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We used fMRI to explore the extent of the anatomical overlap of three neural systems that the literature on developmental dyslexia associates with reading: the auditory phonological, the visual magnocellular, and the motor/cerebellar systems. Twenty‐eight normal subjects performed four tasks during fMRI scans: word and pseudoword reading, auditory rhyming for letter names, visual motion perception, and a motor sequence learning task. We found that the left occipitotemporal cortex (OTC), which previous studies reported to be dysfunctional in dyslexia, can be fractionated into different functional areas: an anterior and lateral area that was activated by both reading and auditory rhyming tasks; a posterior area that was commonly activated by both the reading and the motion perception task and a medial/intermediate area, including the so‐called Visual Word Form Area, which was specifically activated by the reading task. These results show that the left OTC is an area of segregated convergence of different functional systems. We compared our results with the hypoactivation pattern reported for reading in a previous cross‐cultural PET study on 36 dyslexic subjects from three countries. The region of decreased activation in dyslexia overlapped with regions that are specific for reading and those activated during both the auditory rhyming task and the single word and pseudoword reading task described in the present fMRI study. No overlap was found with the activation patterns for the visual motion perception task or for the motor sequence learning task. These observations challenge current theories of dyslexia. Hum Brain Mapp 34:2669–2687, 2013. © 2012 Wiley Periodicals, Inc.

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.

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.

Creative production (related to art-making) and aesthetic appreciation (related to art-viewing) are inherently linked in visual arts, but their relationship has never been explored explicitly in cognitive neuroscience, nor the nature of such connection. The available literature suggests two cognitive processes as possible foundations of these two experiences: motor simulation or inhibitory control. In a meta-analysis of fMRI studies, we addressed this issue: we investigated whether there are shared neurofunctional underpinnings behind aesthetic and creative experiences in the visual domain; further, we examined whether any shared brain activation may reflect either motor simulation or inhibitory processes. A conjunction analysis revealed a common involvement of the pre-SMA in both classes of studies, a brain region, if anything, more concerned with top-down inhibitory motor and volitional cognitive control rather than bottom-up motor simulation. In the art-viewing domain, this finding was primarily driven by figurative rather than abstract art. The methodological limitations in the available literature are discussed together with possible new ways to expand the existing findings.

Highlights • Acute DOC patients with favourable outcome show preserved event-related electrodermal response. • Acute DOC patients showed reduced fALFF in the posterior cingulate cortex. • Event-related electrodermal activity correlated with the fALFFs in the PCC in the acute phase., An accurate prognosis on the outcome of brain-injured patients with disorders of consciousness (DOC) remains a significant challenge, especially in the acute stage. In this study, we applied a multiple-technique approach to provide accurate predictions on functional outcome after 6 months in 15 acute DOC patients. Electrophysiological correlates of implicit cognitive processing of verbal stimuli and data-driven voxel-wise resting-state fMRI signals, such as the fractional amplitude of low-frequency fluctuations (fALFF), were employed. Event-related electrodermal activity, an index of autonomic activation, was recorded in response to emotional words and pseudo-words at baseline (T0). On the same day, patients also underwent a resting-state fMRI scan. Six months later (T1), patients were classified as outcome-negative and outcome-positive using a standard functional outcome scale. We then revisited the baseline measures to test their predictive power for the functional outcome measured at T1. We found that only outcome-positive patients had an earlier, higher autonomic response for words compared to pseudo-words, a pattern similar to that of healthy awake controls. Furthermore, DOC patients showed reduced fALFF in the posterior cingulate cortex (PCC), a brain region that contributes to autonomic regulation and awareness. The event-related electrodermal marker of residual cognitive functioning was found to have a significant correlation with residual local neuronal activity in the PCC. We propose that a residual autonomic response to cognitively salient stimuli, together with a preserved resting-state activity in the PCC, can provide a useful prognostic index in acute DOC.

Dyslexia can have different manifestations: this has motivated different theories on its nature, on its underlying brain bases and enduring controversies on how to best treat it. The relative weight of the different manifestations has never been evaluated using both behavioural and fMRI measures, a challenge taken here to assess the major systems called into play in dyslexia by different theories. We found that adult well-compensated dyslexics were systematically impaired only in reading and in visuo-phonological tasks, while deficits for other systems (e.g., motor/cerebellar, visual magnocellular/motion perception) were only very occasional. In line with these findings, fMRI showed a reliable hypoactivation only for the task of reading, in the left occipito-temporal cortex (l-OTC). The l-OTC, normally a crossroad between the reading system and other systems, did not show the same level of intersection in dyslexics; yet, it was not totally silent because it responded, in segregated parts, during auditory phonological and visual motion perception tasks. This minimal behavioural and functional anatomical comorbidity demonstrates that a specific deficit of reading is the best description for developmental dyslexia, at least for adult well-compensated cases, with clear implications for rehabilitation strategies. The reduced intersection of multiple systems in the l-OTC suggests that dyslexics suffer from a coarser connectivity, leading to disconnection between the multiple domains that normally interact during reading.

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.

According to recent theories, drug addicted patients suffer of an impaired response inhibition and salience attribution (I-RISA) together with a perturbed connectivity between the nuclei accumbens (NAcs) and the orbito-prefrontal (oPFC) and dorsal prefrontal (dPFC) cortices, brain regions associated with motivation and cognitive control. To empirically test these assumptions, we evaluated the (neuro)psychological trait and the functional organization of the resting state brain networks associated with the NAcs in 18 former cocaine abusers (FCAs), while being in drug abstinence since 5 months. The psychological data were grouped into three empirical variables related with emotion regulation, emotion awareness and strategic and controlled behaviour. Comparison of the resting state patterns between the entire sample of FCAs and 19 controls revealed a reduction of functional connectivity between the NAcs and the dPFC and enhanced connectivity between the NAcs and the dorsal-striatum. In the 8 FCAs who relapsed into cocaine use after 3 months, the level of functional connectivity between the NAcs and dPFC was lower than the functional connectivity estimated in the group of patients that did not relapsed. Finally, in the entire sample of FCAs, the higher the connectivity between the NAc and the oPFC the lower was the level of strategic and controlled behaviour. Taken together, these results are compatible with models of the interactions between the NAcs, the dorsal striatum and frontal cortices in the I-RISA syndrome, showing that such interactions are particularly perturbed in patients at greater risk of relapse into cocaine abuse.

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 one's 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 patient's 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. © 2013 The Author.

The HAROLD (hemispheric asymmetry reduction in older adults) model, proposed by Cabeza in 2002, suggests that age-related neurofunctional changes are characterised by a significant reduction in the functional hemispheric lateralisation in the prefrontal cortex (PFC). The supporting evidence, however, has been derived from qualitative explorations of the data rather than from explicit statistical assessments of functional lateralisation. In contrast, the CRUNCH (compensation-related utilisation of neural circuits hypothesis) model posits that elderly subjects recruit additional brain regions that do not necessarily belong to the contralateral hemisphere as much as they rely on additional strategies to solve cognitive problems. To better assess the validity and generalisability of the HAROLD model, we analysed the fMRI patterns of twenty-four young subjects (age range: 18–30 years) and twenty-four healthy elderly subjects (age range: 50–80 years) collected during the performance of two linguistic/semantic tasks (a picture-naming task and a sentence judgment task) and two episodic long-term memory (eLTM) recognition tasks for the same materials. The functional hemispheric lateralisation in each group and the ensuing between-group differences were quantitatively assessed using statistical lateralisation maps (SLMs). The number of clusters showing a genuine HAROLD effect was proportional to the level of task demand. In addition, when quantitatively significant, these effects were not restricted to the PFC. We conclude that, in its original version, the HAROLD model captures only some of the age-related brain patterns observed in graceful ageing. The results observed in our study are compatible with the more general CRUNCH model, suggesting that the former patterns can be considered a special manifestation of age-related compensatory processes.

We studied the linguistic profile and neurolinguistic organization of a 14-year-old adolescent (EB) who underwent a left hemispherectomy at the age of 2.5 years. After initial aphasia, his language skills recovered within 2 years, with the exception of some word finding problems. Over the years, the neuropsychological assessments showed that EB's language was near-to-normal, with the exception of lexical competence, which lagged slightly behind for both auditory and written language. Moreover, EB's accuracy and speed in both reading and writing words and non-words were within the normal range, whereas difficulties emerged in reading loan words and in tasks with homophones. EB's functional magnetic resonance imaging (fMRI) patterns for several linguistic and metalinguistic tasks were similar to those observed in the dominant hemisphere of controls, suggesting that his language network conforms to a left-like linguistic neural blueprint. However, a stronger frontal recruitment suggests that linguistic tasks are more demanding for him. Finally, no specific reading activation was found in EB's occipitotemporal region, a finding consistent with the surface dyslexia-like behavioral pattern of the patient. While a lone right hemisphere may not be sufficient to guarantee full blown linguistic competences after early hemispherectomy, EB's behavioral and fMRI patterns suggest that his lone right hemisphere followed a left-like blueprint of the linguistic network.

We explored the neuropsychological and neuromorphometrical differences between probable Alzheimer's disease patients showing a good or a bad response to nine months treatment with donepezil. Before treatment, the neuropsychological profile of the two patient groups was perfectly matched. By the ninth month after treatment, theBAD-respondersshowed a decline of the MMSE score together with a progressive impairment of executive functions. A voxel-based morphometry investigation (VBM), at the time of the second neuropsychological assessment, showed that theBAD-respondershad larger grey and white matter atrophies involving the substantia innominata of Meynert bilaterally, the ventral part of caudate nuclei and the left uncinate fasciculus, brain areas belonging to the cholinergic pathways. A more widespread degeneration of the central cholinergic pathways may explain the lack of donepezil efficacy in those patients not responding to a treatment that operates on the grounds that some degree of endogeneous release of acetylcholine is still available.

Motor imagery (M.I.) is a mental state in which real movements are evoked without overt actions. There is some behavioural evidence that M.I. declines with ageing. The neurofunctional correlates of these changes have been investigated only in two studies, but none of the these studies has measured explicit correlations between behavioural variables and the brain response, nor the correlation of M.I. and motor execution (M.E.) of the same acts in ageing. In this paper, we report a behavioural and functional magnetic resonance imaging (fMRI) experiment that aimed to address this issue. Twenty-four young subjects (27 ± 5.6 years) and twenty-four elderly subjects (60 ± 4.6 years) performed two block-design fMRI tasks requiring actual movement (M.E.) or the mental rehearsal (M.I.) of finger movements. Participants also underwent a behavioural mental chronometry test in which the temporal correlations between M.I. and M.E. were measured. We found significant neurofunctional and behavioural differences between the elderly subjects and the young subjects during the M.E. and the M.I. tasks: for the M.E. task, the elderly subjects showed increased activation in frontal and prefrontal (pre-SMA) cortices as if M.E. had become more cognitively demanding; during the M.I. task, the elderly over-recruited occipito-temporo-parietal areas, suggesting that they may also use a visual imagery strategy. We also found between-group behavioural differences in the mental chronometry task: M.I. and M.E. were highly correlated in the young participants but not in the elderly participants. The temporal discrepancy between M.I. and M.E. in the elderly subjects correlated with the brain regions that showed increased activation in the occipital lobe in the fMRI. The same index was correlated with the premotor regions in the younger subjects. These observations show that healthy elderly individuals have decreased or qualitatively different M.I. compared to younger subjects.

Graceful aging has been associated with frontal hyperactivations in working- and episodic long-term memory tasks, a compensatory process, according to some, that allows the best normal elders to perform these tasks at a juvenile level, in spite of natural cortical impoverishment. In this study, 24 young and 24 healthy elderly participants were compared. Graceful aging was explored by investigating domains where most healthy elders perform like youngers (e.g. lexical-semantic knowledge) and tasks that are typically more challenging, like episodic long-term recognition memory tasks. With voxel-based morphometry, we also studied to what extent changes of fMRI activation were consistent with the pattern of brain atrophy. We found that hyperactivations and hypoactivations of the elders were not restricted to the frontal lobes, rather they presented with task-dependent patterns. Only hypoactivations and normal levels of activation systematically overlapped with regional atrophy. We conclude that compensatory processes associated with graceful aging may not necessarily be a sign of early saturation of executive resources, if this was to be represented by a systematic frontal hyperactivation, but rather they may represent the ability of recruiting new cognitive strategies. We discuss two possible approaches to further test this hypothesis.

BackgroundWorry 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.MethodEight 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.ResultsWe 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.ConclusionsThe 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.

The main defective manifestations of extra-personal unilateral spatial neglect concern the side of space contralateral to the hemispheric lesion (contralesional). Since the disorder is more frequent and severe after damage to the right hemisphere, patients typically fail to explore the left side and ignore stimuli located in that sector of space. The patients' behaviour in the side of space ipsilateral to the side of the lesion (ipsilesional) is not intact, however. In cancellation tasks, it can be observed that patients with unilateral neglect, in addition to failing to respond to contralesional stimuli, may show perseverative behaviour, crossing out many times the same stimulus in the ipsilesional side of the sheet. We analyzed the occurrence of this phenomenon during the execution of a cancellation task in a large series of brain-damaged patients with left- and right-sided hemispheric lesions, with and without evidence of unilateral spatial neglect; and in a group of patients suffering from senile dementia of the Alzheimer-type. Perseverative responses were found to be much more frequent in patients with spatial neglect and when the frontal lobe or subcortical structures were damaged. The results are interpreted in the context of a multi-componential view of the neglect syndrome. with reference to a distinction originally put forward by Derek Denny-Brown (1958) between 'frontal or magnetic' and 'parietal or repellent' apraxia. In patients with spatial neglect, frontal damage releases drawing perseverative behaviour in the ipsilesional sector of space. Perseveration in exploratory tasks constitutes a main instance of the productive manifestations of spatial neglect. (C) 2002 Elsevier Science Ltd. All rights reserved

We investigated cerebral activity in six normal volunteers using PET to explore the hypothesis that the right hemisphere has a specific role in the interpretation of figurative aspects of language such as metaphors. We also mapped the anatomical structures involved in sentence comprehension. During regional cerebral blood flow measurement subjects were asked to perform three different linguistic tasks: (i) metaphorical comprehension; (ii) literal comprehension of sentences; and (iii) a lexical-decision task. We found that comprehension of sentences compared with the lexical-decision task, induced extensive activation in several regions of the left hemisphere, including the prefrontal and basal frontal cortex, the middle and inferior temporal gyri and temporal pole, the parietal cortex and the precuneus. Comprehension of metaphors was associated with similar activations in the left hemisphere, but in addition, a number of sites were activated in the right hemisphere: the prefrontal cortex, the middle temporal gyrus, the precuneus and the posterior cingulate. We conclude that the interpretation of language involves widespread distributed systems bilaterally with the right hemisphere having a special role in the appreciation of metaphors.

LACK of awareness of touch associated with brain damage may transiently recover after stimulation of the vestibular system1,2. We used positron emission tomographic regional cerebral blood flow measurements to study the neurophysiological effect of vestibular stimulation on touch imperception in a subject with a right brain lesion. We tested the hypothesis that the vestibular system aids conscious tactile perception by introducing a bias in the neural system subserving body representation. We show that in normal subjects touch and vestibular signals share projections to the puta-men, insula, somatosensory area II, premotor cortex and supra-marginal gyrus. In our patient a subset of these regions (right putamen and insula) was spared by the lesion and was maximally active when touch and vestibular stimulations were combined. These results support the suggestion that our phenomenological consciousness is associated with activation in circumscribed brain areas specific to the particular sensation of which we are aware.