Dario Grossi

Tracking the Mind's Image in the Brain I: Time-Resolved fMRI during Visuospatial Mental Imagery

Mental imagery, the generation and manipulation of mental representations in the absence of sensory stimulation, is a core element of numerous cognitive processes. We investigate the cortical mechanisms underlying imagery and spatial analysis in the visual domain using event-related functional magnetic resonance imaging during the mental clock task. The time-resolved analysis of cortical activation from auditory perception to motor response reveals a sequential activation of the left and right posterior parietal cortex, suggesting that these regions perform distinct functions in this imagery task. This is confirmed by a trial-by-trial analysis of correlations between reaction time and onset, width, and amplitude of the hemodynamic response. These findings pose neurophysiological constraints on cognitive models of mental imagery.

Effects of Age, Education and Sex on Two Tests of Immediate Memory: A Study of Normal Subjects from 20 to 99 Years of Age:

Spatial span (Corsis block-tapping test) and verbal span (Wechsler Digits Forward) were measured in 1354 normal subjects, aged from 20 to 99 yr., who were subdivided into seven age groups, into three groups according to education, and according to sex. Analysis of variance showed that the three main factors were significant for the spatial span test, while only age and education were significant for the verbal span test. The two spans examined held well up to the 60s, and only after this age did significant differences appear in the other age groups. On both tests there were significant differences between the groups divided according to education.

Unawareness of dyskinesias in Parkinson's and Huntington's diseases.

Abstract We performed a clinical study to evaluate the unawareness of dyskinesias in patients affected by Parkinsons disease (PD) and Huntingtons disease (HD). Thirteen PD patients with levodopa-induced dyskinesias and 9 HD patients were enrolled. Patients were asked to evaluate the presence of dyskinesias while performing specific motor tasks. The Abnormal Involuntary Movement Scale (AIMS) and Goetz dyskinesia rating scale were administered to determine the severity of dyskinesias. The Unified Parkinsons disease rating scale (UPDRS) and Unified Huntingtons Disease Rating Scale (UHDRS) were used in PD and HD patients, respectively. In PD we found a significant negative relationship between unawareness score at hand pronation-supination and AIMS score for upper limbs. In HD we found a significant positive relationship between total unawareness score and disease duration. In PD the unawareness seems to be inversely related with severity of dyskinesias, while in HD it is directly related to disease duration and severity.

Relationship between depression and cognitive dysfunctions in Parkinson’s disease without dementia

To explore the relationship between depression and cognitive impairment in non-demented PD patients, we evaluated neurological and neuropsychological asset in 65 patients with a diagnosis of major depressive disorder (dPD) according to DSM-IV criteria and 60 patients without depression (nPD).Compared with nPD patients, dPD patients had significantly higher scores on behavioral rating scales and performed worse on the Frontal Assessment Battery (FAB), Semantic Fluency Task, Copying Task (CT), and Stroop Test. Three dPD subgroups were identified based on the first two DSM-IV criteria: patients fulfilling criterion 1 (depressed mood; group 1); patients fulfilling criterion 2 (apathy/anhedonia; group 2); patients fulfilling criteria 1 and 2 (group 3). Patients of group 2 scored significantly lower than patients of group 1 on the CT, FAB and phonological fluency task. Patients of groups 2 and 3 scored significantly lower than nPD patients on visuoconstructional and frontal tasks. Similar results were obtained in dPD patients stratified in four subgroups based on cut-off scores of the Apathy Evaluation Scale and the Snaith Hamilton Pleasure Scale. In summary, PD patients with concomitant apathy and anhedonia may show more severe cognitive impairments. Since such patients are diagnosed to be affected by depression according to clinical DSM-IV criteria, we suggest that DSM-IV criteria may not distinguish an affective from a cognitive disorder in PD.

Comparative neuropsychological profile of pathological gambling, hypersexuality, and compulsive eating in Parkinson's disease

Background: Impulse control disorders (ICDs), in particular pathological gambling, hypersexuality, and compulsive eating, are being increasingly identified in Parkinsons disease (PD) patients. Pathological gambling has been associated with frontal/executive dysfunctions, whereas hypersexuality and compulsive eating, and their relation with cognitive dysfunctions, have not been investigated in PD.

Cognitive dysfunctions and pathological gambling in patients with Parkinson's disease†

The purpose of this study was to investigate the neuropsychological correlates of pathological gambling (PG) in Parkinsons disease (PD). Fifteen patients with PD affected by PG (identified based on DSM‐IV criteria; PD+PG) without clinically evident dementia were compared with 15 nondemented patients with PD not affected by PG (PD−PG). Two groups of patients with PD were matched for age, length of education, and gender. Clinical and neuropsychiatric features were assessed; several cognitive domains, mainly related to executive functions, were explored by means of standardized neuropsychological tasks. PD+PG and PD−PG did not differ on clinical and neuropsychiatric aspects. PD+PG patients performed significantly worse than PD−PG patients on cognitive tasks that evaluated visuo‐spatial long‐term memory and several frontal lobe functions. After Bonferroni correction, differences remained significant on the Frontal Assessment Battery (FAB) (P = 0.001), on phonological fluency task (P = 0.003), and on the Trail Making Test, part B minus part A (P = 0.002). Logistic regression analysis demonstrated that low scores on the FAB were the only independent predictor of PG (odds ratio, 27.9; 95% CI: 2.82–277.95, P = 0.004). The results indicate an association between PG and frontal lobe dysfunctions in nondemented patients with PD. Low scores on the FAB indicate patients with PD at high risk for PG.

A neuropsychological longitudinal study in Parkinson's patients with and without hallucinations

The aim of this work was to determine the progression of cognitive impairment in Parkinsons disease (PD) patients with or without hallucinations. Two years after the first assessment, 36 PD patients were re‐evaluated on standardized neuropsychological tests, including the Frontal Assessment Battery (FAB), and on rating scales for overall cognitive functioning, functional autonomy, behavioral disorders. Nine patients had hallucinations at baseline and endpoint assessments; 12 patients developed hallucinations during the follow‐up; and 15 patients were hallucination‐free throughout the study. Cognitive performance significantly declined in all three groups, but at endpoint assessment PD hallucinators scored significantly lower than nonhallucinators on phonological and semantic fluency tasks, immediate free recall and the go/no‐go FAB subtest; moreover, they showed more severe apathy than nonhallucinators. Reduced phonological fluency at baseline (odds ratio [OR], 13.5; 95% CI: 1.34–135.98, P = 0.027) was the only independent predictor of onset of hallucinations after 2 years, whereas hallucinations (OR, 10.1; 95% CI: 1.94–51.54, P = 0.006) and poor phonological fluency (OR, 6.1; 95% CI: 1.04–35.03, P = 0.045) independently predicted development of diffuse cognitive impairment. We concluded that reduced verbal fluency scores may predict the onset of hallucinations, while hallucinations and poor phonological fluency may predict development of dementia in PD patients.

Evaluation of the motor cortex by magnetic stimulation in patients with Alzheimer disease

Motor evoked potentials (MEPs) from abductor pollicis brevis (APB) and tibialis anterior (TA) muscles elicited by transcranial magnetic stimulation of the motor cortex were studied in 15 patients with Alzheimer disease (AD). An abnormally higher MEP threshold in APB, frequently associated with absence of the MEP in relaxed TA muscles, was found in 40% of patients, almost all of them in the more severe stage of the disease. The MEP amplitude and averaged MEP/MAP ratio were reduced respectively by 20% and 26% in the APB muscle, and by 46.7% and 53.3% in the TA muscle. The less frequent prolongation of the central conduction time (CCT) (20%) might reflect preservation of the impulse propagation along the surviving pyramidal fibers. In 63.6% of the patients the central silent period (cSP) duration in the APB muscle was shortened; the mean value was significantly different between patients and controls. The results of this study suggest that loss and/or dysfunction of motor cortex neurones, including pyramidal cells and inhibitory interneurones may occur in AD patients before clinical signs become apparent.

Memory for visuospatial patterns in Alzheimer's disease

Immediate memory for visuospatial information was assessed in patients affected by Alzheimer-type dementia but with unimpaired visuo-perceptual functions. Patients were given two tasks: one was a traditional visuospatial memory task (Corsis block tapping test), the second explored specifically immediate memory for visuospatial patterns. The experiment was conducted in two parallel groups of patients in Italy and the United States, each with its own appropriate sample of normal control subjects. Results showed a specific deficit of visual working memory in demented patients, even in a task in which control subjects achieved error-free performance. These data are interpreted in the light of the Working Memory Model, and suggest that in dementia the functions of the Visuospatial Scratchpad, unlike the functions of the verbal subsystems, may be impaired.

Categorical and coordinate spatial processing in the imagery domain investigated by rTMS.

Using repetitive transcranical magnetic stimulation (rTMS), we investigated the functional relevance of posterior parietal cortex for categorical and coordinate judgements in the spatial imagery domain. In the coordinate task, subjects were asked to imagine two analogue clock faces based on acoustically presented pairs of times, and to judge at which of the two times the clock hands form the greater angle (mental clock task); in the categorical task subjects were again asked to imagine an analogue clock face showing the time verbally presented by the examiner, but in this case they had to judge whether both hands lay in the half of the clock face cued by an auditorily presented label. We matched the performance of three groups of subjects, two of which received rTMS stimulation over left and right posterior parietal cortex, respectively, while the third group received a sham stimulation. The results showed that right parietal stimulation interfered with the execution of the coordinate task, while left parietal stimulation mainly affected the categorical task, but also reduced the learning effect on the coordinate task. The present findings support the hemispheric specialization of the posterior parietal cortex in different spatial information processing in the imagery domain.