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Biomedical subjects

Carlo Caltagirone

Publications and source records attributed to Carlo Caltagirone.

At least 19 recordsLinked to original sources

Cortical networks of procedural learning: evidence from cerebellar damage.

The lateral cerebellum plays a critical role in procedural learning that goes beyond the strict motor control functions attributed to it. Patients with cerebellar damage show marked impairment in the acquisition of procedures, as revealed by their performance on the serial reaction time task (SRTT). Here we present the case of a patient affected by ischemic damage involving the left cerebellum who showed a selective deficit in procedural learning while performing the SRTT with the left hand. The deficit recovered when the cortical excitability of an extensive network involving both cerebellar hemispheres and the dorsolateral prefrontal cortex (DLPFC) was decreased by low-frequency repetitive transcranial magnetic stimulation (rTMS). Although inhibition of the right DLPFC or a control fronto-parietal region did not modify the patient's performance, inhibition of the right (unaffected) cerebellum and the left DLPFC markedly improved task performance. These findings could be explained by the modulation of a set of inhibitory and excitatory connections between the lateral cerebellum and the contralateral prefrontal area induced by rTMS. The presence of left cerebellar damage is likely associated with a reduced excitatory drive from sub-cortical left cerebellar nuclei towards the right DLPFC, causing reduced excitability of the right DLPFC and, conversely, unbalanced activation of the left DLPFC. Inhibition of the left DLPFC would reduce the unbalancing of cortical activation, thus explaining the observed selective recovery of procedural memory.

Adult↗

Repetitive TMS of cerebellum interferes with millisecond time processing.

Time processing is important in several cognitive and motor functions, but it is still unclear how the human brain perceives time intervals of different durations. Processing of time in millisecond and second intervals may depend on different neural networks and there is now considerable evidence to suggest that these intervals are possibly measured by independent brain mechanisms. Using repetitive transcranial magnetic stimulation (rTMS), we determined that the cerebellum is essential in explicit temporal processing of millisecond time intervals. In the first experiment, subjects' performance in a time reproduction task of short (400-600 ms) and long (1,600-2,400 ms) intervals, were evaluated immediately after application of inhibitory rTMS trains over the left and right lateral cerebellum (Cb) and the right dorsolateral prefrontal cortex (DLPFC). We found that rTMS over the lateral cerebellum impaired time perception in the short interval (millisecond range) only; for the second range intervals, impaired timing was found selectively for stimulation of the right DLPFC. In the second experiment, we observed that cerebellar involvement in millisecond time processing was evident when the time intervals were encoded but not when they were retrieved from memory. Our results are consistent with the hypothesis that the cerebellum can be considered as an internal timing system, deputed to assess millisecond time intervals.

Adult↗

Interactions between pairs of transcranial magnetic stimuli over the human left dorsal premotor cortex differ from those seen in primary motor cortex.

A single TMS pulse (110% resting motor threshold, RMT) to the left dorsal premotor cortex (PMd) (CS2) suppresses the amplitude of motor evoked potentials (MEPs) from a test pulse (TS) over the right motor cortex (M1), and facilitates MEPs from the left motor cortex. We probed how this interaction was changed by a prior conditioning pulse over PMd (CS1) using a paired pulse TMS design. In the main experiments, the intensity of CS1 was 80% RMT. Basal suppression of right M1 was removed when CS1-CS2 was 1 ms or 5 ms with a similar tendency at 15 ms. Basal facilitation of left M1 was suppressed at CS1-CS2 of 5 ms. A similar time course was seen if CS2 was increased to 100% RMT, but there was no significant effect if CS1 was 70% RMT. Preconditioning PMd with continuous or intermittent theta burst repetitive TMS (cTBS, iTBS) abolished the basal CS2-TS interaction between premotor and motor cortices. Finally, if very short interstimulus intervals between CS1 and CS2 were explored to detect interactions similar to I-wave facilitation in M1, we found that the basal suppression of right M1 was abolished at CS1-CS2 intervals of 1.8 and 2.8 ms. We suggest that paired pulse TMS may be capable of investigating properties of intrinsic circuits in PMd and that their properties differ from those in the nearby M1. Paired TMS may be a useful method of studying the excitability of intrinsic circuits in non-primary areas of the motor system.

Adult↗

Differences in temperament, character and psychopathology among subjects with different patterns of cannabis use.

BACKGROUND: Patients who use illicit drugs and suffer from comorbid psychiatric illnesses have worse outcomes than drug users without a dual diagnosis. For this reason we aimed at identifying predictors of cannabis use severity using a multivariate model in which different clinical and socio-demographic variables were included. SAMPLING AND METHODS: We administered the Temperament and Character Inventory, SCID-P, SCID-II, the Beck Depression Inventory and the State-Trait Anxiety Inventory. Of the 84 subjects included, 25 were occasional users, 37 were abusers, and 22 were dependent on cannabis. RESULTS: A stepwise multiple regression analysis identified increased self-transcendence scores and state anxiety severity as the only predictors of a increased cannabis use severity (F = 6.635; d.f. = 2, 81; p = 0.0021). In particular, in a further multivariate analysis of variance, the transpersonal identification issue of self-transcendence was associated significantly (F = 4.267; d.f. = 2, 81; p = 0.017) with greater severity of cannabis use. CONCLUSIONS: Character dimension of self-transcendence and symptoms of state anxiety should be taken into consideration during the assessment procedure of patients with cannabis use as they may be helpful in the discrimination of cannabis use severity.

Adult↗

Implicit learning deficits in dyslexic adults: an fMRI study.

It is assumed that several neuropsychological impairments characterize the cognitive profile of individuals with developmental dyslexia (DD). Phonological and visual processing are often impaired as well as auditory processing, attention, and information processing speed. Although reports in the literature on implicit learning abilities are contradictory, recent neurological and physiological data suggest that these abilities are deficient in individuals with DD. To evaluate implicit learning we administered a classical version of the serial reaction time task (SRTT) related to sequence learning. Using functional magnetic resonance imaging we investigated brain activation patterns associated with implicit learning deficits in 14 adults with DD matched with 14 normal readers. SRTT results indicated the absence of implicit learning in the DD group and different activations between groups mainly in SMA, inferior parietal areas and cerebellar lobule 6. These results can be interpreted in the light of the different capacities for the two groups to build an internal model to guide movements. Further, they explain DD individuals' difficulty in domains not directly related to reading ability.

Adult↗

Functional changes in the activity of cerebellum and frontostriatal regions during externally and internally timed movement in Parkinson's disease.

We used fMRI to investigate the neurofunctional basis of externally and internally timed movements in Parkinson's disease (PD) patients. Ten PD patients whose medication had been withheld for at least 18h and 11 age- and sex-matched healthy controls were scanned while performing continuation paradigm with a visual metronome. Compared with the controls, PD patients displayed an intact capability to store and reproduce movement frequencies but with a significantly increased movement latencies. No differences in BOLD response were found in both groups when comparing the continuation with the preceding synchronization phase and viceversa, except for activity in visually related regions. Relative to healthy controls during the synchronization phase, PD patients exhibited an overall signal increase in the cerebellum and frontostriatal circuit (putamen, SMA and thalamus) activity together with specific brain areas (right inferior frontal gyrus and insula cortex) that are also implicated in primary timekeeper processes. By contrast, in the continuation phase the only neural network involved to a greater extent by the PD group was the cerebello-thalamic pathway. The lack of neurofunctional differences between the two timing phases suggests that rhythmic externally and internally guided movements engage similar neural networks in PD and matched healthy controls. Moreover, between-group comparison indicates that PD patients OFF medication may compensate for their basal ganglia-cortical loop's dysfunction using different motor pathways involving cerebellum and basal ganglia relays during the two phases of rhythmic movement.

Adult↗

Effects of paired pulse TMS of primary somatosensory cortex on perception of a peripheral electrical stimulus.

Paired pulse transcranial magnetic stimulation (paired TMS) was introduced to study local inhibitory or facilitatory intracortical circuits of the primary motor cortex. However, similar interactions can be shown in other areas of cortex. The current study tests the effects of paired pulse TMS of the right primary somatosensory cortex (S1) on the sensory perception of electrical stimuli applied on the contralateral thumb finger. In the main experiment a subthreshold conditioning stimulus (CS) preceded a suprathreshold test stimulus (TS) at different inter-stimulus intervals. We found that perception of a peripheral electrical stimulus was markedly attenuated by paired TMS in comparison to single pulse TMS when the ISIs was 10 or 15 ms, while there was no effect at shorter ISIs. There was no additional effect of the CS pulse if the intensity of the TS was subthreshold. In control experiments we observed that the effect vanished when the delay between the peripheral stimulus and the TS was 10 or 30 ms rather than 20 ms or if the pairs of pulses were applied over the vertex rather than the hand area. Furthermore, there was no change at longer ISIs when paired TMS was applied over the posterior parietal cortex of the same hemisphere. These results demonstrate that paired pulse TMS is able to probe intracortical circuits in S1 and that the intrinsic properties of these circuits differ even between closely adjacent areas of the cortex.

Adult↗

(Category-specific) semantic deficit in Alzheimer's patients: the role of semantic distance.

A semantic battery comprising items from living and nonliving categories was administered to a sample of subjects suffering from probable Alzheimer's type dementia (n=20). The results were analyzed to test the role of semantic distance in predicting group accuracy and its possible causal link with the phenomenon of a category-specific deficit for living things in the experimental population. Our findings confirm a category effect favoring nonliving items (over and above the role of confounding variables) in patients with Alzheimer's disease and support the major role of an imbalance of semantic distance in the testing material in the genesis of this phenomenon.

Aged↗

Cumulative effect of COMT and 5-HTTLPR polymorphisms and their interaction with disease severity and comorbidities on the risk of psychosis in Alzheimer disease.

OBJECTIVE: The objective of this study was to investigate the cumulative effect of the genes likely involved in Alzheimer disease (AD)-related psychosis and their interaction with disease stage and environmental factors. METHODS: Two hundred thirty-four patients with AD underwent clinical and neuropsychologic examination, behavioral and psychiatric disturbances evaluation, and were subsequently divided into two subgroups according to the presence (AD-P) or the absence (AD-nP) of psychotic symptoms. Cathecol-O-methyltransferase (COMT), serotonin gene-linked promoter region (5-HTTLPR), and Apolipoprotein E (ApoE) genotypes were performed. RESULTS: COMT*H (H/H or H/liter; odds ratio [OR]: 2.4; 95% confidence interval [CI]: 1.13-5.11) and 5-HTTLPR*S (S/S or S/liter, OR: 2.14; 95% CI: 1.13-4.07) were associated with AD-P. A gene dose effect was observed; in fact, carriers of both polymorphisms showed a fivefold risk for psychosis compared with patients bearing no polymorphisms. An interaction between these two genetic variations with disease stage and ischemic cardiomyopathy was found, the latter influencing AD-P risk only if "at-risk" genetic polymorphisms were present. The combined trend effect of COMT*H plus 5-HTTLPR*S and advance disease stage on AD-P risk was approximately 200% greater than that predicted by assuming additive effects, whereas the one obtained by COMT*H plus 5-HTTLPR*S and ischemic cardiomyopathy was 50% greater. ApoE genotype did not influence AD-P risk. CONCLUSIONS: These findings claim for a synergic effect of COMT*H and 5-HTTLPR*S polymorphisms on the risk of psychosis in AD and for their interaction with disease stage and ischemic cardiomyopathy. This study suggests that considering both the genetic background and the environmental correlates might provide new insight for understanding psychosis mechanisms related to AD.

Aged↗

Response of emotional unawareness after stroke to antidepressant treatment.

OBJECTIVE: Unawareness of impairment (anosognosia) is a phenomenon associated with right hemisphere lesions. Unawareness of emotion has rarely been studied. METHODS: Patients (N = 50) with poststroke major depression were administered the Toronto, Ontario, Canada, Alexithymia Scale to assess impairment in identifying feelings (F1), describing feelings (F2), and externally oriented thinking (F3). After eight weeks of treatment with sertraline or fluoxetine, patients were reassessed. RESULTS: Alexithymia was significantly associated with right hemisphere lesions. Patients with alexithymia had a significant improvement in identifying and describing feelings, but not in externally oriented thinking. In addition, cognitive functions improved after antidepressant treatment in patients without alexithymia with left lesions only. On the contrary, functional activities of daily living and depressive symptoms improved both in patients with alexithymia and those without alexithymia. CONCLUSIONS: The unawareness of emotions is a common impairment after right hemisphere stroke. This disorder may be significantly improved by antidepressant treatment.

Activities of Daily Living↗

Suppression of extinction with TMS in humans: from healthy controls to patients.

We review a series of studies exemplifying some applications of single-pulse and paired-transcranial magnetic stimulation (TMS) in the study of spatial attention and of its deficits. We will focus primarily on sensory extinction, the failure to consciously perceive a contralesional sensory stimulus only during bilateral stimulation of homologous surfaces. TMS studies in healthy controls show that it is possible either to interfere or modulate the excitability of the parietal cortex during sensory (i.e. tactile and visual) attentional tasks, thus reproducing a condition of virtual extinction. TMS studies in patients with unilateral (mainly right) brain damage show that the modulation of the unbalance in cortical excitability between the two cerebral hemispheres transiently improves contralesional sensory extinction. These studies show the possible application of TMS not only as a research method in healthy subjects, but also as a tool for inducing brain excitability changes in patients with sensory extinction, which could be useful for supporting the rehabilitation of this deficit.

Extinction, Psychological↗

The role of semantic distance in category-specific impairments for living things: evidence from a case of semantic dementia.

In this paper, we describe a patient (LI) suffering from semantic dementia who showed a category-specific naming impairment for living things over and above the effects of several nonsemantic confounding variables. We investigated the characteristics of LI's impairment to address the following three issues raised in three different accounts of category-specific impairments: (i) the role of an imbalance in the loss of sensory compared to nonsensory features (assumed by the Sensory Functional Theory [Warrington, E. K., & Shallice, T. (1984). Category-specific semantic impairments. Brain, 107, 829-859]); (ii) the role of cross domain differences in Feature Correlation (assumed by the Conceptual Structure Account [Moss, H., Tyler, L. K., & Devlin, J. T. (2002). The emergence of category-specific deficits in a distributed semantic system. In: E. M. E. Forde & G. W. Humphreys (Eds.), Category Specificity in Brain and Mind (pp. 115-147). New York: Psychology Press]); (iii) the role of semantic distance (proposed by Cree and McRae [Cree, G. S., & McRae, K. (2003). Analyzing the factors underlying the structure and computation of the meaning of chipmunk, cherry, chisel, cheese, and cello (and many other such concrete nouns). Journal of Experimental Psychology: General, 132, 163-201]). We found that semantic distance was the only factor causally linked to LI's poorer performance on living things. In fact, her naming performance was less accurate on items that had many semantic neighbours, which is typical of living things. On the contrary, a feature listing task revealed that the features available to LI were not predicted by their level of correlation, as expected by the Conceptual Structure Account. Finally, at variance with the Sensory Functional Theory, although LI quoted sensory features less accurately than nonsensory ones, this did not give rise to a disproportionate loss of semantic features in the living domain.

Anomia↗

Prognostic implications of right-sided insular damage, cardiac autonomic derangement, and arrhythmias after acute ischemic stroke.

BACKGROUND AND PURPOSE: Acute stroke is associated with impairment of cardiac autonomic balance and increased incidence of arrhythmias. These abnormalities appear more relevant in the case of involvement of the right insula in the infarct area. The aim of this study was to assess the impact of right-sided insular damage, cardiac autonomic derangement, and arrhythmias on clinical outcome after acute ischemic stroke. METHODS: Holter monitoring for 24 hours was performed in 208 consecutive patients with first-ever acute ischemic stroke. Time- and frequency-domain measures of heart rate variability and arrhythmias were considered in all cases. All patients were followed for a 12-month period after the initial event. RESULTS: During the 12-month follow-up period, 48 patients died (1-year probability of death, 0.23; 95% CI, 0.17 to 0.30). Multivariate analysis demonstrated that age (hazard ratio [HR], 1.06; 95% CI, 1.01 to 1.10; P=0.0087), stroke severity on admission (HR, 1.25; 95% CI, 1.13 to 1.39; P=0.0001), presence of right-sided insular damage (HR, 2.01; 95% CI, 1.13 to 1.39; P=0.0187), as well as lower values of the SD of all normal-to-normal RR intervals (HR, 3.32; 95% CI, 1.67 to 6.24; P=0.002), and presence of nonsustained ventricular tachycardia during Holter monitoring (HR, 2.99; 95% CI, 1.58 to 5.67; P=0.0007) were independent predictors of 1-year mortality. CONCLUSIONS: The integration of traditional risk stratifiers with autonomic and arrhythmic markers, and the careful search for right-sided insular involvement, may represent an effective approach for identification of stroke patients at risk for early mortality.

Aged↗

Alzheimer's disease and frontal variant of frontotemporal dementia-- a very brief battery for cognitive and behavioural distinction.

The aim of this study was to investigate whether a brief neuropsychological battery consisting of a limited number of cognitive tests and an evaluation of the behavioural domains intended to discriminate between frontotemporal dementia (fv-FTD) and Alzheimer's disease (AD), constitutes a useful instrument for making a differential clinical diagnosis between these two pathologies. Nineteen fv-FTD and 39 AD patients were compared on cognitive tasks (assessing memory, executive functions, language and constructional praxis) and on the NPI behavioural assessment. A stepwise discriminant analysis was performed to identify the linear combination of cognitive and behavioural measures able to best discriminate between the two groups. One test for each of the investigated cognitive domains (Delayed Prose Recall, FAS verbal fluency, Boston naming test, Rey's Figure A Copy) and the four subscales of the Neuropsychiatry Inventory (NPI) which best differentiated between fv-FTD and AD patients (apathy, disinhibition, euphoria, aberrant motor behaviour) were used. The analysis selected Rey's Figure A Copy, FAS verbal fluency and NPI apathy subscale as the best discriminants between fv-FTD and AD patients. The final equation assigned 73.7% of the fv-FTD patients and 94.7% of the AD patients to the correct diagnostic group. A validation study conducted on a new independent sample of 11 fv-FTD and 22 AD patients confirmed the high sensitivity (82.6 %) and specificity (81.8%) of the diagnostic equation in assigning fv-FTD and AD patients to the correct dementia group. Although both cognitive and behavioural differences exist between FTD and AD, previous studies have aimed at differentiating the two pathologies by considering the two aspects separately and discriminant analyses were focused only on neuropsychological or neuropsychiatric evaluations. The present results emphasise the importance of rating both cognitive and behavioural clinical features of the two syndromes as objectively as possible to improve differential diagnostic accuracy.

Aged↗

The appreciation of wine by sommeliers: a functional magnetic resonance study of sensory integration.

We set out to investigate how the expertise of a sommelier is embodied in neural circuitry by comparing brain activity elicited by wine tasting with that found in naive drinkers of wine. We used fMRI to study 7 sommeliers and 7 age- and sex-matched control subjects to test the hypothesis that any difference in brain activity would reflect a learned ability to integrate information from gustatory and olfactory senses with past experience. A group analysis showed activation of a cerebral network involving the left insula and adjoining orbito-frontal cortex in sommeliers. Both these areas have been implicated in gustatory/olfactory integration in primates. In addition, activation was found bilaterally in the dorsolateral prefrontal cortex, which is implicated in high-level cognitive processes such as working memory and selection of behavioral strategies. Naive individuals activated the primary gustatory cortex and brain areas, including the amygdala, implicated in emotional processing.

Adult↗

Glutathione S-transferase P1 *C allelic variant increases susceptibility for late-onset Alzheimer disease: association study and relationship with apolipoprotein E epsilon4 allele.

BACKGROUND: Oxidative stress and neuronal cell death have been implicated in the pathogenesis of Alzheimer disease (AD). Considering that the glutathione transferase (GST) supergene family encodes isoenzymes that appear to be critical in protection against oxidative stress, we aimed at determining the various GSTP1, GSTM1, and GSTT1 polymorphisms and ApoE genotypes to investigate their role as susceptibility genes for late-onset AD (LOAD). METHODS: We included 210 LOAD patients and 228 healthy controls matched for age, sex, and educational level in our case-control genetic association study. GSTM1 and GSTT1 genotypes were studied by conventional PCR, whereas GSTP1 and ApoE genotypes were determined by real-time PCR on the LightCycler. RESULTS: We found a significant association between LOAD and the GSTP1*C allelic variant [odds ratio (OR) = 1.9; P < 0.05], but no association between the GSTM1 and GSTT1 deleted genotypes and LOAD. In addition, a preliminary result suggested that carriers of both the GSTP1*C and ApoE epsilon4 allelic variants were at increased risk of LOAD (OR = 19.98; P < 0.0001). CONCLUSION: The GSTP1*C allelic variant should be considered a candidate for LOAD, particularly in persons having the ApoE epsilon4 allelic variant, because the GSTP1 and ApoE gene products are implicated in oxidative stress and apoptosis processes leading to beta-amyloid-mediated neurodegeneration.

Age of Onset↗

rTMS evidence of different delay and decision processes in a fronto-parietal neuronal network activated during spatial working memory.

The existence of a specific and widely distributed network for spatial working memory (WM) in humans, involving the posterior parietal cortex and the prefrontal cortex, is supported by a number of neuroimaging studies. We used a repetitive transcranial magnetic stimulation (rTMS) approach to investigate the temporal dynamics and the reciprocal interactions of the different areas of the parieto-frontal network in normal subjects performing a spatial WM task, with the aim to compare neural activity of the different areas in the delay and decision phases of the task. Trains of rTMS at 25 Hz were delivered over the posterior parietal cortex (PPC), the premotor cortex (SFG) and the dorsolateral prefrontal cortex (DLPFC) of the right hemisphere alternatively during the two phases. We found a pattern of interference of TMS during the delay phase for both parietal and DLPFC sites of stimulation, with no effect observed for the SFG site. When rTMS trains were applied during the decision phase, an interference was observed selectively for DLPFC. The present study shows the existence of a parallel processing in the parieto-frontal network of spatial WM during the delay phase. Furthermore, it provides new evidence of the critical role of the DLPFC during both the delay and the decision phases. We suggest that in DLPFC, two different networks coexist: A local neural network subserving the decisional processes and a second neural population functionally interconnected with the PPC and activated when a certain spatial information has to be kept in memory, available to use.

Adult↗