Brain communication in the locked-in state.

Patients in the completely locked-in state have no means of communication and they represent the target population for brain-computer interface research in the last 15 years. Although different paradigms have been tested and different physiological signals used, to date no sufficiently documented completely locked-in state patient was able to control a brain-computer interface over an extended time period. We introduce Pavlovian semantic conditioning to enable basic communication in completely locked-in state. This novel paradigm is based on semantic conditioning for online classification of neuroelectric or any other physiological signals to discriminate between covert (cognitive) 'yes' and 'no' responses. The paradigm comprised the presentation of affirmative and negative statements used as conditioned stimuli, while the unconditioned stimulus consisted of electrical stimulation of the skin paired with affirmative statements. Three patients with advanced amyotrophic lateral sclerosis participated over an extended time period, one of which was in a completely locked-in state, the other two in the locked-in state. The patients' level of vigilance was assessed through auditory oddball procedures to study the correlation between vigilance level and the classifier's performance. The average online classification accuracies of slow cortical components of electroencephalographic signals were around chance level for all the patients. The use of a non-linear classifier in the offline classification procedure resulted in a substantial improvement of the accuracy in one locked-in state patient achieving 70% correct classification. A reliable level of performance in the completely locked-in state patient was not achieved uniformly throughout the 37 sessions despite intact cognitive processing capacity, but in some sessions communication accuracies up to 70% were achieved. Paradigm modifications are proposed. Rapid drop of vigilance was detected suggesting attentional variations or variations of circadian period as important factors in brain-computer interface communication with locked-in state and completely locked-in state.

Inter-individual differences in successful perspective taking during pain perception mediates emotional responsiveness in self and others: an fMRI study.

Human empathy is an important component of social cognition that involves complex processes of emotional perspective taking and the issue of self/other distinction. Empathic perception enables us to experience negative emotions when someone else undergoes painful events. We investigated the influence of an extended time interval (10s) and subjective performance evaluation (following each trial) of perspective taking on the cortical and subcortical correlates of pain empathy in eighteen healthy subjects using functional magnetic resonance imaging (fMRI). Subjects were presented pictures of hands and feet in painful and non-painful situations. They were instructed to simply view the picture (View) or adopt either their own perspective (Self) or the perspective of a third-person (Other). Prolonged time intervals of stimulus presentation enabled the analysis of different perspective taking processes (Self versus Other). Enhanced activation in the left supramarginal gyrus was detected for adopting the Self compared to the Other perspective. Time course analysis showed an early peak in the trials, suggesting that taking the first-person perspective is an intuitive more automatic process. The comparison between the Other and Self condition evoked stronger activity in dorso- and ventrolateral prefrontal areas and the superior temporal sulcus (STS). For these areas, a peak in the later phase of the trials was found, suggesting that taking the third-person perspective requires more effort and is an ongoing process. This was also supported by the fact that the participants were subjectively more successful in adopting the Self perspective compared to the Other. Our findings support that especially during the Other condition, prolonged time periods seem to facilitate empathic responses. Individual ratings of performance enabled the comparison between subjects that were successful and unsuccessful at taking the Self or Other perspective. For Self, differential activations were found in the left insula and postcentral gyrus. For Other, differential activations were mainly observed in the left pallidum, bilateral VLPFC, the right middle orbitofrontal cortex OFC and the middle cingulate cortex (MCC). These results suggest that trial-specific success ratings allow us to disentangle differences between effort-related and successful engagement in perspective taking. These two adjustments to the well-known paradigm showed new insight into the aspects of perspective taking during pain perception.

Accuracy of Four Different CT Perfusion Thresholds for Ischemic Core Volume and Location Estimation Using IntelliSpace Portal.

Computed tomography perfusion (CTP) is frequently used in the triage of ischemic stroke patients for endovascular thrombectomy (EVT). We aimed to quantify the volumetric and spatial agreement of the CTP ischemic core estimated with different thresholds and follow-up MRI infarct volume on diffusion-weighted imaging (DWI). Patients treated with EVT between November 2017 and September 2020 with available baseline CTP and follow-up DWI were included. Data were processed with Philips IntelliSpace Portal using four different thresholds. Follow-up infarct volume was segmented on DWI. In 55 patients, the median DWI volume was 10 mL, and median estimated CTP ischemic core volumes ranged from 10-42 mL. In patients with complete reperfusion, the intraclass correlation coefficient (ICC) showed moderate-good volumetric agreement (range 0.55-0.76). A poor agreement was found for all methods in patients with successful reperfusion (ICC range 0.36-0.45). Spatial agreement (median Dice) was low for all four methods (range 0.17-0.19). Severe core overestimation was most frequently (27%) seen in Method 3 and patients with carotid-T occlusion. Our study shows moderate-good volumetric agreement between ischemic core estimates for four different thresholds and subsequent infarct volume on DWI in EVT-treated patients with complete reperfusion. The spatial agreement was similar to other commercially available software packages.

Effectiveness of a medication-adherence tool: study protocol for a randomized controlled trial.

BACKGROUND: Research shows that more than half of the people taking medication for a chronic condition are non-adherent. Nonadherence hinders disease control with a burden on patient quality of life and healthcare systems. We developed a tool that provides insight into nonadherence risks and barriers for medication-adherence including an intervention strategy to overcome those barriers. This study aims to assess the effectiveness of using this adherence tool in starters with cardiovascular or oral blood glucose-lowering medication to improve medication-adherence. METHODS/DESIGN: In a cluster-randomized controlled trial 25 pharmacies in the Netherlands will be randomized to the intervention or control arm. Patients registered in a general practice participating in a collaborative can be included when they start cardiovascular or oral blood glucose-lowering medication prescribed by their general practitioner. Participants complete an assessment consisting of measuring nonadherence risk and potential barriers to adherence. For patients with an increased nonadherence risk, a graphic barrier profile is created, showing to what extent eight cognitive, emotional, or practical barriers are present. All patients will fill in the medication-adherence assessment twice: between 1 and 2 weeks after the start of the medication and after 8 months. The intervention strategy consists of discussing this barrier profile to overcome barriers. Pharmacists and assistants of the intervention pharmacies are trained in discussing the profile and to offer a tailored intervention to overcome barriers. In the control arm, patients receive care as usual. The primary outcome is medication-adherence of patients with a high risk of nonadherence at 8 months follow-up. Secondary outcomes include the difference in the percentage of patients with an increased nonadherence risk between intervention and control group after 8 months, the predictive values of the baseline questionnaire in the control group in relation to medication-adherence after 8 months, medication-adherence after 1 year follow-up, and barriers and facilitators in the implementation of the tool. DISCUSSION: This manuscript presents the protocol for a cluster-randomized clinical trial on the use of an adherence tool to improve medication-adherence. This study will provide insight into the effectiveness of the tool in starters with cardiovascular or oral blood glucose-lowering medication in improvement of medication-adherence. TRIAL REGISTRATION: The Netherlands National Trial Register, NTR5186 . Registered on 18 May 2015.

Insula and inferior frontal triangularis activations distinguish between conditioned brain responses using emotional sounds for basic BCI communication.

In order to enable communication through a brain-computer interface (BCI), it is necessary to discriminate between distinct brain responses. As a first step, we probed the possibility to discriminate between affirmative ("yes") and negative ("no") responses using a semantic classical conditioning paradigm, within an fMRI setting. Subjects were presented with congruent and incongruent word-pairs as conditioned stimuli (CS), respectively eliciting affirmative and negative responses. Incongruent word-pairs were associated to an unpleasant unconditioned stimulus (scream, US1) and congruent word-pairs were associated to a pleasant unconditioned stimulus (baby-laughter, US2), in order to elicit emotional conditioned responses (CR). The aim was to discriminate between affirmative and negative responses, enabled by their association with the positive and negative affective stimuli. In the late acquisition phase, when the US were not present anymore, there was a strong significant differential activation for incongruent and congruent word-pairs in a cluster comprising the left insula and the inferior frontal triangularis. This association was not found in the habituation phase. These results suggest that the difference in affirmative and negative brain responses was established as an effect of conditioning, allowing to further investigate the possibility of using this paradigm for a binary choice BCI.

Semantic classical conditioning and brain-computer interface control: encoding of affirmative and negative thinking.

The aim of the study was to investigate conditioned electroencephalography (EEG) responses to factually correct and incorrect statements in order to enable binary communication by means of a brain-computer interface (BCI). In two experiments with healthy participants true and false statements (serving as conditioned stimuli, CSs) were paired with two different tones which served as unconditioned stimuli (USs). The features of the USs were varied and tested for their effectiveness to elicit differentiable conditioned reactions (CRs). After acquisition of the CRs, these CRs to true and false statements were classified offline using a radial basis function kernel support vector machine. A mean single-trial classification accuracy of 50.5% was achieved for differentiating conditioned "yes" versus "no" thinking and mean accuracies of 65.4% for classification of "yes" and 68.8% for "no" thinking (both relative to baseline) were found using the best US. Analysis of the area under the curve of the conditioned EEG responses revealed significant differences between conditioned "yes" and "no" answers. Even though improvements are necessary, these first results indicate that the semantic conditioning paradigm could be a useful basis for further research regarding BCI communication in patients in the complete locked-in state.

Prediction of P300 BCI aptitude in severe motor impairment.

Brain-computer interfaces (BCIs) provide a non-muscular communication channel for persons with severe motor impairments. Previous studies have shown that the aptitude with which a BCI can be controlled varies from person to person. A reliable predictor of performance could facilitate selection of a suitable BCI paradigm. Eleven severely motor impaired participants performed three sessions of a P300 BCI web browsing task. Before each session auditory oddball data were collected to predict the BCI aptitude of the participants exhibited in the current session. We found a strong relationship of early positive and negative potentials around 200 ms (elicited with the auditory oddball task) with performance. The amplitude of the P2 (r  =  -0.77) and of the N2 (r  =  -0.86) had the strongest correlations. Aptitude prediction using an auditory oddball was successful. The finding that the N2 amplitude is a stronger predictor of performance than P3 amplitude was reproduced after initially showing this effect with a healthy sample of BCI users. This will reduce strain on the end-users by minimizing the time needed to find suitable paradigms and inspire new approaches to improve performance.

Prefrontal brain asymmetry and aggression in imprisoned violent offenders.

Anterior brain asymmetry, assessed through the alpha and beta band in resting-state electroencephalogram (EEG) is associated with approach-related behavioral dispositions, particularly with aggression in the general population. To date, the association between frontal asymmetry and aggression has not been examined in highly aggressive groups. We examined the topographic characteristics of alpha and beta activity, the relation of both asymmetry metrics to trait aggression, and whether alpha asymmetry was extreme in anterior regions according to clinical standards in a group of imprisoned violent offenders. As expected, these individuals were characterized by stronger right than left-hemispheric alpha activity, which was putatively extreme in anterior regions in one third of the cases. We also report that in line with observations made in the general population, aggression was associated with stronger right-frontal alpha activity in these violent individuals. This suggests that frontal alpha asymmetry, as a correlate of trait aggression, might be utilizable as an outcome measure in studies which assess the effects of anti-aggressiveness training in violent offenders.

Toward a brain-computer interface for Alzheimer's disease patients by combining classical conditioning and brain state classification.

Brain-computer interfaces (BCIs) provide alternative methods for communicating and acting on the world, since messages or commands are conveyed from the brain to an external device without using the normal output pathways of peripheral nerves and muscles. Alzheimer's disease (AD) patients in the most advanced stages, who have lost the ability to communicate verbally, could benefit from a BCI that may allow them to convey basic thoughts (e.g., "yes" and "no") and emotions. There is currently no report of such research, mostly because the cognitive deficits in AD patients pose serious limitations to the use of traditional BCIs, which are normally based on instrumental learning and require users to self-regulate their brain activation. Recent studies suggest that not only self-regulated brain signals, but also involuntary signals, for instance related to emotional states, may provide useful information about the user, opening up the path for so-called "affective BCIs". These interfaces do not necessarily require users to actively perform a cognitive task, and may therefore be used with patients who are cognitively challenged. In the present hypothesis paper, we propose a paradigm shift from instrumental learning to classical conditioning, with the aim of discriminating "yes" and "no" thoughts after associating them to positive and negative emotional stimuli respectively. This would represent a first step in the development of a BCI that could be used by AD patients, lending a new direction not only for communication, but also for rehabilitation and diagnosis.