A preliminary study of white matter disconnections underlying deficits in praxis in left hemisphere stroke patients.

Limb apraxia is a higher-order motor disorder often occurring post-stroke, which affects skilled actions. It is assessed through tasks involving gesture production or pantomime, recognition, meaningless gesture imitation, complex figure drawing, single and multi-object use. A two-system model for the organisation of actions hypothesizes distinct pathways mediating praxis deficits via conceptual, 'indirect', and perceptual 'direct' routes to action. Traditional lesion- symptom mapping techniques have failed to identify these distinct routes. We assessed 29 left hemisphere stroke patients to investigate white matter disconnections on deficits of praxis tasks from the Birmingham Cognitive Screening. White matter disconnection maps derived from patients' structural T1 lesions were created using a diffusion-weighted healthy participant dataset acquired from the human connectome project (HCP). Initial group-level regression analyses revealed significant disconnection between occipital lobes via the splenium of the corpus callosum and involvement of the inferior longitudinal fasciculus in meaningless gesture imitation deficits. There was a trend of left fornix disconnection in gesture production deficits. Further, voxel-wise Bayesian Crawford single-case analyses performed on two patients with the most severe meaningless gesture imitation and meaningful gesture production deficits, respectively, confirmed distinct posterior interhemispheric disconnection, for the former, and disconnections between temporal and frontal areas via the fornix, rostrum of the corpus callosum and anterior cingulum, for the latter. Our results suggest distinct pathways associated with perceptual and conceptual deficits akin to 'direct' and 'indirect' action routes, with some patients displaying both. Larger studies are needed to validate and elaborate on these findings, advancing our understanding of limb apraxia.

Topographic mapping of the sensorimotor qualities of empathic reactivity: A psychophysiological study in people with spinal cord injuries.

The experience of empathy for pain is underpinned by sensorimotor and affective dimensions which, although interconnected, are at least in part behaviorally and neurally distinct. Spinal cord injuries (SCI) induce a massive, below-lesion level, sensorimotor body-brain disconnection. This condition may make it possible to test whether sensorimotor deprivation alters specific dimensions of empathic reactivity to observed pain. To explore this issue, we asked SCI people with paraplegia and healthy controls to observe videos of painful or neutral stimuli administered to a hand (intact) or a foot (deafferented). The stimuli were displayed by means of a virtual reality set-up and seen from a first person (1PP) or third person (3PP) visual perspective. A number of measures were recorded ranging from explicit behaviors like explicit verbal reports on the videos, to implicit measures of muscular activity (like EMG from the corrugator and zygomatic muscles that may represent a proxy of sensorimotor empathy) and of autonomic reactivity (like the electrodermal response and Respiratory Sinus Arrhythmia that may represent a general proxy of affective empathy). While no across group differences in explicit verbal reports about the pain stimuli were found, SCI people exhibited reduced facial muscle reactivity to the stimuli applied to the foot (but not the hand) seen from the 1PP. Tellingly, the corrugator activity correlated with SCI participants' neuropathic pain. There were no across group differences in autonomic reactivity suggesting that SCI lesions may affect sensorimotor dimensions connected to empathy for pain.

Normative data beyond the total scores: a process score analysis of the Rey's 15 word test in healthy aging and Alzheimer's Disease.

BACKGROUND: The Rey's 15 words test is currently the most frequently used task in Italy to detect memory deficits in AD. The current standardised version is however quite outdated and lacks some cognitive indexes which may highlight problems in recall or encoding processes. The aim of the study was to update the normative data of the test and to consider some variables which were not accounted for in the original study, that is, recognition, learning rate and forgetfulness. We also adopted the process scores approach to ascertain the effects of serial position (primacy and recency). METHODS: Three hundred ninety-six healthy participants were recruited. To detect any variables useful for intercepting the early stages of dementia, a group of 208 patients in the very early stage of AD was also recruited. Linear models were used to calculate the corrections scores for age, education, and gender, and ROCs were used to calculate cut-offs based on the maximum sum of sensitivity and specificity and the positive and negative predictive values. RESULTS: All main indexes showed excellent Area Under the Curve (0.90-1), strong sensitivity and PPVs for distinguishing between the HCs and AD participants. However, the Intrusions index performed poorly in all parameters. CONCLUSION: The study provides updated, normative data which may be reliably used as a cognitive marker to detect early AD. The strength of the study is the large sample size and the number of indexes which make it possible to explore the utility of memory test process scores.

Modulating preferences during intertemporal choices through exogenous midfrontal transcranial alternating current stimulation: A registered report.

Decision conflicts may arise when the costs and benefits of choices are evaluated as a function of outcomes predicted along a temporal dimension. Electrophysiology studies suggest that during performance monitoring a typical oscillatory activity in the theta rhythm, named midfrontal theta, may index conflict processing and resolution. In the present within-subject, sham controlled, cross-over preregistered study, we delivered online midfrontal transcranial Alternating Current Stimulation (tACS) to modulate electrocortical activity during intertemporal decisions. Participants were invited to select choice preference between economic offers at three different intermixed levels of conflict (i.e., low, medium, high) while receiving either theta -, gamma-, or sham tACS in separate blocks and sessions. At the end of each stimulation block, a Letter-Flanker task was also administered to measure behavioural aftereffects. We hypothesized that theta-tACS would have acted on the performance monitoring system inducing behavioural changes (i.e., faster decisions and more impulsive choices) in high conflicting trials, rather than gamma- and sham-tACS. Results very partially confirmed our predictions. Unexpectedly, both theta- and gamma-driven neuromodulation speeded-up decisions compared to sham. However, exploratory analyses revealed that such an effect was stronger in the high-conflict decisions during theta-tACS. These findings were independent from the influence of the sensations induced by the electrical stimulation. Moreover, further analyses highlighted a significant association during theta-tACS between the selection of immediate offers in high-conflict trials and attentional impulsiveness, suggesting that individual factors may account for the tACS effects during intertemporal decisions. Finally, we did not capture long-lasting behavioural changes following tACS in the Flanker task. Our findings may inform scholars to improve experimental designs and boost the knowledge toward a more effective application of tACS.

Examining the role of self-reported somatosensory sensations in body (dis)ownership: A scoping review and empirical study of patients with a disturbed sense of limb ownership.

Patients with a disturbed sense of limb ownership (DSO) offer a unique window of insight into the multisensory processes contributing to the sense of body ownership. A limited amount of past research has examined the role of sensory deficits in DSO, and even less is known regarding the role of patient self-reported somatosensory sensations in the pathogenesis of DSO. To address this lack of knowledge we first conducted a systematic scoping review following PRISMA-SR guidelines, examining current research into somatosensory deficits and patient self-reported somatosensory sensations in patients with DSO. Eighty studies, including 277 DSO patients, were identified. The assessment of sensory deficits was generally limited in scope and quality, and deficits in tactile sensitivity and proprioception were most frequently found. The reporting of somatosensory sensations was even less frequent, with instances of paraesthesia (pins-and-needles), stiffness/rigidity, numbness and warmth, coldness and heaviness amongst the deficits recorded. In a second part of the study, we sought to directly address the lack of evidence concerning the impact of patient self-reported somatosensory sensations in DSO by measuring DSO and self-reported somatosensory sensations in a large (n = 121) sample of right-hemisphere stroke patients including N = 65 with DSO and N = 56 hemiplegic controls. Results show that feelings of coldness and stiffness modulate DSO symptoms. Sense of heaviness and numbness are more frequent in patients with DSO but do not have a clear impact on disownership symptomology. Although preliminary, these results suggest a role of subjective sensations about the felt body in the sense of limb ownership.

Massive body-brain disconnection consequent to spinal cord injuries drives profound changes in higher-order cognitive and emotional functions: A PRISMA scoping review.

Spinal cord injury (SCI) leads to a massive disconnection between the brain and the body parts below the lesion level representing a unique opportunity to explore how the body influences a person's mental life. We performed a systematic scoping review of 59 studies on higher-order cognitive and emotional changes after SCI. The results suggest that fluid abilities (e.g. attention, executive functions) and emotional regulation (e.g. emotional reactivity and discrimination) are impaired in people with SCI, with progressive deterioration over time. Although not systematically explored, the factors that are directly (e.g. the severity and level of the lesion) and indirectly associated (e.g. blood pressure, sleeping disorders, medication) with the damage may play a role in these deficits. The inconsistency which was found in the results may derive from the various methods used and the heterogeneity of samples (i.e. the lesion completeness, the time interval since lesion onset). Future studies which are specifically controlled for methods, clinical and socio-cultural dimensions are needed to better understand the role of the body in cognition.

A fronto-insular-parietal network for the sense of body ownership.

Neuropsychological disturbances in the sense of limb ownership provide unique opportunities to study the neurocognitive basis of body ownership. Previous small sample studies that showed discrete cortical lesions cannot explain why multisensory, affective, and cognitive manipulations alter disownership symptoms. We tested the novel hypothesis that disturbances in the sense of limb ownership would be associated not only with discrete cortical lesions but also with disconnections of white-matter tracts supporting specific functional networks. We drew on an advanced lesion-analysis and Bayesian statistics approach in 49 right-hemisphere patients (23 with and 26 without limb disownership). Our results reveal that disturbances in the sense of ownership are associated with lesions in the supramarginal gyrus and disconnections of a fronto-insular-parietal network, involving the frontal-insular and frontal inferior longitudinal tracts, confirming previous disconnection hypotheses. Together with previous behavioral and neuroanatomical results, these findings lead us to propose that the sense of body ownership involves the convergence of bottom-up, multisensory integration, and top-down monitoring of sensory salience based on contextual demands.

Cognitive flexibility assessment with a new Reversal learning task paradigm compared with the Wisconsin card sorting test exploring the moderating effect of gender and stress.

Cognitive flexibility plays a crucial role in psychological health and this research aimed to investigate its assessment. We developed a novel Reversal learning task (RLT) paradigm adding pure reward (+ 100 points, 0) and punishment (- 100 points, 0) conditions to the classic reward-punishment condition (+ 100, - 100); we also analyzed the RLT convergent validity with approach-avoidance questionnaires (BIS-BAS and Approach-Avoidance Temperament questionnaire) and the Wisconsin card sorting test (WCST) scores through a Principal component analysis. In a sample of 374 participants, we found that these three conditions differently assess flexibility and that high RLT reward sensitivity in the punishment condition (0; - 100) is related with high BAS reward responsiveness. Moreover, we found that RLT and WCST flexibility scores, although associated, detect different facets of cognitive flexibility. Finally, in a second sample (N = 172), we explored the impact of stress, moderated by gender, on RLT and WCST. Whereas, WCST was not impacted by these variables, in RLT stressed women showed increased perseverative errors in punishment condition (- 100, 0) and reduced punishment sensitivity in reward condition (+ 100, 0).Overall, our newly developed RLT paradigm and the WCST seem to provide different ways to assess cognitive flexibility and to be differently affected by moderators, such as gender and stress.

The 'healthy side' of anosognosia for hemiplegia: Increased sense of agency for the unimpaired limb or motor compensation?

OBJECTIVES: Anosognosic patients show a lack of awareness for their hemiplegia coupled with a distorted sense of agency for the actions performed by the plegic limbs. Since anosognosia is often associated with right brain damage, this hemisphere seems to play a dominant role in monitoring awareness for motor actions. Therefore, we would expect that anosognosic patients show distorted awareness and sense of agency also for actions performed with the unimpaired limb. METHOD: To test this hypothesis, we induced illusory actions that could be congruent or incongruent with a preceding verbal command. A group of 16 right brain-damaged patients performed this task and then rated i) their ability to anticipate the actions, ii) their sense of agency and iii) their sense of ownership for each limb. Measures of awareness, neglect and motor impairment were also considered for the patient group. RESULTS: Following incongruent actions with the unimpaired limb, less aware patients showed a relatively mild distortion in all three aspects. In addition, we also found a crucial relationship between motor impairment (for the plegic limb) and sense of agency for both plegic and healthy limbs. CONCLUSION: Although the distortion linked to both limbs supports the initial hypothesis that the right hemisphere is responsible for monitoring awareness for action for the whole body, our data also suggest that the observed distortion may be linked to a motor compensatory phenomenon, not necessarily related to awareness processes.

Electrophysiological correlates of action monitoring in brain-damaged patients: A systematic review.

Action monitoring is crucial to the successful execution of an action and understanding the actions of others. It is often impaired due to brain lesions, in particular after stroke. This systematic review aims to map the literature on the neurophysiological correlates of action monitoring in patients with brain lesions. Eighteen studies were identified and divided into two groups: studies on monitoring of one's own actions and studies on monitoring of the actions of others. The first group included EEG studies on monitoring of self-performed erroneous and correct actions. Impaired error detection (decreased error-related negativity) was observed in patients with lesions in the performance-monitoring network, as compared to healthy controls. Less consistent results were shown for error positivity and behavioral error monitoring performance. The second group of studies on monitoring of others' actions reported decreased mu frequency suppression, impaired readiness potential in the affected hemisphere and decreased EEG indices of error observation (observed error positivity and theta power) in stroke patients. As a whole, these results indicate distinct patterns of impaired neurophysiological activity related to monitoring one's own versus others' actions in patients with brain lesions. EEG recordings of this dissociation in the same patients might be a useful index of motor recovery, and therefore, potentially also beneficial in rehabilitation protocols.

Human but not robotic gaze facilitates action prediction.

Do people ascribe intentions to humanoid robots as they would to humans or non-human-like animated objects? In six experiments, we compared people's ability to extract non-mentalistic (i.e., where an agent is looking) and mentalistic (i.e., what an agent is looking at; what an agent is going to do) information from gaze and directional cues performed by humans, human-like robots, and a non-human-like object. People were faster to infer the mental content of human agents compared to robotic agents. Furthermore, although the absence of differences in control conditions rules out the use of non-mentalizing strategies, the human-like appearance of non-human agents may engage mentalizing processes to solve the task. Overall, results suggest that human-like robotic actions may be processed differently from humans' and objects' behavior. These findings inform our understanding of the relevance of an object's physical features in triggering mentalizing abilities and its relevance for human-robot interaction.

Peripersonal Space from a multisensory perspective: the distinct effect of the visual and tactile components of Visuo-Tactile stimuli.

Peripersonal Space (PPS) is defined as the space close to the body where all interactions between the individual and the environment take place. Behavioural experiments on PPS exploit multisensory integration, using Multisensory Visuo-Tactile stimuli (MVT), whose visual and tactile components target the same body part (i.e. the face, the hand, the foot). However, the effects of visual and tactile stimuli targeting different body parts on PPS representation are unknown, and the relationship with the RTs for Tactile-Only stimuli is unclear. In this study, we addressed two research questions: (1) if the MVT-RTs are independent of Tactile-Only-RTs and if the latter is influenced by time-dependency effects, and (2) if PPS estimations derived from MVT-RTs depend on the location of the Visual or Tactile component of MVTs. We studied 40 right-handed participants, manipulating the body location (right hand, cheek or foot) and the distance of administration. Visual and Tactile components targeted different or the same body parts and were delivered respectively at five distances. RTs to Tactile-Only trials showed a non-monotonic trend, depending on the delay of stimulus administration. Moreover, RTs to Multisensory Visuo-Tactile trials were found to be dependent on the Distance and location of the Visual component of the stimulus. In conclusion, our results show that Tactile-Only RTs should be removed from Visuo-Tactile RTs and that the Visual and Tactile components of Visuo-Tactile stimuli do not necessarily have to target the same body part. These results have a relevant impact on the study of PPS representations, providing new important methodological information.

Cognitive Training Improves Disconnected Limbs' Mental Representation and Peripersonal Space after Spinal Cord Injury.

Paraplegia following spinal cord injury (SCI) affects the mental representation and peripersonal space of the paralysed body parts (i.e., lower limbs). Physical rehabilitation programs can improve these aspects, but the benefits are mostly partial and short-lasting. These limits could be due to the absence of trainings focused on SCI-induced cognitive deficits combined with traditional physical rehabilitation. To test this hypothesis, we assessed in 15 SCI-individuals the effects of adding cognitive recovery protocols (motor imagery-MI) to standard physical rehabilitation programs (Motor + MI training) on mental body representations and space representations, with respect to physical rehabilitation alone (control training). Each training comprised at least eight sessions administered over two weeks. The status of participants' mental body representation and peripersonal space was assessed at three time points: before the training (T0), after the training (T1), and in a follow-up assessment one month later (T2). The Motor + MI training induced short-term recovery of peripersonal space that however did not persist at T2. Body representation showed a slower neuroplastic recovery at T2, without differences between Motor and the Motor + MI. These results show that body and space representations are plastic after lesions, and open new rehabilitation perspectives.

Gesture errors in left and right hemisphere damaged patients: A behavioural and anatomical study.

OBJECTIVE: Erroneous gesture execution is at the core of motor cognition difficulties in apraxia. While a taxonomy of errors may provide important information about the nature of the disorder, classifications are currently often inconsistent. This study aims to identify the error categories which distinguish apraxic from non-apraxic patients. METHOD: Two groups of mixed (bucco-facial and limb) and bucco-facial apraxic patients suffering from stroke were compared to non-apraxic, left and right hemisphere damaged patients in tasks tapping the ability to perform limb and bucco-facial actions. The errors were analysed and classified into 6 categories relating to content, configuration or movement, spatial or temporal parameters and unrecognisable actions. Furthermore, an anatomical investigation (VLMS) was conducted in the whole group of left hemisphere damaged patients to investigate potential correlates of the various error categories. RESULTS: Although all the above error typologies may be observed, the most indicative of mixed apraxia is the content-related one in all the typologies of actions (transitive and intransitive), and configuration errors in transitive ones. Configuration and content errors in mouth actions seem to be typical of bucco-facial apraxia. Spatial errors are similar in both apraxic and right brain damaged, non-apraxic patients. A lesion mapping analysis of left-brain damaged patients demonstrates that all but the spatial error category are associated with the fronto-parietal network. Moreover, content errors are also associated with fronto-insular lesions and movement errors with damage to the paracentral territory (precentral and postcentral gyri). Spatial errors are often associated to ventral frontal lesions. CONCLUSIONS: Bucco-facial and mixed apraxic patients make different types of errors in different types of actions. Not all errors are equally indicative of apraxia. In addition, the various error categories are associated with at least partially different neural correlates.

The Role of White Matter Disconnection in the Symptoms Relating to the Anarchic Hand Syndrome: A Single Case Study.

The anarchic hand syndrome refers to an inability to control the movements of one's own hand, which acts as if it has a will of its own. The symptoms may differ depending on whether the brain lesion is anterior, posterior, callosal or subcortical, but the relative classifications are not conclusive. This study investigates the role of white matter disconnections in a patient whose symptoms are inconsistent with the mapping of the lesion site. A repeated neuropsychological investigation was associated with a review of the literature on the topic to identify the frequency of various different symptoms relating to this syndrome. Furthermore, an analysis of the neuroimaging regarding structural connectivity allowed us to investigate the grey matter lesions and white matter disconnections. The results indicated that some of the patient's symptoms were associated with structures that, although not directly damaged, were dysfunctional due to a disconnection in their networks. This suggests that the anarchic hand may be considered as a disconnection syndrome involving the integration of multiple antero-posterior, insular and interhemispheric networks. In order to comprehend this rare syndrome better, the clinical and neuroimaging data need to be integrated with the clinical reports available in the literature on this topic.

Bayesian multilevel single case models using 'Stan'. A new tool to study single cases in neuropsychology.

Single case studies continue to play an important role in neuropsychological research. However, the range of statistical tools specifically designed for single cases is still limited. The current gold standard is the Crawford's t-test, but it is crucial to note that this is limited to simple designs and it is not possible to make inferences relevant to support for the null hypothesis with it. The Bayesian Multilevel Single Case models (BMSC) provide a novel tool that grants the flexibility of linear mixed model designs. BMSC is also able to support both null and alternative hypotheses in complex experimental designs using the Bayesian framework. We compared the BMSC and Crawford's t-test in a simulation study involving a case of no-dissociation and a case of simple dissociation between a single case patient and a series of control groups of different sizes (N = 5, 15, or 30). We then showed how BMSC is useful in complex designs by means of an example using real data. The BMSC proved to be more reliable than the Crawford's test, in terms of first-type errors and more precise estimating the parameters. Notably, the BMSC model provides a comprehensive vision of the whole experimental design, interpolating a single model. It follows the recent trend which involves a shift in attention from p-values to other inferential indices and estimates.

The impact of multisensory integration and perceptual load in virtual reality settings on performance, workload and presence.

Real-world experience is typically multimodal. Evidence indicates that the facilitation in the detection of multisensory stimuli is modulated by the perceptual load, the amount of information involved in the processing of the stimuli. Here, we used a realistic virtual reality environment while concomitantly acquiring Electroencephalography (EEG) and Galvanic Skin Response (GSR) to investigate how multisensory signals impact target detection in two conditions, high and low perceptual load. Different multimodal stimuli (auditory and vibrotactile) were presented, alone or in combination with the visual target. Results showed that only in the high load condition, multisensory stimuli significantly improve performance, compared to visual stimulation alone. Multisensory stimulation also decreases the EEG-based workload. Instead, the perceived workload, according to the "NASA Task Load Index" questionnaire, was reduced only by the trimodal condition (i.e., visual, auditory, tactile). This trimodal stimulation was more effective in enhancing the sense of presence, that is the feeling of being in the virtual environment, compared to the bimodal or unimodal stimulation. Also, we show that in the high load task, the GSR components are higher compared to the low load condition. Finally, the multimodal stimulation (Visual-Audio-Tactile-VAT and Visual-Audio-VA) induced a significant decrease in latency, and a significant increase in the amplitude of the P300 potentials with respect to the unimodal (visual) and visual and tactile bimodal stimulation, suggesting a faster and more effective processing and detection of stimuli if auditory stimulation is included. Overall, these findings provide insights into the relationship between multisensory integration and human behavior and cognition.

The Motor Unawareness Assessment (MUNA): A new tool for the assessment of Anosognosia for hemiplegia.

Introduction: Anosognosia for hemiplegia (AHP) is a condition in which patients with paralysis are unaware of their motor deficits. Research into AHP is important for improving its treatment and providing insight into the neurocognitive mechanism of motor awareness. Unfortunately, most studies use assessments with widely recognized limitations.The study aims at developing a psychometrically validated assessment of AHP.Method: We developed a 40-item Motor Unawareness Assessment (MUNA) and administered it to 131 right-hemisphere stroke patients. Principal Component Analysis (PCA) was used to identify the underlying factor structure. Receiver Operating Characteristics (ROC) analysis was used to determine diagnostic cutoffs, and Area Under the Curve (AUC) analysis used to assess these cutoffs. Relationships with demographic, clinical and neuropsychological variables were explored.Results: Five factors were identified: explicit motor awareness, implicit motor awareness, impaired sense of ownership, agency and illusory movement, and emotional reactions. Established cutoffs had excellent sensitivity and specificity. Clinical, neuropsychological and demographic variables did not predict overall MUNA score but were related to specific subcomponents.Conclusion: The MUNA can differentiate various facets of AHP and provides a detailed profile of (un)awareness. The MUNA can therefore provide robust assessment for research purposes and assist clinicians when developing targeted rehabilitation.