In the past years, there have been increasing research activities focusing on somatosensory symptoms following stroke. However, as compared to the large number of clinical and neuroimaging studies on motor symptoms, the number of studies tracing somatosensory symptoms after stroke and their recovery is rather small. It is an ongoing discussion, to which extent somatosensory deficits after stroke influence patient's long-term outcome in motor and sensory performance and functional independence in activities of daily living. Modern brain imaging techniques allow for studying the impact of stroke lesion localization and size on acute and persisting clinical impairment. Here, we review the literature on somatosensory symptoms after stroke. We summarize epidemiological information on frequency and characteristics of somatosensory symptoms affecting all parts of the body in the acute and chronic stage of stroke. We further give an overview of brain imaging studies of stroke affecting the somatosensory system. Finally, we identify open questions which need to be addressed in future research and summarize the implications for clinical practice.

Placebo responses have been shown to contribute to clinical treatment outcomes. 1 The pharmacological enhancement of placebo responses therefore has the potential to increase treatment benefits. The neuropeptide oxytocin may mediate processes such as empathy, trust, and social learning. 2 These are key elements of the patient-physician relationship, which is an important mediator of placebo responses. 3 We tested whether oxytocin enhances the placebo response in an experimental placebo analgesia model.

The aim of this study was to investigate the relationship between stroke lesion location and the resulting somatosensory deficit. We studied exteroceptive and proprioceptive somatosensory symptoms and stroke lesions in 38 patients with first-ever acute stroke. The Erasmus modified Nottingham Sensory Assessment was used to clinically evaluate somatosensory functioning in the arm and hand within the first week after stroke onset. Additionally, more objective measures such as the perceptual threshold of touch and somatosensory evoked potentials were recorded. Non-parametric voxel-based lesion-symptom mapping was performed to investigate lesion contribution to different somatosensory deficits in the upper limb. Additionally, structural connectivity of brain areas that demonstrated the strongest association with somatosensory symptoms was determined, using probabilistic fiber tracking based on diffusion tensor imaging data from a healthy age-matched sample. Voxels with a significant association to somatosensory deficits were clustered in two core brain regions: the central parietal white matter, also referred to as the sensory component of the superior thalamic radiation, and the parietal operculum close to the insular cortex, representing the secondary somatosensory cortex. Our objective recordings confirmed findings from clinical assessments. Probabilistic tracking connected the first region to thalamus, internal capsule, brain stem, postcentral gyrus, cerebellum, and frontal pathways, while the second region demonstrated structural connections to thalamus, insular and primary somatosensory cortex. This study reveals that stroke lesions in the sensory fibers of the superior thalamocortical radiation and the parietal operculum are significantly associated with multiple exteroceptive and proprioceptive deficits in the arm and hand.

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Background and Purpose— About 50% to 80% of stroke survivors present with somatosensory deficits. Somatosensory deficits because of an ischemic stroke are determined by the infarct location. However, a detailed understanding of the long-term effect of lesions on somatosensory performance is lacking. Methods— This prospective observational study enrolled 101 ischemic stroke patients. For voxel-based lesion-symptom mapping, magnetic resonance imaging fluid-attenuated inversion recovery imaging infarct lesions were segmented within 5 days after stroke. Standardized tests such as the National Institutes of Health Stroke Scale and the Rivermead Assessment of Somatosensory Performance were performed during acute stage, after 3 and 12 months. This included bilateral testing for multiple tactile and proprioceptive somatosensory modalities (pressure, light touch, sharp-dull discrimination, temperature discrimination, sensory extinction, 2-point discrimination, and joint position and movement sense). We further study the association of acute somatosensory deficit with functional outcome 12 months after stroke assessed by the modified Rankin Scale using univariate and multiple linear regression analysis also including acute motor deficit assessed by the arm research action test. Results— Sixty patients (59.4%) showed impairment in at least one somatosensory modality. Light touch was most frequently affected (38.7%), whereas temperature was least frequently affected (21.8%). After 3 months, significant recovery was observed in all somatosensory modalities, with only minor additional improvements after 12 months. Voxel-based lesion-symptom mapping revealed significant associations of lesions in the primary and secondary somatosensory and insular cortex with somatosensory deficits. Acute somatosensory deficit was associated with functional outcome at 12 months. However, including the acute motor deficit, somatosensory deficit was no longer an independent predictor of functional outcome. Conclusions— Our study confirms that somatosensory deficits are frequent in acute ischemic stroke but largely recover over time. Infarct lesions in the primary and secondary somatosensory cortex and insula show a robust association with somatosensory impairment. Long-term disability is influenced by somatosensory deficits but driven by motor symptoms.

It is increasingly recognized that the efficacy of medical treatments is determined in critical part by the therapeutic context in which it is delivered. An important characteristic of that context is treatment history. We recently reported first evidence for a carry-over of treatment experience to subsequent treatment response across different treatment approaches. Here we expand on these findings by exploring the psychological and neurobiological underpinnings of the effect of treatment experience on future treatment response in an experimental model of placebo analgesia with a conditioning procedure. In a combined behavioral and neuroimaging study we experimentally induced positive or negative experiences with an analgesic treatment in two groups of healthy human subjects. Subsequently we compared responses to a second, different analgesic treatment between both groups. We found that participants with an experimentally induced negative experience with the first treatment showed a substantially reduced response to a second analgesic treatment. Intriguingly, several psychological trait variables including anxiety, depression and locus of control modulate the susceptibility for the effects of prior treatment experiences on future treatment outcome. These behavioral effects were supported by neuroimaging data which showed significant differences in brain regions encoding pain and analgesia between groups. These differences in activation patterns were present not only during the pain phase, but also already prior to painful stimulation and scaled with the individual treatment response. Our data provide behavioral and neurobiological evidence showing that the influence of treatment history transfers over time and over therapeutic approaches. Our experimental findings emphasize the careful consideration of treatment history and a strictly systematic treatment approach to avoid negative carry-over effects.

Failure of medical treatments can hamper responses to subsequent treatments. It has been suggested that changing the route of drug administration could reduce such negative carry-over effects, but direct evidence for this approach is lacking. We therefore investigated in 211 healthy volunteers whether changes in drug administration route reduce such carry-over effects. A positive or negative treatment history with topical analgesic treatments was induced experimentally in a mock clinical trial setting. Subsequently, a different inert drug was introduced via the same (topical) or another (oral) route of administration and its analgesic efficacy was tested. Changing the route of drug administration induced expectations of positive treatment effects in the subjects but did not actually counteract the negative carry-over effects on treatment efficacy. These findings indicate that learned carry-over effects generalize over time and across routes of drug administration-independent of conscious expectations. Other strategies are needed to prevent negative carry-over effects of treatment failure from influencing the results of subsequent treatment attempts.

IntroductionThere is evidence suggesting a detrimental effect of asymptomatic carotid artery stenosis on cognitive function even in the absence of ischemic cerebral lesions. Hypoperfusion has been suggested as pathophysiological mechanism causing cognitive impairment. We aimed to assess cognitive performance and cerebral perfusion changes in patients with carotid artery stenosis without ischemic lesions by arterial spin labeling (ASL) and contrast enhanced (CE) perfusion MRI before and after revascularization therapy.Methods17 asymptomatic patients with unilateral high-grade (≥70%) carotid artery stenosis without evidence of structural brain lesions underwent ASL and CE perfusion MRI and cognitive testing (MMSE, DemTect, Clock-Drawing Test, Trail-Making Test, Stroop Test) before and 6–8 weeks after revascularization therapy by endarterectomy or stenting. Multiparametric perfusion maps (ASL: cerebral blood flow (ASL-CBF), bolus arrival time (ASL-BAT); CE: cerebral blood flow (CE-CBF), mean transit time (CE-MTT), cerebral blood volume (CE-CBV)) were calculated and analyzed by vascular territory. Relative perfusion values were calculated.ResultsMultivariate analysis revealed a significant impact of revascularization therapy on all perfusion measures analyzed. At baseline post-hoc testing showed significant hypoperfusion in MCA borderzones as assessed by ASL-CBF, ASL-BAT, CE-MTT and CE-CBV. All perfusion alterations normalized after revascularization. We did not observe any significant correlation of cognitive test results with perfusion parameters. There was no significant change in cognitive performance after revascularization.ConclusionWe found evidence of traceable perfusion alterations in patients with high grade carotid artery stenosis in the absence of structural brain lesions, which proved fully reversible after revascularization therapy. In this cohort of asymptomatic patients we did not observe an association of hypoperfusion with cognitive performance.