Karen T. Reilly

Prism adaptation in the healthy brain: The shift in line bisection judgments is long lasting and fluctuates

Rightward prism adaptation has been shown to ameliorate visuospatial biases in right brain-damaged patients with neglect, and a single session of prism adaptation can lead to improvements that last up to several hours. Leftward prism adaptation in neurologically healthy individuals induces neglect-like biases in visuospatial tasks. The duration of these effects in healthy individuals, typically assumed to be ephemeral, has never been investigated. Here we assessed the time-course of the adaptation-induced modifications in a classical perceptual line bisection task that was repeatedly administered for approximately 40min after a single session of adaptation to either a leftward or rightward prismatic deviation. Consistent with previous reports, only adaptation to leftward-deviating prisms induced a visuospatial shift on perceptual line bisection judgments. The typical pattern of pseudoneglect was counteracted by a rightward shift in midline judgments, which became significant between 5 and 10 min after adaptation, fluctuated between being significant or not several times in the 40 min following adaptation, and was present as late as 35 min. In contrast, the sensorimotor aftereffect was present immediately after adaptation to both rightward and leftward deviating prisms, decayed initially then remained stable until 40 min. These results demonstrate that both the sensorimotor and visuospatial effects last for at least 35 min, but that the visuospatial shift needs time to fully develop and fluctuates. By showing that the effects of prism adaptation in the undamaged brain are not ephemeral, these findings reveal the presence of another, so-far neglected dimension in the domain of the cognitive effects induced by prism adaptation, namely time. The prolonged duration of the induced visuospatial shift, previously considered to be a feature of prism adaptation unique to brain-damaged subjects, also applies to the normal brain.

Touch improvement at the hand transfers to the face.

Summary The hand–face border is one of the most prominent features of the primate somatosensory cortex. A reduction of somatosensory input, following amputation or anesthesia, induces perceptual changes across this border that are explained by plastic competitive mechanisms [1–4]. Whether cross-border plasticity can be induced by learning processes relying on increased somatosensory input has been unclear. Here we report that training-independent learning [5] improves tactile perception, not only at the stimulated index finger, but also at the unstimulated face. These findings demonstrate that learning-induced tactile improvement can cross the hand–face border, suggesting that facilitation-based plasticity may operate in the healthy human brain.

Experimental tonic hand pain modulates the corticospinal plasticity induced by a subsequent hand deafferentation

Sensorimotor reorganization is believed to play an important role in the development and maintenance of phantom limb pain, but pain itself might modulate sensorimotor plasticity induced by deafferentation. Clinical and basic research support this idea, as pain prior to amputation increases the risk of developing post-amputation pain. The aim of this study was to examine the influence of experimental tonic cutaneous hand pain on the plasticity induced by temporary ischemic hand deafferentation. Sixteen healthy subjects participated in two experimental sessions (Pain, No Pain) in which transcranial magnetic stimulation was used to assess corticospinal excitability in two forearm muscles (flexor carpi radialis and flexor digitorum superficialis) before (T0, T10, T20, and T40) and after (T60 and T75) inflation of a cuff around the wrist. The cuff was inflated at T45 in both sessions and in the Pain session capsaicin cream was applied on the dorsum of the hand at T5. Corticospinal excitability was significantly greater during the Post-inflation phase (p=0.002) and increased similarly in both muscles (p=0.861). Importantly, the excitability increase in the Post-inflation phase was greater for the Pain than the No-Pain condition (p=0.006). Post-hoc analyses revealed a significant difference between the two conditions during the Post-inflation phase (p=0.030) but no difference during the Pre-inflation phase (p=0.601). In other words, the corticospinal facilitation was greater when pain was present prior to cuff inflation. These results indicate that pain can modulate the plasticity induced by another event, and could partially explain the sensorimotor reorganization often reported in chronic pain populations.

Prism Adaptation Alters Electrophysiological Markers of Attentional Processes in the Healthy Brain.

Neglect patients typically show a rightward attentional orienting bias and a strong disengagement deficit, such that they are especially slow in responding to left-sided targets after right-sided cues (Posner et al., 1984). Prism adaptation (PA) can reduce diverse debilitating neglect symptoms and it has been hypothesized that PAs effects are so generalized that they might be mediated by attentional mechanisms (Pisella et al., 2006; Redding and Wallace, 2006). In neglect patients, performance on spatial attention tasks improves after rightward-deviating PA (Jacquin-Courtois et al., 2013). In contrast, in healthy subjects, although there is evidence that leftward-deviating PA induces neglect-like performance on some visuospatial tasks, behavioral studies of spatial attention tasks have mostly yielded negative results (Morris et al., 2004; Bultitude et al., 2013). We hypothesized that these negative behavioral findings might reflect the limitations of behavioral measures in healthy subjects. Here we exploited the sensitivity of event-related potentials to test the hypothesis that electrophysiological markers of attentional processes in the healthy human brain are affected by PA. Leftward-deviating PA generated asymmetries in attentional orienting (reflected in the cue-locked N1) and in attentional disengagement for invalidly cued left targets (reflected in the target-locked P1). This is the first electrophysiological demonstration that leftward-deviating PA in healthy subjects mimics attentional patterns typically seen in neglect patients. SIGNIFICANCE STATEMENT Prism adaptation (PA) is a promising tool for ameliorating many deficits in neglect patients and inducing neglect-like behavior in healthy subjects. The mechanisms underlying PAs effects are poorly understood but one hypothesis suggests that it acts by modulating attention. To date, however, there has been no successful demonstration of attentional modulation in healthy subjects. We provide the first electrophysiological evidence that PA acts on attention in healthy subjects by mimicking the attentional pattern typically reported in neglect patients: both a rightward attentional orienting bias (reflected in the cue-locked N1) and a deficit in attentional disengagement from the right hemispace (reflected in the target-locked P1). This study makes an important contribution to refining current models of the mechanisms underlying PAs cognitive effects.

Effect of Experimental Cutaneous Hand Pain on Corticospinal Excitability and Short Afferent Inhibition

Sensorimotor integration is altered in people with chronic pain. While there is substantial evidence that pain interferes with neural activity in primary sensory and motor cortices, much less is known about its impact on integrative sensorimotor processes. Here, the short latency afferent inhibition (SAI) paradigm was used to assess sensorimotor integration in the presence and absence of experimental cutaneous heat pain applied to the hand. Ulnar nerve stimulation was combined with transcranial magnetic stimulation to condition motor evoked potentials (MEPs) in the first dorsal interosseous muscle. Four interstimulus intervals (ISI) were tested, based on the latency of the N20 component of the afferent sensory volley (N20−5 ms, N20+2 ms, N20+4 ms, N20+10 ms). In the PAIN condition, MEPs were smaller compared to the NEUTRAL condition (p = 0.005), and were modulated as a function of the ISI (p = 0.012). Post-hoc planned comparisons revealed that MEPs at N20+2 and N20+4 were inhibited compared to unconditioned MEPs. However, the level of inhibition (SAI) was similar in the PAIN and NEUTRAL conditions. This suggests that the interplay between pain and sensorimotor integration is not mediated through direct and rapid pathways as assessed by SAI, but rather might involve higher-order integrative areas.

Somatotopy and temporal dynamics of sensorimotor interactions: evidence from double afferent inhibition

Moving and interacting with the world requires that the sensory and motor systems share information, but while some information about tactile events is preserved during sensorimotor transfer the spatial specificity of this information is unknown. Afferent inhibition (AI) studies, in which corticospinal excitability (CSE) is inhibited when a single tactile stimulus is presented before a transcranial magnetic stimulation pulse over the motor cortex, offer contradictory results regarding the sensory‐to‐motor transfer of spatial information. Here, we combined the techniques of AI and tactile repetition suppression (the decreased neurophysiological response following double stimulation of the same vs. different fingers) to investigate whether topographic information is preserved in the sensory‐to‐motor transfer in humans. We developed a double AI paradigm to examine both spatial (same vs. different finger) and temporal (short vs. long delay) aspects of sensorimotor interactions. Two consecutive electrocutaneous stimuli (separated by either 30 or 125 ms) were delivered to either the same or different fingers on the left hand (i.e. index finger stimulated twice or middle finger stimulated before index finger). Information about which fingers were stimulated was reflected in the size of the motor responses in a time‐constrained manner: CSE was modulated differently by same and different finger stimulation only when the two stimuli were separated by the short delay (P = 0.004). We demonstrate that the well‐known response of the somatosensory cortices following repetitive stimulation is mirrored in the motor cortex and that CSE is modulated as a function of the temporal and spatial relationship between afferent stimuli.

Neuromagnetic correlates of adaptive plasticity across the hand-face border in human primary somatosensory cortex

It is well established that permanent or transient reduction of somatosensory inputs, following hand deafferentation or anesthesia, induces plastic changes across the hand-face border, supposedly responsible for some altered perceptual phenomena such as tactile sensations being referred from the face to the phantom hand. It is also known that transient increase of hand somatosensory inputs, via repetitive somatosensory stimulation (RSS) at a fingertip, induces local somatosensory discriminative improvement accompanied by cortical representational changes in the primary somatosensory cortex (SI). We recently demonstrated that RSS at the tip of the right index finger induces similar training-independent perceptual learning across the hand-face border, improving somatosensory perception at the lips (Muret D, Dinse HR, Macchione S, Urquizar C, Farnè A, Reilly KT.Curr Biol24: R736-R737, 2014). Whether neural plastic changes across the hand-face border accompany such remote and adaptive perceptual plasticity remains unknown. Here we used magnetoencephalography to investigate the electrophysiological correlates underlying RSS-induced behavioral changes across the hand-face border. The results highlight significant changes in dipole location after RSS both for the stimulated finger and for the lips. These findings reveal plastic changes that cross the hand-face border after an increase, instead of a decrease, in somatosensory inputs.

The Pointing Errors in Optic Ataxia Reveal the Role of "Peripheral Magnification" of the PPC.

Interaction with visual objects in the environment requires an accurate correspondence between visual space and its internal representation within the brain. Many clinical conditions involve some impairment in visuo-motor control and the errors created by the lesion of a specific brain region are neither random nor uninformative. Modern approaches to studying the neuropsychology of action require powerful data-driven analyses and error modeling in order to understand the function of the lesioned areas. In the present paper we carried out mixed-effect analyses of the pointing errors of seven optic ataxia patients and seven control subjects. We found that a small parameter set is sufficient to explain the pointing errors produced by unilateral optic ataxia patients. In particular, the extremely stereotypical errors made when pointing toward the contralesional visual field can be fitted by mathematical models similar to those used to model central magnification in cortical or sub-cortical structure(s). Our interpretation is that visual areas that contain this footprint of central magnification guide pointing movements when the posterior parietal cortex (PPC) is damaged and that the functional role of the PPC is to actively compensate for the under-representation of peripheral vision that accompanies central magnification. Optic ataxia misreaching reveals what would be hand movement accuracy and precision if the human motor system did not include elaborated corrective processes for reaching and grasping to non-foveated targets.

Adaptation to Leftward Shifting Prisms Alters Motor Interhemispheric Inhibition.

Adaptation to rightward shifting prisms (rightward prism adaptation, RPA) ameliorates neglect symptoms in patients while adaptation to leftward shifting prisms (leftward prism adaptation, LPA) induces neglect-like behaviors in healthy subjects. It has been hypothesized that prism adaptation (PA) modulates interhemispheric balance between the parietal cortices by inhibiting the posterior parietal cortex (PPC) contralateral to the prismatic deviation, but PAs effects on interhemispheric inhibition (IHI) have not been directly investigated. Since there are hyper-excitable connections between the PPC and primary motor cortex (M1) in the left hemisphere of neglect patients, we reasoned that LPA might mimic right hemisphere lesions by reducing parietal IHI, hyper-exciting the left PPC and PPC-M1 connections, and in turn altering IHI at the motor level. Namely, we hypothesized that LPA would increase IHI from the left to the right M1. We examined changes in left-to-right and right-to-left IHI between the 2 M1s using the ipsilateral silent period (iSP) (Meyer et al. 1995) before and after either LPA or RPA. The iSP was significantly longer after LPA but only from left-to-right and it did not change at all after RPA. This is the first physiological demonstration that LPA alters IHI in the healthy brain.

The hands have it: Hand specific vision of touch enhances touch perception and somatosensory evoked potential

Our ability to accurately discriminate information from one sensory modality is often influenced by information from the other senses. Previous research indicates that tactile perception on the hand may be enhanced if participants look at a hand (compared to a neutral object) and if visual information about the origin of touch conveys temporal and/or spatial congruency. The current experiment further assessed the effects of non-informative vision on tactile perception. Participants made speeded discrimination responses (digit 2 or digit 5 of their right hand) to supra-threshold electro-cutaneous stimulation while viewing a video showing a pointer, in a static position or moving (dynamic), towards the same or different digit of a hand or to the corresponding spatial location on a non-corporeal object (engine). Therefore, besides manipulating whether a visual contact was spatially congruent to the simultaneously felt touch, we also manipulated the nature of the recipient object (hand vs. engine). Behaviourally, the temporal cues provided by the dynamic visual information about an upcoming touch decreased reaction times. Additionally, a greater enhancement in tactile discrimination was present when participants viewed a spatially congruent contact compared to a spatially incongruent contact. Most importantly, this visually driven improvement was greater for the view-hand condition compared to the view-object condition. Spatially-congruent, hand-specific visual events also produced the greatest amplitude in the P50 somatosensory evoked potential (SEP). We conclude that tactile perception is enhanced when vision provides non-predictive spatio-temporal cues and that these effects are specifically enhanced when viewing a hand.