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Biomedical subjects

D Perani

Publications and source records attributed to D Perani.

At least 19 recordsLinked to original sources

Action and object processing in aphasia: from nouns and verbs to the effect of manipulability.

The processing of words and pictures representing actions and objects was tested in 21 aphasic patients and 20 healthy controls across three word production tasks: picture-naming (PN), single word reading (WR) and word repetition (WRP). Analysis 1 targeted task and lexical category (noun-verb), revealing worse performance on PN and verb items for both patients and control participants. For Analysis 2 we used data collected in a concurrent gesture norming study to re-categorize the noun-verb items along hand imagery parameters (i.e., objects that can/cannot be manipulated and actions which do/do not involve fine hand movements). Here, patients displayed relative difficulty with the 'manipulable' items, while controls displayed the opposite pattern. Therefore, whereas the noun-verb distinction resulted simply in lower verb accuracy across groups, the 'manipulability' distinction revealed a 'double-dissociation' between patients and control participants. These results carry implications for theories of embodiment, lexico-semantic dissociations, and the organization of meaning in the brain.

Adult↗

Diffusion tensor imaging and voxel based morphometry study in early progressive supranuclear palsy.

BACKGROUND: A comprehensive characterisation of grey and white matter changes in progressive supranuclear palsy (PSP), the second most common extrapyramidal syndrome after Parkinson disease, is still not available. OBJECTIVE: To evaluate grey and white matter changes in mild PSP patients by voxel based morphometry (VBM) and diffusion tensor imaging (DTI), respectively. METHODS: 14 mild PSP patients and 14 healthy controls entered the study and underwent a clinical and neuropsychological evaluation according with a standardised assessment. Each subject had a structural magnetic resonance imaging (MRI) study. Processing analysis of MRI data was carried out according to optimised VBM and fractional anisotropy was determined. RESULTS: Compared with the controls, in PSP patients VBM analysis showed a significant clusters of reduced grey matter in premotor cortex, frontal operculum, anterior insula, hippocampus, and parahippocampal gyrus, bilaterally. With regard to subcortical brain regions, the pulvinar, dorsomedial and anterior nuclei of the thalamus, and superior and inferior culliculum were affected bilaterally. A bilateral decrease in fractional anisotropy in superior longitudinal fasciculus, anterior part of corpus callosum, arcuate fascicolus, posterior thalamic radiations, and internal capsule, probably involving the cortico-bulbar tracts, was present in PSP patients. CONCLUSIONS: These data provide evidence for both grey and white matter degeneration in PSP from the early disease stage. These structural changes suggest that atrophy of cortical and subcortical structures and neurodegeneration of specific fibre tracts contribute to neurological deficits in PSP.

Aged↗

Brain abnormalities underlying altered activation in dyslexia: a voxel based morphometry study.

Voxel-based morphometry was used to assess the consistency among functional imaging and brain morphometry data in developmental dyslexia. Subjects, from three different cultural contexts (UK, France and Italy), were the same as those described in a previous PET activation paper, which revealed a common pattern of reduced activation during reading tasks in the left temporal and occipital lobes. We provide evidence that altered activation observed within the reading system is associated with altered density of grey and white matter of specific brain regions, such as the left middle and inferior temporal gyri and the left arcuate fasciculus. This supports the view that dyslexia is associated with both local grey matter dysfunction and with altered connectivity among phonological/reading areas. The differences were replicable across samples confirming that the neurological disorder underlying dyslexia is the same across the cultures investigated in the study.

Adult↗

Anosognosia in very mild Alzheimer's disease but not in mild cognitive impairment.

OBJECTIVE: To study awareness of cognitive dysfunction in patients with very mild Alzheimer's disease (AD) and subjects with mild cognitive impairment (MCI). METHODS: A complaint interview covering 13 cognitive domains was administered to 82 AD and 79 MCI patients and their caregivers. The patient groups were comparable according to age and education, and Mini Mental State Examination (MMSE) scores were > or =24 in all cases. The discrepancy between the patients' and caregivers' estimations of impairments was taken as a measure of anosognosia. RESULTS: Self-reports of cognitive difficulties were comparable for AD and MCI patients. However, while in comparison to caregivers MCI patients reported significantly more cognitive impairment (p < 0.05), AD patients complained significantly less cognitive dysfunctions (p < 0.001). CONCLUSIONS: While most MCI patients tend to overestimate cognitive deficits when compared to their caregiver's assessment, AD patients in early stages of disease underestimate cognitive dysfunctions. Anosognosia can thus be regarded as a characteristic symptom at a stage of very mild AD (MMSE > or =24) but not MCI. Accordingly, medical history even in mildly affected patients should always include information from both patient and caregiver.

Aged↗

Combined 99mTc-ECD SPECT and neuropsychological studies in MCI for the assessment of conversion to AD.

Identifying pre-clinical Alzheimer's disease (AD) in subjects with mild cognitive impairment (MCI) is a major issue in clinical diagnosis. Establishing a combination of predictive markers from different fields of research might help in increasing the diagnostic accuracy. Aim of this study was to evaluate the potential role of 99mTc-ECD single photon emission computed tomography (SPECT) and memory scores in predicting conversion to AD in MCI subjects. Thirty-one MCI subjects underwent a clinical and neuropsychological examination, and a regional cerebral blood flow (rCBF) SPECT scan at baseline. Subjects had been followed periodically through 2 years in order to monitor the progression of cognitive symptoms. Canonical variate analysis of principal components was able to separate all subjects who converted to AD from those who remained stable, the former being characterized by a specific hypometabolic pattern, involving the parietal and temporal lobes, precuneus, and posterior cingulate cortex. Canonical correlation analysis of combined baseline memory deficits and rCBF SPECT images identified pre-clinical AD with a sensitivity and specificity of 77.8%. The pattern of hypoperfusion 99mTc-ECD SPECT and the severity of memory deficits predict the risk of progression to probable AD dementia in MCI subjects.

Alzheimer Disease↗

Cerebral metabolic correlates of four dementia scales in Alzheimer's disease.

Different scales can be used to evaluate dementia severity in Alzheimer's disease (AD). They do assess different cognitive or functional abilities, but their global scores are frequently in mutual correlation. Functional imaging provides an objective method for the staging of dementia severity. Positron emission tomography was used to assess the relationship between brain metabolism and four dementia scales that reflect a patient's global cognitive abilities (mini mental state), caregiver's evaluation of cognitive impairment (newly designed scale), daily living functioning (instrumental activities of daily living) and global dementia (clinical dementia rating). We wondered whether different clinical dementia scales would be related to severity of metabolic impairment in the same brain regions, and might reflect impairment of common cognitive processes. 225 patients with probable AD were recruited in a prospective multicentre European study. All clinical scales were related to brain metabolism in associative temporal, parietal or frontal areas. A factorial analysis demonstrated that all scales could be classified in a single factor. That factor was highly correlated to decrease of cerebral activity in bilateral parietal and temporal cortices, precuneus, and left middle frontal gyrus. This finding suggests that global scores for all scales provided similar information on the neural substrate of dementia severity. Capitalizing on the neuroimaging literature, dementia severity reflected by reduced metabolism in posterior and frontal associative areas in AD might be related to a decrease of controlled processes.

Activities of Daily Living↗

MCI conversion to dementia and the APOE genotype: a prediction study with FDG-PET.

OBJECTIVES: To investigate whether the combination of fluoro-2-deoxy-d-glucose (FDG) PET measures with the APOE genotype would improve prediction of the conversion from mild cognitive impairment (MCI) to Alzheimer disease (AD). METHOD: After 1 year, 8 of 37 patients with MCI converted to AD (22%). Differences in baseline regional glucose metabolic rate (rCMRglc) across groups were assessed on a voxel-based basis using a two-factor analysis of variance with outcome (converters [n = 8] vs nonconverters [n = 29]) and APOE genotype (E4 carriers [E4+] [n = 16] vs noncarriers [E4-] [n = 21]) as grouping factors. Results were considered significant at p < 0.05, corrected for multiple comparisons. RESULTS: All converters showed reduced rCMRglc in the inferior parietal cortex (IPC) as compared with the nonconverters. Hypometabolism in AD-typical regions, that is, temporoparietal and posterior cingulate cortex, was found for the E4+ as compared with the E4- patients, with the E4+/converters (n = 5) having additional rCMRglc reductions within frontal areas, such as the anterior cingulate (ACC) and inferior frontal (IFC) cortex. For the whole MCI sample, IPC rCMRglc predicted conversion to AD with 84% overall diagnostic accuracy (p = 0.003). Moreover, ACC and IFC rCMRglc improved prediction for the E4+ group, yielding 100% sensitivity, 90% specificity, and 94% accuracy (p < 0.0005), thus leading to an excellent discrimination. CONCLUSION: Fluoro-2-deoxy-d-glucose-PET measures may improve prediction of the conversion to Alzheimer disease, especially in combination with the APOE genotype.

Aged↗

Regional reductions of gray matter volume in familial dyslexia.

An in vivo anatomic study of gray matter volume was performed in a group of familial dyslexic individuals, using an optimized method of voxel-based morphometry. Focal abnormalities in gray matter volume were observed bilaterally in the planum temporale, inferior temporal cortex, and cerebellar nuclei, suggesting that the underlying anatomic abnormalities may be responsible for defective written language acquisition in these subjects.

Adolescent↗

Brain activity during intra- and cross-modal priming: new empirical data and review of the literature.

A positron emission tomography (PET) study was conducted to investigate the neurofunctional correlate of auditory within-modality and auditory-to-visual cross-modality stem completion priming. Compared to the auditory-to-auditory priming condition, cross-modality priming was associated with a significantly larger regional cerebral blood flow (rCBF) decrease at the boundary between left inferior temporal and fusiform gyri, brain regions previously associated with modality independent lexical retrieval and reading. Instead, within-modality auditory priming was associated with a bilateral pattern of prefrontal rCBF increase. This was likely the expression of more efficient access to output lexical representations and involuntary retrieval of the recent episode during which the just generated word had been encountered.

Acoustic Stimulation↗

A functional-anatomical model for lipreading.

Regional cerebral blood flow (rCBF) PET scans were used to study the physiological bases of lipreading, a natural skill of extracting language from mouth movements, which contributes to speech perception in everyday life. Viewing connected mouth movements that could not be lexically identified and that evoke perception of isolated speech sounds (nonlexical lipreading) was associated with bilateral activation of the auditory association cortex around Wernicke's area, of left dorsal premotor cortex, and left opercular-premotor division of the left inferior frontal gyrus (Broca's area). The supplementary motor area was active as well. These areas have all been implicated in phonological processing, speech and mouth motor planning, and execution. In addition, nonlexical lipreading also differentially activated visual motion areas. Lexical access through lipreading was associated with a similar pattern of activation and with additional foci in ventral- and dorsolateral prefrontal cortex bilaterally and in left inferior parietal cortex. Linear regression analysis of cerebral blood flow and proficiency for lexical lipreading further clarified the role of these areas in gaining access to language through lipreading. The results suggest cortical activation circuits for lipreading from action representations that may differentiate lexical access from nonlexical processes.

Adult↗

A fMRI study of word retrieval in aphasia.

The neural mechanisms underlying recovery of cognitive functions are incompletely understood. Aim of this study was to assess, using functional magnetic resonance (fMRI), the pattern of brain activity during covert word retrieval to letter and semantic cues in five aphasic patients after stroke, in order to assess the modifications of brain function which may be related to recovery. Four out of five patients had undergone language recovery, according to standard testing, after at least 6 months of rehabilitation. The cerebral activation of each patient was evaluated and compared with the activation pattern of normal controls studied with the same fMRI paradigm. In the patients, the pattern of brain activation was influenced by the site and extent of the lesion, by the degree of recovery of language, as reflected by task performance outside the scanner, and by task requirements. In the case of word retrieval to letter cues, a good performance was directly related to the activation in Broca's area, or in the right-sided homologue. On the other hand, in the case of semantic fluency, the relationship between performance level and activation was less clear-cut, because of extensive recruitment of frontal areas in patients with defective performance. These findings suggest that the performance in letter fluency is dependent on the integrity of the left inferior frontal cortex, with the participation of the homologous right hemispheric region when the left inferior frontal cortex is entirely of partially damaged. Semantic fluency, which engages the distributed network of semantic memory, is also associated with more extensive patterns of cerebral activation, which however appear to reflect retrieval effort rather than retrieval success.

Aged↗

Executive dysfunction and avoidant personality trait in myotonic dystrophy type 1 (DM-1) and in proximal myotonic myopathy (PROMM/DM-2).

A previous study in proximal myotonic myopathy (PROMM/DM-2) and myotonic dystrophy type 1 (DM-1) using brain positron emission tomography demonstrated a reduced cerebral blood flow in the frontal and temporal regions associated with cognitive impairment. The objective was to investigate further cognitive and behavioural aspects in a new series of patients with DM-1 and PROMM/DM-2. Nineteen patients with genetically determined PROMM/DM-2 and 21 patients with moderately severe DM-1 underwent neuropsychological testing and neuropsychiatric interviews. DM-1 and PROMM/DM-2 patients had significantly lower scores on tests of frontal lobe function compared to controls. Neuropsychiatric interviews demonstrated an avoidant trait personality disorder in both patient groups. Brain single photon emission computed tomography showed frontal and parieto-occipital hypoperfusion. The results suggest that there is a specific cognitive and behavioural profile in PROMM/DM-2 and in DM-1, and that this profile is associated with hypoperfusion in frontal and parieto-occipital regions of the brain.

Adult↗

Apomorphine-induced brain modulation during sexual stimulation: a new look at central phenomena related to erectile dysfunction.

It is well recognized that sexual stimulation leading to penile erection is controlled by different areas in the brain. Animal erection studies have shown that apomorphine (a D2>D1 dopamine receptors nonselective agonist) seems to act on neurons located within the paraventricular nucleus and the medial preoptic area of the hypothalamus. Yet, only recently, was a centrally acting agent, apomorphine sublingual, approved for the treatment of erectile dysfunction. The present functional magnetic resonance imaging placebo-controlled study presents the first in vivo demonstration of the apomorphine-induced modulation of cortical and subcortical brain structures in patients with psychogenic erectile dysfunction. Noteworthy, patients in comparison with potent controls, showed an increased activity in frontal limbic areas that was downregulated by apomorphine. This suggests that psychogenic impotence may be associated with previously unrecognized underlying functional abnormalities of the brain.

Adult↗

Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET.

A new diagnostic indicator of FDG PET scan abnormality, based on age-adjusted t statistics and an automated voxel-based procedure, is presented and validated in a large data set comprising 110 normal controls and 395 patients with probable Alzheimer's disease (AD) that were studied in eight participating centers. The effect of differences in spatial resolution of PET scanners was minimized effectively by filtering and masking. In controls FDG uptake declined significantly with age in anterior cingulate and frontolateral perisylvian cortex. In patients with probable AD decline of FDG uptake in posterior cingulate, temporoparietal, and prefrontal association cortex was related to dementia severity. These effects were clearly distinct from age effects in controls, suggesting that the disease process of AD is not related to normal aging. Women with probable AD had significantly more frontal metabolic impairment than men. The new indicator of metabolic abnormality in AD-related regions provided 93% sensitivity and specificity for distinction of mild to moderate probable AD from normals, and 84% sensitivity at 93% specificity for detection of very mild probable AD (defined by Mini Mental Score 24 or better). All regions related to AD severity were already affected in very mild AD, suggesting that all vulnerable areas are affected to a similar degree already at disease onset. Ventromedial frontal cortex was also abnormal. In conclusion, automated analysis of multicenter FDG PET is feasible, provides insights into AD pathophysiology, and can be used potentially as a sensitive biomarker for early AD diagnosis.

Aged↗

Bilateral paramedian thalamic syndrome: abnormal circadian wake-sleep and autonomic functions.

OBJECTIVES: To describe wake-sleep and body core temperature (t degrees ) rhythm abnormalities in two patients with bilateral paramedian thalamic calcifications. METHODS: Patients underwent (18F)FDG PET scans and 24 hour polygraphic recordings of wake-sleep and t degrees. RESULTS: PET showed bilateral thalamic hypometabolism in both patients with additional basal ganglia or mesiolateral frontal and cingular hypometabolism. Wake-sleep studies showed abnormal sleep organisation and in the case with frontal and limbic PET hypometabolism, pre-sleep behaviour associated with "subwakefulness" EEG activities, lack of EEG spindles and K complexes, and features of status dissociatus. The t degrees rhythms showed increased mesor in both (37.4 degrees C and 37.75 degrees C) and inverted rhythm in one patient. CONCLUSIONS: Paramedian thalamic structures and interconnected, especially frontal and cingular, areas play a part in the organisation of the wake-sleep cycle and attendant autonomic functions.

Autonomic Nervous System Diseases↗

Interhemispheric transmission of visuomotor information in humans: fMRI evidence.

Normal human subjects underwent functional magnetic resonance imaging (fMRI) while performing a simple visual manual reaction-time (RT) task with lateralized brief stimuli, the so-called Poffenberger's paradigm. This paradigm was employed to measure interhemispheric transmission (IT) time by subtracting mean RT for the uncrossed hemifield-hand conditions, that is, those conditions not requiring an IT, from the crossed hemifield-hand conditions, that is, those conditions requiring an IT to relay visual information from the hemisphere of entry to the hemisphere subserving the response. The obtained difference is widely believed to reflect callosal conduction time, but so far there is no direct physiological evidence in humans. The aim of our experiment was twofold: first, to test the hypothesis that IT of visuomotor information requires the corpus callosum and to identify the cortical areas specifically activated during IT. Second, we sought to discover whether IT occurs mainly at premotor or perceptual stages of information processing. We found significant activations in a number of frontal, parietal, and temporal cortical areas and in the genu of the corpus callosum. These activations were present only in the crossed conditions and therefore were specifically related to IT. No selective activation was present in the uncrossed conditions. The location of the activated callosal and cortical areas suggests that IT occurs mainly, but not exclusively, at premotor level. These results provide clear cut evidence in favor of the hypothesis that the crossed-uncrossed difference in the Poffenberger paradigm depends on IT rather than on a differential hemispheric activation.

Adult↗

Remodelling of sensorimotor maps in paraplegia: a functional magnetic resonance imaging study after a surgical nerve transfer.

The adult mammalian brain has the capacity of reorganising its neural connections in response to lesions/modifications of the peripheral and central nervous system. We show in vivo, using functional magnetic resonance imaging (fMRI), that in paraplegics the lower-limb sensorimotor cortex is invaded by the arm representation. This functional reshaping appears to be reversible. Indeed, surgical transfer of the ulnar nerve to the ipsilateral quadriceps and hip muscles allowed their contraction in a paraplegic patient. During fMRI, these voluntary movements activated the hip and thigh representation in sensorimotor cortex. We suggest that the functional recovery of the lower-limb functional maps might have been driven by the restored somatosensory inputs from the reactivated periphery. The voluntary movements of the lower-limbs are regained through the 're-awakening' of the corresponding sensorimotor cortex.

Adult↗