Self-regulating arousal via pupil-based biofeedback.

The brain's arousal state is controlled by several neuromodulatory nuclei known to substantially influence cognition and mental well-being. Here we investigate whether human participants can gain volitional control of their arousal state using a pupil-based biofeedback approach. Our approach inverts a mechanism suggested by previous literature that links activity of the locus coeruleus, one of the key regulators of central arousal and pupil dynamics. We show that pupil-based biofeedback enables participants to acquire volitional control of pupil size. Applying pupil self-regulation systematically modulates activity of the locus coeruleus and other brainstem structures involved in arousal control. Furthermore, it modulates cardiovascular measures such as heart rate, and behavioural and psychophysiological responses during an oddball task. We provide evidence that pupil-based biofeedback makes the brain's arousal system accessible to volitional control, a finding that has tremendous potential for translation to behavioural and clinical applications across various domains, including stress-related and anxiety disorders.

Performing a vibrotactile discrimination task modulates finger representations in primary somatosensory cortex.

It is well established that vibrotactile stimuli are represented in somatotopic maps. However, less is known about whether these somatotopic representations are modulated by task demands and maybe even in the absence of tactile input. Here, we used a vibrotactile discrimination task as a tool to investigate these questions in further detail. Participants were required to actively perceive and process tactile stimuli in comparison to a no-task control condition where identical stimuli were passively perceived (no-memory condition). Importantly, both vibrotactile stimuli were either applied to the right index or little finger, allowing us to investigate whether cognitive task demands shape finger representations in primary somatosensory cortex (S1). Using multivoxel pattern analysis and representational similarity analysis, we found that S1 finger representations were more distinct during the memory than the no-memory condition. Interestingly, this effect was not only observed while tactile stimuli were presented but also during the delay period (i.e., in the absence of tactile stimulation). Our findings imply that when individuals are required to focus on tactile stimuli, retain them in their memory, and engage in active processing of distinctive stimulus features, this exerts a modulatory effect on the finger representations present in S1.NEW & NOTEWORTHY Using multivoxel pattern analysis, we found that discrimination task demands shape finger representations in the contralateral primary somatosensory cortex (S1), and that somatotopic representations are modulated by task demands not only during tactile stimulation but also to a certain extent in the absence of tactile input.

Hand and face somatotopy shown using MRI-safe vibrotactile stimulation with a novel soft pneumatic actuator (SPA)-skin interface.

The exact somatotopy of the human facial representation in the primary somatosensory cortex (S1) remains debated. One reason that progress has been hampered is due to the methodological challenge of how to apply automated vibrotactile stimuli to face areas in a manner that is: (1) reliable despite differences in the curvatures of face locations; and (2) MR-compatible and free of MR-interference artefacts when applied in the MR head-coil. Here we overcome this challenge by using soft pneumatic actuator (SPA) technology. SPAs are made of a soft silicon material and can be in- or deflated by means of airflow, have a small diameter, and are flexible in structure, enabling good skin contact even on curved body surfaces (as on the face). To validate our approach, we first mapped the well-characterised S1 finger layout using this novel device and confirmed that tactile stimulation of the fingers elicited characteristic somatotopic finger activations in S1. We then used the device to automatically and systematically deliver somatosensory stimulation to different face locations. We found that the forehead representation was least distant from the representation of the hand. Within the face representation, we found that the lip representation is most distant from the forehead representation, with the chin represented in between. Together, our results demonstrate that this novel MR compatible device produces robust and clear somatotopic representational patterns using vibrotactile stimulation through SPA-technology.

Malleability of the cortical hand map following a finger nerve block.

Electrophysiological studies in monkeys show that finger amputation triggers local remapping within the deprived primary somatosensory cortex (S1). Human neuroimaging research, however, shows persistent S1 representation of the missing hand's fingers, even decades after amputation. Here, we explore whether this apparent contradiction stems from underestimating the distributed peripheral and central representation of fingers in the hand map. Using pharmacological single-finger nerve block and 7-tesla neuroimaging, we first replicated previous accounts (electrophysiological and other) of local S1 remapping. Local blocking also triggered activity changes to nonblocked fingers across the entire hand area. Using methods exploiting interfinger representational overlap, however, we also show that the blocked finger representation remained persistent despite input loss. Computational modeling suggests that both local stability and global reorganization are driven by distributed processing underlying the topographic map, combined with homeostatic mechanisms. Our findings reveal complex interfinger representational features that play a key role in brain (re)organization, beyond (re)mapping.

Finger somatotopy is preserved after tetraplegia but deteriorates over time.

Previous studies showed reorganised and/or altered activity in the primary sensorimotor cortex after a spinal cord injury (SCI), suggested to reflect abnormal processing. However, little is known about whether somatotopically specific representations can be activated despite reduced or absent afferent hand inputs. In this observational study, we used functional MRI and a (attempted) finger movement task in tetraplegic patients to characterise the somatotopic hand layout in primary somatosensory cortex. We further used structural MRI to assess spared spinal tissue bridges. We found that somatotopic hand representations can be activated through attempted finger movements in the absence of sensory and motor hand functioning, and no spared spinal tissue bridges. Such preserved hand somatotopy could be exploited by rehabilitation approaches that aim to establish new hand-brain functional connections after SCI (e.g. neuroprosthetics). However, over years since SCI the hand representation somatotopy deteriorated, suggesting that somatotopic hand representations are more easily targeted within the first years after SCI.

Mental individuation of imagined finger movements can be achieved using TMS-based neurofeedback.

Neurofeedback (NF) in combination with motor imagery (MI) can be used for training individuals to volitionally modulate sensorimotor activity without producing overt movements. However, until now, NF methods were of limited utility for mentally training specific hand and finger actions. Here we employed a novel transcranial magnetic stimulation (TMS) based protocol to probe and detect MI-induced motor activity patterns in the primary motor cortex (M1) with the aim to reinforce selective facilitation of single finger representations. We showed that TMS-NF training but not MI training with uninformative feedback enabled participants to selectively upregulate corticomotor excitability of one finger, while simultaneously downregulating excitability of other finger representations within the same hand. Successful finger individuation during MI was accompanied by strong desynchronization of sensorimotor brain rhythms, particularly in the beta band, as measured by electroencephalography. Additionally, informative TMS-NF promoted more dissociable EEG activation patterns underlying single finger MI, when compared to MI of the control group where no such feedback was provided. Our findings suggest that selective TMS-NF is a new approach for acquiring the ability of finger individuation even if no overt movements are performed. This might offer new treatment modality for rehabilitation after stroke or spinal cord injury.

Neural basis of induced phantom limb pain relief.

OBJECTIVE: Phantom limb pain (PLP) is notoriously difficult to treat, partly due to an incomplete understanding of PLP-related disease mechanisms. Noninvasive brain stimulation (NIBS) is used to modulate plasticity in various neuropathological diseases, including chronic pain. Although NIBS can alleviate neuropathic pain (including PLP), both disease and treatment mechanisms remain tenuous. Insight into the mechanisms underlying both PLP and NIBS-induced PLP relief is needed for future implementation of such treatment and generalization to related conditions. METHODS: We used a within-participants, double-blind, and sham-controlled design to alleviate PLP via task-concurrent NIBS over the primary sensorimotor missing hand cortex (S1/M1). To specifically influence missing hand signal processing, amputees performed phantom hand movements during anodal transcranial direct current stimulation. Brain activity was monitored using neuroimaging during and after NIBS. PLP ratings were obtained throughout the week after stimulation. RESULTS: A single session of intervention NIBS significantly relieved PLP, with effects lasting at least 1 week. PLP relief associated with reduced activity in the S1/M1 missing hand cortex after stimulation. Critically, PLP relief and reduced S1/M1 activity correlated with preceding activity changes during stimulation in the mid- and posterior insula and secondary somatosensory cortex (S2). INTERPRETATION: The observed correlation between PLP relief and decreased S1/M1 activity confirms our previous findings linking PLP with increased S1/M1 activity. Our results further highlight the driving role of the mid- and posterior insula, as well as S2, in modulating PLP. Lastly, our novel PLP intervention using task-concurrent NIBS opens new avenues for developing treatment for PLP and related pain conditions. ANN NEUROL 2019;85:59-73.

Reaffirming the link between chronic phantom limb pain and maintained missing hand representation.

Phantom limb pain (PLP) is commonly considered to be a result of maladaptive brain plasticity. This model proposes that PLP is mainly caused by reorganisation in the primary somatosensory cortex, presumably characterised by functional degradation of the missing hand representation and remapping of other body part representations. In the current study, we replicate our previous results by showing that chronic PLP correlates with maintained representation of the missing hand in the primary sensorimotor missing hand cortex. We asked unilateral upper-limb amputees to move their phantom hand, lips or other body parts and measured the associated neural responses using functional magnetic resonance imaging (fMRI). We confirm that amputees suffering from worse chronic PLP have stronger activity in the primary sensorimotor missing hand cortex while performing phantom hand movements. We find no evidence of lip representation remapping into the missing hand territory, as assessed by measuring activity in the primary sensorimotor missing hand cortex during lip movements. We further show that the correlation between chronic PLP and maintained representation of the missing hand cannot be explained by the experience of chronic non-painful phantom sensations or compensatory usage of the residual arm or an artificial arm (prosthesis). Together, our results reaffirm a likely relationship between persistent peripheral inputs pertaining to the missing hand representation and chronic PLP. Our findings emphasise a need to further study the role of peripheral inputs from the residual nerves to better understand the mechanisms underlying chronic PLP.

Motor correlates of phantom limb pain.

Following amputation, individuals ubiquitously report experiencing lingering sensations of their missing limb. While phantom sensations can be innocuous, they are often manifested as painful. Phantom limb pain (PLP) is notorious for being difficult to monitor and treat. A major challenge in PLP management is the difficulty in assessing PLP symptoms, given the physical absence of the affected body part. Here, we offer a means of quantifying chronic PLP by harnessing the known ability of amputees to voluntarily move their phantom limbs. Upper-limb amputees suffering from chronic PLP performed a simple finger-tapping task with their phantom hand. We confirm that amputees suffering from worse chronic PLP had worse motor control over their phantom hand. We further demonstrate that task performance was consistent over weeks and did not relate to transient PLP or non-painful phantom sensations. Finally, we explore the neural basis of these behavioural correlates of PLP. Using neuroimaging, we reveal that slower phantom hand movements were coupled with stronger activity in the primary sensorimotor phantom hand cortex, previously shown to associate with chronic PLP. By demonstrating a specific link between phantom hand motor control and chronic PLP, our findings open up new avenues for PLP management and improvement of existing PLP treatments.

Revealing the neural fingerprints of a missing hand.

The hand area of the primary somatosensory cortex contains detailed finger topography, thought to be shaped and maintained by daily life experience. Here we utilise phantom sensations and ultra high-field neuroimaging to uncover preserved, though latent, representation of amputees' missing hand. We show that representation of the missing hand's individual fingers persists in the primary somatosensory cortex even decades after arm amputation. By demonstrating stable topography despite amputation, our finding questions the extent to which continued sensory input is necessary to maintain organisation in sensory cortex, thereby reopening the question what happens to a cortical territory once its main input is lost. The discovery of persistent digit topography of amputees' missing hand could be exploited for the development of intuitive and fine-grained control of neuroprosthetics, requiring neural signals of individual digits.

EEG decoding of spoken words in bilingual listeners: from words to language invariant semantic-conceptual representations.

Spoken word recognition and production require fast transformations between acoustic, phonological, and conceptual neural representations. Bilinguals perform these transformations in native and non-native languages, deriving unified semantic concepts from equivalent, but acoustically different words. Here we exploit this capacity of bilinguals to investigate input invariant semantic representations in the brain. We acquired EEG data while Dutch subjects, highly proficient in English listened to four monosyllabic and acoustically distinct animal words in both languages (e.g., "paard"-"horse"). Multivariate pattern analysis (MVPA) was applied to identify EEG response patterns that discriminate between individual words within one language (within-language discrimination) and generalize meaning across two languages (across-language generalization). Furthermore, employing two EEG feature selection approaches, we assessed the contribution of temporal and oscillatory EEG features to our classification results. MVPA revealed that within-language discrimination was possible in a broad time-window (~50-620 ms) after word onset probably reflecting acoustic-phonetic and semantic-conceptual differences between the words. Most interestingly, significant across-language generalization was possible around 550-600 ms, suggesting the activation of common semantic-conceptual representations from the Dutch and English nouns. Both types of classification, showed a strong contribution of oscillations below 12 Hz, indicating the importance of low frequency oscillations in the neural representation of individual words and concepts. This study demonstrates the feasibility of MVPA to decode individual spoken words from EEG responses and to assess the spectro-temporal dynamics of their language invariant semantic-conceptual representations. We discuss how this method and results could be relevant to track the neural mechanisms underlying conceptual encoding in comprehension and production.