Maurizio Mariotti | Università degli Studi di Milano - State University of Milan (Italy) (original) (raw)
Papers by Maurizio Mariotti
PLOS ONE
Transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) can excite both cortico-... more Transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) can excite both cortico-cortical and cortico-spinal axons resulting in TMS-evoked potentials (TEPs) and motor-evoked potentials (MEPs), respectively. Despite this remarkable difference with other cortical areas, the influence of motor output and its amplitude on TEPs is largely unknown. Here we studied TEPs resulting from M1 stimulation and assessed whether their waveform and spectral features depend on the MEP amplitude. To this aim, we performed two separate experiments. In experiment 1, single-pulse TMS was applied at the same supra-threshold intensity on primary motor, prefrontal, premotor and parietal cortices and the corresponding TEPs were compared by means of local mean field power and time-frequency spectral analysis. In experiment 2 we stimulated M1 at resting motor threshold in order to elicit MEPs characterized by a wide range of amplitudes. TEPs computed from high-MEP and low-MEP trials were then compared using the same methods applied in experiment 1. In line with previous studies, TMS of M1 produced larger TEPs compared to other cortical stimulations. Notably, we found that only TEPs produced by M1 stimulation were accompanied by a late event-related desynchronization (ERD-peaking at~300 ms after TMS), whose magnitude was strongly dependent on the amplitude of MEPs. Overall, these results suggest that M1 produces peculiar responses to TMS possibly reflecting specific anatomo-functional properties, such as the re-entry of proprioceptive feedback associated with target muscle activation.
Journal of Affective Disorders, 2015
Introduction: Recent studies have demonstrated that cortical brain areas tend to oscillate at a s... more Introduction: Recent studies have demonstrated that cortical brain areas tend to oscillate at a specific natural frequency when directly perturbed by transcranial magnetic stimulation (TMS). Fast electroencephalographic (EEG) oscillations, which typically originate from frontal regions, have been reported to be markedly reduced in schizophrenia. Methods: Here we employed TMS/EEG to assess the natural frequency of the premotor area in a sample of 48 age-matched participants (12 each in major depression disorder (MDD)), bipolar disorder (BPD), schizophrenia (SCZ) and healthy controls. Event related spectral perturbations (ERSP) were obtained for each study participant using wavelet decomposition. Results: TMS resulted in a significant activation of the beta/gamma band response (21-50 Hz) to frontal cortical perturbation in healthy control subjects. By contrast, the main frequencies of frontal EEG responses to TMS were significantly reduced in patients with BPD, MDD and SCZ (11-27 Hz) relative to healthy subjects. Conclusions: Patients with bipolar disorder, major depression and schizophrenia showed a significantly lower natural frequency of frontal cortico-thalamocortical circuits compared to healthy controls. These results suggest a common neurobiological mechanism of corticothalamic impairment. The most likely candidates include dysfunction of GABAergic circuits. Limitations: Further studies are needed to consider other biological markers, gene variants, and their interaction with clinical variables.
Journal of sleep research, 2001
We examined the stimulating effect of Substantia Innominata pars anterior (SIa), during the wakin... more We examined the stimulating effect of Substantia Innominata pars anterior (SIa), during the waking state, on the 'central' part of the Mediodorsal nucleus of the thalamus (MD), combining electrophysiological and anatomical techniques in restrained, undrugged, unanaesthetized cats. Thalamic MD units were recorded, after electrical stimulation of the Substantia Innominata, at 1 Hz, with a single pulse or short trains of four pulses. Responses were studied by poststimulus histograms. In about 64 of the 84 recorded MD neurones (76%), stimulation of the Substantia Innominata, during the waking state, induced a brief cell excitation, followed first by prolonged inhibition of firing and then by a strong excitatory rebound discharge; after this comes a second sequence of inhibition and excitation, of decreasing amplitude. After stimulation of the Substantia Innominata, the MD units tended to start a repetitive discharge at 4--7 Hz. To investigate the connections of Substantia Innomi...
Neuroscience, 1998
The present study examined projections of GABAergic and cholinergic neurons from the basal forebr... more The present study examined projections of GABAergic and cholinergic neurons from the basal forebrain and preoptic-anterior hypothalamus to the "intermediate" part of the mediodorsal nucleus of the thalamus. Retrograde transport from this region of the mediodorsal nucleus was investigated using horseradish peroxidase-conjugated wheatgerm agglutinin in combination with peroxidase-antiperoxidase immunohistochemical staining for glutamic acid decarboxylase and choline acetyltransferase. A relatively large number of retrogradely-labelled glutamic acid decarboxylase-positive neurons are located in the basal forebrain, amounting to more than 7% of the total population of glutamic acid decarboxylase-positive cells in this region. Moreover, retrogradely-labelled choline acetyltransferase-positive cells are interspersed among glutamic acid decarboxylase-positive neurons, accounting for about 6% of the total choline acetyltransferase-positive cell population in the basal forebrain. T...
NeuroImage, 2015
During non-rapid eye movement (NREM) sleep (stage N3), when consciousness fades, cortico-cortical... more During non-rapid eye movement (NREM) sleep (stage N3), when consciousness fades, cortico-cortical interactions are impaired while neurons are still active and reactive. Why is this? We compared cortico-cortical evoked-potentials recorded during wakefulness and NREM by means of time-frequency analysis and phase-locking measures in 8 epileptic patients undergoing intra-cerebral stimulations/recordings for clinical evaluation. We observed that, while during wakefulness electrical stimulation triggers a chain of deterministic phase-locked activations in its cortical targets, during NREM the same input induces a slow wave associated with an OFF-period (suppression of power>20Hz), possibly reflecting a neuronal down-state. Crucially, after the OFF-period, cortical activity resumes to wakefulness-like levels, but the deterministic effects of the initial input are lost, as indicated by a sharp drop of phase-locked activity. These findings suggest that the intrinsic tendency of cortical neurons to fall into a down-state after a transient activation (i.e. bistability) prevents the emergence of stable patterns of causal interactions among cortical areas during NREM. Besides sleep, the same basic neurophysiological dynamics may play a role in pathological conditions in which thalmo-cortical information integration and consciousness are impaired in spite of preserved neuronal activity.
Journal of Neuroscience, 2009
The frequency tuning of a system can be directly determined by perturbing it and by observing the... more The frequency tuning of a system can be directly determined by perturbing it and by observing the rate of the ensuing oscillations, the so called natural frequency. This approach is used, for example, in physics, in geology, and also when one tunes a musical instrument. In the present study, we employ transcranial magnetic stimulation (TMS) to directly perturb a set of selected corticothalamic modules (Brodmann areas 19, 7, and 6) and high-density electroencephalogram to measure their natural frequency. TMS consistently evoked dominant ␣-band oscillations (8 -12 Hz) in the occipital cortex, -band oscillations (13-20 Hz) in the parietal cortex, and fast /␥-band oscillations (21-50 Hz) in the frontal cortex. Each cortical area tended to preserve its own natural frequency also when indirectly engaged by TMS through brain connections and when stimulated at different intensities, indicating that the observed oscillations reflect local physiological mechanisms. These findings were reproducible across individuals and represent the first direct characterization of the coarse electrophysiological properties of three associative areas of the human cerebral cortex. Most importantly, they indicate that, in healthy subjects, each corticothalamic module is normally tuned to oscillate at a characteristic rate. The natural frequency can be directly measured in virtually any area of the cerebral cortex and may represent a straightforward and flexible way to probe the state of human thalamocortical circuits at the patient's bedside.
Sleep Medicine Reviews, 2002
Awakening is a crucial event for the organism. The transition from sleep to waking implies physio... more Awakening is a crucial event for the organism. The transition from sleep to waking implies physiological processes which lead to a new behavioural state. Spontaneous awakenings have varying features which may change as a function of several factors. The latter include intrasleep architecture, circadian phase, time awake, age, or disordered sleep. Despite its clear theoretical and clinical importance, the topic of awakening (in humans) has received little attention so far. This contribution focuses on major issues which relate to awakening from both basic (experimental) and clinical research. Recent knowledge on neurophysiological mechanisms is reported. The experimental data which provide in the human suggestions on the regulation of awakening are discussed, mainly those concerning sleep architecture and homeostatic/circadian factors also in a life-span perspective, since age is a powerful factor which may in¯uence awakening. Clinical contributions will examine two main sleep disorders: insomnia and hypersomnia. Daytime functioning is shown in insomniac patients and compared to other pathologies like sleep apnea. A ®nal section evokes links between some types of night waking and psychological factors.
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2009
Aging Cholinergic neurons Diagonal band of Broca Morris maze-water task One group of six male con... more Aging Cholinergic neurons Diagonal band of Broca Morris maze-water task One group of six male control rats [21 months old] and one group of six male rats of the same age, singularly stored in a cage, and treated with acetyl-L-carnitine-HCl (ALCAR: 60 mg/kg/day/p.o.) for six months were tested in the spatial learning/memory Morris maze-water task and for atrophy and cell loss in seven myeloand cytostructurally defined basal forebrain (BF) cholinergic regions [Gritti et al., 1993 J Comp Neurol 329: 438-457]. Coronal sections 25 μm thick were cut through the BF regions and processed every 200 μm for choline acetyltransferase (ChAT) immunohistochemistry. The ALCAR-treated rats had significantly shorter exit times on the Morris maze-water task test than the control rats (ANOVA-enzyme: F 1,39 = 112.5, P = 0.0001; sessions: F 3,39 = 10.41, P = 0.0001; interaction: F 3,39 = 5.09, P = 0.0044). Degenerative morphological changes in the BF ChAT-positive cells were observed in the control rats, but not in the treated animals, in: the diagonal band of Broca, the magnocellular preoptic nucleus, the olfactory tubercle, the substantia innominata, and the globus pallidus (ANOVA-enzyme: F 1,2 = 14, P = 0,0003; structures: F 6,7 =4, P = 0,0018; interaction: F 6,7 =3, P = 0,0043). In the diagonal band of Broca (P b 0.0494) and in the magnocellular preoptic nucleus (P b 0.0117) there were significantly fewer ChAT-positive neurons in the aged control rats than in the ALCAR-treated rats. These results demonstrate that in rats aged from 15 to 21 months ALCAR treatment significantly attenuated spatial learning/memory impairment on the Morris maze-water task and also importantly reduced the degeneration in size and number of cholinergic cells in the BF.
PLoS ONE, 2010
Background: High-density electroencephalography (hd-EEG) combined with transcranial magnetic stim... more Background: High-density electroencephalography (hd-EEG) combined with transcranial magnetic stimulation (TMS) provides a direct and non-invasive measure of cortical excitability and connectivity in humans and may be employed to track over time pathological alterations, plastic changes and therapy-induced modifications in cortical circuits. However, the diagnostic/monitoring applications of this technique would be limited to the extent that TMS-evoked potentials are either stereotypical (non-sensitive) or random (non-repeatable) responses. Here, we used controlled changes in the stimulation parameters (site, intensity, and angle of stimulation) and repeated longitudinal measurements (same day and one week apart) to evaluate the sensitivity and repeatability of TMS/hd-EEG potentials.
Neuropharmacology, 1989
In the present study, the distribution of benzodiazepine recognition site subtypes in the brain o... more In the present study, the distribution of benzodiazepine recognition site subtypes in the brain of the cat was investigated. To this aim, the binding properties of [3H]2-oxo-quazepam ([3H]2OXOQ) and [3H]beta-CCE, two ligands with preferential affinity for Type I benzodiazepine recognition sites, were compared to binding parameters for [3H]flunitrazepam ([3H]FNT) in different areas of the cat brain. The ratio of [3H]2OXOQ to [3H]FNT binding sites indicated that, in the cerebellum, Type I sites accounted for 90% of the total number of benzodiazepine recognition sites. The cerebral cortex, thalamus and mesencephalic reticular formation had also a high proportion of Type I sites (73-78%), whilst the two subtypes were almost equally distributed in the hippocampus, amygdala and bulbar reticular formation. A similar distribution of subtypes of benzodiazepine recognition sites was indicated by the ratio of [3H]beta CCE to [3H]FNT binding sites for different areas of the brain. These results demonstrate the existence of heterogeneity of recognition sites for benzodiazepines in the brain of the cat and support the view that [3H]2OXOQ preferentially labels Type I sites.
NeuroImage, 2010
Transcranial magnetic stimulation (TMS) combined with simultaneous high-density electroencephalog... more Transcranial magnetic stimulation (TMS) combined with simultaneous high-density electroencephalography (hd-EEG) represents a straightforward way to gauge cortical excitability and connectivity in humans. However, the analysis, classification and interpretation of TMS-evoked potentials are hampered by scarce a priori knowledge about the physiological effect of TMS and by lack of an established data analysis framework. Here, we implemented a standardized, data-driven procedure to characterize the electrical response of the cerebral cortex to TMS by means of three synthetic indices: significant current density (SCD), phase-locking (PL) and significant current scattering (SCS). SCD sums up the amplitude of all significant currents induced by TMS, PL reflects the ability of TMS to reset the phase of ongoing cortical oscillations, while SCS measures the average distance of significantly activated sources from the site of stimulation. These indices are aimed at capturing different aspects of brain responsiveness, ranging from global cortical excitability towards global cortical connectivity. We analyzed the EEG responses to TMS of Brodmann's area 19 at increasing intensities in five healthy subjects. The spatial distribution and time course of SCD, PL and SCS revealed a reproducible profile of excitability and connectivity, characterized by a local activation threshold around a TMS-induced electric field of 50 V/m and by a selective propagation of TMS-evoked activation from occipital to ipsilateral frontal areas that reached a maximum at 70-100 ms. These general indices may be used to characterize the effects of TMS on any cortical area and to quantitatively evaluate cortical excitability and connectivity in physiological and pathological conditions.
Journal of Sleep Research, 2001
Journal of Neurophysiology, 2002
8 other HighWire hosted articles, the first 5 are: This article has been cited by [PDF] [Full Tex... more 8 other HighWire hosted articles, the first 5 are: This article has been cited by [PDF] [Full Text] [Abstract] , September 1, 2005; 94 (3): 1904-1911. J Neurophysiol An Oscillatory Hierarchy Controlling Neuronal Excitability and Stimulus Processing in the [PDF] [Full Text] [Abstract] , July 1, 2006; 96 (1): 62-70. J Neurophysiol M. Molle, O. Yeshenko, L. Marshall, S. J. Sara and J. Born Hippocampal Sharp Wave-Ripples Linked to Slow Oscillations in Rat Slow-Wave Sleep [PDF] [Full Text] [Abstract] , September 1, 2006; 96 (3): 1658-1663. J Neurophysiol R. Haslinger, I. Ulbert, C. I. Moore, E. N. Brown and A. Devor Analysis of LFP Phase Predicts Sensory Response of Barrel Cortex [PDF] [Full Text] [Abstract] , February 1, 2007; 17 (2): 400-414. Cereb Cortex M. Mukovski, S. Chauvette, I. Timofeev and M. Volgushev Signal during Slow-Wave Sleep Detection of Active and Silent States in Neocortical Neurons from the Field Potential [PDF] [Full Text] [Abstract]
European Journal of Neuroscience, 2003
Interleukin-1 (IL-1) and IL-1 receptors are constitutively expressed in normal brain. IL-1 increa... more Interleukin-1 (IL-1) and IL-1 receptors are constitutively expressed in normal brain. IL-1 increases non-rapid eye movements (NREM) sleep in several animal species, an effect mediated in part by interactions with the serotonergic system. The site(s) in brain at which interactions between IL-1 and the serotonergic system increase NREM sleep remain to be identi®ed. The dorsal raphe (DRN) is the origin of the major ascending serotonergic pathways to the forebrain, and it contains IL-1 receptors. This study examined the hypothesis that IL-1 increases NREM sleep by acting at the level of the DRN. IL-1b (0.25 and 0.5 ng) was microinjected into the DRN of freely behaving rats and subsequent effects on sleep±wake activity were determined. IL-1b 0.5 ng increased NREM sleep during the ®rst 2 h post-injection from 33.5 AE 3.7% after vehicle microinjection to 42.9 AE 3.0% of recording time. To determine the effects of IL-1b on electrophysiological properties of DRN serotonergic neurons, intracellular recordings were performed in a guinea-pig brain stem slice preparation. In 26 of 32 physiologically and pharmacologically identi®ed serotonergic neurons, IL-1b superfusion (25 ng/mL) decreased spontaneous ®ring rates by 50%, from 1.6 AE 0.2 Hz (before IL-1b superfusion) to 0.8 AE 0.2 Hz. This effect was reversible upon washout. These results show that IL-1b increases NREM sleep when administered directly into the DRN. Serotonin enhances wakefulness and these novel data also suggest that IL-1b-induced enhancement of NREM sleep could be due in part to the inhibition of DRN serotonergic neurons.
Brain Topography, 2013
Electroconvulsive therapy (ECT) has significant short-term antidepressant effects on drug-resista... more Electroconvulsive therapy (ECT) has significant short-term antidepressant effects on drug-resistant patients with severe major depression. Animal studies have demonstrated that electroconvulsive seizures produce potentiation-like synaptic remodeling in both sub-cortical and frontal cortical circuits. However, the electrophysiological effects of ECT in the human brain are not known. In this work, we evaluated whether ECT induces a measurable change in the excitability of frontal cortical circuits in humans. Electroencephalographic (EEG) potentials evoked by transcranial magnetic stimulation (TMS) were collected before and after a course of ECT in eight patients with severe major depression. Cortical excitability was measured from the early and local EEG response to TMS. Clinical assessment confirmed the beneficial effects of ECT on depressive symptoms at the group level. TMS/ EEG measurements revealed a clear-cut increase of frontal cortical excitability after ECT as compared to baseline, that was significant in each and every patient. The present findings corroborate in humans the idea that ECT may produce synaptic potentiation, as previously observed in animal studies. Moreover, results suggest that TMS/EEG may be employed in depressed patients to monitor longitudinally the electrophysiological effects of different therapeutic neuromodulators, e.g. ECT, repetitive TMS, and sleep deprivation. To the extent that depression involves an alteration of frontal cortical excitability, these measurements may be used to guide and evaluate treatment progression over time at the single-patient level.
Brain Research, 1974
... Caudo-rostral brain stem reciprocal influences in the cat. Mauro Mancia a , Maurizio Mariotti... more ... Caudo-rostral brain stem reciprocal influences in the cat. Mauro Mancia a , Maurizio Mariotti a and Roberto Spreafico a. ... 82-t14.14 DEMPSEY, EW, AND MORRISON, RS, The production of rhythmically recurrent cortical poten-tials after localized thalamic stimulation, Amer. ...
Brain Research, 1976
Intracellular recordings were performed from bulbar and caudopontine (BcP), rostropontine (rP) an... more Intracellular recordings were performed from bulbar and caudopontine (BcP), rostropontine (rP) and mesencephalic (Mes) neurons in acute encéphale isolé preparations during low- and high-frequency basal forebrain (BF) and hypothalamic (Hyp) stimulation. Low-frequency BF stimulation induced long-latency (7-8 msec) EPSPs on 31% of BcP neurons. High-frequency stimulation of the same regions induced excitation in 58% of them. No inhibition was observed. The descending influences on BcP neurons disappeared after bilateral acute sensorimotor decortication. Low- and high-frequency BF stimulation influenced a very low percentage of rP and Mes neurons. The only effect was a long-latency slow rising EPSP with or without spikes. No inhibition was found in these neurons. Low- and high-frequency Hyp stimulation produced short-latency EPSPs with or without spikes on a large percentage of BcP, rP and Mes neurons. The effect was more constant on rostral (rP) than on caudal (BcP) neurons and more evident when high-frequency stimulation was applied. At high frequency the activation of brain stem neurons paralleled an EEG desynchronization. IPSPs were seen in a low percentage of Mes and rP neurons. Mes neurons could be also activated antidromically. The results suggest that BF regions do not antagonize directly the mesencephalic activating system and may induce electrocortical synchronization through the activation of caudal brain stem neurons. This circuit involves sensorimotor cortical neurons. The facilitatory effect of Hyp stimulation on rostral brain stem neurons indicates that the EEG desynchronization which follows high-frequency Hyp activation may be mediated by the ascending reticular system. Other mechanisms mainly at the diencephalo-telecephalic level may however be involved in this effect.
Brain Research, 1978
Basal forebrain (BF) stimulation induces in intact brain EEG synchronization 2°, behavioural inhi... more Basal forebrain (BF) stimulation induces in intact brain EEG synchronization 2°, behavioural inhibition and sleep 21, while posterior hypothalamus (HYP) yields EEG desynchronization and arousal 1,11,17,18. Also, stimulation of the amygdaloid nuclei elicits in unanaesthetized animals complex behavioural reactions 7, accompanied by EEG synchronization and desynchronization4, 5.
Journal of Neuroscience Methods, 2011
A single pulse of Transcranial Magnetic Stimulation (TMS) generates electroencephalogram (EEG) os... more A single pulse of Transcranial Magnetic Stimulation (TMS) generates electroencephalogram (EEG) oscillations that are thought to reflect intrinsic properties of the stimulated cortical area and its fast interactions with other cortical areas. Thus, a tool to decompose TMS-evoked oscillations in the time-frequency domain on a millisecond timescale and on a broadband frequency range may help to understand information transfer across cortical oscillators. Some recent studies have employed algorithms based on the Wavelet Transform (WT) to study TMS-evoked EEG oscillations in healthy and pathological conditions. However, these methods do not allow to describe TMS-evoked EEG oscillations with high resolution in time and frequency domains simultaneously.
PLOS ONE
Transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) can excite both cortico-... more Transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) can excite both cortico-cortical and cortico-spinal axons resulting in TMS-evoked potentials (TEPs) and motor-evoked potentials (MEPs), respectively. Despite this remarkable difference with other cortical areas, the influence of motor output and its amplitude on TEPs is largely unknown. Here we studied TEPs resulting from M1 stimulation and assessed whether their waveform and spectral features depend on the MEP amplitude. To this aim, we performed two separate experiments. In experiment 1, single-pulse TMS was applied at the same supra-threshold intensity on primary motor, prefrontal, premotor and parietal cortices and the corresponding TEPs were compared by means of local mean field power and time-frequency spectral analysis. In experiment 2 we stimulated M1 at resting motor threshold in order to elicit MEPs characterized by a wide range of amplitudes. TEPs computed from high-MEP and low-MEP trials were then compared using the same methods applied in experiment 1. In line with previous studies, TMS of M1 produced larger TEPs compared to other cortical stimulations. Notably, we found that only TEPs produced by M1 stimulation were accompanied by a late event-related desynchronization (ERD-peaking at~300 ms after TMS), whose magnitude was strongly dependent on the amplitude of MEPs. Overall, these results suggest that M1 produces peculiar responses to TMS possibly reflecting specific anatomo-functional properties, such as the re-entry of proprioceptive feedback associated with target muscle activation.
Journal of Affective Disorders, 2015
Introduction: Recent studies have demonstrated that cortical brain areas tend to oscillate at a s... more Introduction: Recent studies have demonstrated that cortical brain areas tend to oscillate at a specific natural frequency when directly perturbed by transcranial magnetic stimulation (TMS). Fast electroencephalographic (EEG) oscillations, which typically originate from frontal regions, have been reported to be markedly reduced in schizophrenia. Methods: Here we employed TMS/EEG to assess the natural frequency of the premotor area in a sample of 48 age-matched participants (12 each in major depression disorder (MDD)), bipolar disorder (BPD), schizophrenia (SCZ) and healthy controls. Event related spectral perturbations (ERSP) were obtained for each study participant using wavelet decomposition. Results: TMS resulted in a significant activation of the beta/gamma band response (21-50 Hz) to frontal cortical perturbation in healthy control subjects. By contrast, the main frequencies of frontal EEG responses to TMS were significantly reduced in patients with BPD, MDD and SCZ (11-27 Hz) relative to healthy subjects. Conclusions: Patients with bipolar disorder, major depression and schizophrenia showed a significantly lower natural frequency of frontal cortico-thalamocortical circuits compared to healthy controls. These results suggest a common neurobiological mechanism of corticothalamic impairment. The most likely candidates include dysfunction of GABAergic circuits. Limitations: Further studies are needed to consider other biological markers, gene variants, and their interaction with clinical variables.
Journal of sleep research, 2001
We examined the stimulating effect of Substantia Innominata pars anterior (SIa), during the wakin... more We examined the stimulating effect of Substantia Innominata pars anterior (SIa), during the waking state, on the 'central' part of the Mediodorsal nucleus of the thalamus (MD), combining electrophysiological and anatomical techniques in restrained, undrugged, unanaesthetized cats. Thalamic MD units were recorded, after electrical stimulation of the Substantia Innominata, at 1 Hz, with a single pulse or short trains of four pulses. Responses were studied by poststimulus histograms. In about 64 of the 84 recorded MD neurones (76%), stimulation of the Substantia Innominata, during the waking state, induced a brief cell excitation, followed first by prolonged inhibition of firing and then by a strong excitatory rebound discharge; after this comes a second sequence of inhibition and excitation, of decreasing amplitude. After stimulation of the Substantia Innominata, the MD units tended to start a repetitive discharge at 4--7 Hz. To investigate the connections of Substantia Innomi...
Neuroscience, 1998
The present study examined projections of GABAergic and cholinergic neurons from the basal forebr... more The present study examined projections of GABAergic and cholinergic neurons from the basal forebrain and preoptic-anterior hypothalamus to the "intermediate" part of the mediodorsal nucleus of the thalamus. Retrograde transport from this region of the mediodorsal nucleus was investigated using horseradish peroxidase-conjugated wheatgerm agglutinin in combination with peroxidase-antiperoxidase immunohistochemical staining for glutamic acid decarboxylase and choline acetyltransferase. A relatively large number of retrogradely-labelled glutamic acid decarboxylase-positive neurons are located in the basal forebrain, amounting to more than 7% of the total population of glutamic acid decarboxylase-positive cells in this region. Moreover, retrogradely-labelled choline acetyltransferase-positive cells are interspersed among glutamic acid decarboxylase-positive neurons, accounting for about 6% of the total choline acetyltransferase-positive cell population in the basal forebrain. T...
NeuroImage, 2015
During non-rapid eye movement (NREM) sleep (stage N3), when consciousness fades, cortico-cortical... more During non-rapid eye movement (NREM) sleep (stage N3), when consciousness fades, cortico-cortical interactions are impaired while neurons are still active and reactive. Why is this? We compared cortico-cortical evoked-potentials recorded during wakefulness and NREM by means of time-frequency analysis and phase-locking measures in 8 epileptic patients undergoing intra-cerebral stimulations/recordings for clinical evaluation. We observed that, while during wakefulness electrical stimulation triggers a chain of deterministic phase-locked activations in its cortical targets, during NREM the same input induces a slow wave associated with an OFF-period (suppression of power>20Hz), possibly reflecting a neuronal down-state. Crucially, after the OFF-period, cortical activity resumes to wakefulness-like levels, but the deterministic effects of the initial input are lost, as indicated by a sharp drop of phase-locked activity. These findings suggest that the intrinsic tendency of cortical neurons to fall into a down-state after a transient activation (i.e. bistability) prevents the emergence of stable patterns of causal interactions among cortical areas during NREM. Besides sleep, the same basic neurophysiological dynamics may play a role in pathological conditions in which thalmo-cortical information integration and consciousness are impaired in spite of preserved neuronal activity.
Journal of Neuroscience, 2009
The frequency tuning of a system can be directly determined by perturbing it and by observing the... more The frequency tuning of a system can be directly determined by perturbing it and by observing the rate of the ensuing oscillations, the so called natural frequency. This approach is used, for example, in physics, in geology, and also when one tunes a musical instrument. In the present study, we employ transcranial magnetic stimulation (TMS) to directly perturb a set of selected corticothalamic modules (Brodmann areas 19, 7, and 6) and high-density electroencephalogram to measure their natural frequency. TMS consistently evoked dominant ␣-band oscillations (8 -12 Hz) in the occipital cortex, -band oscillations (13-20 Hz) in the parietal cortex, and fast /␥-band oscillations (21-50 Hz) in the frontal cortex. Each cortical area tended to preserve its own natural frequency also when indirectly engaged by TMS through brain connections and when stimulated at different intensities, indicating that the observed oscillations reflect local physiological mechanisms. These findings were reproducible across individuals and represent the first direct characterization of the coarse electrophysiological properties of three associative areas of the human cerebral cortex. Most importantly, they indicate that, in healthy subjects, each corticothalamic module is normally tuned to oscillate at a characteristic rate. The natural frequency can be directly measured in virtually any area of the cerebral cortex and may represent a straightforward and flexible way to probe the state of human thalamocortical circuits at the patient's bedside.
Sleep Medicine Reviews, 2002
Awakening is a crucial event for the organism. The transition from sleep to waking implies physio... more Awakening is a crucial event for the organism. The transition from sleep to waking implies physiological processes which lead to a new behavioural state. Spontaneous awakenings have varying features which may change as a function of several factors. The latter include intrasleep architecture, circadian phase, time awake, age, or disordered sleep. Despite its clear theoretical and clinical importance, the topic of awakening (in humans) has received little attention so far. This contribution focuses on major issues which relate to awakening from both basic (experimental) and clinical research. Recent knowledge on neurophysiological mechanisms is reported. The experimental data which provide in the human suggestions on the regulation of awakening are discussed, mainly those concerning sleep architecture and homeostatic/circadian factors also in a life-span perspective, since age is a powerful factor which may in¯uence awakening. Clinical contributions will examine two main sleep disorders: insomnia and hypersomnia. Daytime functioning is shown in insomniac patients and compared to other pathologies like sleep apnea. A ®nal section evokes links between some types of night waking and psychological factors.
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2009
Aging Cholinergic neurons Diagonal band of Broca Morris maze-water task One group of six male con... more Aging Cholinergic neurons Diagonal band of Broca Morris maze-water task One group of six male control rats [21 months old] and one group of six male rats of the same age, singularly stored in a cage, and treated with acetyl-L-carnitine-HCl (ALCAR: 60 mg/kg/day/p.o.) for six months were tested in the spatial learning/memory Morris maze-water task and for atrophy and cell loss in seven myeloand cytostructurally defined basal forebrain (BF) cholinergic regions [Gritti et al., 1993 J Comp Neurol 329: 438-457]. Coronal sections 25 μm thick were cut through the BF regions and processed every 200 μm for choline acetyltransferase (ChAT) immunohistochemistry. The ALCAR-treated rats had significantly shorter exit times on the Morris maze-water task test than the control rats (ANOVA-enzyme: F 1,39 = 112.5, P = 0.0001; sessions: F 3,39 = 10.41, P = 0.0001; interaction: F 3,39 = 5.09, P = 0.0044). Degenerative morphological changes in the BF ChAT-positive cells were observed in the control rats, but not in the treated animals, in: the diagonal band of Broca, the magnocellular preoptic nucleus, the olfactory tubercle, the substantia innominata, and the globus pallidus (ANOVA-enzyme: F 1,2 = 14, P = 0,0003; structures: F 6,7 =4, P = 0,0018; interaction: F 6,7 =3, P = 0,0043). In the diagonal band of Broca (P b 0.0494) and in the magnocellular preoptic nucleus (P b 0.0117) there were significantly fewer ChAT-positive neurons in the aged control rats than in the ALCAR-treated rats. These results demonstrate that in rats aged from 15 to 21 months ALCAR treatment significantly attenuated spatial learning/memory impairment on the Morris maze-water task and also importantly reduced the degeneration in size and number of cholinergic cells in the BF.
PLoS ONE, 2010
Background: High-density electroencephalography (hd-EEG) combined with transcranial magnetic stim... more Background: High-density electroencephalography (hd-EEG) combined with transcranial magnetic stimulation (TMS) provides a direct and non-invasive measure of cortical excitability and connectivity in humans and may be employed to track over time pathological alterations, plastic changes and therapy-induced modifications in cortical circuits. However, the diagnostic/monitoring applications of this technique would be limited to the extent that TMS-evoked potentials are either stereotypical (non-sensitive) or random (non-repeatable) responses. Here, we used controlled changes in the stimulation parameters (site, intensity, and angle of stimulation) and repeated longitudinal measurements (same day and one week apart) to evaluate the sensitivity and repeatability of TMS/hd-EEG potentials.
Neuropharmacology, 1989
In the present study, the distribution of benzodiazepine recognition site subtypes in the brain o... more In the present study, the distribution of benzodiazepine recognition site subtypes in the brain of the cat was investigated. To this aim, the binding properties of [3H]2-oxo-quazepam ([3H]2OXOQ) and [3H]beta-CCE, two ligands with preferential affinity for Type I benzodiazepine recognition sites, were compared to binding parameters for [3H]flunitrazepam ([3H]FNT) in different areas of the cat brain. The ratio of [3H]2OXOQ to [3H]FNT binding sites indicated that, in the cerebellum, Type I sites accounted for 90% of the total number of benzodiazepine recognition sites. The cerebral cortex, thalamus and mesencephalic reticular formation had also a high proportion of Type I sites (73-78%), whilst the two subtypes were almost equally distributed in the hippocampus, amygdala and bulbar reticular formation. A similar distribution of subtypes of benzodiazepine recognition sites was indicated by the ratio of [3H]beta CCE to [3H]FNT binding sites for different areas of the brain. These results demonstrate the existence of heterogeneity of recognition sites for benzodiazepines in the brain of the cat and support the view that [3H]2OXOQ preferentially labels Type I sites.
NeuroImage, 2010
Transcranial magnetic stimulation (TMS) combined with simultaneous high-density electroencephalog... more Transcranial magnetic stimulation (TMS) combined with simultaneous high-density electroencephalography (hd-EEG) represents a straightforward way to gauge cortical excitability and connectivity in humans. However, the analysis, classification and interpretation of TMS-evoked potentials are hampered by scarce a priori knowledge about the physiological effect of TMS and by lack of an established data analysis framework. Here, we implemented a standardized, data-driven procedure to characterize the electrical response of the cerebral cortex to TMS by means of three synthetic indices: significant current density (SCD), phase-locking (PL) and significant current scattering (SCS). SCD sums up the amplitude of all significant currents induced by TMS, PL reflects the ability of TMS to reset the phase of ongoing cortical oscillations, while SCS measures the average distance of significantly activated sources from the site of stimulation. These indices are aimed at capturing different aspects of brain responsiveness, ranging from global cortical excitability towards global cortical connectivity. We analyzed the EEG responses to TMS of Brodmann's area 19 at increasing intensities in five healthy subjects. The spatial distribution and time course of SCD, PL and SCS revealed a reproducible profile of excitability and connectivity, characterized by a local activation threshold around a TMS-induced electric field of 50 V/m and by a selective propagation of TMS-evoked activation from occipital to ipsilateral frontal areas that reached a maximum at 70-100 ms. These general indices may be used to characterize the effects of TMS on any cortical area and to quantitatively evaluate cortical excitability and connectivity in physiological and pathological conditions.
Journal of Sleep Research, 2001
Journal of Neurophysiology, 2002
8 other HighWire hosted articles, the first 5 are: This article has been cited by [PDF] [Full Tex... more 8 other HighWire hosted articles, the first 5 are: This article has been cited by [PDF] [Full Text] [Abstract] , September 1, 2005; 94 (3): 1904-1911. J Neurophysiol An Oscillatory Hierarchy Controlling Neuronal Excitability and Stimulus Processing in the [PDF] [Full Text] [Abstract] , July 1, 2006; 96 (1): 62-70. J Neurophysiol M. Molle, O. Yeshenko, L. Marshall, S. J. Sara and J. Born Hippocampal Sharp Wave-Ripples Linked to Slow Oscillations in Rat Slow-Wave Sleep [PDF] [Full Text] [Abstract] , September 1, 2006; 96 (3): 1658-1663. J Neurophysiol R. Haslinger, I. Ulbert, C. I. Moore, E. N. Brown and A. Devor Analysis of LFP Phase Predicts Sensory Response of Barrel Cortex [PDF] [Full Text] [Abstract] , February 1, 2007; 17 (2): 400-414. Cereb Cortex M. Mukovski, S. Chauvette, I. Timofeev and M. Volgushev Signal during Slow-Wave Sleep Detection of Active and Silent States in Neocortical Neurons from the Field Potential [PDF] [Full Text] [Abstract]
European Journal of Neuroscience, 2003
Interleukin-1 (IL-1) and IL-1 receptors are constitutively expressed in normal brain. IL-1 increa... more Interleukin-1 (IL-1) and IL-1 receptors are constitutively expressed in normal brain. IL-1 increases non-rapid eye movements (NREM) sleep in several animal species, an effect mediated in part by interactions with the serotonergic system. The site(s) in brain at which interactions between IL-1 and the serotonergic system increase NREM sleep remain to be identi®ed. The dorsal raphe (DRN) is the origin of the major ascending serotonergic pathways to the forebrain, and it contains IL-1 receptors. This study examined the hypothesis that IL-1 increases NREM sleep by acting at the level of the DRN. IL-1b (0.25 and 0.5 ng) was microinjected into the DRN of freely behaving rats and subsequent effects on sleep±wake activity were determined. IL-1b 0.5 ng increased NREM sleep during the ®rst 2 h post-injection from 33.5 AE 3.7% after vehicle microinjection to 42.9 AE 3.0% of recording time. To determine the effects of IL-1b on electrophysiological properties of DRN serotonergic neurons, intracellular recordings were performed in a guinea-pig brain stem slice preparation. In 26 of 32 physiologically and pharmacologically identi®ed serotonergic neurons, IL-1b superfusion (25 ng/mL) decreased spontaneous ®ring rates by 50%, from 1.6 AE 0.2 Hz (before IL-1b superfusion) to 0.8 AE 0.2 Hz. This effect was reversible upon washout. These results show that IL-1b increases NREM sleep when administered directly into the DRN. Serotonin enhances wakefulness and these novel data also suggest that IL-1b-induced enhancement of NREM sleep could be due in part to the inhibition of DRN serotonergic neurons.
Brain Topography, 2013
Electroconvulsive therapy (ECT) has significant short-term antidepressant effects on drug-resista... more Electroconvulsive therapy (ECT) has significant short-term antidepressant effects on drug-resistant patients with severe major depression. Animal studies have demonstrated that electroconvulsive seizures produce potentiation-like synaptic remodeling in both sub-cortical and frontal cortical circuits. However, the electrophysiological effects of ECT in the human brain are not known. In this work, we evaluated whether ECT induces a measurable change in the excitability of frontal cortical circuits in humans. Electroencephalographic (EEG) potentials evoked by transcranial magnetic stimulation (TMS) were collected before and after a course of ECT in eight patients with severe major depression. Cortical excitability was measured from the early and local EEG response to TMS. Clinical assessment confirmed the beneficial effects of ECT on depressive symptoms at the group level. TMS/ EEG measurements revealed a clear-cut increase of frontal cortical excitability after ECT as compared to baseline, that was significant in each and every patient. The present findings corroborate in humans the idea that ECT may produce synaptic potentiation, as previously observed in animal studies. Moreover, results suggest that TMS/EEG may be employed in depressed patients to monitor longitudinally the electrophysiological effects of different therapeutic neuromodulators, e.g. ECT, repetitive TMS, and sleep deprivation. To the extent that depression involves an alteration of frontal cortical excitability, these measurements may be used to guide and evaluate treatment progression over time at the single-patient level.
Brain Research, 1974
... Caudo-rostral brain stem reciprocal influences in the cat. Mauro Mancia a , Maurizio Mariotti... more ... Caudo-rostral brain stem reciprocal influences in the cat. Mauro Mancia a , Maurizio Mariotti a and Roberto Spreafico a. ... 82-t14.14 DEMPSEY, EW, AND MORRISON, RS, The production of rhythmically recurrent cortical poten-tials after localized thalamic stimulation, Amer. ...
Brain Research, 1976
Intracellular recordings were performed from bulbar and caudopontine (BcP), rostropontine (rP) an... more Intracellular recordings were performed from bulbar and caudopontine (BcP), rostropontine (rP) and mesencephalic (Mes) neurons in acute encéphale isolé preparations during low- and high-frequency basal forebrain (BF) and hypothalamic (Hyp) stimulation. Low-frequency BF stimulation induced long-latency (7-8 msec) EPSPs on 31% of BcP neurons. High-frequency stimulation of the same regions induced excitation in 58% of them. No inhibition was observed. The descending influences on BcP neurons disappeared after bilateral acute sensorimotor decortication. Low- and high-frequency BF stimulation influenced a very low percentage of rP and Mes neurons. The only effect was a long-latency slow rising EPSP with or without spikes. No inhibition was found in these neurons. Low- and high-frequency Hyp stimulation produced short-latency EPSPs with or without spikes on a large percentage of BcP, rP and Mes neurons. The effect was more constant on rostral (rP) than on caudal (BcP) neurons and more evident when high-frequency stimulation was applied. At high frequency the activation of brain stem neurons paralleled an EEG desynchronization. IPSPs were seen in a low percentage of Mes and rP neurons. Mes neurons could be also activated antidromically. The results suggest that BF regions do not antagonize directly the mesencephalic activating system and may induce electrocortical synchronization through the activation of caudal brain stem neurons. This circuit involves sensorimotor cortical neurons. The facilitatory effect of Hyp stimulation on rostral brain stem neurons indicates that the EEG desynchronization which follows high-frequency Hyp activation may be mediated by the ascending reticular system. Other mechanisms mainly at the diencephalo-telecephalic level may however be involved in this effect.
Brain Research, 1978
Basal forebrain (BF) stimulation induces in intact brain EEG synchronization 2°, behavioural inhi... more Basal forebrain (BF) stimulation induces in intact brain EEG synchronization 2°, behavioural inhibition and sleep 21, while posterior hypothalamus (HYP) yields EEG desynchronization and arousal 1,11,17,18. Also, stimulation of the amygdaloid nuclei elicits in unanaesthetized animals complex behavioural reactions 7, accompanied by EEG synchronization and desynchronization4, 5.
Journal of Neuroscience Methods, 2011
A single pulse of Transcranial Magnetic Stimulation (TMS) generates electroencephalogram (EEG) os... more A single pulse of Transcranial Magnetic Stimulation (TMS) generates electroencephalogram (EEG) oscillations that are thought to reflect intrinsic properties of the stimulated cortical area and its fast interactions with other cortical areas. Thus, a tool to decompose TMS-evoked oscillations in the time-frequency domain on a millisecond timescale and on a broadband frequency range may help to understand information transfer across cortical oscillators. Some recent studies have employed algorithms based on the Wavelet Transform (WT) to study TMS-evoked EEG oscillations in healthy and pathological conditions. However, these methods do not allow to describe TMS-evoked EEG oscillations with high resolution in time and frequency domains simultaneously.