Investigation of anatomical thalamo-cortical connectivity and FMRI activation in schizophrenia

The purpose of this study was to examine measures of anatomical connectivity between the thalamus and lateral prefrontal cortex (LPFC) in schizophrenia and to assess their functional implications. We measured thalamocortical connectivity with diffusion tensor imaging (DTI) and probabilistic tractography in 15 patients with schizophrenia and 22 age- and sex-matched controls. The relationship between thalamocortical connectivity and prefrontal cortical blood-oxygenation-level-dependent (BOLD) functional activity as well as behavioral performance during working memory was examined in a subsample of 9 patients and 18 controls. Compared with controls, schizophrenia patients showed reduced total connectivity of the thalamus to only one of six cortical regions, the LPFC. The size of the thalamic region with at least 25% of model fibers reaching the LPFC was also reduced in patients compared with controls. The total thalamocortical connectivity to the LPFC predicted working memory task performance and also correlated with LPFC BOLD activation. Notably, the correlation with BOLD activation was accentuated in patients as compared with controls in the ventral LPFC. These results suggest that thalamocortical connectivity to the LPFC is altered in schizophrenia with functional consequences on working memory processing in LPFC.     

Low-frequency BOLD fluctuations demonstrate altered thalamocortical connectivity in schizophrenia

The thalamus plays a central and dynamic role in information transmission and processing in the brain. Multiple studies reveal increasing association between schizophrenia and dysfunction of the thalamus, in particular the medial dorsal nucleus (MDN), and its projection targets. The medial dorsal thalamic connections to the prefrontal cortex are of particular interest, and explicit in vivo evidence of this connection in healthy humans is sparse. Additionally, recent neuroimaging evidence has demonstrated disconnection among a variety of cortical regions in schizophrenia, though the MDN thalamic prefrontal cortex network has not been extensively probed in schizophrenia. To this end, we have examined thalamo-anterior cingulate cortex connectivity using detection of low-frequency blood oxygen level dependence fluctuations (LFBF) during a resting-state paradigm. Eleven schizophrenic patients and 12 healthy control participants were enrolled in a study of brain thalamocortical connectivity. Resting-state data were collected, and seed-based connectivity analysis was performed to identify the thalamocortical network. First, we have shown there is MDN thalamocortical connectivity in healthy controls, thus demonstrating that LFBF analysis is a manner to probe the thalamocortical network. Additionally, we have found there is statistically significantly reduced thalamocortical connectivity in schizophrenics compared with matched healthy controls. We did not observe any significant difference in motor networks between groups. We have shown that the thalamocortical network is observable using resting-state connectivity in healthy controls and that this network is altered in schizophrenia. These data support a disruption model of the thalamocortical network and are consistent with a disconnection hypothesis of schizophrenia.     

Metabolic disconnection between the mediodorsal nucleus of the thalamus and cortical Brodmann's areas of the left hemisphere in schizophrenia

OBJECTIVE: The authors' goal was to examine interregional correlations of thalamocortical metabolic activity during a verbal learning task in schizophrenia. METHOD: They used [18F]fluorodeoxyglucose positron emission tomography in 41 unmedicated patients with schizophrenia and 59 normal comparison subjects. RESULTS: A metabolic disconnection was observed in patients with schizophrenia in the left hemisphere between the mediodorsal nucleus and widespread frontotemporal cortical regions, and stronger-than-normal intercorrelations were found between the pulvinar and superior temporal, selected parietal, posterior cingulate, and occipital areas. CONCLUSIONS: Deficits in the functional interrelationships between the left frontotemporal cortices and the left mediodorsal nucleus of the thalamus complement inferences from postmortem and magnetic resonance imaging volumetric studies identifying a thalamic diathesis in schizophrenia.     

Correlations between MRI-assessed volumes of the thalamus and cortical Brodmann's areas in schizophrenia

BACKGROUND: We compared the thalamic-cortical volumetric correlational patterns in patients with schizophrenia and normal comparison subjects, and evaluated their relations to outcome. METHODS: High-resolution MR images were acquired in patients with schizophrenia (n=106) and normal comparison subjects (n=42). Patients were divided into good-outcome (n=52) and poor-outcome (Kraepelinian, n=54) subtypes based on their ability for self-care. Correlations between the relative gray and white matter volumes of the individual cortical Brodmann's areas and five dorsoventral levels of the thalamus were assessed. RESULTS: Compared to normal subjects, schizophrenia patients lacked significant thalamic gray matter volume correlations with the prefrontal and medial temporal cortical regions in the right hemisphere, and with frontal, cingulate, posterior parietal and occipital regions in the left hemisphere, while normal white matter volume cortical-thalamic correlations along the cingulate gyrus and in the temporal lobe were not found in schizophrenia patients in both hemispheres. In contrast to both normal comparison subjects and good-outcome group, schizophrenia patients with poor outcomes showed significant bilateral gray matter volume correlations between the dorsal thalamus and ventral prefrontal cortex, while the group differences in the white matter volume correlations were mostly restricted to the cingulate arch. CONCLUSIONS: Whereas patients with schizophrenia exhibit deficiencies in cortical-thalamic correlational patterns, poor outcome is associated with abnormal interregional correlations not observed in either normal subjects or patients with good outcomes. This latter finding may be explained by a core neurodevelopmental disturbance that results in aberrant cortical-thalamic connectivity in poor-outcome schizophrenia.     

Alterations of fronto-temporal connectivity during word encoding in schizophrenia

Cognitive deficits, including impaired verbal memory, are prominent in schizophrenia and lead to increased disability. Functional neuroimaging of patients with schizophrenia performing memory tasks has revealed abnormal activation patterns in prefrontal cortex and temporo-limbic regions. Aberrant fronto-temporal interactions thus represent a potential pathophysiological mechanism underlying verbal memory deficits, yet this hypothesis of disturbed connectivity is not tested directly with standard activation studies. We performed within-subject correlations of frontal and temporal timeseries to measure functional connectivity during verbal encoding. Our results confirm earlier findings of aberrant fronto-temporal connectivity in schizophrenia, and extend them by identifying distinct alterations within dorsal and ventral prefrontal cortex. Relative to healthy controls, patients with schizophrenia had reduced connectivity between the dorsolateral prefrontal cortex (DLPFC) and temporal lobe areas including parahippocampus and superior temporal gyrus. In contrast, patients showed increased connectivity between a region of ventrolateral prefrontal cortex (VLPFC) and these same temporal lobe regions. Higher temporal-DLPFC connectivity during encoding was associated with better subsequent recognition accuracy in controls, but not patients. Temporal-VLPFC connectivity was uncorrelated with recognition accuracy in either group. The results suggest that reduced temporal-DLPFC connectivity in schizophrenia could underlie encoding deficits, and increased temporal-VLPFC connectivity may represent an ineffective compensatory effort.     

Preferential networks of the mediodorsal nucleus and centromedian-parafascicular complex of the thalamus-A DTI tractography study

Distinct thalamic nuclei, like the mediodorsal (MD) nucleus and the centromedian/parafascicular complex (CM/Pf), are embedded in different basal ganglia—thalamocortical loops, which were shown to integrate cognitive and emotional aspects of human behavior. Despite well described connections on a microscopic scale, derived from tracing studies in animals, little is known about the intrinsic anatomical connections of these nuclei in humans. This lack of knowledge limits not only interpretation of functional imaging studies but also estimation of direct effects of deep brain stimulation which treats diseases as different as epilepsy or major depression. Therefore, non‐invasive diffusion tensor imaging (DTI) studies are key to analyzing connectivity patterns and elaborate approaches to close this gap. For our study, we explored the structural connectivity of the MD thalamic nuclei and the CM/Pf complex towards five cortical and six subcortical regions by using a preferential fiber calculation. We found both thalamic nuclei to be preferentially associated to distinct networks: whereas the MD is preferentially connected to prefrontal and limbic cortical regions, the CM is linked to subcortical regions. The anterior insula was the only cortical region associated with the subcortical network of the CM and the cortical network of the MD comprised one subcortical hub, the caudate nucleus, suggesting an integrative role of these two regions. Adding to predescribed anatomical tract tracing connectivities in animal studies, our finding lends support to the existence of similar basal ganglia‐thalamocortical circuits in humans and we could show a robust distinction of preferential connectivity for both thalamic nuclei. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.     

Reduction of early thalamic input alters adult corticocortical connectivity

The functional specificity of mammalian isocortex requires that precise connections be established between cortical areas and their targets. While recent studies of cortical development have focused on intrinsic specification, the role of extrinsic factors has received considerably less attention. In the present study, we examined how early removal of thalamic input affects the development of visual corticocortical connections. Hamster pups received ablations of visual thalamic nuclei on the day of birth. At 30 days of age, an injection of horseradish peroxidase (HRP) was placed into the area of cortex deafferented by the early thalamic ablation to retrogradely label adult corticocortical connections. Ablated animals displayed a significant increase in the number of corticocortical connections compared to control animals. The increased connectivity in ablated animals was primarily due to a significant increase in the number of corticocortical projections arising from non-visual areas. These results demonstrate that an intact thalamocortical projection is necessary for the development of normal cortical connectivity.     

Reduced frontopolar activation during verbal fluency task in schizophrenia: a multi-channel near-infrared spectroscopy study

Functional neuroimaging studies to date have shown prefrontal dysfunction during executive tasks in schizophrenia. However, relationships between hemodynamic response in prefrontal sub-regions and clinical characteristics have been unclear. The objective of this study is to evaluate prefrontal hemodynamic response related to an executive task in schizophrenia and to assess the relationship between activation in the prefrontal sub-regions and clinical status. Fifty-five subjects with schizophrenia and age- and gender-matched 70 healthy subjects were recruited for this case-control study in a medical school affiliated hospital in the Tokyo metropolitan area, Japan. We measured hemoglobin concentration changes in the prefrontal (dorsolateral, ventrolateral, and frontopolar regions) and superior temporal cortical surface area during verbal fluency test using 52-channel near-infrared spectroscopy, which enables real-time monitoring of cerebral blood volumes in the cortical surface area under a more restraint-free environment than positron emission tomography or functional magnetic resonance imaging. The two groups showed distinct spatiotemporal pattern of oxy-hemoglobin concentration change during verbal fluency test. Schizophrenia patients were associated with slower and reduced increase in prefrontal activation than healthy controls. In particular, reduced activations of the frontopolar region, rather than lateral prefrontal or superior temporal regions, showed significant positive correlations with lower global assessment of functioning scores in the patient group, although task performance was not significantly associated with the scores. These results suggest that reduced frontopolar cortical activation is associated with functional impairment in patients with schizophrenia and that near-infrared spectroscopy may be an efficient clinical tool for monitoring these characteristics.     

Key functional circuitry altered in schizophrenia involves parietal regions associated with sense of self

There is still no clear consensus as to which of the many functional and structural changes in the brain in schizophrenia are of most importance, although the main focus to date has been on those in the frontal and cingulate cortices. In the present study, we have used a novel holistic approach to identify brain‐wide functional connectivity changes in medicated schizophrenia patients, and functional connectivity changes were analyzed using resting‐state fMRI data from 69 medicated schizophrenia patients and 62 healthy controls. As far as we are aware, this is the largest population reported in the literature for a resting‐state study. Voxel‐based morphometry was also used to investigate gray and white matter volume changes. Changes were correlated with illness duration/symptom severity and a support vector machine analysis assessed predictive validity. A network involving the inferior parietal lobule, superior parietal gyrus, precuneus, superior marginal, and angular gyri was by far the most affected (68% predictive validity compared with 82% using all connections) and different components correlated with illness duration and positive and negative symptom severity. Smaller changes occurred in emotional memory and sensory and motor processing networks along with weakened interhemispheric connections. Our findings identify the key functional circuitry altered in schizophrenia involving the default network midline cortical system and the cortical mirror neuron system, both playing important roles in sensory and cognitive processing and particularly self‐processing, all of which are affected in this disorder. Interestingly, the functional connectivity changes with the strongest links to schizophrenia involved parietal rather than frontal regions. Hum Brain Mapp 35:123–139, 2014. © 2012 Wiley Periodicals, Inc.     

Schizophrenia,neurodevelopment and corpus callosum

The Zeitgeist favors an interpretation of schizophrenia as a condition of abnormal connectivity of cortical neurons, particularly in the prefrontal and temporal cortex. The available evidence points to reduced connectivity, a possible consequence of excessive synaptic pruning in development. A decreased thalamic input to the cerebral cortex appears likely, and developmental studies predict that this decrease should entail a secondary loss of both long- and short-range cortico-cortical connections, including connections between the hemispheres. Indeed, morphological, electrophysiological and neuropsychological studies over the last two decades suggest that the callosal connections are altered in schizophrenics. However, the alterations are subtle and sometimes inconsistent across studies, and need to be investigated further with new methodologies.     

Schizophrenia, hypocretin (orexin), and the thalamocortical activating system

Diminished connectivity between midline-intralaminar thalamic nuclei and prefrontal cortex has been suggested to contribute to cognitive deficits that are detectable even in early stages of schizophrenia. The midline-intralaminar relay cells comprise the final link in the ascending arousal pathway and are selectively excited by the wake-promoting peptides hypocretin 1 and 2 (orexin A and B). This excitation occurs both at the level of the relay cell bodies and their axon terminals within prefrontal cortex. In rat brain slices, the release of glutamate from midline-intralaminar thalamocortical terminals induces excitatory postsynaptic currents (EPSCs) in layer V pyramidal cells in prefrontal cortex. When hypocretin is infused into medial prefrontal cortex of behaving animals, it improves performance in a complex cognitive task requiring divided attention. Chronic restraint stress causes atrophy of the apical dendritic arbors in layer V prefrontal pyramidal cells and leads to a reduction in hypocretin-induced EPSCs, indicating impairment in excitatory thalamocortical transmission. Thus, taken together with evidence for an underlying loss of excitatory thalamocortical connectivity in schizophrenia, stress in this illness could further exacerbate a breakdown in cortical processing of incoming information from the ascending arousal system.     

Regionally specific disturbance of dorsolateral prefrontal-hippocampal functional connectivity in schizophrenia

BACKGROUND: Two brain regions often implicated in schizophrenia are the dorsolateral prefrontal cortex (DLPFC) and the hippocampal formation (HF). It has been hypothesized that the pathophysiology of the disorder might involve an alteration of functional interactions between medial temporal and prefrontal areas. METHODS: We used neuroimaging data acquired during a working memory challenge and a sensorimotor control task in 22 medication-free schizophrenic patients and 22 performance-, age-, and sex-matched healthy subjects to investigate "functional connectivity" between HF and DLPFC in schizophrenia. The HF blood flow, measured with positron emission tomography, was assessed within a probabilistic template. Brain areas whose activity was positively or negatively coupled to HF were identified using voxelwise analysis of covariance throughout the entire brain and analyzed using a random effects model. RESULTS: During working memory, patients showed reduced activation of the right DLPFC and left cerebellum. In both groups, inverse correlations were observed between the HF and the contralateral DLPFC and inferior parietal lobule. While these did not differ between diagnostic groups during the control task, the working memory challenge revealed a specific abnormality in DLPFC-HF functional connectivity-while the right DLPFC was significantly coupled to the left HF in both groups during the control task, this correlation was not seen in healthy subjects during working memory but persisted undiminished in patients, resulting in a significant task-by-group interaction. CONCLUSIONS: Our results suggest a regionally specific alteration of HF-DLPFC functional connectivity in schizophrenia that manifests as an unmodulated persistence of an HF-DLPFC linkage during working memory activation. Thus, a mechanism by which HF dysfunction may manifest in schizophrenia is by inappropriate reciprocal modulatory interaction with the DLPFC.     

Thalamo-cortical functional connectivity in schizophrenia and bipolar disorder

The thalamus is a highly connected subcortical structure that relays and integrates sensory and cortical information, which is critical for coherent and accurate perceptual awareness and cognition. Thalamic dysfunction is a classical finding in schizophrenia (SZ), and resting-state functional MRI has implicated somatomotor and frontal lobe thalamic dysconnectivity. However, it remains unclear whether these findings generalize to different psychotic disorders, are confined to specific thalamic sub-regions, and how they relate to structural thalamic alterations. Within-thalamic and thalamo-cortical functional connectivity was assessed using resting-state functional MRI data obtained from patients with SZ (n = 96), bipolar disorder (BD, n = 57), and healthy controls (HC, n = 280). Further, we used thalamic sub-regions as seeds to investigate specific cortical connectivity patterns, and performed structural analyses of thalamic volume and shape. Results showed reduced within-thalamic connectivity and thalamo-frontoparietal coupling in SZ and increased thalamo-somatomotor connectivity in BD. One thalamic sub-region showed increased sensory connectivity in SZ and eight sub-regions showed reductions with frontal and posterior areas. Reduced gray matter and shape abnormalities were found in frontal-projecting regions in both SZ and BD, but did not seem to explain reduced functional connectivity. Aberrant thalamo-cortical connectivity patterns in SZ and BD supports the notion of the thalamus as a key structure in the functional connectome across the psychosis spectrum, and the frontal and somatomotor anatomical distribution is in line with the characteristic cognitive and perceptual symptoms in psychotic disorders.     

Alterations in cortical and thalamic connections of somatosensory cortex following early loss of vision

Early loss of vision produces dramatic changes in the functional organization and connectivity of the neocortex in cortical areas that normally process visual inputs, such as the primary and second visual area. This loss also results in alterations in the size, functional organization, and neural response properties of the primary somatosensory area, S1. However, the anatomical substrate for these functional changes in S1 has never been described. In the present investigation, we quantified the cortical and subcortical connections of S1 in animals that were bilaterally enucleated very early in development, prior to the formation of retino-geniculate and thalamocortical pathways. We found that S1 receives dense inputs from novel cortical fields, and that the density of existing cortical and thalamocortical connections was altered. Our results demonstrate that sensory systems develop in tandem and that alterations in sensory input in one system can affect the connections and organization of other sensory systems. Thus, therapeutic intervention following early loss of vision should focus not only on restoring vision, but also on augmenting the natural plasticity of the spared systems.     

颞叶内侧癫癎海马功能连接的功能磁共振成像研究

目的研究颞叶内侧癫癎患者右侧海马与全脑,尤其是默认网络功能连接的关系,探讨颞叶内侧癫癎患者默认网络异常的机制及其形成的颞叶癫癎网络。方法23例颞叶内侧癫癎患者,采用静息功能连接的功能磁共振成像,选择右侧海马作为兴趣区,获得正常对照组和颞叶内侧癫癎组受试者的脑功能连接激活图,观察其右侧海马与全脑的功能连接。结果正常对照组受试者默认网络包括海马、后扣带回和（或）楔前叶、前扣带回和（或）前额叶内侧、角回及前颞叶。颞叶内侧癫癎组患者右侧海马与默认网络的正向功能连接明显减弱,与右侧额下回、颞上回及第一运动感觉皮质下部的正向功能连接增强;与前额叶背侧、顶间沟及第一运动感觉皮质上部的负向功能连接减弱。结论在颞叶内侧癫癎患者功能连接网络中,默认网络及部分正向功能连接网络受损,提示患者存在广泛的、与海马相关的生理功能丧失;与右侧额下回、颞上回及第一感觉运动皮质下部的功能连接增强则可能与颞叶癫癎网络有关。     

A 4.0-T fMRI study of brain connectivity during word fluency in first-episode schizophrenia

OBJECTIVE: To use functional magnetic resonance imaging (fMRI) to investigate functional connectivity, and hence, underlying neural networks, in never-treated, first-episode patients with schizophrenia using a word fluency paradigm known to activate prefrontal, anterior cingulate, and thalamic regions. Abnormal connectivity between the prefrontal cortex (PFC) and other brain regions has been demonstrated in chronic, medicated patients in previous positron emission tomography (PET) studies, but has not to our knowledge, previously been demonstrated using both first-episode, drug-na?ve patients and fMRI technology. METHODS: A 4.0-Tesla (T) fMRI was used to examine activation and functional connectivity [psychophysiological interactions (PPIs)] during a word fluency task compared to silent reading in 10 never-treated, first-episode patients with schizophrenia and 10 healthy volunteers of comparable age, sex, handedness, and parental education. RESULTS: Compared to healthy volunteers, the schizophrenia patient group exhibited less activation during the word fluency task, mostly in the right anterior cingulate and prefrontal regions. Psychophysiological interactions between right anterior cingulate and other parts of the brain revealed a localized interaction with the left temporal lobe in healthy volunteers during the task and a widespread unfocussed interaction in patients. CONCLUSION: These findings suggest anterior cingulate involvement in the neuronal circuitry underlying schizophrenia.     

Parallel inputs from the mediodorsal thalamus to the prefrontal cortex in the rat

There is a growing interest in determining the functional contribution of thalamic inputs to cortical functions. In the context of adaptive behaviours, identifying the precise role of the mediodorsal thalamus (MD) in particular remains difficult despite the large amount of experimental data available. A better understanding of the thalamocortical connectivity of this region may help to capture its functional role. To address this issue, this study focused exclusively on the specific connections from the MD to the prefrontal cortex (PFC) by means of direct comparisons of labelling produced by single and dual injections of retrograde tracers in the different subdivisions of the PFC in the rat. We show that at least three parallel and essentially separate thalamocortical pathways originate from the MD, as follows: projections to the dorsal (1) and the ventral (2) subdivisions of the mPFC follow a mediolateral topography at the thalamic level (i.e. medial thalamic neurons target the mPFC ventrally whereas lateral thalamic neurons project dorsally), whereas a considerable innervation to the OFC (3) includes thalamic cells projecting to both the lateral and the ventral OFC subdivisions. These observations provide new insight on the functions of the MD and suggest a specific focus on each of these pathways for future functional studies.     

Resting state cerebral blood flow and objective motor activity reveal basal ganglia dysfunction in schizophrenia

Reduced motor activity has been reported in schizophrenia and was associated with subtype, psychopathology and medication. Still, little is known about the neurobiology of motor retardation. To identify neural correlates of motor activity, resting state cerebral blood flow (CBF) was correlated with objective motor activity of the same day. Participants comprised 11 schizophrenia patients and 14 controls who underwent magnetic resonance imaging with arterial spin labeling and wrist actigraphy. Patients had reduced activity levels and reduced perfusion of the left parahippocampal gyrus, left middle temporal gyrus, right thalamus, and right prefrontal cortex. In controls, but not in schizophrenia, CBF was correlated with activity in the right thalamic ventral anterior (VA) nucleus, a key module within basal ganglia-cortical motor circuits. In contrast, only in schizophrenia patients positive correlations of CBF and motor activity were found in bilateral prefrontal areas and in the right rostral cingulate motor area (rCMA). Grey matter volume correlated with motor activity only in the left posterior cingulate cortex of the patients. The findings suggest that basal ganglia motor control is impaired in schizophrenia. In addition, CBF of cortical areas critical for motor control was associated with volitional motor behavior, which may be a compensatory mechanism for basal ganglia dysfunction.     

Parkinson's disease patients show reduced cortical‐subcortical sensorimotor connectivity

Reduced dopamine input to cortical and subcortical brain structures, particularly those in the sensorimotor network, is a hallmark of Parkinson's disease (PD). The extent to which dopamine dysfunction affects connectivity within this and other brain networks remains to be investigated. The purpose of this study was to measure anatomical and functional connectivity in groups of PD patients and controls to determine whether connectivity deficits within the cortico–basal ganglia thalamocortical system could be attributed to PD, particularly in sensorimotor connections. A neuroimaging paradigm involving diffusion‐weighted magnetic resonance imaging (MRI) and resting‐state functional MRI was implemented in a large cohort of PD patients and control subjects. Probabilistic tractography and functional correlation analyses were performed to map connections between brain structures and to derive indices of connectivity that were then used to compare groups. Anatomical connectivity deficits were demonstrated in PD patients, specifically for sensorimotor connections. Functional deficits were also found in some of the same connections. In addition, functional connectivity was found to increase in associative and limbic connections in PD patients compared with controls. This study lends support to findings regarding the dysfunction of the sensorimotor circuit in PD. As deficits in anatomical and functional connectivity within this circuit were in some cases concordant in PD patients, a possible link between brain structure and function is suggested. Increases in functional connectivity in other cortico–basal ganglia thalamocortical circuits may be indicative of compensatory effects in response to system deficits elsewhere. © 2012 Movement Disorder Society     

A computational model of thalamocortical dysrhythmia

Functional stereotactic lesions in the central lateral nucleus of the medial thalamus have proved to be an effective treatment of neurogenic pain and other neurological disorders associated with thalamocortical dysrhythmia. The mechanisms underlying patient recovery after surgery are currently being explored using quantitative electroencephalography. Here we test the hypothesis that the particular role played by the non-specific medial thalamic nuclei in thalamocortical dysrhythmia is based on the divergent connectivity between these non-specific and reticular nuclei. We built a spiking computer model of the human thalamocortical system consisting of specific, non-specific and reticular thalamic nuclei. In our simulations of the thalamocortical system, deafferentation of peripheral thalamic afferents leads to hyperpolarization and subsequent bursting in the reticular nucleus. This provides strong inhibitory feedback to both the specific and the non-specific thalamic nuclei and initiates a feedback cycle of thalamic bursts in the theta frequency range. The divergent connections between the reticular and non-specific thalamic nuclei provide synchronization of the oscillating circuits. Functional silencing of the non-specific model nucleus limits reverberation and rescues the system from these oscillations. The same effect could be achieved by increasing the input to the non-specific nucleus from cortical areas. The model predicts that the invasiveness of functional neurosurgery can be reduced by targeting only deafferented areas in the medial nuclei as these are the key areas for generation and maintenance of pathological rhythms.