic fronto-striatal connectivity. This scheme could provide an alternative to unpleasant and distressing, long stimulation protocols in experimental and therapeutic settings. Specifically, it was demonstrated that three repeated bouts of iTBS, spaced by short intervals, achieve larger effects than one single stimulation. This finding has implications for the planning of therapeutic interventions, for example, treatment of major depression.

Investigating function and connectivity of morphometric findings--exemplified on cerebellar atrophy in spinocerebellar ataxia 17 (SCA17).

Spinocerebellar ataxia type 17 (SCA17) is a rare autosomal dominant neurodegenerative disorder characterized by progressive cerebellar ataxia but also a broad spectrum of other neuropsychiatric signs. As anatomical and structural studies have shown severe cerebellar atrophy in SCA17 and a differentiation of the human cerebellum into an anterior sensorimotor and posterior cognitive/emotional partition has been implicated, we aimed at investigating functional connectivity patterns of two cerebellar clusters of atrophy revealed by a morphometric analysis in SCA17 patients. In particular, voxel-based morphometry (VBM) revealed a large cluster of atrophy in SCA17 in the bilateral anterior cerebellum (lobule V) and another one in the left posterior cerebellum (lobules IX, VIIb, VIIIA, VIIIB). These two cerebellar clusters were used as seeds for functional connectivity analyses using task-based meta-analytic connectivity modeling (MACM) and task-free resting state connectivity analysis. Results demonstrated first consistent functional connectivity throughout the cerebellum itself; the anterior cerebellar seed showed stronger connectivity to lobules V, VI and to some extent I-IV, and the posterior cerebellar seed to the posterior lobules VI-IX. Importantly, the cerebellar anterior seed also showed consistently stronger functional connectivity than the posterior one with pre- and motor areas as well as the primary somatosensory cortex. In turn, task-based task-independent functional connectivity analyses revealed that the cerebellar posterior seed was linked with fronto-temporo-parietal areas as well as partly the insula and the thalamus, i.e., brain regions implicated in cognitive and affective processes. Functional characterization of experiments activating either cerebellar seed further corroborated this notion, revealing mainly motor-related functions for the anterior cluster and predominantly cognitive functions were associated for the posterior one. The differential functional connectivity of the cerebellar anterior and posterior cluster highlights the manifold connections and dichotomy of the human cerebellum, providing additional valuable information about probably disrupted cerebellar-cerebral connections and reflecting the brunt of motor but also the broad spectrum of neuropsychiatric deficits in SCA17.

Observation and execution of upper-limb movements as a tool for rehabilitation of motor deficits in paretic stroke patients: protocol of a randomized clinical trial.

BACKGROUND: Evidence exist that motor observation activates the same cortical motor areas that are involved in the performance of the observed actions. The so called "mirror neuron system" has been proposed to be responsible for this phenomenon. We employ this neural system and its capability to re-enact stored motor representations as a tool for rehabilitating motor control. In our new neurorehabilitative schema (videotherapy) we combine observation of daily actions with concomitant physical training of the observed actions focusing on the upper limbs. Following a pilot study in chronic patients in an ambulatory setting, we currently designed a new multicenter clinical study dedicated to patients in the sub-acute state after stroke using a home-based self-induced training. Within our protocol we assess 1) the capability of action observation to elicit rehabilitational effects in the motor system, and 2) the capacity of this schema to be performed by patients without assistance from a physiotherapist. The results of this study would be of high health and economical relevance. METHODS/DESIGN: A controlled, randomized, multicenter, paralleled, 6 month follow-up study will be conducted on three groups of patients: one group will be given the experimental treatment whereas the other two will participate in control treatments. All patients will undergo their usual rehabilitative treatment beside participation in the study. The experimental condition consists in the observation and immediate imitation of common daily hand and arm actions. The two parallel control groups are a placebo group and a group receiving usual rehabilitation without any trial-related treatment. Trial randomization is provided via external data management. The primary efficacy endpoint is the improvement of the experimental group in a standardized motor function test (Wolf Motor Function Test) relative to control groups. Further assessments refer to subjective and qualitative rehabilitational scores. This study has been reviewed and approved by the ethics committee of Aachen University. DISCUSSION: This therapy provides an extension of therapeutic procedures for recovery after stroke and emphasizes the importance of action perception in neurorehabilitation The results of the study could become implemented into the wide physiotherapeutic practice, for example as an ad on and individualized therapy.