Minimal changes of thyroid axis activity influence brain functions in young females affected by subclinical hypothyroidism.

There is evidence of an association between thyroid hormones (TH) alterations and mental dysfunctions related to procedural and working memory functions, but the physiological link between these domains is still under debate, also for the presence of age as a confounding factor. Thus, we investigated the TH tuning of cerebral functions in young females affected by the borderline condition of subclinical hypothyroidism (SH) and in euthyroid females of the same age. The experiment consisted in the characterization of the affective state and cognitive abilities of the subjects by means of specific neuropsychological questionnaires, and of brain activity (EEG) in resting state and during the passive viewing of emotional video-clips. We found that SH had i) increased anxiety for Physical Danger; ii) better scores for both Mental Control and no-working-memory-related functions; iii) association between anxiety for Physical Danger and fT4 levels. Thus, in young adults, SH increases inward attention and paradoxically improves some cognitive functions. In addition, self-assessed questionnaires showed that SH had a greater susceptibility to unpleasant emotional stimulation. As for EEG data, SH compared to controls showed: i) reduction of alpha activity and of gamma left lateralization in resting state; ii) increased, and lateralized to the right, beta2 activity during stimulations. Both results indicated that SH have higher levels of arousal and greater susceptibility to negative emotion than controls. In conclusion, our study indicates that minimal changes in TH levels produce subtle but well-defined mental changes, thus encouraging further studies for the prediction of pathology evolution.

Watching neutral and threatening movies: subjective experience and autonomic responses in subjects with different hypnotizability levels.

Subjects with high hypnotizability scores (Highs) have been considered more prone to experience negative affect and more vulnerable to its autonomic effects with respect to low hypnotizable individuals (Lows). The aim of the study was to analyze the subjective experience, tonic skin conductance (SC), respiratory frequency (RF), heart rate (HR) and heart rate variability (HRV) of healthy Highs and Lows during a long-lasting, emotionally neutral task (Session R, 46 subjects) and a moderately threatening one (Session T, 35 subjects). At the end of the relaxing Session R, all participants reported an increased relaxation. At the end of the threatening Session T, only 20 subjects reported a decreased relaxation (effective T: eT subsample). Highs and Lows of this subsample reported a similarly reduced relaxation and showed a similarly increased skin conductance. HR and HRV did not differ between the two sessions and between Highs and Lows. Among the subjects not reporting decreased relaxation at the end of Session T (ineffective T: iT subsample, n=15), relaxation was deeper and associated with lower skin conductance in Highs, although HR and HRV did not differ between Highs and Lows. All together, the results do not support the hypothesis of higher proneness of Highs to experience negative affect and to exhibit the autonomic correlates of negative emotion.

Can imagery become reality?

Previous studies showed that highly hypnotizable persons imagining a specific sensory context behave according to the corresponding real stimulation and perceive their behaviour as involuntary. The aim of the study was to confirm the hypothesis of a translation of sensory imagery into real perception and, thus, of a true involuntary response. We studied the imagery-induced modulation of the vestibulospinal (VS) reflex earlier component in highly (Highs) and low hypnotizable subjects (Lows), as it is not affected by voluntary control, its amplitude depends on the stimulus intensity, and the plane of body sway depends on the position of the head with respect to the trunk. Results showed that the effects of the "obstructive" imagery of anaesthesia are different from those elicited by the "constructive" imagery of head rotation. Indeed, both Highs and Lows having their face forward and reporting high vividness of imagery experienced anaesthesia and reduced their VS reflex amplitude in the frontal plane, while only Highs changed the plane of body sway according to the imagined head rotation that is from the frontal to the sagittal one. These effects cannot be voluntary and should be attributed to translation of sensory imagery into the corresponding real perception.

Objective selection of EEG late potentials through residual dependence estimation of independent components.

This paper presents a novel method to objectively select electroencephalographic (EEG) cortical sources estimated by independent component analysis (ICA) in event-related potential (ERP) studies. A proximity measure based on mutual information is employed to estimate residual dependences of the components that are then hierarchically clustered based on these residual dependences. Next, the properties of each group of components are evaluated at each level of the hierarchical tree by two indices that aim to assess both cluster tightness and physiological reliability through a template matching process. These two indices are combined in three different approaches to bring to light the hierarchical structure of the cluster organizations. Our method is tested on a set of experiments with the purpose of enhancing late positive ERPs elicited by emotional picture stimuli. Results suggest that the best way to look for physiologically plausible late positive potential (LPP) sources is to explore in depth the tightness of those clusters that, taken together, best resemble the template. According to our results, after brain sources clustering, LPPs are always identified more accurately than from ensemble-averaged raw data. Since the late components of an ERP involve the same associative areas, regardless of the modality of stimulation or specific tasks administered, the proposed method can be simply adapted to other ERP studies, and extended from psychophysiological studies to pathological or sport training evaluation support.

Residual dependency estimation of independent components applied to EEG event related potentials associated with emotional processing.

Independent component analysis can be employed as an exploratory method in electroencephalographic (EEG) data analysis. However, the assumption of statistical independence among the estimated components is not always fulfilled by ICA-based numerical methods. Furthermore it may happen that one physiological source can be split in two or more components. As a consequence, the estimated components must be further investigated to assess the existence of reciprocal similarities. In this work a method for finding residual dependency subsets of component is proposed. Firstly a hierarchical clustering stage is carried out to classify ICA results. Then the hierarchical tree is investigated at each level by two indices to evaluate the tightness of all clusters. At the same time clustered scalp projections are compared with a template, which is shaped by applying ensemble ICA to a training dataset. Results are shown on EEG data acquired in event-related brain potentials (ERPs) studies for emotional pictures processing. In this kind of experiment ERPs are measured whilst unpleasant and neutral images are shown to a subject. The clustering procedure and the performance indices succeeded in isolating compact groups of components. These components, taken together, reflect the brain's biopotentials related to emotional processing at different cortical areas.

Relaxation as a cognitive task.

In the present experiment the instruction to relax was given to awake highly (Highs) and non hypnotizable subjects (Lows), while their heart rate, respirogram and skin resistance were recorded together with electroencephalogram, electroculogram and corrugator electromiogram. At the beginning of the experiment, Highs exhibited no significant difference in heart rate (HR), respiratory frequency (RF) and heart rate variability (HRV) with respect to Lows, but showed a higher EEG alpha and theta1 power. During the session, both groups decreased their heart rate, but changes were significant only in Lows, which increased significantly also the parasympathetic component of their HRV (high frequency, HF). In both groups, EEG showed alpha, beta2 and theta2 power decrements; theta1 activity decreased only in Lows, while gamma power increased in Highs and decreased in Lows. Results suggest that Highs and Lows used different cognitive strategies in the elaboration of the relaxation request and that Highs performed the task through a higher integrative activity.

Kinematic strategies for lowering of upper limbs during suggestions of heaviness: a real-simulator design.

The aim of the experiment was to study possible differences between the kinematic strategies for the "involuntary" arm lowering of hypnotized highly susceptible subjects (H-Highs) and for the voluntary movement of non-hypnotizable simulators (Sims) during suggestions of arm heaviness (Part I). In addition, a comparison between awake susceptible subjects (W-Highs) and H-Highs was carried out to clarify the specific role of the hypnotic state and hypnotizability (Part II). Subjects' absorption and attentional/imagery capabilities were evaluated through neuropsychological tests. Their arm movements were monitored three-dimensionally at hand, wrist and elbow level through a Polhemus Fastrack system. A final interview collected self-reports concerning the perception of movement involuntariness. Neuropsychological tests showed better "absorption" and imagery capabilities in Highs. In the interview, H-Highs perceived a higher involvement in the task and greater involuntariness and difficulties in contrasting the arm lowering than the Sims. Kinematic analysis showed significant differences between H-Highs and Sims for arm displacements along the vertical axis and on the horizontal plane. In fact, the former lowered the left arm earlier and to a greater degree than the right arm; on the horizontal plane, a forearm flexion was observed for H-Highs on the right side. On comparing W-Highs and H-Highs, hypnosis appeared to magnify the waking motor strategies, but also to induce specific changes, mainly concerning the horizontal plane. These results cannot be interpreted on the basis of "role playing" and socio-cognitive factors. They are believed to be due to a balance between the effectiveness of the frontal executive control towards the selection of behaviors and movement automaticity, which is in line with the neo-dissociation theory of hypnosis.

Sensory-motor cortex activity modulation by hypnotic susceptibility and hypnosis during finger movement.

The aim of the experiment was to study whether the activity of the primary sensory-motor (S1/M1), supplementary motor (SMA) and pre-motor (PMA) areas during fingers movement is modulated by hypnotic susceptibility and hypnosis. Cortical activity was studied through functional Magnetic Resonance Imaging (fMRI) during a finger-to-thumb opposition task in awake (Highs) and hypnotized highly susceptible (H-Highs) as well as in awake non susceptible subjects (Lows). Results did not show any significant difference in sensory-motor areas activation between Highs and Lows (trait effect) and between Highs and H-Highs (state effect). The activation in 3 subjects among Highs and only 1 among Lows (out of 5) of the caudal S1, receiving the most part of the cutaneous input, appears noteworthy and prompts further investigation on possible hypnotizability-related differences in sensory-motor integration.

Influence of mental motor imagery on the execution of a finger-to-thumb opposition task.

The present fMRI study compares regional distribution of the cortical activity during the execution of unilateral hand movements (finger-to-thumb opposition) preceded or not by their motor simulation (S + E and E condition, respectively). The results show that, overall, the number and the spatial distribution of activated voxels are both increased in the S + E with respect to the E condition. The motor performance preceded by mental rehearsal is related to selective increase of the cortical activity. Among the motor areas that are found active during the simple motor execution a significant enhancement of functional activation during the S + E condition ipsilateral primary motor regions (M1). The activity increase may be accounted by a sort of neural recruiting that is made possible by the overlapping of cortical networks involved in both motor output and motor imagery. The beneficial effects of "mental practice" on the physical performance may rely to the close temporal association between motor rehearsal and actual performance.

Autonomic and EEG correlates of emotional imagery in subjects with different hypnotic susceptibility.

The autonomic and EEG correlates of the response to a cognitive unpleasant stimulation (US) verbally administered to awake hypnotizable and non hypnotizable subjects were studied. They were compared with the values obtained during a resting condition immediately preceding the stimulus and with those produced by a cognitive neutral stimulation (NS), also administered after a basal resting period. Results showed hypnotic trait effects on skin resistance, heart and respiratory rate as well as on EEG theta, alpha, beta and gamma relative power changes. The autonomic and EEG patterns observed indicated different strategies in the task execution for hypnotizable and non hypnotizable subjects and a discrepancy between the autonomic and EEG changes associated to the US in susceptible subjects. Results support dissociation theories of hypnosis and suggest for hypnotizable persons an active mechanism of protection against cardiac hazard.

Human hypnosis: autonomic and electroencephalographic correlates of a guided multimodal cognitive-emotional imagery.

The effects of a guided neutral and unpleasant imagery involving several sensory modalities were studied in hypnotized subjects. Heart rate (HR), respiratory frequency (RF), tonic skin resistance and different electroencephalographic rhythms were evaluated during a long-lasting hypnotic session including the guided suggestion of a neutral (NS) and an unpleasant (US) imagery, each preceded by a hypnotic relaxation rest period. During NS, the absence of autonomic changes, associated with electroencephalographic gamma power decrement and theta1 power increment, indicated the prevalence of relaxation on the expected task-related modifications. In contrast, US elicited HR and RF increments together with higher electroencephalographic gamma, beta3 and beta2 activities. Thus, hypnotic state appears to prevent the autonomic responses expected during the neutral stimulation, while the emotional valence of the unpleasant imagery overwhelms the hypnosis-related relaxation.

Reorganisation of the sensorimotor cortex after early focal brain lesion: a functional MRI study in monozygotic twins.

Sensorimotor cortical reorganization after early brain lesions was studied by means of fMRI in two pairs of monozygotic twins, in each of which one member had a focal brain injury. This offered a unique opportunity to reduce the wide intersubject variability of the controls often found in similar studies. Activation images were acquired during a motor task (sequential opposition finger movements) and a sensory task (passive brushing of palm and fingers). During the tasks with the recovered hand, constant findings in the lesioned subjects were the activation of the undamaged areas adjacent to lesion site and the activation of the ipsilateral sensorimotor cortex. Bilateral activation of the primary sensorimotor cortex was never observed in the healthy co-twin controls.

Safety of ergot stress echocardiography for non-invasive detection of coronary vasospasm.

BACKGROUND: The safety of ergonovine/ergometrine stress testing for coronary vasospasm when performed outside the cardiac catheterization laboratory (cath lab) has been questioned vigorously. AIM: To assess the tolerability and safety of ergonovine/ergometrine stress testing performed in the echocardiographic laboratory (echo lab). METHODS: We retrospectively reviewed the data prospectively collected in the echo lab of the Institute of Clinical Physiology from 1 January 1985 to 1 June 2000, from 587 tests performed on 573 patients (either ergonovine or ergometrine stress echocardiography testing). By selection, all patients had a history of chest pain, consistent with vasospastic angina, negative exercise stress testing or stress echocardiography (with dipyridamole, dobutamine or exercise), and normal or near normal resting left ventricular function. Ergonovine or ergometrine maleate was injected up to a total cumulative dosage of 0.35 mg, under continuous 12-lead electrocardiographic and two-dimensional echocardiographic monitoring. RESULTS: There were no deaths, myocardial infarctions, ventricular fibrillations or third degree AV blocks. One patient had non-sustained ventricular tachycardia associated with transient ST segment elevation 30 min after the test. Three patients had second degree AV block associated with a positive echocardiography test that was promptly reversed by nitrates administration. Transient regional myocardial dysfunction occurred in 79 patients (13%). Limiting ischaemia-independent side effects were present in 17 patients (3%): hypotension in one, arterial hypertension in five, non-sustained ventricular tachycardia in two and nausea or vomiting in ten. The test was well tolerated and echocardiograms were interpretable in 97% of the tests performed. CONCLUSION: Pharmacological stress echocardiography with either ergonovine or ergometrine is well tolerated and can be performed with relatively low risk in the echo lab in properly selected patients in whom coronary vasospasm is suspected.

Changes in autonomic and EEG patterns induced by hypnotic imagination of aversive stimuli in man.

Autonomic and electroencephalographic (EEG) responses to aversive stimuli presented by means of hypnotic suggestion have been studied in man.Healthy volunteers with simple phobia were screened for susceptibility to hypnosis. The experimental paradigm included periods of rest during which the hypnotized subjects were asked to produce an emotionally neutral mental image and periods of emotional activation in which they were asked to image a phobic object. Heart rate (HR), respiratory frequency (RF) and EEG were processed to obtain the HR-related indexes of sympatho-vagal balance and the EEG spectral components. The results showed a significant increase in HR and RF with a shift of the sympatho-vagal indexes towards a sympathetic predominance during the hypnotic emotional activation. EEG activity showed a significant increase in the gamma band with a left fronto-central prevalence. There was also a less pronounced increase in the beta band. In conclusion, by means of hypnosis, autonomic and behavioral responses to fear-like stimuli can be induced in man in a reproducible and controlled manner. Such a paradigm could be applied in human neuroimaging studies to identify central nervous structures that modulate stress and fear-related reactions.

The action of steroid hormones on peripheral myelin proteins: a possible new tool for the rebuilding of myelin?

The present paper summarizes recent results we have obtained while studying the effect of sex steroids on the gene expression of two peripheral myelin proteins, the glycoprotein Po (Po) and the peripheral myelin protein 22 (PMP22). In particular, we have analyzed the effect of progesterone (P), testosterone (T) and their 5alpha- and 3alpha-5alpha-reduced derivatives [respectively, dihydrotestosterone (DHTT) and 5alpha-androstan-3alpha, 17beta-diol (3alpha-diol) for T, and dihydroprogesterone (DHP) and tetrahydroprogesterone (THP) for P]. The data obtained, utilizing different in vivo and in vitro experimental models, have indicated that: a) DHP is able to enhance the low messenger levels of Po present in the sciatic nerve of aged male rats; b) P, DHP and THP treatments stimulate the gene expression of Po in the sciatic nerve of adult male rats or in cultures of rat Schwann cells, while only THP is effective on PMP22; c) P and DHP are also able to increase the low messenger levels of Po present in transected sciatic nerve; d) the removal of circulating androgens by castration is able to decrease the mRNA levels of Po in the sciatic nerve, a phenomenon which is counteracted by the consequent treatment with DHT; e) the stimulatory effect of DHT on the gene expression of Po is also evident in cultures of rat Schwann cells, but in this case the effect seems to be due to the interaction of this steroid with the progesterone receptor; f) in cultures of Schwann cells PMP22 mRNA levels are stimulated only by 3alpha-diol treatment. Taken together, these observations showing the positive effects of sex steroid hormones on the gene expressions of Po and PMP22, suggest that a treatment with these molecules or their synthetic agonists may be useful in cases in which the rebuilding of myelin is necessary.

Role of the medial prefrontal cortex in the development of conditioned bradycardia in rabbits with lesions of the cerebellar vermis.

The effects on the expression of conditioned bradycardia of pairing an early (fourth postnatal day) cerebellar vermal lesion with a lesion of the medial prefrontal cortex (mPFC) were studied in adult New Zealand rabbits. In the conditioning procedure, an auditory stimulus (5 s, 1000 Hz) served as a conditioning stimulus (CS) and a train of electrical impulses applied to the ear (500 ms, 100 Hz, 1.5 mA) was used as the unconditioned stimulus (US). Heart rate (HR) responses exhibited by rabbits with the early double lesion (PFCBs) during orientation (CS-alone) and conditioning (CS-US paired) were analyzed and compared with those shown by unoperated controls as well as by a group of animals in which a cerebellar lesion alone had been performed on the fourth postnatal day (CBs). In all the experimental groups vermal lesions were localized in the cortex of lobules V-VII and the underlying white matter. As for mPFC ablation, the lesioned area involved the agranular precentral region (Brodmann's area 8), the anterior cingulate cortex (Brodmann's area 24) and the prelimbic area (Brodmann's area 32). All the experimental animals had a normal baseline HR as well as a marked orientation response, both comparable with those exhibited by controls. In contrast, while CB rabbits showed an increase in the amplitude of the conditioned bradycardic response when compared with controls, the HR conditioned response of PFCB animals was comparable to that exhibited by controls. These results suggest that, since the double lesion produces a conditioned bradycardia similar to that of the controls, the increase in the amplitude of this response observed after early cerebellar removal may depend on the mPFC which, in the absence of specific cerebellar circuits, is unable to produce a properly calibrated HR conditioned response.

Neural interfaces for regenerated nerve stimulation and recording.

A class of implantable, regeneration-type neural interfaces (NI's) for mammalian peripheral nerve recording and stimulation were developed using different fabrication processes and integrating purposely designed components. A typical NI comprises three main components: 1) a microfabricated silicon die incorporating a microelectrode array on multiple through-holes, 2) a polymer guidance channel housing the die, and 3) a flexible flat cable connecting the die to an external electronic circuitry. The design and fabrication of the NI's were aimed at achieving long term, reliable implants by taking into careful account the biological, electrical, and mechanical requirements of the specific implant site. Different versions of the NI were fabricated and implanted between the severed ends of the sciatic nerve in a mammalian animal model (rabbit). Morphological and histological evidence showed that nerves regenerated through the NI's and electrophysiological results demonstrated the recovery of electrical functionality. Moreover, the NI's allowed stimulation of the regenerated nerve producing a visible leg/foot contraction. The NI's presented in this paper are being further improved in the authors' laboratories with the ultimate goal of allowing the control of nerve motor and sensory functions in future prosthetic devices.

Classical heart rate conditioning and affective behavior: the role of the cerebellar vermis.

The involvement of the cerebellar vermis in the control of affective behaviors and in the coordination of fear-related somatic and autonomic conditioned responses is reviewed in this paper. In particular, the review focuses on the role of the midline cerebellum (vermis) on the acquisition and/or expression of classically conditioned bradycardia in the rabbit. The results of both lesioning and electrophysiological experiments indicate that the cortex of lobule III through VII is important, although not essential, in the acquisition and retention of this response, but it is not the site of its memory trace. The time course of the development of the conditioned bradycardia in neonatal rabbits is also described. The results obtained are consistent with the possibility that the expression of conditioned bradycardia may depend on the complete maturation of cerebellum. Moreover, preliminary data on the effects of the ablation of cerebellar vermis, performed at early stages of development, on the characteristics of conditioned bradycardia showed by adult rabbits are presented. These results indicate that cerebellar vermis is essential for the correct maturation of the response and that the timing of the lesion is critical for determining the characteristics of conditioned bradycardia in the adult.

Effects of early cerebellar removal on the classically conditioned bradycardia of adult rabbits.

The magnitude of classically conditioned bradycardia was studied in 18-day-old and adult rabbits in which the cerebellar vermis had been surgically removed on either the 5th or 18th postnatal day. In the conditioning procedure, an auditory stimulus (5 s, 1000 Hz) served as conditioned stimulus (CS) and a train of electric impulses applied to the ear (100 Hz, 500 ms, 1.5 mA) was employed as the unconditioned stimulus (US). Heart rate (HR) responses developed in the operated animals during the CS-alone (orientation), and CS-US paired presentations (conditioning) were analyzed and compared with those developed in control animals. In all the experimental groups, lesions were localized to the cortex of lobules IV-VII and the underlying white matter, sparing the deep cerebellar nuclei. None of the lesioned animals showed any behavioral or somatomotor deficit. All the operated animals exhibited a normal baseline HR and a marked orienting response, both comparable with those of controls. In contrast, while the animals tested at 18 days showed a normal pattern of conditioned bradycardia, at the age of 3 months the HR conditioned response differed significantly from that observed in control rabbits: the animals that received the earliest cerebellar lesion showed a conditioned bradycardia greater than that of controls, the rabbits lesioned on the 18th postnatal day exhibited a reduced bradycardic response. These results suggest that the timing of cerebellar vermis removal, at early stages of development, represents a crucial factor in the organization of the bradycardic response in the adult.