Effects of prism adaptation and visual scanning training on perceptual and response bias in unilateral spatial neglect.

In some patients with unilateral spatial neglect, symptoms reflect impaired lateralized spatial attention and representation (perceptual bias) whereas in others the inability to respond to stimuli located in contralesional space (response bias). Here, we investigated whether prismatic adaptation (PA) and visual scanning training (VST) differentially affect perceptual and response bias and whether rehabilitation outcome depends on the type of bias underlying symptoms. Two groups of neglect patients in the subacute phase were evaluated before, immediately after, and two weeks following 10 days of PA (n = 9) or VST (n = 9). Standard neuropsychological tests (i.e., Behavioural Inattentional Test, Diller cancellation test, and Line Bisection test) were administered to assess neglect symptoms, while the Landmark task was used to disentangle perceptual and response biases. Performance on the Landmark task revealed that PA was more effective in improving the perceptual bias, while VST mainly modulated the response bias. Neuropsychological tests performance suggested that VST is better suited to modulate neglect in patients with response bias, while PA may be effective in patients with both types of bias. These findings may offer novel insights into the efficacy of PA and VST in the rehabilitation of perceptual and response biases in patients with neglect.

Self-other distinction modulates the social softness illusion.

The social softness illusion (i.e., the tendency to perceive another person's skin as softer than our own) is thought to promote the sharing of social-emotional experiences because of the rewarding properties of receiving and giving social affective touch. Here we investigated whether the ability to distinguish someone else's body from our own modulates the social softness illusion. In particular, we tested whether the spatial perspective taken by the participants and seeing or not the touched arms could alter this illusion. Pairs of female participants were assigned the roles of either the giver (i.e., delivering the touches) or the receiver (i.e., being touched). We manipulated the location of the touch (palm or forearm), the spatial perspective of the receiver's body with respect to the giver's body (egocentric or allocentric perspective), and the vision of the touched body part (the giver could either see both her own and the receiver's body part, or she was blindfolded). Consistently with previous findings, the skin of another person was perceived as softer than the own one. Additionally, the illusion was present for both the forearm and the palm, and it was stronger in allocentric compared to the egocentric perspective (i.e., when the self-other distinction was clearer). These findings show that the mechanisms underpinning the ability to represent another person's body as distinct from our own modulates the social softness illusion, and thus support the role of the social softness illusion in fostering social relationships.

Callosal anisotropy predicts attentional network changes after parietal inhibitory stimulation.

Hemispatial neglect is thought to result from disruption of interhemispheric equilibrium. Right hemisphere lesions deactivate the right frontoparietal network and hyperactivate the left via release from interhemispheric inhibition. Support for this putative mechanism comes from neuropsychological evidence as well as transcranial magnetic stimulation (TMS) studies in healthy subjects, in whom right posterior parietal cortex (PPC) inhibition causes neglect-like, rightward, visuospatial bias. Concurrent TMS and fMRI after right PPC TMS show task-dependent changes but may fail to identify effects of stimulation in areas not directly activated by the specific task, complicating interpretations. We used resting-state functional connectivity (RSFC) after inhibitory TMS over the right PPC to examine changes in the networks underlying visuospatial attention and used diffusion-weighted imaging to measure the structural properties of relevant white matter pathways. In a crossover experiment in healthy individuals, we delivered continuous theta burst TMS to the right PPC and vertex as control condition. We hypothesized that PPC inhibitory stimulation would result in a rightward visuospatial bias, decrease frontoparietal RSFC, and increase the PPC RSFC with the attentional network in the left hemisphere. We also expected that individual differences in fractional anisotropy (FA) of the frontoparietal network and the callosal pathway between the PPCs would account for variability of the TMS-induced RSFC changes. As hypothesized, TMS over the right PPC caused a rightward shift in line bisection judgment and increased RSFC between the right PPC and the left superior temporal gyrus. This effect was inversely related to FA in the posterior corpus callosum. Local inhibition of the right PPC reshapes connectivity in the attentional network and depends significantly on interhemispheric connections.

Prism Adaptation Modulates Connectivity of the Intraparietal Sulcus with Multiple Brain Networks.

Prism adaptation (PA) alters spatial cognition according to the direction of visual displacement by temporarily modifying sensorimotor mapping. Right-shifting prisms (right PA) improve neglect of left visual field in patients, possibly by decreasing activity in the left hemisphere and increasing it in the right. Left PA shifts attention rightward in healthy individuals by an opposite mechanism. However, functional imaging studies of PA are inconsistent, perhaps because of differing activation tasks. We measured resting-state functional connectivity (RSFC) in healthy individuals before and after PA. When contrasted, right versus left PA decreased RSFC in the spatial navigation network defined by the right posterior parietal cortex (PPC), hippocampus, and cerebellum. Within-PA-direction comparisons showed that right PA increased RSFC in subregions of the PPCs and between the PPCs and the right middle frontal gyrus and left PA decreased RSFC between these regions. Both right and left PA decreased RSFC between the PPCs and bilateral temporal areas. In summary, right PA increases connectivity in the right frontoparietal network and left PA produces essentially opposite effects. Furthermore, right, compared with left, PA modulates RSFC in the right hemisphere navigation network.

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 PA's 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.

Paired-Pulse Parietal-Motor Stimulation Differentially Modulates Corticospinal Excitability across Hemispheres When Combined with Prism Adaptation.

Rightward prism adaptation ameliorates neglect symptoms while leftward prism adaptation (LPA) induces neglect-like biases in healthy individuals. Similarly, inhibitory repetitive transcranial magnetic stimulation (rTMS) on the right posterior parietal cortex (PPC) induces neglect-like behavior, whereas on the left PPC it ameliorates neglect symptoms and normalizes hyperexcitability of left hemisphere parietal-motor (PPC-M1) connectivity. Based on this analogy we hypothesized that LPA increases PPC-M1 excitability in the left hemisphere and decreases it in the right one. In an attempt to shed some light on the mechanisms underlying LPA's effects on cognition, we investigated this hypothesis in healthy individuals measuring PPC-M1 excitability with dual-site paired-pulse TMS (ppTMS). We found a left hemisphere increase and a right hemisphere decrease in the amplitude of motor evoked potentials elicited by paired as well as single pulses on M1. While this could indicate that LPA biases interhemispheric connectivity, it contradicts previous evidence that M1-only MEPs are unchanged after LPA. A control experiment showed that input-output curves were not affected by LPA per se. We conclude that LPA combined with ppTMS on PPC-M1 differentially alters the excitability of the left and right M1.

Areas of Brain Damage Underlying Increased Reports of Behavioral Disinhibition.

Disinhibition, the inability to inhibit inappropriate behavior, is seen in frontal-temporal degeneration, Alzheimer's disease, and stroke. Behavioral disinhibition leads to social and emotional impairments, including impulsive behavior and disregard for social conventions. The authors investigated the effects of lesions on behavioral disinhibition measured by the Neuropsychiatric Inventory in 177 veterans with traumatic brain injuries. The authors performed voxel-based lesion-symptom mapping using MEDx. Damage in the frontal and temporal lobes, gyrus rectus, and insula was associated with greater behavioral disinhibition, providing further evidence of the frontal lobe's involvement in behavioral inhibition and suggesting that these regions are necessary to inhibit improper behavior.

Isolated theory of mind deficits and risk for frontotemporal dementia: a longitudinal pilot study.

OBJECTIVE: Recent data suggest that theory of mind (ToM) deficits represent an early symptom of the behavioural variant of frontotemporal dementia (bvFTD). However, longitudinal data on the natural history of subjects presenting with isolated ToM deficits are lacking. The aim of the study was to verify if isolated ToM deficits represent an at-risk state for prefrontal dysfunction and bvFTD. METHODS: A population of healthy subjects (n=4150, age range: 50-60 years) completed a clinical and neuropsychological evaluation including the Reading the Mind in the Eyes Test (RMET), a widely used ToM task. From this group, we recruited a low-RMET group (n=83) including subjects with RMET scores lower than 2 SDs but an otherwise normal neuropsychological evaluation and a control group. All subjects underwent evaluation at baseline and after 2 years. RESULTS: Subjects in the low-RMET group showed decline in prefrontal functions at follow-up. Moreover, at follow-up 12 subjects in the low-RMET group presented with findings suggestive of bvFTD. Neuropsychological performance was stable in the control group. CONCLUSIONS: Our data suggest that isolated ToM deficits could represent an at-risk situation for the development of future prefrontal dysfunction and bvFTD. ToM evaluation should be included in neuropsychological protocols aimed to evaluate the early phases of dementia.

Hedonic and autonomic responses in promoting affective touch.

Interpersonal touch is intrinsically reciprocal since it entails a person promoting and another receiving the touch. While several studies have investigated the beneficial effects of receiving affective touch, the affective experience of caressing another individual remains largely unknown. Here, we investigated the hedonic and autonomic responses (skin conductance and heart rate) in the person promoting affective touch. We also examined whether interpersonal relationship, gender, and eye contact modulate these responses. As expected, caressing the partner was perceived as more pleasant than caressing a stranger, especially if the affective touch occurred together with mutual eye contact. Promoting affective touch to the partner also resulted in a decrease of both autonomic responses and anxiety levels, suggesting the occurrence of a calming effect. Additionally, these effects were more pronounced in females compared to males, indicating that hedonic and autonomic aspects of affective touch are modulated by both social relationship and gender. These findings show for the first time that caressing a beloved one is not only pleasant but also reduces autonomic responses and anxiety in the person promoting the touch. This might suggest that affective touch has an instrumental role for romantic partners in promoting and reinforcing their affective bonding.

Beyond alpha-band: The neural correlate of creative thinking.

The compound nature of creativity entails the interplay of multiple cognitive processes, making it difficult to attribute creativity to a single neural signature. Divergent thinking paradigms, widely adopted to investigate creative production, have highlighted the key role of specific mental operations subserving creativity, such as inhibition of external stimuli, loose semantic associations, and mental imagery. Neurophysiological studies have typically shown a high alpha rhythm synchronization when individuals are engaged in creative ideation. Also, oculomotor activity and pupil diameter have been proposed as useful indicators of mental operations involved in such a thinking process. The goal of this study was to investigate whether beyond alpha-band activity other higher frequency bands, such as beta and gamma, may subserve divergent and convergent thinking and whether those could be associated with a different gaze bias and pupil response during ideas generation. Implementing a within-subjects design we collected behavioral measures, neural activity, gaze patterns, and pupil dilation while participants performed a revised version of the Alternative Uses Task, in which divergent thinking is contrasted to convergent thinking. As expected, participants took longer to generate creative ideas as compared to common ones. Interestingly, during divergent thinking participants displayed alpha synchronization along with beta and gamma desynchronization, more pronounced leftward gaze shift, and greater pupil dilation. During convergent thinking, an opposite pattern was observed: desynchronization in alpha and an increase in beta and gamma rhythm, along with a reduction of leftward gaze shift and greater pupil constriction. The present study uncovered specific neural dynamics and physiological patterns during idea generation, providing novel insight into the complex physiological signature of creative production.

Effective connectivity underlying neural and behavioral components of prism adaptation.

Prism adaptation (PA) is a form of visuomotor training that produces both sensorimotor and cognitive aftereffects depending on the direction of the visual displacement. Recently, a neural framework explaining both types of PA-induced aftereffects has been proposed, but direct evidence for it is lacking. We employed Structural Equation Modeling (SEM), a form of effective connectivity analysis, to establish directionality among connected nodes of the brain network thought to subserve PA. The findings reveal two distinct network branches: (1) a loop involving connections from the parietal cortices to the right parahippocampal gyrus, and (2) a branch linking the lateral premotor cortex to the parahippocampal gyrus via the cerebellum. Like the sensorimotor aftereffects, the first branch exhibited qualitatively different modulations for left versus right PA, and critically, changes in these connections were correlated with the magnitude of the sensorimotor aftereffects. Like the cognitive aftereffects, changes in the second branch were qualitatively similar for left and right PA, with greater change for left PA and a trend correlation with cognitive aftereffects. These results provide direct evidence that PA is supported by two functionally distinct subnetworks, a parietal-temporal network responsible for sensorimotor aftereffects and a fronto-cerebellar network responsible for cognitive aftereffects.

Severity of unilateral spatial neglect is an independent predictor of functional outcome after acute inpatient rehabilitation in individuals with right hemispheric stroke.

OBJECTIVE: To investigate the relationship between severity of unilateral spatial neglect (USN) and functional recovery in activities of daily living after a right-hemisphere stroke. DESIGN: Observational study. SETTING: Rehabilitation hospital in Italy. PARTICIPANTS: We investigated 107 of 131 inpatients with right-hemisphere stroke who were consecutively admitted to our rehabilitation hospital. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: To assess USN severity, conventional and nonconventional Behavioral Inattention Tests (BITs) were performed at admission to inpatient rehabilitation at a median of 19 days after stroke occurrence. FIM was performed both on admission to and discharge from inpatient rehabilitation to assess functional autonomy. FIM efficiency (improvement of FIM score per day of stay length) and FIM effectiveness (proportion of potential improvement achieved) were calculated. RESULTS: Fifty-four (50.5%) of the 107 patients were affected by USN. In these 54 patients, both conventional and nonconventional BIT scores were significantly correlated with FIM scores assessed at discharge from rehabilitation: ρ values were .385 (P=.004) and .396 (P=.003), respectively. After adjustment for 7 potential confounders, including FIM scores before rehabilitation, we found a significant positive association between either conventional or nonconventional BIT scores and FIM scores after rehabilitation (r=.276, P=.047 and r=.296, P=.033, respectively), FIM efficiency (r=.315, P=.022 and r=.307, P=.025, respectively), and FIM effectiveness (r=.371, P=.006 and r=.306, P=.026, respectively). CONCLUSIONS: Data support the independent prognostic role of USN severity assessed at admission to inpatient rehabilitation after a right-hemisphere stroke. Models aimed at predicting the functional outcome in stroke survivors may benefit from inclusion of USN severity.

Changing your body changes your eating attitudes: embodiment of a slim virtual avatar induces avoidance of high-calorie food.

The virtual-reality full-body illusion paradigm has been suggested to not only trigger the illusory ownership of the avatar's body but also the attitudinal and behavioral components stereotypically associated to that kind of virtual body. In the present study, we investigated whether this was true for stereotypes related to body size: body satisfaction and eating control behavior. Healthy participants underwent the full-body illusion paradigm with an avatar having either a larger or a slimmer body than their own, and were assessed for implicit attitudes towards body image and food calorie content at baseline and after each full-body illusion session. Results showed that the illusion emerged regardless of the avatar's body size, whereas the perceived dimension of the own body size changed according to the avatar's body size (i.e., participants felt to be slimmer after embodying their slim avatar and larger after embodying their large avatar). Crucially, we found that implicit attitudes towards food, but not those towards one's own body, were modulated by the size of the virtual body. Compared to baseline, ownership of a slimmer avatar increased the avoidance of high-calorie food, whereas ownership of a larger avatar did not induce changes. Our findings suggest that the illusory feeling of being slimmer drives also the food-related stereotypes associated with that body size, increasing the regulation of eating behaviors.

Left-shifting prism adaptation boosts reward-based learning.

Visuospatial cognition has an inherent lateralized bias. Individual differences in the direction and magnitude of this bias are associated with asymmetrical D2/3 dopamine binding and dopamine system genotypes. Dopamine level affects feedback-based learning and dopamine signaling asymmetry is related to differential learning from reward and punishment. High D2 binding in the left hemisphere is associated with preference for reward. Prism adaptation (PA) is a simple sensorimotor technique, which modulates visuospatial bias according to the direction of the deviation. Left-deviating prism adaptation (LPA) induces rightward bias in healthy subjects. It is therefore possible that the right side of space increases in saliency along with left hemisphere dopaminergic activity. Right-deviating prism adaptation (RPA) has been used mainly as a control condition because it does not modulate behavior in healthy individuals. Since LPA induces a rightward visuospatial bias as a result of left hemisphere modulation, and higher dopaminergic activity in the left hemisphere is associated with preference for rewarding events we hypothesized that LPA would increase the preference for learning with reward. Healthy volunteers performed a computer-based probabilistic classification task before and after LPA or RPA. Consistent with our predictions, PA altered the preference for rewarded versus punished learning, with the LPA group exhibiting increased learning from reward. These results suggest that PA modulates dopaminergic activity in a lateralized fashion.

The asymmetrical effect of leftward and rightward prisms on intact visuospatial cognition.

Rightward prismatic adaptation (RPA) can reduce neglect symptoms in patients whereas adaptation to leftward deviating prisms (LPA) can induce neglect-like behavior in healthy subjects. One influential anatomo-functional model of prismatic adaptation (PA) postulates that it inhibits activity of the posterior parietal cortex (PPC) contralateral to the prismatic deviation. By hypo-activating the PPC and thus eventually acting on interhemispheric balance, both LPA and RPA could possibly affect visuospatial perception in healthy subjects, however, such behavioral modulation has seldom been reported after RPA. In the light of recent evidence showing that LPA-induced visuospatial shift need time to develop we hypothesized that RPA might induce significant changes in visuospatial cognition on a longer time scale. We thus assessed the Landmark task, as well as sensorimotor aftereffects, several times over 8 h after a single session of either LPA or RPA. In agreement with previous reports, sensorimotor effects were symmetrical and long-lasting, with both LPA and RPA inducing shifts of comparable amplitudes in the direction opposite to the deviation that lasted up to 8 h. Visuospatial cognition assessed by Landmark performance, was also significantly modulated for up to 8 h, but only after LPA. Interestingly, the timing and direction of this modulation differed according to participants' baseline bias. An initial leftward bias led to a rapid, but short-lasting rightward shift, whereas an initial rightward bias led to a slower-developing and longer-lasting leftward shift. These findings shed new light on a so-far relatively overlooked feature of spatial cognition that may interact with the effect of PA: the state of the visuospatial system prior to PA should be taken into account when attempting to understand and modulate visuospatial cognition in healthy and brain-damaged populations. This highlights the need for refining current models of PA's mechanisms of action.

Motor cortex inhibition by TMS reduces cognitive non-motor procedural learning when immediate incentives are present.

Inhibitory repetitive transcranial magnetic stimulation (rTMS) of the primary motor area (M1) impairs motor sequence-learning, but not basic motor function. It is unknown if this is specific for motor forms of procedural learning or a more general effect. To investigate, we tested the effect of M1-inhibition on the weather prediction task (WPT), a learning task with minimal motor learning component. In the WPT, participants learn arbitrary, probabilistic, associations between sets of meaningless cues and fictional outcomes. In our "Feedback" (FB) condition, they received monetary rewards/punishments during learning. In the "paired associate" (PA) condition they learned the same information by passive observation of associations. The observational and feedback learning conditions were matched for their non-learning-specific motor demands. In each of two FB or PA sessions, we delivered Real (inhibitory) or Sham continuous theta-burst (cTBS) to the left-M1, before 150 training-trials. We then tested learning with 42 trials without feedback immediately after learning and again 1-h after cTBS. Compared to Sham, Real cTBS reduced performance during FB-learning, when learning was immediately reinforced, but not when knowledge was tested after PA learning. Furthermore, when FB-based memory was tested after learning without immediate incentive, there was no effect of TMS compared to post-PA test performance, showing the TMS effect operated only in the presence of incentive and feedback. We conclude that M1 is a node in a network underlying feedback-driven procedural learning and inhibitory rTMS there results in decreased network efficiency.

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.

The left inferior frontal gyrus is crucial for reading the mind in the eyes: brain lesion evidence.

Deficit in the ability to understand and predict the mental states of others is one of the central features of traumatic brain injury (TBI), leading to problems in social-daily life such as social withdrawal and the inability to maintain work or family relationships. Although several functional neuroimaging studies have identified a widely distributed brain network involved in the Reading the Mind in the Eyes Test (RMET), the necessary brain regions engaged in this capacity are still heavily debated. In this study, we combined the RMET with a whole-brain voxel-based lesion symptom mapping (VLSM) approach to identify brain regions necessary for adequate RMET performance in a large sample of patients with penetrating TBI (pTBI). Our results revealed that pTBI patients performed worse on the RMET compared to non-head injured controls, and impaired RMET performance was associated with lesions in the left inferior frontal gyrus (IFG). Our findings suggest that the left IFG is a key region in reading the mind in the eyes, probably involved in a more general impairment of a semantic working memory system that facilitates reasoning about what others are feeling and thinking as expressed by the eyes.

Object and space perception - is it a matter of hemisphere?

In the 1980s, following Newcombe's observations, Ungerleider and Mishkin put forward the functional subdivision of the visual system into a ventral stream dedicated to object perception and a dorsal stream dedicated to space perception. Ten years after this discovery, the perception-action model re-defined the dorsal stream as responsible for non-conscious visual guidance, and most recently a tripartition has been suggested to account for a variety of visuospatial functions. Here, we investigated the neural underpinnings of object and space perception by combining the administration of the Visual Object Space Perception (VOSP) battery with a voxel-based lesion symptom mapping (VLSM) approach in a large sample of patients with penetrating traumatic brain injury (pTBI). First, our results provided new support for the complementary role of both hemispheres in object recognition. The right lateral occipital complex was found to be critical in early perceptual discrimination, whereas more anterior temporal and frontal regions in the left hemisphere were found to be critical in more complex forms of object discrimination and recognition. Second, our findings confirmed that space perception depended on the integrity of the right inferior parietal lobule (IPL) and revealed that a network linking the right IPL with the right premotor cortex was critical for the perception of spatial relationships in both 2D and 3D representations. Taken together, our results supported the functional subdivision of the visual system and shed new light on the specific processes involved along both the dorsal and the ventral streams.