Biomedical subjects

Marcello Massimini

Publications and source records attributed to Marcello Massimini.

10 recordsLinked to original sources

PubMed2006

Sleepy dialogues between cortex and hippocampus: who talks to whom?

During NREM sleep, neocortical neurons undergo near-synchronous transitions, every second or so, between UP states, during which they are depolarized and fire actively, and DOWN states, during which they are hyperpolarized and completely silent. In this issue of Neuron, Isomura et al. report that slow oscillations of membrane potential occur near-synchronously not only in neocortex but also in entorhinal cortex and subiculum. Within the hippocampus proper, pyramidal neurons lack the bistability of UP and DOWN states, but their firing is strongly modulated by cortical activity during the UP state. Intriguingly, many hippocampal neurons fire during the cortical DOWN state. Thus, during sleep UP states, the cortex can talk to the hippocampus, but it is unclear whether the hippocampus talks back.

Animals↗

PubMed2006

Arm immobilization causes cortical plastic changes and locally decreases sleep slow wave activity.

Sleep slow wave activity (SWA) is thought to reflect sleep need, increasing after wakefulness and decreasing after sleep. We showed recently that a learning task involving a circumscribed brain region produces a local increase in sleep SWA. We hypothesized that increases in cortical SWA reflect synaptic potentiation triggered by learning. To further investigate the link between synaptic plasticity and sleep, we asked whether a procedure leading to synaptic depression would cause instead a decrease in sleep SWA. We show here that if a subject's arm is immobilized during the day, motor performance deteriorates and both somatosensory and motor evoked potentials decrease over contralateral sensorimotor cortex, indicative of local synaptic depression. Notably, during subsequent sleep, SWA over the same cortical area is markedly reduced. Thus, cortical plasticity is linked to local sleep regulation without learning in the classical sense. Moreover, when synaptic strength is reduced, local sleep need is also reduced.

Adult↗

PubMed2006

Repetitive transcranial magnetic stimulation dissociates working memory manipulation from retention functions in the prefrontal, but not posterior parietal, cortex.

Understanding the contributions of the prefrontal cortex (PFC) to working memory is central to understanding the neural bases of high-level cognition. One question that remains controversial is whether the same areas of the dorsolateral PFC (dlPFC) that participate in the manipulation of information in working memory also contribute to its short-term retention (STR). We evaluated this question by first identifying, with functional magnetic resonance imaging (fMRI), brain areas involved in manipulation. Next, these areas were targeted with repetitive transcranial magnetic stimulation (rTMS) while subjects performed tasks requiring only the STR or the STR plus manipulation of information in working memory. fMRI indicated that manipulation-related activity was independent of retention-related activity in both the PFC and superior parietal lobule (SPL). rTMS, however, yielded a different pattern of results. Although rTMS of the dlPFC selectively disrupted manipulation, rTMS of the SPL disrupted manipulation and STR to the same extent. rTMS of the postcentral gyrus (a control region) had no effect on performance. The implications of these results are twofold. In the PFC, they are consistent with the view that this region contributes more importantly to the control of information in working memory than to its STR. In the SPL, they illustrate the importance of supplementing the fundamentally correlational data from neuroimaging with a disruptive method, which affords stronger inference about structure-function relations.

Adult↗

PubMed2005

Breakdown of cortical effective connectivity during sleep.

When we fall asleep, consciousness fades yet the brain remains active. Why is this so? To investigate whether changes in cortical information transmission play a role, we used transcranial magnetic stimulation together with high-density electroencephalography and asked how the activation of one cortical area (the premotor area) is transmitted to the rest of the brain. During quiet wakefulness, an initial response (approximately 15 milliseconds) at the stimulation site was followed by a sequence of waves that moved to connected cortical areas several centimeters away. During non-rapid eye movement sleep, the initial response was stronger but was rapidly extinguished and did not propagate beyond the stimulation site. Thus, the fading of consciousness during certain stages of sleep may be related to a breakdown in cortical effective connectivity.

Adult↗

PubMed2004

A [17F]-fluoromethane PET/TMS study of effective connectivity.

We used transcranial magnetic stimulation (TMS) in combination with positron emission tomography (PET) to investigate the effective connectivity of four cortical regions within the same study. By employing [17F]-[CH3F] ([17F]-fluoromethane) as a radiotracer of blood-flow, we were able to obtain increased sensitivity compared to [15O]-H2O for both cortical and subcortical structures. The brain areas investigated were left primary motor cortex, right primary visual cortex, and left and right prefrontal areas. We found that each site of stimulation yielded a different pattern of activation/deactivation consistent with its anatomical connectivity. Moreover, we found that TMS of prefrontal and motor cortical areas gave rise to trans-synaptic activation of subcortical circuits.

Adult↗

PubMed2004

The sleep slow oscillation as a traveling wave.

During much of sleep, virtually all cortical neurons undergo a slow oscillation (<1 Hz) in membrane potential, cycling from a hyperpolarized state of silence to a depolarized state of intense firing. This slow oscillation is the fundamental cellular phenomenon that organizes other sleep rhythms such as spindles and slow waves. Using high-density electroencephalogram recordings in humans, we show here that each cycle of the slow oscillation is a traveling wave. Each wave originates at a definite site and travels over the scalp at an estimated speed of 1.2-7.0 m/sec. Waves originate more frequently in prefrontal-orbitofrontal regions and propagate in an anteroposterior direction. Their rate of occurrence increases progressively reaching almost once per second as sleep deepens. The pattern of origin and propagation of sleep slow oscillations is reproducible across nights and subjects and provides a blueprint of cortical excitability and connectivity. The orderly propagation of correlated activity along connected pathways may play a role in spike timing-dependent synaptic plasticity during sleep.

Adult↗

PubMed2004

Local sleep and learning.

Human sleep is a global state whose functions remain unclear. During much of sleep, cortical neurons undergo slow oscillations in membrane potential, which appear in electroencephalograms as slow wave activity (SWA) of <4 Hz. The amount of SWA is homeostatically regulated, increasing after wakefulness and returning to baseline during sleep. It has been suggested that SWA homeostasis may reflect synaptic changes underlying a cellular need for sleep. If this were so, inducing local synaptic changes should induce local SWA changes, and these should benefit neural function. Here we show that sleep homeostasis indeed has a local component, which can be triggered by a learning task involving specific brain regions. Furthermore, we show that the local increase in SWA after learning correlates with improved performance of the task after sleep. Thus, sleep homeostasis can be induced on a local level and can benefit performance.

Brain↗

PubMed2003

EEG slow (approximately 1 Hz) waves are associated with nonstationarity of thalamo-cortical sensory processing in the sleeping human.

Intracellular studies reveal that, during slow wave sleep (SWS), the entire cortical network can swing rhythmically between extremely different microstates, ranging from wakefulness-like network activation to functional disconnection in the space of a few hundred milliseconds. This alternation of states also involves the thalamic neurons and is reflected in the EEG by a slow (<1 Hz) oscillation. These rhythmic changes, occurring in the thalamo-cortical circuits during SWS, may have relevant, phasic effects on the transmission and processing of sensory information. However, brain reactivity to sensory stimuli, during SWS, has traditionally been studied by means of sequential averaging, a procedure that necessarily masks any short-term fluctuation of responsiveness. The aim of this study was to provide a dynamic evaluation of brain reactivity to sensory stimuli in naturally sleeping humans. To this aim, single-trial somatosensory evoked potentials (SEPs) were grouped and averaged as a function of the phase of the ongoing sleep slow (<1 Hz) oscillation. This procedure revealed a dynamic profile of responsiveness, which was conditioned by the phase of the spontaneous sleep EEG. Overall, the amplitude of the evoked potential changed sistematically, increasing and approaching wakefulness levels along the negative slope of the EEG oscillation and decaying below SWS average levels along the positive drift. These marked and fast changes of stimulus-correlated electrical activity involved both short (N20) and long latency (P60 and P100) components of SEPs. In addition, the observed short-term response variability appeared to be centrally generated and specifically related to the evolution of the spontaneous oscillatory pattern. The present findings demonstrate that thalamo-cortical processing of sensory information is not stationary in the very short period (approximately 500 ms) during natural SWS.

Cerebral Cortex↗

PubMed2002

Spatial buffering during slow and paroxysmal sleep oscillations in cortical networks of glial cells in vivo.

The ability of neuroglia to buffer local increases of extracellular K(+) has been known from in vitro studies. This property may confer on these cells an active role in the modulation and spreading of cortical oscillatory activities. We addressed the question of the spatial buffering in vivo by performing single and double intraglial recordings, together with measures of the extracellular K(+) and Ca(2+) concentrations ([K(+)](out) and [Ca(2+)](out)) in the cerebral cortex of cats under ketamine and xylazine anesthesia during patterns of slow sleep oscillations and spike-wave seizures. In addition, we estimated the fluctuations of intraglial K(+) concentrations ([K(+)](in)). Measurements obtained during the slow oscillation indicated that glial cells phasically take up part of the extracellular K(+) extruded by neurons during the depolarizing phase of the slow oscillation. During this condition, the redistribution of K(+) appeared to be local. Large steady increases of [K(+)](out) and phasic potassium accumulations were measured during spike-wave seizures. In this condition, [K(+)](in) rose before [K(+)](out) if the glial cells were located at some distance from the epileptic focus, suggesting faster K(+) diffusion through the interglial syncytium. The simultaneously recorded [Ca(2+)](out) dropped steadily during the seizures to levels incompatible with efficient synaptic transmission, but also displayed periodic oscillations, in phase with the intraseizure spike-wave complexes. In view of this fact, and considering the capability of K(+) to modulate neuronal excitability both at the presynaptic and postsynaptic levels, we suggest that the K(+) long-range spatial buffering operated by glia is a parallel synchronizing and/or spreading mechanism during paroxysmal oscillations.

Action Potentials↗

PubMed2002

Glial and neuronal interactions during slow wave and paroxysmal activities in the neocortex.

Increasing evidence suggests that glial cells are endowed with the ability to externalize their activity to the extracellular space and to neurons. Since the same activity is influenced by the extracellular ionic concentrations and the neurotransmitters released by neurons, it is suggested that neurons and glia entertain a continuous exchange of information. This behavior might have a particular significance during cortical oscillations. In this study we analyzed the time and voltage relationships within simultaneously recorded neuron-glia pairs during normal states characterized by a slow (<1 Hz) sleep oscillation and during paroxysmal epileptic discharges. Our data show that cortical neurons and glia display coherent activities during the tested spontaneous oscillations. The onset of the depolarizing phase of the slow oscillation started in neurons and followed with a lag of 88 ms in nearby (1-2 mm) recorded glial cells. In contrast, the beginning of the hyperpolarizing phase was initiated in glial cells, and neurons followed after 79 ms, suggesting that glial activities are not exclusively the reflection of neuronal ones. Moreover, we tested neuronal excitability that resulted in phase opposition with the glial membrane potential, establishing that only the first 30% of the neuronal depolarization is efficient for synaptic volleys within cortical neuronal networks. Seizures were associated with shorter time lags at onset of depolarization (1.8 ms) and with delayed glial offset (102 ms). The voltage slope and amplitude at the onset of the paroxysmal depolarizations were higher than in the case of the slow oscillation. Together with the variation of neuronal excitability, these results suggest that the glial uptake of K(+) contributes to the abridged duration of the paroxysmal depolarization.

Animals↗