Methods matter: A primer on permanent and reversible interference techniques in animals for investigators of human neuropsychology.

The study of patients with brain lesions has contributed greatly to our understanding of the biological bases of human cognition, but this approach also has several unavoidable limitations. Research that uses animal models complements and extends human neuropsychology by addressing many of these limitations. In this review, we provide an overview of permanent and reversible animal lesion techniques for researchers of human neuropsychology, with the aim of highlighting how these methods provide a valuable adjunct to behavioural, neuroimaging, physiological, and clinical investigations in humans. Research in animals has provided important lessons about how the limitations of one or more techniques, or differences in their mechanism of action, has impacted upon the understanding of brain organisation and function. These cautionary tales highlight the importance of striving for a thorough understanding of how any intereference technique works (whether in animal or human), and for how to best use animal research to clarify the precise mechanisms underlying temporary lesion methods in humans

Predictors of Self-Reported Neglect-like Symptoms and Involuntary Movements in Complex Regional Pain Syndrome Compared to Other Chronic Limb Pain Conditions

OBJECTIVE: In addition to pain, people with complex regional pain syndrome (CRPS) often report inattention to and disengagement from their affected limb (i.e., "neglect-like symptoms"). Understanding how these symptoms relate to other characteristics of CRPS, and chronic pain generally, could provide insights for preventing and treating CRPS. METHODS: We administered an online survey to people who received a diagnosis of CRPS (n = 335) and other chronic limb pain (n = 407). Neglect-like symptoms were assessed using the Neurobehavioral questionnaire. RESULTS: A principal component analysis identified two components: motor and cognitive neglect-like symptoms, and involuntary movements. Internal consistency of the components was acceptable. We conducted regression analyses with these as outcomes. Having CRPS, a painful lower limb, higher pain intensity, and somatic symptoms were associated with more motor and cognitive neglect-like symptoms. Having CRPS, higher pain intensity, depression, and somatic symptoms were associated with more involuntary movements. Age, gender, anxiety, disease duration, hours of pain per day, affected side, whether the limb was the most painful body part, and number of pain-related medical diagnoses were no predictors. Finally, motor and cognitive neglect-like symptoms were related to tremor; and involuntary movements to changes in skin color, swelling, sweating, toenails, weakness, and tremor. CONCLUSIONS: This study confirms the specificity of inattention to and disengagement from the affected limb in CRPS, independent of other factors. Furthermore, two components of the Neurobehavioral questionnaire were disentangled: motor and cognitive neglect-like symptoms, and involuntary movements. Results could potentially help clinicians to better assess neglect-like symptoms in chronic pain

The effect of prism adaptation on state estimates of eye position in the orbit

Prism adaptation (PA) after-effects are assessed using tests that measure changes in sensorimotor systems. After-effects on pointing without feedback to a visual target (open loop pointing – OLP) are traditionally described as being larger than those measured by straight ahead pointing (SAP) with eyes closed, and the difference between them is attributed to a shift in visual localisation. However, neither differences between OLP and SAP, nor shifts in perceptual judgement of visual straight ahead (VSA), are consistently reported. Moreover, since very few studies have directly recorded direction of gaze, an effect of PA on the state estimate of gaze direction has not been reliably documented. The current research aimed to isolate the effects of PA on state estimates of eye position. We measured sensorimotor after-effects through common (OLP, SAP, and VSA) measures, and also recorded eye position and additional after-effect measures to interrogate changes to the oculomotor system and how these might relate to other measures of sensorimotor change. To ascertain if PA's effects on estimates of eye position could be attributed to eye muscle potentiation, we compared the effects of PA to sustained gaze deviation without adaptation. PA induced no effect on visual straight-ahead and no change in direction of gaze, when measured while positioning a target, looking straight ahead in the dark, or looking toward the passively positioned and occluded unexposed hand. We also found that after-effects measured by SAP with the eyes open were larger than SAP with the eyes closed and equal to those observed with OLP. The findings challenge the concept that total adaptation after-effect is a direct sum of arm proprioceptive and visual after-effects as conventionally measured, and suggest that the oculomotor system is altered by prism adaptation only in interaction with an arm motor command when vision is available

Validation of the Leiden Visual Sensitivity Scale and Visual Discomfort Scale in Chronic Pain Conditions

Discomfort provoked by normally innocuous visual stimuli has been reported by people with chronic pain. Visual discomfort may be higher in pain conditions in which central sensitization is implicated, such as Complex Regional Pain Syndrome (CRPS) and fibromyalgia. In an online study, we validated the Leiden Visual Sensitivity Scale (L-VISS) and Visual Discomfort Scale (VDS) in people with CRPS (n = 57), fibromyalgia (n = 75), and general chronic pain (n = 53); investigated whether these groups and pain-free controls (n = 125) differed in visual discomfort; and evaluated the effect of age. The L-VISS and VDS had good internal consistency. Both scales were positively related with experimentally induced visual distortions for mid-spatial frequency striped patterns, suggesting good construct validity. The scales were positively related with each other, and dissociated between the pain and pain-free groups in similar ways, suggesting good construct validity. There was no relationship between age and L-VISS scores and a small negative relationship between age and VDS scores. Visual discomfort was highest in the fibromyalgia group, followed by the CRPS group. This research confirms the utility of the L-VISS and VDS for measuring visual sensitivity in chronic pain and adds to evidence that central sensitization is an important mechanism of visual discomfort

Visual sensitivity in Complex Regional Pain Syndrome and fibromyalgia: an online study

Perceptual anomalies can provide insights into underlying pathologies even when they are not the main symptom of many clinical conditions. Complex regional pain syndrome (CRPS) and fibromyalgia are chronic pain conditions associated with changes in the central nervous system, possibly leading to enhanced visual sensitivity. It is unclear whether this occurs more than for people with other types of pain. We examined visual sensitivity elicited by different stimuli and in daily life, through an online study of people with CRPS (n = 57), fibromyalgia (n = 74), other pain (n = 50), and no pain (n = 89). Respondents rated changes in pain, discomfort, or distress from viewing patterns with different spatial frequencies (lower-order visual processing), and reversible figures (bistable images; higher-order visual processing). We assessed visual sensitivity in daily life using the Leiden Visual Sensitivity Scale and Visual Discomfort Scale. Respondents with CRPS or fibromyalgia reported more visual discomfort than pain-related and pain-free controls while viewing striped patterns and a circle, with no effect of spatial frequency. They reported more pain while viewing a nonreversible square, but not reversible figures (Necker Cube, Duck/Rabbit). Finally, they reported more daily visual sensitivity than pain-related and pain-free controls. Suppressing visual cortical activity might benefit people with CRPS or fibromyalgia

Tactile gap detection deteriorates during bimanual symmetrical movements under mirror visual feedback

It has been suggested that incongruence between signals for motor intention and sensory input can cause pain and other sensory abnormalities. This claim is supported by reports that moving in an environment of induced sensorimotor conflict leads to elevated pain and sensory symptoms in those with certain painful conditions. Similar procedures can lead to reports of anomalous sensations in healthy volunteers too. In the present study, we used mirror visual feedback to investigate the effects of sensorimotor incongruence on responses to stimuli that arise from sources external to the body, in particular, touch. Incongruence between the sensory and motor signals for the right arm was manipulated by having the participants make symmetrical or asymmetrical movements while watching a reflection of their left arm in a parasagittal mirror, or the left hand surface of a similarly positioned opaque board. In contrast to our prediction, sensitivity to the presence of gaps in tactile stimulation of the right forearm was not reduced when participants made asymmetrical movements during mirror visual feedback, as compared to when they made symmetrical or asymmetrical movements with no visual feedback. Instead, sensitivity was reduced when participants made symmetrical movements during mirror visual feedback relative to the other three conditions. We suggest that small discrepancies between sensory and motor information, as they occur during mirror visual feedback with symmetrical movements, can impair tactile processing. In contrast, asymmetrical movements with mirror visual feedback may not impact tactile processing because the larger discrepancies between sensory and motor information may prevent the integration of these sources of information. These results contrast with previous reports of anomalous sensations during exposure to both low and high sensorimotor conflict, but are nevertheless in agreement with a forward model interpretation of perceptual modulations during goal directed movement

Studying the neural bases of prism adaptation using fMRI:a technical and design challenge

Prism adaptation induces rapid recalibration of visuomotor coordination. The neural mechanisms of prism adaptation have come under scrutiny since the observations that the technique can alleviate hemispatial neglect following stroke, and can alter spatial cognition in healthy controls. Relative to non-imaging behavioral studies, fMRI investigations of prism adaptation face several challenges arising from the confined physical environment of the scanner and the supine position of the participants. Any researcher who wishes to administer prism adaptation in an fMRI environment must adjust their procedures enough to enable the experiment to be performed, but not so much that the behavioral task departs too much from true prism adaptation. Furthermore, the specific temporal dynamics of behavioral components of prism adaptation present additional challenges for measuring their neural correlates. We developed a system for measuring the key features of prism adaptation behavior within an fMRI environment. To validate our configuration, we present behavioral (pointing) and head movement data from 11 right-hemisphere lesioned patients and 17 older controls who underwent sham and real prism adaptation in an MRI scanner. Most participants could adapt to prismatic displacement with minimal head movements, and the procedure was well tolerated. We propose recommendations for fMRI studies of prism adaptation based on the design-specific constraints and our results