Temporal and Potential Predictive Relationships between Sleep Spindle Density and Spike-and-Wave Discharges.

Spike-and-wave discharges (SWDs) and sleep spindles are characteristic electroencephalographic (EEG) hallmarks of absence seizures and nonrapid eye movement sleep, respectively. They are commonly generated by the cortico-thalamo-cortical network including the thalamic reticular nucleus (TRN). It has been reported that SWD development is accompanied by a decrease in sleep spindle density in absence seizure patients and animal models. However, whether the decrease in sleep spindle density precedes, coincides with, or follows, the SWD development remains unknown. To clarify this, we exploited Pvalb-tetracycline transactivator (tTA)::tetO-ArchT (PV-ArchT) double-transgenic mouse, which can induce an absence seizure phenotype in a time-controllable manner by expressing ArchT in PV neurons of the TRN. In these mice, EEG recordings demonstrated that a decrease in sleep spindle density occurred 1 week before the onset of typical SWDs, with the expression of ArchT. To confirm such temporal relationship observed in these genetic model mice, we used a gamma-butyrolactone (GBL) pharmacological model of SWDs. Prior to GBL administration, we administered caffeine to wild-type mice for 3 consecutive days to induce a decrease in sleep spindle density. We then administered low-dose GBL, which cannot induce SWDs in normally conditioned mice but led to the occurrence of SWDs in caffeine-conditioned mice. These findings indicate a temporal relationship in which the decrease in sleep spindle density consistently precedes SWD development. Furthermore, the decrease in sleep spindle activity may have a role in facilitating the development of SWDs. Our findings suggest that sleep spindle reductions could serve as early indicators of seizure susceptibility.

Ventral frontostriatal circuitry mediates the computation of reinforcement from symbolic gains and losses.

Reinforcement learning (RL), particularly in primates, is often driven by symbolic outcomes. However, it is usually studied with primary reinforcers. To examine the neural mechanisms underlying learning from symbolic outcomes, we trained monkeys on a task in which they learned to choose options that led to gains of tokens and avoid choosing options that led to losses of tokens. We then recorded simultaneously from the orbitofrontal cortex (OFC), ventral striatum (VS), amygdala (AMY), and mediodorsal thalamus (MDt). We found that the OFC played a dominant role in coding token outcomes and token prediction errors. The other areas contributed complementary functions, with the VS coding appetitive outcomes and the AMY coding the salience of outcomes. The MDt coded actions and relayed information about tokens between the OFC and VS. Thus, the OFC leads the processing of symbolic RL in the ventral frontostriatal circuitry.

Functional dysconnectivity and microstructural impairment of the cortico-thalamo-cortical network in women with rheumatoid arthritis: A multimodal MRI study.

Background: Cognitive deficits are common in rheumatoid arthritis (RA) patients, but the mechanisms remain unclear. We investigated the effective connectivity and structural alterations of the core brain regions in RA patients with cognitive impairment. Methods: Twenty-four female patients with RA and twenty-four healthy controls were enrolled. We analyzed abnormal brain activity patterns using functional MRI during the Iowa gambling task (IGT) and core regions effective connectivity using dynamic causal model (DCM). Structural alterations of white matter volume (WMV) and gray matter volume (GMV) were detected using voxel-based morphometry (VBM). Results: RA patients showed altered activation patterns of the cortico-thalamo-cortical network, increased coupling strength from the left ventromedial prefrontal gyrus to the anterior cingulate cortex (ACC), the ACC to the right thalamus, and decreased connectivity from the thalamus to left hippocampus. VBM structural analysis showed increased GMV in the bilateral orbital frontal gyrus, bilateral hippocampus and right putamen, and reduced GMV and WMV in the bilateral thalamus in RA patients. Right thalamic GMV and WMV were positively correlated with the right thalamus-to-hippocampus connective strength. Additionally, the bold signal, GMV and WMV of the right thalamus were positively correlated with cognitive performance (IGT score) in RA patients. Conclusion: Results suggest a structural and functional deficiency in the cortico-thalamo-cortical network, which is characterized by increased ACC-to-thalamus strength and reduced thalamus-to-hippocampus coupling in RA patients. The cognitive dysfunction may be the result of compensatory measures against imbalanced cortico-thalamic-cortical coupling.

Causal oscillations in the visual thalamo-cortical network in sustained attention in ferrets.

Sustained visual attention allows us to process and react to unpredictable, behaviorally relevant sensory input. Sustained attention engages communication between the higher-order visual thalamus and its connected cortical regions. However, it remains unclear whether there is a causal relationship between oscillatory circuit dynamics and attentional behavior in these thalamo-cortical circuits. By using rhythmic optogenetic stimulation in the ferret, we provide causal evidence that higher-order visual thalamus coordinates thalamo-cortical and cortico-cortical functional connectivity during sustained attention via spike-field phase locking. Increasing theta but not alpha power in the thalamus improved accuracy and reduced omission rates in a sustained attention task. Further, the enhancement of effective connectivity by stimulation was correlated with improved behavioral performance. Our work demonstrates a potential circuit-level causal mechanism for how the higher-order visual thalamus modulates cortical communication through rhythmic synchronization during sustained attention.

Electrophysiological insights into deep brain stimulation of the network disorder dystonia.

Deep brain stimulation (DBS), a treatment for modulating the abnormal central neuronal circuitry, has become the standard of care nowadays and is sometimes the only option to reduce symptoms of movement disorders such as dystonia. However, on the one hand, there are still open questions regarding the pathomechanisms of dystonia and, on the other hand, the mechanisms of DBS on neuronal circuitry. That lack of knowledge limits the therapeutic effect and makes it hard to predict the outcome of DBS for individual dystonia patients. Finding electrophysiological biomarkers seems to be a promising option to enable adapted individualised DBS treatment. However, biomarker search studies cannot be conducted on patients on a large scale and experimental approaches with animal models of dystonia are needed. In this review, physiological findings of deep brain stimulation studies in humans and animal models of dystonia are summarised and the current pathophysiological concepts of dystonia are discussed.

mGlu3 Metabotropic Glutamate Receptors as a Target for the Treatment of Absence Epilepsy: Preclinical and Human Genetics Data.

BACKGROUND: Previous studies suggest that different metabotropic glutamate (mGlu) receptor subtypes are potential drug targets for treating absence epilepsy. However, no information is available on mGlu3 receptors. OBJECTIVE: To examine whether (i) changes of mGlu3 receptor expression/signaling are found in the somatosensory cortex and thalamus of WAG/Rij rats developing spontaneous absence seizures; (ii) selective activation of mGlu3 receptors with LY2794193 affects the number and duration of spikewave discharges (SWDs) in WAG/Rij rats; and (iii) a genetic variant of GRM3 (encoding the mGlu3 receptor) is associated with absence epilepsy. METHODS: Animals: immunoblot analysis of mGlu3 receptors, GAT-1, GLAST, and GLT-1; realtime PCR analysis of mGlu3 mRNA levels; assessment of mGlu3 receptor signaling; EEG analysis of SWDs; assessment of depressive-like behavior. Humans: search for GRM3 and GRM5 missense variants in 196 patients with absence epilepsy or other Idiopathic Generalized Epilepsy (IGE)/ Genetic Generalized Epilepsy (GGE) and 125,748 controls. RESULTS: mGlu3 protein levels and mGlu3-mediated inhibition of cAMP formation were reduced in the thalamus and somatosensory cortex of pre-symptomatic (25-27 days old) and symptomatic (6-7 months old) WAG/Rij rats compared to age-matched controls. Treatment with LY2794193 (1 or 10 mg/kg, i.p.) reduced absence seizures and depressive-like behavior in WAG/Rij rats. LY2794193 also enhanced GAT1, GLAST, and GLT-1 protein levels in the thalamus and somatosensory cortex. GRM3 and GRM5 gene variants did not differ between epileptic patients and controls. CONCLUSION: We suggest that mGlu3 receptors modulate the activity of the cortico-thalamo-cortical circuit underlying SWDs and that selective mGlu3 receptor agonists are promising candidate drugs for absence epilepsy treatment.

An Update on the Diagnosis and Management of Tic Disorders.

Tic disorders (TDs) are a group of common neuropsychiatric disorders of childhood and adolescence. TDs may impact the physical, emotional, and social well-being of the affected person. In this review, we present an update on the clinical manifestations, pathophysiology, diagnosis, and treatment of TDs. We searched the PubMed database for articles on tics and Tourette syndrome. More than 400 articles were reviewed, of which 141 are included in this review. TDs are more prevalent in children than in adults and in males than in females. It may result from a complex interaction between various genetic, environmental, and immunological factors. Dysregulation in the cortico-striato-pallido-thalamo-cortical network is the most plausible pathophysiology resulting in tics. TD is a clinical diagnosis based on clinical features and findings on neurological examination, especially the identification of tic phenomenology. In addition to tics, TD patients may have sensory features, including premonitory urge; enhanced and persistent sensitivity to non-noxious external or internal stimuli; and behavioral manifestations, including attention deficit hyperactivity disorders, obsessive-compulsive disorders, and autism spectrum disorders. Clinical findings of hyperkinetic movements that usually mimic tics have been compared and contrasted with those of TD. Patients with TD may not require specific treatment if tics are not distressing. Psychoeducation and supportive therapy can help reduce tics when combined with medication. Dispelling myths and promoting acceptance are important to improve patient outcomes. Using European, Canadian, and American guidelines, the treatment of TD, including behavioral therapy, medical therapy, and emerging/experimental therapy, has been discussed.

Thalamo-cortical network is associated with harmaline-induced tremor in rodent model.

Essential tremor (ET) is the most frequent form of pathologic tremor and one of the most common adult-onset neurologic impairments. However, underlying mechanisms by which structural alterations within the tremor circuit generate the pathological state and how rhythmic neuronal activities propagate and drive tremor remains unclear. Harmaline (HA)-induced tremor model has been most frequently utilized animal model for ET studies, however, there is still a dearth of knowledge over the degree to whether HA-induced tremor mimics the actual underlying pathophysiology of ET, particularly the involvement of thalamo-cortical region. In this study, we investigated the electrophysiological response of the motor circuit including the ventrolateral thalamus (vlTh) and the primary motor cortex (M1), and the modulatory effect of thalamic deep brain stimulation (DBS) using a rat HA-induced tremor model. We found that the theta and high-frequency oscillation (HFO) band power significantly increased after HA administration in both vlTh and M1, and the activity was modulated by the tremor suppression drug (propranolol) and the thalamic DBS. The theta band phase synchronization between the vlTh and M1 was significantly enhanced during the HA-induced tremor, and the transition of cross-frequency coupling in vlTh was found to be associated with the state of HA-induced tremor. Our findings support that the HA tremor could be useful as a valid preclinical model of ET in the context of thalamo-cortical neural network interaction.

Aberrant functional connectivity of neural circuits associated with thought-action fusion in patients with obsessive-compulsive disorder.

BACKGROUND: Cognitive theories of obsessive-compulsive disorder (OCD) stress the importance of dysfunctional beliefs in the development and maintenance of the disorder. However, a neurobiological understanding of these cognitive models, including thought-action fusion (TAF), is surprisingly lacking. Thus, this functional magnetic resonance imaging study aimed to investigate whether altered functional connectivity (FC) is associated with the TAF paradigm in OCD patients. METHODS: Forty-one OCD patients and 47 healthy controls (HCs) participated in a functional magnetic resonance imaging study using a TAF task, in which they were asked to read the name of a close or a neutral person in association with positive and negative statements. RESULTS: The conventional TAF condition (negative statements/close person) induced significant FC between the regions of interest (ROIs) identified using multivoxel pattern analysis and the visual association areas, default mode network subregions, affective processing, and several subcortical regions in both groups. Notably, sparser FC was observed in OCD patients. Further analysis confined to the cortico-striato-thalamo-cortical (CSTC) and affective networks demonstrated that OCD patients exhibited reduced ROI FC with affective regions and greater ROI FC with CSTC components in the TAF condition compared to HCs. Within the OCD patients, middle cingulate cortex-insula FC was correlated with TAF and responsibility scores. CONCLUSIONS: Our TAF paradigm revealed altered context-dependent engagement of the CSTC and affective networks in OCD patients. These findings suggest that the neurobiology of cognitive models corresponds to current neuroanatomical models of OCD. Further, they elucidate the underlying neurobiological mechanisms of OCD at the circuit-based level.

Modulatory effect of continuous theta burst stimulation in patients with essential tremor.

INTRODUCTION: We aimed to study the cortical and intracortical functions in patients of ET using transcranial magnetic stimulation (TMS) and to evaluate the effect of continuous theta burst stimulation (cTBS) on the tremor characteristics. METHODS: Ten ET and 20 healthy controls were included in the study. All the participants were evaluated with TMS with recording of resting motor threshold (RMT), central motor conduction time, contralateral silent period (cSP), short interval intracortical inhibition (SICI) and intracortical facilitation (ICF). Subsequently only ET patients underwent cTBS of the motor cortex (M1) followed by repeat TMS. RESULTS: The mean age of the patients (46.5 ± 17.2 years) was comparable to healthy controls (55.4 ± 9.2 years; p = 0.16). There was a non-significant increase in RMT in ET patients (44 ± 12.5%) when compared to healthy controls (40.9 ± 6.9%; p = 0.48). There was a significant reduction of cSP in the ET group (102.03 ± 15.26 msec) compared to healthy controls (116.1 ± 15.2, p = 0.03). In addition, a significant reduction in ICF was observed in ET patients (0.9 ± 0.7) compared to healthy controls (1.8 ± 0.8, p = 0.01). Following cTBS there was a significant reduction in the tremor scores [FTMRS (Pre-cTBS: 29.3 ± 18.7, Post-cTBS: 25.3 ± 16.8; p < 0.001) and TETRAS (pre-cTBS: 34.4 ± 16.2, post-cTBS: 29.8 ± 12.1; p = 0.01)] and improvement (increase) of the duration of cSP (pre-cTBS: 102.03 ± 15.3 msec., post-cTBS: 119.4 ± 12.03 msec; p = 0.05). CONCLUSIONS: Patients with ET have GABAergic and glutaminergic dysfunction as demonstrated by reduced cSP and ICF. However, only the cSP improved following cTBS of M1 region, with a corresponding improvement of tremor severity suggesting the effect of cTBS on the cerebello-thalamo-cortical network.

The Orexin System: A Potential Player in the Pathophysiology of Absence Epilepsy.

BACKGROUND: Absence epilepsy is characterized by the presence of spike-and-wave discharges (SWDs) at the EEG generated within the cortico-thalamo-cortical circuit. The molecular mechanisms involved in the pathophysiology of absence epilepsy are only partially known. WAG/Rij rats older than 2-3 months develop spontaneous SWDs, and they are sensitive to anti- absence medications. Hence, WAG/Rij rats are extensively used as a model for absence epilepsy with predictive validity. OBJECTIVE: The aim of the study was to examine the possibility that the orexin system, which supports the wake status in experimental animals and humans, plays a role in the pathophysiology of absence seizures. METHODS: The perspective grounds its method from recent literature along with measurements of orexin receptor type-1 (OX1) protein levels in the thalamus and somatosensory cortex of WAG/Rij rats and non-epileptic Wistar control rats at two ages (25 days and 6-7 months). OX1 protein levels were measured by immunoblotting. RESULTS: The analysis of the current literature suggests that the orexin system might be involved in the pathophysiology of absence epilepsy and might be targeted by therapeutic intervention. Experimental data are in line with this hypothesis, showing that OX1 protein levels were reduced in the thalamus and somatosensory cortex of symptomatic WAG/Rij rats (6-7 months of age) with respect to non-epileptic controls, whereas these differences were not seen in pre-symptomatic, 25 days-old WAG/Rij rats. CONCLUSION: This perspective might pave the way for future studies on the involvement of the orexinergic system in the pathophysiology of SWDs associated with absence epilepsy and its comorbidities.

Theta burst stimulation for the treatment of obsessive-compulsive disorder: a pilot study.

A non-negligible part of patients with obsessive-compulsive disorder (OCD) experiences inadequate response to pharmacological and cognitive therapies. Therefore, new approaches are required to overcome this problem. The present pilot study estimates the capacity of theta burst stimulation (TBS) in reducing OCD symptoms, also focusing on the neurophysiological basis of TBS aftereffects. Ten patients with OCD who were unsatisfactorily responsive to the pharmacological and neuropsychological treatment, participated to the present randomized crossover pilot study, in which they were subjected to a real or sham intermittent TBS (iTBS) paradigm over the left dorsolateral prefrontal cortex (L-DLPFC) as add-on treatment. They were randomly assigned to a real or sham iTBS in a 1:1 allocation ratio. Patients received the TBS treatment every morning, 5 days a week for 1 month, and were clinically and electrophysiologically evaluated (EEG phase synchronization and coherence) before, immediately after (T0), and one (T1), three (T3) and six (T6) months after the end of the TBS treatment. Then, each patient was subjected to the alternative treatment (that was not practiced before), and followed up to 6 months. We found that all the patients improved in OCD symptomatology up to T1, while four among them improved up to T3. These patients were those showing a more extensive reshape of frontal areas phase synchronization and frontoparietal coherence compared to the other participants. Our pilot study suggests that iTBS over L-DLPFC may represent a feasible approach to improve OCD symptoms. The efficacy of iTBS seems to depend on the extent of frontal and frontoparietal connectivity modulation.

New Graph-Theoretical-Multimodal Approach Using Temporal and Structural Correlations Reveals Disruption in the Thalamo-Cortical Network in Patients with Schizophrenia.

Schizophrenia has been understood as a network disease with altered functional and structural connectivity in multiple brain networks compatible to the extremely broad spectrum of psychopathological, cognitive, and behavioral symptoms in this disorder. When building brain networks, functional and structural networks are typically modeled independently: Functional network models are based on temporal correlations among brain regions, whereas structural network models are based on anatomical characteristics. Combining both features may give rise to more realistic and reliable models of brain networks. In this study, we applied a new flexible graph-theoretical-multimodal model called FD (F, the functional connectivity matrix, and D, the structural matrix) to construct brain networks combining functional, structural, and topological information of magnetic resonance imaging (MRI) measurements (structural and resting-state imaging) to patients with schizophrenia (n = 35) and matched healthy individuals (n = 41). As a reference condition, the traditional pure functional connectivity (pFC) analysis was carried out. By using the FD model, we found disrupted connectivity in the thalamo-cortical network in schizophrenic patients, whereas the pFC model failed to extract group differences after multiple comparison correction. We interpret this observation as evidence that the FD model is superior to conventional connectivity analysis, by stressing relevant features of the whole-brain connectivity, including functional, structural, and topological signatures. The FD model can be used in future research to model subtle alterations of functional and structural connectivity, resulting in pronounced clinical syndromes and major psychiatric disorders. Lastly, FD is not limited to the analysis of resting-state functional MRI, and it can be applied to electro-encephalography, magneto-encephalography, etc.

Quantify neuromagnetic network changes from pre-ictal to ictal activities in absence seizures.

OBJECTIVE: The cortico-thalamo-cortical network plays a key role in childhood absence epilepsy (CAE). However, the exact interaction between the cortex and the thalamus remains incompletely understood. This study aimed to investigate the dynamic changes of frequency-dependent neural networks during the initialization of absence seizures. METHODS: Magnetoencephalography data from 14 patients with CAE were recorded during and between seizures at a sampling rate of 6000Hz and analyzed in seven frequency bands. Neuromagnetic sources were volumetrically scanned with accumulated source imaging. Effective connectivity networks of the entire brain, including the cortico-thalamo-cortical network, were evaluated at the source level through Granger causality analysis. RESULTS: The low-frequency (1-80Hz) activities showed significant frontal cortical and parieto-occipito-temporal junction source localization around seizures. The high-frequency (80-250Hz) oscillations showed predominant activities consistently localized in deep brain areas and medial frontal cortex. The increased cortico-thalamic effective connectivity was observed around seizures in both low- and high-frequency ranges. The direction was predominantly from the cortex to the thalamus at the early time, although the cortex that drove connectivity varied among subjects. CONCLUSIONS: The cerebral cortex plays a key role in driving the cortico-thalamic connections at the early portion of the initialization of absence seizures. The oscillatory activities in the thalamus could be triggered by networks from various regions in the cortex. SIGNIFICANCE: The dynamic changes of neural network provide evidences that absence seizures are probably resulted from cortical initialized cortico-thalamic network.

Abnormal structural connectivity between the basal ganglia, thalamus, and frontal cortex in patients with disorders of consciousness.

Consciousness loss in patients with severe brain injuries is associated with reduced functional connectivity of the default mode network (DMN), fronto-parietal network, and thalamo-cortical network. However, it is still unclear if the brain white matter connectivity between the above mentioned networks is changed in patients with disorders of consciousness (DOC). In this study, we collected diffusion tensor imaging (DTI) data from 13 patients and 17 healthy controls, constructed whole-brain white matter (WM) structural networks with probabilistic tractography. Afterward, we estimated and compared topological properties, and revealed an altered structural organization in the patients. We found a disturbance in the normal balance between segregation and integration in brain structural networks and detected significantly decreased nodal centralities primarily in the basal ganglia and thalamus in the patients. A network-based statistical analysis detected a subnetwork with uniformly significantly decreased structural connections between the basal ganglia, thalamus, and frontal cortex in the patients. Further analysis indicated that along the WM fiber tracts linking the basal ganglia, thalamus, and frontal cortex, the fractional anisotropy was decreased and the radial diffusivity was increased in the patients compared to the controls. Finally, using the receiver operating characteristic method, we found that the structural connections within the NBS-derived component that showed differences between the groups demonstrated high sensitivity and specificity (>90%). Our results suggested that major consciousness deficits in DOC patients may be related to the altered WM connections between the basal ganglia, thalamus, and frontal cortex.

Prefrontal-hippocampal coupling by theta rhythm and by 2-5 Hz oscillation in the delta band: The role of the nucleus reuniens of the thalamus.

Rhythmic synchronizations of hippocampus (HC) and prefrontal cortex (PFC) at theta frequencies (4-8 Hz) are thought to mediate key cognitive functions, and disruptions of HC-PFC coupling were implicated in psychiatric diseases. Theta coupling is thought to represent a HC-to-PFC drive transmitted via the well-described unidirectional HC projection to PFC. In comparison, communication in the PFC-to-HC direction is less understood, partly because no known direct anatomical connection exists. Two recent findings, i.e., reciprocal projections between the thalamic nucleus reuniens (nRE) with both PFC and HC and a unique 2-5 Hz rhythm reported in the PFC, indicate, however, that a second low-frequency oscillation may provide a synchronizing signal from PFC to HC via nRE. Thus, in this study, we recorded local field potentials in the PFC, HC, and nRE to investigate the role of nRE in PFC-HC coupling established by the two low-frequency oscillations. Using urethane-anesthetized rats and stimulation of pontine reticular formation to experimentally control the parameters of both forebrain rhythms, we found that theta and 2-5 Hz rhythm were dominant in HC and PFC, respectively, but were present and correlated in all three signals. Removal of nRE influence, either statistically (by partialization of PFC-HC correlation when controlling for the nRE signal) or pharmacologically (by lidocaine microinjection in nRE), resulted in decreased coherence between the PFC and HC 2-5-Hz oscillations, but had minimal effect on theta coupling. This study proposes a novel thalamo-cortical network by which PFC-to-HC coupling occurs via a 2-5 Hz oscillation and is mediated through the nRe.

Meta-analytic investigations of structural grey matter, executive domain-related functional activations, and white matter diffusivity in obsessive compulsive disorder: an integrative review.

Obsessive-compulsive disorder (OCD) is a debilitating disorder. However, existing neuroimaging findings involving executive function and structural abnormalities in OCD have been mixed. Here we conducted meta-analyses to investigate differences in OCD samples and controls in: Study 1 - grey matter structure; Study 2 - executive function task-related activations during (i) response inhibition, (ii) interference, and (iii) switching tasks; and Study 3 - white matter diffusivity. Results showed grey matter differences in the frontal, striatal, thalamus, parietal and cerebellar regions; task domain-specific neural differences in similar regions; and abnormal diffusivity in major white matter regions in OCD samples compared to controls. Our results reported concurrence of abnormal white matter diffusivity with corresponding abnormalities in grey matter and task-related functional activations. Our findings suggested the involvement of other brain regions not included in the cortico-striato-thalamo-cortical network, such as the cerebellum and parietal cortex, and questioned the involvement of the orbitofrontal region in OCD pathophysiology. Future research is needed to clarify the roles of these brain regions in the disorder.

Disrupted thalamo-cortical connectivity in schizophrenia: a morphometric correlation analysis.

Increasing studies have implicated the thalamus in schizophrenia, supporting the view that this structure has an important role in this disorder. Given that extensive reciprocal connections exist between the thalamus and the cerebral cortex, it is believed that disruptions of the thalamo-cortical connections may underlie the multiplicity of schizophrenic symptoms. Therefore, assessing the relationship between the thalamus and the neocortex may provide new insights into the pathophysiology of schizophrenia. We analyzed magnetic resonance images from a sample of 101 schizophrenic patients and 101 healthy controls. By assessing the correlation between the thalamic volume and cortical thickness at each vertex on the cortical surface, a thalamo-cortical network was obtained for each group. We compared the patterns of thalamo-cortical connectivity between the two groups. Compared with healthy controls, less distributed cortical regions were identified in the thalamo-cortical network in patients with schizophrenia. Vertex-wise comparison revealed decreased thalamo-cortical connectivity in bilateral inferior frontal gyrus, the left superior temporal gyrus and the right parieto-occipital region in schizophrenia. The observed disruptions in thalamo-cortical connectivity might be the substrate underlying the wide range of schizophrenic symptoms and provide further evidence to support the notion of schizophrenia as a disorder of brain dysconnectivity.

Total intravenous anesthesia affecting spike sources of magnetoencephalography in pediatric epilepsy patients: focal seizures vs. non-focal seizures.

PURPOSE: Magnetoencephalography (MEG) provides source localization of interictal spikes. This study evaluated the inhibitory effects of propofol on MEG spike sources (MEGSSs) among different types of seizures in patients who underwent two separate MEG studies with and without total intravenous anesthesia (TIVA) using propofol. METHODS: We studied 19 children (1-14 years; mean, 6.2 years) who had MEG with and without TIVA. TIVA was administered using propofol (0.03-0.06 mg/kg/min) to record MEG with simultaneous EEG. We analyzed number of spikes of MEG and MEGSSs comparing MEG studies done with and without TIVA. RESULTS: Seizures were divided into nine focal seizure (FS) with/without secondary generalization, five epileptic spasm (ES), and five generalized seizure (GS). TIVA significantly decreased the number of MEG spikes/min (from 4.5 to 2.0) in five FS without secondary generalization (p<0.05). The number of MEG spikes/min was significantly lower (1.9) in FS than that in non-FS (ES+GS, 6.1) (p<0.01). MEGSSs without TIVA were clustered in 15 patients (6FS; 4ES; 5GS), scattered in four (3FS; 1ES). MEG under TIVA showed clusters in 10 patients (1FS; 4ES; 5GS), scatters in three (2FS; 1ES) and no MEGSS in six patients with FS. Under TIVA, nine (90%) of ten patients with non-FS showed MEGSSs clusters compared to one (11%) of nine patients with FS (p<0.01). CONCLUSIONS: Reduction of MEGSSs occurred in patients with FS under TIVA. Diffuse/generalized spikes in non-FS are not affected by TIVA. Propofol may decrease focal spikes in the epileptic cortex in FS. Cortical hyperexcitability in non-FS group would be stronger or more extensive than that in the FS group of patients.