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Vocabulary acquisition is such a major aspect of language learning in children, but also in adults when learning a foreign language, that a dedicated vocabulary learning device may exist within the language organ. To identify the relevant brain systems, we performed regional cerebral blood flow measurements in normal subjects while they were learning a list of neologisms or a list of word-nonwords pairs. Structures implicated in phonological short-term memory (Broca's area, left temporo-parietal junction) were steadily activated during nonwords learning, while the left temporal lobe neocortical and paralimbic structures (parahippocampal region), associated with long-term memory, contributed to learning in a time-dependent manner, with maximal activation at the beginning of the process. The neural system specifically activated when learning new vocabulary was strongly lateralized to the left hemisphere. This evidence refines current models of memory function and supports theories which emphasise the importance of phonological competence in hemispheric dominance for language.

BACKGROUND: Left caloric vestibular stimulation (CVS) transiently reduces impairments of right-brain-damaged patients with left unilateral neglect, including left hemianesthesia, contralateral to the side of the lesion (contralesional). Conversely, no effect on right contralesional hemianesthesia in left-brain-damaged patients is seen with right CVS. This discrepancy is unexplained. METHODS: The authors explored the effect of CVS on right- and left-brain-damaged patients with hemianesthesia. One left-brain-damaged patient had an fMRI study during tactile stimulation before and after left CVS. The same fMRI touch study, without CVS, was performed in neurologically unimpaired subjects. RESULTS: A transient remission of right hemianesthesia associated with left brain damage was observed, provided that cold CVS was administered to the left ear. In the left-brain-damaged patient studied with fMRI, left CVS modulated the neural response to right hand tactile stimuli of a portion of the secondary somatosensory area (SII) of the right hemisphere. In neurologically unimpaired subjects, fMRI scans showed that the same part of area SII in the right hemisphere was activated by ipsilateral right-sided touches and to a larger extent than area SII in the left hemisphere by left-sided touches. CONCLUSIONS: Left caloric vestibular stimulation is effective on both left and right hemianesthesia because it modulates the hemisphere that has a more complete representation of, or is capable to attend to, the whole somatosensory surface of the body. These results suggest a hardwired hemispheric asymmetry in hand representation, starting from a somatotopically organized brain region such as area SII.

This study investigated the dissociation between reading aloud and lexical decision in six Italian right-brain-damaged patients with left neglect dyslexia. Patients were requested to perform two tasks: (a) Reading aloud and lexical decision on monomorphemic words of different frequencies and nonwords with different degrees of similarity to real words (Experiment 1); (b) Reading aloud and lexical decision on morphologically complex (suffixed) derived words and morphologically complex (suffixed) nonwords (Experiment 2). The patients’ performance on lexical decision was compared to that of a group of matched control subjects. Patients showed left neglect dyslexia in the reading aloud task, but had a normal level of performance in the lexical decision task. Furthermore, patients were affected by the same morpho-lexical variables that influence lexical decision in normal subjects, suggesting a largely preserved morpho-lexical-processing of written letter strings, as assessed by the task of lexical decision. The mechanisms underlying the preservation of lexical decision in patients with left neglect dyslexia are discussed in the light of dual route models of reading.

Regional cerebral perfusion was evaluated by single photon emission computed tomography (SPECT) using technetium-99m hexamethylpropyleneamine oxime ([99mTc]HM-PAO) in sixteen patients with Alzheimer's disease (AD) in early clinical phase and in 16 healthy elderly controls. In all patients transmission computed tomography (TCT) and/or magnetic resonance imaging (MRI) did not show focal brain abnormalities. Relative to normal subjects, AD patients showed significant reductions in cortical/cerebellar activity ratio: cortical perfusion was globally depressed with the largest reductions in frontal and posterior temporo-parietal cortices. Asymmetries of relative perfusion between cerebral hemispheres were also demonstrated when language was affected or visuospatial functions were unevenly impaired. In patients with early AD, SPECT provides functional information to be compared with clinical and psychometric data.

Multisensory processing can be assessed by measuring susceptibility to crossmodal illusions such as the Sound-Induced Flash Illusion (SIFI). When a single flash is accompanied by 2 or more beeps, it is perceived as multiple flashes (fission illusion); conversely, a fusion illusion is experienced when more flashes are matched with a single beep, leading to the perception of a single flash. Such illusory perceptions are associated to crossmodal changes in visual cortical excitability. Indeed, increasing occipital cortical excitability, by means of transcranial electrical currents, disrupts the SIFI (ie, fission illusion). Similarly, a reduced fission illusion was shown in patients with episodic migraine, especially during the attack, in agreement with the pathophysiological model of cortical hyperexcitability of this disease. If episodic migraine patients present with reduced SIFI especially during the attack, we hypothesize that chronic migraine (CM) patients should consistently report less illusory effects than healthy controls; drugs intake could also affect SIFI. On such a basis, we studied the proneness to SIFI in CM patients (n = 63), including 52 patients with Medication Overuse Headache (MOH), compared to 24 healthy controls. All migraine patients showed reduced fission phenomena than controls (P

Objective: Sound-induced flash illusions depend on visual cortical excitability. In this study, we explored whether sound-induced flash illusions are perceived differently in migraine, a condition associated with pathologic cortical hyperexcitability. Methods: Sound-induced flash illusions were examined in 59 migraine patients (mean age = 32 ± 16 years; 36 females), 32 without aura and 27 with aura, and in 24 healthy controls (mean age = 42 ± 17 years; 16 females). Patients were studied during attacks and interictally. Visual stimuli (flashes) accompanied by sounds (beeps) were presented in different combinations: a single flash with multiple beeps was given to induce the perception of multiple flashes (“fission” illusion), and multiple flashes with a single beep were used to reduce the number of perceived flashes (“fusion” illusion). Results: For migraineurs, the fission illusion was reduced, especially during the attack, and almost abolished when a single flash was combined with 2 beeps (except for those without aura tested interictally); the fusion illusion was less consistently reported in both migraine groups, but not completely disrupted. Conclusions: Results from this study add novel clues to our understanding of visual cortex hyperexcitability in migraine, especially migraine with aura. Furthermore, these analyses underscore how pathologic changes in cortical excitability affect multisensory interactions. Cross-modal illusions represent a valid tool for exploration of functional connectivity between sensory areas, which likely has an important role in the pathophysiology of migraine.

Recent neuropsychological evidence suggests that acquired brain lesions can, in some instances, abolish the ability to integrate inputs from different sensory modalities, disrupting multisensory perception. We explored the ability to perceive multisensory events, in particular the integrity of audio-visual processing in the temporal domain, in brain-damaged patients with visual field defects (VFD), or with unilateral spatial neglect (USN), by assessing their sensitivity to the 'Sound-Induced Flash Illusion' (SIFI). The study yielded two key findings. Firstly, the 'fission' illusion (namely, seeing multiple flashes when a single flash is paired with multiple sounds) is reduced in both left- and right-brain-damaged patients with VFD, but not in right-brain-damaged patients with left USN. The disruption of the fission illusion is proportional to the extent of the occipital damage. Secondly, a reliable 'fusion' illusion (namely, seeing less flashes when a single sound is paired with multiple flashes) is evoked in USN patients, but neither in VFD patients nor in healthy participants. A control experiment showed that the fusion, but not the fission, illusion is lost in older participants (>50 year-old), as compared with younger healthy participants (

Recent anatomo-clinical correlation studies have extended to the superior temporal gyrus, the right hemisphere lesion sites associated with the left unilateral spatial neglect, in addition to the traditional posterior-inferior-parietal localization of the responsible lesion (supramarginal gyrus, at the temporo-parietal junction). The study aimed at teasing apart, by means of repetitive transcranial magnetic stimulation (rTMS), the contribution of the inferior parietal lobule (angular gyrus versus supramarginal gyrus) and of the superior temporal gyrus of the right hemisphere, in making judgments about the mid-point of a horizontal line, a widely used task for detecting and investigating spatial neglect. rTMS trains at 25 Hz frequency were delivered over the inferior parietal lobule (angular gyrus and supramarginal gyrus), the superior temporal gyrus and the anterior parietal lobe of the right hemisphere, in 10 neurologically unimpaired participants, performing a line bisection judgment task. rTMS of the inferior parietal lobule at the level of the supramarginal gyrus brought about a rightward error in the bisection judgment, ipsilateral to the side of the rTMS, with stimulation over the other sites being ineffective. The neural correlates of computing the mid-point of a horizontal segment include the right supramarginal gyrus in the inferior parietal lobule and do not extend to the angular gyrus and the superior temporal gyrus. These rTMS data in unimpaired subjects constrain the evidence from lesion studies in brain-damaged patients, emphasizing the major role of a subset of relevant regions.

Motor learning interacts with and shapes experience-dependent cerebral plasticity. In stroke patients with paresis of the upper limb, motor recovery was proposed to reflect a process of re-learning the lost/impaired skill, which interacts with rehabilitation. However, to what extent stroke patients with hemiparesis may retain the ability of learning with their affected limb remains an unsolved issue, that was addressed by this study. Nineteen patients, with a cerebrovascular lesion affecting the right or the left hemisphere, underwent an explicit motor learning task (finger tapping task, FTT), which was performed with the paretic hand. Eighteen age-matched healthy participants served as controls. Motor performance was assessed during the learning phase (i.e., online learning), as well as immediately at the end of practice, and after 90 min and 24 h (i.e., retention). Results show that overall, as compared to the control group, stroke patients, regardless of the side (left/right) of the hemispheric lesion, do not show a reliable practice-dependent improvement; consequently, no retention could be detected in the long-term (after 90 min and 24 h). The motor learning impairment was associated with subcortical damage, predominantly affecting the basal ganglia; conversely, it was not associated with age, time elapsed from stroke, severity of upper-limb motor and sensory deficits, and the general neurological condition. This evidence expands our understanding regarding the potential of post-stroke motor recovery through motor practice, suggesting a potential key role of basal ganglia, not only in implicit motor learning as previously pointed out, but also in explicit finger tapping motor tasks.

A 2-[18F]-Fluoro-2-Deoxy- D -Glucose ([18F]FDG) and positron emission tomography (PET) study was performed in the acute and chronic phase of stroke in one patient with unilateral neglect due to a right hemispheric lesion. In the acute phase, severe neglect, as well as hypometabolism in both the right and in the left unaffected cerebral hemisphere, was demonstrated. At follow-up evaluation the patient showed an almost complete recovery fromunilateral neglect. This was associated with a return of left hemisphere metabolism to normal values and partial metabolic recovery in the right hemisphere, where frontal and parietal areas remained functionally impaired. Another patient with an extensive right cerebral ischaemic lesion on CT and severe unilateral neglect was studied by PET in chronic phase. A severe metabolic depression in the left unaffected hemisphere and in the right cerebral areas spared by the lesion, was found. These data suggest that the remission of unilateral neglect might be associated to a functional metabolic recovery in both the undamaged left hemisphere and the unaffected regions of the right hemisphere.

Unilateral spatial neglect is a neuropsychological syndrome commonly observed after stroke and defined by the inability to attend or respond to contralesional stimuli. Typically, symptoms are assessed using clinical tests that rely upon visual/perceptual abilities. However, neglect may affect high-level representations controlling attention in other modalities as well. Here we developed a novel manual exploration test using a touch screen computer to quantify spatial search behaviour without visual input. Twelve chronic stroke patients with left neglect and 27 patients without neglect (based on clinical tests) completed our task. Four of the 12 "neglect" patients exhibited clear signs of neglect on our task as compared to "non-neglect" patients and healthy controls, and six other patients (from both groups) also demonstrated signs of neglect compared to healthy controls only. While some patients made asymmetrical responses on only one task, generally, patients with the strongest neglect performed poorly on multiple tasks. This suggests that representations associated with different modalities may be affected separately, but that severe forms of neglect are more likely related to damage in a common underlying representation. Our manual exploration task is easy to administer and can be added to standard neglect screenings to better measure symptom severity.

Background and purpose: Neuromodulation is a promising approach to increasing motor recovery in stroke; however, to date, there is a scarcity of evidence documenting the clinical potential of transcranial direct current stimulation (tDCS) administered in the acute phase of stroke. The present study aims to examine the clinical effects of a treatment involving the application of tDCS in the acute stage post-stroke. Methods: This was a randomized, double-blind, sham-controlled trial. A cohort of 32 stroke patients with severe motor impairment underwent 5 days of treatment with real or sham bi-hemispheric tDCS over the motor cortex. During the treatment, tDCS was applied twice per day (two daily applications each of 15 min), starting 48 to 72 h after stroke onset. Results: We found statistically significant improvements after both real and sham tDCS treatments in primary (hand grip strength, Motricity Index) and secondary (National Institutes of Health Stroke Scale score, Barthel Index) outcomes. Patients receiving real tDCS showed a larger improvement of upper-limb muscle strength at the end of treatment phase; this advantage was no longer present after 6 months. Conclusions: Transcranial direct current stimulation may be used to accelerate the rate of upper-limb motor recovery during the spontaneous recovery period.

Human amnesia is a clinical syndrome exhibiting the failure to recall past events and to learn new information. Its “pure” form, characterized by a selective impairment of long-term memory without any disorder of general intelligence or other cognitive functions, has been associated with lesions localized within Papez's circuit and some connected areas. Thus, amnesia could be due to a functional disconnection between components of this or other neural structures involved in long-term learning and retention. To test this hypothesis, we measured regional cerebral metabolism with 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) and positron emission tomography (PET) in 11 patients with “pure” amnesia. A significant bilateral reduction in metabolism in a number of interconnected cerebral regions (hippocampal formation, thalamus, cingulate gyrus, and frontal basal cortex) was found in the amnesic patients in comparison with normal controls. The metabolic impairment did not correspond to alterations in structural anatomy as assessed by magnetic resonance imaging (MRI). These results are the first in vivo evidence for the role of a functional network as a basis of human memory.

Both visuo-spatial neglect and visual extinction may occur following right-brain damage. So far, studies on brain-damaged patients have not provided definite evidence about which lesion patterns may lead to the association or dissociation of these deficits. This study was set out to address this issue using Intracranial Electrical Stimulation (IES) in a group of nine patients affected by refractory epilepsy. Cerebral regions associated with visuo-spatial neglect and visual extinction were stimulated, including the right frontal, temporal, and posterior parietal areas. During IES, patients with intracranial implantation involving at least one of these cortical regions were administered with a manual line bisection task (N = 9) to assess visuo-spatial neglect, and a computerized task (N = 8) assessing visual extinction. Results showed that parietal IES induced a rightward bias at the manual bisection task, together with a general improvement in reaction times at bilateral and unilateral visual stimuli detection at the extinction task. The occurrence of visual extinction did not vary across stimulations. By adopting a complementary approach to anatomo-clinical correlation studies, our work corroborates the notion that lesions to the right inferior parietal lobule play a pivotal role in the pathogenesis of visuo-spatial neglect. Importantly, our results also suggest that temporarily interfering with the activity of this region is not sufficient per se to generate visual extinction, which instead may involve a broader and/or different network, possibly extending beyond the cerebral regions considered here, posing important theoretical and clinical implications.

The brain preserves its capacity to integrate information from different senses in many pathological conditions, including stroke. Multisensory integration mechanisms, which may be spared by brain damage, provide a tool for setting up rehabilitation programs of poststroke sensory and cognitive disorders. Indeed, proper multisensory stimulation can ameliorate some unisensory perceptual and spatial impairments of brain-damaged patients. In the case of postchiasmatic visual field defects, intensive audiovisual stimulation of the blind hemifield allows the development of compensatory eye movements, in turn reducing vision-related functional disability in daily living. This approach is effective in both adult stroke patients and in children with cerebral palsy. In the rehabilitation of unilateral spatial neglect, many available treatments are intrinsically multisensory, because they primarily act through a crossmodal reinforcement of spatial representations. This is the case of adaptation to optical prisms displacing the visual scene, a widely used method that affects sensorimotor neuroplasticity. In patients with spatial neglect, prism adaptation induces a remapping of spatial coordinates, enabling the reconstruction of a stable representation of space across different sensory modalities. Other promising therapeutic strategies are offered by multisensory illusions, which can be used for restoring disarranged spatial and body representations, thereby improving the resulting deficits.

Our motor behavior and interactions with the external world are mediated by many spatial systems. This study investigated the absence of visual control of performance in the manual line bisection task, with the goal of teasing apart the role of the motor component of the visuomotor spatial system. Results show a rightward bias when right-handed individuals bisect lines using their right hand. This effect is traced back to a motor-spatial representation of space centered on the dominant hand. This finding was replicated and further explored in 4 experiments, with the same "open loop" bisection procedure. The mechanism underlying the rightward bias does not interact with the visuo-perceptual processing involved in visual illusions of extension. Besides, this bias no longer appears when perceptual judgments of prebisected lines are required, and is substantially reduced when the influence of visual feedback is minimized by a ballistic movement. The emergence of a leftward shift in left-handed individuals, when using their left hand, confirms the hypothesis of a dominant-hand-centered motor-spatial bias. Finally, when the lines to be bisected are placed to the left or to the right of the midsagittal plane of the participants' trunk, the error shifts overall toward the side of displacement of the stimulus, both in left- and right-handers, independent of the bisection bias, which does not appear related to the egocentric position of the stimulus. We reexamined the spatial biases occurring both in healthy (i.e., pseudoneglect) and neurological (i.e., neglect) populations, by emphasizing the integration mechanism of different spatial coordinate systems. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Since the 1960s, evidence from healthy participants and brain-damaged patients, neuroimaging and non-invasive brain stimulation studies has specified the neurofunctional architecture of the short-term memory (STM) system, supporting the temporary retention of a limited amount of verbal material. Auditory-verbal, later termed Phonological (Ph) STM or Phonological Loop, comprises two sub-components: i) the main storage system, the Phonological Short-Term Store (PhSTS), to which auditory verbal stimuli have direct access and where phonologically coded information is retained for a few seconds; ii) a Rehearsal Process (REH), which actively maintains the trace held in the PhSTS, preventing its decay and conveys visual verbal material to the PhSTS, after the process of Phonological Recoding (PhREC, or Grapheme-to-Phoneme Conversion) has taken place. PhREC converts visuo-verbal graphemic representations into phonological ones. The neural correlates of PhSTM include two discrete regions in the left hemisphere: the temporo-parietal junction (PhSTS) and the inferior frontal gyrus in the premotor cortex (REH). The neural basis of PhREC has been much less investigated. A few single case studies of patients made anarthric by focal or degenerative cortical damage, who show a pattern of impairment indicative of a deficit of PhREC, sparing the REH process, suggest that the primary motor cortex (M1) might be involved. To test this hypothesis in healthy participants with a neurophysiological approach, we measured the corticospinal excitability of M1, by means of Transcranial Magnetic Stimulation (TMS)-induced Motor Evoked Potentials (MEPs), during the execution of phonological judgements on auditorily vs. visually presented words (Experiment #1). Crucially, these phonological tasks involve REH, while PhREC is required only with visual presentation. Results show MEPs with larger amplitude when stimuli are presented visually. Task difficulty does not account for this difference and the result is specific for linguistic stimuli, indeed visual and auditory stimuli that cannot be verbalized lead to different behavioral and neurophysiological patterns (Experiment #2). The increase of corticospinal excitability when words are presented visually can be then interpreted as an indication of the involvement of M1 in PhREC. The present findings elucidate the neural correlates of PhREC, suggesting an involvement of the peripheral motor system in its activity.

The human brain has a remarkable capacity to focus processing resources based on the features and the relevance of the task at hand. The two cerebral hemispheres contribute differentially to this capacity, with the left hemisphere linguistic and right hemisphere visuo-spatial abilities each offering unique contributions. For example, previous research has established that healthy participants set the subjective mid-point of written sentences more leftwards of center, compared to unpronounceable letter strings or simple lines. Remarkably, patients with right hemisphere damage exhibiting unilateral spatial neglect also show this pattern, even though, as well known in the literature, they tend toward a rightward bias for non-linguistic stimuli. This evidence suggests that the leftward bias for sentential material is due to linguistic, mainly left-hemisphere mediated processes, which are largely unimpaired in right brain-damaged patients, and intact in heathy participants. To test this hypothesis, we compared sentence bisection performance to that of letter strings and simple lines in left brain-damaged patients (with and without aphasia). If the larger leftward bias in the bisection of sentential material is based on linguistic processes, then the left brain-damaged patients should show a reduction or absence of a leftward bias in sentence bisection. We tested twenty-four left brain-damaged patients (12 with aphasia and 12 without aphasia), and 24 age-matched elderly participants (patients and controls were all right-handed). Participants were asked to bisect 240 stimuli, comprising: (i) affirmative and interrogative clauses, (ii) sentences with lexical and syntactic violations, (iii) letter strings and (iv) simple lines. As predicted, neurologically intact participants showed larger leftward biases in bisecting written readable sentences compared to strings of letters. In contrast, the left hemisphere damaged patients (both with and without aphasia) showed no differences in bisecting sentences and letter strings or lines. These findings indicate that the larger leftward bias exhibited by healthy participants in the bisection of sentences is likely due to ortho-phonological coding taking place implicitly during the bisection task. This ortho-phonological coding is impaired with left brain damage - also in absence of apparent aphasia - leading to the left-hemisphere damaged patients showing a reduced leftward bias in sentence bisection. These findings support the hypothesis that the leftward bias in the bisection of written sentences is the result of ortho-phonological influences rather than visual-spatial biases.

Spatial neglect is a debilitating disorder frequently observed after damage to the right cerebral hemisphere. Previous investigations have revealed that prism adaptation (PA) therapy can lead to improvements in neglect-related symptoms. In the typical PA protocol patients repeatedly point toward a visual target while wearing prism goggles. A few years ago, a novel PA procedure, involving a variety of more "ecological" visuo-motor activities during adaptation, less repetitive than a sequence of pointings, was introduced by our research group, and shown to be able to improve neglect-related symptoms to the same extent as the standard pointing task. The ecological procedure was easy to administer and pleasant for the patients. In all previous studies, patients were treated by specialized personnel during hospitalization. In the current study, we investigated the effectiveness of the ecological PA method when performed in a home-based setting, with the help of caregivers and family members. Seven right-brain-damaged patients with chronic left spatial neglect underwent a two-week ecological PA treatment, extended, for two extra weeks, in 6 patients, who were available for this additional rehabilitation session. As a control treatment, patients performed the same activities while wearing neutral goggles, before the PA procedure. Two weeks of ecological PA training proved to be able to significantly improve performance in neuropsychological tests (BIT, Cancellation tasks), a neurological scale (NIH), and functional abilities (CBS), when compared to both the baseline and the neutral control treatment, with improvements being maintained over 6 months. The ecological home-based PA training is effective in alleviating signs of spatial neglect. Importantly, this training is affordable, pleasant, and feasible to be performed in the comfort of the patient's home. Easily extendable to larger patient populations and prolonged periods, this method has a real potential to benefit the quality of life of brain-damaged patients with left spatial neglect.

Unilateral spatial neglect is a disabling neurologic deficit, most frequent and severe after right-hemispheric lesions. In most patients neglect involves the left side of space, contralateral to a right-hemispheric lesion. About 50% of stroke patients exhibit neglect in the acute phase. Patients fail to orient, respond to, and report sensory events occurring in the contralateral sides of space and of the body, to explore these portions of space through movements by action effectors (eye, limbs), and to move the contralateral limbs. Neglect is a multicomponent higher-level disorder of spatial awareness, cognition, and attention. Spatial neglect may occur independently of elementary sensory and motor neurologic deficits, but it can mimic and make them more severe. Diagnostic tests include: motor exploratory target cancellation; setting the midpoint of a horizontal line (bisection), that requires the estimation of lateral extent; drawing by copy and from memory; reading, assessing neglect dyslexia; and exploring the side of the body contralateral to the lesion. Activities of daily living scales are also used. Patients are typically not aware of neglect, although they may exhibit varying degrees of awareness toward different components of the deficit. The neural correlates include lesions to the inferior parietal lobule of the posterior parietal cortex, which was long considered the unique neuropathologic correlate of neglect, to the premotor and to the dorsolateral prefrontal cortices, to the posterior superior temporal gyrus, at the temporoparietal junction, to subcortical gray nuclei (thalamus, basal ganglia), and to parietofrontal white-matter fiber tracts, such as the superior longitudinal fascicle. Damage to the inferior parietal lobule of the posterior parietal cortex is specifically associated with the mainly egocentric, perceptual, and exploratory extrapersonal, and with the personal, bodily components of neglect. Productive manifestations, such as perseveration, are not a correlate of posterior parietal cortex damage.

The development and change of knowledge on the function of the parietal lobe from the second half of the 19th century to the early 1970s are reviewed. Motor and somatosensory functions were initially localized in a broad frontoparietal region. At the beginning of the 20th century the motor cortex was restricted to the posterior frontal lobe. The separate attribution of somatosensory functions to the parietal lobe was initially based on anatomic considerations, but mostly on localized bodily sensations elicited by electric stimulation in awake patients. Patients and nonhuman primates with anterior parietal damage showed deficits in somatic sensation (tactile discrimination and position sense, less markedly pain and thermal sensitivity). Somatosensory evoked potentials demonstrated in all mammals that the body is orderly and multiply represented in the anterior parietal cortex. The parietal lobe was divided into an anterior and a posterior cortex (PPC). The PPC is particularly developed in primates, where it includes a superior and an inferior parietal lobule. The PPC was initially thought to be a higher-order region for somatosensory information processing, but its functional specialization proved soon to be greater and more complex. PPC damage in humans gives rise to a variety of neuropsychologic disorders: pain asymbolia, sensory extinction, spatial neglect, optic ataxia and limb apraxia, alexia and agraphia. Single-neuron recordings in freely behaving monkeys furnished the complementary information that the PPC is involved in body-environment interactions, for visual exploration and hand use as a sensor and a tool. The PPC is now believed to underpin higher-order processes of sensory inputs, multisensory and sensorimotor integration, spatial attention, intention, and the conjoint representation of external space and the body. The symptoms in which disorders of these processes manifest after PPC damage are considerably different in humans and nonhuman primates.

Transcranial magnetic stimulation (TMS) and transcranial electric stimulation (tES) are noninvasive brain stimulation (NIBS) tools that are now widely used in neuroscientific research in humans. The fact that both TMS and tES are able to modulate brain plasticity and, in turn, affect behavior is opening up new horizons in the treatment of brain circuit and plasticity disorders. In the present chapter, we will first provide the reader with a brief background on the basic principles of NIBS, describing the electromagnetic and physical foundations of TMS and tES, as well as the current knowledge of the neurophysiologic basis of their effects on brain activity and plasticity. In the main part, we will outline studies aimed at improving persistent symptoms and deficits in patients suffering from neurologic and neuropsychiatric disorders featured by dysfunction of the parietal lobe. The emerging view is that NIBS of parietal areas holds the promise to overcome various sensory, motor, and cognitive disorders that are often refractory to standard medical or behavioral therapies. The chapter closes with an outlook on further developments in this realm, discussing novel therapeutic approaches that could lead to more effective rehabilitation procedures, better suited for the specific parietal lobe dysfunction.

In this chapter, the neuropsychologic literature concerning memory deficits following parietal lesions is reviewed. Left inferior parietal lobule lesions definitely cause verbal short-term memory impairments, while right parietal lesions disrupt visuospatial short-term memory. Episodic memory, as well as autobiographic memory, does not seem to be impaired after both unilateral and bilateral parietal lesions, in contrast with neuroimaging studies reporting activation of the lateral parietal cortex during memory tasks. The most substantiated hypothesis is that the parietal lobe is involved in the subjective experience of recollection. Indeed, patients with parietal lesions produce fewer false memories and show lower confidence in their source recollections, possibly due to a limited number of details that they are able to report. Finally, the parietal lobes contribute to semantic memory as far as abstract concepts are concerned; in addition some sparse evidence on traumatic brain injury suggests that the parietal lobe is part of the distributed network involved in prospective memory.

Cortical regional cerebral perfusion was assessed by N, N, N1-trimethyl-N1-(2)-hydroxy-3-methyl-5-(I-123) iodobenzyl-1, 3-propanediamine 2 HCl I-123 (HIPDM) and single photon emission computerised tomography (SPECT) in six aphasic and two neglect patients with unilateral subcortical vascular lesions. Assessments were carried out both in the acute phase and after a period ranging from 1 to 6 months after stroke onset. In all patients an almost complete spontaneous recovery occurred and was associated with a significant improvement of cortical perfusion. A relationship between severity of aphasia and degree of cortical hypoperfusion was found, in both the acute and the follow up assessments, in the aphasic subgroup.

Adaptation to optical prisms displacing the visual scene laterally is a widely investigated instance of visuo-motor plasticity, also because prism adaptation (PA) has been extensively used as a treatment for right-brain-damaged patients suffering from left spatial neglect. The lateral visual displacement brought about by prisms, as indexed by a pointing error in the direction of the displacement, is progressively corrected through repeated pointings: after prism removal, a shift in the direction opposite to the prism-induced deviation occurs in visual, proprioceptive, and visuo-proprioceptive straight-ahead tasks (aftereffects, AEs). The cerebellum and the posterior parietal cortex (PPC) are key components of the bilateral cerebral network subserving the AEs, and the reduction of the pointing error during prism exposure in PA. We report the experimental study of a patient with bilateral occipital and left cerebellar damage, who showed a preserved reduction of the pointing errors to rightward displacing prisms, but not the leftward AEs in the proprioceptive straight-ahead task; instead, visual-proprioceptive and visual AEs were preserved. Anodal transcranial Direct Current Stimulation (tDCS) over the left PPC restored the leftward proprioceptive AEs, and anodal tDCS over the left cerebellum abolished the rightward deviation. Conversely, stimulation over the right PPC or the right cerebellum was ineffective. These results provide novel evidence for neuromodulatory effects of tDCS on defective AEs, through the stimulation over dedicated cortical regions.

Visuo-motor adaptation to optical prisms displacing the visual scene (prism adaptation, PA) is a method used for investigating visuo-motor plasticity in healthy individuals and, in clinical settings, for the rehabilitation of unilateral spatial neglect. In the standard paradigm, the adaptation phase involves repeated pointings to visual targets, while wearing optical prisms displacing the visual scene laterally. Here we explored differences in PA, and its aftereffects (AEs), as related to the sensory modality of the target. Visual, auditory, and multisensory – audio-visual – targets in the adaptation phase were used, while participants wore prisms displacing the visual field rightward by 10°. Proprioceptive, visual, visual-proprioceptive, auditory-proprioceptive straight-ahead shifts were measured. Pointing to auditory and to audio-visual targets in the adaptation phase produces proprioceptive, visual-proprioceptive, and auditory-proprioceptive AEs, as the typical visual targets did. This finding reveals that cross-modal plasticity effects involve both the auditory and the visual modality, and their interactions (Experiment 1). Even a shortened PA phase, requiring only 24 pointings to visual and audio-visual targets (Experiment 2), is sufficient to bring about AEs, as compared to the standard 92-pointings procedure. Finally, pointings to auditory targets cause AEs, although PA with a reduced number of pointings (24) to auditory targets brings about smaller AEs, as compared to the 92-pointings procedure (Experiment 3). Together, results from the three experiments extend to the auditory modality the sensorimotor plasticity underlying the typical AEs produced by PA to visual targets. Importantly, PA to auditory targets appears characterized by less accurate pointings and error correction, suggesting that the auditory component of the PA process may be less central to the building up of the AEs, than the sensorimotor pointing activity per se. These findings highlight both the effectiveness of a reduced number of pointings for bringing about AEs, and the possibility of inducing PA with auditory targets, which may be used as a compensatory route in patients with visual deficits.

Despite transcranial direct current stimulation (tDCS) is increasingly used in experimental and clinical settings, its precise mechanisms of action remain largely unknown. At a neuronal level, tDCS modulates the resting membrane potential in a polarity-dependent fashion: anodal stimulation increases cortical excitability in the stimulated region, while cathodal decreases it. So far, the neurophysiological underpinnings of the immediate and delayed effects of tDCS, and to what extent the stimulation of a given cerebral region may affect the activity of anatomically connected regions, remain unclear. In the present study, we used a combination of Transcranial Magnetic Stimulation (TMS) and Electroencephalography (EEG) in order to explore local and global cortical excitability modulation during and after active and sham tDCS. Single pulse TMS was delivered over the left posterior parietal cortex (PPC), before, during, and after 15 min of tDCS over the right PPC, while EEG was recorded from 60 channels. For each session, indexes of global and local cerebral excitability were obtained, computed as global and local mean field power (Global Mean Field Power, GMFP and Local Mean Field Power, LMFP) on mean TMS-evoked potentials (TEPs) for three temporal windows: 0–50, 50–100, and 100–150 msec. The global index was computed on all 60 channels. The local indexes were computed in six clusters of electrodes: left and right in frontal, parietal and temporal regions. GMFP increased, compared to baseline, both during and after active tDCS in the 0–100 msec temporal window. LMFP increased after the end of stimulation in parietal and frontal clusters bilaterally, while no difference was found in the temporal clusters. In sum, a diffuse rise of cortical excitability occurred, both during and after active tDCS. This evidence highlights the spreading of the effects of anodal tDCS over remote cortical regions of stimulated and contralateral hemispheres.

Touch has an emotional and communicative meaning, and it plays a crucial role in social perception and empathy. The intuitive link between others' somatosensations and our sense of touch becomes ostensible in mirror-touch synesthesia, a condition in which the view of a touch on another person's body elicits conscious tactile sensations on the observer's own body [1]. This peculiar phenomenon may implicate normal social mirror mechanisms [2]. Here, we show that mirror-touch interference effects, synesthesia-like sensations, and even phantom touches can be induced in nonsynesthetes by priming the primary somatosensory cortex (SI) directly or indirectly via the posterior parietal cortex. These results were obtained by means of facilitatory paired-pulse transcranial magnetic stimulation (ppTMS) contingent upon the observation of touch. For these vicarious effects, the SI is engaged at 150 ms from the onset of the visual touch. Intriguingly, individual differences in empathic abilities, assessed with the Interpersonal Reactivity Index [3], drive the activity of the SI when nonsynesthetes witness others' tactile sensations. This evidence implies that, under normal conditions, touch observation activates the SI below the threshold for perceptual awareness [4]; through the visual-dependent tuning of SI activity by ppTMS, what is seen becomes felt, namely, mirror-touch synesthesia. On a broader perspective, the visual responsivity of the SI may allow an automatic and unconscious transference of the sensation that another person is experiencing onto oneself, and, in turn, the empathic sharing of somatosensations [2]. © 2014 Elsevier Ltd.

Numbers induce shifts of spatial attention on the left or the right sides of external space as a function of their magnitude. However, whether this number-space association is restricted to the linear horizontal extensions, or extends to the whole visual scene, is still an open question. This study investigates, by means of a cancellation paradigm, the influence of numerical magnitude during scanning tasks in which participants freely explore complex visual scenes unconstrained towards either the horizontal or the vertical unidimensional axes. Five cancellation tasks were adapted in which Arabic digits were used as targets or distracters, in structured (lines and columns) or unstructured visual displays, with a smaller (2 or 3 types of distracters) or larger (10 or more types of distracters) sets of stimuli. Results show that the participants' hits distribution was a function of number magnitude: shifted on the left for small and on the right for large numbers. This effect was maximised when numerical cues were sparse, randomly arranged and, critically, irrelevant to the task. Overall, this study provides novel evidence from visuo-spatial exploratory cancellation tasks for an attentional shift induced by number magnitude. © Springer-Verlag Berlin Heidelberg 2013.

Optimal motor performance requires the monitoring of sensorimotor input to ensure that the motor output matches current intentions. The brain is thought to be equipped with a “comparator” system, which monitors and detects the congruence between intended and actual movement; results of such a comparison can reach awareness. This study explored in healthy participants whether the cathodal transcranial direct current stimulation (tDCS) of the right premotor cortex (PM) and right posterior parietal cortex (PPC) can disrupt performance monitoring in a skilled motor task. Before and after tDCS, participants underwent a two-digit sequence motor task; in post-tDCS session, single-pulse TMS (sTMS) was applied to the right motor cortex, contralateral to the performing hand, with the aim of interfering with motor execution. Then, participants rated on a five-item questionnaire their performance at the motor task. Cathodal tDCS of PM (but not sham or PPC tDCS) impaired the participants' ability to evaluate their motor performance reliably, making them unconfident about their judgments. Congruently with the worsened motor performance induced by sTMS, participants reported to have committed more errors after sham and PPC tDCS; such a correlation was not significant after PM tDCS. In line with current computational and neuropsychological models of motor control and awareness, the present results show that a mechanism in the PM monitors and compares intended versus actual movements, evaluating their congruence. Cathodal tDCS of the PM impairs the activity of such a “comparator,” disrupting self-confidence about own motor performance.

Distracting gaze has been shown to elicit automatic gaze following. However, it is still debated whether the effects of perceived gaze are a simple automatic spatial orienting response or are instead sensitive to the context (i.e. goals and task demands). In three experiments, we investigated the conditions under which gaze following occurs. Participants were instructed to saccade towards one of two lateral targets. A face distracter, always present in the background, could gaze towards: (a) a taskrelevant target––(‘‘matching’’ goal-directed gaze shift)––congruent or incongruent with the instructed direction, (b) a task-irrelevant target, orthogonal to the one instructed (‘‘non-matching’’ goal-directed gaze shift), or (c) an empty spatial location (no-goal-directed gaze shift). Eye movement recordings showed faster saccadic latencies in correct trials in congruent conditions especially when the distracting gaze shift occurred before the instruction to make a saccade. Interestingly, while participants made a higher proportion of gaze-following errors (i.e. errors in the direction of the distracting gaze) in the incongruent conditions when the distracter’s gaze shift preceded the instruction onset indicating an automatic gaze following, they never followed the distracting gaze when it was directed towards an empty location or a stimulus that was never the target. Taken together, these findings suggest that gaze following is likely to be a product of both automatic and goal-driven orienting mechanisms.

Macro- and micro-somatognosia refer to rare disorders of the cerebral representation of the body whereby patients perceive body parts as disproportionately large or small. Here we report the experimental study of a patient who, following a left lateral medullary stroke (Wallenberg's syndrome, including vestibular deficits) complained of a persistent somatosensory illusory sensation of swelling, confined to the left side of his face (i.e., left macrosomatognosia). This hemifacial somatosensory distortion was associated with a left facial anesthesia, and a neuropathic pain affecting the three branches of the left trigeminal nerve. In this study, we first document quantitatively the patient's somatosensory illusion by using a somatosensory-to-visual matching task in which the patient modified the picture of his own face to fit his left-sided somatosensory misperception. The patient's performance revealed that macrosomatognosia was confined to the second branch of the left trigeminal nerve. Perception of the size of visual objects was comparatively preserved. Second, we investigated the effects of two peripheral stimulations, which may affect the spatial component of somatosensory deficits (caloric vestibular stimulation, CVS; transcutaneous electrical nervous stimulation, TENS) and pain (TENS). Left CVS abolished the facial somatosensory illusion, for about 30min, but had no effect on the left facial pain. Conversely, left TENS substantially reduced the neuropathic pain during stimulation, but had no effect on macrosomatognosia, indicating a double dissociation between the two disorders. These results reveal that facial macrosomatognosia may be regarded as a high-order deficit of somatosensory perception of the shape and volume of the face, which fits the definition of 'hyperschematia' (i.e., when the body takes up too much room) originally proposed by Bonnier (1905). Our data also indicate that CVS may favor the restoration of the conscious representation of the shape and size of the face. Overall, these findings lend support to the view that afferent inputs from the vestibular system can affect in a specific fashion the activity of cerebral structures involved in the building up and updating of the topological description of body parts.

This special issue of Neuropsychological Rehabilitation aims to present new knowledge about a recent and innovative approach that can possibly ameliorate the outcome of the rehabilitation of cognitive deficits, namely: non-invasive brain stimulation (NIBS). The issue includes a series of papers on NIBS and combined rehabilitation studies (reviews and some original contributions), highlighting the challenges, as well as the power, of this novel approach

Background. Recovery of motor function after stroke may depend on a balance of activity in the neural network involving the affected and the unaffected motor cortices. Objective. To assess whether transcranial direct current stimulation (tDCS) can increase the training-induced recovery of motor functions. Methods. In an exploratory study, 14 patients with chronic stroke and mean Fugl-Meyer Upper Extremity Motor Assessment of 29 (range = 8-50) entered a double-blind sham-controlled study, aimed to investigate neurophysiological and behavioral effects of bihemispheric tDCS (cathodal stimulation of the unaffected motor cortex and anodal stimulation of the affected motor cortex), combined with constraint-induced movement therapy (CIMT). Results. Patients in both groups demonstrated gains on primary outcome measures, that is, Jebsen Taylor Hand Function Test, Handgrip Strength, Motor Activity Log Scale, and Fugl-Meyer Motor Score. Gains were larger in the active tDCS group. Neurophysiological measurements showed a reduction in transcallosal inhibition from the intact to the affected hemisphere and increased corticospinal excitability in the affected hemisphere only in the active tDCS/CIMT group. Such neurophysiological changes correlated with the magnitude of the behavioral gains. Both groups showed a reduction in corticospinal excitability of the unaffected hemisphere. Conclusions. CIMT alone appears effective in modulating local excitability but not in removing the imbalance in transcallosal inhibition. Bihemispheric tDCS may achieve this goal and foster greater functional recovery.

Objective: Adaptation to prisms displacing the visual scene rightward is a therapeutic tool for left unilateral spatial neglect (USN). We aimed at comparing the effects of the classic adaptation procedure (repeated pointing toward visual targets, control treatment, C), with those of a novel adaptation method, involving ecological visuomotor activities (experimental treatment, E). Method: In 10 right-brain-damaged USN patients, each treatment was given for 1 week, with a crossover design, for a total of 20 sessions, twice per day. USN was assessed by cancellation, reading, and drawing tasks, and by a standardized scale. Neurological severity was assessed by the National Institutes of Health (NIH) stroke scale (Brott et al., 1989), disability by the Functional Independence Measure (FIM) scale. Results: The 2-week treatments (EC, CE) were equally effective, improving both USN, confirming previous reports (Frassinetti, Angeli, Meneghello, Avanzi, & Làdavas, 2002) and, importantly, disability. The improvement was independent of baseline performance, duration of disease, and neurological severity. Recovery took place after the first week, continued in the second week, and was stable at the follow-up of 3 months. The improvement of USN, measured by cancellation performance, and, in part, that of disability, measured through the FIM scale, were mediated by the size of the leftward aftereffects, suggesting a causal relationship between prism exposure and recovery. The E protocol was better tolerated. Conclusions: Daily life visuomotor activities, associated with prism exposure, are a useful tool for rehabilitating USN patients. This new treatment may widen the compliance with prism exposure treatments and their feasibility within home-based programs.

Recent evidence suggests that behavioural gains induced by behavioural training are maximized when combined with techniques of cortical neuromodulation, such as transcranial Direct Current Stimulation (tDCS). Here we address the validity of this appealing approach by investigating the effect of coupling a multisensory visual field exploration training with tDCS of the posterior parietal cortex (PPC). The multisensory visual field exploration training consisted in the practice of visual search through the systematic audio-visual stimulation of the visual field. Neurologically unimpaired participants performed a bimodal exploration training for 30 min, while simultaneously receiving anodal-excitatory PPC tDCS or sham tDCS. In two different experiments, the left and the right hemisphere were stimulated. Outcome measures included visual exploration speed at different time intervals during the training, and the post-training effects on tests assessing visual scanning and visuo-spatial orienting. Results show that PPC tDCS applied to the right, but not to the left, hemisphere increases the training-induced behavioural improvement of visual exploration, as compared to sham tDCS. In addition, right PPC tDCS brings about an improvement of covert visual orienting, in a task different from the visual search practice. In an additional experiment, we confirm that right parietal tDCS by itself, even without the associated training, can lead to enhancement of visual search. Overall, anodal PPC tDCS is a promising technique to enhance visuo-spatial abilities, when combined to a visual field exploration training task. © 2010 Elsevier B.V.

The Müller-Lyer figure is a powerful illusion in both vision and touch, although it is still unclear whether the visual and haptic illusory effects are due to modality-specific or shared processes. In order to investigate the hypothesis of a common underlying mechanism, the performance of 24 undergraduates in a manual bisection task of the Judd variant of the Müller-Lyer figure was assessed under visual, haptic, and visuo-haptic presentations (Experiment 1). In the bimodal condition participants saw the arrowheads on the front and touched the shaft on the back of a stimulus-supporting board. Illusory effects were comparable in touch and vision and were present, albeit reduced, in the bimodal visuo-haptic condition. In Experiment 2 we used the bimodal task of Experiment 1, manipulating the spatial position of the horizontal shaft on the backside of the board. The visual arrowheads affected haptic bisection, bringing about the illusory effects, only when the shaft was aligned with them. In conclusion, illusory effects transfer cross-modally from vision to haptics only in the presence of spatial coincidence, which appears to be a crucial factor for cross-modal integration. Implications for multisensory processes are discussed.

Department of Psychology, University of Milano-Bicocca, Milan, Italy Neuropsychological Laboratory, IRCCS Istituto Auxologico Italiano, Milan, Italy Universite de Lyon, Universite Lyon 1, Inserm UMR-S 864, Bron, et Hospices Civils de Lyon, Service de Medecine Physique et Readaptation, Hopital Henry Gabrielle, Saint-Genis-Laval, France Universite de Lyon, Universite Lyon 1, ‘Mouvement et Handicap’ Plateforme IFNL-HCL, Institut Federatif des Neurosciences de Lyon, Hospices Civils de Lyon, Lyon, France

Sixteen patients with unilateral subcortical haemorrhagic or ischaemic stroke, confirmed by CT, were evaluated for the presence of aphasia and neglect. Compared with patients without neuropsychological deficits, left brain-damaged aphasic and right brain-damaged neglect patients showed a significantly greater reduction of cortical perfusion on N,N,N1-trimethyl-N1-(2)-hydroxy-3-methyl-5-(I-123) iodobenzyl-1,3-propanediamine 2 HCl I-123 (HIPDM) and single photon emission computerized tomography (SPECT). These results suggest that major cortical derangement is the crucial factor for the appearance of aphasia or neglect after a subcortical stroke. These remote effects, which are related to the size of the subcortical lesion, are interpreted in terms of interruption of neural connections (diaschisis).

BACKGROUND: The cerebellum plays a role in higher-order cognitive processes, although the evidence concerning spatial cognition is not definite. OBJECTIVE: To investigate the role of the cerebellum in setting the midpoint of a horizontal line and to assess the role of visual monitoring of the movement of the upper limb. METHODS: Twelve patients, 6 with left-sided and 6 with right-sided cerebellar damage, and 12 control participants, marked the midpoint of horizontal lines with their left or right hand, under conditions of present versus absent visual control of the movement of the upper limb. RESULTS: When visual feedback was available, the patients' accuracy was comparable to that of control participants with a minor leftward bias. Without visual feedback, controls and right-sided cerebellar patients exhibited a rightward bias. Conversely, left-sided cerebellar patients still showed a leftward bias. CONCLUSIONS: The leftward bias may be related to the visual monitoring of the movement of the upper limb, being reversed when this is not available. Under these conditions, kinesthetic information becomes more relevant, and may contribute to the rightward bias. This effect is not shown by left cerebellar patients, possibly due to the disconnection between the left cerebellum and the right hemisphere, involved in spatial cognition. © 2008 by Lippincott Williams & Wilkins.