Martina Gandola

An anatomical account of somatoparaphrenia

Somatoparaphrenia is a delusional belief whereby a patient feels that a paralyzed limb does not belong to his body; the symptom is typically associated with unilateral neglect and most frequently with anosognosia for hemiplegia. This association of symptoms makes anatomical inference based on single case studies not sufficiently specific. On the other hand, the only three anatomical group studies on somatoparaphrenia are contradictory: the right posterior insula, the supramarginal gyrus and the posterior corona radiata, or the right medial or orbito-frontal regions were all proposed as specific lesional correlates. We compared 11 patients with and 11 without somatoparaphrenia matched for the presence and severity of other associated symptoms (neglect, motor deficits and anosognosia). To take into account the frequent association of SP and neglect and hemiplegia, patients with and without somatoparaphrenia were also compared with a group of fifteen right brain damage patients without neglect and hemiplegia. We found a lesion pattern involving a fronto-temporo-parietal network typically associated with spatial neglect, hemiplegia and anosognosia. Somatoparaphrenic patients showed an additional lesion pattern primarily involving white matter and subcortical grey structures (thalamus, basal ganglia and amygdala). Further cortical damage was present in the middle and inferior frontal gyrus, postcentral gyrus and hippocampus. We propose that somatoparaphrenia occurs providing that a distributed cortical lesion pattern is present together with a subcortical lesion load that prevents most sensory input from being processed in neocortical structures; involvement of deep cortical and subcortical grey structures of the temporal lobe may contribute to reduce the sense of familiarity experienced by somatoparaphrenic patients for their paralyzed limb.

Left caloric vestibular stimulation ameliorates right hemianesthesia

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.

Arousal responses to noxious stimuli in somatoparaphrenia and anosognosia: clues to body awareness

A complex brain representation of our body allows us to monitor incoming sensory stimuli and plan actions towards the external world. A critical element of such a complex representation is the sense of ownership towards our own body parts. Brain damage may disrupt this representation, leading to the striking neuropsychological condition called somatoparaphrenia, that is, the delusion that ones own limbs belong to someone else. The clinical features characterizing somatoparaphrenia are well known, however, physiological clues of the level at which this condition may disrupt sensory functions are unknown. In the present study we investigated this issue by measuring the anticipatory skin conductance response to noxious stimuli approaching either the affected or the intact body side in a group of patients with somatoparaphrenia (n=5; three females, age range=66-84), and in a group of patients with anosognosia for sensory deficits, i.e. preserved ownership but decreased awareness of somatosensory deficit, (n=5; one female, age range=62-81 years) and in a group of purely hemiplegic patients (n=5; two females, age range=63-74 years) with no deficits of ownership or sensory awareness. Results show that anticipatory skin conductance responses to noxious stimuli directed to the contralesional hand are significantly reduced as compared to noxious stimuli directed to the ipsilesional hand in patients with somatoparaphrenia. By contrast a non-reduced anticipatory skin conductance response was observed in control participants as well as in patients affected by anosognosia for the somatosensory deficit and in patients affected by pure motor deficits. Furthermore, a pain anticipation response was always measured when the stimuli were directed towards the ipsilesional, unaffected hand in all groups. Our results show for the first time that the delusions shown by somatoparaphrenic patients are associated with an altered physiological index of perceptual analysis. The reduced response to sensory threats approaching the body suggests a deep detachment of the affected body part from the patients body representation. Conversely, normal reactions to incoming threats are found in the presence of impaired sensory awareness but intact body ownership, supporting the notion that representation of the body may be affected at different levels following brain damage.

Productive and defective impairments in the neglect syndrome: Graphic perseveration, drawing productions and optic prism exposure

The effects of adaptation to prisms displacing rightwards the field of vision on omission errors, and on perseveration and other graphic productions in a line cancellation task, were assessed in nine right-brain-damaged patients with left unilateral spatial neglect. Prism adaptation improved both neglect, as indexed by omission errors, and perseveration behaviour, up to a delay of 60 min. No correlation was found between omission and perseveration errors in all assessments. The suggestion is made that perseveration and other complex graphic productions made by right brain-damaged-patients with left spatial unilateral neglect is due to a defective monitoring of complex motor behaviour, frequently associated to cerebral damage involving the right frontal lobe. Interpretations of perseveration behaviour in terms of allochiria and directional hypokinesia are considered, and their limits discussed.

Productive symptoms in right brain damage

Purpose of reviewThe purpose of this review is to summarize the more recent studies on productive symptoms from the neuropsychological, neurophysiological and anatomical points of view. The integration of these aspects may provide some clarifications on the cognitive impairments underpinning the main productive disorders, also contributing to better understand the normal functioning of the brain. Recent findingsProductive symptoms are closely associated to spatial neglect and are distinguished in relation to the part of space they manifest. The investigation of perseveration in extrapersonal space with different manipulations helps to understand the neuropathological mechanisms underlying this symptom. Anosognosia for hemiplegia and somatoparaphrenia may be considered as disorders of body representation (personal space). Recently it has been proposed that these disorders may be ascribed to an impairment of different levels of motor control. The identification of the anatomical correlates of these two disorders contributes to better understanding of their the cognitive nature. SummaryProductive behaviours have diverse clinical manifestations and may be induced by different mechanisms. Lesional studies are beginning to provide evidence for specific anatomical correlates of these disorders. Further investigations are needed to better understand to what extent productive symptoms can be disentagled from spatial neglect. These attempts may contribute to clarifying the role of the right hemisphere in monitoring spatial cognition.

Caloric vestibular stimulation: interaction between somatosensory system and vestibular apparatus

Spatial and bodily representations are multisensory processes that imply the integration of several afferent signals into a coherent internal model of our egocentric space. Crucially, this model involves also the vestibular information from the balance organs in the inner ear (Ventre et al., 1984). Accordingly, vestibular system projections have been proven to overlap with the somatosensory system and with brain regions involved in body and space representation (Bottini et al., 1994, 1995; Fasold et al., 2002). These representations can be altered by a brain lesion and dramatically restored by physiological manipulations targeting specific sensory components, such as the caloric vestibular stimulation (CVS; see for a review Rossetti and Rode, 2002). CVS consists in a water irrigation of the external auditory canal, which induces a change in the temperature that leads to convection currents in the semicircular canals. This evokes a slow-phase nystagmus toward the stimulated ear and it elicits sensations of virtual body rotations and vertigo (Barany, 1906; Silberpfennig, 1941; Barany, 1967). CVS has been used to modulate a wide range of cognitive and sensory functions in brain-damaged patients and in healthy participants (Utz et al., 2011). For instance, in right brain-damaged patients, CVS produces a temporary recovery of visuo-spatial neglect and associated symptoms, such as representational and personal neglect, anosognosia, somatoparaphrenia and motor neglect (see reviews in Rossetti and Rode, 2002; Kerkhoff and Schenk, 2012). Additionally, CVS also influences tactile perception: cold CVS delivered on the left ear transiently reduces tactile imperception (hemianesthesia) in both right and left brain-damaged patients (Vallar et al., 1990, 1993; Bottini et al., 2005). By contrast, the reversed stimulation (i.e., right ear cold CVS) is ineffective in left brain-damaged patients with the interesting exception of left brain-damaged patients with right visuo-spatial neglect (Vallar et al., 1993). More recently, similar cross-modal modulations have been described in healthy participants (Ferre et al., 2010, 2011, 2012, 2013). Various hypotheses have been suggested to explain the CVS-induced modulation on tactile perception. In particular, one of the most controversial issues in the classical and current literature concerns the specificity of these effects. Does CVS directly affect the somatosensory processing? Are the observed effects mediated by non-specific factors, such as ocular movements, spatial attention or general arousal? Since Rubens (1985), most of the scientists believed that positive (e.g., deficits reduction) or negative (e.g., deficits worsening) effects of CVS on spatial deficits in neurological patients can be explained by low-level visuo-vestibular interactions reflecting the direction of the nystagmus (Rubens, 1985). When a leftward nystagmus is present, for instance during left-cold CVS or right-warm CVS, there is a positive effect. Conversely, with a rightward nystagmus (left-warm CVS and right-cold CVS) a deficits worsening is observed (Rubens, 1985; Vallar et al., 1990). However, this traditional explanation has been challenged by several clinical reports which highlighted an effective CVS-induced modulation on deficits that do not require visual control such as personal neglect (Cappa et al., 1987), anosognosia and somatoparaphrenia (Cappa et al., 1987; Bisiach et al., 1991; Rode et al., 1992). Similarly, the remission of hemianesthesia in blind-folded patients (Vallar et al., 1990) rules out this low-level interpretation. Conversely, the role of non-specific effects such as spatial attention is still a matter of debate. This hypothesis argues that CVS may induce a reorientation of spatial attention toward the hemispace ipsilateral to the stimulated ear. Strong evidence against this hypothesis derives from a recent study on brain-damaged patients (Bottini et al., 2005) demonstrating that left-cold CVS also ameliorates right hemianesthesia in left brain-damaged patients (i.e., CVS at same water temperature, same stimulated ear and same leftwards slow-phase nystagmus), independently from the side of stimulation. These behavioral observations have been combined with neuroimaging data to identify the neurofunctional basis of CVS effects on touch perception in a group of normal participants and in one left brain-damaged patient. In this patient, we found that the remission of right hemianesthesia after cold-left CVS was associated with neural activity in the secondary somatosensory cortex (SII) of the undamaged hemisphere. The same region was bilaterally activated in healthy volunteers while they were touched on their right and left hand. Interestingly, the activation of SII for ipsilateral stimuli was of a greater extent in the right than in the left hemisphere in case of left tactile stimulation. These observations have been interpreted as a modulation that did not depend on a lower-level lateral cueing effect, but rather on the activation of the hemisphere that contains a more complete representation of the tactile and body space, the right hemisphere (Bottini et al., 2005). The involvement of SII clearly indicates an overlap between tactile and vestibular projections in the human brain (case RF; Bottini et al., 1995), and it makes explanations in terms of pure spatial effects improbable. More recent behavioral and electrophysiological studies, in healthy participants, have strengthened this suggestion. There are at least three main crucial observations ruling out interpretation in terms of non-specific attentional effects. First, left-cold CVS affects the perception of distinct somatosensory sub-modalities, i.e., touch and pain, for both the ipsilateral and contralateral hand (Ferre et al., 2011, 2013). A simple change in the level of spatial attention would have induced a predominant effect on the hand ipsilateral to the stimulated ear. Second, CVS differentially affects touch and pain. Indeed, while CVS increased sensitivity to tactile stimuli, it reduced levels of pain (Ferre et al., 2013). These further observations cannot be attributed merely to a spatial attention orientation effect, as in this case we would expect the same modulatory effect in both sub-modalities. Finally, CVS enhanced the N80 wave of the somatosensory-evoked potentials (SEPs) elicited by electrical stimulation of tactile afferents (Ferre et al., 2012). Interestingly, the N80 wave is generated in the parietal operculum (Jung et al., 2009; Eickhoff et al., 2010), a region receiving strong vestibular projections. Taken together, clinical observations and psychophysical studies give support to the notion of powerful cross-modal interactions between vestibular and somatosensory systems. Previous studies exploring more widely CVS effects also support the idea that spatial attention does not have a pivotal role. Rorden et al. (2001) did not find an effect of left-cold CVS on covert visual attention in healthy subjects. Furthermore, cold-water bilateral CVS (simultaneous stimulations of the right and left ear) was ineffective on visual neglect in brain-damaged patients, suggesting that CVS might improve neglect through a vestibular-induced specific effect (Rode et al., 2002). Moreover, it has been suggested that CVS can also modify the internal representation of the body (see for an extensive review Lopez et al., 2008). These well documented effects have been explained by the anatomical overlap and interactions of vestibular cortex and somatosensory networks subserving elementary and more structured perceptions concerning the body representation (Lopez et al., 2008, 2012). To conclude, this evidence suggests that in healthy volunteers the effects of CVS are specific and related to the activation of cortico-subcortical networks (Lopez et al., 2012) involved in cross-modal interactions between somatosensory and vestibular signals. We propose that future studies are necessary to extend these findings in neurological patients to better detail the neurophysiological interaction between the somatosensory and the vestibular systems.

What is Mine? Behavioral and Anatomical Dissociations between Somatoparaphrenia and Anosognosia for Hemiplegia

We describe the clinical manifestations and the lesion patterns of five patients with somatoparaphrenia, the denial of ownership for a paralyzed limb, who showed the rare dissociation from anosognosia for hemiplegia. Similar cases have been only occasionally cited in the literature with scanty descriptions of their symptoms and no detailed anatomical assessment. All patients had extrapersonal and at least mild personal neglect. The lesions pattern was mainly subcortical, with a significant involvement of the right thalamus, the basal ganglia and the internal capsule. A formal comparison between the anatomical pattern previously associated with anosognosia in a study performed in 2005 by Berti and colleagues, and the lesion distribution of each patient clearly shows that our pure somatoparaphrenic patients had a sparing of most of the regions associated with anosognosia for hemiplegia. The behavioral dissociation between SP and anosognosia for hemiplegia, together with this new anatomical evidence, suggests that motor awareness is not sufficient to build up a sense of ownership and therefore these two cognitive abilities are at least in part functionally independent and qualitatively different.

Like the back of the (right) hand? A new fMRI look on the hand laterality task

AbstractThere is a common saying for expressing familiarity with something. It refers to our hands, and strangely enough, in English, one says to know something like the back of the hand, whereas in other cultures, for example, Italy, Spain and France, the same expression is with the palm. Previous behavioural data have suggested that our ability to visually discriminate a right from a left hand is influenced by perspective. This behavioural finding has remained without neurophysiological counterparts. We used an implicit motor imagery task in which 30 right-handed subjects were asked to decide whether a picture portrayed a right rather than a left hand during an fMRI event-related experiment. Both views (back and palm) were used, and the hands were rotated by 45° in 8 possible angles. We replicated previous behavioural evidence by showing faster reaction times for the back-view and view-specific interaction effects with the angle of rotation: for the back view, the longest RTs were with the hand facing down at 180°; for the palm view, the longest RTs were at 90° with the hand pointing away from the midline. In addition, the RTs were particularly faster for back views of the right hand. fMRI measurements revealed a stronger BOLD signal increase in left premotor and parietal cortices for stimuli viewed from the palm, whereas back-view stimuli were associated with stronger occipital activations, suggesting a view-specific cognitive strategy: more visually oriented for the back of the hand; more in need of the support of a motoric imagery process for the palms. Right-hand back views were associated with comparatively smaller BOLD responses, attesting, together with the faster reaction times, to the lesser need for neural labour because of greater familiarity with that view of the hand. These differences suggest the existence of brain-encoded, view-dependent representations of body segments.

Canceling out both the real and the spectral lines

Neglect patients typically show motor perseveration while canceling targets on the ipsilesional side. This behavior can be influenced by the presence vs. absence of targets on the (neglected) contralesional side (). As alternative explanations, the authors proposed (i) directional hypokinesia--the patient cannot perform reaching movements towards detected left-sided targets, and thus carries on canceling on the right side, and (ii) allochiria--the patient misperceives left-sided targets as located on the right side, and cancels them there. We report here data from a patient (EZ) that might confirm the second hypothesis. EZ was presented with 19 displays in which the number and position of cancellation targets on both sides were varied systematically. EZ showed motor perseveration while canceling, but this tendency did not vary across conditions. Interestingly though, EZ also drew cancellation marks in the empty space between the ipsilesional targets, and this phenomenon was significantly more intense when there were more targets on the neglected side. As EZs comments suggested, such a behavior might reflect the attempt to cancel out delusional targets. Our speculation is that those objects were generated by allochiria.

The physiology of motor delusions in anosognosia for hemiplegia: implications for current models of motor awareness.

Right brain damaged patients sometimes deny that their left arm is paralysed or even claim to have just moved it. This condition is known as anosognosia for hemiplegia (AHP). Here, we used fMRI to study patients with and without AHP during the execution of a motor task. We found that the delusional belief of having moved was preceded by brain activation of the cortical regions that are implicated in motor control in the left intact hemisphere and in the spared motor regions of the right hemisphere; patients without anosognosia did not present with the same degree of activation. We conclude that the false belief of movement is associated with a combination of strategically placed brain lesions and the preceding residual neural activity of the fronto-parietal motor network. These findings provide evidence that the activity of motor cortices contributes to our beliefs about the state of our motor system.