Thalamocortical Connections Research Articles

Deep brain stimulation induced normalization of the human functional connectome in Parkinson's disease.

Neuroimaging has seen a paradigm shift away from a formal description of local activity patterns towards studying distributed brain networks. The recently defined framework of the 'human connectome' enables global analysis of parts of the brain and their interconnections. Deep brain stimulation (DBS) is an invasive therapy for patients with severe movement disorders aiming to retune abnormal brain network activity by local high frequency stimulation of the basal ganglia. Beyond clinical utility, DBS represents a powerful research platform to study functional connectomics and the modulation of distributed brain networks in the human brain. We acquired resting-state functional MRI in 20 patients with Parkinson's disease with subthalamic DBS switched on and off. An age-matched control cohort of 15 subjects was acquired from an open data repository. DBS lead placement in the subthalamic nucleus was localized using a state-of-the art pipeline that involved brain shift correction, multispectral image registration and use of a precise subcortical atlas. Based on a realistic 3D model of the electrode and surrounding anatomy, the amount of local impact of DBS was estimated using a finite element method approach. On a global level, average connectivity increases and decreases throughout the brain were estimated by contrasting on and off DBS scans on a voxel-wise graph comprising eight thousand nodes. Local impact of DBS on the motor subthalamic nucleus explained half the variance in global connectivity increases within the motor network (R = 0.711, P < 0.001). Moreover, local impact of DBS on the motor subthalamic nucleus could explain the degree to how much voxel-wise average brain connectivity normalized towards healthy controls (R = 0.713, P < 0.001). Finally, a network-based statistics analysis revealed that DBS attenuated specific couplings known to be pathological in Parkinson's disease. Namely, coupling between motor thalamus and motor cortex was increased while striatal coupling with cerebellum, external pallidum and subthalamic nucleus was decreased by DBS. Our results show that resting state functional MRI may be acquired in DBS on and off conditions on clinical MRI hardware and that data are useful to gain additional insight into how DBS modulates the functional connectome of the human brain. We demonstrate that effective DBS increases overall connectivity in the motor network, normalizes the network profile towards healthy controls and specifically strengthens thalamo-cortical connectivity while reducing striatal control over basal ganglia and cerebellar structures.

Unstable wakefulness during resting-state fMRI and its associations with network connectivity and affective psychopathology in young adults

BackgroundDrifts between wakefulness and sleep are common during resting state functional MRI (rsfMRI). Among healthy adults, within-scanner sleep can impact functional connectivity of default mode (DMN), task-positive (TPN), and thalamo-cortical networks. Because dysfunctional arousal states (i.e., sleepiness, sleep disturbance) are common in affective disorders, individuals with affective psychopathology may be more prone to unstable wakefulness during rsfMRI, hampering the estimation of clinically meaningful functional connectivity biomarkers. MethodsA transdiagnostic sample of 150 young adults (68 psychologically distressed; 82 psychiatrically healthy) completed rsfMRI and reported whether they experienced within-scanner sleep. Symptom scales were reduced into depression/anxiety and mania proneness dimensions using principal component analysis. We evaluated associations between within-scanner sleep, clinical status, and functional connectivity of the DMN, TPN, and thalamus. ResultsWithin-scanner sleep during rsfMRI was reported by 44% of participants (n = 66) but was unrelated to psychiatric diagnoses or mood symptom severity (p-values > 0.05). Across all participants, self-reported within-scanner sleep was associated with connectivity signatures akin to objectively-assessed sleep, including lower within-DMN connectivity, lower DMN-TPN anti-correlation, and altered thalamo-cortical connectivity (p < 0.05, corrected). Among participants reporting sustained wakefulness (n = 84), depression/anxiety severity positively associated with averaged DMN-TPN connectivity and mania proneness negatively associated with averaged thalamus-DMN connectivity (p-values < 0.05). Both relationships were attenuated and became non-significant when participants reporting within-scanner sleep were included (p-values > 0.05). LimitationsSubjective report of within-scanner sleep. ConclusionsFindings implicate within-scanner sleep as a source of variance in network connectivity; careful monitoring and correction for within-scanner sleep may enhance our ability to characterize network signatures underlying affective psychopathology.

Feedforward Thalamocortical Connectivity Preserves Stimulus Timing Information in Sensory Pathways.

Reliable timing of cortical spikes in response to visual events is crucial in representing visual inputs to the brain. Spikes in the primary visual cortex (V1) need to occur at the same time within a repeated visual stimulus. Two classical mechanisms are employed by the cortex to enhance reliable timing. First, cortical neurons respond reliably to a restricted set of stimuli through their preference for certain patterns of membrane potential due to their intrinsic properties. Second, intracortical networking of excitatory and inhibitory neurons induces lateral inhibition that, through the timing and strength of IPSCs and EPSCs, produces sparse and reliably timed cortical neuron spike trains to be transmitted downstream. Here, we describe a third mechanism that, through preferential thalamocortical synaptic connectivity, enhances the trial-to-trial timing precision of cortical spikes in the presence of spike train variability within each trial that is introduced between LGN neurons in the retino-thalamic pathway. Applying experimentally recorded LGN spike trains from the anesthetized cat to a detailed model of a spiny stellate V1 neuron, we found that output spike timing precision improved with increasing numbers of convergent LGN inputs. The improvement was consistent with the predicted proportionality of [Formula: see text] for n LGN source neurons. We also found connectivity configurations that maximize reliability and that generate V1 cell output spike trains quantitatively similar to the experimental recordings. Our findings suggest a general principle, namely intra-trial variability among converging inputs, that increases stimulus response precision and is widely applicable to synaptically connected spiking neurons.SIGNIFICANCE STATEMENT The early visual pathway of the cat is favorable for studying the effects of trial-to-trial variability of synaptic inputs and intra-trial variability of thalamocortical connectivity on information transmission into the visual cortex. We have used a detailed model to show that there are preferred combinations of the number of thalamic afferents and the number of synapses per afferent that maximize the output reliability and spike-timing precision of cortical neurons. This provides additional insights into how synchrony in thalamic spike trains can reduce trial-to-trial variability to produce highly reliable reporting of sensory events to the cortex. The same principles may apply to other converging pathways where temporally jittered spike trains can reliably drive the downstream neuron and improve temporal precision.

Optochemogenetic Stimulation of Transplanted iPS-NPCs Enhances Neuronal Repair and Functional Recovery after Ischemic Stroke.

Cell transplantation therapy provides a regenerative strategy for neural repair. We tested the hypothesis that selective excitation of transplanted induced pluripotent stem cell-derived neural progenitor cells (iPS-NPCs) could recapitulate an activity-enriched microenvironment that confers regenerative benefits for the treatment of stroke. Mouse iPS-NPCs were transduced with a novel optochemogenetics fusion protein, luminopsin 3 (LMO3), which consisted of a bioluminescent luciferase, Gaussia luciferase, and an opsin, Volvox Channelrhodopsin 1. These LMO3-iPS-NPCs can be activated by either photostimulation using light or by the luciferase substrate coelenterazine (CTZ). In vitro stimulations of LMO3-iPS-NPCs increased expression of synapsin-1, postsynaptic density 95, brain derived neurotrophic factor (BDNF), and stromal cell-derived factor 1 and promoted neurite outgrowth. After transplantation into the ischemic cortex of mice, LMO3-iPS-NPCs differentiated into mature neurons. Synapse formation between implanted and host neurons was identified using immunogold electron microscopy and patch-clamp recordings. Stimulation of transplanted cells with daily intranasal administration of CTZ enhanced axonal myelination, synaptic transmission, improved thalamocortical connectivity, and functional recovery. Patch-clamp and multielectrode array recordings in brain slices showed that CTZ or light stimulation facilitated synaptic transmission and induced neuroplasticity mimicking the LTP of EPSPs. Stroke mice received the combined LMO3-iPS-NPC/CTZ treatment, but not cell or CTZ alone, showed enhanced neural network connections in the peri-infarct region, promoted optimal functional recoveries after stroke in male and female, young and aged mice. Thus, excitation of transplanted cells via the noninvasive optochemogenetics treatment provides a novel integrative cell therapy with comprehensive regenerative benefits after stroke.SIGNIFICANCE STATEMENT Neural network reconnection is critical for repairing damaged brain. Strategies that promote this repair are expected to improve functional outcomes. This study pioneers the generation and application of an optochemogenetics approach in stem cell transplantation therapy after stroke for optimal neural repair and functional recovery. Using induced pluripotent stem cell-derived neural progenitor cells (iPS-NPCs) expressing the novel optochemogenetic probe luminopsin (LMO3), and intranasally delivered luciferase substrate coelenterazine, we show enhanced regenerative properties of LMO3-iPS-NPCs in vitro and after transplantation into the ischemic brain of different genders and ages. The noninvasive repeated coelenterazine stimulation of transplanted cells is feasible for clinical applications. The synergetic effects of the combinatorial cell therapy may have significant impacts on regenerative approach for treatments of CNS injuries.

Propofol-induced loss of consciousness is associated with a decrease in thalamocortical connectivity in humans

Although the molecular effects of many anaesthetics have been well characterized, a network-level explanation for how these changes lead to loss of consciousness remains unclear. Studies using electroencephalography have characterized changes in neural oscillations in the cortex at specific frequency bands during propofol-induced anaesthesia and modelling work suggests these changes result from changes in thalamocortical functional connectivity. However, it is unclear if the neurophysiological changes seen at the cortex are due to enhanced or disrupted thalamocortical communication. Direct recordings from these sites during anaesthesia that could be used to confirm such models are rare. We recorded local field potentials from the ventral intermediate nucleus of the thalamus and electrocorticography signals from the ipsilateral sensorimotor cortex in 10 patients undergoing deep brain stimulation surgery. Signals were acquired during induction of propofol anaesthesia while subjects were resting. After confirming direct structural connectivity between the thalamus and the cortical recording site, we investigated propofol-associated changes in thalamic and cortical local power as well as thalamocortical functional connectivity, as measured with coherence, debiased weighted phase lag index, and phase amplitude coupling. Propofol anaesthesia resulted in local power increases at α frequencies (8-12 Hz) across both thalamic and cortical areas. At sensorimotor cortices, there was a broadband power increase (12-100 Hz), while the power of this same broad frequency band was suppressed within the thalamus. Despite the increase in local α power both within the thalamus and cortex, thalamocortical coherence and debiased weighted phase lag index in the α/low β frequencies (8-16 Hz, which was present in the awake state) significantly decreased with propofol administration (P < 0.05, two group test of coherence). Likewise, propofol administration resulted in decreased phase amplitude coupling between the phase of α/low β in the thalamus and the amplitude of broadband gamma (50-200 Hz) in the cortex (P = 0.031, Wilcoxon signed-rank test). We also report phase amplitude coupling between the phase of slow wave oscillations (0.1-1 Hz) and amplitude of broadband frequencies (8-200 Hz) within the cortex and across thalamocortical connections, during anaesthesia, both following a peak-max pattern. While confirming α-power increases with propofol administration both in thalamus and cortex, we observed decreased thalamocortical connectivity, contradicting models that suggest increasing cortical low frequency power is necessarily related to increased thalamocortical coherence but in support of the theory that propofol-induced loss of consciousness is associated with disrupted thalamocortical communication.

Abnormal Thalamic Functional Connectivity During Light Non–Rapid Eye Movement Sleep in Children With Primary Nocturnal Enuresis

To investigate abnormalities of thalamocortical and intrathalamic functional connectivity (FC) in children with primary nocturnal enuresis (PNE) during light non-rapid eye movement (NREM) sleep using a simultaneous electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) method. Polysomnographic and EEG-fMRI data were obtained during sleep from 61 children with PNE (age 10.2 ± 1.7 years, 59% boys) and 61 age-matched controls (age 10.1 ± 1.4 years, 54% boys). All subjects first participated in one overnight video-polysomnographic study. Total sleep time, percentage of total sleep time in each sleep stage, arousal index, and awakening index were calculated. Simultaneous EEG-fMRI studies were then performed using a 3T MRI system with a 32-channel MRI-compatible EEG system. Visual scoring of EEG data permitted sleep staging. Thalamocortical and intrathalamic FCs in the waking state and at different stages of light sleep were calculated and compared. Children with PNE had a higher percentage of total sleep time in light sleep and a higher arousal index compared with controls. Abnormal thalamocortical FCs were detected in the lateral prefrontal cortex, medial prefrontal cortex, and inferior parietal lobule during light NREM sleep. Abnormal intrathalamic FCs were also detected during light NREM sleep among the motor, occipital, prefrontal, and temporal subdivisions of the thalamus. Abnormal prefrontal and parietal thalamocortical FCs, accompanied by abnormal intrathalamic FCs among the motor, occipital, prefrontal, and temporal subdivision of thalamus during light NREM sleep, may be related to abnormal sleep and enuresis in children with PNE.

Brain map of touch sensation

Neurodevelopment The brain's somatosensory cortex contains a topographical map that reflects touch sensation inputs. During embryonic development, axons from the midbrain thalamus build columnar connections to the cortex in the absence of sensory input. Working in mice, Anton-Bolanos et al. found that these thalamocortical connections are responsible for organizing the somatosensory cortex (see the Perspective by Tiriac and Feller). Organization of the map in the cortex depends on spontaneous calcium waves in the embryonic thalamus. Thus, the somatosensory map is sketched out before actual sensory input begins to refine the details. Science , this issue p. [987][1]; see also p. [933][2] [1]: /lookup/doi/10.1126/science.aav7617 [2]: /lookup/doi/10.1126/science.aax8048

We have to find a way – growth and guidance of thalamocortical axons

The thalamus is a major part of the diencephalon and a hub for integrating sensory, motor and emotional information. Thalamocortical neuronal loops are involved in processing of sensory stimuli, directing attention, regulating the level of conscious awareness and selecting behavioural responses. The establishment of topographic thalamo-cortical connections is critical for brain performance, and their dysfunctions can contribute to the development of mental disorders. Thalamic axon guidance is regulated by the expression of molecular cues along the way to the cortex. In this review we outline the guiding process from the early growth of thalamic axons to their topographic targeting to specific cortical areas.

Differential Patterns of Visual Sensory Alteration Underlying Face Emotion Recognition Impairment and Motion Perception Deficits in Schizophrenia and Autism Spectrum Disorder

BackgroundImpaired face emotion recognition (FER) and abnormal motion processing are core features in schizophrenia (SZ) and autism spectrum disorder (ASD) that have been linked to atypical activity within the visual cortex. Despite overlaps, only a few studies have directly explored convergent versus divergent neural mechanisms of altered visual processing in ASD and SZ. We employed a multimodal imaging approach to evaluate FER and motion perception in relation to functioning of subcortical and cortical visual regions. MethodsSubjects were 20 high-functioning adults with ASD, 19 patients with SZ, and 17 control participants. Behavioral measures of coherent motion sensitivity and FER along with electrophysiological and functional magnetic resonance imaging measures of visual pattern and motion processing were obtained. Resting-state functional magnetic resonance imaging was used to assess the relationship between corticocortical and thalamocortical connectivity and atypical visual processing. ResultsSZ and ASD participants had intercorrelated deficits in FER and motion sensitivity. In both groups, reduced motion sensitivity was associated with reduced functional magnetic resonance imaging activation in the occipitotemporal cortex and lower delta-band electroencephalogram power. In ASD, FER deficits correlated with hyperactivation of dorsal stream regions and increased evoked theta power. Activation of the pulvinar correlated with abnormal alpha-band modulation in SZ and ASD with under- and overmodulation, respectively, predicting increased clinical symptoms in both groups. ConclusionsSZ and ASD participants showed equivalent deficits in FER and motion sensitivity but markedly different profiles of physiological dysfunction. The specific pattern of deficits observed in each group may help guide development of treatments designed to downregulate versus upregulate visual processing within the respective clinical groups.

Integrate-and-fire network model of activity propagation from thalamus to cortex

The thalamus plays a crucial role in modulating the cortical activity underlying sensory and cognitive processes. In particular, recent experimental findings highlighted that the thalamus does not merely act as a binary gate for sensory stimuli, but rather participates to the processing of sensory information. Clarifying such thalamic influence on cortical dynamics is also important as the thalamus is the target of therapies such as DBS for Tourette patients. In this perspective, various computational models have been proposed in the last decades. However, a detailed description of the propagation of thalamic activity to the cortex is missing. Here we present a simple computational model of thalamocortical connectivity accounting for the propagation of activity from the thalamus to the cortex. The model includes both the single-neuron scale and the mesoscopic level of Local Field Potential (LFP) signals. Numerical simulations at both levels reproduce typical thalamocortical dynamics which are consistent with experimental measurements and robust to parameters changes. In particular, our model correctly reproduces locally generated rhythms as spindle oscillations in the thalamus and gamma oscillations in the cortex. Our model paves the way to deeper investigations of the thalamic influence on cortical dynamics, with and without sensory inputs or therapeutic electrical stimulation.

Plasticity of neonatal neuronal networks in very premature infants: Source localization of temporal theta activity, the first endogenous neural biomarker, in temporoparietal areas

Background Temporal theta slow-wave activity (TTA-SW) in premature infants is a specific signature of the early development of temporal networks, as it is observed at the turning point between nonsensory driven spontaneous local processing and cortical network functioning. Previous studies have demonstrated that preterms from 28 weeks of gestational age (wGA) are able to discriminate phonemes and voice, supporting the idea of a prior genetic structural or activity-dependent fingerprint that would prepare the auditory network to compute auditory information at the onset of thalamocortical connectivity. Objectives To specify the role in development and the specific location of TTA-SW. Methods We recorded TTA-SW in 26–32 wGA preterms. The rate of TTA-SW in response to click stimuli was evaluated using low-density EEG in 30 preterms. The sources of TTA-SW were localized by high-density EEG using different tissues conductivities, head models and mathematical models. Results We observed that TTA-SW is not sensory driven. Regardless of age, conductivities, head models and mathematical models, sources of TTA-SW were located adjacent to auditory and temporal junction areas. These sources become situated closer to the surface during development. Conclusion TTA-SW corresponds to spontaneous transient endogenous activities independent of sensory information at this period, which might participate in the implementation of auditory, language, memory, attention and or social cognition and represents a general interaction between the subplate and the cortical plate.

P09-F Anterior EEG slowing in Dementia with Lewy Bodies: A multicenter European cohort study

Background EEG slowing with pre-alpha dominant frequency in posterior derivations is a supportive biomarker for Dementia with Lewy Bodies diagnosis, with high predictive value for the differential diagnosis with Alzheimer’s Disease. The appearance of a pre-alpha rhythm is considered to be linked to a dysfunctional thalamo-cortical connection. We hypothesize that the intra-subject evaluation would give information on possible different involvement of anterior and posterior cortical areas in Dementia with Lewy Bodies. Objectives Our aim was to analyse the anterior-posterior scalp distribution of dominant frequencies with an intra-subject evaluation in a dementia with Lewy bodies patient group. Methods We quantitatively analyzed EEGs of 122 patients from 5 Centers of the European dementia with Lewy bodies Consortium. EEG spectra values, divided into delta, theta, pre-alpha, alpha frequency bands were described by dominant frequency, dominant frequency variability, frequency prevalence. Results Dominant frequency in anterior derivations was lower than in posterior derivations (p = 2 · 10–4). Dominant frequency variability, frequency prevalence in delta and theta was higher in anterior derivations (3 · 10–7; 1 · 10–16; 1 · 10–5). As a consequence, frequency prevalence in pre-alpha and alpha was lower in anterior than posterior derivations (4 · 10–3; 1 · 10–7), due to the prevalence of delta/theta in anterior derivations. In 11% of patients, pre-alpha was dominant in anterior leads while alpha rhythm was still dominant in posterior derivations. Conclusions EEG slowing was more severe in anterior derivations. A future longitudinal study should address the possibility that the anterior EEG abnormalities appear earlier in the disease course.

Abnormal thalamocortical network dynamics in migraine.

To investigate the dynamic functional connectivity of thalamocortical networks in interictal migraine patients and whether clinical features are associated with abnormal connectivity. We investigated dynamic functional network connectivity (dFNC) of the migraine brain in 89 interictal migraine patients and 70 healthy controls. We focused on the temporal properties of thalamocortical connectivity using sliding window cross-correlation, clustering state analysis, and graph-theory methods. Relationships between clinical symptoms and abnormal dFNC were evaluated using a multivariate linear regression model. Five dFNC brain states were identified to characterize and compare dynamic functional connectivity patterns. We demonstrated that migraineurs spent more time in a strongly interconnected between-network state, but they spent less time in a sparsely connected state. Interestingly, we found that abnormal posterior thalamus (pulvinar nucleus) dFNC with the visual cortex and the precuneus were significantly correlated with headache frequency of migraine. Further topologic measures revealed that migraineurs had significantly lower efficiency of information transfer in both global and local dFNC. Our results demonstrated a transient pathologic state with atypical thalamocortical connectivity in migraineurs and extended current findings regarding abnormal thalamocortical networks and dysrhythmia in migraine.

Increased Thalamocortical Connectivity in Schizophrenia Correlates With Sleep Spindle Deficits: Evidence for a Common Pathophysiology

BackgroundConverging evidence implicates abnormal thalamocortical interactions in the pathophysiology of schizophrenia. This evidence includes consistent findings of increased resting-state functional connectivity of the thalamus with somatosensory and motor cortex during wake and reduced spindle activity during sleep. We hypothesized that these abnormalities would be correlated, reflecting a common mechanism: reduced inhibition of thalamocortical neurons by the thalamic reticular nucleus (TRN). The TRN is the major inhibitory nucleus of the thalamus and is abnormal in schizophrenia. Reduced TRN inhibition would be expected to lead to increased and less filtered thalamic relay of sensory and motor information to the cortex during wake and reduced burst firing necessary for spindle initiation during sleep. MethodsOvernight polysomnography and resting-state functional connectivity magnetic resonance imaging were performed in 26 outpatients with schizophrenia and 30 demographically matched healthy individuals. We examined the relations of sleep spindle density during stage 2 non–rapid eye movement sleep with connectivity of the thalamus to the cortex during wakeful rest. ResultsAs in prior studies, patients with schizophrenia exhibited increased functional connectivity of the thalamus with bilateral somatosensory and motor cortex and reduced sleep spindle density. Spindle density inversely correlated with thalamocortical connectivity, including in somotosensory and motor cortex, regardless of diagnosis. ConclusionsThese findings link two biomarkers of schizophrenia—the sleep spindle density deficit and abnormally increased thalamocortical functional connectivity—and point to deficient TRN inhibition as a plausible mechanism. If TRN-mediated thalamocortical dysfunction increases risk for schizophrenia and contributes to its manifestations, understanding its mechanism could guide the development of targeted interventions.

T200. Abnormal Thalamocortical Functional Connectivity and Sensory Gating Deficits in Psychotic Disorders: Are These Two Biomarkers Related?

T200. Abnormal Thalamocortical Functional Connectivity and Sensory Gating Deficits in Psychotic Disorders: Are These Two Biomarkers Related?

Thalamocortical Connection Topography Mapping in Human by Co-clustering

Connection topography mapping is crucial for understanding how information is processed in the brain, which is an essential precursor for revealing principles of brain organization. However, existing connectopic mapping methods are dependent on prior knowledge, or not completely driven by data. Accordingly, the constructed connection topographies by these methods are biased towards hypotheses, or deviate from data. For these challenges, we propose a novel co-clustering based method for connection topography mapping in a fully data-driven manner. The proposed method aims to construct the connection topography between two ROIs of a certain neural circuit in consideration by leveraging the power of co-clustering. More precisely, the proposed method parcellates one ROI into subregions and identified their respective connected subregions from the other ROI simultaneously. The effectiveness of our method was validated on the mapping of the human thalamocortical system for 57 subjects based on their resting state fMRI data. The validation experiment results have demonstrated that our method can construct neurobiologically meaningful thalamocortical connection topography. Compared with existing methods, our method yields more meaningful and interpretable connection topography.

An Activation Likelihood Estimate Meta-analysis of Thalamocortical Dysconnectivity in Psychosis

BackgroundThalamocortical dysconnectivity is hypothesized to underlie the pathophysiology of psychotic disorders, including schizophrenia and bipolar disorder, and individuals at clinical high risk. Numerous studies have examined connectivity networks seeding from the thalamus during rest, revealing a pattern of thalamo-fronto-cerebellar hypoconnectivity and thalamosensory hyperconnectivity. However, given variability in these networks, as well as their relationships with clinical and cognitive symptoms, thalamocortical connectivity’s status as a biomarker and treatment target for psychotic disorders remains unclear. MethodsA literature search was performed to identify thalamic seed-based connectivity studies conducted in patients with psychotic disorders. Activation likelihood estimate analysis examined the reported coordinates for hypoconnectivity (healthy control participants > patients with psychosis) and hyperconnectivity (patients with psychosis > healthy control participants). The relationship between hypoconnectivity and hyperconnectivity, as well as their relationships with clinical and cognitive measures, was meta-analyzed. ResultsEach activation likelihood estimate included 20 experiments (from 17 publications). Thalamocortical hypoconnectivity was observed in middle frontal, cingulate, and thalamic regions, while hyperconnectivity was observed in motor, somatosensory, temporal, occipital, and insular cortical regions. Meta-analysis of the studies reporting correlations between hypo- and hyperconnectivity showed a strong negative relationship. Meta-analysis of studies reporting correlations between hyperconnectivity and symptoms showed small but significant positive relationships. ConclusionsActivation likelihood estimates of thalamocortical hypoconnectivity revealed a network of prefrontal and thalamic regions, while hyperconnections identified sensory areas. The strong negative relationship between these thalamocortical deflections suggests that they arrive from a common mechanism and may account for aspects of psychosis. These findings identify reliable thalamocortical networks that may guide future studies and serve as crucial treatment targets for psychotic disorders.

The Integrative Function of Silent Synapses on Subplate Neurons in Cortical Development and Dysfunction.

The thalamocortical circuit is of central importance in relaying information to the cortex. In development, subplate neurons (SPNs) form an integral part of the thalamocortical pathway. These early born cortical neurons are the first neurons to receive thalamic inputs and excite neurons in the cortical plate. This feed-forward circuit topology of SPNs supports the role of SPNs in shaping the formation and plasticity of thalamocortical connections. Recently it has been shown that SPNs also receive inputs from the developing cortical plate and project to the thalamus. The cortical inputs to SPNs in early ages are mediated by N-methyl-D-aspartate (NMDA)-receptor only containing synapses while at later ages α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-receptors are present. Thus, SPNs perform a changing integrative function over development. NMDA-receptor only synapses are crucially influenced by the resting potential and thus insults to the developing brain that causes depolarizations, e.g., hypoxia, can influence the integrative function of SPNs. Since such insults in humans cause symptoms of neurodevelopmental disorders, NMDA-receptor only synapses on SPNs might provide a crucial link between early injuries and later circuit dysfunction. We thus here review subplate associated circuits, their changing functions, and discuss possible roles in development and disease.

0065 Sleep and Wake Biomarkers of Psychotic Disorders and Their Relations with Thalamocortical Connectivity

0065 Sleep and Wake Biomarkers of Psychotic Disorders and Their Relations with Thalamocortical Connectivity

0066 Disrupted Thalamocortical Connectivity following Mild Traumatic Brain Injury: Associations with Daytime Sleepiness

0066 Disrupted Thalamocortical Connectivity following Mild Traumatic Brain Injury: Associations with Daytime Sleepiness