[show abstract][hide abstract] ABSTRACT: The aim of this study was to verify whether the repetition abilities in Alzheimer patients interact with the linguistic properties of individual languages, such that speakers will omit nominal referents more often only if the omission is a grammatical option in their language. Unlike English, where an overt nominal referent is always required in grammatical subject position, Italian allows grammatical subjects to be unexpressed. In Experiment 1, twelve Italian speakers with Alzheimer’s disease (AD) and twelve age- and education-matched controls repeated sentences of varying length and complexity. As predicted, Italian AD speakers omitted sentence subjects in complex sentences while control participants very rarely did. In Experiment 2, ten English AD speakers, matched with the Italian AD participants with respect to age and severity of the disease, and ten age- and education-matched controls repeated translation equivalent materials. Unlike the Italian AD participants, English AD participants did not omit sentence subjects. Italian and English AD participants, however, were comparable in their global ability to repeat sentences of varying length. Together these results indicate that the performance of AD speakers in repeating sentences interacts with language-specific properties.
[show abstract][hide abstract] ABSTRACT: This study investigated the cognitive profile and the cerebral perfusion pattern in a highly educated 70 year old gentleman with posterior cortical atrophy (PCA). Visuo-perceptual abilities, spatial memory, spatial representation and navigation, visuo-spatial mental imagery, semantic and episodic-autobiographical memory were assessed. Regional cerebral blood flow (rCBF) was imaged with SPECT. Cognitive testing showed visual-perceptual impairment, apperceptive visual and landmark agnosia, topographical disorientation with way-finding deficits, impaired map learning and poor mental image generation. Semantic memory was normal, while episodic-autobiographical memory was impaired. Reduced rCBF was found mainly in the right hemisphere, in the precentral gyrus, posterior cingulate and middle temporal gyri, cuneus and precuneus, in the left superior temporal and lingual gyri and in the parahippocampus bilaterally. Hypoperfusion in occipito-parietal regions was associated with visuo-spatial deficits, whereas deficits in visuo-spatial mental imagery might reflect dysfunction related to hypoperfusion in the parahippocampus and precuneus, structures which are responsible for spatial and imagery processing. Dissociating performance between preserved semantic memory and poor episodic-autobiographical recall is consistent with a pattern of normal perfusion in frontal and anterior temporal regions but abnormal rCBF in the parahippocampi. The present findings indicate that PCA involves visuo-spatial imagery deficits and provide further validation to current neuro-cognitive models of spatial representation and topographical disorientation.
[show abstract][hide abstract] ABSTRACT: Lexical-semantic competency in mild cognitive impairment (MCI) ε4 carriers was used as an endophenotype, and gray matter volume in MCI ε4 carriers/noncarriers and in noncarrier controls was compared. Residual gray matter volumes were correlated with age of acquisition values for words from a category fluency task, an index of semantic competency. MCI patients had significantly impoverished lexical-semantic output compared with controls, more marked in MCI ε4 carriers. Smaller volumes in the left hippocampus, bilateral regions of the uncus, and posterior cingulate cortex were associated with a tendency to retrieve earlier acquired words in the category fluency task in MCI ε4 carriers, whereas poor semantic performance in MCI noncarriers was associated with smaller volumes in the left uncus, bilateral regions of the parahippocampal gyrus, and hippocampus, and also in a large number of neocortical regions. There was a significant semantic competency by genotype interaction in the left perirhinal cortex, in a number of left frontal and temporal areas and in the right inferior parietal lobule and precuneus. MCI ε4 carriers, when compared with noncarriers, had lower gray matter volume values confined to the right precuneus and the cerebellum bilaterally, but the converse comparison showed that MCI noncarriers had lower values in extensive frontal, temporal, and parietal regions of the neocortex. Similar brain volumetric variations linked to genotype were found in minimal-to-mild AD. The results suggest a relatively specific impact of apolipoprotein E (APOE) ε4 burden and underline the value of linguistic assessment in preclinical diagnosis.
[show abstract][hide abstract] ABSTRACT: Stewart G, McGeown WJ, Shanks MF, Venneri A. Anosognosia for memory impairment in Alzheimer's disease.Objective: To investigate whether patients with Alzheimer's disease (AD) were able to alter their awareness of memory deficits after exposure to a memory task.Methods: Thirty normal older adults and 23 mild AD patients participated in the study. Anosognosia was assessed using discrepancies between self- and informant-evaluations of cognitive and functional performance. Participants estimated their performance on the Verbal Paired Associates task at different points in time (before, immediately after the task and after a 1-h delay).Results: AD patients were generally less able to judge their memory abilities than healthy older adults, and tended to overestimate their task performance beforehand. Their prediction accuracy increased immediately after the task, but after a 1-h delay, they again misjudged their abilities at pretesting accuracy levels. Self-carer discrepancy scores of awareness of deficits in memory and other areas correlated significantly with memory tests but not with other neuropsychological tasks in the assessment, and larger discrepancy scores were associated with poorer performance.Conclusion: AD patients can monitor their task performance online, but are unable to maintain awareness of their deficits over time. Loss of awareness of memory deficits (or of any other deficits) in early stage AD may indicate damage to a system which updates a personal knowledge base with recent information. Failure to retain this information impedes abstraction from episodic to semantic memory.
[show abstract][hide abstract] ABSTRACT: Neuroimaging studies of cholinesterase inhibitor (ChEI) treatment in Alzheimer's disease (AD) have shown the different short and long term actions of ChEIs. fMRI studies of the ChEI donepezil have focused on its short to medium term action without exploring the effects of established treatment. In this exploratory study the effect of 20 weeks donepezil treatment on regional brain activity was measured with fMRI in patients with mild AD. Twelve patients with probable AD and nine age-matched controls were assessed with a Pyramids and Palm Trees semantic association fMRI paradigm and an n-back working memory fMRI paradigm. In the patient group only, the assessment was repeated after 20 weeks of treatment. After treatment, differences from normal healthy elderly became more pronounced. There was also a spread of deactivation which at retest was detectable in task relevant areas. Behaviourally, however, there were no significant differences between group baseline and retest scores, with a range of performance probably reflecting variation in drug efficacy across patients. Parametric analyses established that increased behavioural scores at retest correlated significantly with higher activation levels in non task relevant areas. Behavioural stability with donepezil treatment was not paralleled by the pattern of improved task specific brain activation reported in similar studies of other ChEIs. This is arguably related to the different mechanisms of action of the ChEIs and might be a clinical correlate of the reported synaptic upregulation following long term donepezil treatment.
Current Alzheimer research 05/2010; 7(5):415-27. · 4.97 Impact Factor
[show abstract][hide abstract] ABSTRACT: A patient who suffered a transient global amnesia (TGA) attack underwent regional cerebral blood flow (rCBF) SPECT imaging and neuropsychological testing in the acute phase, after one month and after one year. Neuropsychological testing in the acute phase showed a pattern of anterograde and retrograde amnesia, whereas memory was within age normal limits at follow up. SPECT data were analysed with a within subject comparison and also compared with those of a group of healthy controls. Within subject comparison between the one month follow up and the acute phase detected increases in rCBF in the hippocampus bilaterally; further rCBF increases in the right hippocampus were detected after one year. Compared to controls, significant hypoperfusion was found in the right precentral, cingulate and medial frontal gyri in the acute phase; after one month significant hypoperfusion was detected in the right precentral and cingulate gyri and the left postcentral gyrus; after one year no significant hypoperfusion appeared. The restoration of memory was paralleled by rCBF increases in the hippocampus and fronto-limbic-parietal cortex; after one year neither significant rCBF differences nor cognitive deficits were detectable. In conclusion, these data indicate that TGA had no long lasting cognitive and neural alterations in this patient.
[show abstract][hide abstract] ABSTRACT: The 'default mode' network refers to cortical areas that are active in the absence of goal-directed activity. In previous studies, decreased activity in the 'default mode' has always been associated with increased activation in task-relevant areas. We show that the induction of hypnosis can reduce anterior default mode activity during rest without increasing activity in other cortical regions. We assessed brain activation patterns of high and low suggestible people while resting in the fMRI scanner and while engaged in visual tasks, in and out of hypnosis. High suggestible participants in hypnosis showed decreased brain activity in the anterior parts of the default mode circuit. In low suggestible people, hypnotic induction produced no detectable changes in these regions, but instead deactivated areas involved in alertness. The findings indicate that hypnotic induction creates a distinctive and unique pattern of brain activation in highly suggestible subjects.
Consciousness and Cognition 09/2009; 18(4):848-55. · 2.31 Impact Factor
[show abstract][hide abstract] ABSTRACT: In a study of the effects of normal and pathological aging on semantic-related brain activity, 29 patients with Alzheimer's disease (AD) and 19 controls subjects (10 young and 9 older controls) performed a version of the Pyramids and Palm Trees Test that had been adapted for use during functional magnetic resonance imaging (fMRI). Young and older controls activated the left inferior and middle frontal gyri, precuneus and superior parietal lobule. Right frontal and left temporal cortices were activated only in the young. The AD group activated only the left prefrontal and cingulate cortex. Separate analyses of high- and low-performing AD subgroups showed a similar pattern of activation in the left frontal lobe, although activiation was more widespread in low performers. High performers significantly deactivated anterior midline frontal structures, however, while low performers did not. When the older adult and AD groups were combined, there was a significant positive correlation between left frontal and parietal activation and Mini-Mental State Examination (MMSE) score (covarying for age), suggesting a disease effect. A significant negative correlation between activation in the left temporal cortex and age (covarying for MMSE score) reflected a possible age effect. These differential effects suggest that semantic activation paradigms might aid diagnosis in those cases for whom conventional assessments lack the necessary sensitivity to detect subtle changes.
Psychiatry Research 09/2009; 173(3):218-27. · 2.46 Impact Factor
[show abstract][hide abstract] ABSTRACT: Asomatognosia is broadly defined as unawareness of ownership of one's arm, while somatoparaphrenia is a subtype in which patients also display delusional misidentification and confabulation. Studies differ with regard to the underlying neuroanatomy of these syndromes.
Three groups of patients with right-hemisphere strokes and left hemiplegia were analysed: G1, asomatognosia+neglect; G2, non-asomatognosia+neglect; G3, hemiplegia only. The asomatognosic group was further subdivided into somatoparaphrenia (G1-SP: asomatognosia+delusions/confabulation) and simple asomatognosia (G1-SA; asomatognosia without delusions/confabulation).
Patients with all forms of asomatognosia (G1) had larger lesions than non-asomatognosic patients in all sectors. While patients with or without asomatognosia had significant temporoparietal involvement, we found that the subset of patients with somatoparaphrenia had the largest lesions overall, and somatoparaphrenia cases had significantly more frontal involvement than patients with simple asomatognosia. All patients with asomotognosia (G1-SP and G1-SA) had significant medial frontal damage, suggesting that this region may play a role in the development of asomatognosia in general. Somatoparaphrenia cases also had greater orbitofrontal damage than simple asomatognosia cases, suggesting that the orbitofrontal lesion was critical in the development of somatoparaphrenia.
Asomatognosia results from large lesions involving multiple--including temporoparietal--sectors, but the addition of medial frontal involvement appears important. The addition of orbitofrontal dysfunction distinguishes somatoparaphrenia from simple asomatognosia. The data indicate roles for the right medial and orbitofrontal regions in confabulation and self-related systems.
Journal of neurology, neurosurgery, and psychiatry 09/2009; 81(3):276-81. · 4.87 Impact Factor
[show abstract][hide abstract] ABSTRACT: Objective: The present study investigated the attentional bias induced by drug-related stimuli in active abusers; abstinent abusers on opioid substitution therapy; and abstinent drug-dependent patients in recovery on a community-based non-pharmacological therapy programme. Drug-dependent groups included both cocaine and heroin abusers.Methods: Classical and emotional Stroop tasks were used to test all drug-dependent patients and controls with no history of addiction. Response times were recorded. An interference effect was obtained by comparing the congruent and incongruent conditions in the classical Stroop version. An attentional bias towards drug cues was derived by comparing latencies in the neutral and emotional conditions of the emotional Stroop.Results: No between-group differences were found in the classical Stroop. In the emotional Stroop, active drug-dependent patients showed higher attentional bias (i.e. longer response times to drug-related words) than any of the other three groups.Conclusion: The attentional bias induced by drug cues in patients with addiction disorder might change depending on the patients' clinical status. All treated patients, whether on opioid substitution therapy or on community therapy, showed less attentional bias towards drug-related stimuli than active drug users, although the observed smaller bias was most likely induced by therapy acting through different mechanisms. Although drug-cues response is influenced by other multiple variables, e.g. motivation, craving, classical conditioning and substance availability, these data lend support to the hypothesis that treatment might contribute to decrease the attentional bias towards drug cues, which seems to play a critical role in achieving a positive outcome in the treatment of addiction.
[show abstract][hide abstract] ABSTRACT: Personality dimensions such as novelty seeking (NS), harm avoidance (HA), reward dependence (RD) and persistence (PER) are said to be heritable, stable across time and dependent on genetic and neurobiological factors. Recently a better understanding of the relationship between personality traits and brain structures/systems has become possible due to advances in neuroimaging techniques. This Magnetic Resonance Imaging (MRI) study investigated if individual differences in these personality traits reflected structural variance in specific brain regions. A large sample of eighty five young adult participants completed the Three-dimensional Personality Questionnaire (TPQ) and had their brain imaged with MRI. A voxel-based correlation analysis was carried out between individuals' personality trait scores and grey matter volume values extracted from 3D brain scans. NS correlated positively with grey matter volume in frontal and posterior cingulate regions. HA showed a negative correlation with grey matter volume in orbito-frontal, occipital and parietal structures. RD was negatively correlated with grey matter volume in the caudate nucleus and in the rectal frontal gyrus. PER showed a positive correlation with grey matter volume in the precuneus, paracentral lobule and parahippocampal gyrus. These results indicate that individual differences in the main personality dimensions of NS, HA, RD and PER, may reflect structural variance in specific brain areas.
Brain research bulletin 07/2009; 79(5):265-70. · 2.18 Impact Factor
[show abstract][hide abstract] ABSTRACT: Clinical trials of cholinesterase inhibitor (ChEI) drugs, although generally reporting only minimal improvements in patients with Alzheimer's disease (AD), indicate that a subgroup of patients may respond substantially to treatment. This study aimed to assess the clinically variable ChEI treatment effects in a group of patients with mild AD using a semantic association and an N-back light working memory activation paradigm. Twenty-six patients with probable mild AD treated with a ChEI for 20 weeks were retrospectively divided into responders and non-responders. Patients were classified as responders if their Clinician's Interview Based Impression of Change (CIBIC - Plus) score was four or less and if they had an increase of at least two points on the MMSE. These criteria resulted in two subgroups comprising nine responders and seventeen non responders. Nine healthy elderly age-matched controls were also recruited as a comparison group. ChEI treatment was accompanied by significant modulation of task induced activation increases in both fMRI tasks in AD responders. The effect of ChEI response was in effect a restoration of regional brain function in the same areas used by elderly controls when performing these tasks. In non-responders decrements in task related activation were observed and over time activation patterns appeared less like the elderly controls. Screening semantic fluency scores correlated negatively with activation increases at retest. In the paper, a tentative explanation is offered of why subgroups of patients with a similar clinical diagnosis and level of clinical severity show a different physiological response to ChE inhibition.
Current Alzheimer research 05/2009; 6(2):97-111. · 4.97 Impact Factor