Thalamocortical Mechanisms Research Articles

Underlying mechanisms for altered reactivity of posterior cortical electroencephalographic alpha rhythms in DLB and PDD

AbstractBackgroundThe amplitude of resting‐state electroencephalographic (rsEEG) rhythms is a promising neurophysiological biomarker to investigate the abnormalities of oscillatory neurophysiological thalamocortical mechanisms related to the general cortical arousal and vigilance in wakefulness in patients with dementia due to neurodegenerative diseases as Alzheimer’s disease (ADD), Parkinson’s disease (PDD) and Lewy Body disease (DLB). Here, we tested the hypothesis that the reactivity of posterior rsEEG alpha (about 8‐12 Hz) rhythms during the transition from eyes‐closed to ‐open condition may be lower in PDD patients than in DLB patients.MethodsA Eurasian database provided clinical‐demographic‐rsEEG datasets in 35 ADD patients, 65 PDD patients, 30 DLB patients, and 25 matched cognitively unimpaired (Healthy) persons. The rsEEG rhythms were investigated at individual delta, theta, and alpha frequency bands, as well as fixed beta (14‐30 Hz) and gamma (30‐40 Hz) bands. The eLORETA freeware was used to estimate cortical rsEEG sources.ResultsResults showed substantial (i.e., greater than ‐10%) reduction (reactivity) in the posterior alpha source activities from the eyes‐closed to the eyes‐open condition in 88% of the Healthy seniors, 53% of ADD patients, 53% of the DLB patients, and only 37% of the PDD patients (Figure 1). In these alpha‐reactive participants, there was lower reactivity in the posterior alpha source activities in the three neurodegenerative (i.e., ADD, PDD, and DLB) groups than in the Healthy group. Furthermore, the reduction of the occipital alpha reactivity was stronger in the PDD and DLB groups than in the ADD group. Finally, the reduction of the parietal alpha reactivity was stronger in the PDD group than in the ADD and DLB groups (Figure 2).ConclusionThese results suggest that ADD, PDD, and DLB patients may be characterized by very poor reactivity in the posterior cortical mechanisms desynchronizing rsEEG alpha rhythms in relation to increased vigilance levels as an interesting neurophysiological biomarker. This biomarker may be used as a primary endpoint for interventions with drugs or brain electromagnetic stimulations to improve vigilance regulation and quality of life in neurodegenerative patients, allowing them to follow TV programs and interactions in their social environment.

Calcium-Sensitive Subthreshold Oscillations and Electrical Coupling in Principal Cells of Mouse Dorsal Cochlear Nucleus.

In higher sensory brain regions, slow oscillations (0.5-5 Hz) associated with quiet wakefulness and attention modulate multisensory integration, predictive coding, and perception. Although often assumed to originate via thalamocortical mechanisms, the extent to which subcortical sensory pathways are independently capable of slow oscillatory activity is unclear. We find that in the first station for auditory processing, the cochlear nucleus, fusiform cells from juvenile mice (of either sex) generate robust 1-2 Hz oscillations in membrane potential and exhibit electrical resonance. Such oscillations were absent prior to the onset of hearing, intrinsically generated by hyperpolarization-activated cyclic nucleotide-gated (HCN) and persistent Na+ conductances (NaP) interacting with passive membrane properties, and reflected the intrinsic resonance properties of fusiform cells. Cx36-containing gap junctions facilitated oscillation strength and promoted pairwise synchrony of oscillations between neighboring neurons. The strength of oscillations were strikingly sensitive to external Ca2+, disappearing at concentrations >1.7 mM, due in part to the shunting effect of small-conductance calcium-activated potassium (SK) channels. This effect explains their apparent absence in previous in vitro studies of cochlear nucleus which routinely employed high-Ca2+ extracellular solution. In contrast, oscillations were amplified in reduced Ca2+ solutions, due to relief of suppression by Ca2+ of Na+ channel gating. Our results thus reveal mechanisms for synchronous oscillatory activity in auditory brainstem, suggesting that slow oscillations, and by extension their perceptual effects, may originate at the earliest stages of sensory processing.

The Thalamocortical Mechanism Underlying the Generation and Regulation of the Auditory Steady-State Responses in Awake Mice.

The auditory steady-state response (ASSR) is a cortical oscillation induced by trains of 40 Hz acoustic stimuli. While the ASSR has been widely used in clinic measurement, the underlying neural mechanism remains poorly understood. In this study, we investigated the contribution of different stages of auditory thalamocortical pathway-medial geniculate body (MGB), thalamic reticular nucleus (TRN), and auditory cortex (AC)-to the generation and regulation of 40 Hz ASSR in C57BL/6 mice of both sexes. We found that the neural response synchronizing to 40 Hz sound stimuli was most prominent in the GABAergic neurons in the granular layer of AC and the ventral division of MGB (MGBv), which were regulated by optogenetic manipulation of TRN neurons. Behavioral experiments confirmed that disrupting TRN activity has a detrimental effect on the ability of mice to discriminate 40 Hz sounds. These findings revealed a thalamocortical mechanism helpful to interpret the results of clinical ASSR examinations.Significance Statement Our study contributes to clarifying the thalamocortical mechanisms underlying the generation and regulation of the auditory steady-state response (ASSR), which is commonly used in both clinical and neuroscience research to assess the integrity of auditory function. Combining a series of electrophysiological and optogenetic experiments, we demonstrate that the generation of cortical ASSR is dependent on the lemniscal thalamocortical projections originating from the ventral division of medial geniculate body to the GABAergic interneurons in the granule layer of the auditory cortex. Furthermore, the thalamocortical process for ASSR is strictly regulated by the activity of thalamic reticular nucleus (TRN) neurons. Behavioral experiments confirmed that dysfunction of TRN would cause a disruption of mice's behavioral performance in the auditory discrimination task.

A thalamocortical substrate for integrated information via critical synchronous bursting.

Understanding the neurobiological mechanisms underlying consciousness remains a significant challenge. Recent evidence suggests that the coupling between distal-apical and basal-somatic dendrites in thick-tufted layer 5 pyramidal neurons (L5PN), regulated by the nonspecific-projecting thalamus, is crucial for consciousness. Yet, it is uncertain whether this thalamocortical mechanism can support emergent signatures of consciousness, such as integrated information. To address this question, we constructed a biophysical network of dual-compartment thick-tufted L5PN, with dendrosomatic coupling controlled by thalamic inputs. Our findings demonstrate that integrated information is maximized when nonspecific thalamic inputs drive the system into a regime of time-varying synchronous bursting. Here, the system exhibits variable spiking dynamics with broad pairwise correlations, supporting the enhanced integrated information. Further, the observed peak in integrated information aligns with criticality signatures and empirically observed layer 5 pyramidal bursting rates. These results suggest that the thalamocortical core of the mammalian brain may be evolutionarily configured to optimize effective information processing, providing a potential neuronal mechanism that integrates microscale theories with macroscale signatures of consciousness.

Thalamocortical Mechanisms Underlying Real and Imagined Acupuncture.

Both acupuncture and imagery have shown potential for chronic pain management. However, the mechanisms underlying their analgesic effects remain unclear. This study aims to explore the thalamocortical mechanisms underlying acupuncture and video-guided acupuncture imagery treatment (VGAIT), a combination of acupuncture and guided imagery, using the resting-state functional connectivity (rsFC) of three thalamic subdivisions-the ventral posterolateral thalamus (VPL), mediodorsal thalamus (MD), and motor thalamus subregion (Mthal)-associated with somatosensory, limbic, and motor circuity. Twenty-seven healthy individuals participated in a within-subject randomized crossover design study. Results showed that compared to sham acupuncture, real acupuncture altered the rsFC between the thalamus and default mode network (DMN) (i.e., mPFC, PCC, and precuneus), as well as the prefrontal and somatosensory cortex (SI/SII). Compared to the VGAIT control, VGAIT demonstrated greater rsFC between the thalamus and key nodes within the interoceptive network (i.e., anterior insula, ACC, PFC, and SI/SII), as well as the motor and sensory cortices (i.e., M1, SMA, and temporal/occipital cortices). Furthermore, compared to real acupuncture, VGAIT demonstrated increased rsFC between the thalamus (VPL/MD/Mthal) and task-positive network (TPN). Further correlations between differences in rsFC and changes in the heat or pressure pain threshold were also observed. These findings suggest that both acupuncture- and VGAIT-induced analgesia are associated with thalamocortical networks. Elucidating the underlying mechanism of VGAIT and acupuncture may facilitate their development, particularly VGAIT, which may be used as a potential remote-delivered pain management approach.

Abnormal resting state EEG and vigilance in neurodegenerative dementias

AbstractBackgroundAlzheimer’s disease dementia (ADD) is the most common neurodegenerative dementing disorder explaining about 60‐70% of 50 million patients worldwide (www.who.int). Dementia with Lewy Bodies (DLB) is another diffuse neurodegenerative dementing disorder inducing abnormalities in vigilance (visual hallucinations, cognitive fluctuations, and REM sleep behavior disorder). These abnormalities may be reflected in the reduction in amplitude (“reactivity”) of resting‐state EEG (rsEEG) alpha rhythms (7‐9 Hz) in posterior cortical areas from eye‐closed to ‐open conditions. Indeed, this “reactivity” probes cholinergic inputs from the basal forebrain to thalamocortical mechanisms regulating vigilance. The present study tested such a hypothesis.MethodClinical and rsEEG rhythms in demographic‐ and age‐matched AD (N = 48), DLB (N = 42), and healthy cognitively unimpaired (Nold, N = 38) persons were enrolled. Pathological groups were matched as cognitive status (i.e., dementia grade). The eLORETA freeware estimated rsEEG alpha cortical sources on individual basis.ResultThere was a substantial (> ‐10%) reduction in the posterior alpha source activities from the eyes‐closed to the eyes‐open condition in 93% of the Nold seniors, 77% of the ADD patients, and 64% of the DLB patients. In these participants, there was less reactivity of the posterior rsEEG alpha source activities in the ADD and DLB groups than in the Nold group. Furthermore, there was less reactivity of the occipital rsEEG alpha source activities in the DLB than in the ADD group (p < 0.05 corrected; Figure 1).ConclusionThese novel results suggest that neurophysiological oscillatory mechanisms regulating cortical arousal in the visual system during changes in vigilance may be more abnormal in DLB than ADD patients with dementia, possibly concurring to visual misperceptions, hallucinations, and vigilance fluctuations reported in DLB patients as a function of cholinergic functional connectivity to visual cortical areas. Furthermore, the present results suggest that many DLB patients may suffer from a pathological transition from “reactive” posterior rsEEG alpha rhythms during eye‐opening to “unreactive” theta rhythms becoming a dominant background frequency. Importantly, this transition may be erroneously considered as “alpha” if the reactivity of those rsEEG rhythms is not tested during both eyes‐closed and ‐opening conditions.

Central-positive complexes in ECT-induced seizures: Possible evidence for thalamocortical mechanisms

ObjectiveCentral-positive complexes (CPCs) are elicited during electroconvulsive therapy (ECT) as generalized high-amplitude waveforms with maximum positive voltage over the vertex. While these complexes have been qualitatively assessed in previous literature, quantitative analyses are lacking. This study aims to characterize CPCs across temporal, spatial, and spectral domains. MethodsHigh-density 64-electrode electroencephalogram (EEG) recordings during 50 seizures acquired from 11 patients undergoing right unilateral ECT allowed for evaluation of spatiotemporal characteristics of CPCs via source localization and spectral analysis. ResultsPeak-amplitude CPC scalp topology was consistent across seizures, showing maximal positive polarity over the midline fronto-central region and maximal negative polarity over the suborbital regions. The sources of these peak potentials were localized to the bilateral medial thalamus and cingulate cortical regions. Delta, beta, and gamma oscillations were correlated with the peak amplitude of CPCs during seizures induced during ketamine, whereas delta and gamma oscillations were associated with CPC peaks during etomidate anesthesia (excluding the dose-charge titration). ConclusionsOur findings demonstrate the consistency of CPC presence across participant, stimulus charge, time, and anesthetic agent, with peaks localized to bilateral medial thalamus and cingulate cortical regions and associated with delta, beta, and gamma band oscillations (depending on the anesthetic condition). SignificanceThe consistency and reproducibility of CPCs offers ECT as a new avenue for studying the dynamics of generalized seizure activity and thalamocortical networks.

0092 The Effects of Slow-Oscillatory Galvanic Vestibular Stimulation on Sleep Physiology in Healthy Humans

Abstract Introduction Recent studies have demonstrated that rocking promotes sleep in animals and humans. The application of an alternating current galvanic vestibular stimulation (GVS) can elicit body sway like rocking sensation. Here, we examined the effects of slow-oscillatory GVS, which can evoke the virtual rocking sensation in the brain, on objective and subjective sleep quality in healthy young adults. Methods We studied 14 healthy subjects (age: 22.7 p/m 1.4 years) who underwent 3 nap conditions (adaptation, sham [SHAM], and stimulation [STIM]), where SHAM and STIM were randomly allocated with a 1-week interval in general. The polysomnographic recordings were started at 2 pm and time in bed was restricted to 90 min for all subjects. In both conditions, electrodes were placed on both mastoids for GVS; in STIM condition, the slow-oscillatory (0.25 Hz sinusoidal) GVS was applied throughout the nap period with a current intensity of approximately 80% of sensory thresholds of each subject. The pattern of center of pressure during quiet standing was also measured using a force plate, with or without the same slow-oscillatory GVS. We analyzed sleep variables and electroencephalographic (EEG) spectral power and compared them between STIM and SHAM. Subjective sleep quality was also measured and compared between STIM and SHAM. Results We confirmed that subsensory slow-oscillatory GVS induced body sway corresponding to the stimulation frequency for all subjects. We found that sleep latency was significantly shorter and total sleep time as well as N2 duration were significantly longer in STIM than in SHAM. N3 duration did not differ significantly between the conditions. EEG power spectrum densities in delta, theta, and sigma bands were significantly greater in STIM than in SHAM. Subjective sleep quality was significantly better in STIM than in SHAM. Conclusion We demonstrated that subsensory slow-oscillatory GVS facilitated wake-sleep transition and improved objective and subjective sleep quality. The results suggest that weak periodic inputs into vestibular systems promote sleep by modulating the thalamocortical mechanisms in humans. This finding may open a new avenue toward a development of novel techniques for human sleep augmentation. Support (If Any) JST PRESTO (JPMJPR19J3) and JSPS KAKENHI (18K17891) to AK.

Thalamocortical Mechanisms for Nostalgia-Induced Analgesia.

As a predominately positive emotion, nostalgia serves various adaptive functions, including a recently revealed analgesic effect. The current fMRI study aimed to explore the neural mechanisms underlying the nostalgia-induced analgesic effect on noxious thermal stimuli of different intensities. Human participants' (males and females) behavior results showed that the nostalgia paradigm significantly reduced participants' perception of pain, particularly at low pain intensities. fMRI analysis revealed that analgesia was related to decreased brain activity in pain-related brain regions, including the lingual and parahippocampal gyrus. Notably, anterior thalamic activation during the nostalgia stage predicted posterior parietal thalamus activation during the pain stage, suggesting that the thalamus might play a key role as a central functional linkage in the analgesic effect. Moreover, while thalamus-PAG functional connectivity was found to be related to nostalgic strength, periaqueductal gray-dorsolateral prefrontal cortex (PAG-dlPFC) functional connectivity was found to be associated with pain perception, suggesting possible analgesic modulatory pathways. These findings demonstrate the analgesic effect of nostalgia and, more importantly, shed light on its neural mechanism.SIGNIFICANCE STATEMENT Nostalgia is known to reduce individuals' perception of physical pain. The underlying brain mechanisms, however, are unclear. Our study found that the thalamus plays a key role as a functional linkage between nostalgia and pain, suggesting a possible analgesic modulatory mechanism of nostalgia. These findings have implications for the underlying brain mechanisms of psychological analgesia.

Lateralisation of subcortical functional connectivity during and after general anaesthesia

BackgroundArousal and awareness are two important components of consciousness states. Functional neuroimaging has furthered our understanding of cortical and thalamocortical mechanisms of awareness. Investigating the relationship between subcortical functional connectivity and arousal has been challenging owing to the relatively small size of brainstem structures and thalamic nuclei, and their depth in the brain. MethodsResting state functional MRI scans of 72 healthy volunteers were acquired before, during, 1 h after, and 1 day after sevoflurane general anaesthesia. Functional connectivity of subcortical regions of interest vs whole brain and homotopic functional connectivity for assessment of left–right symmetry analyses of both cortical and subcortical regions of interest were performed. Both analyses used high resolution atlases generated from deep brain stimulation applications. ResultsFunctional connectivity in subcortical loci within the thalamus and of the ascending reticular activating system was sharply restricted under anaesthesia, featuring a general lateralisation of connectivity. Similarly, left–right homology was sharply reduced under anaesthesia. Subcortical bilateral functional connectivity was not fully restored after emergence from anaesthesia, although greater restoration was seen between ascending reticular activating system loci and specific thalamic nuclei thought to be involved in promoting and maintaining arousal. Functional connectivity was fully restored to baseline by the following day. ConclusionsFunctional connectivity in the subcortex is sharply restricted and lateralised under general anaesthesia. This restriction may play a part in loss and return of consciousness. Clinical trial registrationNCT02275026.

Visual thalamocortical mechanisms of waking state-dependent activity and alpha oscillations

The brain exhibits distinct patterns of recurrent activity closely related to behavioral state. The neural mechanisms that underlie state-dependent activity in the awake animal are incompletely understood. Here, we demonstrate that two types of state-dependent activity, rapid arousal/movement-related signals and a 3-5 Hz alpha-like rhythm, in the primary visual cortex (V1) of mice strongly correlate with activity inthe visual thalamus. Inactivation of V1 does not interrupt arousal/movement signals in most visual thalamicneurons, but it abolishes the 3-5 Hz oscillation. Silencing of the visual thalamus similarly eradicates the alpha-like rhythm and perturbs arousal/movement-related activation in V1. Intracellular recordings in thalamic neurons reveal the 3-5 Hz oscillation to be associated with rhythmic low-threshold Ca2+ spikes. Our results indicate that thalamocortical interactions through ionotropic signaling, together with cell-intrinsic properties of thalamocortical cells, play a crucial role in shaping state-dependent activity in V1 of the awake animal.

Thalamocortical Mechanisms Regulating the Relationship between Transient Beta Events and Human Tactile Perception.

Transient neocortical events with high spectral power in the 15–29 Hz beta band are among the most reliable predictors of sensory perception. Prestimulus beta event rates in primary somatosensory cortex correlate with sensory suppression, most effectively 100–300 ms before stimulus onset. However, the neural mechanisms underlying this perceptual association are unknown. We combined human magnetoencephalography (MEG) measurements with biophysical neural modeling to test potential cellular and circuit mechanisms that underlie observed correlations between prestimulus beta events and tactile detection. Extending prior studies, we found that simulated bursts from higher-order, nonlemniscal thalamus were sufficient to drive beta event generation and to recruit slow supragranular inhibition acting on a 300 ms timescale to suppress sensory information. Further analysis showed that the same beta-generating mechanism can lead to facilitated perception for a brief period when beta events occur simultaneously with tactile stimulation before inhibition is recruited. These findings were supported by close agreement between model-derived predictions and empirical MEG data. The postevent suppressive mechanism explains an array of studies that associate beta with decreased processing, whereas the during-event facilitatory mechanism may demand a reinterpretation of the role of beta events in the context of coincident timing.

072 Sleep Spindle Harmonics in Insomnia

Abstract Introduction Prior research has reported NREM spectral EEG differences between individuals with insomnia and good-sleeper controls, including elevated high-frequency EEG power (beta/gamma bands, ~16-50Hz) and, to a lesser extent, elevations in sleep spindle parameters. However, the mechanisms driving these differences remain unclear. Harmonics have been observed in EEG data as spectral peaks at multiples of a fundamental frequency associated with an event (e.g., for a 14Hz spindle, the 2nd harmonic is expected to be a peak at 28Hz). Thus far, there has been very limited application of this idea of spectral harmonics to sleep spindles, even though these patterns can indeed be seen in some existing literature. We sought to build on this literature to apply spectral harmonic analysis to better understand differences between insomnia and good sleepers. Methods 15 individuals with insomnia disorder (DSM-5 criteria, 13 female, age 18–32 years) and 15 good-sleeper controls (matched for sex, age, and BMI) completed an overnight polysomnography recording in the laboratory and subsequent daytime testing. Insomnia diagnosis was determined by a board-certified sleep specialist, and exclusion criteria included psychiatric history within past 6 months, other sleep disorders, significant medical conditions, and medications with significant effects on inflammation, autonomic function, or other psychotropic effects. Results Consistent with prior studies, we found elevated sleep spindle density and fast sigma power (14-16Hz). Despite no difference in beta or gamma band power when averaged across NREM sleep, time-frequency analysis centered on the peaks of detected spindles revealed a phasic elevation in spectral power surrounding the 28Hz harmonic peak in the insomnia group, especially for spindles coupled with slow waves. We also observed an overall pattern of time-locked delay in the 28Hz harmonic peak, occurring approximately 40 msec after spindle peaks. Furthermore, we observed a 42Hz ‘3rd harmonic’ peak, not yet predicted by the existing modeling work, which was also elevated for insomnia. Conclusion In conjunction with existing mathematical modeling work that has linked sleep spindle harmonic peaks with thalamic relay nuclei as the primary generators of this EEG signature, these findings may enable novel insights into specific thalamocortical mechanisms of insomnia and non-restorative sleep. Support (if any) NIH 5T32HL007901-22

Характеристики ЭЭГ в процессе кратковременных самопроизвольных пробуждений разной длительности при изменениях в психомоторной деятельности, вызванных засыпанием

During daytime sleep, the changes in the spectral characteristics of the EEG during recovery periods of the psychomotor test with spontaneous short-term awakenings were studied in 17 healthy subjects. The test contained two successively alternating tasks: the “silent” counting from 1 to 10, synchronized with the clicks on the button, and only the “silent” count. The monotonous nature of the test leads to a rapid decrease in the level of wakefulness and in most cases causes falling asleep. The appearance of button clicks is a behavioral indicator of the resumption of cognitive processes inhibited during sleep. Situations were compared for a small (2–5) and relatively large (6–10) number of button presses. The onset of button presses is preceded by the appearance of a generalized alpha rhythm, which decreases during psychomotor activity. At the same time, its power was always greater in a situation with longer periods of observed behavioral activity. The cessation of the button presses is accompanied with the return of the alpha activity power to values observed before the awakening. The EEG alpha rhythm at the reduced wakefulness during short-term awakenings apparently characterizes the activation of the thalamo-cortical mechanism, and is required for the motor interaction of the body with the environment. The absence of differences in the frontal areas at the initial stage of performing short-term and longer-term activity (approaching the full cycle of clicks) suggests that during this period they are involved to the same extent, regardless of the number of clicks. These results indirectly confirm that the observed psychomotor activity, even with a small number of clicks, is not automatic and unconscious, but is accompanied by a reduced, fragmented consciousness.

The pacemaker role of thalamic reticular nucleus in controlling spike-wave discharges and spindles.

Absence epilepsy, characterized by 2-4 Hz spike-wave discharges (SWDs), can be caused by pathological interactions within the thalamocortical system. Cortical spindling oscillations are also demonstrated to involve the oscillatory thalamocortical rhythms generated by the synaptic circuitry of the thalamus and cortex. This implies that SWDs and spindling oscillations can share the common thalamocortical mechanism. Additionally, the thalamic reticular nucleus (RE) is hypothesized to regulate the onsets and propagations of both the epileptic SWDs and sleep spindles. Based on the proposed single-compartment thalamocortical neural field model, we firstly investigate the stimulation effect of RE on the initiations, terminations, and transitions of SWDs. It is shown that the activations and deactivations of RE triggered by single-pulse stimuli can drive the cortical subsystem to behave as the experimentally observed onsets and self-abatements of SWDs, as well as the transitions from 2-spike and wave discharges (2-SWDs) to SWDs. In particular, with increasing inhibition from RE to the specific relay nucleus (TC), rich transition behaviors in cortex can be obtained through the upstream projection path, RE→TC→Cortex. Although some of the complex dynamical patterns can be expected from the earlier single compartment thalamocortical model, the effect of brain network topology on the emergence of SWDs and spindles, as well as the transitions between them, has not been fully investigated. We thereby develop a spatially extended 3-compartment coupled network model with open-/closed-end connective configurations, to investigate the spatiotemporal effect of RE on the SWDs and spindles. Results show that the degrees of activations of RE1 can induce the rich spatiotemporal evolution properties including the propagations from SWDs to spindles within different compartments and the transitions between them, through the RE1→TC1→Cortex1 and Cortex1→Cortex2→Cortex3 projecting paths, respectively. Overall, those results imply that RE possesses the pacemaker function in controlling SWDs and spindling oscillations, which computationally provide causal support for the involvement of RE in absence seizures and sleep spindles.

Further evidences for sleep instability and impaired spindle-delta dynamics in schizophrenia: a whole-night polysomnography study with neuroloop-gain and sleep-cycle analysis

ObjectiveSleep offers a unique window into the brain dysfunctions in schizophrenia. Many past sleep studies have reported abnormalities in both macro-sleep architecture (like increased awakenings) as well as micro-sleep-architecture (like spindle deficits) in patients with schizophrenia (PSZ). The present study attempts to replicate previous reports of macro- and micro-sleep-architectural abnormalities in schizophrenia. In addition, the study also examined sleep-stage changes and spindle-delta dynamics across sleep-cycles to provide further evidence in support of the dysfunctional thalamocortical mechanisms causing sleep instability and poor sleep maintenance associated with schizophrenia pathophysiology. MethodsWhole-night polysomnography was carried out among 45 PSZ and 39 age- and gender-matched healthy control subjects. Sleep-stage dynamics were assessed across sleep-cycles using a customized software algorithm. Spindle-delta dynamics across sleep-cycles were determined using neuroloop-gain analysis. ResultsPSZ showed macro-sleep architecture abnormalities such as prolonged sleeplessness, increased intermittent-awakenings, long sleep-onset latency, reduced non-rapid eye movement (NREM) stage 2 sleep, increased stage transitions, and poor sleep efficiency. They also showed reduced spindle density (sigma neuroloop-gain) but comparable slow wave density (delta neuroloop-gain) throughout the sleep. Sleep-cycle-wise analysis revealed transient features of sleep instability due to significantly increased intermittent awakenings especially in the first and third sleep-cycles, and unstable and recurrent stage transitions in both NREM (first sleep-cycle) and rapid eye movement (REM) sleep-periods (second sleep-cycle). Spindle deficits were persistent across the first three cycles and were positively correlated with sleep disruption during the subsequent REM sleep. ConclusionsIn addition to replicating previously reported sleep deficits in PSZ, the current study showed subtle deficits in NREM–REM alterations across whole-night polysomnography. These results point towards a possible maladaptive interplay between unstable thalamocortical networks, resulting in sleep-cycle-specific instability patterns associated with schizophrenia pathophysiology.

Reconsidering Tonotopic Maps in the Auditory Cortex and Lemniscal Auditory Thalamus in Mice.

The auditory thalamus and auditory cortex (AC) are pivotal structures in the central auditory system. However, the thalamocortical mechanisms of processing sounds are largely unknown. Investigation of this process benefits greatly from the use of mice because the mouse is a powerful animal model in which various experimental techniques, especially genetic tools, can be applied. However, the use of mice has been limited in auditory research, and thus even basic anatomical knowledge of the mouse central auditory system has not been sufficiently collected. Recently, optical imaging combined with morphological analyses has enabled the elucidation of detailed anatomical properties of the mouse auditory system. These techniques have uncovered fine AC maps with multiple frequency-organized regions, each of which receives point-to-point thalamocortical projections from different origins inside the lemniscal auditory thalamus, the ventral division of the medial geniculate body (MGv). This precise anatomy now provides a platform for physiological research. In this mini review article, we summarize these recent achievements that will facilitate physiological investigations in the mouse auditory system.

Layer 4 fast-spiking interneurons filter thalamocortical signals during active somatosensation.

We rely on movement to explore the environment, for example, by palpating an object. In somatosensory cortex, activity related to movement of digits or whiskers is suppressed, which could facilitate detection of touch. Movement-related suppression is generally assumed to involve corollary discharges. Here we uncovered a thalamocortical mechanism in which cortical fast-spiking interneurons, driven by sensory input, suppress movement-related activity in layer 4 (L4) excitatory neurons. In mice locating objects with their whiskers, neurons in the ventral posteromedial nucleus (VPM) fired in response to touch and whisker movement. Cortical L4 fast-spiking interneurons inherited these responses from VPM. In contrast, L4 excitatory neurons responded mainly to touch. Optogenetic experiments revealed that fast-spiking interneurons reduced movement-related spiking in excitatory neurons, enhancing selectivity for touch-related information during active tactile sensation. These observations suggest a fundamental computation performed by the thalamocortical circuit to accentuate salient tactile information.

Reinforcement learning in a bio-connectionist model based in the thalamo-cortical neural circuit

Abstract In a previous study, we presented a program to simulate a particular dynamic of the thalamo-cortical biological system. The method used was called bio-connectionism which linked the thalamo-cortical mechanism reproduced with animal perception. In this presentation, a reinforcement learning program is supported by this mechanism. In a game world designed to test the model developed, the agent is assigned to a character that must learn by trial and error from its own experience upon recognition of aversive and appetitive patterns. The results confirm, support and extend the notion of configuration, a term familiar with sparse coding principles. If, as it is documented, this mechanism observed in sensory areas can be thought as condition of perception, the brain areas taken together – each in its interaction with a respective sub-thalamic nucleus – are suspected to be considered as condition of cognition. We introduce some philosophical questions derived from the experimental results in the discussion section.

Putting theoretical dynamics into networks constructed from patient data: how do seizures start?

Idiopathic (genetic) generalised epilepsy (IGE) is assumed to have a complex genetic aetiology, and is characterised by generalised spike-wave (GSW) discharges on EEG. Rodent models of GSW implicate thalamocortical mechanisms. Human imaging with simultaneous EEG-fMRI shows an extended network of cortical and subcortical regions engaged during GSW discharges. Therefore it is possible that inherited characteristics of extended cortical–subcortical brain networks are a component of the mechanism of IGE. In theoretical work, we have shown that the tendency of a connected network of simulated brain regions to generate highly synchronised discharges is dependent on the topological structure of the network. We hypothesised that the topology of brain networks is abnormal in IGE, and that the abnormal topology predisposes to seizure onset. Therefore, we investigated functionally connected brain networks derived from EEG, in a group of patients with IGE, their unaffected relatives, and healthy controls. Our data showed that the topological structure of networks based on EEG data is abnormal in IGE and some of these abnormalities were also present in unaffected relatives. Furthermore, using a model to estimate the tendency for these networks to initiate seizures, we found elevated seizure tendency in patients. The implications of these findings will be discussed.