Tactile event-related potentials in amyotrophic lateral sclerosis (ALS): Implications for brain-computer interface.

OBJECTIVE: We investigated neurophysiological brain responses elicited by a tactile event-related potential paradigm in a sample of ALS patients. Underlying cognitive processes and neurophysiological signatures for brain-computer interface (BCI) are addressed. METHODS: We stimulated the palm of the hand in a group of fourteen ALS patients and a control group of ten healthy participants and recorded electroencephalographic signals in eyes-closed condition. Target and non-target brain responses were analyzed and classified offline. Classification errors served as the basis for neurophysiological brain response sub-grouping. RESULTS: A combined behavioral and quantitative neurophysiological analysis of sub-grouped data showed neither significant between-group differences, nor significant correlations between classification performance and the ALS patients' clinical state. Taking sequential effects of stimuli presentation into account, analyses revealed mean classification errors of 19.4% and 24.3% in healthy participants and ALS patients respectively. CONCLUSIONS: Neurophysiological correlates of tactile stimuli presentation are not altered by ALS. Tactile event-related potentials can be used to monitor attention level and task performance in ALS and may constitute a viable basis for future BCIs. SIGNIFICANCE: Implications for brain-computer interface implementation of the proposed method for patients in critical conditions, such as the late stage of ALS and the (completely) locked-in state, are discussed.

Insight into the relationship between brain/behavioral speed and variability in patients with minimal hepatic encephalopathy.

OBJECTIVE: Intra-individual variability (IIV) of response reaction times (RTs) and psychomotor slowing were proposed as markers of brain dysfunction in patients with minimal hepatic encephalopathy (MHE), a subclinical disorder of the central nervous system frequently detectable in patients with liver cirrhosis. However, behavioral measures alone do not enable investigations into the neural correlates of these phenomena. The aim of this study was to investigate the electrophysiological correlates of psychomotor slowing and increased IIV of RTs in patients with MHE. METHODS: Event-related potentials (ERPs), evoked by a stimulus-response (S-R) conflict task, were recorded from a sample of patients with liver cirrhosis, with and without MHE, and a group of healthy controls. A recently presented Bayesian approach was used to estimate single-trial P300 parameters. RESULTS: Patients with MHE, with both psychomotor slowing and higher IIV of RTs, showed higher P300 latency jittering and lower single-trial P300 amplitude compared to healthy controls. In healthy controls, distribution analysis revealed that single-trial P300 latency increased and amplitude decreased as RTs became longer; however, in patients with MHE the linkage between P300 and RTs was weaker or even absent. CONCLUSIONS: These findings suggest that in patients with MHE, the loss of the relationship between P300 parameters and RTs is related to both higher IIV of RTs and psychomotor slowing. SIGNIFICANCE: This study highlights the utility of investigating the relationship between single-trial ERPs parameters along with RT distributions to explore brain functioning in normal or pathological conditions.

Modulation of affective symptoms and resting state activity by brain stimulation in a treatment-resistant case of obsessive-compulsive disorder.

The effect of transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) on psychopathological symptoms and resting state brain activity was assessed in a patient with obsessive-compulsive disorder (OCD). tDCS and rTMS had no effect on OC symptoms. tDCS, however, improved depression and anxiety. Functional magnetic resonance imaging at baseline showed an interhemispheric asymmetry with hyperactivation of the left and hypoactivation of the right anterior neural circuits. A reduction of interhemispheric imbalance was detected after tDCS but not after rTMS. tDCS seems to be more effective than rTMS in restoring interhemispheric imbalance and improving anxiety and depression in OCD.

Event-related brain potential modulation in patients with severe brain damage.

OBJECTIVE: The limited evidence and inconsistency of purposeful behaviors in patients in a minimally conscious state (MCS) asks for objective electrophysiological marker of the level of consciousness. Here, a comparison between event-related potentials (ERPs) was investigated using different level of stimulus complexity. METHODS: The patients in vegetative state were 11 and the MCS patients were 6 [corrected]. Three oddball paradigms with different level of complexity were applied: sine tones, the subject's own name versus sine tones and other first names. Latencies and amplitudes of N1 and P3 waves were compared. RESULTS: Cortical responses were found in all MCS patients, and in 6 of 11 patients in VS. Healthy controls and MCS patients showed a progressive increase of P3 latency in relation to the level of stimulus complexity. No modulation of P3 latency was observed in the vegetative patients. CONCLUSIONS: These results suggest that the modulation of P3 latency related to stimulus complexity may represent an objective index of higher-order processing integration that predicts the recovery of consciousness from VS to MCS when clinical manifestations are inconsistent. SIGNIFICANCE: Modulation of P3 latency related to stimulus complexity could provide valuable information about the cognitive capabilities of unresponsive patients.

Right hemisphere dysfunction and emotional processing in ALS: an fMRI study.

Emotional processing may be abnormal in amyotrophic lateral sclerosis (ALS). Our aim was to explore functional anatomical correlates in the processing of aversive information in ALS patients. We examined the performance of nine non-demented ALS patients and 10 healthy controls on two functional MRI (fMRI) tasks, consisting of an emotional attribution task and a memory recognition task of unpleasant versus neutral stimuli. During the emotional decision task, subjects were asked to select one of three unpleasant or neutral words. During the memory task, subjects were asked to recognize words presented during the previous task. Controls showed, as expected, greater activation in the right middle frontal gyrus during selection of unpleasant than neutral words, and a greater activation mainly in right-sided cerebral areas during the emotional recognition task. Conversely, patients showed a general increase in activation of the left hemisphere, and reduced activation in right hemisphere in both emotional tasks. Such findings may suggest extra-motor neurodegeneration involving key circuits of emotions, mostly negative, commonly involved in FTD.

Population isolates in South Tyrol and their value for genetic dissection of complex diseases.

The study of genetic isolates is a promising approach for the study of complex genetic traits. The small and constant population size, lack of migration, and multiple relationships between individuals in the isolate population could reduce the genetic diversity, and lead to increased levels of linkage disequilibrium (LD). We studied the extent of LD on Xq13 in six population isolates from South Tyrol in the Eastern Italian Alps. We found different levels of LD in our study samples, probably reflecting their degrees of isolation and their demographic histories. The highest values were obtained in Val Gardena (ranking among the highest levels of LD in Europe) and in Stelvio, which qualified as a microisolate according to historical information, and biodemographic and genealogical criteria. Phylogenetic analysis revealed that the two Ladin-speaking populations are genetically distant from each other, and from their German-speaking neighbours, and are characterized by a smaller effective population size than the neighbouring valleys. These peculiar characteristics suggest that South Tyrol could be a unique resource for the study of complex diseases, showing all the characteristics of isolated populations with the advantage of including, in a fairly homogeneous environment, two genetically differentiated sub-populations. This could allow investigators to gain an insight into the contribution of genetic heterogeneity in complex diseases.

Functional evidence for the presence of type II 5'-deiodinase in somatotropes and its adaptive role in hypothyroidism.

The anterior pituitary contains abundant type II iodothyronine 5'-deiodinase (D2). The role of this enzyme in mediating thyroid hormone action in the pituitary has been proven only for thyrotropes, although there is evidence that it exists in other cell types, including somatotropes and lactotropes. Here we investigated the potential of D2 to mediate thyroid hormone regulation of growth hormone (GH). Using GH mRNA as an end point, we demonstrate that in hyperthyroid states GH mRNA levels are stimulated by triiodothyronine (T(3)) generated via D1, whereas in hypothyroidism, when D2 activity is markedly increased, GH mRNA is more responsive to tetraiodothyronine (T(4)) in a propylthiouracil-insensitive, reverse T(3)-suppressible manner. Under short-term hyperthyroid conditions, GH levels correlate with plasma T(3); in contrast, the correlation is not observed in hypothyroidism, a condition in which plasma T(3) levels are too low to account for the response. These results add support to the concept that D2 is present in the pituitary and that the enzyme plays an important role in mediating stimulation of GH by thyroid hormones, particularly in hypothyroid states in which they could alleviate the impact of hypothyroxinemia on GH secretion.

Role of thyroid hormone in the control of growth hormone gene expression.

Growth hormone (GH) gene expression was examined in male Wistar rats (200 g) subjected to different manipulations of thyroid status. Thyroidectomy followed by 10 days of treatment with 0.03% methimazole added to drinking water caused a marked decrease in GH mRNA levels estimated by Northern Blot analysis. T3 administration (100 micrograms/100 g body weight, ip, twice daily) to euthyroid rats for one week caused a substantial increase in GH mRNA levels. In another set of experiments, thyroidectomized methimazole-treated rats were killed at different times after a single T3 injection (100 micrograms/100 g body weight, ip). T3 induced a prompt response in GH gene expression by 15 min that reached a maximum after 1 h, remaining so up to 4 h. We conclude that in the rat, GH gene expression is highly dependent on thyroid hormones. Because of the rapidity of the response, the effect is probably mediated by a transcriptional mechanism.

Role of thyroid hormone in the control of growth hormone gene expression

Growth hormone (GH) gene expression was examined in male Wistar rats (200 g) subjected to different manipulations of thyroid status. Thyroidectomy followed by 10 days of treatment with 0.03 methimazole added to drinking water caused a marked decrease in GH mRNA levels estimated by Northern Blot analysis. T3 administration (100 micrograms/100 g body weight, ip, twice daily) to euthyroid rats for one week caused a substantial increase in GH mRNA levels. In another set of experiments, thyroidectomized methimazole-treated rats were killed at different times after a single T3 injection (100 micrograms/100 g body weight, ip). T3 induced a prompt response in GH gene expression by 15 min that reached a maximum after 1 h, remaining so up to 4 h. We conclude that in the rat, GH gene expression is highly dependent on thyroid hormones. Because of the rapidity of the response, the effect is probably mediated by a transcriptional mechanism.

Categorical differentiation and intergroup relationships.

In this study we attempted to replicate the well-known Doise & Sinclair (1973) procedure for manipulating category salience, in a different social context. We considered the relationship between two groups of professionals: doctors and nurses, as perceived by 40 members of the superior group. The results did not confirm those obtained by Doise & Sinclair since they showed reduced categorical differentiation when the out-group was evoked in advance of the intergroup evaluations. The implications of these findings for theories of social categorization and social identity are discussed.

[Management of disease carriers]. / Gestione dei portatori.

In the present communication there are exposed the treatment modalities of health carriers. The difficulties of action depends primarily on scarcity of health education and of adequate structures and manufacturing equipment in the places of work.

[Prevalence of tetanus immunity in metal mechanical workers]. / Prevalenza dell'immunita; antitetanica in lavoratori metalmeccanici.

The results of a seroepidemiological prevalence survey on the immune status against tetanus of steelmill workers (who, limited to the new work call ups, had to be vaccinated since 1968) are reported. We did not observe remarkable differences in protection against tetanus among those who had begun work before 1968 (46.4% protected) and after 1968 (53.5% protected). In both cases, the protective values were the result of immunization procedures that were performed exclusively in consequence of the military service and/or on the occasion of industrial accident and/or road accident or of accidents of other kinds. It appears, moreover, that the protection of workers against this disease is, nowadays, too often relying on serum prophylaxis, which was the only preventive measure adopted for over half of the workers. In the light of the reported data we need to enforce the existing legislative measures.

Experiences from the accident of Seveso.

Provisional data on selected sanitary events which took place at Seveso after July 10 1976 are reported. 187 cases of chloracne, mostly in children, were detected, 50 just after the accident, the others within a year. Most polluted area (zone A) provided almost all "early" and most severe cases, but the territorial distribution of chloracne prevalence rates showed some inconsistencies with the soil TCDD pollution map; interpretations for such findings are discussed. Thirty-eight birth defects were detected in 1977 (none in zones A and B), more than in previous years, but still less than expected in a well controlled "normal" population: no clustering around a given type was observed. Spontaneous abortions, evaluated both as abortion rates and as pregnancy loss rates, showed scattered and statistically non-significant variations, inconsistent with the pollution map. No differences in birth and death rates compared to surrounding areas were observed. Data on ad hoc cytogenetic, neurological and immunological surveys are commented. Limitations of the presently available data are discussed and further research lines are anticipated.