Recovered grasping performance after stroke depends on interhemispheric frontoparietal connectivity.

Activity changes in the ipsi- and contralesional parietal cortex and abnormal interhemispheric connectivity between these regions are commonly observed after stroke, however, their significance for motor recovery remains poorly understood. We here assessed the contribution of ipsilesional and contralesional anterior intraparietal cortex (aIPS) for hand motor function in 18 recovered chronic stroke patients and 18 healthy control subjects using a multimodal assessment consisting of resting-state functional MRI, motor task functional MRI, online-repetitive transcranial magnetic stimulation (rTMS) interference, and 3D movement kinematics. Effects were compared against two control stimulation sites, i.e. contralesional M1 and a sham stimulation condition. We found that patients with good motor outcome compared to patients with more substantial residual deficits featured increased resting-state connectivity between ipsilesional aIPS and contralesional aIPS as well as between ipsilesional aIPS and dorsal premotor cortex. Moreover, interhemispheric connectivity between ipsilesional M1 and contralesional M1 as well as ipsilesional aIPS and contralesional M1 correlated with better motor performance across tasks. TMS interference at individual aIPS and M1 coordinates led to differential effects depending on the motor task that was tested, i.e. index finger-tapping, rapid pointing movements, or a reach-grasp-lift task. Interfering with contralesional aIPS deteriorated the accuracy of grasping, especially in patients featuring higher connectivity between ipsi- and contralesional aIPS. In contrast, interference with the contralesional M1 led to impaired grasping speed in patients featuring higher connectivity between bilateral M1. These findings suggest differential roles of contralesional M1 and aIPS for distinct aspects of recovered hand motor function, depending on the reorganization of interhemispheric connectivity.

Robustness of individualized inferences from longitudinal resting state EEG dynamics.

Tracking how individual human brains change over extended timescales is crucial to clinical scenarios ranging from stroke recovery to healthy aging. The use of resting state (RS) activity for tracking is a promising possibility. However, it is unresolved how a person's RS activity over time can be decoded to distinguish neurophysiological changes from confounding cognitive variability. Here, we develop a method to screen RS activity changes for these confounding effects by formulating it as a problem of change classification. We demonstrate a novel solution to change classification by linking individual-specific change to inter-individual differences. Individual RS-electroencephalography (EEG) was acquired over 5 consecutive days including task states devised to simulate the effects of inter-day cognitive variation. As inter-individual differences are shaped by neurophysiological differences, the inter-individual differences in RS activity on 1 day were analysed (using machine learning) to identify distinctive configurations in each individual's RS activity. Using this configuration as a decision rule, an individual could be re-identified from 2-s samples of the instantaneous oscillatory power spectrum acquired on a different day both from RS and confounded RS with a limited loss in accuracy. Importantly, the low loss in accuracy in cross-day versus same-day classification was achieved with classifiers that combined information from multiple frequency bands at channels across the scalp (with a concentration at characteristic fronto-central and occipital zones). Taken together, these findings support the technical feasibility of screening RS activity for confounding effects and the suitability of longitudinal RS for robust individualized inferences about neurophysiological change in health and disease.

A response-locking protocol to boost sensitivity for fMRI-based neurochronometry.

The timeline of brain-wide neural activity relative to a behavioral event is crucial when decoding the neural implementation of a cognitive process. Yet, fMRI assesses neural processes indirectly via delayed and regionally variable hemodynamics. This method-inherent temporal distortion impacts the interpretation of behavior-linked neural timing. Here we describe a novel behavioral protocol that aims at disentangling the BOLD dynamics of the pre- and post-response periods in response time tasks. We tested this response-locking protocol in a perceptual decision-making (random dot) task. Increasing perceptual difficulty produced expected activity increases over a broad network involving the lateral/medial prefrontal cortex and the anterior insula. However, response-locking revealed a previously unreported functional dissociation within this network. preSMA and anterior premotor cortex (prePMV) showed post-response activity modulations while anterior insula and anterior cingulate cortex did not. Furthermore, post-response BOLD activity at preSMA showed a modulation in timing but not amplitude while this pattern was reversed at prePMV. These timeline dissociations with response-locking thus revealed three functionally distinct sub-networks in what was seemingly one shared distributed network modulated by perceptual difficulty. These findings suggest that our novel response-locked protocol could boost the timing-related sensitivity of fMRI.

Invasive versus non-invasive mapping of the motor cortex.

Precise and comprehensive mapping of somatotopic representations in the motor cortex is clinically essential to achieve maximum resection of brain tumours whilst preserving motor function, especially since the current gold standard, that is, intraoperative direct cortical stimulation (DCS), holds limitations linked to the intraoperative setting such as time constraints or anatomical restrictions. Non-invasive techniques are increasingly relevant with regard to pre-operative risk-assessment. Here, we assessed the congruency of neuronavigated transcranial magnetic stimulation (nTMS) and functional magnetic resonance imaging (fMRI) with DCS. The motor representations of the hand, the foot and the tongue regions of 36 patients with intracranial tumours were mapped pre-operatively using nTMS and fMRI and by intraoperative DCS. Euclidean distances (ED) between hotspots/centres of gravity and (relative) overlaps of the maps were compared. We found significantly smaller EDs (11.4 ± 8.3 vs. 16.8 ± 7.0 mm) and better spatial overlaps (64 ± 38% vs. 37 ± 37%) between DCS and nTMS compared with DCS and fMRI. In contrast to DCS, fMRI and nTMS mappings were feasible for all regions and patients without complications. In summary, nTMS seems to be the more promising non-invasive motor cortex mapping technique to approximate the gold standard DCS results.

Freely chosen and instructed actions are terminated by different neural mechanisms revealed by kinematics-informed EEG.

Neurophysiological accounts of human volition are dominated by debates on the origin of voluntary choices but the neural consequences that follow such choices remain poorly understood. For instance, could one predict whether or not an action was chosen voluntarily based only on how that action is motorically executed? We investigated this possibility by integrating scalp electroencephalograms and index-finger accelerometer recordings acquired while people chose between pressing a left or right button either freely or as instructed by a visual cue. Even though freely selected and instructed actions were executed with equal vigor, the timing of the movement to release the button was comparatively delayed for freely selected actions. This chronometric difference was six-times larger for the ß-oscillations over the sensorimotor cortex that characteristically accompany an action's termination. This surprising modulation of an action's termination by volition was traceable to volition-modulated differences in how the competing yet non-selected action was represented and regulated.

Frequency-specific modulation of connectivity in the ipsilateral sensorimotor cortex by different forms of movement initiation.

A consistent finding in motor EEG research is a bilateral attenuation of oscillatory activity over sensorimotor regions close to the onset of an upcoming unilateral hand movement. In contrast, little is known about how movement initiation affects oscillatory activity, especially in the hemisphere ipsilateral to the moving hand. We here investigated the neural mechanisms modulating oscillatory activity in the ipsilateral motor cortex prior to movement onset under the control of two different initiating networks, namely, Self-initiated and Visually-cued actions. During motor preparation, a contralateral preponderance of power over sensorimotor cortex (SM) was observed in α and ß bands during Visually-cued movements, whereas power changes were more bilateral during Self-initiated movements. Coherence between ipsilateral SM (iSM) and contralateral SM (cSM) in the α-band was significantly increased compared to the respective baseline values, independent of the context of movement initiation. However, this context-independent cSM-iSM coherence modulated the power changes in iSM in a context-dependent manner, that is, a stronger cSM-iSM coherence correlated with a larger decrease in high-ß power over iSM in the Self-initiated condition, in contrast to a smaller decrease in α power in the Visually-cued condition. In addition, the context-dependent coherence between SMA and iSM in the α-band and δ-θ-band for the Self-initiated and Visually-cued condition, respectively, exhibited a similar context-dependent modulation for power changes. Our findings suggest that the initiation of regional oscillations over iSM reflects changes in the information flow with the contralateral sensorimotor and premotor areas dependent upon the context of movement initiation. Importantly, the interaction between regional oscillations and network-like oscillatory couplings indicates different frequency-specific inhibitory mechanisms that modulate the activity in the ipsilateral sensorimotor cortex dependent upon how the movement is initiated.

Dopaminergic modulation of motor network dynamics in Parkinson's disease.

Although characteristic motor symptoms of Parkinson's disease such as bradykinesia typically improve under dopaminergic medication, deficits in higher motor control are less responsive. We here investigated the dopaminergic modulation of network dynamics underlying basic motor performance, i.e. finger tapping, and higher motor control, i.e. internally and externally cued movement preparation and selection. Twelve patients, assessed ON and OFF medication, and 12 age-matched healthy subjects underwent functional magnetic resonance imaging. Dynamic causal modelling was used to assess effective connectivity in a motor network comprising cortical and subcortical regions. In particular, we investigated whether impairments in basic and higher motor control, and the effects induced by dopaminergic treatment are due to connectivity changes in (i) the mesial premotor loop comprising the supplementary motor area; (ii) the lateral premotor loop comprising lateral premotor cortex; and (iii) cortico-subcortical interactions. At the behavioural level, we observed a marked slowing of movement preparation and selection when patients were internally as opposed to externally cued. Preserved performance during external cueing was associated with enhanced connectivity between prefrontal cortex and lateral premotor cortex OFF medication, compatible with a context-dependent compensatory role of the lateral premotor loop in the hypodopaminergic state. Dopaminergic medication significantly improved finger tapping speed in patients, which correlated with a drug-induced coupling increase of prefrontal cortex with the supplementary motor area, i.e. the mesial premotor loop. In addition, only in the finger tapping condition, patients ON medication showed enhanced excitatory influences exerted by cortical premotor regions and the thalamus upon the putamen. In conclusion, the amelioration of bradykinesia by dopaminergic medication seems to be driven by enhanced connectivity within the mesial premotor loop and cortico-striatal interactions. In contrast, medication did not improve internal motor control deficits concurrent to missing effects at the connectivity level. This differential effect of dopaminergic medication on the network dynamics underlying motor control provides new insights into the clinical finding that in Parkinson's disease dopaminergic drugs especially impact on bradykinesia but less on executive functions.

Feature interactions enable decoding of sensorimotor transformations for goal-directed movement.

Neurophysiology and neuroimaging evidence shows that the brain represents multiple environmental and body-related features to compute transformations from sensory input to motor output. However, it is unclear how these features interact during goal-directed movement. To investigate this issue, we examined the representations of sensory and motor features of human hand movements within the left-hemisphere motor network. In a rapid event-related fMRI design, we measured cortical activity as participants performed right-handed movements at the wrist, with either of two postures and two amplitudes, to move a cursor to targets at different locations. Using a multivoxel analysis technique with rigorous generalization tests, we reliably distinguished representations of task-related features (primarily target location, movement direction, and posture) in multiple regions. In particular, we identified an interaction between target location and movement direction in the superior parietal lobule, which may underlie a transformation from the location of the target in space to a movement vector. In addition, we found an influence of posture on primary motor, premotor, and parietal regions. Together, these results reveal the complex interactions between different sensory and motor features that drive the computation of sensorimotor transformations.

Differentiated, rather than shared, strategies for time-coordinated action in social and non-social domains in autistic individuals.

Autism spectrum disorder (ASD) is a neurodevelopmental condition with a highly heterogeneous adult phenotype that includes social and non-social behavioral characteristics. The link between the characteristics assignable to the different domains remains unresolved. One possibility is that social and non-social behaviors in autism are modulated by a common underlying deficit. However, here we report evidence supporting an alternative concept that is individual-centered rather than deficit-centered. Individuals are assumed to have a distinctive style in the strategies they adopt to perform social and non-social tasks with these styles presumably being structured differently between autistic individuals and typically-developed (TD) individuals. We tested this hypothesis for the execution of time-coordinated (synchronized) actions. Participants performed (i) a social task that required synchronized gaze and pointing actions to interact with another person, and (ii) a non-social task that required finger-tapping actions synchronized to periodic stimuli at different time-scales and sensory modalities. In both tasks, synchronization behavior differed between ASD and TD groups. However, a principal component analysis of individual behaviors across tasks revealed associations between social and non-social features for the TD persons but such cross-domain associations were strikingly absent for autistic individuals. The highly differentiated strategies between domains in ASD are inconsistent with a general synchronization deficit and instead highlight the individualized developmental heterogeneity in the acquisition of domain-specific behaviors. We propose a cognitive model to help disentangle individual-centered from deficit-centered effects in other domains. Our findings reinforce the importance to identify individually differentiated phenotypes to personalize autism therapies.

To engage or not engage: Early incentive motivation prevents symptoms of chronic post-stroke depression - A longitudinal study.

BACKGROUND: Although post-stroke depression (PSD) is known to disrupt motor rehabilitation after stroke, PSD is often undertreated and its relationship with motor impairment remains poorly understood. METHODS: In a longitudinal study design we investigated, which factors at the early post-acute stage may increase the risk for PSD symptoms. We were especially interested in whether interindividual differences in the motivational drive to engage in physically demanding tasks indicate PSD development in patients suffering from motor impairments. Accordingly, we used a monetary incentive grip force task where participants were asked to hold their grip force for high and low rewards at stake to maximize their monetary outcome. Individual grip force was normalized according to the maximal force prior to the experiment. Experimental data, depression, and motor impairment were assessed from 20 stroke patients (12 male; 7.7 ± 6.78 days post-stroke) with mild-to-moderate hand motor impairment and 24 age-matched healthy participants (12 male). RESULTS: Both groups showed incentive motivation as indicated by stronger grip force for high versus low reward trials and the overall monetary outcome in the task. In stroke patients, severely impaired patients showed stronger incentive motivation, whereas early PSD symptoms were associated with reduced incentive motivation in the task. Larger lesions in corticostriatal tracts correlated with reduced incentive motivation. Importantly, chronic motivational deficits were preceded by initially reduced incentive motivation and larger corticostriatal lesions in the early stage post-stroke. CONCLUSIONS: More severe motor impairment motivates reward-dependent motor engagement, whereas PSD and corticostriatal lesions potentially disturb incentive motivational behavior, thereby increasing the risk of chronic motivational PSD symptoms. Acute interventions should address motivational aspects of behavior to improve motor rehabilitation post-stroke.

Telling the right hand from the left hand: multisensory integration, not motor imagery, solves the problem.

Judging the laterality of a hand seen at unanticipated orientations evokes a robust feeling of bodily movement, even though no movement is produced. In two experiments, we tested a novel hypothesis to explain this phenomenon: A hand's laterality is determined via a multisensory binding of the visual representation of the seen hand and a proprioceptive representation of the observer's felt hand, and the felt "movement" is an obligatory aftereffect of intersensory recalibration. Consistent with the predictions implied by such a cross-modal mechanism, our results in Experiment 1 showed that manipulating observers' selective attention can evoke illusory feelings of movement in the "wrong" hand (i.e., the hand whose laterality does not match that of the stimulus). In Experiment 2, these illusions were readily extinguished in conditions in which binding was predicted to fail, a result indicating that cross-modal binding was necessary to produce them. These results are not explained by imagery, a mechanism widely assumed to account for how hand laterality is identified.

Dissociating passage and duration of time experiences through the intensity of ongoing visual change.

The experience of passage of time is assumed to be a constitutive component of our subjective phenomenal experience and our everyday life that is detached from the estimation of time durations. However, our understanding of the factors contributing to passage of time experience has been mostly restricted to associated emotional and cognitive experiences in temporally extended situations. Here, we tested the influence of low-level visual stimuli on the experience of passage and duration of time in 10-30 s intervals. We introduce a new paradigm in a starfield environment that allows to study the effects of basic visual aspects of a scene (velocity and density of stars in the starfield) and the duration of the situation, both embedded in a color tracking task. Results from two experiments show that velocity and density of stars in the starfield affect passage of time experience independent from duration estimation and the color tracking task: the experienced passage of time is accelerated with higher rates of moment-to-moment changes in the starfield while duration estimations are comparably unaffected. The results strongly suggest differential psychological processes underlying the experience of time passing by and the ability to estimate time durations. Potential mechanisms behind these results and the prospects of experimental approaches towards passage of time experience in psychological and neuroscientific research are discussed.

The capacity and organization of gustatory working memory.

Remembering a particular taste is crucial in food intake and associative learning. We investigated whether taste can be dynamically encoded, maintained, and retrieved on short time scales consistent with working memory (WM). We use novel single and multi-item taste recognition tasks to show that a single taste can be reliably recognized despite repeated oro-sensory interference suggesting active and resilient maintenance (Experiment 1, N = 21). When multiple tastes were presented (Experiment 2, N = 20), the resolution with which these were maintained depended on their serial position, and recognition was reliable for up to three tastes suggesting a limited capacity of gustatory WM. Lastly, stimulus similarity impaired recognition with increasing set size, which seemed to mask the awareness of capacity limitations. Together, the results advocate a hybrid model of gustatory WM with a limited number of slots where items are stored with varying precision.

An individualized functional magnetic resonance imaging protocol to assess semantic congruency effects on episodic memory in an aging multilingual population.

The cognitive stimulation induced by multilingualism may slow down age-related memory impairment. However, a suitable neuroscientific framework to assess the influence of multilingualism on age-related memory processes is missing. We propose an experimental paradigm that assesses the effects of semantic congruency on episodic memory using functional magnetic resonance imaging (fMRI). To this end, we modified the picture-word interference (PWI) task to be suitable for the assessment of older multilingual subjects undergoing fMRI. In particular, stimulus materials were prepared in multiple languages (French, German, Luxembourgish, English) and closely matched in semantic properties, thus enabling participants to perform the experiment in a language of their choice. This paradigm was validated in a group (n = 62) of healthy, older participants (over 64 years) who were multilingual, all practicing three or more languages. Consistent with the engagement of semantic congruency processes, we found that the encoding and recognition of semantically related vs. unrelated picture-word pairs evoked robust differences in behavior and the neural activity of parietal-temporal networks. These effects were negligibly modulated by the language used to perform the task. Based on this validation in a multilingual population, we conclude that the proposed paradigm will allow future studies to evaluate whether multilingualism aptitude engages neural systems in a manner that protects long-term memory from aging-related decline.

The role of dopamine in dynamic effort-reward integration.

When deciding to act, the neurotransmitter dopamine is implicated in a valuation of prospective effort and reward. However, its role in dynamic effort-reward integration during action, a process central to everyday behaviour, remains unclear. In a placebo-controlled, within-subject, study, we probed the impact of increasing brain dopamine levels (150 mg of levodopa) and blocking dopamine receptors (1.5 mg of haloperidol) in the context of a novel dynamic effort task in healthy human subjects. We show that modulating homoeostatic dopamine balance distinctly alters implicit and explicit effort allocation as a function of instantaneous reward. Pharmacologically boosting dopamine enhanced motor vigour, reflected in an implicit increase in effort allocation for high rewards. Conversely, pharmacological blockade of dopamine attenuated sensitivity to differences in reward context, reflected in reduced strategic effort discounting. These findings implicate dopamine in an integration of momentary physical experience and instantaneous reward, suggesting a key role of dopamine in acting to maximise reward on the fly.

Combined FET PET/MRI radiomics differentiates radiation injury from recurrent brain metastasis.

Background: The aim of this study was to investigate the potential of combined textural feature analysis of contrast-enhanced MRI (CE-MRI) and static O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET for the differentiation between local recurrent brain metastasis and radiation injury since CE-MRI often remains inconclusive. Methods: Fifty-two patients with new or progressive contrast-enhancing brain lesions on MRI after radiotherapy (predominantly stereotactic radiosurgery) of brain metastases were additionally investigated using FET PET. Based on histology (n = 19) or clinicoradiological follow-up (n = 33), local recurrent brain metastases were diagnosed in 21 patients (40%) and radiation injury in 31 patients (60%). Forty-two textural features were calculated on both unfiltered and filtered CE-MRI and summed FET PET images (20-40 min p.i.), using the software LIFEx. After feature selection, logistic regression models using a maximum of five features to avoid overfitting were calculated for each imaging modality separately and for the combined FET PET/MRI features. The resulting models were validated using cross-validation. Diagnostic accuracies were calculated for each imaging modality separately as well as for the combined model. Results: For the differentiation between radiation injury and recurrence of brain metastasis, textural features extracted from CE-MRI had a diagnostic accuracy of 81% (sensitivity, 67%; specificity, 90%). FET PET textural features revealed a slightly higher diagnostic accuracy of 83% (sensitivity, 88%; specificity, 75%). However, the highest diagnostic accuracy was obtained when combining CE-MRI and FET PET features (accuracy, 89%; sensitivity, 85%; specificity, 96%). Conclusions: Our findings suggest that combined FET PET/CE-MRI radiomics using textural feature analysis offers a great potential to contribute significantly to the management of patients with brain metastases.

Aging-associated changes of movement-related functional connectivity in the human brain.

Motor performance declines with normal aging. Previous neuroimaging work revealed aging-related general increases in neural activity, especially in the prefrontal and pre-motor areas, associated with a loss of hemispheric lateralization. However, the functional mechanisms underlying these changes and their relation to aging-associated motor decline to date remain elusive. To further elucidate the neural processes underlying aging-related motor decline, we recorded EEG from younger and older subjects while they performed a finger-tapping task. As a measure of synchronization between motor areas, we computed the inter-regional phase-locking value which reflects functional connectivity between distinct neural populations. Behavioral data revealed increased movement times in older subjects. EEG data showed that phase locking in the δ-θ frequencies is a general, age-independent phenomenon underlying the execution of simple finger movements. In stark contrast, the extent of synchronization between motor areas significantly differed dependent upon age of subjects: multiple additional intra- and inter-hemispheric connections were observed in older subjects. Our data shed light upon the results of previous neuroimaging studies showing aging-related increases in neural activation. In particular, data suggest that the observed aging-dependent substantial intra- and inter-hemispheric reorganization of connectivity between the corresponding motor areas underlies the previously reported loss of lateralization in older subjects. The changes observed are likely to represent compensatory mechanisms aiming at preserved task performance in older subjects.

Predicting IDH genotype in gliomas using FET PET radiomics.

Mutations in the isocitrate dehydrogenase (IDH mut) gene have gained paramount importance for the prognosis of glioma patients. To date, reliable techniques for a preoperative evaluation of IDH genotype remain scarce. Therefore, we investigated the potential of O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET radiomics using textural features combined with static and dynamic parameters of FET uptake for noninvasive prediction of IDH genotype. Prior to surgery, 84 patients with newly diagnosed and untreated gliomas underwent FET PET using a standard scanner (15 of 56 patients with IDH mut) or a dedicated high-resolution hybrid PET/MR scanner (11 of 28 patients with IDH mut). Static, dynamic and textural parameters of FET uptake in the tumor area were evaluated. Diagnostic accuracy of the parameters was evaluated using the neuropathological result as reference. Additionally, FET PET and textural parameters were combined to further increase the diagnostic accuracy. The resulting models were validated using cross-validation. Independent of scanner type, the combination of standard PET parameters with textural features increased significantly diagnostic accuracy. The highest diagnostic accuracy of 93% for prediction of IDH genotype was achieved with the hybrid PET/MR scanner. Our findings suggest that the combination of conventional FET PET parameters with textural features provides important diagnostic information for the non-invasive prediction of the IDH genotype.

Age-related changes in oscillatory power affect motor action.

With increasing age cognitive performance slows down. This includes cognitive processes essential for motor performance. Additionally, performance of motor tasks becomes less accurate. The objective of the present study was to identify general neural correlates underlying age-related behavioral slowing and the reduction in motor task accuracy. To this end, we continuously recorded EEG activity from 18 younger and 24 older right-handed healthy participants while they were performing a simple finger tapping task. We analyzed the EEG records with respect to local changes in amplitude (power spectrum) as well as phase locking between the two age groups. We found differences between younger and older subjects in the amplitude of post-movement synchronization in the ß band of the sensory-motor and medial prefrontal cortex (mPFC). This post-movement ß amplitude was significantly reduced in older subjects. Moreover, it positively correlated with the accuracy with which subjects performed the motor task at the electrode FCz, which detects activity of the mPFC and the supplementary motor area. In contrast, we found no correlation between the accurate timing of local neural activity, i.e. phase locking in the δ-θ frequency band, with the reaction and movement time or the accuracy with which the motor task was performed. Our results show that only post-movement ß amplitude and not δ-θ phase locking is involved in the control of movement accuracy. The decreased post-movement ß amplitude in the mPFC of older subjects hints at an impaired deactivation of this area, which may affect the cognitive control of stimulus-induced motor tasks and thereby motor output.