Prof. Dr. Dr. h.c. Dr. h.c. Herta Flor
Department of Clinical Psychology and Neuropsychology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University
Dr. Jamila Andoh
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University

Neural circuits involved in phantom limb pain

Virtual Reality

real-time fMRIy

The causal role of neuroplastic alterations in brain circuits and interacting peripheral factors in shaping the experience of phantom limb pain (PLP) is not yet well understood. In the first funding period, we aimed to identify brain circuits underlying the onset and continued presence of phantom limb pain (PLP). We used a multimodal imaging appoach (i.e. functional and structural magnetic resonance imaging, electroencephalography) to obtain complementary information regarding PLP-associated neural changes. Using both sensory stimulation and a virtual phantom movement task we found evidence for different roles of functional maladaptive reorganization and for preserved organization depending on the input modality being used, i.e. sensory or motor inputs and the consideration of the presence of severity of PLP. PLP-related functional changes were also associated with structural changes (e.g. grey matter volume, fractional anisotropy) in primary somatosensory (S1) and motor (M1) cortices. We also observed that input from a prosthesis or compensatory input from the intact limb shape the cortical changes and are associated with different levels of PLP.


Such findings raise questions as to how sensory and motor inputs alter phantom pain and brain structure-function, which deserve further investigation. We also found that PLP and residual limb pain (RLP) could be induced when non-painful sensory stimuli were applied at the residual limb nerve in amputees with PLP and not in amputees without PLP. Moreover, stimulation-induced PLP was associated with evoked activity in S1, and RLP with spinal activity. In the longitudinal study we found evidence that pain before the amputation as well as psychological factors such as anxiety and depression best predict the presence of PLP one year after an amputation.

In the new funding period we plan to complement the examination of amputees pre and post amputation with an analysis of patients with pain that have a high likelihood of having an amputation. Since pre-amputation pain is a major determinant for PLP and also a major determinant for amputation in diabetic patients, we will test diabetic patients at risk for an amputation well before the amputation and follow them to determine central and peripheral as well as psychological predictors of both amputation and PLP.

Transcranial alternating current stimulation


We will also use virtual and augmented reality applications in addition to electromyographic recordings from the residual limb to model the differential role of somatosensory, motor and visual inputs from the phantom for brain changes and PLP. Further, we will ask how the PLP percept can be modulated by altering activation patterns and cortical rhythms employing fMRI neurofeedback and transcranial alternating current stimulation (tACS).