Error-based training and emergent awareness in anosognosia for hemiplegia.

Residual forms of awareness have recently been demonstrated in subjects affected by anosognosia for hemiplegia, but their potential effects in recovery of awareness remain to date unexplored. Emergent awareness refers to a specific facet of motor unawareness in which anosognosic subjects recognise their motor deficits only when they have been requested to perform an action and they realise their errors. Four participants in the chronic phase after a stroke with anosognosia for hemiplegia were recruited. They took part in an "error-full" or "analysis of error-based" rehabilitative training programme. They were asked to attempt to execute specific actions, analyse their own strategies and errors and discuss the reasons for their failures. Pre- and post-training and follow-up assessments showed that motor unawareness improved in all four patients. These results indicate that unsuccessful action attempts with concomitant error analysis may facilitate the recovery of emergent awareness and, sometimes, of more general aspects of awareness.

Awareness of cognitive deficits and clinical competence in mild to moderate Alzheimer's disease: their relevance in clinical practice.

Awareness of cognitive deficits and clinical competence were investigated in 79 mild to moderate Alzheimer's disease patients. Awareness was assessed by the anosognosia questionnaire for dementia, and clinical competence by specific neuropsychological tests such as trail making test-A, Babcock story recall test, semantic and phonemic verbal fluency. The findings show that 66 % of the patients were aware of memory deficits, while the 34 % were unaware. Deficit in awareness correlated with lower scores on the Mini Mental State Examination test that, in the score range from 24.51 to 30 and from 19.50 to 24.50, appeared to be a significant predictor of level of awareness. None of the AD patients had fully preserved clinical competence, only 7 patients (9 %) had partially preserved clinical competence and 72 patients (91 %) had completely lost clinical competence. All the patients with partially preserved clinical competence (9 %) were aware of their memory deficit. The study indicates that neuropsychological tests used for the assessment of executive functions are not suitable for investigating clinical competence. Therefore, additional and specific tools for the evaluation of clinical competence are necessary. Indeed, these might allow clinicians to identify AD patients who, despite their deficits in selected functions, retain their autonomy of choice as well as recognize those patients who should proceed to the nomination of a legal representative.

Massive somatic deafferentation and motor deefferentation of the lower part of the body impair its visual recognition: a psychophysical study of patients with spinal cord injury.

Embodied cognition theories postulate that perceiving and understanding the body states of other individuals are underpinned by the neural structures activated during first-hand experience of the same states. This suggests that one's own sensorimotor system may be used to identify the actions and sensations of others. Virtual and real brain lesion studies show that visual processing of body action and body form relies upon neural activity in the ventral premotor and the extrastriate body areas, respectively. We explored whether visual body perception may also be altered in the absence of damage to the above cortical regions by testing healthy controls and spinal cord injury (SCI) patients whose brain was unable to receive somatic information from and send motor commands to the lower limbs. Participants performed tasks investigating the ability to visually discriminate changes in the form or action of body parts affected by somatosensory and motor disconnection. SCI patients showed a specific, cross-modal deficit in the visual recognition of the disconnected lower body parts. This deficit affected both body action and body form perception, hinting at a pervasive influence of ongoing body signals on the brain network dedicated to visual body processing. Testing SCI patients who did or did not practise sports allowed us to test the influence of motor practice on visual body recognition. We found better upper body action recognition in sport-practising SCI patients, indicating that motor practice is useful for maintaining visual representation of actions after deafferentation and deefferentation. This may be a potential resource to be exploited for rehabilitation.

What the study of spinal cord injured patients can tell us about the significance of the body in cognition.

Although in the last three decades philosophers, psychologists and neuroscientists have produced numerous studies on human cognition, the debate concerning its nature is still heated and current views on the subject are somewhat antithetical. On the one hand, there are those who adhere to a view implying 'disembodiment' which suggests that cognition is based entirely on symbolic processes. On the other hand, a family of theories referred to as the Embodied Cognition Theories (ECT) postulate that creating and maintaining cognition is linked with varying degrees of inherence to somatosensory and motor representations. Spinal cord injury induces a massive body-brain disconnection with the loss of sensory and motor bodily functions below the lesion level but without directly affecting the brain. Thus, SCI may represent an optimal model for testing the role of the body in cognition. In this review, we describe post-lesional cognitive modifications in relation to body, space and action representations and various instances of ECT. We discuss the interaction between body-grounded and symbolic processes in adulthood with relevant modifications after body-brain disconnection.

Back in control of intentional action: Improvement of ideomotor apraxia by mirror box treatment.

OBJECTIVES: A novel method of rehabilitation for ideomotor apraxia (IMA), using a modified version of the mirror box (MB), is proposed. The rationale is based on the theory that disrupted body representation occurs in IMA and that MB training may improve body representation. In the present MB training, patients observed and reproduced movements made by the experimenter in a mirror. The visual perspective gave the illusory sensation of seeing one's own affected hand in the mirror. METHODS: Thirteen patients were included in the study; apraxia was measured four times: i) at baseline; ii) after a week of unspecific poststroke rehabilitation (rest); iii) after a week of imitation training for apraxia, used as a control; and iv) after a week of MB training. Imitation and mirror box training were presented in counterbalanced order between participants. The effect of the mirror box on a measure of body representation was also assessed. RESULTS: The results show that MB training improved apraxia when compared to the outcomes in both the imitation and rest conditions. The improvement correlates with the impact of the mirror box on the body representation (i.e., the degree of embodiment). CONCLUSIONS: MB training shows promising effects in promoting recovery from apraxia. The hypothesis is that the mirror box triggers a quickly generated sense of embodiment of the reflected moving arm into the observer's body representation. This embodiment of the visuomotor features of the observed movements would positively affect motor programming, promoting motor improvement. Crucially, this effect seems to extend to actions performed outside the mirror box setup, enhancing patients' performance on an apraxia test.

Finger recognition and gesture imitation in Gerstmann's syndrome.

We report the association between finger agnosia and gesture imitation deficits in a right-handed, right-hemisphere damaged patient with Gerstmann's syndrome (GS), a neuropsychological syndrome characterized by finger and toe agnosia, left-right disorientation and dyscalculia. No language deficits were found. The patient showed a gestural imitation deficit that specifically involved finger movements and postures. The association between finger recognition and imitation deficits suggests that both static and dynamic aspects of finger representations are impaired in GS. We suggest that GS is a disorder of body representation that involves hands and fingers, that is, the non-facial body parts most involved in social interactions.

[Treadmills in rehabilitation medicine: technical characteristics and selection criteria]. / Il treadmill in medicina riabilitativa: caratteristiche tecniche e criteri di selezione.

The treadmill is a commonly used means of testing and training patients with cardiopulmonary diseases. There is growing interest in the use of the treadmill also for rehabilitation of patients with orthopaedic and neurological diseases. Commercially available treadmills show wide differences in terms of structure and function that have a direct impact on the specific rehabilitation protocols. The aims of this paper are: a) to briefly review the physiology and biomechanics of treadmill exercise as compared to overground walking; b) to point out the technical specifications of treadmills suitable for rehabilitation settings; c) to provide guidelines for treadmill selection in the different categories of rehabilitation patients. First, the different physiological and biomechanical characteristics of walking on a treadmill and overground are discussed. Uphill and downhill walking as well as backward walking are also presented together with the spin-offs for rehabilitation practice. Then, the technical features of treadmills (treadbelt, frame, bars, deck, rollers, shock absorption, elevation motor, drive motor, flywheel, display) are described and the specific requisites for the different patient categories undergoing rehabilitation are discussed in detail. Finally, guidelines and a flow-chart for identifying the main technical requisites for appropriate treadmill selection in the different disabilities are provided. A summary table of the technical specifications of the commercially available rehabilitation treadmills is also included.

Cognitive stimulation of executive functions in mild cognitive impairment: specific efficacy and impact in memory.

Executive functions play an important role in the maintenance of autonomy in day-to-day activities. Nevertheless, there is little research into specific cognitive training for Mild Cognitive Impairment (MCI). We present the results of a program which aims to teach specific strategies and metacognitive abilities in order for patients to be able to carry out attentional and executive tasks. Two groups (A and B) were compared in a cross-over design. After the first evaluation, Group A (but not B) participated in a six month cognitive stimulation program. After a second assessment, only Group B received treatment and then a final evaluation was carried out on both groups. The results show that: i) both groups improved their performance as an effect of training; ii) improvements generalized to memory and general cognitive tasks; iii) in the interval without training, Group B's performance worsened and iv) Group A partially maintained their results over time.

The Italian validation of the Anosognosia Questionnaire for Dementia in Alzheimer's disease.

Although the Anosognosia Questionnaire-Dementia (AQ-D) is one of the main instruments for assessing awareness in Alzheimer's disease (AD), the normative data were until now limited to people from Argentina and Japan. This study aims to validate this instrument in an European context, in particular in an Italian sample. In a multicenter project (Verona, Padova, and Trapani), 130 patients with AD and their caregivers participated in the study. Psychometric characteristics of AQ-D are confirmed indicating that the scale permits the early identification of anosognosia and the correct care management of patients. Indeed, anosognosia results to be present also in patients with very mild AD (moderate: 44.44%; mild: 47.17%; and very mild: 23.73%). Moreover, the results indicate that deficits in awareness may vary in severity and that different types of anosognosia may be identified.

Microvessels isolated from brain: localization of muscarinic sites by radioligand binding and immunofluorescent techniques.

The present investigation was carried out to determine the extent to which muscarinic acetylcholine receptors (mAChRs) in vascular and perivascular structures were colocalized with glial fibrillary acidic protein (GFAP)-positive structures. To this aim, an immunocytochemical approach on free-floating cryosections and isolated microvessels obtained from rat brain was performed to study the possible colocalization of immunostaining with the anti-mAChR protein antibody (M35) and an anti-GFAP antibody. Double-labeling experiments were carried out by fluorescent techniques. Confocal microscopic observations of GFAP and M35 immunoreactivities on free-floating sections showed a high degree of colocalization on astrocyte processes associated with large vessels or capillaries. This pattern suggests that muscarinic receptors are associated with astrocytic endfeet. Confocal microscopic observations of immunoreactivity from isolated cerebral microvessels strengthen this conclusion since double-labeling of M35 and GFAP showed that perivascular astrocytic structures remained attached to the isolated microvessels and were present on vascular segments showing M35 immunoreactivity. In another set of experiments, the specific binding of [3H]quinuclidinylbenzylate ([3H]QNB) to isolated microvessel membrane preparations from cerebral cortex, caudate nucleus, thalamus, and cerebellum showed that a constant binding yield (20% in bovine and 40% in rat) was observed for microvessels compared with the corresponding brain region. According to our immunocytochemical results, the astrocytic membrane remaining attached to microvessels may account for the majority of the muscarinic binding to isolated microvessels. [3H]QNB binding values found in isolated microvessels cannot therefore be considered as artifacts without any link with vascular function. Taken together, the present study strengthens the idea that the muscarinic receptors may be implicated in the functional relationship between glial and vascular structures.

Tactile salience influences extinction.

We delivered unilateral (left or right) or bilateral tactile stimuli to hands or feet of right-brain-damaged patients, six with tactile extinction and two without. Stimuli were simple touches or sliding stimuli directed proximo-distally (e.g., toward the fingers) or disto-proximally (e.g., toward the forearm). Patients were asked to report number (one or two), type (touch or slide), and direction (proximo-distally or disto-proximally) of the experimental stimuli. Nonextinction patients performed perfectly. Extinction patients, although accurate in reporting single stimuli, omitted left stimuli under double-stimuli conditions. However, the number of left stimuli detected consciously was related to an imbalance of the salience between left and right stimuli. Moreover, in three patients the extinguished, left-sided stimulus, even when inaccessible to consciousness, influenced implicitly the report of the features of the right stimulus. Thus, the relationships between left and right stimuli can modulate both overtly and covertly the performance of extinction patients.

Influence of perceptual and semantic conflicts between the two halves of chimeric stimuli on the expression of visuo-spatial neglect.

We investigated how perceptual and semantic relationships between the left and right half of chimeric stimuli influence overt and covert visual processing by asking eight right brain damaged (RBD) patients with hemispatial neglect to identify complete, half-, and chimeric drawings. Chimeric stimuli belonged in one of four categories defined according to the perceptual and semantic relatedness between the two compounding hemi-figures. Thus, the hemi-figures could be related both perceptually and semantically, only perceptually, only semantically, or neither perceptually nor semantically. Although patients often appeared to base their report on the right part of the chimerics, the number of errors was minimal when conflicts between the two hemi-figures were maximal. Moreover, perceptual conflicts, which mainly affect the perception of the shape, appeared to influence the performance more than semantic conflicts. Since the analysis of shape incongruency is probably accomplished at early levels of information processing, the result suggests that preattentive analysis is largely spared in the experimental patients and that, in our task, bottom-up factors more than top-down factors modulate the expression of left neglect.

Regional study of the co-localization of neuronal nitric oxide synthase with muscarinic receptors in the rat cerebral cortex.

There is increasing evidence that nitric oxide is an important molecular messenger involved in a wide variety of biological processes including the regulation of the cerebral circulation. For instance, it has been implicated in the vascular response to nucleus basalis magnocellularis stimulation, a structure which is widely recognized as the predominant source of cholinergic fibres projecting to the neocortex. The present investigation was carried out to determine if muscarinic receptors are present on cortical neurons expressing neuronal nitric oxide synthase (nitric oxide-producing enzyme). To this aim, double labelling of both neuronal nitric oxide synthase/vessels and neuronal nitric oxide synthase/muscarinic receptors was performed on free-floating cryosections obtained from rat brain. The observations were made by confocal laser scanning microscopy. The double labelling of neuronal nitric oxide synthase with the arterioles demonstrated the presence of nitroxidergic fibres in the wall of intraparenchymal vessels. A rich network of nitroxidergic fibres independent of the vessels was also seen in the parenchyma. Since the maximal surface of a square of tissue without any nitroxidergic fibres corresponded to 1400 +/- 105 microns2, the distance separating any cortical point from its closest neuronal nitric oxide synthase-positive fibre was never higher than 25 microns (half diagonal of square). According to models of the diffusional spread of nitric oxide, it is likely that nitric oxide can reach the whole cortical volume. Our results on the regional study of neuronal nitric oxide synthase/muscarinic receptors showed a high density of neuronal nitric oxide synthase-positive neurons principally in the frontal and perirhinal cortices and a low density in the occipital cortex. These data fit well with the known pattern of cortical projections from the nucleus basalis magnocellularis as revealed by anterogradely transported markers. The double labelling showed that about 10% of neuronal nitric oxide synthase-positive neurons were co-localized with muscarinic receptors in the frontoparietal cortex. In agreement with previous papers, the vascular innervation by nitroxidergic neuronal processes was often found to lie near the branching points of arterioles. Such localization allows neuronal nitric oxide synthase-positive neurons an extensive control of the vascular tree without requiring a large number of neuronal commands. Therefore, despite the low level of neuronal nitric oxide synthase/muscarinic receptor co-localization, this neuronal subpopulation could represent a possible relay implicated in the vascular effects of the nucleus basalis magnocellularis.

Acromegaly and bronchial carcinoid. Effect of removal of the latter.

A patient with a long-standing history of bronchial carcinoid and acromegaly was studied. There was pituitary enlargement with an intrasellar mass (brain computed tomography scan), high basal GH levels, and abnormal GH and other pituitary hormones response to oral glucose and a combined test (LHRH, TRH, insulin). After resection of the bronchial carcinoid, basal GH was normal, GH was normally suppressed during OGTT, pituitary function was within expected normal range, and there was regression of the pituitary tumor together with clinical improvement. These data suggest that the patient's acromegaly was secondary to pituitary stimulation due to the bronchial carcinoid.

Distribution of muscarinic receptors on the endothelium of cortical vessels in the rat brain.

Functional and pharmacological studies have suggested that there are muscarinic receptors (mAChRs) on the endothelial cells of major cerebral arteries, while recent immunological studies indicate that there are no mAChRs on the endothelium of brain capillaries. This difference may be because the distribution of mAChR on the endothelium varies with the type of vessel. This paper examines the distribution of mAChR on the vascular endothelium along intraparenchymal blood vessels in the rat brain by immunolabelling and laser confocal microscopy. Sections were immunostained by combinations of an anti-mAChR antibody (M35) with antibodies to endothelial (anti-GLUT1), or to smooth muscle markers (anti-actin). Antibody labellings were detected with fluorescent second antibodies. Most of the penetrating vessels bore mAChR immunolabelling which coincided over almost all the vessel surface with endothelial labelling. The mAChR immunolabelling was less widespread over the endothelium on the medium sized vessels (diameter < 50 microm) and only 50% of these vessels had mAChR staining on the endothelium. There was no mAChR immunostaining on the endothelium of the capillaries. In contrast with the basilar artery, there was no mAChR immunolabelling on the smooth muscle layer of the intracortical vessels. These data indicate that the intensity of mAChR immunolabelling decreases along the vascular tree from large conducting vessels to capillaries.

["Occult" ectopic ACTH secretion syndrome: a case report]. / Síndrome de secreción ectópica de ACTH "oculto": a propósito de un caso.

The occult ectopic ACTH syndrome is ACTH-dependent hypercortisolemia of non pituitary origin, and of more than 6 months duration without the diagnosis of the origin. We report a 55 years old woman diagnosed of Cushing syndrome and treated by mean of bilateral adrenalectomy, in which is discovered an ACTH-secreting carcinoid tumor 20 years later.

[An adrenal carcinoma producing androgens, estrogens and cortisol]. / Carcinoma suprarrenal productor de andrógenos, estrógenos y cortisol.

Carcinoma of the adrenal cortex is a fairly rare entity, usually with a somber prognosis. The efficacy of treatment depends on early prognosis. We are reporting here a case of carcinoma of the adrenal cortex producing androgens, estrogens and cortisol, in which diagnosis was not achieved until two years after the onset of symptoms. Morphologic studies by CT showed local extension and metastases. After mass-reduction surgery, the patient died due to respiratory failure. This case remarks the importance of early diagnosis in this syndrome.

Cognitive stimulation in a-MCI: an experimental study.

Nowadays, preventing the effects of mental decline is an international priority, but there is little research into cognitive training in mild cognitive impairment (MCI). We present the results of a program aimed at teaching memory strategies and improving metacognitive abilities. This was associated with training to ameliorate caregivers' assistance. Two groups (A and B) were compared in a crossover design. After the first evaluation, group A (but not B) participated in a 6-month cognitive stimulation program. After a second assessment, only B received treatment and then a final evaluation was carried out on both the groups. The results show that (1) both the groups improved their performance as an effect of training; (2) improvements are specific to the functions trained; (3) in the interval without intervention, performance of group B worsened; and (4) group A has maintained their results over time. In conclusion, our results show that specific training may reduce memory impairment in MCI.

Visual body recognition in a prosopagnosic patient.

Conspicuous deficits in face recognition characterize prosopagnosia. Information on whether agnosic deficits may extend to non-facial body parts is lacking. Here we report the neuropsychological description of FM, a patient affected by a complete deficit in face recognition in the presence of mild clinical signs of visual object agnosia. His deficit involves both overt and covert recognition of faces (i.e. recognition of familiar faces, but also categorization of faces for gender or age) as well as the visual mental imagery of faces. By means of a series of matching-to-sample tasks we investigated: (i) a possible association between prosopagnosia and disorders in visual body perception; (ii) the effect of the emotional content of stimuli on the visual discrimination of faces, bodies and objects; (iii) the existence of a dissociation between identity recognition and the emotional discrimination of faces and bodies. Our results document, for the first time, the co-occurrence of body agnosia, i.e. the visual inability to discriminate body forms and body actions, and prosopagnosia. Moreover, the results show better performance in the discrimination of emotional face and body expressions with respect to body identity and neutral actions. Since FM's lesions involve bilateral fusiform areas, it is unlikely that the amygdala-temporal projections explain the relative sparing of emotion discrimination performance. Indeed, the emotional content of the stimuli did not improve the discrimination of their identity. The results hint at the existence of two segregated brain networks involved in identity and emotional discrimination that are at least partially shared by face and body processing.