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.

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.

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.

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.

The role of the posterior cerebellar vermis in cardiovascular control.

The effects of electrical stimulation of the posterior cerebellar vermis in anaesthetized, decerebrate and conscious animals are described, and include marked changes in blood pressure and heart rate and an inhibition of the baroreceptor reflex. These effects appear to be restricted to lobule IX, and can be duplicated by chemical stimulation, indicating that they are a genuine cerebellar phenomenon. The results of both neuroanatomical and neurophysiological experiments to investigate the pathways responsible for the effects are described, and these show there to be a direct projection of Purkinje cell axons to the parabrachial nucleus. Experiments designed to test a possible involvement of lobule IX in the alerting response have proved negative, and while lobule IX itself appears to have no role in conditioned cardiovascular responses, lesions of lobules VI and VII do result in a significant impairment of the acquisition of conditioned bradycardia in the rabbit.

Development of vertical vestibulo-ocular reflex characteristics in intact and flocculectomized rabbits visually deprived from birth.

The vertical vestibulo-ocular reflex (VOR) was recorded in dark-reared rabbits 3 months of age submitted in the dark to lateral sinusoidal oscillations of different frequencies and fixed amplitude. While the phase of the response was perfectly adequate to ensure head movements compensation, the gain values recorded showed a clear reduction with respect to the values obtained in a normally raised control group of the same age. After exposure to light, the visually deprived animals showed a complete and rapid recovery of normal VOR gain values. Another group of animals was flocculectomized prior to light exposure. The bilateral ablation of flocculus and paraflocculus did not affect the VOR characteristics of the deprived animals. After exposure to light, in the flocculectomized animals, no recovery of the VOR gain values was observed. The present results confirm that visual experience in early life is necessary for a correct development of the VOR. If visual deprivation is limited to the first few months of life, the impairment of the reflex characteristics is completely reversible. Finally our data suggest that in the rabbit, the flocculus controls the early life development of the VOR.

Dark-rearing modifies serotonin and 5-hydroxyindoleacetic acid contents in specific regions of rabbit brain.

The contents of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in specific brain regions of rabbits dark-reared from birth until 3 months of age are higher than those of controls. After light exposure, 5-HT and 5-HIAA levels become similar to normal values. In adult rabbits kept in darkness for 3 months, 5-HT and 5-HIAA contents increase only in the superior colliculi. These results are discussed in relation to the early development of the vestibulo-ocular reflex.

Phase changes induced by ketamine in the vertical vestibulo-ocular reflex in the rabbit.

The effect of ketamine has been tested on the phase of the vertical vestibulo-ocular reflex of rabbits sinusoidally oscillated at various frequencies. A significant phase lag, predominantly affecting the macular component of the reflex, was observed. This action resembles that induced by Nembutal in the same preparation. A specific action of ketamine on synaptic transmission is suggested. Erroneous phase relationship between natural stimuli responses can be obtained in experiments employing ketamine.

EMG responses of the vertical eye muscles to dynamic and static natural vestibular stimulation about different axes in alert rabbits.

The EMG responses of the vertical eye muscles have been recorded in alert intact rabbits submitted to both dynamic and static natural vestibular stimulations about different axes. Following dynamic vestibular stimulation, the phase lead of the EMG response with respect to head position as well as its sensitivity increased with stimulus frequency in all the stimulation modalities. This indicates a progressive recruitment by the stimulus of the second-order vestibular neurons related to semicircular canals. The sensitivity of the response was consistently higher in the effective intermediate roll-pitch modality for all the 4 muscles. Following static stimulation, the EMG response showed an asymmetric modulation. The excitatory response was always higher than the inhibitory one and linearly related with the stimulus. Also for the static stimulation the amplitude of the response was significantly higher when the animal was tilted about the effective intermediate roll-pitch axis for all the 4 muscles. The presence of a maximal EMG response in the same modality for both static and dynamic stimulation indicates a similar spatial organization of those subgroups of ampullar and macular receptors projecting to the same eye muscle.

The dynamic discharge properties of oculomotor neurons in rabbits with intact and canal-plugged labyrinths during sinusoidal lateral tilt.

The characteristics of the control exerted by macular and ampullar vestibular receptors on oculomotor neurons (OMN) have been investigated by submitting unanesthetized, encéphale isolé rabbits, with intact and canal-plugged labyrinths, to sinusoidal lateral tilts of varying frequencies (0.013-0.2 Hz). For frequencies of tilt above 0.025 Hz, corresponding to peak angular accelerations suprathreshold for canal related vestibular neurons, both phase and sensitivity of the OMN response differ significantly in the two types of preparation. At lower frequencies of tilt the characteristics of the OMN response are, on the contrary, very similar, thus indicating that also in the intact animals the control of the vertical vestibulo-ocular reflex, in this frequency range, is exerted almost exclusively by the otoliths.

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.

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.

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.

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.

Vestibular mechanisms related to vertical and torsional eye movements.

1. A series of experiments concerning the organization of the vertical vestibuloocular reflex (VOR) of the rabbit are reviewed. 2. Unanesthetized, encéphale isolé and intact, alert rabbits have been submitted to natural stimulation of the labyrinth consisting in sinusoidal oscillations and static tilts around the longitudinal axis. The oculomotor responses have been recorded at the level of the III nucleus oculomotor neurons (OMN) and from the four vertical eye muscles. 3. The phase and gain of the OMN response at different frequencies of oscillation indicate a serial involvement of the macular ampullar labyrinthine receptors in the activation of the OMN. In the low frequency range of head movements, macular receptors alone can provide adequate ocular compensation. By raising the frequency of head movements, the threshold value of acceleration for recruiting second order vestibular neurons related to semicircular canals is reached and the vertical VOR is controlled predominantly by the ampullar receptors of the vertical canals. 4. These results have been confirmed and extended in the alert, intact rabbit. By orienting the animal in different positions with respect to the axis of oscillation it has been possible to activate selectively one or the other pair of complementary vertical canals. The EMG responses recorded from the vertical eye muscle exhibited different magnitudes in the different orientations, while the phase curve remained the same. 5. The static otolith-ocular reflex has also been investigated by tilting the alert animals oriented in the same way. The pattern of the EMG responses elicited by the pure macular input coincides with that obtained during dynamic stimulation. The existence of separate functional macular regions specifically connected with the different eye muscles and a close convergent action of the two types of labyrinthine receptors in ocular compensation, are suggested.

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.

Recovery of the vertical vestibulo-ocular reflex gain in rabbits submitted to bilateral and unilateral visual deprivation from birth.

Rabbits were raised in complete darkness from birth to the age of 3 months. At this age, the animals were submitted to dynamic vestibular stimulation consisting of lateral sinusoidal oscillations of different frequencies and fixed amplitude. The vertical VOR, elicited in complete darkness, was then recorded. While the phase of the response was perfectly adequate to ensure head movements compensation, the gain values recorded were clearly reduced with respect to the values obtained in a normally raised control group of the same age. After exposure to light, the visually deprived animals showed a complete recovery of normal VOR gain values in a relatively short period of time. Another group of animals was submitted to monocular prolongation of light deprivation during the fourth month of life. After 2 weeks these rabbits displayed a clear unbalance of the VOR between the two eyes: the eye in which vision was allowed showed a complete recovery of VOR gain values, while the gain of the occluded eye remained unchanged. The present results confirm that visual experience in early life is necessary for a correct development of the VOR. If visual deprivation is limited to the first few months of life, the impairment of the reflex characteristics is completely reversible. Finally, data on monocular deprivation suggest that, in the rabbit, the neural structures which preside to the development of the vertical VOR compensatory properties are lateralized.

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.

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.