Antonio Daniele

Evidence for a possible neuroanatomical basis for lexical processing of nouns and verbs

Neuropsychological studies have revealed that brain-damaged patients may show impairments of specific word categories. This study reports the performance of three patients with impairments of the categories noun and verb. The first and second patients, with left frontal lobe atrophy, were impaired in naming and comprehension of verbs. The third patient, with striking atrophy of the left temporal lobe, was disproportionately impaired in naming and comprehension of nouns. These findings suggest that anatomically distinct neural systems in the temporal and frontal lobes of the dominant hemisphere might play a critical role in lexical processing of nouns and verbs, respectively.

Motor and cognitive outcome in patients with Parkinson's disease 8 years after subthalamic implants.

Deep brain stimulation of the subthalamic nucleus represents the most important innovation for treatment of advanced Parkinsons disease. Prospective studies have shown that although the beneficial effects of this procedure are maintained at 5 years, axial motor features and cognitive decline may occur in the long term after the implants. In order to address some unsolved questions raised by previous studies, we evaluated a series of 20 consecutive patients who received continuous stimulation for 8 years. The overall motor improvement reported at 5 years (55.5% at Unified Parkinsons Disease Rating Scale-motor part, P < 0.001 compared with baseline) was only partly retained 3 years later (39%, P < 0.001, compared with baseline; -16.5%, P < 0.01, compared with 5 years), with differential effects on motor features: speech did not improve and postural stability worsened (P < 0.05). The preoperative levodopa equivalent daily dose was reduced by 58.2% at 5 years and by 60.3% at 8 years. In spite of subtle worsening of motor features, a dramatic impairment in functional state (-56.6% at Unified Parkinsons Disease Rating Scale-Activities of Daily Living, P < 0.01) emerged after the fifth year of stimulation. The present study did not reveal a predictive value of preoperative levodopa response, whereas few single features at baseline (such as gait and postural stability motor scores and the preoperative levodopa equivalent daily dose) could predict long-term motor outcome. A decline in verbal fluency (slightly more pronounced than after 5 years) was detected after 8 years. A significant but slight decline in tasks of abstract reasoning, episodic memory and executive function was also found. One patient had developed dementia at 5 years with further progression at 8 years. Executive dysfunction correlated significantly with postural stability, suggesting interplay between axial motor deterioration and cognition. Eight years after surgery, no significant change was observed on scales assessing depression or anxiety when compared with baseline. At 8 years, there was no significant increase of side-effects when compared with 5-year follow-up. In conclusion, deep brain stimulation of the subthalamic nucleus is a safe procedure with regard to cognitive and behavioural morbidity over long-term follow-up. However, the global benefit partly decreases later in the course of the disease, due to progression of Parkinsons disease and the appearance of medication- and stimulation-resistant symptoms.

Transient mania with hypersexuality after surgery for high frequency stimulation of the subthalamic nucleus in Parkinson's disease

Among 30 Parkinsons disease patients who received high frequency stimulation of the subthalamic nucleus, 5 developed remarkable disorders of mood or sexual behavior after the implant. We describe 2 men who developed mania and hypersexuality a few days after the implant that lasted for some months and then gradually disappeared spontaneously.

Treatment of motor and non-motor features of Parkinson's disease with deep brain stimulation

Deep brain stimulation (DBS) is an established procedure for the symptomatic treatment of Parkinsons disease. Several deep brain nuclei have been stimulated, producing a wide range of effects on the motor and non-motor symptoms of Parkinsons disease. Long-term, high-quality evidence is available for stimulation of the subthalamic nucleus and globus pallidus internus, both of which uniformly improve motor features, and for stimulation of the thalamic ventralis intermedius, which improves tremor. Short-term data are available for stimulation of other deep brain targets, such as the pedunculopontine nucleus and the centremedian/parafascicular thalamic complex. Some non-motor symptoms improve after DBS, partly because of motor benefit or reduction of drug treatment, and partly as a direct effect of stimulation. More evidence on the effects of DBS on non-motor symptoms is needed and specifically designed studies are warranted.

Noninvasive in vivo assessment of cholinergic cortical circuits in AD using transcranial magnetic stimulation

BackgroundA recently devised test of motor cortex excitability (short latency afferent inhibition) was shown to be sensitive to the blockade of muscarinic acetylcholine receptors in healthy subjects. The authors used this test to assess cholinergic transmission in the motor cortex of patients with AD. MethodsThe authors evaluated short latency afferent inhibition in 15 patients with AD and compared the data with those of 12 age-matched healthy controls. ResultsAfferent inhibition was reduced in the patients (mean responses ± SD reduced to 85.7% ± 15.8% of the test size) compared with controls (mean responses ± SD reduced to 45.3% ± 16.2% of the test size;p < 0.001, unpaired t-test). Administration of a single oral dose of rivastigmine improved afferent inhibition in a subgroup of six patients. ConclusionsThe findings suggest that this method can be used as a noninvasive test of cholinergic pathways in AD. Future studies are required to evaluate whether short latency afferent inhibition measurements have any consistent clinical correlates.

Motor cortex hyperexcitability to transcranial magnetic stimulation in Alzheimer’s disease

Objectives: Recent transcranial magnetic stimulation (TMS) studies demonstrate that motor cortex excitability is increased in Alzheimer’s disease (AD) and that intracortical inhibitory phenomena are impaired. The aim of the present study was to determine whether hyperexcitability is due to the impairment of intracortical inhibitory circuits or to an independent abnormality of excitatory circuits. Methods: We assessed the excitability of the motor cortex with TMS in 28 patients with AD using several TMS paradigms and compared the data of cortical excitability (evaluated by measuring resting motor threshold) with the amount of motor cortex disinhibition as evaluated using the test for motor cortex cholinergic inhibition (short latency afferent inhibition) and GABAergic inhibition (short latency intracortical inhibition). The data in AD patients were also compared with that from 12 age matched healthy individuals. Results: The mean resting motor threshold was significantly lower in AD patients than in controls. The amount of short latency afferent inhibition was significantly smaller in AD patients than in normal controls. There was also a tendency for AD patients to have less pronounced short latency intracortical inhibition than controls, but this difference was not significant. There was no correlation between resting motor threshold and measures of either short latency afferent or intracortical inhibition (r = −0.19 and 0.18 respectively, NS). In 14 AD patients the electrophysiological study was repeated after a single oral dose of the cholinesterase inhibitor rivastigmine. Resting motor threshold was not significantly modified by the administration of rivastigmine. In contrast, short latency afferent inhibition from the median nerve was significantly increased by the administration of rivastigmine. Conclusions: The change in threshold did not seem to correlate with dysfunction of inhibitory intracortical cholinergic and GABAergic circuits, nor with the central cholinergic activity. We propose that the hyperexcitability of the motor cortex is caused by an abnormality of intracortical excitatory circuits.

Cognitive and behavioural effects of chronic stimulation of the subthalamic nucleus in patients with Parkinson’s disease

Objective: To investigate cognitive and behavioural effects of bilateral lead implants for high frequency stimulation (HFS) of the subthalamic nucleus in patients with Parkinson’s disease; and to discriminate between HFS and the effects of surgical intervention on cognitive function by carrying out postoperative cognitive assessments with the stimulators turned on or off. Methods: Motor, cognitive, behavioural, and functional assessments were undertaken in 20 patients with Parkinson’s disease before implantation and then at three, six, and 12 months afterwards. Nine patients were also examined 18 months after surgery. Postoperative cognitive assessments were carried out with stimulators turned off at three and 18 months, and turned on at six and 12 months. Results: Cognitive assessment showed a significant postoperative decline in performance on tasks of letter verbal fluency (across all postoperative assessments, but more pronounced at three months) and episodic verbal memory (only at three months, with stimulators off). At three, six, and 12 months after surgery, there was a significant improvement in the mini-mental state examination and in a task of executive function (modified Wisconsin card sorting test). On all postoperative assessments, there was an improvement in parkinsonian motor symptoms, quality of life, and activities of daily living while off antiparkinsonian drugs. A significant postoperative decrease in depressive and anxiety symptoms was observed across all assessments. Similar results were seen in the subgroup of nine patients with an 18 month follow up. Following implantation, three patients developed transient manic symptoms and one showed persistent psychic akinesia. Conclusions: Bilateral HFS of the subthalamic nucleus is a relatively safe procedure with respect to long term cognitive and behavioural morbidity, although individual variability in postoperative cognitive and behavioural outcome invites caution. Stimulation of the subthalamic nucleus does not per se appear to impair cognitive performance in patients with Parkinson’s disease and may alleviate the postpoperative decline in verbal fluency.

Dissociation between knowledge of living and nonliving things in dementia of the Alzheimer type

Patients who survive herpes simplex encephalitis (HSE) sometimes present a category-specific disorder for living things. Since HSE specifically involves the temporolimbic structures of both hemispheres, these structures could play a critical role in processing and storing information about living things. If this were the case, a category-specific disorder for the same items should also be observed in the early stages of dementia of the Alzheimer type (DAT) as the temporolimbic structures are often severely affected in this condition. To test this hypothesis, we administered to 15 DAT patients and to 10 normal controls a confrontation-naming task and a verbal associates recognition task, with both living and nonliving items as stimuli. The hypothesis was confirmed, since DAT patients performed worse with living than with nonliving items, and scored worse than normal controls on the living but not the nonliving items.

Cognitive outcome 5 years after bilateral chronic stimulation of subthalamic nucleus in patients with Parkinson’s disease

Aim: To assess the long-term cognitive and behavioural outcome after bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients affected by Parkinson’s disease, with a 5-year follow-up after surgery. Methods: 11 patients with Parkinson’s disease treated by bilateral DBS of STN underwent cognitive and behavioural assessments before implantation, and 1 and 5 years after surgery. Postoperative cognitive assessments were carried out with stimulators turned on. Results: A year after surgery, there was a marginally significant decline on a letter verbal fluency task (p = 0.045) and a significant improvement on Mini-Mental State Examination (p = 0.009). 5 years after surgery, a significant decline was observed on a letter verbal fluency task (p = 0.007) and an abstract reasoning task (p = 0.009), namely Raven’s Progressive Matrices 1947. No significant postoperative change was observed on other cognitive variables. No patient developed dementia 5 years after surgery. A few days after the implantation, two patients developed transient manic symptoms with hypersexuality and one patient developed persistent apathy. Conclusion: The decline of verbal fluency observed 5 years after implantation for DBS in STN did not have a clinically meaningful effect on daily living activities in our patients with Parkinson’s disease. As no patient developed global cognitive deterioration in our sample, these findings suggest that DBS of STN is associated with a low cognitive and behavioural morbidity over a 5-year follow-up, when selection criteria for neurosurgery are strict.

Early rightwards orienting of attention on simple reaction time performance in patients with left-sided neglect

A specific disruption in the ability to automatically disengage attention from its previous focus has been hypothesized to account for the extinction phenomenon often observed in the unilateral spatial neglect syndrome. Recent literature, however, also brings out the role played in neglect by an imbalance in the attentional orienting systems, resulting in an early shift of attention towards the side of space ipsilateral to the brain lesion. In the present study we hypothesized that this attentional bias in orienting of attention might be demonstrated in a paradigm of simple reaction time to lateralized visual stimuli by contrasting the presence vs the absence on the computer screen of the square boxes used to facilitate position expectancy. A main prediction was made that patients with neglect would show a significant increase in reaction time to contralateral visual stimuli in the presence of bilateral reference boxes as compared to conditions in which no boxes were displayed. The right-sided box was in fact expected to exert an early attraction on the patients attention, thus modifying the pattern of reaction times to the proper targets. This prediction was confirmed in right brain-damaged patients with moderate to severe neglect.