[Show abstract][Hide abstract] ABSTRACT: Purpose: We describe the case of a subject in a post-traumatic Minimally Conscious State (MCS) who retrieved full interaction with the environment after midazolam infusion. We studied EEG correlates of the "awakening reaction" in the different domains of frequency, time and cortical topography, along with the intrinsic connectivity within both the task-positive and the linguistic network. Methods: EEG recorded before and after midazolam administration has been submitted to spectral power analysis, sLORETA analysis and intrinsic connectivity analysis within both functional networks. Results: A critical change in the power spectrum profile was observed after midazolam: a) the power between 1 and 12 Hz decreased, reaching its maximum difference with respect to pre-infusion at about 7 Hz and b) the power between 12 and 30 Hz increased, with a maximum difference at about 15 Hz. At the same time, midazolam induced significant connectivity changes, especially for these two frequency bands, within both functional networks. Conclusions: We advance some hypotheses about certain aspects of the recovery from the MCS both in terms of anatomo-functional correlations and functional brain systems and we make inferences about the role that some kind of 'catatonic' symptoms might play in determining and/or maintaining this peculiar clinical state.
Restorative neurology and neuroscience 10/2014; · 4.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report the neuropsychological and MRI investigation of a patient (GP) who developed a selective impairment of spatial short-term memory (STM) following damage to the dorso-mesial areas of the right frontal lobe. We assessed in this patient spatial STM with an experimental procedure that evaluated immediate and 5-20 sec delayed recall of verbal, visual and spatial stimuli. The patient scored significantly worse than normal controls on tests that required delayed recall of spatial data. This could not be ascribed to a deficit of spatial episodic long-term memory because amnesic patients performed normally on these tests. Conversely, the patient scored in the normal range on tests of immediate recall of verbal, visual and spatial data and tests of delayed recall of verbal and visual data. Comparison with a previously described patient who had a selective deficit in immediate spatial recall and an ischemic lesion that affected frontal and parietal dorso-mesial areas in the right hemisphere (Carlesimo GA, Perri R, Turriziani P, Tomaiuolo F, Caltagirone C. Remembering what but not where: independence of spatial and visual working memory in the human brain. Cortex. 2001 Sep;37(4):519-34) suggests that the right parietal areas are involved in the short-term storage of spatial information and that the dorso-mesial regions of the right frontal underlie mechanisms for the delayed maintenance of the same data.
[Show abstract][Hide abstract] ABSTRACT: We examined the effects of visual deprivation at birth on the development of the corpus callosum in a large group of congenitally blind individuals. We acquired high-resolution T1-weighted MRI scans in 28 congenitally blind and 28 normal sighted subjects matched for age and gender. There was no overall group effect of visual deprivation on the total surface area of the corpus callosum. However, subdividing the corpus callosum into five subdivisions revealed significant regional changes in its three most posterior parts. Compared to the sighted controls, congenitally blind individuals showed a 12% reduction in the splenium, and a 20% increase in the isthmus and the posterior part of the body. A shape analysis further revealed that the bending angle of the corpus callosum was more convex in congenitally blind compared to the sighted control subjects. The observed morphometric changes in the corpus callosum are in line with the well-described cross-modal functional and structural neuroplastic changes in congenital blindness.
PLoS ONE 09/2014; 9(9):e107871. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Motivational valence plays a key role in orienting spatial attention. Nonetheless, clinical documentation and understanding of motivationally based deficits of spatial orienting in the human is limited. Here in a series of one group-study and two single-case studies, we have examined right brain damaged patients (RBD) with and without left spatial neglect in a spatial reward-learning task, in which the motivational valence of the left contralesional and the right ipsilesional space was contrasted. In each trial two visual boxes were presented, one to the left and one to the right of central fixation. In one session monetary rewards were released more frequently in the box on the left side (75 % of trials) whereas in another session they were released more frequently on the right side. In each trial patients were required to: 1) point to each one of the two boxes; 2) choose one of the boxes for obtaining monetary reward; 3) report explicitly the position of reward and whether this position matched or not the original choice. Despite defective spontaneous allocation of attention toward the contralesional space, RBD patients with left spatial neglect showed preserved contralesional reward learning, i.e. comparable to ispilesional learning and to reward learning displayed by patients without neglect. A notable exception in the group of neglect patients was L.R., who showed no sign of contralesional reward learning in a series of 120 consecutive trials despite being able of reaching learning criterion in only 20 trials in the ipsilesional space. L.R. suffered a cortical-subcortical brain damage affecting the anterior components of the parietal-frontal attentional network and, compared with all other neglect and non-neglect patients, had additional lesion involvement of the medial anterior cingulate cortex (ACC) and of the adjacent sectors of the corpus callosum. In contrast to his lateralized motivational learning deficit, L.R. had no lateral bias in the early phases of attentional processing as he suffered no contralesional visual or auditory extinction on double simultaneous tachistoscopic and dichotic stimulation and detected, with no exception, single contralesional visual and auditory stimuli. In a separate study, we were able to compare L.R. with another RBD patient, G.P., who had a selective lesion in the right ACC, in the adjacent callosal connections and the medial-basal prefrontal cortex. MC had no contralesional neglect and displayed normal reward learning both in the left and right side of space. These findings show that contralesional reward learning is generally preserved in RBD patients with left spatial neglect and that this can be exploited in rehabilitation protocols. Contralesional reward learning is severely disrupted in neglect patients when an additional lesion of the ACC is present: however, as demonstrated by the comparison between L.R. and G.P. cases, selective unilateral lesion of the right ACC does not produce motivational neglect for the contralesional space.
[Show abstract][Hide abstract] ABSTRACT: Objective: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects the corpus callosum (CC), which plays a key role in interhemispheric coupling in high-demand conditions. Using 3D callosal measurements and a letter-matching paradigm, this 2-part study investigated the neural substrate of interhemispheric coupling in individuals with AD or amnestic mild cognitive impairment (a-MCI) and age-matched healthy individuals (HC). Method: Thirty-three right-handed participants were MRI scanned to measure the volume of the CC in 5 sections. In Study 1, AD, a-MCI, and HC individuals performed a low-demand perceptual letter shape-matching task (e.g., A-A); in Study 2, a-MCI and HC individuals performed a "case-sensitive" letter-matching task (Study 2A) and a "load-sensitive" letter-matching task (Study 2B). Results: The results showed a positive correlation between Response Times and the midbody of the CC at the lowest cognitive demand level (Study 1) in participants with AD, and the total CC, midbody, caudal body, and isthmus of the CC at high cognitive demand levels (Study 2A) in normal aging. The volume of the anterior part of the CC was significantly negatively correlated with the interhemispheric behavioral indices for the a-MCI group (Study 1 and Study 2B). Conclusion: This study provides evidence that interhemispheric coupling may constitute a flexible mechanism that can improve the brain's ability to meet processing demands for low cognitive demand in AD and for high cognitive demand in normal aging. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
[Show abstract][Hide abstract] ABSTRACT: Backgrounds: Evidence exists that the observation of actions performed by others enhance word retrieval and can be used in aphasia rehabilitation to treat naming impairments. Aim: The aim of the present study was to assess to what extent action observation treatment may improve verb retrieval in chronic aphasics. Design: This was an observational study. Setting: Patients were recruited from the Neurorehabilitation Centre of Ancona Hospital. Population: Six aphasic patients underwent an intensive language training to improve verb naming. Methods:Language evaluation was carried out before and after the treatment. A rehabilitation therapy based on observation of actions was administered daily to each patient for two consecutive weeks. Four different rehabilitation procedures were adopted: 1) "observation of action performed by the examiner"; 2) "observation and then execution of action"; 3) "observation of videoclips of actions"; and, as a control condition; 4) "observation of action and execution of meaningless movement". Results: In four participants, a significant improvement in verb retrieval was found for the three experimental procedures (χ2 (3)=75.212, P<0.0001), with respect to the control condition. No significant improvement was observed in the two patients with severe deficits in verb semantics (χ2 (3)=0.592, P=0.892). Conclusions: Action observation therapy may become a useful intervention strategy to promote verb retrieval in aphasic patients. Clinical Rehabilitation Impact: The observation of videoclips of actions may be an efficacious alternative approach to traditional rehabilitation programs for lexical deficits. This finding endorses the planning of innovative low-cost interventions in language rehabilitation.
European journal of physical and rehabilitation medicine 03/2013; · 1.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The exact anatomical localization of right hemisphere lesions that lead to left spatial neglect is still debated. The effect of confounding factors such as acute diaschisis and hypoperfusion, visual field defects, and lesion size may account for conflicting results that have been reported in the literature. Here, we present a comprehensive anatomical investigation of the gray- and white matter lesion correlates of left spatial neglect, which was run in a sample 58 patients with subacute or chronic vascular strokes in the territory of the right middle cerebral artery. Standard voxel-based correlates confirmed the role played by lesions in the posterior parietal cortex (supramarginal gyrus, angular gyrus, and temporal-parietal junction), in the frontal cortex (frontal eye field, middle and inferior frontal gyrus), and in the underlying parietal-frontal white matter. Using a new diffusion tensor imaging-based atlas of the human brain, we were able to run, for the first time, a detailed analysis of the lesion involvement of subcortical white matter pathways. The results of this analysis revealed that, among the different pathways linking parietal with frontal areas, damage to the second branch of the superior longitudinal fasciculus (SLF II) was the best predictor of left spatial neglect. The group study also revealed a subsample of patients with neglect due to focal lesion in the lateral-dorsal portion of the thalamus, which connects the premotor cortex with the inferior parietal lobule. The relevance of fronto-parietal disconnection was further supported by complete in vivo tractography dissection of white matter pathways in 2 patients, one with and the other without signs of neglect. These 2 patients were studied both in the acute phase and 1 year after stroke and were perfectly matched for age, handedness, stroke onset, lesion size, and for cortical lesion involvement. Taken together, the results of the present study support the hypothesis that anatomical disconnections leading to a functional breakdown of parietal-frontal networks are an important pathophysiological factor leading to chronic left spatial neglect. Here, we propose that different loci of SLF disconnection on the rostro-caudal axis can also be associated with disconnection of short-range white matter pathways within the frontal or parietal areas. Such different local disconnection patterns can play a role in the important clinical variability of the neglect syndrome.
[Show abstract][Hide abstract] ABSTRACT: Spatial reasoning has a relevant role in mathematics and helps daily computational activities. It is widely assumed that in cultures with left-to-right reading, numbers are organized along the mental equivalent of a ruler, the mental number line, with small magnitudes located to the left of larger ones. Patients with right brain damage can disregard smaller numbers while mentally setting the midpoint of number intervals. This has been interpreted as a sign of spatial neglect for numbers on the left side of the mental number line and taken as a strong argument for the intrinsic left-to-right organization of the mental number line. Here, we put forward the understanding of this cognitive disability by discovering that patients with right brain damage disregard smaller numbers both when these are mapped on the left side of the mental number line and on the right side of an imagined clock face. This shows that the right hemisphere supports the representation of small numerical magnitudes independently from their mapping on the left or the right side of a spatial-mental layout. In addition, the study of the anatomical correlates through voxel-based lesion-symptom mapping and the mapping of lesion peaks on the diffusion tensor imaging-based reconstruction of white matter pathways showed that the rightward bias in the imagined clock-face was correlated with lesions of high-level middle temporal visual areas that code stimuli in object-centred spatial coordinates, i.e. stimuli that, like a clock face, have an inherent left and right side. In contrast, bias towards higher numbers on the mental number line was linked to white matter damage in the frontal component of the parietal-frontal number network. These anatomical findings show that the human brain does not represent the mental number line as an object with an inherent left and right side. We conclude that the bias towards higher numbers in the mental bisection of number intervals does not depend on left side spatial, imagery or object-centred neglect and that it rather depends on disruption of an abstract non-spatial representation of small numerical magnitudes.
[Show abstract][Hide abstract] ABSTRACT: In previous studies, we investigated a group of subjects who had suffered from a severe non missile traumatic brain injury (nmTBI) without macroscopic focal lesions and we found brain atrophy involving the hippocampus, fornix, corpus callosum, optic chiasm, and optic radiations. Memory test scores correlated mainly with fornix volumes [37,38]. In the present study, we re-examined 11 of these nmTBI subjects approximately 8 yr later. High-spatial resolution T1 weighted magnetic resonance images of the brain (1mm(3)) and standardised memory tests were performed once more in order to compare brain morphology and memory performance originally assessed 3-13 months after head injury (first study) and after 8-10 yr (present study). An overall improvement of memory test performance was demonstrated in the latest assessment, indicating that cognitive recovery in severe nmTBI subjects had not been completed within 3-13 months post-injury. It is notable that the volumes of the fornix and the hippocampus were reduced significantly from normal controls, but these volumes do not differ appreciatively between nmTBI subjects at first (after ∼1 yr) and at second (after ∼8 yr) scans. On the contrary, a clear reduction in the volume of the corpus callosus can be observed after ∼1 yr and a further significant reduction is evident after ∼8 yr, indicating that the neural degeneration in severe nmTBI continues long after the head trauma and relates to specific structures and not to the overall brain.
Brain research bulletin 03/2012; 87(4-5):373-82. · 2.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study tested the hypothesis of electroencephalographic reactivity (EEG-R) as a reliable tool for the prognostic evaluation of consciousness recovery in post-acute brain injury.
EEG was recorded in 50 unconscious patients. All patients had a GCS ≤8 and LCF score ≤2. They suffered from traumatic brain injury, cerebrovascular disease or anoxia. EEG was classified according to Synek classification (1988) as benign, malignant and 'uncertain significance'. EEG-R to painful stimuli was tested.
Twenty per cent of patients fulfilled the criteria for benign prognosis, 38% for malignant prognosis, while 42% of them were included in the 'uncertain' category, preventing them from stating a prognosis. EEG-R was detected in 48% of patients classified 'uncertain' and 92% of them recovered consciousness within 5 months from EEG recording. Multivariable analysis indicates that an unconscious patient admitted to the Rehabilitation Unit within 2 months from brain injury, with a LCF score equal to 2 and the presence of EEG-R has a probability of recovery of consciousness higher than 97%.
EEG-R is a good positive factor for the prognosis of recovery of consciousness in the post-acute phase of brain injury, with a high specificity (88.9%). Nevertheless, its absence is not invariably associated with a poor prognosis.
[Show abstract][Hide abstract] ABSTRACT: A number of studies have shown that modulating cortical activity by means of transcranial direct current stimulation (tDCS) affects the performance of both healthy and brain-damaged subjects. In this study, we investigated the potential of tDCS for the recovery of apraxia of speech in 3 patients with stroke-induced aphasia. Over 2 weeks, three aphasic subjects participated in a randomized double-blinded experiment involving intensive language training for their articulatory difficulties in two tDCS conditions. Each subject participated in five consecutive daily sessions of anodic tDCS (20 min, 1 mA) and sham stimulation over the left inferior frontal gyrus (referred to as Broca's area) while they performed a repetition task. By the end of each week, a significant improvement was found in both conditions. However, all three subjects showed greater response accuracy in the anodic than in the sham condition. Moreover, results for transfer of treatment effects, although different across subjects, indicate a generalization of the recovery at the language test. Subjects 2 and 3 showed a significant improvement in oral production tasks, such as word repetition and reading, while Subjects 1 and 2 had an unexpected significant recovery in written naming and word writing under dictation tasks. At three follow-ups (1 week, 1 and 2 months after the end of treatment), response accuracy was still significantly better in the anodic than in sham condition, suggesting a long-term effect on the recovery of their articulatory gestures.
Behavioural brain research 08/2011; 225(2):498-504. · 3.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Detailed cytoarchitectonic studies of the human cerebral cortex appeared during the first quarter of the 20th century. The incorporation of the cytoarchitectonic map by Brodmann (1909) in the Talairach proportional stereotaxic space (Talairach and Tournoux, 1988) has established the Brodmann numerical nomenclature as the basis for describing the cortical location of structural and functional findings obtained with modern neuroimaging. In experimental anatomical and physiological investigations of the macaque monkey performed during the last 50 years, the numerical architectonic nomenclature used to describe findings in the prefrontal cortex has been largely based on the map by Walker (1940). Unfortunately, the map by Walker was not based on a comparative investigation of the cytoarchitecture of the human and macaque monkey prefrontal cortex and, as a result, the nomenclature and the criteria for demarcating areas in the two primate species are not always consistent. These discrepancies are a major obstacle in the ability to compare experimental findings from nonhuman primates with results obtained in functional and structural neuroimaging of the human brain. The present article outlines these discrepancies in the classical maps and describes comparative investigations of the cytoarchitecture of the prefrontal cortex of the macaque monkey and human (Petrides and Pandya, 1994, 1999, 2002a) in order to resolve these discrepancies and enable easy translation of experimental research in the monkey to findings in the human brain obtained with modern neuroimaging.
[Show abstract][Hide abstract] ABSTRACT: One dimension of understanding the functions of the prefrontal cortex is knowledge of cortical connectivity. We have surveyed three aspects of prefrontal cortical connections: local projections (within the frontal lobe), the termination patterns of long association (post-Rolandic) projections, and the trajectories of major fiber pathways. The local connections appear to be organized in relation to dorsal (hippocampal origin) and ventral (paleocortical origin) architectonic trends. According to the proposal of a dual origin of the cerebral cortex, cortical areas can be traced as originating from archicortex (hippocampus) on the one hand, and paleocortex, on the other hand, in a stepwise manner (e.g., Sanides, 1969; Pandya and Yeterian, 1985). Prefrontal areas within each trend are connected with less architectonically differentiated areas, and also with more differentiated areas. Such organization may allow for the systematic exchange of information within each architectonic trend. The long connections of the prefrontal cortex with post-Rolandic regions seem to be organized preferentially in relation to dorsal and ventral prefrontal architectonic trends. Prefrontal areas are connected with post-Rolandic auditory, visual and somatosensory association areas, and with multimodal and paralimbic regions. This long connectivity likely works in conjunction with local connections to serve prefrontal cortical functions. The afferent and efferent connections of the prefrontal cortex with post-Rolandic regions are conveyed by specific long association pathways. These pathways as well appear to be organized in relation to dorsal and ventral prefrontal architectonic trends. Finally, although prefrontal areas have preferential connections in relation to dual architectonic trends, it is clear that there are interconnections between and among areas in each trend, which may provide a substrate for the overall integrative function of the prefrontal cortex. Prefrontal corticocortical connectivity may help to elucidate both region-specific and integrative perspectives on the functions of the prefrontal cortex.
[Show abstract][Hide abstract] ABSTRACT: A number of studies have shown that modulating cortical activity by means of transcranial direct current stimulation (tDCS) affects performances of both healthy and brain-damaged subjects. In this study, we investigated the potential of tDCS to enhance associative verbal learning in 10 healthy individuals and to improve word retrieval deficits in three patients with stroke-induced aphasia. In healthy individuals, tDCS (20 min, 1 mA) was applied over Wernicke's area (position CP5 of the International 10-20 EEG System) while they learned 20 new "words" (legal nonwords arbitrarily assigned to 20 different pictures). The healthy subjects participated in a randomized counterbalanced double-blind procedure in which they were subjected to one session of anodic tDCS over left Wernicke's area, one sham session over this location and one session of anodic tDCS stimulating the right occipito-parietal area. Each experimental session was performed during a different week (over three consecutive weeks) with 6 days of intersession interval. Over 2 weeks, three aphasic subjects participated in a randomized double-blind experiment involving intensive language training for their anomic difficulties in two tDCS conditions. Each subject participated in five consecutive daily sessions of anodic tDCS (20 min, 1 mA) and sham stimulation over Wernicke's area while they performed a picture-naming task. By the end of each week, anodic tDCS had significantly improved their accuracy on the picture-naming task. Both normal subjects and aphasic patients also had shorter naming latencies during anodic tDCS than during sham condition. At two follow-ups (1 and 3 weeks after the end of treatment), performed only in two aphasic subjects, response accuracy and reaction times were still significantly better in the anodic than in the sham condition, suggesting a long-term effect on recovery of their anomic disturbances.
Journal of Cognitive Neuroscience 10/2010; 23(9):2309-23. · 4.49 Impact Factor