Gabriella Bottini

Identification of the central vestibular projections in man: a positron emission tomography activation study

The cerebral representation of space depends on the integration of many different sensory inputs. The vestibular system provides one such input and its dysfunction can cause profound spatial disorientation. Using positron emission tomography (PET), we measured regional cerebral perfusion with various vestibular stimulations to map central vestibular projections and to investigate the cerebral basis of spatial disorientation. We showed that the temporoparietal cortex, the insula, the putamen, and the anterior cingulate cortex are the cerebral projections of the vestibular system in man and that the spatial disorientation caused by unilateral vestibular stimulation is associated with their asymmetric activation.

EXPLORING SOMATOSENSORY HEMINEGLECT BY VESTIBULAR STIMULATION

The effects of vestibular stimulation upon somatosensory deficits or tactile extinction contralateral to a hemispheric lesion were investigated in 20 right brain-damaged patients and 11 left brain-damaged patients. After stimulation, right brain-damaged patients showed a temporary partial recovery from left hemianaesthesia or extinction. Conversely, right somatosensory deficits associated with left brain damage were virtually unaffected by vestibular stimulation. Temporary recovery from somatosensory deficits was independent of the presence of visuo-spatial hemineglect. The suggestion is made that somatosensory deficits and extinction produced by right brain damage have an important non-sensory or perceptual component, that may be positively affected by vestibular stimulation. The mechanisms whereby this treatment may ameliorate somatosensory deficits may involve the restoration of the normal correspondence between somatotopic and egocentric representations of the body.

Neural correlates of worry in generalized anxiety disorder and in normal controls: a functional MRI study.

BACKGROUND Worry is considered a key feature of generalized anxiety disorder (GAD), whose neural correlates are poorly understood. It is not known whether the brain regions involved in pathological worry are similar to those involved in worry-like mental activity in normal subjects or whether brain areas associated with worry are the same for different triggers such as verbal stimuli or faces. This study was designed to clarify these issues. METHOD Eight subjects with GAD and 12 normal controls underwent functional magnetic resonance imaging (fMRI) mood induction paradigms based on spoken sentences or faces. Sentences were either neutral or designed to induce worry. Faces conveyed a sad or a neutral mood and subjects were instructed to empathize with those moods. RESULTS We found that the anterior cingulate and dorsal medial prefrontal cortex [Brodmann area (BA) 32/23 and BA 10/11] were associated with worry triggered by sentences in both subjects with GAD and normal controls. However, GAD subjects showed a persistent activation of these areas even during resting state scans that followed the worrying phase, activation that correlated with scores on the Penn State Worry Questionnaire (PSWQ). This region was activated during the empathy experiment for sad faces. CONCLUSIONS The results show that worry in normal subjects and in subjects with GAD is based on activation of the medial prefrontal and anterior cingulate regions, known to be involved in mentalization and introspective thinking. A dysregulation of the activity of this region and its circuitry may underpin the inability of GAD patients to stop worrying.

Feeling touches in someone else's hand.

Cerebral damage may induce a delusional belief so that patients claim that their limbs contralateral to the side of the lesion belong to someone else (somatoparaphrenia). This disorder, which is not due to a general delirium, is frequently accompanied by the inability to feel tactile sensations in the ‘non-belonging’ part of the body. We report the unique case of a patient with somatoparaphrenia in whom dense tactile imperception in the left hand dramatically recovered when she was instructed to report touches delivered to her nieces hand, rather than to her own hand. We suggest that, through this verbal instruction, the mismatch between the patients belief about the ownership of her left hand and her ability to perceive touch on it was transiently recomposed. This is evidence that apparently elementary deficits, such as hemianesthesia, and selective delusional behavior, such as somatoparaphrenia, may both originate from an impairment of the body image.

Dopaminergic stimulation in unilateral neglect

OBJECTIVE To explore the hypothesis that dopaminergic circuits play a part in the premotor components of the unilateral neglect syndrome, the effects of acute dopaminergic stimulation in patients with neglect were studied. METHODS Two tasks were evaluated before and after subcutaneous administration of apomorphine and placebo: a circle crossing test and a test of target exploration (a modified version of the bell test), performed both in perceptual (counting) and in perceptual-motor (pointing) conditions. SUBJECTS Four patients with left neglect. RESULTS After dopaminergic stimulation, a significant improvement was found compared with placebo administration and baseline evaluation, in the performance of the two tests. Three of the patients had a more marked improvement in the perceptual-motor condition (pointing) of the task than the perceptual condition (counting). CONCLUSIONS The findings suggest that dopaminergic neuronal networks may mediate, in different ways, both perceptive and premotor components of the unilateral neglect syndrome.

Anosognosia for left-sided motor and sensory deficits, motor neglect, and sensory hemiinattention: is there a relationship?

In recent years, research on unilateral spatial neglect has focused on dissociations between different aspects of the clinical syndrome, which is now considered by many students as a multi-componential disorder. Notwithstanding this leading view, there is at least one empirical argument which supports a unitary interpretation of the disorder. This is based on the observation, now replicated many times, that a variety of sensory stimulations (vestibular, optokinetic, transcutaneous mechanical vibration and nervous electrical, visual prism adaptation) involving a lateral change (left-right asymmetry) in the input pattern, affect in a very similar fashion virtually all manifestations of the syndrome, including: visuo-spatial neglect; hemianaesthesia (somatosensory hemi-inattention); extinction, hemiparesis, hemiplegia, and anosognosia for these motor disorders; somatoparaphrenia. These effects may be accounted for with reference to a spatial medium, articulated in a number of specific components, which is modulated by sensory input in a fundamentally similar fashion. Recent investigations concerning the neural bases of some of these stimulations support this view. In this chapter the case of the co-variation of the effects of vestibular stimulation on motor deficits and on anosognosia for hemiplegia is considered. The suggestion is made that one mechanism underlying anosognosia for hemiplegia is unawareness of a deficit of intention, or movement planning component, rather than, or in addition to, unawareness of a primary motor deficit. Temporary remission of anosognosia after vestibular stimulation may represent recovery from this neglect-related component, of which, as of other manifestations of the syndrome, patients are typically unaware. The recovered intention to move may allow the detection by the patient of the presence of a residual primary motor deficit, through a feedback mechanism.

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.

VISUAL NEGLECT FOR FAR AND NEAR EXTRA-PERSONAL SPACE IN HUMANS

The possible dissociation of unilateral neglect in far and near extra-personal space was systematically investigated using a modified version of the Wundt-Jastrow area illusion test. This task, which requires no motor response, has been shown to be sensitive to unilateral neglect. Stimuli were presented at two different distances (near and far) to a group of 70 patients with right hemispheric lesion (18 in acute and 52 in chronic stage). Twenty-eight patients evidenced unilateral neglect; that is, they displayed unexpected (i.e., contrary to the known illusory effect) responses when the stimuli were perceived as oriented toward the left side. However, performances in the two conditions were highly correlated and there were no individual instances of dissociation. These results suggest that the presence of a motor response may be necessary to show behavioral dissociations between different parts of extra-personal space.

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.