MEG-measured visually induced gamma-band oscillations in chronic schizophrenia: Evidence for impaired generation of rhythmic activity in ventral stream regions

Background: Gamma-band oscillations are prominently impaired in schizophrenia, but the nature of the deficit and relationship to perceptual processes is unclear. Methods: 16 patients with chronic schizophrenia (ScZ) and 16 age-matched healthy controls completed a visual paradigm while magnetoencephalographic (MEG) data was recorded. Participants had to detect randomly occurring stimulus acceleration while viewing a concentric moving grating. MEG data were analyzed for spectral power (1-100 Hz) at sensorand source-level to examine the brain regions involved in aberrant rhythmic activity, and for contribution of differences in baseline activity towards the generation of low- and highfrequency power. Results: Our data show reduced gamma-band power at sensor level in schizophrenia patients during stimulus processing while alpha-band and baseline spectrum were intact. Differences in oscillatory activity correlated with reduced behavioral detection rates in the schizophrenia group and higher scores on the “Cognitive Factor” of the Positive and Negative Syndrome Scale. Source reconstruction revealed that extra-striate (fusiform/lingual gyrus), but not striate (cuneus), visual cortices contributed towards the reduced activity observed at sensorlevel in ScZ patients. Importantly, differences in stimulus-related activity were not due to differences in baseline activity. Conclusions: Our findings highlight that MEG-measured high-frequency oscillations during visual processing can be robustly identified in ScZ. Our data further suggest impairments that involve dysfunctions in ventral stream processing and a failure to increase gamma-band activity in a task-context. Implications of these findings are discussed in the context of current theories of cortical-subcortical circuit dysfunctions and perceptual processing in ScZ.

Analysis of the EEG Dynamics of Epileptic Activity in Gelastic Seizures Using Decomposition in Independent Components

Objective: Gelastic seizures are a frequent and well established manifestation of the epilepsy associated with hypothalamic hamartomas. The scalp EEG recordings very seldom demonstrate clear spike activity and the information about the ictal epilepsy dynamics is limited. In this work, we try to isolate epileptic rhythms in gelastic seizures and study their generators. Methods: We extracted rhythmic activity from EEG scalp recordings of gelastic seizures using decomposition in independent components (ICA) in three patients, two with hypothalamic hamartomas and one with no hypothalamic lesion. Time analysis of these rhythms and inverse source analysis was done to recover their foci of origin and temporal dynamics. Results: In the two patients with hypothalamic hamartomas consistent ictal delta (2–3 Hz) rhythms were present, with subcortical generators in both and a superficial one in a single patient. The latter pattern was observed in the patient with no hypothalamic hamartoma visible in MRI. The deep generators activated earlier than the superficial ones, suggesting a consistent sub-cortical origin of the rhythmical activity. Conclusions: Our data is compatible with early and brief epileptic generators in deep sub-cortical regions and more superficial ones activating later. Significance: Gelastic seizures express rhythms on scalp EEG compatible with epileptic activity originating in sub-cortical generators and secondarily involving cortical ones.

Synaptic depression and slow oscillatory activity in a biophysical network model of the cerebral cortex

Short-term synaptic depression (STD) is a form of synaptic plasticity that has a large impact on network computations. Experimental results suggest that STD is modulated by cortical activity, decreasing with activity in the network and increasing during silent states. Here, we explored different activity-modulation protocols in a biophysical network model for which the model displayed less STD when the network was active than when it was silent, in agreement with experimental results. Furthermore, we studied how trains of synaptic potentials had lesser decay during periods of activity (UP states) than during silent periods (DOWN states), providing new experimental predictions. We next tackled the inverse question of what is the impact of modifying STD parameters on the emergent activity of the network, a question difficult to answer experimentally. We found that synaptic depression of cortical connections had a critical role to determine the regime of rhythmic cortical activity. While low STD resulted in an emergent rhythmic activity with short UP states and long DOWN states, increasing STD resulted in longer and more frequent UP states interleaved with short silent periods. A still higher synaptic depression set the network into a non-oscillatory firing regime where DOWN states no longer occurred. The speed of propagation of UP states along the network was not found to be modulated by STD during the oscillatory regime; it remained relatively stable over a range of values of STD. Overall, we found that the mutual interactions between synaptic depression and ongoing network activity are critical to determine the mechanisms that modulate cortical emergent patterns.

Alpha-band suppression in the visual word form area as a functional bottleneck to consciousness.

The current state of empirical investigations refers to consciousness as an all-or-none phenomenon. However, a recent theoretical account opens up this perspective by proposing a partial level (between nil and full) of conscious perception. In the well-studied case of single-word reading, short-lived exposure can trigger incomplete word-form recognition wherein letters fall short of forming a whole word in one's conscious perception thereby hindering word-meaning access and report. Hence, the processing from incomplete to complete word-form recognition straightforwardly mirrors a transition from partial to full-blown consciousness. We therefore hypothesized that this putative functional bottleneck to consciousness (i.e. the perceptual boundary between partial and full conscious perception) would emerge at a major key hub region for word-form recognition during reading, namely the left occipito-temporal junction. We applied a real-time staircase procedure and titrated subjective reports at the threshold between partial (letters) and full (whole word) conscious perception. This experimental approach allowed us to collect trials with identical physical stimulation, yet reflecting distinct perceptual experience levels. Oscillatory brain activity was monitored with magnetoencephalography and revealed that the transition from partial-to-full word-form perception was accompanied by alpha-band (7-11 Hz) power suppression in the posterior left occipito-temporal cortex. This modulation of rhythmic activity extended anteriorly towards the visual word form area (VWFA), a region whose selectivity for word-forms in perception is highly debated. The current findings provide electrophysiological evidence for a functional bottleneck to consciousness thereby empirically instantiating a recently proposed partial perspective on consciousness. Moreover, the findings provide an entirely new outlook on the functioning of the VWFA as a late bottleneck to full-blown conscious word-form perception.

Stimulus statistics shape oscillations in nonlinear recurrent neural networks.

Rhythmic activity plays a central role in neural computations and brain functions ranging from homeostasis to attention, as well as in neurological and neuropsychiatric disorders. Despite this pervasiveness, little is known about the mechanisms whereby the frequency and power of oscillatory activity are modulated, and how they reflect the inputs received by neurons. Numerous studies have reported input-dependent fluctuations in peak frequency and power (as well as couplings across these features). However, it remains unresolved what mediates these spectral shifts among neural populations. Extending previous findings regarding stochastic nonlinear systems and experimental observations, we provide analytical insights regarding oscillatory responses of neural populations to stimulation from either endogenous or exogenous origins. Using a deceptively simple yet sparse and randomly connected network of neurons, we show how spiking inputs can reliably modulate the peak frequency and power expressed by synchronous neural populations without any changes in circuitry. Our results reveal that a generic, non-nonlinear and input-induced mechanism can robustly mediate these spectral fluctuations, and thus provide a framework in which inputs to the neurons bidirectionally regulate both the frequency and power expressed by synchronous populations. Theoretical and computational analysis of the ensuing spectral fluctuations was found to reflect the underlying dynamics of the input stimuli driving the neurons. Our results provide insights regarding a generic mechanism supporting spectral transitions observed across cortical networks and spanning multiple frequency bands.

Développement de l’activité rythmique chez l’embryon du poisson-zébré

Les circuits neuronaux peuvent générer une panoplie de rythmes. Nous pouvons séparer les mécanismes de création de ces rythmes en deux grands types. Le premier consiste de circuits contrôlés par des cellules « pacemakers », ayant une activité rythmique intrinsèque, comme dans le ganglion stomatogastique des crustacés. Le deuxième consiste de circuits multi-neuronaux connectés par un réseau synaptique qui permet une activité rythmique sans la présence de neurones pacemakers, tel que démontré pour les circuits de la nage chez plusieurs vertébrés. Malgré nos connaissances des mécanismes de rhythmogénèse chez les vertébrés adultes, les mécanismes de la création et la maturation de ces circuits locomoteurs chez les embryons restent encore inconnus. Nous avons étudié cette question à l’aide du poisson-zébré où les embryons débutent leur activité motrice par des contractions spontanées alternantes à 17 heures post-fertilisation (hpf). Des études ont démontré que cette activité spontanée n’est pas sensible aux antagonistes de la transmission synaptique chimique et ne requiert pas le rhombencéphale. Après 28 hpf, les embryons commencent à nager et se propulser en réponse au toucher. Des études antérieures on démontré que l’apparition de la nage nécessite le rhombencéphale et la transmission synaptique chimique. Cette thèse explore la possibilité que ces changements comportementaux représentent la progression d’un circuit contrôle par un pacemaker à un circuit ou le rythme provient d’un circuit distribué. En mesurant le groupement des contractions de l’activité spontanée, plutôt que la fréquence moyenne, nous avons découvert une nouvelle forme d’activité spontanée qui débute à 22 hpf. Cette activité consiste de deux contractions alternantes à succession très rapide. Contrairement à l’activité spontanée présente dès 17 hpf cette nouvelle forme d’activité requiert le rhombencéphale et la transmission synaptique chimique, comme démontré pour la nage qui apparait à 28 hpf. Cette forme de comportement intermédiaire représente potentiellement une étape transitoire lors de la maturation des circuits moteurs.

Effect of ion reduction of sodium, calcium and potassium on spontaneous contraction of the esophagus of Pomacea lineata SPIX, 1827 (Mollusca-Gastropoda-Prosobranchia)

The invertebrate's musculature still presents many elusive points, especially in molluscs that generally present smooth and cracked fibers with peculiar characteristics. It was found that the molluscs reactions to the ion variation in the bathing are not very clear, mainly in view of the isolated reduction or equivalent of the ions. Suspended in bath, the isolated esophagus of the P. lineata exhibited spontaneous activity. This rhythmic activity was sensitive to the ion variation of the perfusion liquid, evidenced by alterations in the spontaneous contractions. The equivalent reduction of the ion reduced the spontaneous activity, evidenced by the amplitude reduction of the response, besides maintaning an organ contraction, primarily in the reductions below 50%. When the isolated reductions of the Na, Ca or K ion were performed, occurred interference in the spontaneous contractions of the organs, principally in amplitude of the response and maintenance of the contracture in reductions of 50 and 25% of the ion.

Physiological and pathophysiological interactions between the respiratory central pattern generator and the sympathetic nervous system

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Disruption of endogenous tidal rhythms of larval release linked to food supply and heat stress in an intertidal barnacle

The timing of larval release may greatly affect the survivorship and distribution of pelagic stages and reveal important aspects of life history tactics in marine invertebrates. Endogenous rhythms of breeding individuals and populations are valuable indicators of selected strategies because they are free of the neutral effect of stochastic environmental variation. The high-shore intertidal barnacle Chthamalus bisinuatus exhibits endogenous tidal and tidal amplitude rhythms in a way that larval release would more likely occur during fortnightly neap periods at high tide. Such timing would minimize larval loss due to stranding and promote larval retention close to shore. This fully explains temporal patterns in populations facing the open sea and inhabiting eutrophic areas. However, rhythmic activity breaks down to an irregular pattern in a population within the São Sebastião Channel subjected to large variation of food supply around a mesotrophic average. Peaks of chl a concentration precede release events by 6 d, suggesting resource limitation for egg production within the channel. Also, extreme daily temperatures imposing mortality risk correlate to release rate just 1 d ahead, suggesting a terminal reproductive strategy. Oceanographic conditions apparently dictate whether barnacles follow a rhythmic trend of larval release supported by endogenous timing or, alternatively, respond to the stochastic variation of key environmental factors, resulting in an erratic temporal pattern.

Spindle burst like spike discharge oscillations in organotypic cultures of neonatal rat cortex

Early network oscillations and spindle bursts are typical patterns of spontaneous rhythmic activity in cortical networks of neonatal rodents in vivo and in vitro. The latter can also be triggered in vivo by stimulation of afferent inputs. The mechanisms underlying such oscillations undergo profound developmental changes in the first postnatal weeks. Their possible role in cortical development is postulated but not known in detail. We have studied spontaneous and evoked patterns of activity in organotypic cultures of slices from neonatal rat cortex grown on multielectrode arrays (MEAs) for extracellular single- and multi-unit recording. Episodes of spontaneous spike discharge oscillations at 7 - 25 Hz lasting for 0.6 - 3 seconds appeared in about half of these cultures spontaneously and could be triggered by electrical stimulation of few distinct electrodes. These oscillations usually covered only restricted areas of the slices. Besides oscillations, single population bursts that spread in a wavelike manner over the whole slice also appeared spontaneously and were triggered by electrical stimulation. In most but not all cultures, population bursts preceded the oscillations. Both population bursts and spike discharge oscillations required intact glutamatergic synaptic transmission since they were suppressed by the AMPA/kainate glutamate receptor antagonist CNQX. The NMDA antagonist d-APV suppressed the oscillations but not the population bursts, suggesting an involvement of NMDA receptors in the oscillations. These findings show that spindle burst like cortical rhythms are reproduced in organotypic cultures of neonatal cortex. The culture model thus allows investigating the role of such rhythms in cortical circuit formation. Supported by SNF grant No. 3100A0-107641/1.

Cellular and network mechanisms of rhythm generation in spinal cord circuits

The generation of rhythmic electrical activity is a prominent feature of spinal cord circuits that is used for locomotion and also for circuit refinement during development. The mechanisms involved in rhythm generation in spinal cord networks are not fully understood. It is for example not known whether spinal cord rhythms are driven by pacemaker neurons and if yes, which neurons are involved in this function. We studied the mechanisms involved in rhythm generation in slice cultures from fetal rats that were grown on multielectrode arrays (MEAs). We combined multisite extracellular recordings from the MEA electrodes with intracellular patch clamp recordings from single neurons. We found that spatially restricted oscillations of activity appeared in most of the cultures spontaneously. Such activity was based on intrinsic activity in a percentage of the neurons that could activate the spinal networks through recurrent excitation. The local oscillator networks critically involved NMDA, AMPA and GABA / glycine receptors at subsequent phases of the oscillation cycle. Intrinsic spiking in individual neurons (in the absence of functional synaptic coupling) was based on persistent sodium currents. Intrinsic firing as well as persistent sodium currents were increased by 5-HT through 5-HT2 receptors. Comparing neuronal activity to muscle activity in co-cultures of spinal cord slices with muscle fibers we found that a percentage of the intrinsically spiking neurons were motoneurons. These motoneurons were electrically coupled among each other and they could drive the spinal networks through cholinergic recurrent excitation. These findings open the possibility that during development rhythmic activity in motoneurons is not only involved in circuit refinement downstream at the neuromuscular endplates but also upstream at the level of spinal cord circuits.

Sensory regulation of network components underlying ciliary locomotion in Hermissenda.

Ciliary locomotion in the nudibranch mollusk Hermissenda is modulated by the visual and graviceptive systems. Components of the neural network mediating ciliary locomotion have been identified including aggregates of polysensory interneurons that receive monosynaptic input from identified photoreceptors and efferent neurons that activate cilia. Illumination produces an inhibition of type I(i) (off-cell) spike activity, excitation of type I(e) (on-cell) spike activity, decreased spike activity in type III(i) inhibitory interneurons, and increased spike activity of ciliary efferent neurons. Here we show that pairs of type I(i) interneurons and pairs of type I(e) interneurons are electrically coupled. Neither electrical coupling or synaptic connections were observed between I(e) and I(i) interneurons. Coupling is effective in synchronizing dark-adapted spontaneous firing between pairs of I(e) and pairs of I(i) interneurons. Out-of-phase burst activity, occasionally observed in dark-adapted and light-adapted pairs of I(e) and I(i) interneurons, suggests that they receive synaptic input from a common presynaptic source or sources. Rhythmic activity is typically not a characteristic of dark-adapted, light-adapted, or light-evoked firing of type I interneurons. However, burst activity in I(e) and I(i) interneurons may be elicited by electrical stimulation of pedal nerves or generated at the offset of light. Our results indicate that type I interneurons can support the generation of both rhythmic activity and changes in tonic firing depending on sensory input. This suggests that the neural network supporting ciliary locomotion may be multifunctional. However, consistent with the nonmuscular and nonrhythmic characteristics of visually modulated ciliary locomotion, type I interneurons exhibit changes in tonic activity evoked by illumination.