The electrophysiological basis of resting‐state networks (RSN) is still under debate. In particular, no principled mechanism has been determined that is capable of explaining all RSN equally well. ...While magnetoencephalography (MEG) and electroencephalography are the methods of choice to determine the electrophysiological basis of RSN, no standard analysis pipeline of RSN yet exists. In this article, we compare the two main existing data‐driven analysis strategies for extracting RSNs from MEG data and introduce a third approach. The first approach uses phase–amplitude coupling to determine the RSN. The second approach extracts RSN through an independent component analysis of the Hilbert envelope in different frequency bands, while the third new approach uses a singular value decomposition instead. To evaluate these approaches, we compare the MEG‐RSN to the functional magnetic resonance imaging (fMRI)‐RSN from the same subjects. Overall, it was possible to extract RSN with MEG using all three techniques, which matched the group‐specific fMRI‐RSN. Interestingly the new approach based on SVD yielded significantly higher correspondence to five out of seven fMRI‐RSN than the two existing approaches. Importantly, with this approach, all networks—except for the visual network—had the highest correspondence to the fMRI networks within one frequency band. Thereby we provide further insights into the electrophysiological underpinnings of the fMRI‐RSNs. This knowledge will be important for the analysis of the electrophysiological connectome.
We compare the two main existing data‐driven analysis strategies for extracting resting‐state network (RSN) from magnetoencephalography (MEG) data and introduce a third approach. While it is possible to extract RSN with MEG using all three techniques, the new approach yielded significantly higher correspondence for most RSN.
Cerebellum and basal ganglia are reciprocally interconnected with the neocortex via oligosynaptic loops. The signal pathways of these loops predominantly converge in motor areas of the frontal cortex ...and are mainly segregated on subcortical level. Recent evidence, however, indicates subcortical interaction of these systems. We have reviewed literature that addresses the question whether, and to what extent, projections of main output nuclei of basal ganglia (reticular part of the substantia nigra, internal segment of the globus pallidus) and cerebellum (deep cerebellar nuclei) interact with each other in the thalamus. To this end, we compiled data from electrophysiological and anatomical studies in rats, cats, dogs, and non-human primates. Evidence suggests the existence of convergence of thalamic projections originating in basal ganglia and cerebellum, albeit sparse and restricted to certain regions. Four regions come into question to contain converging inputs: (1) lateral parts of medial dorsal nucleus (MD); (2) parts of anterior intralaminar nuclei and centromedian and parafascicular nuclei (CM/Pf); (3) ventromedial nucleus (VM); and (4) border regions of cerebellar and ganglia terminal territories in ventral anterior and ventral lateral nuclei (VA–VL). The amount of convergences was found to exhibit marked interspecies differences. To explain the rather sparse convergences of projection territories and to estimate their physiological relevance, we present two conceivable principles of anatomical organization: (1) a “core-and-shell” organization, in which a central core is exclusive to one projection system, while peripheral shell regions intermingle and occasionally converge with other projection systems and (2) convergences that are characteristic to distinct functional networks. The physiological relevance of these convergences is not yet clear. An oculomotor network proposed in this work is an interesting candidate to examine potential ganglia and cerebellar subcortical interactions.
Basal ganglia and the cerebellum are part of a densely interconnected network. While both subcortical structures process information in basically segregated loops that primarily interact in the ...neocortex, direct subcortical interaction has been recently confirmed by neuroanatomical studies using viral transneuronal tracers in non-human primate brains. The thalamus is thought to be the main relay station of both projection systems. Yet, our understanding of subcortical basal ganglia and cerebellar interconnectivity within the human thalamus is rather sparse, primarily due to limitation in the acquisition of in vivo tracing. Consequently, we strive to characterize projections of both systems and their potential overlap within the human thalamus by diffusion MRI and tractography. Our analysis revealed a decreasing anterior-to-posterior gradient for pallido-thalamic connections in: (1) the ventral-anterior thalamus, (2) the intralaminar nuclei, and (3) midline regions. Conversely, we found a decreasing posterior-to-anterior gradient for dentato-thalamic projections predominantly in: (1) the ventral-lateral and posterior nucleus; (2) dorsal parts of the intralaminar nuclei and the subparafascicular nucleus, and (3) the medioventral and lateral mediodorsal nucleus. A considerable overlap of connectivity pattern was apparent in intralaminar nuclei and midline regions. Notably, pallidal and cerebellar projections were both hemispherically lateralized to the left thalamus. While strikingly consistent with findings from transneuronal studies in non-human primates as well as with pre-existing anatomical studies on developmentally expressed markers or pathological human brains, our assessment provides distinctive connectional fingerprints that illustrate the anatomical substrate of integrated functional networks between basal ganglia and the cerebellum. Thereby, our findings furnish useful implications for cerebellar contributions to the clinical symptomatology of movement disorders.
An imbalance of iron metabolism with consecutive aggregation of α-synuclein and axonal degeneration of neurons has been postulated as the main pathological feature in the development of Parkinson's ...disease (PD). Quantitative susceptibility mapping (QSM) is a new imaging technique, which enables to measure structural changes caused by defective iron deposition in parkinsonian brains. Due to its novelty, its potential as a new imaging technique remains elusive for disease-specific characterization of motor and non-motor symptoms (characterizing the individual parkinsonian phenotype). Functional network changes associated with these symptoms are however frequently described for both magnetoencephalography (MEG) and resting state functional magnetic imaging (rs-fMRI). Here, we performed a systematic review of the current literature about QSM imaging, MEG and rs-fMRI in order to collect existing data about structural and functional changes caused by motor and non-motor symptoms in PD. Whereas all three techniques provide an effect in the motor domain, the understanding of network changes caused by non-motor symptoms is much more lacking for MEG and rs-fMRI, and does not yet really exist for QSM imaging. In order to better understand the influence of pathological iron distribution onto the functional outcome, whole-brain QSM analyses should be integrated in functional analyses (especially for the non-motor domain), to enable a proper pathophysiological interpretation of MEG and rs-fMRI network changes in PD. Herewith, a better understanding of the relationship between neuropathological changes, functional network changes and clinical phenotype might become possible.
The dysregulation of endogenous rhythms within brain networks have been implicated in a broad range of motor and non-motor pathologies. Essential tremor (ET), classically the purview of a single ...aberrant pacemaker, has recently become associated with network-level dysfunction across multiple brain regions. Specifically, it has been suggested that motor cortex constitutes an important node in a tremor-generating network involving the cerebellum. Yet the mechanisms by which these regions relate to tremor remain a matter of considerable debate. We sought to discriminate the contributions of cerebral and cerebellar dysregulation by combining high-density electroencephalography with subject-specific structural MRI. For that, we contrasted ET with voluntary (mimicked) tremor before and after ingestion of alcohol to regulate the tremorgenic networks. Our results demonstrate distinct loci of cortical tremor coherence, most pronounced over the sensorimotor cortices in healthy controls, but more frontal motor areas in ET-patients consistent with a heightened involvement of the supplementary motor area. We further demonstrate that the reduction in tremor amplitude associated with alcohol intake is reflected in altered cerebellar – but not cerebral – coupling with movement. Taken together, these findings implicate tremor emergence as principally associated with increases in activity within frontal motor regions, whereas modulation of the amplitude of established tremor relates to changes in cerebellar activity. These findings progress a mechanistic understanding of ET and implicate network-level vulnerabilities in the rhythmic nature of communication throughout the brain.
•Cortical involvement in ET diverges spatially from the one throughout mimicked tremor.•Alcohol effects revealed segregated networks underlying ET onset and its subsistence.•Our data emphasize the idea of cortical involvement gating cerebellar dysfunction.
The ventrolateral thalamic nucleus (VL), as part of the ‘motor thalamus’, is main relay station of cerebellar and pallidal projections. It comprises anterior (VLa) and posterior (VLpd and VLpv) ...subnuclei. Though the fibre architecture of cerebellar and pallidal projections to of the VL nucleus has already been focus in a numerous amount of in vitro studies mainly in animals, probabilistic tractography now offers the possibility of an in vivo comparison in healthy humans. In this study we performed a (a) qualitative and (b) quantitative examination of VL-cerebellar and VL-pallidal pathways and compared the probability distributions between both projection fields in the VL after an (I) atlas-based and (II) manual-based segmentation procedure. Both procedures led to high congruent results of cerebellar and pallidal connectivity distributions: the maximum of pallidal projections was located in anterior and medial parts of the VL nucleus, whereas cerebellar connectivity was more located in lateral and posterior parts. The median connectivity for cerebellar connections in both approaches (manual and atlas-based segmentation) was
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Magnetic resonance imaging studies typically use standard anatomical atlases for identification and analyses of (patho-)physiological effects on specific brain areas; these atlases often fail to ...incorporate neuroanatomical alterations that may occur with both age and disease. The present study utilizes Parkinson's disease and age-specific anatomical atlases of the subthalamic nucleus for diffusion tractography, assessing tracts that run between the subthalamic nucleus and a-priori defined cortical areas known to be affected by Parkinson's disease. The results show that the strength of white matter fiber tracts appear to remain structurally unaffected by disease. Contrary to that, Fractional Anisotropy values were shown to decrease in Parkinson's disease patients for connections between the subthalamic nucleus and the pars opercularis of the inferior frontal gyrus, anterior cingulate cortex, the dorsolateral prefrontal cortex and the pre-supplementary motor, collectively involved in preparatory motor control, decision making and task monitoring. While the biological underpinnings of fractional anisotropy alterations remain elusive, they may nonetheless be used as an index of Parkinson's disease. Moreover, we find that failing to account for structural changes occurring in the subthalamic nucleus with age and disease reduce the accuracy and influence the results of tractography, highlighting the importance of using appropriate atlases for tractography.
Stress conditions in patients with intellectual disabilities and psychiatric disorders are among all factors the most disabling in their quality of life. We aimed to develop a self-rating and ...third-person rating instrument verifying the effect of psychiatric and psychotherapeutic treatments in these patients.
First, we asked 150 caregivers of residential facility for patients with intellectual disabilities and psychiatric disorders to define 20 words, which describe stress conditions most accurately. Secondly, out of the list of collected words, two independent observers (neurologist, Germanist) defined subgroups, to which the words could be referred. Out of the most frequent subgroups, a questionnaire was developed in order to measure the expression of a target symptom.
Out of 150 surveyed persons only 40 caregivers participated in the study with resulting 680 words defining stress condition in mentally disabled patients. Out of these, 31 words were excluded by observer A and 30 words by observer B, because according to their assessment, the words did not correctly cover the term 'stress condition'. Out of the remaining words, 13 subgroups were worked out. Exclusion of subgroups with less than 15 words in the development of the questionnaire resulted in following categories: (1) auto-aggression; (2) externalized aggression; (3) verbal aggression (4) isolation; (5) (motoric) restlessness; (6) autonomic changes; (7) emotional changes; (8) behavioral changes. For self- and third-person rating, a Likert scale was introduced, for self-rating, answers were visually supported with symbols.
The development of an instrument to measure stress conditions in these patients is important for the improvement of therapies. Such an instrument for the measurement of psychological, social or medical therapy effects allows disentangling efficient strategies improving the patients' quality of life, as the assessment can be quickly integrated during a hospital intervention.
Bimanual coordination is impaired in Parkinson's disease (PD), affecting patients' quality of life. Besides dysfunction of the basal ganglia network, alterations of cortical oscillatory coupling, ...particularly between prefrontal and (pre-)motoric areas, are thought to underlie this impairment. Here, we studied 16 PD patients OFF and ON medication and age-matched healthy controls recording high-resolution electroencephalography (EEG) during performance of spatially coupled and uncoupled bimanual finger movements. Dynamic causal modeling (DCM) for induced responses was used to infer task-induced effective connectivity within a network comprising bilateral prefrontal cortex (PFC), lateral premotor cortex (lPM), supplementary motor area (SMA), and primary motor cortex (M1). Performing spatially coupled movements, excitatory left-hemispheric PFC to lPM coupling was significantly stronger in controls compared to unmedicated PD patients. Levodopa-induced enhancement of this connection correlated with increased movement accuracy. During performance of spatially uncoupled movements, PD patients OFF medication exhibited inhibitory connectivity from left PFC to SMA. Levodopa intake diminished these inhibitory influences and restored excitatory PFC to lPM coupling. This restoration, however, did not improve motor function.
Concluding, our results indicate that lateralization of prefrontal to premotor connectivity in PD can be augmented by levodopa substitution and is of compensatory nature up to a certain extent of complexity.
•Bimanual coordination is impaired in Parkinson's Disease (PD).•In PD, β-activity in left primary motor cortex (M1) induces γ-activity in right M1.•β-γ-coupling between primary motor cortices is associated with poor motor performance.•Levodopa increases left prefrontal to lateral premotor coupling in PD.•This enhancement relates to improved motor control up to a certain complexity level.
Abstract Background Quality of life (QoL) improves under subthalamic deep brain stimulation (STN-DBS) in Parkinson's disease (PD), whereas social functioning may be disrupted. This disruption could ...negatively influence the family dynamic, leading to different perceptions of the STN-DBS outcome by patients and caregivers. Methods We recruited 34 PD patients for this prospective, controlled trial, 28 of whom were examined preoperatively, three months and one year after STN-DBS surgery. The primary outcome was QoL. We compared the patients' ratings and caregivers' proxy QoL ratings. The secondary outcome was social functioning. Additionally, neurological, neuropsychiatric and cognitive domains were analyzed. Changes were analyzed with repeated-measures ANOVA. Regression analysis was used to determine the association between QoL and social functioning. Results Patients' QoL improved significantly under STN-DBS ( p = .003). At baseline, patients' and caregivers' QoL ratings were similar. However, one year postoperatively, QoL ratings differed significantly ( p = .010), whereby QoL was rated worse by caregivers. Social functioning was positively influenced during the first months postoperatively, but did not improve longitudinally. One year postoperatively, social functioning was significantly associated with QoL ratings (patients: p = .004, caregivers: p = .002). Motor scores significantly improved, whereas verbal fluency and apathy worsened. Conclusions Unequal perception of QoL between patients and caregivers exists under STN-DBS. The fact that social functioning does not improve longitudinally is perhaps due to patient's higher levels of apathy and reduced motivation following surgery. Our findings stress the importance of considering caregiver's input in DBS patients' outcomes and the need for pre-operative preparation.
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