Early functional connectivity alterations in contralesional motor networks influence outcome after severe stroke: a preliminary analysis.

Connectivity studies have significantly extended the knowledge on motor network alterations after stroke. Compared to interhemispheric or ipsilesional networks, changes in the contralesional hemisphere are poorly understood. Data obtained in the acute stage after stroke and in severely impaired patients are remarkably limited. This exploratory, preliminary study aimed to investigate early functional connectivity changes of the contralesional parieto-frontal motor network and their relevance for the functional outcome after severe motor stroke. Resting-state functional imaging data were acquired in 19 patients within the first 2 weeks after severe stroke. Nineteen healthy participants served as a control group. Functional connectivity was calculated from five key motor areas of the parieto-frontal network on the contralesional hemisphere as seed regions and compared between the groups. Connections exhibiting stroke-related alterations were correlated with clinical follow-up data obtained after 3-6 months. The main finding was an increase in coupling strength between the contralesional supplementary motor area and the sensorimotor cortex. This increase was linked to persistent clinical deficits at follow-up. Thus, an upregulation in contralesional motor network connectivity might be an early pattern in severely impaired stroke patients. It might carry relevant information regarding the outcome which adds to the current concepts of brain network alterations and recovery processes after severe stroke.

Management and Outcome of Acute Ischemic Stroke Complicating Transcatheter Aortic Valve Replacement.

BACKGROUND: Despite advances in transcatheter aortic valve replacement (TAVR), periprocedural acute ischemic stroke remains a concern. OBJECTIVES: The aims of this study were to investigate acute ischemic stroke complicating TAVR (AISCT) and to describe the indications and outcomes of interventions to treat AISCT. METHODS: An international multicenter registry was established focusing on AISCT within 30 days of TAVR. Stroke severity was assessed using the National Institutes of Health Stroke Scale. Primary outcomes were 1-year all-cause death and neurologic disability status at 90 days according to modified Rankin scale score. RESULTS: Of 16,615 TAVR procedures, 387 patients with AISCT were included (2.3%). Rates of 1-year death were 28.9%, 35.9%, and 77.5% in patients with mild, moderate, and severe stroke, respectively (P < 0.001). Although 348 patients were managed conservatively, 39 patients (10.1%) underwent neurointervention (NI) with either mechanical thrombectomy (n = 26) or thrombolytic therapy (n = 13). In a subanalysis excluding patients with mild stroke, there was no clear 1-year survival benefit for NI compared with conservative management (47.6% vs 41.1%, respectively; P = 0.78). In a logistic regression model controlling for stroke severity, NI was associated with 2.9-fold odds (95% CI: 1.2-7.0; P = 0.016) of independent survival at 90 days. CONCLUSIONS: AISCT carries significant morbidity and mortality, which is correlated with stroke severity. The present findings suggest that neurologic disability for patients with moderate or worse stroke could potentially be improved by timely intervention and highlight the importance of collaboration between cardiologists and neurologists to optimize AISCT outcomes.

Normalization of Aperiodic Electrocorticography Components Indicates Fine Motor Recovery After Sensory Cortical Stroke in Mice.

BACKGROUND: Electrophysiological signatures of ischemic stroke might help to develop a deeper understanding of the mechanisms of recovery. However, to identify critical windows for novel treatment approaches, suitable readout parameters in vivo with the potential to close the gap between functional modifications within the peri-infarct cortex and behavioral outcome on the systems-level are still lacking. METHODS: Wild-type mice were trained in a skilled reaching task and underwent permanent distal medial cerebral artery occlusion or sham intervention. Functional deficits and their recovery were monitored both behaviorally and electrophysiologically recording multichannel electrocorticography from both hemispheres. RESULTS: Ischemic strokes are located in sensory cortical areas. Affected mice presented fine motor deficits of their contralateral forepaw. Analyses of electrocorticography signals from awake animals demonstrated a modulation of the shape of power spectral density in the vicinity of the infarct. While power spectral density consists of both rhythmic oscillatory and nonrhythmic, aperiodic components, the alteration of spectrum shape was reflected in a transient increase of aperiodic exponents in the peri-infarct cortex. The relative power and frequency of slow oscillations remained unchanged. Exponents derived from motor areas significantly correlated with fine motor recovery, thus indicating functional modifications of neuronal activity. CONCLUSIONS: Aperiodic spectral exponents exhibited a unique spatiotemporal profile in the mouse cortex after stroke and might complement future translational studies providing a dynamic link from pathophysiology to behavior.

Reduced frontal white matter microstructure in healthy older adults with low tactile recognition performance.

The aging of the nervous system is a heterogeneous process. It remains a significant challenge to identify relevant markers of pathological and healthy brain aging. A central aspect of aging are decreased sensory acuities, especially because they correlate with the decline in higher cognitive functioning. Sensory and higher cognitive processing relies on information flow between distant brain areas. Aging leads to disintegration of the underlying white matter tracts. While this disintegration is assumed to contribute to higher cognitive decline, data linking structural integrity and sensory function are sparse. The investigation of their interrelation may provide valuable insight into the mechanisms of brain aging. We used a combined behavioral and neuroimaging approach and investigated to what extent changes in microstructural white matter integrity reflect performance declines in tactile pattern recognition with aging. Poor performance in older participants was related to decreased integrity in the anterior corpus callosum. Probabilistic tractography showed that this structure is connected to the prefrontal cortices. Our data point to decreased integrity in the anterior corpus callosum as a marker for advanced brain aging. The correlation between impaired tactile recognition and disintegration in frontal brain networks could provide an explanation why the decrease of sensory function predicts cognitive decline.

Early parietofrontal network upregulation relates to future persistent deficits after severe stroke-a prospective cohort study.

Recent brain imaging has evidenced that parietofrontal networks show alterations after stroke which also relate to motor recovery processes. There is converging evidence for an upregulation of parietofrontal coupling between parietal brain regions and frontal motor cortices. The majority of studies though have included only moderately to mildly affected patients, particularly in the subacute or chronic stage. Whether these network alterations will also be present in severely affected patients and early after stroke and whether such information can improve correlative models to infer motor recovery remains unclear. In this prospective cohort study, 19 severely affected first-ever stroke patients (mean age 74 years, 12 females) were analysed which underwent resting-state functional MRI and clinical testing during the initial week after the event. Clinical evaluation of neurological and motor impairment as well as global disability was repeated after three and six months. Nineteen healthy participants of similar age and gender were also recruited. MRI data were used to calculate functional connectivity values between the ipsilesional primary motor cortex, the ventral premotor cortex, the supplementary motor area and the anterior and caudal intraparietal sulcus of the ipsilesional hemisphere. Linear regression models were estimated to compare parietofrontal functional connectivity between stroke patients and healthy controls and to relate them to motor recovery. The main finding was a significant increase in ipsilesional parietofrontal coupling between anterior intraparietal sulcus and the primary motor cortex in severely affected stroke patients (P < 0.003). This upregulation significantly contributed to correlative models explaining variability in subsequent neurological and global disability as quantified by National Institute of Health Stroke Scale and modified Rankin Scale, respectively. Patients with increased parietofrontal coupling in the acute stage showed higher levels of persistent deficits in the late subacute stage of recovery (P < 0.05). This study provides novel insights that parietofrontal networks of the ipsilesional hemisphere undergo neuroplastic alteration already very early after severe motor stroke. The association between early parietofrontal upregulation and future levels of persistent functional deficits and dependence from help in daily living might be useful in models to enhance clinical neurorehabilitative decision making.

Higher white matter hyperintensity lesion load is associated with reduced long-range functional connectivity.

Cerebral small vessel disease is a common disease in the older population and is recognized as a major risk factor for cognitive decline and stroke. Small vessel disease is considered a global brain disease impacting the integrity of neuronal networks resulting in disturbances of structural and functional connectivity. A core feature of cerebral small vessel disease commonly present on neuroimaging is white matter hyperintensities. We studied high-resolution resting-state EEG, leveraging source reconstruction methods, in 35 participants with varying degree of white matter hyperintensities without clinically evident cognitive impairment in an observational study. In patients with increasing white matter lesion load, global theta power was increased independently of age. Whole-brain functional connectivity revealed a disrupted network confined to the alpha band in participants with higher white matter hyperintensities lesion load. The decrease of functional connectivity was evident in long-range connections, mostly originating or terminating in the frontal lobe. Cognitive testing revealed no global cognitive impairment; however, some participants revealed deficits of executive functions that were related to larger white matter hyperintensities lesion load. In summary, participants without clinical signs of mild cognitive impairment or dementia showed oscillatory changes that were significantly related to white matter lesion load. Hence, oscillatory neuronal network changes due to white matter lesions might act as biomarker prior to clinically relevant behavioural impairment.

Crossmodal Congruency Enhances Performance of Healthy Older Adults in Visual-Tactile Pattern Matching.

One of the pivotal challenges of aging is to maintain independence in the activities of daily life. In order to adapt to changes in the environment, it is crucial to continuously process and accurately combine simultaneous input from different sensory systems, i.e., crossmodal or multisensory integration. With aging, performance decreases in multiple domains, affecting bottom-up sensory processing as well as top-down control. However, whether this decline leads to impairments in crossmodal interactions remains an unresolved question. While some researchers propose that crossmodal interactions degrade with age, others suggest that they are conserved or even gain compensatory importance. To address this question, we compared the behavioral performance of older and young participants in a well-established crossmodal matching task, requiring the evaluation of congruency in simultaneously presented visual and tactile patterns. Older participants performed significantly worse than young controls in the crossmodal task when being stimulated at their individual unimodal visual and tactile perception thresholds. Performance increased with adjustment of stimulus intensities. This improvement was driven by better detection of congruent stimulus pairs, while the detection of incongruent pairs was not significantly enhanced. These results indicate that age-related impairments lead to poor performance in complex crossmodal scenarios and demanding cognitive tasks. Crossmodal congruency effects attenuate the difficulties of older adults in visuotactile pattern matching and might be an important factor to drive the benefits of older adults demonstrated in various crossmodal integration scenarios. Congruency effects might, therefore, be used to develop strategies for cognitive training and neurological rehabilitation.

Sensory capability and information integration independently explain the cognitive status of healthy older adults.

While there is evidence that sensory processing and multisensory integration change with age, links between these alterations and their relation to cognitive status remain unclear. In this study, we assessed sensory thresholds and performance of healthy younger and older adults in a visuotactile delayed match-to-sample task. Using Bayesian structural equation modelling (BSEM), we explored the factors explaining cognitive status in the group of older adults. Additionally, we applied transcranial alternating current stimulation (tACS) to a parieto-central network found to underlie visuotactile interactions and working memory matching in our previous work. Response times and signal detection measures indicated enhanced multisensory integration and enhanced benefit from successful working memory matching in older adults. Further, tACS caused a frequency-specific speeding (20 Hz) and delaying (70 Hz) of responses. Data exploration suggested distinct underlying factors for sensory acuity and sensitivity d' on the one side, and multisensory and working memory enhancement on the other side. Finally, BSEM showed that these two factors labelled 'sensory capability' and 'information integration' independently explained cognitive status. We conclude that sensory decline and enhanced information integration might relate to distinct processes of ageing and discuss a potential role of the parietal cortex in mediating augmented integration in older adults.

Crossmodal Pattern Discrimination in Humans and Robots: A Visuo-Tactile Case Study.

The quality of crossmodal perception hinges on two factors: The accuracy of the independent unimodal perception and the ability to integrate information from different sensory systems. In humans, the ability for cognitively demanding crossmodal perception diminishes from young to old age. Here, we propose a new approach to research to which degree the different factors contribute to crossmodal processing and the age-related decline by replicating a medical study on visuo-tactile crossmodal pattern discrimination utilizing state-of-the-art tactile sensing technology and artificial neural networks (ANN). We implemented two ANN models to specifically focus on the relevance of early integration of sensory information during the crossmodal processing stream as a mechanism proposed for efficient processing in the human brain. Applying an adaptive staircase procedure, we approached comparable unimodal classification performance for both modalities in the human participants as well as the ANN. This allowed us to compare crossmodal performance between and within the systems, independent of the underlying unimodal processes. Our data show that unimodal classification accuracies of the tactile sensing technology are comparable to humans. For crossmodal discrimination of the ANN the integration of high-level unimodal features on earlier stages of the crossmodal processing stream shows higher accuracies compared to the late integration of independent unimodal classifications. In comparison to humans, the ANN show higher accuracies than older participants in the unimodal as well as the crossmodal condition, but lower accuracies than younger participants in the crossmodal task. Taken together, we can show that state-of-the-art tactile sensing technology is able to perform a complex tactile recognition task at levels comparable to humans. For crossmodal processing, human inspired early sensory integration seems to improve the performance of artificial neural networks. Still, younger participants seem to employ more efficient crossmodal integration mechanisms than modeled in the proposed ANN. Our work demonstrates how collaborative research in neuroscience and embodied artificial neurocognitive models can help to derive models to inform the design of future neurocomputational architectures.

Mid-Latency Auditory Evoked Potentials Differentially Predict Sedation and Drug Level Under Opioid and Hypnotic Agents.

Background: Auditory-evoked brain potentials (AEPs) are widely used to assess depth of the sedative component of general anesthesia. Depth of sedation as induced by hypnotic drugs (e.g., propofol) is characterized by a gradual decline of mid-latency cortical AEPs (10-50 ms). Using the decline of mid-latency AEPs as a reliable index for sedation requires its robustness against confounding pharmaceutical influences, e.g., analgesic opioids such as remifentanil. Critically, in this context the following two questions remained unresolved so far: First, it is unclear whether opioids directly affect mid-latency AEPs. Second, high doses of opioids decrease arousal, but it is unknown whether opioid-induced sedation is reflected by the diminution of mid-latency AEPs. We hypothesized that opioids affect mid-latency AEPs and that these effects rely on different mechanisms compared to hypnotic agents. Methods: To address both questions, we performed a series of experiments under the participation of healthy human volunteers. We measured AEPs and quantified participants' sedation state by a standardized rating scale during stepwise increase of different pharmaceutical agents (remifentanil, propofol or placebo). Results: Our results revealed a decline of mid-latency AEPs during remifentanil medication. This decrease was predicted by drug dose, rather than sedation level. In contrast, attenuation of the mid-latency AEPs during propofol was predicted by sedation level and was not related to hypnotic drug dose. We did not find any drug-induced changes of brainstem AEPs (1-10 ms). Conclusion: As remifentanil reduced mid-latency AEPs without inducing strong sedation levels, a decrease of this evoked brain component does not constitute an unequivocal index for the depth of sedation. These results challenge the use of mid-latency AEPs as a reliable marker of depth of the sedative component of anesthesia if hypnotic drugs are combined with opioids.