Sanne Kikkert

Last Name

Kikkert

First Name

Sanne

ORCID

0000-0001-9952-4864

Organisational unit

03963 - Wenderoth, Nicole / Wenderoth, Nicole

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Publications 1 - 6 of 6

Neural basis of induced phantom limb pain relief
Kikkert, Sanne; Mezue, Melvin; O'Shea, Jacinta; et al. (2019)
Annals of Neurology
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.
Mental individuation of imagined finger movements can be achieved using TMS-based neurofeedback
Mihelj, Ernest; Bächinger, Marc; Kikkert, Sanne; et al. (2021)
NeuroImage
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.
Wearable non-invasive neuroprosthesis for targeted sensory restoration in neuropathy
Gozzi, Noemi; Chee, Lauren; Odermatt, Ingrid; et al. (2024)
Nature Communications
Peripheral neuropathy (PN), the most common complication of diabetes, leads to sensory loss and associated health issues as pain and increased fall risk. However, present treatments do not counteract sensory loss, but only partially manage its consequences. Electrical neural stimulation holds promise to restore sensations, but its efficacy and benefits in PN damaged nerves are yet unknown. We designed a wearable sensory neuroprosthesis (NeuroStep) providing targeted neurostimulation of the undamaged nerve portion and assessed its functionality in 14 PN participants. Our system partially restored lost sensations in all participants through a purposely calibrated neurostimulation, despite PN nerves being less sensitive than healthy nerves (N = 22). Participants improved cadence and functional gait and reported a decrease of neuropathic pain after one day. Restored sensations activated cortical patterns resembling naturally located foot sensations. NeuroStep restores real-time intuitive sensations in PN participants, holding potential to enhance functional and health outcomes while advancing effective non-invasive neuromodulation.
Cortical reorganization in the adult primary sensorimotor cortex
Kikkert, Sanne; Root, Victoria; Buehler, Sarah; et al. (2025)
Encyclopedia of the Human Brain
Seminal work on sensorimotor plasticity has established the notion that the adult cortex has the capacity to functionally reorganize in order to adapt itself to the changed capabilities of the body. Limb loss provides a key model for studying brain reorganization as it combines two main drivers of brain plasticity—sensory input loss and altered behavior. Here we explore how the highly structured and consistent hand representation in the primary somatosensory cortex (S1) changes following hand loss. We review classical findings demonstrating that following amputation, the neighboring body part representations “invade” the deprived hand area. We further review potential perceptual consequences of such reorganization, both maladaptive (e.g., phantom limb pain) and adaptive (e.g., compensatory strategies). We highlight recent evidence demonstrating that the functional organization in the deprived cortex is preserved even decades after amputation, consistent with the view that S1 reorganization reflects plasticity occurring at the brainstem level. Finally we highlight alternative models of deprivation-driven S1 plasticity, such as hand transplantation, temporary deafferentation, congenital handlessness, and neuroprostheses, providing further insights into the scope and functional consequences of S1 reorganization.
Finger somatotopy is preserved after tetraplegia but deteriorates over time
Kikkert, Sanne; Pfyffer, Dario; Verling, Michaela; et al. (2021)
eLife
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.
Distinguishing the activity of adjacent somatosensory nuclei within the brainstem using 3T fMRI
Howell, Paige; Odermatt, Ingrid; Harrison, Olivia; et al. (2025)
Imaging Neuroscience
Experimental evidence in animal models indicates that the brainstem plays a major role in sensory modulation. However, mapping functional activity within the human brainstem presents many methodological challenges. These constraints have deterred essential research into human sensory brainstem processing. Here, using a 3T functional Magnetic Resonance Imaging (fMRI) sequence optimised for the brainstem, combined with uni- and multivariate analysis approaches, we investigated the extent to which functional activity of neighbouring somatosensory nuclei can be delineated in the brainstem, thalamus, and primary somatosensory cortex (S1). Whilst traditional univariate approaches offered limited differentiation between adjacent hand and face activation in the brainstem, multivariate classification enabled above-chance decoding of these activity patterns across S1, the thalamus, and the brainstem. Our findings establish a robust methodological approach to explore signal processing within the brainstem and across the entire somatosensory stream. This is a fundamental step towards broadening our understanding of somatosensory processing within humans and determining what changes in sensory integration may occur in clinical populations following sensory deprivation.

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Sanne Kikkert

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