Interregional compensatory mechanisms of motor functioning in progressing preclinical neurodegeneration.

Understanding brain reserve in preclinical stages of neurodegenerative disorders allows determination of which brain regions contribute to normal functioning despite accelerated neuronal loss. Besides the recruitment of additional regions, a reorganisation and shift of relevance between normally engaged regions are a suggested key mechanism. Thus, network analysis methods seem critical for investigation of changes in directed causal interactions between such candidate brain regions. To identify core compensatory regions, fifteen preclinical patients carrying the genetic mutation leading to Huntington's disease and twelve controls underwent fMRI scanning. They accomplished an auditory paced finger sequence tapping task, which challenged cognitive as well as executive aspects of motor functioning by varying speed and complexity of movements. To investigate causal interactions among brain regions a single Dynamic Causal Model (DCM) was constructed and fitted to the data from each subject. The DCM parameters were analysed using statistical methods to assess group differences in connectivity, and the relationship between connectivity patterns and predicted years to clinical onset was assessed in gene carriers. In preclinical patients, we found indications for neural reserve mechanisms predominantly driven by bilateral dorsal premotor cortex, which increasingly activated superior parietal cortices the closer individuals were to estimated clinical onset. This compensatory mechanism was restricted to complex movements characterised by high cognitive demand. Additionally, we identified task-induced connectivity changes in both groups of subjects towards pre- and caudal supplementary motor areas, which were linked to either faster or more complex task conditions. Interestingly, coupling of dorsal premotor cortex and supplementary motor area was more negative in controls compared to gene mutation carriers. Furthermore, changes in the connectivity pattern of gene carriers allowed prediction of the years to estimated disease onset in individuals. Our study characterises the connectivity pattern of core cortical regions maintaining motor function in relation to varying task demand. We identified connections of bilateral dorsal premotor cortex as critical for compensation as well as task-dependent recruitment of pre- and caudal supplementary motor area. The latter finding nicely mirrors a previously published general linear model-based analysis of the same data. Such knowledge about disease specific inter-regional effective connectivity may help identify foci for interventions based on transcranial magnetic stimulation designed to stimulate functioning and also to predict their impact on other regions in motor-associated networks

A Guide to Localized Frames and Applications to Galerkin-like Representations of Operators

This chapter offers a detailed survey on intrinsically localized frames and the corresponding matrix representation of operators. We re-investigate the properties of localized frames and the associated Banach spaces in full detail. We investigate the representation of operators using localized frames in a Galerkin-type scheme. We show how the boundedness and the invertibility of matrices and operators are linked and give some sufficient and necessary conditions for the boundedness of operators between the associated Banach spaces.Comment: 32 page

Brain Effective Connectivity During Motor-Imagery and Execution Following Stroke and Rehabilitation

Brain areas within the motor system interact directly or indirectly during motor-imagery and motor-execution tasks. These interactions and their functionality can change following stroke and recovery. How brain network interactions reorganize and recover their functionality during recovery and treatment following stroke are not well understood. To contribute to answering these questions, we recorded blood oxygenation-level dependent (BOLD) functional magnetic resonance imaging (fMRI) signals from10 stroke survivors and evaluated dynamical causal modeling (DCM)-based effective connectivity among three motor areas: primary motor cortex (M1), premotor cortex (PMC) and supplementary motor area (SMA), during motor-imagery and motor-execution tasks. We compared the connectivity between affected and unaffected hemispheres before and after mental practice and combined mental practice and physical therapy as treatments. The treatment (intervention) period varied in length between 14 to 51 days but all patients received the same dose of 60 h of treatment. Using Bayesian model selection (BMS) approach in the DCMapproach, wefound that, after intervention, the same network dominated during motor-imagery and motor-execution tasks butmodulatory parameters suggested a suppressive influence of SM A on M1 during the motor-imagery task whereas the influence of SM A on M1 was unrestricted during themotor-execution task.We found that the intervention caused a reorganization of the network during both tasks for unaffected as well as for the affected hemisphere. Using Bayesian model averaging (BMA) approach, we found that the intervention improved the regional connectivity among the motor areas during both the tasks. The connectivity between PMCandM1was stronger inmotor-imagery taskswhereas the connectivity from PMC to M1, SM A to M1 dominated in motor-execution tasks. There was significant behavioral improvement (p = 0.001) in sensation and motor movements because of the intervention as reflected by behavioral Fugl-Meyer (FMA)measures,whichwere significantly correlated (p=0.05)with a subset of connectivity. These findings suggest that PMC andM1 play a crucial role duringmotor-imagery aswell as during motorexecution task. In addition,M1 causesmore exchange of causal information amongmotor areas during a motorexecution task than during a motor-imagery task due to its interaction with SM A. This study expands our understanding of motor network involved during two different tasks, which are commonly used during rehabilitation following stroke. A clear understanding of the effective connectivity networks leads to a better treatment in helping stroke survivors regain motor ability

Dynamic causal modelling of effective connectivity during perspective taking in a communicative task

Previous studies have shown that taking into account another person's perspective to guide decisions is more difficult when their perspective is incongruent from one's own compared to when it is congruent. Here we used dynamic causal modelling (DCM) for functional magnetic resonance imaging (fMRI) to investigate effective connectivity between prefrontal and posterior brain regions in a task that requires participants to take into account another person's perspective in order to guide the selection of an action. Using a new procedure to score model evidence without computationally costly estimation, we conducted an exhaustive search for the best of all possible models. The results elucidate how the activity in the areas from our previously reported analysis (Dumontheil et al., 2010) are causally linked and how the connections are modulated by both the social as well as executive task demands of the task. We find that the social demands modulate the backward connections from the medial prefrontal cortex (MPFC) more strongly than the forward connections from the superior occipital gyrus (SOG) and the medial temporal gyrus (MTG) to the MPFC. This was also the case for the backward connection from the MTG to the SOG. Conversely, the executive task demands modulated the forward connections of the SOG and the MTG to the MPFC more strongly than the backward connections. We interpret the results in terms of hierarchical predictive coding

Functional Organization and Restoration of the Brain Motor-Execution Network After Stroke and Rehabilitation

Multiple cortical areas of the human brain motor system interact coherently in the low frequency range (\u3c0.1 Hz), even in the absence of explicit tasks. Following stroke, cortical interactions are functionally disturbed. How these interactions are affected and how the functional organization is regained from rehabilitative treatments as people begin to recover motor behaviors has not been systematically studied. We recorded the intrinsic functional magnetic resonance imaging (fMRI) signals from 30 participants: 17 young healthy controls and 13 aged stroke survivors. Stroke participants underwent mental practice (MP) or both mental practice and physical therapy (MP+PT) within 14–51 days following stroke. We investigated the network activity of five core areas in the motor-execution network, consisting of the left primary motor area (LM1), the right primary motor area (RM1), the left pre-motor cortex (LPMC), the right pre-motor cortex (RPMC) and the supplementary motor area (SMA). We discovered that (i) the network activity dominated in the frequency range 0.06–0.08 Hz for all the regions, and for both able-bodied and stroke participants (ii) the causal information flow between the regions: LM1 and SMA, RPMC and SMA, RPMC and LM1, SMA and RM1, SMA and LPMC, was reduced significantly for stroke survivors (iii) the flow did not increase significantly after MP alone and (iv) the flow among the regions during MP+PT increased significantly. We also found that sensation and motor scores were significantly higher and correlated with directed functional connectivity measures when the stroke-survivors underwent MP+PT but not MP alone. The findings provide evidence that a combination of mental practice and physical therapy can be an effective means of treatment for stroke survivors to recover or regain the strength of motor behaviors, and that the spectra of causal information flow can be used as a reliable biomarker for evaluating rehabilitation in stroke survivors

Feedforward and feedback pathways of nociceptive and tactile processing in human somatosensory system: A study of dynamic causal modeling of fMRI data

Nociceptive and tactile information is processed in the somatosensory system via reciprocal (i.e., feedforward and feedback) projections between the thalamus, the primary (S1) and secondary (S2) somatosensory cortices. The exact hierarchy of nociceptive and tactile information processing within this ‘thalamus-S1-S2’ network and whether the processing hierarchy differs between the two somatosensory submodalities remains unclear. In particular, two questions related to the ascending and descending pathways have not been addressed. For the ascending pathways, whether tactile or nociceptive information is processed in parallel (i.e., 'thalamus-S1′ and 'thalamus-S2′) or in serial (i.e., 'thalamus-S1-S2′) remains controversial. For the descending pathways, how corticothalamic feedback regulates nociceptive and tactile processing also remains elusive. Here, we aimed to investigate the hierarchical organization for the processing of nociceptive and tactile information in the ‘thalamus-S1-S2’ network using dynamic causal modeling (DCM) combined with high-temporal-resolution fMRI. We found that, for both nociceptive and tactile information processing, both S1 and S2 received inputs from thalamus, indicating a parallel structure of ascending pathways for nociceptive and tactile information processing. Furthermore, we observed distinct corticothalamic feedback regulations from S1 and S2, showing that S1 generally exerts inhibitory feedback regulation independent of external stimulation whereas S2 provides additional inhibition to the thalamic activity during nociceptive and tactile information processing in humans. These findings revealed that nociceptive and tactile information processing have similar hierarchical organization within the somatosensory system in the human brain

Parallel Alterations of Functional Connectivity during Execution and Imagination after Motor Imagery Learning

BACKGROUND: Neural substrates underlying motor learning have been widely investigated with neuroimaging technologies. Investigations have illustrated the critical regions of motor learning and further revealed parallel alterations of functional activation during imagination and execution after learning. However, little is known about the functional connectivity associated with motor learning, especially motor imagery learning, although benefits from functional connectivity analysis attract more attention to the related explorations. We explored whether motor imagery (MI) and motor execution (ME) shared parallel alterations of functional connectivity after MI learning. METHODOLOGY/PRINCIPAL FINDINGS: Graph theory analysis, which is widely used in functional connectivity exploration, was performed on the functional magnetic resonance imaging (fMRI) data of MI and ME tasks before and after 14 days of consecutive MI learning. The control group had no learning. Two measures, connectivity degree and interregional connectivity, were calculated and further assessed at a statistical level. Two interesting results were obtained: (1) The connectivity degree of the right posterior parietal lobe decreased in both MI and ME tasks after MI learning in the experimental group; (2) The parallel alterations of interregional connectivity related to the right posterior parietal lobe occurred in the supplementary motor area for both tasks. CONCLUSIONS/SIGNIFICANCE: These computational results may provide the following insights: (1) The establishment of motor schema through MI learning may induce the significant decrease of connectivity degree in the posterior parietal lobe; (2) The decreased interregional connectivity between the supplementary motor area and the right posterior parietal lobe in post-test implicates the dissociation between motor learning and task performing. These findings and explanations further revealed the neural substrates underpinning MI learning and supported that the potential value of MI learning in motor function rehabilitation and motor skill learning deserves more attention and further investigation

Effects of rumble strip parameters on acoustics, vibration, and perception

Rumble strips aim to alert the driver of dangerous situations via acoustic and tactile stimulation. They can, however, also lead to increased noise in the surroundings. Strip parameters and the vehicle type determines the size of these acoustic and vibratory effects. In our work, 16 rumble strip types (including strips with irregular spacing) were evaluated with respect to their effects on acoustics, vibration, and perception. Interior and exterior emissions caused by controlled pass-overs of a car and a truck were recorded. Annoyance, urgency, and reaction time of 16 listeners were tested in a laboratory experiment and models mapping acoustics to perception were developed. Steering wheel and seat vibrations were acquired. Our results show a high correlation of interior and exterior noise. The loudness level was the best predictor of perceived annoyance and urgency. Irregular spacing reduced the tonality at the cost of a difficult production process. While a large variety of strip types produced a sufficient acoustic effect in the passenger car, the acoustic response was lower in the truck. Combined with the low vibration levels found in the truck, an identification of an optimal strip type for both vehicle types turns out to be difficult