Thalamic white matter in multiple sclerosis: A combined diffusion-tensor imaging and quantitative susceptibility mapping study.

PubMed

Bergsland, Niels; Schweser, Ferdinand; Dwyer, Michael G; Weinstock-Guttman, Bianca; Benedict, Ralph H B; Zivadinov, Robert

2018-06-19

Thalamic white matter (WM) injury in multiple sclerosis (MS) remains relatively poorly understood. Combining multiple imaging modalities, sensitive to different tissue properties, may aid in further characterizing thalamic damage. Forty-five MS patients and 17 demographically-matched healthy controls (HC) were scanned with 3T MRI to obtain quantitative measures of diffusivity and magnetic susceptibility. Participants underwent cognitive evaluation with the Brief International Cognitive Assessment for Multiple Sclerosis battery. Tract-based spatial statistics identified thalamic WM. Non-parametric combination (NPC) analysis was used to perform joint inference on fractional anisotropy (FA), mean diffusivity (MD) and magnetic susceptibility measures. The association of surrounding WM lesions and thalamic WM pathology was investigated with lesion probability mapping. Compared to HCs, the greatest extent of thalamic WM damage was reflected by the combination of increased MD and decreased magnetic susceptibility (63.0% of thalamic WM, peak p = .001). Controlling for thalamic volume resulted in decreased FA and magnetic susceptibility (34.1%, peak p = .004) as showing the greatest extent. In MS patients, the most widespread association with information processing speed was found with the combination of MD and magnetic susceptibility (67.6%, peak p = .0005), although this was not evident after controlling for thalamic volume. For memory measures, MD alone yielded the most widespread associations (45.9%, peak p = .012 or 76.7%, peak p = .001), even after considering thalamic volume, albeit with smaller percentages. White matter lesions were related to decreased FA (peak p = .0063) and increased MD (peak p = .007), but not magnetic susceptibility, of thalamic WM. Our study highlights the complex nature of thalamic pathology in MS. © 2018 Wiley Periodicals, Inc.

Fatigue Is Associated With Global and Regional Thalamic Morphometry in Veterans With a History of Mild Traumatic Brain Injury.

PubMed

Clark, Alexandra L; Sorg, Scott F; Holiday, Kelsey; Bigler, Erin D; Bangen, Katherine J; Evangelista, Nicole D; Bondi, Mark W; Schiehser, Dawn M; Delano-Wood, Lisa

2018-01-30

Fatigue is a complex, multidimensional phenomenon that commonly occurs following traumatic brain injury (TBI). The thalamus-a structure vulnerable to both primary and secondary injuries in TBI-is thought to play a pivotal role in the manifestation of fatigue. We explored how neuroimaging markers of local and global thalamic morphometry relate to the subjective experience of fatigue post-TBI. Sixty-three Veterans with a history of mild TBI underwent structural magnetic resonance imaging and completed questionnaires related to fatigue and psychiatric symptoms. FMRIB's Software (FSL) was utilized to obtain whole brain and thalamic volume estimates, as well as to perform regional thalamic morphometry analyses. Independent of age, sex, intracranial volume, posttraumatic stress disorder, and depressive symptoms, greater levels of self-reported fatigue were significantly associated with decreased right (P = .026) and left (P = .046) thalamic volumes. Regional morphometry analyses revealed that fatigue was significantly associated with reductions in the anterior and dorsomedial aspects of the right thalamic body (P < .05). Similar trends were observed for the left thalamic body (P < .10). Both global and regional thalamic morphometric changes are associated with the subjective experience of fatigue in Veterans with a history of mild TBI. These findings support a theory in which disruption of thalamocorticostriatal circuitry may result in the manifestation of fatigue in individuals with a history of neurotrauma.

Progressive deterioration of thalamic nuclei relates to cortical network decline in schizophrenia

PubMed Central

Cobia, Derin J.; Smith, Matthew J.; Salinas, Ilse; Ng, Charlene; Gado, Mohktar; Csernansky, John G.; Wang, Lei

2016-01-01

Thalamic abnormalities are considered part of the complex pathophysiology of schizophrenia, particularly the involvement of specific thalamic nuclei. The goals of this study were to: introduce a novel atlas-based parcellation scheme for defining various thalamic nuclei; compare their integrity in a schizophrenia sample against healthy individuals at baseline and follow-up time points, as well as rates of change over time; examine relationships between the nuclei and abnormalities in known connected cortical regions; and finally, to determine if schizophrenia-related thalamic nuclei changes relate to cognitive functioning and clinical symptoms. Subjects were from a larger longitudinal 2-year follow-up study, schizophrenia (n=20) and healthy individuals (n=20) were group-matched for age, gender, and recent-alcohol use. We used high-dimensional brain mapping to obtain thalamic morphology, and applied a novel atlas-based method for delineating anterior, mediodorsal, and pulvinar nuclei. Results from cross sectional GLMs revealed group differences in bilateral mediodorsal and anterior nuclei, while longitudinal models revealed significant group-by-time interactions for the mediodorsal and pulvinar nuclei. Cortical correlations were the strongest for the pulvinar in frontal, temporal and parietal regions, followed by the mediodorsal nucleus in frontal regions, but none in the anterior nucleus. Thalamic measures did not correlate with cognitive and clinical scores at any time point or longitudinally. Overall, findings revealed a pattern of persistent progressive abnormalities in thalamic nuclei that relate to advancing cortical decline in schizophrenia, but not with measures of behavior. PMID:27613507

Progressive deterioration of thalamic nuclei relates to cortical network decline in schizophrenia.

PubMed

Cobia, Derin J; Smith, Matthew J; Salinas, Ilse; Ng, Charlene; Gado, Mokhtar; Csernansky, John G; Wang, Lei

2017-02-01

Thalamic abnormalities are considered part of the complex pathophysiology of schizophrenia, particularly the involvement of specific thalamic nuclei. The goals of this study were to: introduce a novel atlas-based parcellation scheme for defining various thalamic nuclei; compare their integrity in a schizophrenia sample against healthy individuals at baseline and follow-up time points, as well as rates of change over time; examine relationships between the nuclei and abnormalities in known connected cortical regions; and finally, to determine if schizophrenia-related thalamic nuclei changes relate to cognitive functioning and clinical symptoms. Subjects were from a larger longitudinal 2-year follow-up study, schizophrenia (n=20) and healthy individuals (n=20) were group-matched for age, gender, and recent-alcohol use. We used high-dimensional brain mapping to obtain thalamic morphology, and applied a novel atlas-based method for delineating anterior, mediodorsal, and pulvinar nuclei. Results from cross sectional GLMs revealed group differences in bilateral mediodorsal and anterior nuclei, while longitudinal models revealed significant group-by-time interactions for the mediodorsal and pulvinar nuclei. Cortical correlations were the strongest for the pulvinar in frontal, temporal and parietal regions, followed by the mediodorsal nucleus in frontal regions, but none in the anterior nucleus. Thalamic measures did not correlate with cognitive and clinical scores at any time point or longitudinally. Overall, findings revealed a pattern of persistent progressive abnormalities in thalamic nuclei that relate to advancing cortical decline in schizophrenia, but not with measures of behavior. Copyright © 2016 Elsevier B.V. All rights reserved.

Input-Specific Gain Modulation by Local Sensory Context Shapes Cortical and Thalamic Responses to Complex Sounds.

PubMed

Williamson, Ross S; Ahrens, Misha B; Linden, Jennifer F; Sahani, Maneesh

2016-07-20

Sensory neurons are customarily characterized by one or more linearly weighted receptive fields describing sensitivity in sensory space and time. We show that in auditory cortical and thalamic neurons, the weight of each receptive field element depends on the pattern of sound falling within a local neighborhood surrounding it in time and frequency. Accounting for this change in effective receptive field with spectrotemporal context improves predictions of both cortical and thalamic responses to stationary complex sounds. Although context dependence varies among neurons and across brain areas, there are strong shared qualitative characteristics. In a spectrotemporally rich soundscape, sound elements modulate neuronal responsiveness more effectively when they coincide with sounds at other frequencies, and less effectively when they are preceded by sounds at similar frequencies. This local-context-driven lability in the representation of complex sounds-a modulation of "input-specific gain" rather than "output gain"-may be a widespread motif in sensory processing. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Complex neurological symptoms in bilateral thalamic stroke due to Percheron artery occlusion.

PubMed

Caruso, Paola; Manganotti, Paolo; Moretti, Rita

2017-01-01

The artery of Percheron is a rare anatomical variant where a single thalamic perforating artery arises from the proximal posterior cerebral artery (P1 segment) between the basilar artery and the posterior communicating artery and supplies the rostral mesencephalon and both paramedian territories of the thalami. Almost one-third of human brains present this variant. Occlusion of the artery of Percheron mostly results in a bilateral medial thalamic infarction, which usually manifests with altered consciousness (including coma), vertical gaze paresis, and cognitive disturbance. The presentation is similar to the "top of the basilar syndrome", and early recognition should be prompted. We describe the case of a young female with this vessel variant who experienced a bilateral thalamic stroke. Magnetic resonance angiography demonstrated bilateral thalamic infarcts and a truncated artery of Percheron. Occlusion of the vessel was presumably due to embolism from a patent foramen ovale. Thrombolysis was performed, with incomplete symptom remission, cognitive impairment, and persistence of speech disorders. Early recognition and treatment of posterior circulation strokes is mandatory, and further investigation for underlying stroke etiologies is needed.

Group II and III metabotropic glutamate receptors and the control of the nucleus reticularis thalami input to rat thalamocortical neurones in vitro.

PubMed

Turner, J P; Salt, T E

2003-01-01

Intracellular recordings were made from neurones in the thalamic reticular nucleus (TRN) and ventro-basal (VB) thalamus in slices of rat midbrain in vitro. Electrical stimulation of the medial lemniscus or TRN resulted in the generation of complex synaptic potentials containing disynaptic inhibitory post-synaptic potentials (IPSPs) in VB thalamocortical neurones. Analysis of the excitatory synaptic responses in TRN neurones indicates they can produce burst output response irrespective of the level of sub-threshold membrane potential. This suggests that network-evoked IPSPs in VB thalamocortical neurones occur following a burst of TRN action potentials. Using ionotropic glutamate receptor antagonists, the activation of these disynaptic events was blocked, and the monosynaptic IPSPs that resulted from the direct activation of the TRN could be isolated. The selective Group II agonists LY354740 (1-10 microM) and N-acetyl-aspartyl-glutamate (NAAG; 100-500 microM) both caused a reversible depression of these monosynaptic TRN IPSPs without any effect on membrane potential or input resistance. Likewise, the specific Group III agonist L-2-amino-4-phosphonobutanoate (10-500 microM), but not (RS)-4-phosphonophenylglycine (1 and 30 microM) also caused a reversible depression of these IPSPs, again without any effect on membrane potential or input resistance.Thus, the IPSPs recorded in VB thalamocortical neurones, evoked by TRN activation, can be depressed by the activation of either Group II or III metabotropic glutamate receptors. This is consistent with the location of these receptor types on the presynaptic terminals of TRN axons in the VB thalamus. This raises the possibility that, during periods of intense excitatory activity, glutamate release could influence the release of GABA from TRN axon terminals in the thalamus. In addition, as NAAG is located in the axons and terminals arising from the TRN, there is the possibility that this dipeptide is also released by these terminals to control the release of GABA during periods of high activity in the TRN.

Drivers of the primate thalamus

PubMed Central

Rovó, Zita; Ulbert, István; Acsády, László

2012-01-01

The activity of thalamocortical neurons is largely determined by giant excitatory terminals, called drivers. These afferents may arise from neocortex or from subcortical centers; however their exact distribution, segregation or putative absence in given thalamic nuclei are unknown. To unravel the nucleus-specific composition of drivers, we mapped the entire macaque thalamus utilizing vesicular glutamate transporters 1 and 2 to label cortical and subcortical afferents, respectively. Large thalamic territories were innervated exclusively either by giant vGLUT2- or vGLUT1-positive boutons. Co-distribution of drivers with different origin was not abundant. In several thalamic regions, no giant terminals of any type could be detected at light microscopic level. Electron microscopic observation of these territories revealed either the complete absence of large multisynaptic excitatory terminals (basal ganglia-recipient nuclei) or the presence of both vGLUT1- and vGLUT2-positive terminals, which were significantly smaller than their giant counterparts (intralaminar nuclei, medial pulvinar). In the basal ganglia-recipient thalamus, giant inhibitory terminals replaced the excitatory driver inputs. The pulvinar and the mediodorsal nucleus displayed subnuclear heterogeneity in their driver assemblies. These results show that distinct thalamic territories can be under pure subcortical or cortical control; however there is significant variability in the composition of major excitatory inputs in several thalamic regions. Since thalamic information transfer depends on the origin and complexity of the excitatory inputs, this suggests that the computations performed by individual thalamic regions display considerable variability. Finally, the map of driver distribution may help to resolve the morphological basis of human diseases involving different parts of the thalamus. PMID:23223308

Synaptic physiology of the flow of information in the cat's visual cortex in vivo

PubMed Central

Hirsch, Judith A; Martinez, Luis M; Alonso, José-Manuel; Desai, Komal; Pillai, Cinthi; Pierre, Carhine

2002-01-01

Each stage of the striate cortical circuit extracts novel information about the visual environment. We asked if this analytic process reflected laminar variations in synaptic physiology by making whole-cell recording with dye-filled electrodes from the cat's visual cortex and thalamus; the stimuli were flashed spots. Thalamic afferents terminate in layer 4, which contains two types of cell, simple and complex, distinguished by the spatial structure of the receptive field. Previously, we had found that the postsynaptic and spike responses of simple cells reliably followed the time course of flash-evoked thalamic activity. Here we report that complex cells in layer 4 (or cells intermediate between simple and complex) similarly reprised thalamic activity (response/trial, 99 ± 1.9 %; response duration 159 ± 57 ms; latency 25 ± 4 ms; average ± standard deviation; n = 7). Thus, all cells in layer 4 share a common synaptic physiology that allows secure integration of thalamic input. By contrast, at the second cortical stage (layer 2+3), where layer 4 directs its output, postsynaptic responses did not track simple patterns of antecedent activity. Typical responses to the static stimulus were intermittent and brief (response/trial, 31 ± 40 %; response duration 72 ± 60 ms, latency 39 ± 7 ms; n = 11). Only richer stimuli like those including motion evoked reliable responses. All told, the second level of cortical processing differs markedly from the first. At that later stage, ascending information seems strongly gated by connections between cortical neurons. Inputs must be combined in newly specified patterns to influence intracortical stages of processing. PMID:11927691

Temporal precision in the visual pathway through the interplay of excitation and stimulus-driven suppression.

PubMed

Butts, Daniel A; Weng, Chong; Jin, Jianzhong; Alonso, Jose-Manuel; Paninski, Liam

2011-08-03

Visual neurons can respond with extremely precise temporal patterning to visual stimuli that change on much slower time scales. Here, we investigate how the precise timing of cat thalamic spike trains-which can have timing as precise as 1 ms-is related to the stimulus, in the context of both artificial noise and natural visual stimuli. Using a nonlinear modeling framework applied to extracellular data, we demonstrate that the precise timing of thalamic spike trains can be explained by the interplay between an excitatory input and a delayed suppressive input that resembles inhibition, such that neuronal responses only occur in brief windows where excitation exceeds suppression. The resulting description of thalamic computation resembles earlier models of contrast adaptation, suggesting a more general role for mechanisms of contrast adaptation in visual processing. Thus, we describe a more complex computation underlying thalamic responses to artificial and natural stimuli that has implications for understanding how visual information is represented in the early stages of visual processing.

Bilateral thalamic stroke transiently reduces arousals and NREM sleep instability.

PubMed

Luigetti, Marco; Di Lazzaro, Vincenzo; Broccolini, Aldobrando; Vollono, Catello; Dittoni, Serena; Frisullo, Giovanni; Pilato, Fabio; Profice, Paolo; Losurdo, Anna; Morosetti, Roberta; Testani, Elisa; Colicchio, Salvatore; Della Marca, Giacomo

2011-01-15

The vascularization of the human thalami is supplied by many perforating arteries, which exhibit complex distribution and many possible individual variations. One rare variant is the artery of Percheron that supplies the paramedian thalami bilaterally. Its ictal occlusion may result in a symmetric paramedian infarction, which generally leads to impairment of consciousness associated with hypersomnia. Our aim is to describe in detail sleep-wake schedules, sleep structure and microstructure in a 68-year-old patient with occlusion of Percheron's artery. EEG monitoring, performed 24 h after the onset of symptoms, showed severe disruption of the sleep-wake cycle, with episodes of sleep and wakefulness recurring irregularly during day and night. Thalamic nuclei are part of the human arousal system; medial thalamic nuclei play a pivotal role in sleep regulation at different levels. A diagnosis of paramedian thalamic infarction should be considered in patients who present with recurrent episodes of unresponsiveness. Copyright © 2010 Elsevier B.V. All rights reserved.

Investigating local and long-range neuronal network dynamics by simultaneous optogenetics, reverse microdialysis and silicon probe recordings in vivo

PubMed Central

Taylor, Hannah; Schmiedt, Joscha T.; Çarçak, Nihan; Onat, Filiz; Di Giovanni, Giuseppe; Lambert, Régis; Leresche, Nathalie; Crunelli, Vincenzo; David, Francois

2014-01-01

Background The advent of optogenetics has given neuroscientists the opportunity to excite or inhibit neuronal population activity with high temporal resolution and cellular selectivity. Thus, when combined with recordings of neuronal ensemble activity in freely moving animals optogenetics can provide an unprecedented snapshot of the contribution of neuronal assemblies to (patho)physiological conditions in vivo. Still, the combination of optogenetic and silicone probe (or tetrode) recordings does not allow investigation of the role played by voltage- and transmitter-gated channels of the opsin-transfected neurons and/or other adjacent neurons in controlling neuronal activity. New method and results We demonstrate that optogenetics and silicone probe recordings can be combined with intracerebral reverse microdialysis for the long-term delivery of neuroactive drugs around the optic fiber and silicone probe. In particular, we show the effect of antagonists of T-type Ca2+ channels, hyperpolarization-activated cyclic nucleotide-gated channels and metabotropic glutamate receptors on silicone probe-recorded activity of the local opsin-transfected neurons in the ventrobasal thalamus, and demonstrate the changes that the block of these thalamic channels/receptors brings about in the network dynamics of distant somatotopic cortical neuronal ensembles. Comparison with existing methods This is the first demonstration of successfully combining optogenetics and neuronal ensemble recordings with reverse microdialysis. This combination of techniques overcomes some of the disadvantages that are associated with the use of intracerebral injection of a drug-containing solution at the site of laser activation. Conclusions The combination of reverse microdialysis, silicone probe recordings and optogenetics can unravel the short and long-term effects of specific transmitter- and voltage-gated channels on laser-modulated firing at the site of optogenetic stimulation and the actions that these manipulations exert on distant neuronal populations. PMID:25004203

Role of Neurotrophins on Postnatal Neurogenesis in the Thalamus: Prenatal Exposure to Ethanol

PubMed Central

Mooney, Sandra M.; Miller, Michael W.

2011-01-01

A second wave of neuronal generation occurs in the ventrobasal nucleus of the rat thalamus (VB) during the first three postnatal weeks. The present study tested the hypotheses (1) that postnatal neurogenesis in the VB is neurotrophin-regulated and (2) that ethanol-induced changes in this proliferation are mediated by neurotrophins. The first studies examined the effects of neurotrophins on the numbers of cycling cells in ex vivo preparations of the VB from three-day-old rats. The proportion of cycling (Ki-67-positive) VB cells was higher in cultured thalamic slices treated with neurotrophins than in controls. Interestingly, this increase occurred with nerve growth factor (NGF) alone or with a combination of NGF and brain-derived neurotrophic factor (BDNF), but not with BDNF alone. Based on these data, the VBs from young offspring of pregnant rats fed an ethanol-containing or an isocaloric non-alcoholic liquid diet were examined between postnatal day (P) 1 and P31. Studies used enzyme-linked immunosorbent assays and immunoblots to explore the effects of ethanol on the expression of neurotrophins, their receptors, and representative signaling proteins. Ethanol altered the expression of neurotrophins and receptors throughout the first postnatal month. Expression of NGF increased, but there was no change in the expression of BDNF. The high affinity receptors (TrkA and TrkB) were unchanged but ethanol decreased expression of the low affinity receptor, p75. One downstream signaling protein, extracellular signal-regulated kinase (ERK), decreased but Akt expression was unchanged. Thus, postnatal cell proliferation in the VB of young rat pups is neurotrophin-responsive and is affected by ethanol. PMID:21277941

Inhibition of Cav3.2 T-type Calcium Channels by Its Intracellular I-II Loop*

PubMed Central

Monteil, Arnaud; Chausson, Patrick; Boutourlinsky, Katia; Mezghrani, Alexandre; Huc-Brandt, Sylvaine; Blesneac, Iulia; Bidaud, Isabelle; Lemmers, Céline; Leresche, Nathalie; Lambert, Régis C.; Lory, Philippe

2015-01-01

Voltage-dependent calcium channels (Cav) of the T-type family (Cav3.1, Cav3.2, and Cav3.3) are activated by low threshold membrane depolarization and contribute greatly to neuronal network excitability. Enhanced T-type channel activity, especially Cav3.2, contributes to disease states, including absence epilepsy. Interestingly, the intracellular loop connecting domains I and II (I-II loop) of Cav3.2 channels is implicated in the control of both surface expression and channel gating, indicating that this I-II loop plays an important regulatory role in T-type current. Here we describe that co-expression of this I-II loop or its proximal region (Δ1-Cav3.2; Ser423–Pro542) together with recombinant full-length Cav3.2 channel inhibited T-type current without affecting channel expression and membrane incorporation. Similar T-type current inhibition was obtained in NG 108-15 neuroblastoma cells that constitutively express Cav3.2 channels. Of interest, Δ1-Cav3.2 inhibited both Cav3.2 and Cav3.1 but not Cav3.3 currents. Efficacy of Δ1-Cav3.2 to inhibit native T-type channels was assessed in thalamic neurons using viral transduction. We describe that T-type current was significantly inhibited in the ventrobasal neurons that express Cav3.1, whereas in nucleus reticularis thalami neurons that express Cav3.2 and Cav3.3 channels, only the fast inactivating T-type current (Cav3.2 component) was significantly inhibited. Altogether, these data describe a new strategy to differentially inhibit Cav3 isoforms of the T-type calcium channels. PMID:25931121

Investigating local and long-range neuronal network dynamics by simultaneous optogenetics, reverse microdialysis and silicon probe recordings in vivo.

PubMed

Taylor, Hannah; Schmiedt, Joscha T; Carçak, Nihan; Onat, Filiz; Di Giovanni, Giuseppe; Lambert, Régis; Leresche, Nathalie; Crunelli, Vincenzo; David, Francois

2014-09-30

The advent of optogenetics has given neuroscientists the opportunity to excite or inhibit neuronal population activity with high temporal resolution and cellular selectivity. Thus, when combined with recordings of neuronal ensemble activity in freely moving animals optogenetics can provide an unprecedented snapshot of the contribution of neuronal assemblies to (patho)physiological conditions in vivo. Still, the combination of optogenetic and silicone probe (or tetrode) recordings does not allow investigation of the role played by voltage- and transmitter-gated channels of the opsin-transfected neurons and/or other adjacent neurons in controlling neuronal activity. We demonstrate that optogenetics and silicone probe recordings can be combined with intracerebral reverse microdialysis for the long-term delivery of neuroactive drugs around the optic fiber and silicone probe. In particular, we show the effect of antagonists of T-type Ca(2+) channels, hyperpolarization-activated cyclic nucleotide-gated channels and metabotropic glutamate receptors on silicone probe-recorded activity of the local opsin-transfected neurons in the ventrobasal thalamus, and demonstrate the changes that the block of these thalamic channels/receptors brings about in the network dynamics of distant somatotopic cortical neuronal ensembles. This is the first demonstration of successfully combining optogenetics and neuronal ensemble recordings with reverse microdialysis. This combination of techniques overcomes some of the disadvantages that are associated with the use of intracerebral injection of a drug-containing solution at the site of laser activation. The combination of reverse microdialysis, silicone probe recordings and optogenetics can unravel the short and long-term effects of specific transmitter- and voltage-gated channels on laser-modulated firing at the site of optogenetic stimulation and the actions that these manipulations exert on distant neuronal populations. Copyright © 2014. Published by Elsevier B.V.

Effective connectivity of ascending and descending frontal-thalamic pathways during sustained attention: Complex brain network interactions in adolescence

PubMed Central

Jagtap, Pranav; Diwadkar, Vaibhav A.

2016-01-01

Frontal-thalamic interactions are crucial for bottom-up gating and top-down control, yet have not been well studied from brain network perspectives. We applied network modeling of fMRI signals (Dynamic Causal Modeling; DCM) to investigate frontal-thalamic interactions during an attention task with parametrically varying levels of demand. fMRI was collected while subjects participated in a sustained continuous performance task with low and high attention demands. 162 competing model architectures were employed in DCM to evaluate hypotheses on bilateral frontal-thalamic connections and their modulation by attention demand, selected at a second level using Bayesian Model Selection. The model architecture evinced significant contextual modulation by attention of ascending (thalamus → dPFC) and descending (dPFC → thalamus) pathways. However, modulation of these pathways was asymmetric: While positive modulation of the ascending pathway was comparable across attention demand, modulation of the descending pathway was significantly greater when attention demands were increased. Increased modulation of the (dPFC → thalamus) pathway in response to increased attention demand constitutes novel evidence of attention-related gain in the connectivity of the descending attention pathway. By comparison demand-independent modulation of the ascending (thalamus → dPFC) pathway suggests unbiased thalamic inputs to the cortex in the context of the paradigm. PMID:27145923

Model-based iterative learning control of Parkinsonian state in thalamic relay neuron

NASA Astrophysics Data System (ADS)

Liu, Chen; Wang, Jiang; Li, Huiyan; Xue, Zhiqin; Deng, Bin; Wei, Xile

2014-09-01

Although the beneficial effects of chronic deep brain stimulation on Parkinson's disease motor symptoms are now largely confirmed, the underlying mechanisms behind deep brain stimulation remain unclear and under debate. Hence, the selection of stimulation parameters is full of challenges. Additionally, due to the complexity of neural system, together with omnipresent noises, the accurate model of thalamic relay neuron is unknown. Thus, the iterative learning control of the thalamic relay neuron's Parkinsonian state based on various variables is presented. Combining the iterative learning control with typical proportional-integral control algorithm, a novel and efficient control strategy is proposed, which does not require any particular knowledge on the detailed physiological characteristics of cortico-basal ganglia-thalamocortical loop and can automatically adjust the stimulation parameters. Simulation results demonstrate the feasibility of the proposed control strategy to restore the fidelity of thalamic relay in the Parkinsonian condition. Furthermore, through changing the important parameter—the maximum ionic conductance densities of low-threshold calcium current, the dominant characteristic of the proposed method which is independent of the accurate model can be further verified.

Motion illusion – evidence towards human vestibulo-thalamic projections

PubMed Central

Shaikh, Aasef G.; Straumann, Dominik; Palla, Antonella

2017-01-01

Introduction Contemporary studies speculated that cerebellar network responsible for motion perception projects to the cerebral cortex via vestibulo-thalamus. Here we sought for the physiological properties of vestibulo-thalamic pathway responsible for the motion perception. Methods Healthy subjects and the patient with focal vestibulo-thalamic lacunar stroke spun a hand-held rheostat to approximate the value of perceived angular velocity during whole-body passive earth-vertical axis rotations in yaw plane. Vestibulo-ocular reflex was simultaneously measured with high-resolution search coils (paradigm 1). In primates the vestibulo-thalamic projections remain medial and then dorsomedial to the subthalamus. Therefore the paradigm 2 assessed the effects of high-frequency subthalamic nucleus electrical stimulation through the medial and caudal deep brain stimulation electrode in five subjects with Parkinson’s disease. Results Paradigm 1 discovered directional mismatch of perceived rotation in a patient with vestiblo-thalamic lacune. There was no such mismatch in vestibulo-ocular reflex. Healthy subjects did not have such directional discrepancy of perceived motion. The results confirmed that perceived angular motion is relayed through the thalamus. Stimulation through medial and caudal-most electrode of subthalamic deep brain stimulator in paradigm 2 resulted in perception of rotational motion in the horizontal semicircular canal plane. One patient perceived riding a swing, a complex motion, possibly the combination of vertical canal and otolith derived signals representing pitch and fore-aft motion respectively. Conclusion The results examined physiological properties of the vestibulo-thalamic pathway that passes in proximity to the subthalamic nucleus conducting pure semicircular canal signals and convergent signals from the semicircular canals and the otoliths. PMID:28127679

Abnormalities of thalamic activation and cognition in schizophrenia.

PubMed

Andrews, Jessica; Wang, Lei; Csernansky, John G; Gado, Mokhtar H; Barch, Deanna M

2006-03-01

Functional and structural magnetic resonance imaging (MRI) was used to investigate relationships among structure, functional activation, and cognitive deficits related to the thalamus in individuals with schizophrenia and healthy comparison subjects. Thirty-six schizophrenia subjects and 28 healthy comparison subjects matched by age, gender, race, and parental socioeconomic status underwent structural and functional MRI while performing a series of memory tasks, including an N-back task (working memory), intentional memorization of a series of pictures or words (episodic encoding), and a yes/no recognition task. Functional activation magnitudes in seven regions of interest within the thalamic complex, as defined by anatomical and functional criteria, were computed for each group. Participants with schizophrenia exhibited decreased activation within the whole thalamus, the anterior nuclei, and the medial dorsal nucleus. These nuclei overlap with subregions of the thalamic surface that the authors previously reported to exhibit morphological abnormalities in schizophrenia. However, there were no significant correlations between specific dimensions of thalamic shape variation (i.e., eigenvectors) and the activation patterns within thalamic regions of interest. Better performance on the working memory task among individuals with schizophrenia was significantly associated with increased activation in the anterior nuclei, the centromedian nucleus, the pulvinar, and the ventrolateral nuclei. These results suggest that there are limited relationships between morphological and functional abnormalities of the thalamus in schizophrenia subjects and highlight the importance of investigating relationships between brain structure and function.

Thalamus and Language: What do we know from vascular and degenerative pathologies.

PubMed

Moretti, Rita; Caruso, Paola; Crisman, Elena; Gazzin, Silvia

2018-01-01

Language is a complex cognitive task that is essential in our daily life. For decades, researchers have tried to understand the different role of cortical and subcortical areas in cerebral language representations and language processing. Language-related cortical zones are richly interconnected with other cortical regions (particularly via myelinated fibre tracts), but they also participate in subcortical feedback loops within the basal ganglia (caudate nucleus and putamen) and thalamus. The most relevant thalamic functions are the control and adaptation of cortico-cortical connectivity and bandwidth for information exchange. Despite having the knowledge of thalamic and basal ganglionic involvement in linguistic operations, the specific functions of these subcortical structures remain rather controversial. The aim of this study is to better understand the role of thalamus in language network, exploring the functional configuration of basal network components. The language specificity of subcortical supporting activity and the associated clinical features in thalamic involvement are also highlighted.

Holmes' tremor as a delayed complication of thalamic stroke.

PubMed

Martins, William Alves; Marrone, Luiz Carlos Porcello; Fussiger, Helena; Vedana, Viviane Maria; Cristovam, Rafael do Amaral; Taietti, Marjorye Z; Marrone, Antonio Carlos Huf

2016-04-01

Movement disorders are not commonly associated with stroke. Accordingly, thalamic strokes have rarely been associated with tremor, pseudo-athetosis and dystonic postures. We present a 75-year-old man who developed a disabling tremor 1 year after a posterolateral thalamic stroke. This tremor had low frequency (3-4 Hz), did not disappear on focus and was exacerbated by maintaining a static posture and on target pursuit, which made it very difficult to perform basic functions. MRI demonstrated an old ischemic lesion at the left posterolateral thalamus. Treatment with levodopa led to symptom control. Lesions in the midbrain, cerebellum and thalamus may cause Holmes' tremor. Delayed onset of symptoms is usually seen, sometimes appearing 2 years after the original injury. This may be due to maturation of a complex neuronal network, leading to slow dopaminergic denervation. Further studies are needed to improve our understanding of this unique disconnection syndrome. Copyright © 2015 Elsevier Ltd. All rights reserved.

What is the Thalamus in Zebrafish?

PubMed Central

Mueller, Thomas

2012-01-01

Current research on the thalamus and related structures in the zebrafish diencephalon identifies an increasing number of both neurological structures and ontogenetic processes as evolutionary conserved between teleosts and mammals. The patterning processes, for example, which during the embryonic development of zebrafish form the thalamus proper appear largely conserved. Yet also striking differences between zebrafish and other vertebrates have been observed, particularly when we look at mature and histologically differentiated brains. A case in point is the migrated preglomerular complex of zebrafish which evolved only within the lineage of ray-finned fish and has no counterpart in mammals or tetrapod vertebrates. Based on its function as a sensory relay station with projections to pallial zones, the preglomerular complex has been compared to specific thalamic nuclei in mammals. However, no thalamic projections to the zebrafish dorsal pallium, which corresponds topologically to the mammalian isocortex, have been identified. Merely one teleostean thalamic nucleus proper, the auditory nucleus, projects to a part of the dorsal telencephalon, the pallial amygdala. Studies on patterning mechanisms identify a rostral and caudal domain in the embryonic thalamus proper. In both, teleosts and mammals, the rostral domain gives rise to GABAergic neurons, whereas glutamatergic neurons originate in the caudal domain of the zebrafish thalamus. The distribution of GABAergic derivatives in the adult zebrafish brain, furthermore, revealed previously overlooked thalamic nuclei and redefined already established ones. These findings require some reconsideration regarding the topological origin of these adult structures. In what follows, I discuss how evolutionary conserved and newly acquired features of the developing and adult zebrafish thalamus can be compared to the mammalian situation. PMID:22586363

Thalamic Deep Brain Stimulation for Writer's Cramp.

PubMed

Cho, Chul Bum; Park, Hae Kwan; Lee, Kyung Jin; Rha, Hyoung Kyun

2009-07-01

Writer's cramp is a type of idiopathic focal hand dystonia characterized by muscle cramps that accompany execution of the writing task specifically. There has been renewed interest in neurosurgical procedures for the treatment of dystonia over the past several years. In particular, deep brain stimulation (DBS) has received increasing attention as a therapeutic option for patients with dystonia. However, to date, limited reporters made investigations into DBS in relation to the Writer's cramp. In this case, unilateral Ventro-oralis complex (Vo) DBS resulted in a major improvement in patient's focal dystonic movement disorders. Her post-operative Burke-Fahn-Marsden Dystonia Rating (BFMDR) scale demonstrated 1 compared with pre-operative BFMDR scale 4. We conclude that thalamic Vo complex DBS may be an important neurosurgical therapeutic option for Writer's cramp.

Midline thalamic reuniens lesions improve executive behaviors.

PubMed

Prasad, J A; Abela, A R; Chudasama, Y

2017-03-14

The role of the thalamus in complex cognitive behavior is a topic of increasing interest. Here we demonstrate that lesions of the nucleus reuniens (NRe), a midline thalamic nucleus interconnected with both hippocampal and prefrontal circuitry, lead to enhancement of executive behaviors typically associated with the prefrontal cortex. Rats were tested on four behavioral tasks: (1) the combined attention-memory (CAM) task, which simultaneously assessed attention to a visual target and memory for that target over a variable delay; (2) spatial memory using a radial arm maze, (3) discrimination and reversal learning using a touchscreen operant platform, and (4) decision-making with delayed outcomes. Following NRe lesions, the animals became more efficient in their performance, responding with shorter reaction times but also less impulsively than controls. This change, combined with a decrease in perseverative responses, led to focused attention in the CAM task and accelerated learning in the visual discrimination task. There were no observed changes in tasks involving either spatial memory or value-based decision making. These data complement ongoing efforts to understand the role of midline thalamic structures in human cognition, including the development of thalamic stimulation as a therapeutic strategy for acquired cognitive disabilities (Schiff, 2008; Mair et al., 2011), and point to the NRe as a potential target for clinical intervention. Published by Elsevier Ltd.

The neurobiology of thalamic amnesia: Contributions of medial thalamus and prefrontal cortex to delayed conditional discrimination.

PubMed

Mair, Robert G; Miller, Rikki L A; Wormwood, Benjamin A; Francoeur, Miranda J; Onos, Kristen D; Gibson, Brett M

2015-07-01

Although medial thalamus is well established as a site of pathology associated with global amnesia, there is uncertainty about which structures are critical and how they affect memory function. Evidence from human and animal research suggests that damage to the mammillothalamic tract and the anterior, mediodorsal (MD), midline (M), and intralaminar (IL) nuclei contribute to different signs of thalamic amnesia. Here we focus on MD and the adjacent M and IL nuclei, structures identified in animal studies as critical nodes in prefrontal cortex (PFC)-related pathways that are necessary for delayed conditional discrimination. Recordings of PFC neurons in rats performing a dynamic delayed non-matching-to position (DNMTP) task revealed discrete populations encoding information related to planning, execution, and outcome of DNMTP-related actions and delay-related activity signaling previous reinforcement. Parallel studies recording the activity of MD and IL neurons and examining the effects of unilateral thalamic inactivation on the responses of PFC neurons demonstrated a close coupling of central thalamic and PFC neurons responding to diverse aspects of DNMTP and provide evidence that thalamus interacts with PFC neurons to give rise to complex goal-directed behavior exemplified by the DNMTP task. Copyright © 2015 Elsevier Ltd. All rights reserved.

Functional Connectivity Parcellation of the Human Thalamus by Independent Component Analysis.

PubMed

Zhang, Sheng; Li, Chiang-Shan R

2017-11-01

As a key structure to relay and integrate information, the thalamus supports multiple cognitive and affective functions through the connectivity between its subnuclei and cortical and subcortical regions. Although extant studies have largely described thalamic regional functions in anatomical terms, evidence accumulates to suggest a more complex picture of subareal activities and connectivities of the thalamus. In this study, we aimed to parcellate the thalamus and examine whole-brain connectivity of its functional clusters. With resting state functional magnetic resonance imaging data from 96 adults, we used independent component analysis (ICA) to parcellate the thalamus into 10 components. On the basis of the independence assumption, ICA helps to identify how subclusters overlap spatially. Whole brain functional connectivity of each subdivision was computed for independent component's time course (ICtc), which is a unique time series to represent an IC. For comparison, we computed seed-region-based functional connectivity using the averaged time course across all voxels within a thalamic subdivision. The results showed that, at p < 10 -6 , corrected, 49% of voxels on average overlapped among subdivisions. Compared with seed-region analysis, ICtc analysis revealed patterns of connectivity that were more distinguished between thalamic clusters. ICtc analysis demonstrated thalamic connectivity to the primary motor cortex, which has eluded the analysis as well as previous studies based on averaged time series, and clarified thalamic connectivity to the hippocampus, caudate nucleus, and precuneus. The new findings elucidate functional organization of the thalamus and suggest that ICA clustering in combination with ICtc rather than seed-region analysis better distinguishes whole-brain connectivities among functional clusters of a brain region.

Influence of anesthesia on cerebral blood flow, cerebral metabolic rate, and brain functional connectivity.

PubMed

Bonhomme, Vincent; Boveroux, Pierre; Hans, Pol; Brichant, Jean François; Vanhaudenhuyse, Audrey; Boly, Melanie; Laureys, Steven

2011-10-01

To describe recent studies exploring brain function under the influence of hypnotic anesthetic agents, and their implications on the understanding of consciousness physiology and anesthesia-induced alteration of consciousness. Cerebral cortex is the primary target of the hypnotic effect of anesthetic agents, and higher-order association areas are more sensitive to this effect than lower-order processing regions. Increasing concentration of anesthetic agents progressively attenuates connectivity in the consciousness networks, while connectivity in lower-order sensory and motor networks is preserved. Alteration of thalamic sub-cortical regulation could compromise the cortical integration of information despite preserved thalamic activation by external stimuli. At concentrations producing unresponsiveness, the activity of consciousness networks becomes anticorrelated with thalamic activity, while connectivity in lower-order sensory networks persists, although with cross-modal interaction alterations. Accumulating evidence suggests that hypnotic anesthetic agents disrupt large-scale cerebral connectivity. This would result in an inability of the brain to generate and integrate information, while external sensory information is still processed at a lower order of complexity.

Dissociable Contributions of Thalamic Nuclei to Recognition Memory: Novel Evidence from a Case of Medial Dorsal Thalamic Damage

ERIC Educational Resources Information Center

Newsome, Rachel N.; Trelle, Alexandra N.; Fidalgo, Celia; Hong, Bryan; Smith, Victoria M.; Jacob, Alexander; Ryan, Jennifer D.; Rosenbaum, R. Shayna; Cowell, Rosemary A.; Barense, Morgan D.

2018-01-01

The thalamic nuclei are thought to play a critical role in recognition memory. Specifically, the anterior thalamic nuclei and medial dorsal nuclei may serve as critical output structures in distinct hippocampal and perirhinal cortex systems, respectively. Existing evidence indicates that damage to the anterior thalamic nuclei leads to impairments…

Thalamic Hemorrhagic Stroke in the Term Newborn: A Specific Neonatal Syndrome With Non-uniform Outcome.

PubMed

Merlini, Laura; Hanquinet, Sylviane; Fluss, Joel

2017-07-01

Neonatal thalamic hemorrhagic stroke is related to cerebral sinus venous thrombosis and associated with neurological sequelae. Predicting factors are however lacking. Clinical and radiological findings at onset and on follow-up of 5 neonates with thalamic hemorrhage stroke are described. All neonates presented with abrupt lethargy, ophistotonos, irritability and/or seizures. The thalamic hemorrhagic stroke was most often unilateral (4/5), involving the posterior/entire thalamus in 3 cases and the anterior thalamus in 2. Cerebral venous thrombosis was identified in a single patient. At follow-up, children with unilateral anterior thalamic hemorrhagic stroke demonstrated thalamic atrophy without neurological symptoms, whereas children whose thalamus lesion was extensive exhibit a porencephalic cavity and presented with late-onset epilepsy. Although deep cerebral venous thrombosis is probably the cause of neonatal thalamic hemorrhagic stroke, its radiological evidence is challenging. Outcome seems dependent of the size and location of thalamic hemorrhagic stroke. Epilepsy is a frequent morbidity after thalamic hemorrhagic stroke.

High Field fMRI Reveals Thalamocortical Integration of Segregated Cognitive and Emotional Processing in Mediodorsal and Intralaminar Thalamic Nuclei

PubMed Central

Metzger, C. D.; Eckert, U.; Steiner, J.; Sartorius, A.; Buchmann, J. E.; Stadler, J.; Tempelmann, C.; Speck, O.; Bogerts, B.; Abler, B.; Walter, M.

2010-01-01

Thalamocortical loops, connecting functionally segregated, higher order cortical regions, and basal ganglia, have been proposed not only for well described motor and sensory regions, but also for limbic and prefrontal areas relevant for affective and cognitive processes. These functions are, however, more specific to humans, rendering most invasive neuroanatomical approaches impossible and interspecies translations difficult. In contrast, non-invasive imaging of functional neuroanatomy using fMRI allows for the development of elaborate task paradigms capable of testing the specific functionalities proposed for these circuits. Until recently, spatial resolution largely limited the anatomical definition of functional clusters at the level of distinct thalamic nuclei. Since their anatomical distinction seems crucial not only for the segregation of cognitive and limbic loops but also for the detection of their functional interaction during cognitive–emotional integration, we applied high resolution fMRI on 7 Tesla. Using an event-related design, we could isolate thalamic effects for preceding attention as well as experience of erotic stimuli. We could demonstrate specific thalamic effects of general emotional arousal in mediodorsal nucleus and effects specific to preceding attention and expectancy in intralaminar centromedian/parafascicular complex. These thalamic effects were paralleled by specific coactivations in the head of caudate nucleus as well as segregated portions of rostral or caudal cingulate cortex and anterior insula supporting distinct thalamo–striato–cortical loops. In addition to predescribed effects of sexual arousal in hypothalamus and ventral striatum, high resolution fMRI could extent this network to paraventricular thalamus encompassing laterodorsal and parataenial nuclei. We could lend evidence to segregated subcortical loops which integrate cognitive and emotional aspects of basic human behavior such as sexual processing. PMID:21088699

Involvement of Neuroinflammation during Brain Development in Social Cognitive Deficits in Autism Spectrum Disorder and Schizophrenia.

PubMed

Nakagawa, Yutaka; Chiba, Kenji

2016-09-01

Development of social cognition, a unique and high-order function, depends on brain maturation from childhood to adulthood in humans. Autism spectrum disorder (ASD) and schizophrenia have similar social cognitive deficits, although age of onset in each disorder is different. Pathogenesis of these disorders is complex and contains several features, including genetic risk factors, environmental risk factors, and sites of abnormalities in the brain. Although several hypotheses have been postulated, they seem to be insufficient to explain how brain alterations associated with symptoms in these disorders develop at distinct developmental stages. Development of ASD appears to be related to cerebellar dysfunction and subsequent thalamic hyperactivation in early childhood. By contrast, schizophrenia seems to be triggered by thalamic hyperactivation in late adolescence, whereas hippocampal aberration has been possibly initiated in childhood. One of the possible culprits is metal homeostasis disturbances that can induce dysfunction of blood-cerebrospinal fluid barrier. Thalamic hyperactivation is thought to be induced by microglia-mediated neuroinflammation and abnormalities of intracerebral environment. Consequently, it is likely that the thalamic hyperactivation triggers dysregulation of the dorsolateral prefrontal cortex for lower brain regions related to social cognition. In this review, we summarize the brain aberration in ASD and schizophrenia and provide a possible mechanism underlying social cognitive deficits in these disorders based on their distinct ages of onset. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Connectivity-based parcellation of the thalamus in multiple sclerosis and its implications for cognitive impairment: A multicenter study.

PubMed

Bisecco, Alvino; Rocca, Maria A; Pagani, Elisabetta; Mancini, Laura; Enzinger, Christian; Gallo, Antonio; Vrenken, Hugo; Stromillo, Maria Laura; Copetti, Massimiliano; Thomas, David L; Fazekas, Franz; Tedeschi, Gioacchino; Barkhof, Frederik; Stefano, Nicola De; Filippi, Massimo

2015-07-01

In this multicenter study, we performed a tractography-based parcellation of the thalamus and its white matter connections to investigate the relationship between thalamic connectivity abnormalities and cognitive impairment in multiple sclerosis (MS). Dual-echo, morphological and diffusion tensor (DT) magnetic resonance imaging (MRI) scans were collected from 52 relapsing-remitting MS patients and 57 healthy controls from six European centers. Patients underwent an extensive neuropsychological assessment. Thalamic connectivity defined regions (CDRs) were segmented based on their cortical connectivity using diffusion tractography-based parcellation. Between-group differences of CDRs and cortico-thalamic tracts DT MRI indices were assessed. A vertex analysis of thalamic shape was also performed. A random forest analysis was run to identify the best imaging predictor of global cognitive impairment and deficits of specific cognitive domains. Twenty-two (43%) MS patients were cognitively impaired (CI). Compared to cognitively preserved, CI MS patients had increased fractional anisotropy of frontal, motor, postcentral and occipital connected CDRs (0.002

Thalamic inhibition: diverse sources, diverse scales

PubMed Central

Halassa, Michael M.; Acsády, László

2016-01-01

The thalamus is the major source of cortical inputs shaping sensation, action and cognition. Thalamic circuits are targeted by two major inhibitory systems: the thalamic reticular nucleus (TRN) and extra-thalamic inhibitory (ETI) inputs. A unifying framework of how these systems operate is currently lacking. Here, we propose that TRN circuits are specialized to exert thalamic control at different spatiotemporal scales. Local inhibition of thalamic spike rates prevails during attentional selection whereas global inhibition more likely during sleep. In contrast, the ETI (arising from basal ganglia, zona incerta, anterior pretectum and pontine reticular formation) provides temporally-precise and focal inhibition, impacting spike timing. Together, these inhibitory systems allow graded control of thalamic output, enabling thalamocortical operations to dynamically match ongoing behavioral demands. PMID:27589879

The pathways connecting the hippocampal formation, the thalamic reuniens nucleus and the thalamic reticular nucleus in the rat.

PubMed

Cavdar, Safiye; Onat, Filiz Y; Cakmak, Yusuf Ozgür; Yananli, Hasan R; Gülçebi, Medine; Aker, Rezzan

2008-03-01

Most dorsal thalamic nuclei send axons to specific areas of the neocortex and to specific sectors of the thalamic reticular nucleus; the neocortex then sends reciprocal connections back to the same thalamic nucleus, directly as well indirectly through a relay in the thalamic reticular nucleus. This can be regarded as a 'canonical' circuit of the sensory thalamus. For the pathways that link the thalamus and the hippocampal formation, only a few comparable connections have been described. The reuniens nucleus of the thalamus sends some of its major cortical efferents to the hippocampal formation. The present study shows that cells of the hippocampal formation as well as cells in the reuniens nucleus are retrogradely labelled following injections of horseradish peroxidase or fluoro-gold into the rostral part of the thalamic reticular nucleus in the rat. Within the hippocampal formation, labelled neurons were localized in the subiculum, predominantly on the ipsilateral side, with fewer neurons labelled contralaterally. Labelled neurons were seen in the hippocampal formation and nucleus reuniens only after injections made in the rostral thalamic reticular nucleus (1.6-1.8 mm caudal to bregma). In addition, the present study confirmed the presence of afferent connections to the rostral thalamic reticular nucleus from cortical (cingulate, orbital and infralimbic, retrosplenial and frontal), midline thalamic (paraventricular, anteromedial, centromedial and mediodorsal thalamic nuclei) and brainstem structures (substantia nigra pars reticularis, ventral tegmental area, periaqueductal grey, superior vestibular and pontine reticular nuclei). These results demonstrate a potential for the thalamo-hippocampal circuitry to influence the functional roles of the thalamic reticular nucleus, and show that thalamo-hippocampal connections resemble the circuitry that links the sensory thalamus and neocortex.

The pathways connecting the hippocampal formation, the thalamic reuniens nucleus and the thalamic reticular nucleus in the rat

PubMed Central

Çavdar, Safiye; Onat, Filiz Y; Çakmak, Yusuf Özgür; Yananli, Hasan R; Gülçebi, Medine; Aker, Rezzan

2008-01-01

Most dorsal thalamic nuclei send axons to specific areas of the neocortex and to specific sectors of the thalamic reticular nucleus; the neocortex then sends reciprocal connections back to the same thalamic nucleus, directly as well indirectly through a relay in the thalamic reticular nucleus. This can be regarded as a ‘canonical’ circuit of the sensory thalamus. For the pathways that link the thalamus and the hippocampal formation, only a few comparable connections have been described. The reuniens nucleus of the thalamus sends some of its major cortical efferents to the hippocampal formation. The present study shows that cells of the hippocampal formation as well as cells in the reuniens nucleus are retrogradely labelled following injections of horseradish peroxidase or fluoro-gold into the rostral part of the thalamic reticular nucleus in the rat. Within the hippocampal formation, labelled neurons were localized in the subiculum, predominantly on the ipsilateral side, with fewer neurons labelled contralaterally. Labelled neurons were seen in the hippocampal formation and nucleus reuniens only after injections made in the rostral thalamic reticular nucleus (1.6–1.8 mm caudal to bregma). In addition, the present study confirmed the presence of afferent connections to the rostral thalamic reticular nucleus from cortical (cingulate, orbital and infralimbic, retrosplenial and frontal), midline thalamic (paraventricular, anteromedial, centromedial and mediodorsal thalamic nuclei) and brainstem structures (substantia nigra pars reticularis, ventral tegmental area, periaqueductal grey, superior vestibular and pontine reticular nuclei). These results demonstrate a potential for the thalamo-hippocampal circuitry to influence the functional roles of the thalamic reticular nucleus, and show that thalamo-hippocampal connections resemble the circuitry that links the sensory thalamus and neocortex. PMID:18221482

Thalamic projections to visual and visuomotor areas (V6 and V6A) in the Rostral Bank of the parieto-occipital sulcus of the Macaque.

PubMed

Gamberini, Michela; Bakola, Sophia; Passarelli, Lauretta; Burman, Kathleen J; Rosa, Marcello G P; Fattori, Patrizia; Galletti, Claudio

2016-04-01

The medial posterior parietal cortex of the primate brain includes different functional areas, which have been defined based on the functional properties, cyto- and myeloarchitectural criteria, and cortico-cortical connections. Here, we describe the thalamic projections to two of these areas (V6 and V6A), based on 14 retrograde neuronal tracer injections in 11 hemispheres of 9 Macaca fascicularis. The injections were placed either by direct visualisation or using electrophysiological guidance, and the location of injection sites was determined post mortem based on cyto- and myeloarchitectural criteria. We found that the majority of the thalamic afferents to the visual area V6 originate in subdivisions of the lateral and inferior pulvinar nuclei, with weaker inputs originating from the central densocellular, paracentral, lateral posterior, lateral geniculate, ventral anterior and mediodorsal nuclei. In contrast, injections in both the dorsal and ventral parts of the visuomotor area V6A revealed strong inputs from the lateral posterior and medial pulvinar nuclei, as well as smaller inputs from the ventrolateral complex and from the central densocellular, paracentral, and mediodorsal nuclei. These projection patterns are in line with the functional properties of injected areas: "dorsal stream" extrastriate area V6 receives information from visuotopically organised subdivisions of the thalamus; whereas visuomotor area V6A, which is involved in the sensory guidance of arm movement, receives its primary afferents from thalamic nuclei that provide high-order somatic and visual input.

Effective connectivity of ascending and descending frontalthalamic pathways during sustained attention: Complex brain network interactions in adolescence.

PubMed

Jagtap, Pranav; Diwadkar, Vaibhav A

2016-07-01

Frontal-thalamic interactions are crucial for bottom-up gating and top-down control, yet have not been well studied from brain network perspectives. We applied network modeling of fMRI signals [dynamic causal modeling (DCM)] to investigate frontal-thalamic interactions during an attention task with parametrically varying levels of demand. fMRI was collected while subjects participated in a sustained continuous performance task with low and high attention demands. 162 competing model architectures were employed in DCM to evaluate hypotheses on bilateral frontal-thalamic connections and their modulation by attention demand, selected at a second level using Bayesian model selection. The model architecture evinced significant contextual modulation by attention of ascending (thalamus → dPFC) and descending (dPFC → thalamus) pathways. However, modulation of these pathways was asymmetric: while positive modulation of the ascending pathway was comparable across attention demand, modulation of the descending pathway was significantly greater when attention demands were increased. Increased modulation of the (dPFC → thalamus) pathway in response to increased attention demand constitutes novel evidence of attention-related gain in the connectivity of the descending attention pathway. By comparison demand-independent modulation of the ascending (thalamus → dPFC) pathway suggests unbiased thalamic inputs to the cortex in the context of the paradigm. Hum Brain Mapp 37:2557-2570, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Localization of mRNA for CHRNA7 in human fetal brain.

PubMed

Agulhon, C; Abitbol, M; Bertrand, D; Malafosse, A

1999-08-02

The aim of this study was to determine the regional distribution in situ of the mRNA for the alpha 7 subunit of the neuronal nicotinic acetylcholine receptor in human fetal brain. We found high levels of alpha 7 gene expression in nuclei that receive sensory information, such as those of the neocortex and hippocampus, the thalamic nuclei, the reticular thalamic nucleus, the pontine nuclei and the superior olive complex. These data support a possible regulatory function for alpha 7-containing receptors in sensory processing, which may be involved in the pathological physiology of schizophrenia and autism. Early alpha 7 gene expression is also consistent with a morphogenetic role for alpha 7 receptors in central nervous system development.

[Deep brain stimulation in the treatment of movement disorders].

PubMed

Goto, Satoshi

2007-11-01

The introduction of deep brain stimulation (DBS) was a historical step forward for the treatment of advanced and medically intractable movement disorders that include Parkinson's disease, dystonias, essential tremor, and Holmes' tremor. DBS is able to modulate the target region electrically in a reversible and adjustable fashion in contrast to an irreversible and destructive lesioning procedure. In the treatment of movement disorders, the potential targets are the thalamic ventral intermediate nucleus (Vim), globus pallidus internus (GPi), subthalamic nucleus (STN), pedunculopontine nucleus (PPN), and thalamic Vo-complex nucleus. With the development of DBS technology and stereotactic neurosurgical techniques, its therapeutic efficacy has been increased while reducing surgical complications. DBS has become an established therapy for disabling movement disorders and is currently being used to treat neuropsychiatric disorders.

Bidirectional modulation of fear extinction by mediodorsal thalamic firing in mice.

PubMed

Lee, Sukchan; Ahmed, Touqeer; Lee, Soojung; Kim, Huisu; Choi, Sukwoo; Kim, Duk-Soo; Kim, Sang Jeong; Cho, Jeiwon; Shin, Hee-Sup

2011-12-25

The mediodorsal thalamic nucleus has been implicated in the control of memory processes. However, the underlying neural mechanism remains unclear. Here we provide evidence for bidirectional modulation of fear extinction by the mediodorsal thalamic nucleus. Mice with a knockout or mediodorsal thalamic nucleus-specific knockdown of phospholipase C β4 exhibited impaired fear extinction. Mutant mediodorsal thalamic nucleus neurons in slices showed enhanced burst firing accompanied by increased T-type Ca(2+) currents; blocking of T channels in vivo rescued the fear extinction. Tetrode recordings in freely moving mice revealed that, during extinction, the single-spike (tonic) frequency of mediodorsal thalamic nucleus neurons increased in wild-type mice, but was static in mutant mice. Furthermore, tonic-evoking microstimulations of the mediodorsal thalamic nucleus, contemporaneous with the extinction tones, rescued fear extinction in mutant mice and facilitated it in wild-type mice. In contrast, burst-evoking microstimulation suppressed extinction in wild-type mice, mimicking the mutation. These results suggest that the firing mode of the mediodorsal thalamic nucleus is critical for the modulation of fear extinction.

The H3.3 K27M mutation results in a poorer prognosis in brainstem gliomas than thalamic gliomas in adults.

PubMed

Feng, Jie; Hao, Shuyu; Pan, Changcun; Wang, Yu; Wu, Zhen; Zhang, Junting; Yan, Hai; Zhang, Liwei; Wan, Hong

2015-11-01

Brainstem and thalamic gliomas are rare, and they are poorly understood in adults. Genetic aberrations that occur in these tumors are still unknown. In this study, we investigated whether thalamic gliomas have different genetic aberrations and clinical outcomes compared with brainstem gliomas in adults. Forty-three glioma samples were selected, including 28 brainstem and 15 thalamic gliomas. The frequency of the K27M mutation in adult midline gliomas was 58.1%. High-grade gliomas in the thalamus were statistically significantly more numerous than brainstem gliomas. Patients with K27M mutant brainstem gliomas had a significantly shorter overall survival than patients with wild-type tumors (P = .020) by Cox regression after adjustment for other independent risk factors. However, there was no statistical tendency toward a poorer overall survival in thalamic gliomas containing the K27M mutation compared with wild-type tumors. The presence of the K27M mutation significantly corresponded with mutations in TP53 in thalamic gliomas. Interestingly, the K27M mutation was mutually exclusive with mutations in IDH1, which was detected only in brainstem gliomas. The microarray data identified 86 differentially expressed genes between brainstem and thalamic gliomas with the K27M mutation. The cyclin-dependent kinase 6 (CDK6) gene, which plays an important role in cancer pathways, was found to be differentially expressed between brainstem and thalamic gliomas with K27M mutations. Although the K27M mutation was frequently observed in adult brainstem and thalamic gliomas, this mutation tended to be associated with a poorer prognosis in brainstem gliomas but not in thalamic gliomas. Brainstem gliomas may present different genetic aberrations from thalamic gliomas. These differences may provide guidance for therapeutic decisions for the treatment of adult brainstem and thalamic gliomas, which may have different molecular targets. Copyright © 2015. Published by Elsevier Inc.

Impaired brainstem and thalamic high-frequency oscillatory EEG activity in migraine between attacks.

PubMed

Porcaro, Camillo; Di Lorenzo, Giorgio; Seri, Stefano; Pierelli, Francesco; Tecchio, Franca; Coppola, Gianluca

2017-09-01

Introduction We investigated whether interictal thalamic dysfunction in migraine without aura (MO) patients is a primary determinant or the expression of its functional disconnection from proximal or distal areas along the somatosensory pathway. Methods Twenty MO patients and twenty healthy volunteers (HVs) underwent an electroencephalographic (EEG) recording during electrical stimulation of the median nerve at the wrist. We used the functional source separation algorithm to extract four functionally constrained nodes (brainstem, thalamus, primary sensory radial, and primary sensory motor tangential parietal sources) along the somatosensory pathway. Two digital filters (1-400 Hz and 450-750 Hz) were applied in order to extract low- (LFO) and high- frequency (HFO) oscillatory activity from the broadband signal. Results Compared to HVs, patients presented significantly lower brainstem (BS) and thalamic (Th) HFO activation bilaterally. No difference between the two cortical HFO as well as in LFO peak activations between the two groups was seen. The age of onset of the headache was positively correlated with HFO power in the right brainstem and thalamus. Conclusions This study provides evidence for complex dysfunction of brainstem and thalamocortical networks under the control of genetic factors that might act by modulating the severity of migraine phenotype.

GABA receptors and T-type Ca2+ channels crosstalk in thalamic networks.

PubMed

Leresche, Nathalie; Lambert, Régis C

2017-06-07

Although the thalamus presents a rather limited repertoire of GABAergic cell types compare to other CNS area, this structure is a privileged system to study how GABA impacts neuronal network excitability. Indeed both glutamatergic thalamocortical (TC) and GABAergic nucleus reticularis thalami (NRT) neurons present a high expression of T-type voltage-dependent Ca 2+ channels whose activation that shapes the output of the thalamus critically depends upon a preceding hyperpolarisation. Because of this strict dependence, a tight functional link between GABA mediated hyperpolarization and T-currents characterizes the thalamic network excitability. In this review we summarize a number of studies showing that the relationships between the various thalamic GABA A/B receptors and T-channels are complex and bidirectional. We discuss how this dynamic interaction sets the global intrathalamic network activity and its long-term plasticity and highlight how the functional relationship between GABA release and T-channel-dependent excitability is finely tuned by the T-channel activation itself. Finally, we illustrate how an impaired balance between T-channels and GABA receptors can lead to pathologically abnormal cellular and network behaviours. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impaired visual short-term memory capacity is distinctively associated with structural connectivity of the posterior thalamic radiation and the splenium of the corpus callosum in preterm-born adults.

PubMed

Menegaux, Aurore; Meng, Chun; Neitzel, Julia; Bäuml, Josef G; Müller, Hermann J; Bartmann, Peter; Wolke, Dieter; Wohlschläger, Afra M; Finke, Kathrin; Sorg, Christian

2017-04-15

Preterm birth is associated with an increased risk for lasting changes in both the cortico-thalamic system and attention; however, the link between cortico-thalamic and attention changes is as yet little understood. In preterm newborns, cortico-cortical and cortico-thalamic structural connectivity are distinctively altered, with increased local clustering for cortico-cortical and decreased integrity for cortico-thalamic connectivity. In preterm-born adults, among the various attention functions, visual short-term memory (vSTM) capacity is selectively impaired. We hypothesized distinct associations between vSTM capacity and the structural integrity of cortico-thalamic and cortico-cortical connections, respectively, in preterm-born adults. A whole-report paradigm of briefly presented letter arrays based on the computationally formalized Theory of Visual Attention (TVA) was used to quantify parameter vSTM capacity in 26 preterm- and 21 full-term-born adults. Fractional anisotropy (FA) of posterior thalamic radiations and the splenium of the corpus callosum obtained by diffusion tensor imaging were analyzed by tract-based spatial statistics and used as proxies for cortico-thalamic and cortico-cortical structural connectivity. The relationship between vSTM capacity and cortico-thalamic and cortico-cortical connectivity, respectively, was significantly modified by prematurity. In full-term-born adults, the higher FA in the right posterior thalamic radiation the higher vSTM capacity; in preterm-born adults this FA-vSTM-relationship was inversed. In the splenium, higher FA was correlated with higher vSTM capacity in preterm-born adults, whereas no significant relationship was evident in full-term-born adults. These results indicate distinct associations between cortico-thalamic and cortico-cortical integrity and vSTM capacity in preterm-and full-term-born adults. Data suggest compensatory cortico-cortical fiber re-organization for attention deficits after preterm delivery. Copyright © 2017 Elsevier Inc. All rights reserved.

Mapping thalamocortical functional connectivity in chronic and early stages of psychotic disorders

PubMed Central

Woodward, Neil D.; Heckers, Stephan

2015-01-01

Objective There is considerable evidence that the thalamus is abnormal in psychotic disorders. Resting-state fMRI (RS-fMRI) has revealed an intriguing pattern of thalamic dysconnectivity in psychosis characterized by reduced prefrontal cortex (PFC) connectivity and increased somatomotor-thalamic connectivity. However, critical knowledge gaps remain with respect to the onset, anatomical specificity, and clinical correlates of thalamic dysconnectivity in psychosis. Method RS-fMRI was collected on 105 healthy subjects and 148 individuals with psychosis, including 53 early stage psychosis patients. Using all 253 subjects, the thalamus was parceled into functional regions-of-interest (ROIs) on the basis of connectivity with six a-priori defined cortical ROIs covering most of the cortical mantle. Functional connectivity between each cortical ROI and its corresponding thalamic ROI was quantified and compared across groups. Significant differences in the ROI-to-ROI analysis were followed up with voxel-wise seed-based analyses to further localize thalamic dysconnectivity. Results ROI analysis revealed reduced PFC-thalamic connectivity and increased somatomotor-thalamic connectivity in both chronic and early stages psychosis patients. PFC hypo-connectivity and motor cortex hyper-connectivity correlated in patients suggesting they result from a common pathophysiological mechanism. Seed-based analyses revealed thalamic hypo-connectivity in psychosis localized to dorsolateral PFC, medial PFC, and cerebellar areas of the well-described ‘executive control’ network. Across all subjects, thalamic connectivity with areas of the fronto-parietal network correlated with cognitive functioning, including verbal learning and memory. Conclusions Thalamocortical dysconnectivity is present in both chronic and early stages of psychosis, includes reduced thalamic connectivity with the executive control network, and is related to cognitive impairment. PMID:26248537

Subcortical mechanisms in language: lexical-semantic mechanisms and the thalamus.

PubMed

Crosson, B

1999-07-01

Four previously published cases of dominant thalamic lesion in which the author has participated are reviewed to gain a better understanding of thalamic participation in lexical-semantic functions. Naming deficits in two cases support Nadeau and Crosson's (1997) hypothesis of a selective engagement mechanism involving the frontal lobes, inferior thalamic peduncle, nucleus reticularis, and other thalamic nuclei, possibly the centromedian nucleus. This mechanism selectively engages those cortical areas required to perform a cognitive task, while maintaining other areas in a state of relative disengagement. Deficits in selective engagement disproportionately affect lexical retrieval based on semantic input, as opposed to lexical and sublexical processes, because the former is more dependent upon this attentional system. The concept of selective engagement is also useful in understanding thalamic participation in working memory, as supported by data from one recent functional neuroimaging study. Other processes also may be compromised in more posterior thalamic lesions which damage the pulvinar but not other components of this selective engagement system. A third case with aphasia after a more superior and posterior thalamic lesion also had oral reading errors similar to those in neglect dyslexia. The pattern of deficits suggested a visual processing problem in the early stages of reading. The fourth case had a category-specific naming deficit after posterior thalamic lesion. Taken together, the latter two cases indicate that the nature of language functions in more posterior regions of the dominant thalamus depends upon the cortical connectivity of the thalamic region. Together, findings from the four cases suggest that thalamic nuclei and systems are involved in multiple processes which directly or indirectly support cortical language functions. Copyright 1999 Academic Press.

Thalamic sensory strokes with and without pain: differences in lesion patterns in the ventral posterior thalamus.

PubMed

Krause, Thomas; Brunecker, Peter; Pittl, Sandra; Taskin, Birol; Laubisch, Dinah; Winter, Benjamin; Lentza, Malamati Eleni; Malzahn, Uwe; Villringer, Kersten; Villringer, Arno; Jungehulsing, Gerhard J

2012-08-01

Vascular lesions of the posterolateral thalamus typically result in a somatosensory syndrome in which some patients develop central neuropathic post-stroke pain (CPSP). Damage to the spinothalamic tract terminus is assumed to be a prerequisite for thalamic CPSP. At the nuclear level, it remains a matter of debate whether the ventral posterolateral nucleus (VPL) or the posterior portion of the ventral medial nucleus (VMpo) constitutes the decisive lesion site. The hypothesis of the study was that lesion location in thalamic CPSP patients differs from that in thalamic stroke patients without pain, and the aim was to identify whether this difference comprises the VPL and/or the VMpo. 30 patients with chronic thalamic stroke and a persistent contralateral somatosensory syndrome were examined. CPSP patients (n=18) were compared with non-pain control patients. By coregistration of a digitised thalamic atlas with T1 weighted MR images, lesion clusters were allocated to the thalamic nuclei. VPL was affected in both groups, but CPSP lesion clusters comprised the more posterior, inferior and lateral parts of the VPL compared with controls. Additional partial involvement of the VMpo was seen in only three pain patients. In three other pain patients, lesions involved neither the VPL nor the VMpo, but mainly affected the anterior pulvinar. This study specifies the role of the VPL in thalamic CPSP and shows that the posterolateratal and inferior parts in particular are critically lesioned in pain patients. In this thalamic subregion, afferents of the spinothalamic tract are known to terminate. In contrast, the data do not support a pivotal impact of the VMpo on thalamic CPSP.

Embryonic development of connections in turtle pallium.

PubMed

Cordery, P; Molnár, Z

1999-10-11

We are interested in similarities and conserved mechanisms in early development of the reptilian and mammalian thalamocortical connections. We set out to analyse connectivity in embryonic turtle brains (Pseudemys scripta elegans, between stages 17 and 25), by using carbocyanine dye tracing. From the earliest stages studied, labelling from dorsal and ventral thalamus revealed backlabelled cells among developing thalamic fibres within the lateral forebrain bundle and striatum, which had similar morphology to backlabelled internal capsule cells in embryonic rat (Molnár and Cordery, 1999). However, thalamic crystal placements did not label cells in the dorsal ventricular ridge (DVR) at any stage examined. Crystal placements into both dorsal and lateral cortex labelled cells in the DVR and, reciprocally, DVR crystal placements labelled cells in the dorsal and lateral cortices. Retrograde labelling revealed that thalamic fibres arrive in the DVR and dorsal cortex by stage 19. The DVR received projections from the nucleus rotundus and the dorsal cortex exclusively from the perirotundal complex (including lateral geniculate nucleus). Thalamic fibres show this remarkable degree of specificity from the earliest stage we could examine with selective retrograde labelling (stage 19). Our study demonstrates that axons of similar cells are among the first to reach dorsal and ventral thalamus in mammals and reptiles. Our connectional analysis in turtle suggests that some cells of the mammalian primitive internal capsule are homologous to a cell group within the reptilian lateral forebrain bundle and striatum and that diverse vertebrate brains might use a highly conserved pattern of early thalamocortical development. Copyright 1999 Wiley-Liss, Inc.

Thalamic Mechanisms in Language: A Reconsideration Based on Recent Findings and Concepts

PubMed Central

Crosson, Bruce

2012-01-01

Recent literature on thalamic aphasia and thalamic activity during neuroimaging is selectively reviewed followed by a consideration of recent anatomic and physiological findings regarding thalamic structure and functions. It is concluded that four related corticothalamic and/or thalamocortical mechanisms impact language processing: (1) selective engagement of task-relevant cortical areas in a heightened state of responsiveness in part through the nucleus reticularis (NR), (2) passing information from one cortical area to another through corticothalamo-cortical mechanisms, (3) sharpening the focus on task-relevant information through corticothalamo-cortical feedback mechanisms, and (4) selection of one language unit over another in the expression of a concept, accomplished in concert with basal ganglia loops. The relationship and interaction of these mechanisms is discussed and integrated with thalamic aphasia and neuroimaging data into a theory of thalamic functions in language. PMID:22831779

Resting-state thalamic dysconnectivity in schizophrenia and relationships with symptoms.

PubMed

Ferri, J; Ford, J M; Roach, B J; Turner, J A; van Erp, T G; Voyvodic, J; Preda, A; Belger, A; Bustillo, J; O'Leary, D; Mueller, B A; Lim, K O; McEwen, S C; Calhoun, V D; Diaz, M; Glover, G; Greve, D; Wible, C G; Vaidya, J G; Potkin, S G; Mathalon, D H

2018-02-15

Schizophrenia (SZ) is a severe neuropsychiatric disorder associated with disrupted connectivity within the thalamic-cortico-cerebellar network. Resting-state functional connectivity studies have reported thalamic hypoconnectivity with the cerebellum and prefrontal cortex as well as thalamic hyperconnectivity with sensory cortical regions in SZ patients compared with healthy comparison participants (HCs). However, fundamental questions remain regarding the clinical significance of these connectivity abnormalities. Resting state seed-based functional connectivity was used to investigate thalamus to whole brain connectivity using multi-site data including 183 SZ patients and 178 matched HCs. Statistical significance was based on a voxel-level FWE-corrected height threshold of p < 0.001. The relationships between positive and negative symptoms of SZ and regions of the brain demonstrating group differences in thalamic connectivity were examined. HC and SZ participants both demonstrated widespread positive connectivity between the thalamus and cortical regions. Compared with HCs, SZ patients had reduced thalamic connectivity with bilateral cerebellum and anterior cingulate cortex. In contrast, SZ patients had greater thalamic connectivity with multiple sensory-motor regions, including bilateral pre- and post-central gyrus, middle/inferior occipital gyrus, and middle/superior temporal gyrus. Thalamus to middle temporal gyrus connectivity was positively correlated with hallucinations and delusions, while thalamus to cerebellar connectivity was negatively correlated with delusions and bizarre behavior. Thalamic hyperconnectivity with sensory regions and hypoconnectivity with cerebellar regions in combination with their relationship to clinical features of SZ suggest that thalamic dysconnectivity may be a core neurobiological feature of SZ that underpins positive symptoms.

Generation of thalamic neurons from mouse embryonic stem cells.

PubMed

Shiraishi, Atsushi; Muguruma, Keiko; Sasai, Yoshiki

2017-04-01

The thalamus is a diencephalic structure that plays crucial roles in relaying and modulating sensory and motor information to the neocortex. The thalamus develops in the dorsal part of the neural tube at the level of the caudal forebrain. However, the molecular mechanisms that are essential for thalamic differentiation are still unknown. Here, we have succeeded in generating thalamic neurons from mouse embryonic stem cells (mESCs) by modifying the default method that induces the most-anterior neural type in self-organizing culture. A low concentration of the caudalizing factor insulin and a MAPK/ERK kinase inhibitor enhanced the expression of the caudal forebrain markers Otx2 and Pax6. BMP7 promoted an increase in thalamic precursors such as Tcf7l2 + /Gbx2 + and Tcf7l2 + /Olig3 + cells. mESC thalamic precursors began to express the glutamate transporter vGlut2 and the axon-specific marker VGF, similar to mature projection neurons. The mESC thalamic neurons extended their axons to cortical layers in both organotypic culture and subcortical transplantation. Thus, we have identified the minimum elements sufficient for in vitro generation of thalamic neurons. These findings expand our knowledge of thalamic development. © 2017. Published by The Company of Biologists Ltd.

Unified thalamic model generates multiple distinct oscillations with state-dependent entrainment by stimulation

PubMed Central

2017-01-01

The thalamus plays a critical role in the genesis of thalamocortical oscillations, yet the underlying mechanisms remain elusive. To understand whether the isolated thalamus can generate multiple distinct oscillations, we developed a biophysical thalamic model to test the hypothesis that generation of and transition between distinct thalamic oscillations can be explained as a function of neuromodulation by acetylcholine (ACh) and norepinephrine (NE) and afferent synaptic excitation. Indeed, the model exhibited four distinct thalamic rhythms (delta, sleep spindle, alpha and gamma oscillations) that span the physiological states corresponding to different arousal levels from deep sleep to focused attention. Our simulation results indicate that generation of these distinct thalamic oscillations is a result of both intrinsic oscillatory cellular properties and specific network connectivity patterns. We then systematically varied the ACh/NE and input levels to generate a complete map of the different oscillatory states and their transitions. Lastly, we applied periodic stimulation to the thalamic network and found that entrainment of thalamic oscillations is highly state-dependent. Our results support the hypothesis that ACh/NE modulation and afferent excitation define thalamic oscillatory states and their response to brain stimulation. Our model proposes a broader and more central role of the thalamus in the genesis of multiple distinct thalamo-cortical rhythms than previously assumed. PMID:29073146

Why do lesions in the rodent anterior thalamic nuclei cause such severe spatial deficits?

PubMed Central

Aggleton, John P.; Nelson, Andrew J.D.

2015-01-01

Lesions of the rodent anterior thalamic nuclei cause severe deficits to multiple spatial learning tasks. Possible explanations for these effects are examined, with particular reference to T-maze alternation. Anterior thalamic lesions not only impair allocentric place learning but also disrupt other spatial processes, including direction learning, path integration, and relative length discriminations, as well as aspects of nonspatial learning, e.g., temporal discriminations. Working memory tasks, such as T-maze alternation, appear particularly sensitive as they combine an array of these spatial and nonspatial demands. This sensitivity partly reflects the different functions supported by individual anterior thalamic nuclei, though it is argued that anterior thalamic lesion effects also arise from covert pathology in sites distal to the thalamus, most critically in the retrosplenial cortex and hippocampus. This two-level account, involving both local and distal lesion effects, explains the range and severity of the spatial deficits following anterior thalamic lesions. These findings highlight how the anterior thalamic nuclei form a key component in a series of interdependent systems that support multiple spatial functions. PMID:25195980

Organization of diencephalic projections from the medullary subnucleus reticularis dorsalis and the adjacent cuneate nucleus: a retrograde and anterograde tracer study in the rat.

PubMed

Villanueva, L; Desbois, C; Le Bars, D; Bernard, J F

1998-01-05

The distribution and organization of diencephalic projections from the subnucleus reticularis dorsalis (SRD) and the neighbouring cuneate nucleus (Cu) were studied in the rat by using microinjections of Phaseolus vulgaris leucoagglutinin in SRD and Cu and wheat germ agglutinin-apo horseradish peroxidase-gold in some selected thalamic areas. As previously reported, the efferent projections from the Cu were essentially contralateral and terminated mainly in the ventroposterolateral thalamic nucleus. Less dense terminals from the Cu were also observed in the posterior thalamic group, the ventral aspect of the zona incerta and the caudal and dorsal portion of the reuniens area. Retrograde tracer injections in the medial ventroposterolateral thalamic nucleus labeled numerous cells in the contralateral Cu, with a smaller number in the gracile nucleus. From the SRD, terminals were observed in the lateral aspect of the ventromedial thalamic nucleus, the lateral parafascicular area and, to a lesser extent, in the ventral aspect of the zona incerta and the core of the reuniens area. Retrograde tracer injections in the lateral part of the ventromedial thalamic nucleus labeled cells in the caudal medulla, many of which were located in the dorsal-most aspect of the SRD throughout its caudo-rostral extent. The existence of SRD-thalamic connections reinforces the idea that the caudal reticular formation is an important nociceptive relay to the thalamus. Our data shed new light on old hypotheses suggesting that, in addition to spino-thalamic pathways, spino-reticulo-thalamic pathways may play an important role in distributing pain signals to the forebrain.

Pre-synaptic kainate receptor-mediated facilitation of glutamate release involves PKA and Ca(2+) -calmodulin at thalamocortical synapses.

PubMed

Andrade-Talavera, Yuniesky; Duque-Feria, Paloma; Sihra, Talvinder S; Rodríguez-Moreno, Antonio

2013-09-01

We have investigated the mechanisms underlying the facilitatory modulation mediated by kainate receptor (KAR) activation in the cortex, using isolated nerve terminals (synaptosomes) and slice preparations. In cortical nerve terminals, kainate (KA, 100 μM) produced an increase in 4-aminopyridine (4-AP)-evoked glutamate release. In thalamocortical slices, KA (1 μM) produced an increase in the amplitude of evoked excitatory post-synaptic currents (eEPSCs) at synapses established between thalamic axon terminals from the ventrobasal nucleus onto stellate neurons of L4 of the somatosensory cortex. In both, synaptosomes and slices, the effect of KA was antagonized by 6-cyano-7-nitroquinoxaline-2,3-dione, and persisted after pre-treatment with a cocktail of antagonists of other receptors whose activation could potentially have produced facilitation of release indirectly. Mechanistically, the observed effects of KA appear to be congruent in synaptosomal and slice preparations. Thus, the facilitation by KA of synaptosomal glutamate release and thalamocortical synaptic transmission were suppressed by the inhibition of protein kinase A and occluded by the stimulation of adenylyl cyclase. Dissecting this G-protein-independent regulation further in thalamocortical slices, the KAR-mediated facilitation of synaptic transmission was found to be sensitive to the block of Ca(2+) permeant KARs by philanthotoxin. Intriguingly, the synaptic facilitation was abrogated by depletion of intracellular Ca(2+) stores by thapsigargin, or inhibition of Ca(2+) -induced Ca(2+) -release by ryanodine. Thus, the KA-mediated modulation was contingent on both Ca(2+) entry through Ca(2+) -permeable KARs and liberation of intracellular Ca(2+) stores. Finally, sensitivity to W-7 indicated that the increased cytosolic [Ca(2+) ] underpinning KAR-mediated regulation of synaptic transmission at thalamocortical synapses, requires downstream activation of calmodulin. We conclude that neocortical pre-synaptic KARs mediate the facilitation of glutamate release and synaptic transmission by a Ca(2+) -calmodulin dependent activation of an adenylyl cyclase/cAMP/protein kinase A signalling cascade, independent of G-protein involvement. © 2013 International Society for Neurochemistry.

Posterior thalamic hemorrhage induces "pusher syndrome".

PubMed

Karnath, Hans-Otto; Johannsen, Leif; Broetz, Doris; Küker, Wilhelm

2005-03-22

Recent findings argue for a pathway in humans for sensing the orientation of gravity and controlling upright body posture, separate from the one for orientation perception of the visual world. Stroke patients with contraversive pushing were shown to experience their body as oriented upright when actually tilted about 20 degrees to the ipsilesional side, in spite of normal visual-vestibular functioning. A recent study suggested the involvement of posterolateral thalamus typically associated with the disorder. To evaluate the relationship between pushing behavior and thalamic function. Over a 3-year period the authors prospectively investigated 40 patients with left- or right-sided thalamic strokes. Twenty-eight percent showed contraversive pushing. The authors found a strong relationship between etiology, vascular territory, lesion size, and neurologic disorders associated with contraversive pushing. Pusher patients had larger lesions that typically were caused by hemorrhage (vs infarcts) located in the posterior thalamus (vs anterior thalamic lesions in those patients without pushing behavior). A paresis of the contralesional extremities was more frequent and more severe in pusher patients. Further, these patients showed more additional spatial neglect with right thalamic lesions, while they tended to be more aphasic with left thalamic lesions. Posterior thalamus seems to be fundamentally involved in our control of upright body posture. Higher pressure, swelling, and other secondary pathologic processes associated with posterior thalamic hemorrhage (vs thalamic infarction) may provoke contraversive pushing in combination with additional neurologic symptoms.

Thalamic deep brain stimulation for writer's cramp.

PubMed

Fukaya, Chikashi; Katayama, Yoichi; Kano, Toshikazu; Nagaoka, Takafumi; Kobayashi, Kazutaka; Oshima, Hideki; Yamamoto, Takamitsu

2007-11-01

Writer's cramp is a type of idiopathic focal hand dystonia characterized by muscle cramps that accompany execution of the writing task specifically. In this report, the authors describe the clinical outcome after thalamic deep brain stimulation (DBS) therapy in patients with writer's cramp and present an illustrative case with which they compare the effects of pallidal and thalamic stimulation. In addition to these results for the clinical effectiveness, they also examine the best point and pattern for therapeutic stimulation of the motor thalamus, including the nucleus ventrooralis (VO) and the ventralis intermedius nucleus (VIM), for writer's cramp. The authors applied thalamic DBS in five patients with writer's cramp. The inclusion criteria for the DBS trial in this disorder were a diagnosis of idiopathic writer's cramp and the absence of a positive response to medication. The exclusion criteria included significant cognitive dysfunction, active psychiatric symptoms, and evidence of other central nervous system diseases or other medical disorders. In one of the cases, DBS leads were implanted into both the globus pallidus internus and the VO/VIM, and test stimulation was performed for 1 week. The authors thus had an opportunity to compare the effects of pallidal and thalamic stimulation in this patient. Immediately after the initiation of thalamic stimulation, the neurological deficits associated with writer's cramp were improved in all five cases. Postoperatively all preoperative scale scores indicating the seriousness of the writer's cramp were significantly lower (p < 0.001). In the patient in whom two DBS leads were implanted, the clinical effect of thalamic stimulation was better than that of pallidal stimulation. During the thalamic stimulation, the maximum effect was obtained when stimulation was applied to both the VO and the VIM widely, compared with being applied only within the VO. The authors successfully treated patients with writer's cramp by thalamic DBS. Insofar as they are aware, this is the first series in which writer's cramp has been treated with DBS. Thalamic stimulation appears to be a safe and valuable therapeutic option for writer's cramp.

Foxp2 Regulates Identities and Projection Patterns of Thalamic Nuclei During Development.

PubMed

Ebisu, Haruka; Iwai-Takekoshi, Lena; Fujita-Jimbo, Eriko; Momoi, Takashi; Kawasaki, Hiroshi

2017-07-01

The molecular mechanisms underlying the formation of the thalamus during development have been investigated intensively. Although transcription factors distinguishing the thalamic primordium from adjacent brain structures have been uncovered, those involved in patterning inside the thalamus are largely unclear. Here, we show that Foxp2, a member of the forkhead transcription factor family, regulates thalamic patterning during development. We found a graded expression pattern of Foxp2 in the thalamic primordium of the mouse embryo. The expression levels of Foxp2 were high in the posterior region and low in the anterior region of the thalamic primordium. In Foxp2 (R552H) knockin mice, which have a missense loss-of-function mutation in the forkhead domain of Foxp2, thalamic nuclei of the posterior region of the thalamus were shrunken, while those of the intermediate region were expanded. Consistently, Foxp2 (R552H) knockin mice showed changes in thalamocortical projection patterns. Our results uncovered important roles of Foxp2 in thalamic patterning and thalamocortical projections during development. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Midline thalamic neurons are differentially engaged during hippocampus network oscillations.

PubMed

Lara-Vásquez, Ariel; Espinosa, Nelson; Durán, Ernesto; Stockle, Marcelo; Fuentealba, Pablo

2016-07-14

The midline thalamus is reciprocally connected with the medial temporal lobe, where neural circuitry essential for spatial navigation and memory formation resides. Yet, little information is available on the dynamic relationship between activity patterns in the midline thalamus and medial temporal lobe. Here, we report on the functional heterogeneity of anatomically-identified thalamic neurons and the differential modulation of their activity with respect to dorsal hippocampal rhythms in the anesthetized mouse. Midline thalamic neurons expressing the calcium-binding protein calretinin, irrespective of their selective co-expression of calbindin, discharged at overall low levels, did not increase their activity during hippocampal theta oscillations, and their firing rates were inhibited during hippocampal sharp wave-ripples. Conversely, thalamic neurons lacking calretinin discharged at higher rates, increased their activity during hippocampal theta waves, but remained unaffected during sharp wave-ripples. Our results indicate that the midline thalamic system comprises at least two different classes of thalamic projection neuron, which can be partly defined by their differential engagement by hippocampal pathways during specific network oscillations that accompany distinct behavioral contexts. Thus, different midline thalamic neuronal populations might be selectively recruited to support distinct stages of memory processing, consistent with the thalamus being pivotal in the dialogue of cortical circuits.

Loss of thalamic serotonin transporters in early drug-naïve Parkinson’s disease patients is associated with tremor: an [123I]β-CIT SPECT study

PubMed Central

Stoffers, D.; Winogrodzka, A.; Isaias, I.-U.; Costantino, G.; Pezzoli, G.; Ferrarese, C.; Antonini, A.; Wolters, E.-Ch.; Booij, J.

2008-01-01

In vitro studies revealed serotonin transporter (5-HTT) decline in Parkinson’s disease (PD). Yet, few studies investigated thalamic 5-HTT in vivo and its effect on PD heterogeneity. We analyzed thalamic [123I]β-CIT binding (mainly reflecting 5-HTT binding) in 32 drug-naïve PD patients and 13 controls with SPECT. Twenty-six patients were examined twice (17 months apart). Based on UPDRS scores, we identified subgroups of patients with moderate/severe tremor (PDT) and without tremor (PDWT) at the time of clinical diagnosis. Additionally, depressive symptoms were evaluated using the Beck Depression Inventory (BDI) at baseline. Mean thalamic specific to non-specific [123I]β-CIT binding ratio was lower in patients when compared to controls, and further decreased during follow-up. At baseline, average thalamic ratio was significantly lower in the PDT than in the PDWT subgroup. No correlation was found between BDI scores and thalamic binding ratios. Our findings show decline of [123I]β-CIT binding to thalamic 5-HTT in PD and its possible contribution to tremor onset. PMID:18335163

Grey matter volume patterns in thalamic nuclei are associated with familial risk for schizophrenia.

PubMed

Pergola, Giulio; Trizio, Silvestro; Di Carlo, Pasquale; Taurisano, Paolo; Mancini, Marina; Amoroso, Nicola; Nettis, Maria Antonietta; Andriola, Ileana; Caforio, Grazia; Popolizio, Teresa; Rampino, Antonio; Di Giorgio, Annabella; Bertolino, Alessandro; Blasi, Giuseppe

2017-02-01

Previous evidence suggests reduced thalamic grey matter volume (GMV) in patients with schizophrenia (SCZ). However, it is not considered an intermediate phenotype for schizophrenia, possibly because previous studies did not assess the contribution of individual thalamic nuclei and employed univariate statistics. Here, we hypothesized that multivariate statistics would reveal an association of GMV in different thalamic nuclei with familial risk for schizophrenia. We also hypothesized that accounting for the heterogeneity of thalamic GMV in healthy controls would improve the detection of subjects at familial risk for the disorder. We acquired MRI scans for 96 clinically stable SCZ, 55 non-affected siblings of patients with schizophrenia (SIB), and 249 HC. The thalamus was parceled into seven regions of interest (ROIs). After a canonical univariate analysis, we used GMV estimates of thalamic ROIs, together with total thalamic GMV and premorbid intelligence, as features in Random Forests to classify HC, SIB, and SCZ. Then, we computed a Misclassification Index for each individual and tested the improvement in SIB detection after excluding a subsample of HC misclassified as patients. Random Forests discriminated SCZ from HC (accuracy=81%) and SIB from HC (accuracy=75%). Left anteromedial thalamic volumes were significantly associated with both multivariate classifications (p<0.05). Excluding HC misclassified as SCZ improved greatly HC vs. SIB classification (Cohen's d=1.39). These findings suggest that multivariate statistics identify a familial background associated with thalamic GMV reduction in SCZ. They also suggest the relevance of inter-individual variability of GMV patterns for the discrimination of individuals at familial risk for the disorder. Copyright © 2016 Elsevier B.V. All rights reserved.

Integration of cortical and pallidal inputs in the basal ganglia-recipient thalamus of singing birds

PubMed Central

Goldberg, Jesse H.; Farries, Michael A.

2012-01-01

The basal ganglia-recipient thalamus receives inhibitory inputs from the pallidum and excitatory inputs from cortex, but it is unclear how these inputs interact during behavior. We recorded simultaneously from thalamic neurons and their putative synaptically connected pallidal inputs in singing zebra finches. We find, first, that each pallidal spike produces an extremely brief (∼5 ms) pulse of inhibition that completely suppresses thalamic spiking. As a result, thalamic spikes are entrained to pallidal spikes with submillisecond precision. Second, we find that the number of thalamic spikes that discharge within a single pallidal interspike interval (ISI) depends linearly on the duration of that interval but does not depend on pallidal activity prior to the interval. In a detailed biophysical model, our results were not easily explained by the postinhibitory “rebound” mechanism previously observed in anesthetized birds and in brain slices, nor could most of our data be characterized as “gating” of excitatory transmission by inhibitory pallidal input. Instead, we propose a novel “entrainment” mechanism of pallidothalamic transmission that highlights the importance of an excitatory conductance that drives spiking, interacting with brief pulses of pallidal inhibition. Building on our recent finding that cortical inputs can drive syllable-locked rate modulations in thalamic neurons during singing, we report here that excitatory inputs affect thalamic spiking in two ways: by shortening the latency of a thalamic spike after a pallidal spike and by increasing thalamic firing rates within individual pallidal ISIs. We present a unifying biophysical model that can reproduce all known modes of pallidothalamic transmission—rebound, gating, and entrainment—depending on the amount of excitation the thalamic neuron receives. PMID:22673333

Functional connectivity and dynamics of cortical-thalamic networks co-cultured in a dual compartment device

NASA Astrophysics Data System (ADS)

Kanagasabapathi, Thirukumaran T.; Massobrio, Paolo; Barone, Rocco Andrea; Tedesco, Mariateresa; Martinoia, Sergio; Wadman, Wytse J.; Decré, Michel M. J.

2012-06-01

Co-cultures containing dissociated cortical and thalamic cells may provide a unique model for understanding the pathophysiology in the respective neuronal sub-circuitry. In addition, developing an in vitro dissociated co-culture model offers the possibility of studying the system without influence from other neuronal sub-populations. Here we demonstrate a dual compartment system coupled to microelectrode arrays (MEAs) for co-culturing and recording spontaneous activities from neuronal sub-populations. Propagation of electrical activities between cortical and thalamic regions and their interdependence in connectivity is verified by means of a cross-correlation algorithm. We found that burst events originate in the cortical region and drive the entire cortical-thalamic network bursting behavior while mutually weak thalamic connections play a relevant role in sustaining longer burst events in cortical cells. To support these experimental findings, a neuronal network model was developed and used to investigate the interplay between network dynamics and connectivity in the cortical-thalamic system.

Resting-State Alpha in Autism Spectrum Disorder and Alpha Associations with Thalamic Volume

ERIC Educational Resources Information Center

Edgar, J. Christopher; Heiken, Kory; Chen, Yu-Han; Herrington, John D.; Chow, Vivian; Liu, Song; Bloy, Luke; Huang, Mingxiong; Pandey, Juhi; Cannon, Katelyn M.; Qasmieh, Saba; Levy, Susan E.; Schultz, Robert T.; Roberts, Timothy P. L.

2015-01-01

Alpha circuits (8-12 Hz), necessary for basic and complex brain processes, are abnormal in autism spectrum disorder (ASD). The present study obtained estimates of resting-state (RS) alpha activity in children with ASD and examined associations between alpha activity, age, and clinical symptoms. Given that the thalamus modulates cortical RS alpha…

Developmental Alterations of Frontal-Striatal-Thalamic Connectivity in Obsessive-Compulsive Disorder

ERIC Educational Resources Information Center

Fitzgerald, Kate Dimond; Welsh, Robert C.; Stern, Emily R.; Angstadt, Mike; Hanna, Gregory L.; Abelson, James L.; Taylor, Stephan F.

2011-01-01

Objective: Pediatric obsessive-compulsive disorder is characterized by abnormalities of frontal-striatal-thalamic circuitry that appear near illness onset and persist over its course. Distinct frontal-striatal-thalamic loops through cortical centers for cognitive control (anterior cingulate cortex) and emotion processing (ventral medial frontal…

Inhibitory effects of acetylcholine on neurones in the feline nucleus reticularis thalami.

PubMed

Ben-Ari, Y; Dingledine, R; Kanazawa, I; Kelly, J S

1976-10-01

1. Short iontophoretic pulses of acetylcholine (ACh) inhibited almost every spontaneously active cell encountered in the nucleus reticularis thalami of cats anaesthetized with a mixture of halothane, nitrous oxide and oxygen. On 200 cells the mean current needed to eject an effective inhibitory dose of ACh was 67 +/- 2 nA. When the ACh-evoked inhibition was mimicked by gamma-aminobutyric acid (GABA) or glycine on the same cell, the current required to release ACh was found to be approximately twice as great as that required to release an equally effective dose of GABA or glycine. 2. ACh inhibitions developed with a latency which was very much shorter than that for ACh excitation in cells of the ventrobasal complex. The latency of the ACh-evoked inhibition was as rapid as the onset and offset of the excitation of the same cells glutamate and their inhibition by GABA or glycine. 3. The firing pattern of ACh-inhibited neurones in the nucleus reticularis was characterized by periods of prolonged, high frequency bursts, and their mean firing frequency was 22 Hz. Raster dot displays and interspike interval histograms showed that whereas ACh suppressed the spikes that occurred between bursts much more readily than those that occurred during bursts, all spikes were equally sensitive to the depressant action of GABA and glycine. Large doses of ACh provoked or exaggerated burst activity. 4. ACh-evoked inhibition was extremely sensitive to blockade by short iontophoretic applications of atropine, which had no effect on the inhibitions evoked on the same cell equipotent doses of GABA or glycine. The ACh-evoked inhibitions were also antagonized by dihydro-beta-erythroidine released with slightly larger currents. When tested on the same cell, small iontophoretic applications of picrotoxin and bicuculline methoiodide blocked the inhibition evoked by GABA but had no effect on that evoked by ACh. Iontophoretic strychnine only rarely affected the inhibition evoked by ACh, while readily blocking the inhibition evoked on the same cell by an equipotent dose of glycine. In two cats, intravenous strychnine (1-2 mg/kg) had no effect on the ACh-evoked inhibition, while greatly reducing the sensitivity of the cell under study to glycine. 5. Only four out of forty-eight ACh-inhibted cells tested were inhibited by iontophoretic applications of either guanosine or adenosine 3':5'-phosphate. 6. Cells of the nucleus reticularis have been shown to have an inhibitory action on the thalamic relay cells, which are excited by ACh. It is suggested that the presence of both ACh excited and inhibited cells in different nuclei of the thalamus could be of considerable functional significance in gating sensory transmission through the thalamus.

Thalamic lesions in multiple sclerosis by 7T MRI: Clinical implications and relationship to cortical pathology.

PubMed

Harrison, Daniel M; Oh, Jiwon; Roy, Snehashis; Wood, Emily T; Whetstone, Anna; Seigo, Michaela A; Jones, Craig K; Pham, Dzung; van Zijl, Peter; Reich, Daniel S; Calabresi, Peter A

2015-08-01

Pathology in both cortex and deep gray matter contribute to disability in multiple sclerosis (MS). We used the increased signal-to-noise ratio of 7-tesla (7T) MRI to visualize small lesions within the thalamus and to relate this to clinical information and cortical lesions. We obtained 7T MRI scans on 34 MS cases and 15 healthy volunteers. Thalamic lesion number and volume were related to demographic data, clinical disability measures, and lesions in cortical gray matter. Thalamic lesions were found in 24/34 of MS cases. Two lesion subtypes were noted: discrete, ovoid lesions, and more diffuse lesional areas lining the periventricular surface. The number of thalamic lesions was greater in progressive MS compared to relapsing-remitting (mean ±SD, 10.7 ±0.7 vs. 3.0 ±0.7, respectively, p < 0.001). Thalamic lesion burden (count and volume) correlated with EDSS score and measures of cortical lesion burden, but not with white matter lesion burden or white matter volume. Using 7T MRI allows identification of thalamic lesions in MS, which are associated with disability, progressive disease, and cortical lesions. Thalamic lesion analysis may be a simpler, more rapid estimate of overall gray matter lesion burden in MS. © The Author(s), 2015.

Diffusion Tensor Imaging Based Thalamic Segmentation in Deep Brain Stimulation for Chronic Pain Conditions

PubMed Central

Kim, Won; Chivukula, Srinivas; Hauptman, Jason; Pouratian, Nader

2016-01-01

Background/Aims Thalamic deep brain stimulation (DBS) for the treatment of medically refractory pain has largely been abandoned on account of its inconsistent and oftentimes poor efficacy. Our aim here was to use diffusion tensor imaging (DTI)-based segmentation to assess the internal thalamic nuclei of patients who have undergone thalamic DBS for intractable pain and retrospectively correlate lead position with clinical outcome. Methods DTI-based segmentation was performed on 5 patients who underwent sensory thalamus DBS for chronic pain. Postoperative computed tomography (CT) images obtained for electrode placement were fused with preoperative MRIs that had undergone DTI-based thalamic segmentation. Sensory thalamus maps of 4 patients were analyzed for lead positioning and interpatient variability. Results Four patients who experienced significant pain relief following DBS demonstrated contact positions within the DTI-determined sensory thalamus or in its vicinity, whereas one who did not respond to stimulation did not. Only four voxels (2%) within the sensory thalamus were mutually shared among patients; 108 voxels (58%) were uniquely represented. Conclusions DTI-based segmentation of the thalamus can be used to confirm thalamic lead placement relative to the sensory thalamus, and may serve as a useful tool to guide thalamic DBS electrode implantation in the future. PMID:27537848

[Thalamus and Attention].

PubMed

Tokoro, Kazuhiko; Sato, Hironobu; Yamamoto, Mayumi; Nagai, Yoshiko

2015-12-01

Attention is the process by which information and selection occurs, the thalamus plays an important role in the selective attention of visual and auditory information. Selective attention is a conscious effort; however, it occurs subconsciously, as well. The lateral geniculate body (LGB) filters visual information before it reaches the cortex (bottom-up attention). The thalamic reticular nucleus (TRN) provides a strong inhibitory input to both the LGB and pulvinar. This regulation involves focusing a spotlight on important information, as well as inhibiting unnecessary background information. Behavioral contexts more strongly modulate activity of the TRN and pulvinar influencing feedforward and feedback information transmission between the frontal, temporal, parietal and occipital cortical areas (top-down attention). The medial geniculate body (MGB) filters auditory information the TRN inhibits the MGB. Attentional modulation occurring in the auditory pathway among the cochlea, cochlear nucleus, superior olivary complex, and inferior colliculus is more important than that of the MGB and TRN. We also discuss the attentional consequence of thalamic hemorrhage.

Somato-dendritic synapses in the nucleus reticularis thalami of the rat.

PubMed

Csillik, B; Pálfi, A; Gulya, K; Mihály, A; Knyihár-Csillik, Elizabeth

2002-01-01

In the reticular nucleus of the rat thalamus, about 30% of the synapses are brought about by the perikarya of parvalbumin-immunopositive neurons, which establish somato-dendritic synapses with large dendrites of nerve cells of specific thalamic nuclei. Although the parvalbumin-immunopositive presynaptic structures bear resemblance to goblet-like or calyciform axonal endings, electron microscopic immunocytochemistry and in situ hybridization revealed that these structures are parts of the perikaryal cytoplasm studded with synaptic vesicles. In about 15% of the somato-dendritic synapses, axons are seen to be in synaptic contact with the parvalbumin-immunoreactive perikaryon. Double immunohistochemical staining revealed that the parvalbumin immunoreactive presynaptic perikarya and dendrites contained GABA. It is assumed that the peculiar somato-dendritic synaptic complexes subserve the goal of filtration of impulses arriving at the reticular nucleus from various thalamic nuclei, thus processing them for further sampling.

Transient Relay Function of Midline Thalamic Nuclei during Long-Term Memory Consolidation in Humans

ERIC Educational Resources Information Center

Thielen, Jan-Willem; Takashima, Atsuko; Rutters, Femke; Tendolkar, Indira; Fernández, Guillén

2015-01-01

To test the hypothesis that thalamic midline nuclei play a transient role in memory consolidation, we reanalyzed a prospective functional MRI study, contrasting recent and progressively more remote memory retrieval. We revealed a transient thalamic connectivity increase with the hippocampus, the medial prefrontal cortex (mPFC), and a…

Dissociable spatial and non-spatial attentional deficits after circumscribed thalamic stroke.

PubMed

Kraft, Antje; Irlbacher, Kerstin; Finke, Kathrin; Kaufmann, Christian; Kehrer, Stefanie; Liebermann, Daniela; Bundesen, Claus; Brandt, Stephan A

2015-03-01

Thalamic nuclei act as sensory, motor and cognitive relays between multiple subcortical areas and the cerebral cortex. They play a crucial role in cognitive functions such as executive functioning, memory and attention. In the acute period after thalamic stroke attentional deficits are common. The precise functional relevance of specific nuclei or vascular sub regions of the thalamus for attentional sub functions is still unclear. The theory of visual attention (TVA) allows the measurement of four independent attentional parameters (visual short term memory storage capacity (VSTM), visual perceptual processing speed, selective control and spatial weighting). We combined parameter-based assessment based on TVA with lesion symptom mapping in standard stereotactic space in sixteen patients (mean age 41.2 ± 11.0 SD, 6 females), with focal thalamic lesions in the medial (N = 9), lateral (N = 5), anterior (N = 1) or posterior (N = 1) vascular territories of the thalamus. Compared with an age-matched control group of 52 subjects (mean age 40.1 ± 6.4, 35 females), the patients with thalamic lesions were, on the group level, mildly impaired in visual processing speed and VSTM. Patients with lateral thalamic lesions showed a deficit in processing speed while all other TVA parameters were within the normal range. Medial thalamic lesions can be associated with a spatial bias and extinction of targets either in the ipsilesional or the contralesional field. A posterior case with a thalamic lesion of the pulvinar replicated a finding of Habekost and Rostrup (2006), demonstrating a spatial bias to the ipsilesional field, as suggested by the neural theory of visual attention (NTVA) (Bundesen, Habekost, & Kyllingsbæk, 2011). A case with an anterior-medial thalamic lesion showed reduced selective attentional control. We conclude that lesions in distinct vascular sub regions of the thalamus are associated with distinct attentional syndromes (medial = spatial bias, lateral = processing speed). Copyright © 2015 Elsevier Ltd. All rights reserved.

[Neuronal organization of thalamic nucleus reticularis in adult man].

PubMed

Berezhnaia, L A

2005-01-01

The neuronal content of human thalamic nucleus reticularis was studied in serial sections cut in sagittal and frontal projections and impregnated with silver nitrate using Golgi method. The neuronal content of human thalamic nucleus reticularis was found to be more diverse than previously reported in animals and man. Besides two types of sparsely-branched long-dendritic spineless R1 and R2 neurons, this nucleus contained spiny cells. Medium and small-sized sparsely-branched short-dendritic neurons and densely-branched spiny cells were demonstrated. The principle of organization of human thalamic nucleus reticularis is described.

Cognitive And Neural Sciences Division 1992 Programs

DTIC Science & Technology

1992-08-01

Thalamic short-term plasticity in the auditory system: Associative retuning of receptive fields in the ventral medial geniculate body . Behavioral...prediction and enhancement of human performance in training and operational environments. A second goal is to understand the neurobiological constraints and...such complex, structured bodies of knowledge and skill are acquired. Fourth, to provide a precise theory of instruction, founded on cognitive theory

Evidence That Descending Cortical Axons Are Essential for Thalamocortical Axons to Cross the Pallial-Subpallial Boundary in the Embryonic Forebrain

PubMed Central

Chen, Yijing; Magnani, Dario; Theil, Thomas; Pratt, Thomas; Price, David J.

2012-01-01

Developing thalamocortical axons traverse the subpallium to reach the cortex located in the pallium. We tested the hypothesis that descending corticofugal axons are important for guiding thalamocortical axons across the pallial-subpallial boundary, using conditional mutagenesis to assess the effects of blocking corticofugal axonal development without disrupting thalamus, subpallium or the pallial-subpallial boundary. We found that thalamic axons still traversed the subpallium in topographic order but did not cross the pallial-subpallial boundary. Co-culture experiments indicated that the inability of thalamic axons to cross the boundary was not explained by mutant cortex developing a long-range chemorepulsive action on thalamic axons. On the contrary, cortex from conditional mutants retained its thalamic axonal growth-promoting activity and continued to express Nrg-1, which is responsible for this stimulatory effect. When mutant cortex was replaced with control cortex, corticofugal efferents were restored and thalamic axons from conditional mutants associated with them and crossed the pallial-subpallial boundary. Our study provides the most compelling evidence to date that cortical efferents are required to guide thalamocortical axons across the pallial-subpallial boundary, which is otherwise hostile to thalamic axons. These results support the hypothesis that thalamic axons grow from subpallium to cortex guided by cortical efferents, with stimulation from diffusible cortical growth-promoting factors. PMID:22412988

Cocaine dependence and thalamic functional connectivity: a multivariate pattern analysis.

PubMed

Zhang, Sheng; Hu, Sien; Sinha, Rajita; Potenza, Marc N; Malison, Robert T; Li, Chiang-Shan R

2016-01-01

Cocaine dependence is associated with deficits in cognitive control. Previous studies demonstrated that chronic cocaine use affects the activity and functional connectivity of the thalamus, a subcortical structure critical for cognitive functioning. However, the thalamus contains nuclei heterogeneous in functions, and it is not known how thalamic subregions contribute to cognitive dysfunctions in cocaine dependence. To address this issue, we used multivariate pattern analysis (MVPA) to examine how functional connectivity of the thalamus distinguishes 100 cocaine-dependent participants (CD) from 100 demographically matched healthy control individuals (HC). We characterized six task-related networks with independent component analysis of fMRI data of a stop signal task and employed MVPA to distinguish CD from HC on the basis of voxel-wise thalamic connectivity to the six independent components. In an unbiased model of distinct training and testing data, the analysis correctly classified 72% of subjects with leave-one-out cross-validation (p < 0.001), superior to comparison brain regions with similar voxel counts (p < 0.004, two-sample t test). Thalamic voxels that form the basis of classification aggregate in distinct subclusters, suggesting that connectivities of thalamic subnuclei distinguish CD from HC. Further, linear regressions provided suggestive evidence for a correlation of the thalamic connectivities with clinical variables and performance measures on the stop signal task. Together, these findings support thalamic circuit dysfunction in cognitive control as an important neural marker of cocaine dependence.

Voxel-based statistical analysis of thalamic glucose metabolism in traumatic brain injury: relationship with consciousness and cognition.

PubMed

Lull, Nuria; Noé, Enrique; Lull, Juan José; García-Panach, Javier; Chirivella, Javier; Ferri, Joan; López-Aznar, Diego; Sopena, Pablo; Robles, Montse

2010-01-01

To study the relationship between thalamic glucose metabolism and neurological outcome after severe traumatic brain injury (TBI). Forty-nine patients with severe and closed TBI and 10 healthy control subjects with (18)F-FDG PET were studied. Patients were divided into three groups: MCS&VS group (n = 17), patients in a vegetative or a minimally conscious state; In-PTA group (n = 12), patients in a state of post-traumatic amnesia (PTA); and Out-PTA group (n = 20), patients who had emerged from PTA. SPM5 software implemented in MATLAB 7 was used to determine the quantitative differences between patients and controls. FDG-PET images were spatially normalized and an automated thalamic ROI mask was generated. Group differences were analysed with two sample voxel-wise t-tests. Thalamic hypometabolism was the most prominent in patients with low consciousness (MCS&VS group) and the thalamic hypometabolism in the In-PTA group was more prominent than that in the Out-PTA group. Healthy control subjects showed the greatest thalamic metabolism. These differences in metabolism were more pronounced in the internal regions of the thalamus. The results confirm the vulnerability of the thalamus to suffer the effect of the dynamic forces generated during a TBI. Patients with thalamic hypometabolism could represent a sub-set of subjects that are highly vulnerable to neurological disability after TBI.

Thalamotemporal impairment in temporal lobe epilepsy: a combined MRI analysis of structure, integrity, and connectivity.

PubMed

Keller, Simon S; O'Muircheartaigh, Jonathan; Traynor, Catherine; Towgood, Karren; Barker, Gareth J; Richardson, Mark P

2014-02-01

Thalamic abnormality in temporal lobe epilepsy (TLE) is well known from imaging studies, but evidence is lacking regarding connectivity profiles of the thalamus and their involvement in the disease process. We used a novel multisequence magnetic resonance imaging (MRI) protocol to elucidate the relationship between mesial temporal and thalamic pathology in TLE. For 23 patients with TLE and 23 healthy controls, we performed T1 -weighted (for analysis of tissue structure), diffusion tensor imaging (tissue connectivity), and T1 and T2 relaxation (tissue integrity) MRI across the whole brain. We used connectivity-based segmentation to determine connectivity patterns of thalamus to ipsilateral cortical regions (occipital, parietal, prefrontal, postcentral, precentral, and temporal). We subsequently determined volumes, mean tractography streamlines, and mean T1 and T2 relaxometry values for each thalamic segment preferentially connecting to a given cortical region, and of the hippocampus and entorhinal cortex. As expected, patients had significant volume reduction and increased T2 relaxation time in ipsilateral hippocampus and entorhinal cortex. There was bilateral volume loss, mean streamline reduction, and T2 increase of the thalamic segment preferentially connected to temporal lobe, corresponding to anterior, dorsomedial, and pulvinar thalamic regions, with no evidence of significant change in any other thalamic segments. Left and right thalamotemporal segment volume and T2 were significantly correlated with volume and T2 of ipsilateral (epileptogenic), but not contralateral (nonepileptogenic), mesial temporal structures. These convergent and robust data indicate that thalamic abnormality in TLE is restricted to the area of the thalamus that is preferentially connected to the epileptogenic temporal lobe. The degree of thalamic pathology is related to the extent of mesial temporal lobe damage in TLE. © 2014 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

Prenatal thalamic waves regulate cortical area size prior to sensory processing.

PubMed

Moreno-Juan, Verónica; Filipchuk, Anton; Antón-Bolaños, Noelia; Mezzera, Cecilia; Gezelius, Henrik; Andrés, Belen; Rodríguez-Malmierca, Luis; Susín, Rafael; Schaad, Olivier; Iwasato, Takuji; Schüle, Roland; Rutlin, Michael; Nelson, Sacha; Ducret, Sebastien; Valdeolmillos, Miguel; Rijli, Filippo M; López-Bendito, Guillermina

2017-02-03

The cerebral cortex is organized into specialized sensory areas, whose initial territory is determined by intracortical molecular determinants. Yet, sensory cortical area size appears to be fine tuned during development to respond to functional adaptations. Here we demonstrate the existence of a prenatal sub-cortical mechanism that regulates the cortical areas size in mice. This mechanism is mediated by spontaneous thalamic calcium waves that propagate among sensory-modality thalamic nuclei up to the cortex and that provide a means of communication among sensory systems. Wave pattern alterations in one nucleus lead to changes in the pattern of the remaining ones, triggering changes in thalamic gene expression and cortical area size. Thus, silencing calcium waves in the auditory thalamus induces Rorβ upregulation in a neighbouring somatosensory nucleus preluding the enlargement of the barrel-field. These findings reveal that embryonic thalamic calcium waves coordinate cortical sensory area patterning and plasticity prior to sensory information processing.

Prenatal thalamic waves regulate cortical area size prior to sensory processing

PubMed Central

Moreno-Juan, Verónica; Filipchuk, Anton; Antón-Bolaños, Noelia; Mezzera, Cecilia; Gezelius, Henrik; Andrés, Belen; Rodríguez-Malmierca, Luis; Susín, Rafael; Schaad, Olivier; Iwasato, Takuji; Schüle, Roland; Rutlin, Michael; Nelson, Sacha; Ducret, Sebastien; Valdeolmillos, Miguel; Rijli, Filippo M.; López-Bendito, Guillermina

2017-01-01

The cerebral cortex is organized into specialized sensory areas, whose initial territory is determined by intracortical molecular determinants. Yet, sensory cortical area size appears to be fine tuned during development to respond to functional adaptations. Here we demonstrate the existence of a prenatal sub-cortical mechanism that regulates the cortical areas size in mice. This mechanism is mediated by spontaneous thalamic calcium waves that propagate among sensory-modality thalamic nuclei up to the cortex and that provide a means of communication among sensory systems. Wave pattern alterations in one nucleus lead to changes in the pattern of the remaining ones, triggering changes in thalamic gene expression and cortical area size. Thus, silencing calcium waves in the auditory thalamus induces Rorβ upregulation in a neighbouring somatosensory nucleus preluding the enlargement of the barrel-field. These findings reveal that embryonic thalamic calcium waves coordinate cortical sensory area patterning and plasticity prior to sensory information processing. PMID:28155854

Thalamic diffusion differences related to cognitive function in white matter lesions.

PubMed

Fernández-Andújar, Marina; Soriano-Raya, Juan José; Miralbell, Júlia; López-Cancio, Elena; Cáceres, Cynthia; Bargalló, Núria; Barrios, Maite; Arenillas, Juan Francisco; Toran, Pere; Alzamora, Maite; Clemente, Imma; Dávalos, Antoni; Mataró, Maria

2014-05-01

Cerebral white matter lesions (WMLs) are related to cognitive deficits, probably due to a disruption of frontal-subcortical circuits. We explored thalamic diffusion differences related to white matter lesions (WMLs) and their association with cognitive function in middle-aged individuals. Ninety-six participants from the Barcelona-AsIA Neuropsychology Study were included. Participants were classified into groups based on low grade and high grade of periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs). Tract-Based Spatial Statistics was used to study thalamic diffusion differences between groups. Mean fractional anisotropy (FA) values in significant areas were calculated for each subject and correlated with cognitive performance. Participants with high-grade PVHs and DWMHs showed lower FA thalamic values compared to those with low-grade PVHs and DWMHs, respectively. Decreased FA thalamic values in high-grade DWMHs, but not high-grade PVH, were related to lower levels of performance in psychomotor speed, verbal fluency, and visuospatial skills. Thalamic diffusion differences are related to lower cognitive function only in participants with high-grade DWMHs. These results support the hypothesis that fronto-subcortical disruption is associated with cognitive function only in DWMHs. Copyright © 2014 Elsevier Inc. All rights reserved.

Volumetric abnormalities in connectivity-based subregions of the thalamus in patients with chronic schizophrenia.

PubMed

Kim, Jae-Jin; Kim, Dae-Jin; Kim, Tae-Gyun; Seok, Jeong-Ho; Chun, Ji Won; Oh, Maeng-Keun; Park, Hae-Jeong

2007-12-01

The thalamus, which consists of multiple subnuclei, has been of particular interest in the study of schizophrenia. This study aimed to identify abnormalities in the connectivity-based subregions of the thalamus in patients with schizophrenia. Thalamic volume was measured by a manual tracing on superimposed images of T1-weighted and diffusion tensor images in 30 patients with schizophrenia and 22 normal volunteers. Cortical regional volumes automatically measured by a surface-based approach and thalamic subregional volumes measured by a connectivity-based technique were compared between the two groups and their correlations between the connected regions were calculated in each group. Volume reduction was observed in the bilateral orbitofrontal cortices and the left cingulate gyrus on the cortical side, whereas in subregions connected to the right orbitofrontal cortex and bilateral parietal cortices on the thalamic side. Significant volumetric correlations were identified between the right dorsal prefrontal cortex and its related thalamic subregion and between the left parietal cortex and its related thalamic subregion only in the normal group. Our results suggest that patients with schizophrenia have a structural deficit in the corticothalamic systems, especially in the orbitofrontal-thalamic system. Our findings may present evidence of corticothalamic connection problems in schizophrenia.

Thalamic stimulation to improve level of consciousness after seizures: evaluation of electrophysiology and behavior.

PubMed

Gummadavelli, Abhijeet; Motelow, Joshua E; Smith, Nicholas; Zhan, Qiong; Schiff, Nicholas D; Blumenfeld, Hal

2015-01-01

Understanding the neural mechanisms that support human consciousness is an important frontier in neuroscience and medicine. We previously developed a rodent model of temporal lobe seizures that recapitulates the human electroencephalography (EEG) signature of ictal and postictal neocortical slow waves associated with behavioral impairments in level of consciousness. The mechanism of slow-wave production in epilepsy may involve suppression of the subcortical arousal systems including the brainstem and intralaminar thalamic nuclei. We hypothesized that intralaminar thalamic stimulation may lead to electrophysiologic and functional rescue from postictal slow waves and behavioral arrest. We electrically stimulated the central lateral thalamic nucleus (a member of the intralaminar nuclei) under anesthesia and after electrically induced hippocampal seizures in anesthetized and in awake-behaving animal model preparations. We demonstrated a proof-of-principle restoration of electrophysiologic and behavioral measures of consciousness by stimulating the intralaminar thalamic nuclei after seizures. We measured decreased cortical slow waves and increased desynchronization and multiunit activity in the cortex with thalamic stimulation following seizures. Functionally, thalamic stimulation produced resumption of exploratory behaviors in the postictal state. Targeting of nodes in the neural circuitry of consciousness has important medical implications. Impaired consciousness with epilepsy has dangerous consequences including decreased school/work performance, social stigmatization, and impaired airway protection. These data suggest a novel therapeutic approach for restoring consciousness after seizures. If paired with responsive neurostimulation, this may allow rapid implementation to improve level of consciousness in patients with epilepsy. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Connectivity derived thalamic segmentation in deep brain stimulation for tremor.

PubMed

Akram, Harith; Dayal, Viswas; Mahlknecht, Philipp; Georgiev, Dejan; Hyam, Jonathan; Foltynie, Thomas; Limousin, Patricia; De Vita, Enrico; Jahanshahi, Marjan; Ashburner, John; Behrens, Tim; Hariz, Marwan; Zrinzo, Ludvic

2018-01-01

The ventral intermediate nucleus (VIM) of the thalamus is an established surgical target for stereotactic ablation and deep brain stimulation (DBS) in the treatment of tremor in Parkinson's disease (PD) and essential tremor (ET). It is centrally placed on a cerebello-thalamo-cortical network connecting the primary motor cortex, to the dentate nucleus of the contralateral cerebellum through the dentato-rubro-thalamic tract (DRT). The VIM is not readily visible on conventional MR imaging, so identifying the surgical target traditionally involved indirect targeting that relies on atlas-defined coordinates. Unfortunately, this approach does not fully account for individual variability and requires surgery to be performed with the patient awake to allow for intraoperative targeting confirmation. The aim of this study is to identify the VIM and the DRT using probabilistic tractography in patients that will undergo thalamic DBS for tremor. Four male patients with tremor dominant PD and five patients (three female) with ET underwent high angular resolution diffusion imaging (HARDI) (128 diffusion directions, 1.5 mm isotropic voxels and b value = 1500) preoperatively. Patients received VIM-DBS using an MR image guided and MR image verified approach with indirect targeting. Postoperatively, using parallel Graphical Processing Unit (GPU) processing, thalamic areas with the highest diffusion connectivity to the primary motor area (M1), supplementary motor area (SMA), primary sensory area (S1) and contralateral dentate nucleus were identified. Additionally, volume of tissue activation (VTA) corresponding to active DBS contacts were modelled. Response to treatment was defined as 40% reduction in the total Fahn-Tolosa-Martin Tremor Rating Score (FTMTRS) with DBS-ON, one year from surgery. Three out of nine patients had a suboptimal, long-term response to treatment. The segmented thalamic areas corresponded well to anatomically known counterparts in the ventrolateral (VL) and ventroposterior (VP) thalamus. The dentate-thalamic area, lay within the M1-thalamic area in a ventral and lateral location. Streamlines corresponding to the DRT connected M1 to the contralateral dentate nucleus via the dentate-thalamic area, clearly crossing the midline in the mesencephalon. Good response was seen when the active contact VTA was in the thalamic area with highest connectivity to the contralateral dentate nucleus. Non-responders had active contact VTAs outside the dentate-thalamic area. We conclude that probabilistic tractography techniques can be used to segment the VL and VP thalamus based on cortical and cerebellar connectivity. The thalamic area, best representing the VIM, is connected to the contralateral dentate cerebellar nucleus. Connectivity based segmentation of the VIM can be achieved in individual patients in a clinically feasible timescale, using HARDI and high performance computing with parallel GPU processing. This same technique can map out the DRT tract with clear mesencephalic crossing.

Non-neuronal, slow GABA signalling in the ventrobasal thalamus targets δ-subunit-containing GABAA receptors

PubMed Central

Jiménez-González, Cristina; Pirttimaki, Tiina; Cope, David W; Parri, H R

2011-01-01

The rodent ventrobasal (VB) thalamus contains a relatively uniform population of thalamocortical (TC) neurons that receive glutamatergic input from the vibrissae and the somatosensory cortex, and inhibitory input from the nucleus reticularis thalami (nRT). In this study we describe γ-aminobutyric acid (GABA)A receptor-dependent slow outward currents (SOCs) in TC neurons that are distinct from fast inhibitory postsynaptic currents (IPSCs) and tonic currents. SOCs occurred spontaneously or could be evoked by hypo-osmotic stimulus, and were not blocked by tetrodotoxin, removal of extracellular Ca2+ or bafilomycin A1, indicating a non-synaptic, non-vesicular GABA origin. SOCs were more common in TC neurons of the VB compared with the dorsal lateral geniculate nucleus, and were rarely observed in nRT neurons, whilst SOC frequency in the VB increased with age. Application of THIP, a selective agonist at δ-subunit-containing GABAA receptors, occluded SOCs, whereas the benzodiazepine site inverse agonist β-CCB had no effect, but did inhibit spontaneous and evoked IPSCs. In addition, the occurrence of SOCs was reduced in mice lacking the δ-subunit, and their kinetics were also altered. The anti-epileptic drug vigabatrin increased SOC frequency in a time-dependent manner, but this effect was not due to reversal of GABA transporters. Together, these data indicate that SOCs in TC neurons arise from astrocytic GABA release, and are mediated by δ-subunit-containing GABAA receptors. Furthermore, these findings suggest that the therapeutic action of vigabatrin may occur through the augmentation of this astrocyte–neuron interaction, and highlight the importance of glial cells in CNS (patho) physiology. PMID:21395866

A practical guide for the identification of major sulcogyral structures of the human cortex.

PubMed

Destrieux, Christophe; Terrier, Louis Marie; Andersson, Frédéric; Love, Scott A; Cottier, Jean-Philippe; Duvernoy, Henri; Velut, Stéphane; Janot, Kevin; Zemmoura, Ilyess

2017-05-01

The precise sulcogyral localization of cortical lesions is mandatory to improve communication between practitioners and to predict and prevent post-operative deficits. This process, which assumes a good knowledge of the cortex anatomy and a systematic analysis of images, is, nevertheless, sometimes neglected in the neurological and neurosurgical training. This didactic paper proposes a brief overview of the sulcogyral anatomy, using conventional MR-slices, and also reconstructions of the cortical surface after a more or less extended inflation process. This method simplifies the cortical anatomy by removing part of the cortical complexity induced by the folding process, and makes it more understandable. We then reviewed several methods for localizing cortical structures, and proposed a three-step identification: after localizing the lateral, medial or ventro-basal aspect of the hemisphere (step 1), the main interlobar sulci were located to limit the lobes (step 2). Finally, intralobar sulci and gyri were identified (step 3) thanks to the same set of rules. This paper does not propose any new identification method but should be regarded as a set of practical guidelines, useful in daily clinical practice, for detecting the main sulci and gyri of the human cortex.

Residual effect of a 7-amino metabolite of clonazepam on GABAA receptor function in the nucleus reticularis thalami of the rat.

PubMed

Munakata, Mitsutoshi; Tsuchiya, Shigeru

2008-10-01

A considerable amount of 7-aminoclonazepam (ACZP), a major metabolite of clonazepam (CZP), is present in the brain during CZP treatment, yet the pharmacological properties of ACZP remain unknown. We investigated the effects of ACZP on the GABA(A) receptor-mediated currents (I(GABA)) in neurons from the nucleus reticularis thalami (NRT) of the rat, using a nystatin-perforated patch technique. Neurons in which CZP (10 nM) exerted prominent augmentation (>100% augmentation) of I(GABA), which comprised 32% of the neurons tested, were included for the analysis of ACZP. In these neurons, ACZP augmented I(GABA), which was blocked by 10 microM flumazenil, a benzodiazepine receptor (BZR) antagonist. The half-maximal effective concentration of ACZP was 124 nM, whereas that of CZP was 1.8 nM. The maximal enhancements induced by ACZP and CZP were 38% and 170%, respectively. In neurons from the ventrobasal complex of the thalamus, the effect of ACZP was negligible. Our results suggest that ACZP was a weak partial BZR agonist and that ACZP may competitively modify the effect of CZP, leading to clinical consequences for patients with high levels of ACZP.

Oscillatory neural representations in the sensory thalamus predict neuropathic pain relief by deep brain stimulation.

PubMed

Huang, Yongzhi; Green, Alexander L; Hyam, Jonathan; Fitzgerald, James; Aziz, Tipu Z; Wang, Shouyan

2018-01-01

Understanding the function of sensory thalamic neural activity is essential for developing and improving interventions for neuropathic pain. However, there is a lack of investigation of the relationship between sensory thalamic oscillations and pain relief in patients with neuropathic pain. This study aims to identify the oscillatory neural characteristics correlated with pain relief induced by deep brain stimulation (DBS), and develop a quantitative model to predict pain relief by integrating characteristic measures of the neural oscillations. Measures of sensory thalamic local field potentials (LFPs) in thirteen patients with neuropathic pain were screened in three dimensional feature space according to the rhythm, balancing, and coupling neural behaviours, and correlated with pain relief. An integrated approach based on principal component analysis (PCA) and multiple regression analysis is proposed to integrate the multiple measures and provide a predictive model. This study reveals distinct thalamic rhythms of theta, alpha, high beta and high gamma oscillations correlating with pain relief. The balancing and coupling measures between these neural oscillations were also significantly correlated with pain relief. The study enriches the series research on the function of thalamic neural oscillations in neuropathic pain and relief, and provides a quantitative approach for predicting pain relief by DBS using thalamic neural oscillations. Copyright © 2017 Elsevier Inc. All rights reserved.

Morphological abnormalities in prefrontal surface area and thalamic volume in attention deficit/hyperactivity disorder.

PubMed

Batty, Martin J; Palaniyappan, Lena; Scerif, Gaia; Groom, Madeleine J; Liddle, Elizabeth B; Liddle, Peter F; Hollis, Chris

2015-08-30

Although previous morphological studies have demonstrated abnormalities in prefrontal cortical thickness in children with attention deficit/hyperactivity disorder (ADHD), studies investigating cortical surface area are lacking. As the development of cortical surface is closely linked to the establishment of thalam-ocortical connections, any abnormalities in the structure of the thalamus are likely to relate to altered cortical surface area. Using a clinically well-defined sample of children with ADHD (n = 25, 1 female) and typically developing controls (n = 24, 1 female), we studied surface area across the cortex to determine whether children with ADHD had reduced thalamic volume that related to prefrontal cortical surface area. Relative to controls, children with ADHD had a significant reduction in thalamic volume and dorsolateral prefrontal cortical area in both hemispheres. Furthermore, children with ADHD with smaller thalamic volumes were found to have greater reductions in surface area, a pattern not evident in the control children. Our results are further evidence of reduced lateral prefrontal cortical area in ADHD. Moreover, for the first time, we have also shown a direct association between thalamic anatomy and frontal anatomy in ADHD, suggesting the pathophysiological process that alters surface area maturation is likely to be linked to the development of the thalamus. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Differential impact of thalamic versus subthalamic deep brain stimulation on lexical processing.

PubMed

Krugel, Lea K; Ehlen, Felicitas; Tiedt, Hannes O; Kühn, Andrea A; Klostermann, Fabian

2014-10-01

Roles of subcortical structures in language processing are vague, but, interestingly, basal ganglia and thalamic Deep Brain Stimulation can go along with reduced lexical capacities. To deepen the understanding of this impact, we assessed word processing as a function of thalamic versus subthalamic Deep Brain Stimulation. Ten essential tremor patients treated with thalamic and 14 Parkinson׳s disease patients with subthalamic Deep Brain Stimulation performed an acoustic Lexical Decision Task ON and OFF stimulation. Combined analysis of task performance and event-related potentials allowed the determination of processing speed, priming effects, and N400 as neurophysiological correlate of lexical stimulus processing. 12 age-matched healthy participants acted as control subjects. Thalamic Deep Brain Stimulation prolonged word decisions and reduced N400 potentials. No comparable ON-OFF effects were present in patients with subthalamic Deep Brain Stimulation. In the latter group of patients with Parkinson' disease, N400 amplitudes were, however, abnormally low, whether under active or inactive Deep Brain Stimulation. In conclusion, performance speed and N400 appear to be influenced by state functions, modulated by thalamic, but not subthalamic Deep Brain Stimulation, compatible with concepts of thalamo-cortical engagement in word processing. Clinically, these findings specify cognitive sequels of Deep Brain Stimulation in a target-specific way. Copyright © 2014 Elsevier Ltd. All rights reserved.

Response sensitivity of barrel neuron subpopulations to simulated thalamic input.

PubMed

Pesavento, Michael J; Rittenhouse, Cynthia D; Pinto, David J

2010-06-01

Our goal is to examine the relationship between neuron- and network-level processing in the context of a well-studied cortical function, the processing of thalamic input by whisker-barrel circuits in rodent neocortex. Here we focus on neuron-level processing and investigate the responses of excitatory and inhibitory barrel neurons to simulated thalamic inputs applied using the dynamic clamp method in brain slices. Simulated inputs are modeled after real thalamic inputs recorded in vivo in response to brief whisker deflections. Our results suggest that inhibitory neurons require more input to reach firing threshold, but then fire earlier, with less variability, and respond to a broader range of inputs than do excitatory neurons. Differences in the responses of barrel neuron subtypes depend on their intrinsic membrane properties. Neurons with a low input resistance require more input to reach threshold but then fire earlier than neurons with a higher input resistance, regardless of the neuron's classification. Our results also suggest that the response properties of excitatory versus inhibitory barrel neurons are consistent with the response sensitivities of the ensemble barrel network. The short response latency of inhibitory neurons may serve to suppress ensemble barrel responses to asynchronous thalamic input. Correspondingly, whereas neurons acting as part of the barrel circuit in vivo are highly selective for temporally correlated thalamic input, excitatory barrel neurons acting alone in vitro are less so. These data suggest that network-level processing of thalamic input in barrel cortex depends on neuron-level processing of the same input by excitatory and inhibitory barrel neurons.

Thalamocortical functional connectivity in Lennox-Gastaut syndrome is abnormally enhanced in executive-control and default-mode networks.

PubMed

Warren, Aaron E L; Abbott, David F; Jackson, Graeme D; Archer, John S

2017-12-01

To identify abnormal thalamocortical circuits in the severe epilepsy of Lennox-Gastaut syndrome (LGS) that may explain the shared electroclinical phenotype and provide potential treatment targets. Twenty patients with a diagnosis of LGS (mean age = 28.5 years) and 26 healthy controls (mean age = 27.6 years) were compared using task-free functional magnetic resonance imaging (MRI). The thalamus was parcellated according to functional connectivity with 10 cortical networks derived using group-level independent component analysis. For each cortical network, we assessed between-group differences in thalamic functional connectivity strength using nonparametric permutation-based tests. Anatomical locations were identified by quantifying spatial overlap with a histologically informed thalamic MRI atlas. In both groups, posterior thalamic regions showed functional connectivity with visual, auditory, and sensorimotor networks, whereas anterior, medial, and dorsal thalamic regions were connected with networks of distributed association cortex (including the default-mode, anterior-salience, and executive-control networks). Four cortical networks (left and right executive-control network; ventral and dorsal default-mode network) showed significantly enhanced thalamic functional connectivity strength in patients relative to controls. Abnormal connectivity was maximal in mediodorsal and ventrolateral thalamic nuclei. Specific thalamocortical circuits are affected in LGS. Functional connectivity is abnormally enhanced between the mediodorsal and ventrolateral thalamus and the default-mode and executive-control networks, thalamocortical circuits that normally support diverse cognitive processes. In contrast, thalamic regions connecting with primary and sensory cortical networks appear to be less affected. Our previous neuroimaging studies show that epileptic activity in LGS is expressed via the default-mode and executive-control networks. Results of the present study suggest that the mediodorsal and ventrolateral thalamus may be candidate targets for modulating abnormal network behavior underlying LGS, potentially via emerging thalamic neurostimulation therapies. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Thalamic reticular nucleus in Caiman crocodilus: Relationship with the dorsal thalamus.

PubMed

Pritz, M B

2016-05-13

The thalamic reticular nucleus was investigated in one group of crocodilians, Caiman crocodilus. This neuronal aggregate is composed of two parts: a compact portion and a diffuse region made up of scattered cells within the forebrain bundles. In Caiman, both the lateral and medial forebrain bundles project to the telencephalon and the thalamic reticular nucleus is associated with each fiber tract. In the lateral forebrain bundle, the compact area is termed the nucleus of the dorsal peduncle (dorsal peduncular nucleus) while the diffuse part is called the perireticular area. In the medial forebrain bundle, the interstitial nucleus comprises one part of the compact area while another region without a specific neuronal label is also present. Similar to the perireticular cells of the lateral forebrain bundle, scattered cells are also present in the medial forebrain bundle. Morphological features of the thalamic reticular nucleus are revealed with stains for the following: fibers; cells; succinic acid dehydrogenase; and acetylcholinesterase. Regardless of which dorsal thalamic nucleus was injected, a localized region of the thalamic reticular nucleus contained retrogradely labeled cells and anterogradely labeled axons and terminals. This grouping was termed clusters and was felt to represent the densest interconnection between the dorsal thalamus and the reticular nucleus. Using clusters as an index of interconnections, the reticular nucleus was divided into sectors, each of which was associated with a specific dorsal thalamic nucleus. An organization similar to that found in Caiman is present in other sauropsids as well as in mammals. These data suggest that a thalamic reticular nucleus is present in all amniotes and has morphological properties similar to those described in this analysis. Lastly, a hypothesis is presented to explain how the external shape of the reticular nucleus in Caiman might be transformed into the homologous area in a representative bird and mammal. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Alleviation of acquired stuttering with human centremedian thalamic stimulation.

PubMed Central

Bhatnagar, S C; Andy, O J

1989-01-01

Despite many investigations, the cerebral mechanism for stuttering remains unknown. Recently, increased attention has been paid to acquired stuttering of adult onset in the hope that the events associated with it might provide clues to the biological mechanism underlying stuttering. This attention has focused exclusively on the cortical substrates. We present our observations of acquired dysfluency, presumably of subcortical origin in a neurosurgical subject with intractable pain. The stuttering was relieved by thalamic electric stimulation. The effect of thalamic stimulation on the stuttering suggests that the pathophysiology of transient asynchronisation in the balancing and sequencing of multiple impulses is amenable to a diffusely orchestrated functional tuning of the thalamic and brainstem implicated subcortical structures and pathways. Images PMID:2795045

Neuroanatomical term generation and comparison between two terminologies.

PubMed

Srinivas, Prashanti R; Gusfield, Daniel; Mason, Oliver; Gertz, Michael; Hogarth, Michael; Stone, James; Jones, Edward G; Gorin, Fredric A

2003-01-01

An approach and software tools are described for identifying and extracting compound terms (CTs), acronyms and their associated contexts from textual material that is associated with neuroanatomical atlases. A set of simple syntactic rules were appended to the output of a commercially available part of speech (POS) tagger (Qtag v 3.01) that extracts CTs and their associated context from the texts of neuroanatomical atlases. This "hybrid" parser. appears to be highly sensitive and recognized 96% of the potentially germane neuroanatomical CTs and acronyms present in the cat and primate thalamic atlases. A comparison of neuroanatomical CTs and acronymsbetween the cat and primate atlas texts was initially performed using exact-term matching. The implementation of string-matching algorithms significantly improved the identification of relevant terms and acronyms between the two domains. The End Gap Free string matcher identified 98% of CTs and the Needleman Wunsch (NW) string matcher matched 36% of acronyms between the two atlases. Combining several simple grammatical and lexical rules with the POS tagger ("hybrid parser") (1) extracted complex neuroanatomical terms and acronyms from selected cat and primate thalamic atlases and (2) and facilitated the semi-automated generation of a highly granular thalamic terminology. The implementation of string-matching algorithms (1) reconciled terminological errors generated by optical character recognition (OCR) software used to generate the neuroanatomical text information and (2) increased the sensitivity of matching neuroanatomical terms and acronyms between the two neuroanatomical domains that were generated by the "hybrid" parser.

Distribution of L-type calcium channels in rat thalamic neurones.

PubMed

Budde, T; Munsch, T; Pape, H C

1998-02-01

One major pathway for calcium entry into neurones is through voltage-activated calcium channels. The distribution of calcium channels over the membrane surface is important for their contribution to neuronal function. Electrophysiological recordings from thalamic cells in situ and after acute isolation demonstrated the presence of high-voltage activated calcium currents. The use of specific L-type calcium channel agonists and antagonists of the dihydropyridine type revealed an about 40% contribution of L-type channels to the total high-voltage-activated calcium current. In order to localize L-type calcium channels in thalamic neurones, fluorescent dihydropyridines were used. They were combined with the fluorescent dye RH414, which allowed the use of a ratio technique and thereby the determination of channel density. The distribution of L-type channels was analysed in the three main thalamic cell types: thalamocortical relay cells, local interneurones and reticular thalamic neurones. While channel density was highest in the soma and decreased significantly in the dendritic region, channels appeared to be clustered differentially in the three types of cells. In thalamocortical cells, L-type channels were clustered in high density around the base of dendrites, while they were more evenly distributed on the soma of interneurones. Reticular thalamic neurones exhibited high density of L-type channels in more central somatic regions. The differential localization of L-type calcium channels found in this study implies their predominate involvement in the regulation of somatic and proximal dendritic calcium-dependent processes, which may be of importance for specific thalamic functions, such as those mediating the transition from rhythmic burst activity during sleep to single spike activity during wakefulness or regulating the relay of visual information.

Mapping thalamocortical network pathology in temporal lobe epilepsy.

PubMed

Bernhardt, Boris C; Bernasconi, Neda; Kim, Hosung; Bernasconi, Andrea

2012-01-10

Although experimental work has provided evidence that the thalamus is a crucial relay structure in temporal lobe epilepsy (TLE), the relation of the thalamus to neocortical pathology remains unclear. To assess thalamocortical network pathology in TLE, we mapped pointwise patterns of thalamic atrophy and statistically related them to neocortical thinning. We studied cross-sectionally 36 patients with drug-resistant TLE and 19 age- and sex-matched healthy control subjects using high-resolution MRI. To localize thalamic pathology, we converted manual labels into surface meshes using the spherical harmonic description and calculated local deformations relative to a template. In addition, we measured cortical thickness by means of the constrained Laplacian anatomic segmentation using proximity algorithm. Compared with control subjects, patients with TLE showed ipsilateral thalamic atrophy that was located along the medial surface, encompassing anterior, medial, and posterior divisions. Unbiased analysis correlating the degree of medial thalamic atrophy with cortical thickness measurements mapped bilateral frontocentral, lateral temporal, and mesiotemporal cortices. These areas overlapped with those of cortical thinning found when patients were compared with control subjects. Thalamic atrophy intensified with a longer duration of epilepsy and was more severe in patients with a history of febrile convulsions. The degree and distribution of thalamic pathology relates to the topography and extent of neocortical atrophy, lending support to the concept that the thalamus is an important hub in the pathologic network of TLE.

Contributions of volumetrics of the hippocampus and thalamus to verbal memory in temporal lobe epilepsy patients.

PubMed

Stewart, Christopher C; Griffith, H Randall; Okonkwo, Ozioma C; Martin, Roy C; Knowlton, Robert K; Richardson, Elizabeth J; Hermann, Bruce P; Seidenberg, Michael

2009-02-01

Recent theories have posited that the hippocampus and thalamus serve distinct, yet related, roles in episodic memory. Whereas the hippocampus has been implicated in long-term memory encoding and storage, the thalamus, as a whole, has been implicated in the selection of items for subsequent encoding and the use of retrieval strategies. However, dissociating the memory impairment that occurs following thalamic injury as distinguished from that following hippocampal injury has proven difficult. This study examined relationships between MRI volumetric measures of the hippocampus and thalamus and their contributions to prose and rote verbal memory functioning in 18 patients with intractable temporal lobe epilepsy (TLE). Results revealed that bilateral hippocampal and thalamic volume independently predicted delayed prose verbal memory functioning. However, bilateral hippocampal, but not thalamic, volume predicted delayed rote verbal memory functioning. Follow-up analyses indicated that bilateral thalamic volume independently predicted immediate prose, but not immediate rote, verbal recall, whereas bilateral hippocampal volume was not associated with any of these immediate memory measures. These findings underscore the cognitive significance of thalamic atrophy in chronic TLE, demonstrating that hippocampal and thalamic volume make quantitatively, and perhaps qualitatively, distinct contributions to episodic memory functioning in TLE patients. They are also consistent with theories proposing that the hippocampus supports long-term memory encoding and storage, whereas the thalamus is implicated in the executive aspects of episodic memory.

Lack of Intrinsic GABAergic Connections in the Thalamic Reticular Nucleus of the Mouse.

PubMed

Hou, Guoqiang; Smith, Alison G; Zhang, Zhong-Wei

2016-07-06

It is generally thought that neurons in the thalamic reticular nucleus (TRN) form GABAergic synapses with other TRN neurons and that these interconnections are important for the function of the TRN. However, the existence of such intrinsic connections is controversial. We combine two complementary approaches to examine intrinsic GABAergic connections in the TRN of the mouse. We find that optogenetic stimulation of TRN neurons and their axons evokes GABAergic IPSCs in TRN neurons in mice younger than 2 weeks of age but fails to do so after that age. Blocking synaptic release from TRN neurons through conditional deletion of vesicular GABA transporter has no effect on spontaneous IPSCs recorded in TRN neurons aged 2 weeks or older while dramatically reducing GABAergic transmission in thalamic relay neurons. These results demonstrate that except for a short period after birth, the TRN of the mouse lacks intrinsic GABAergic connections. The thalamic reticular nucleus has a critical role in modulating information transfer from the thalamus to the cortex. It has been proposed that neurons in the thalamic reticular nucleus are interconnected through GABAergic synapses and that these connections serve important functions. Our results show that except for the first 2 weeks after birth, the thalamic reticular nucleus of the mouse lacks intrinsic GABAergic connections. Copyright © 2016 the authors 0270-6474/16/367246-07$15.00/0.

Silent diabetes mellitus, periodontitis and a new case of thalamic abscess

PubMed Central

Karageorgiou, Ioannis; Chandler, Christopher; Whyte, Martin Brunel

2014-01-01

Brain abscess is an unusual complication of uncontrolled diabetes. A solitary thalamic abscess is an uncommon type of brain abscess. We report a case of thalamic abscess, whereupon diabetes mellitus and periodontitis were diagnosed. The diagnosis and management of thalamic abscess, and the interplay of type 2 diabetes and periodontitis are discussed. A 56-year-old, Caucasian, man with no medical or travel history, presented with 5-day symptoms of meningeal irritation. Body mass index 30.6 kg/m2. CT demonstrated a solitary midline lesion with neoplasia as a differential diagnosis. It was biopsied and cultures grew Streptococcus milleri. He was treated by stereotactic puncture, external drainage and targeted intrathecal and systemic antibiotic therapy. HIV negative but glycated haemoglobin (HbA1c) 10.7% (93 mmol/mol). Dental examination revealed a small molar abscess. Radiological resolution of the thalamic abscess occurred within 2 months. Diabetes improved with 7 weeks of insulin, and maintained on metformin, HbA1c 6.9% (51 mmol/mol). There was no residual neurological disability. PMID:25053670

Thalamic Spindles Promote Memory Formation during Sleep through Triple Phase-Locking of Cortical, Thalamic, and Hippocampal Rhythms.

PubMed

Latchoumane, Charles-Francois V; Ngo, Hong-Viet V; Born, Jan; Shin, Hee-Sup

2017-07-19

While the interaction of the cardinal rhythms of non-rapid-eye-movement (NREM) sleep-the thalamo-cortical spindles, hippocampal ripples, and the cortical slow oscillations-is thought to be critical for memory consolidation during sleep, the role spindles play in this interaction is elusive. Combining optogenetics with a closed-loop stimulation approach in mice, we show here that only thalamic spindles induced in-phase with cortical slow oscillation up-states, but not out-of-phase-induced spindles, improve consolidation of hippocampus-dependent memory during sleep. Whereas optogenetically stimulated spindles were as efficient as spontaneous spindles in nesting hippocampal ripples within their excitable troughs, stimulation in-phase with the slow oscillation up-state increased spindle co-occurrence and frontal spindle-ripple co-occurrence, eventually resulting in increased triple coupling of slow oscillation-spindle-ripple events. In-phase optogenetic suppression of thalamic spindles impaired hippocampus-dependent memory. Our results suggest a causal role for thalamic sleep spindles in hippocampus-dependent memory consolidation, conveyed through triple coupling of slow oscillations, spindles, and ripples. Copyright © 2017 Elsevier Inc. All rights reserved.

Changes in sensorimotor-related thalamic diffusion properties and cerebrospinal fluid hydrodynamics predict gait responses to tap test in idiopathic normal-pressure hydrocephalus.

PubMed

Tsai, Ping-Huei; Chen, Yung-Chieh; Chiang, Shih-Wei; Huang, Teng-Yi; Chou, Ming-Chung; Liu, Hua-Shan; Chung, Hsiao-Wen; Peng, Giia-Sheun; Ma, Hsin-I; Kao, Hung-Wen; Chen, Cheng-Yu

2018-05-07

To compare diffusion tensor (DT)-derived indices from the thalamic nuclei and cerebrospinal fluid (CSF) hydrodynamic parameters for the prediction of gait responsiveness to the CSF tap test in early iNPH patients. In this study, 22 patients with iNPH and 16 normal controls were enrolled with the approval of an institutional review board. DT imaging and phase-contrast magnetic resonance imaging were performed in patients and controls to determine DT-related indices of the sensorimotor-related thalamic nuclei and CSF hydrodynamics. Gait performance was assessed in patients using gait scale before and after the tap test. The Mann-Whitney U test and receiver operating characteristic (ROC) curve analysis were applied to compare group differences between patients and controls and assess the predictive performance of gait responsiveness to the tap test in the patients. Fractional anisotropy (FA) and axial diffusivity showed significant increases in the ventrolateral (VL) and ventroposterolateral (VPL) nuclei of the iNPH group compared with those of the control group (p < 0.05). The predictions of gait responsiveness of ventral thalamic FA alone (area under the ROC curve [AUC] < 0.8) significantly outperformed those of CSF hydrodynamics alone (AUC < 0.6). The AUC curve was elevated to 0.812 when the CSF peak systolic velocity and FA value were combined for the VPL nucleus, yielding the highest sensitivity (0.769) and specificity (0.778) to predict gait responses. Combined measurements of sensorimotor-related thalamic FA and CSF hydrodynamics can provide potential biomarkers for gait response to the CSF tap test in patients with iNPH. • Ventrolateral and ventroposterolateral thalamic FA may predict gait responsiveness to tap test. • Thalamic neuroplasticity can be assessed through DTI in idiopathic normal-pressure hydrocephalus. • Changes in the CST associated with gait control could trigger thalamic neuroplasticity. • Activities of sensorimotor-related circuits could alter in patients with gait disturbance. • Management of patients with iNPH could be more appropriate.

Nigrothalamic projections in the monkey demonstrated by autoradiographic technics.

PubMed

Carpenter, M B; Nakano, K; Kim, R

1976-02-15

In spite of repeated demonstrations by degeneration technics, nigrothalamic fibers have been regarded with some skepticism. Attempts were made to trace nigral efferent projections in the monkey by autoradiographic technics. Tritiated amino acids (L-leucine, L-lysine and L-proline), injected into portions of the substantia nigra (SN), labeled cells in four regions, designated as, (1) rostrolateral, (2) caudolateral, (3) rostromedial and (4) central. Rostrolateral nigral neurons transported radioactive label preferentially and abundantly to thalamic nuclei; localized isotope was found in parts of three thalamic nuclei, the medial part of the ventral lateral nucleus (VLm), the magnocellular part of the ventral anterior nucleus (VAmc), and the paralaminar part of the dorsomedial nucleus (DMpl)9 Lateral neurons in the caudal half of the SN transmitted radioactive label to the same thalamic nuclei as rostrolateral nigral neuron. Isotope transported to portions of the striatum was modest and localized. Radioactive label taken up by large cells in the caudal third of the SN was transported to portions of the striatum, but not to thalamic nuclei. Labeled nigral neurons in the medial two-thirds of the rostral half of the SN, and in the middle third of the central part of the SN, transported the label mainly to parts of the caudate nucleus and putamen. In these animals modest radioactive label was seen in VLm and VAmc, but not in other thalamic nuclei. There was no evidence that nigral neurons project to the subthalamic nucleus. No radioactive transport from nigral neurons was detected in the superior colliculus, the midbrain tegmentum, or the red nucleus, and none was transported to more caudal brain stem nuclei. Nigrothalamic fibers arise particularly from cells in rostral and lateral parts of the substantia nigra. While some cells in other parts of the nigra project to thalamic nuclei, these appear scattered and less numerous. Large cells in caudal parts of the SN do not project to thalamic nuclei. These observations confirm nigrothalamic projections to VLm and VAmc, and identify a new nigral projection to part of the dorsomedial nucleus of the thalamus (DMpl). No nigral efferent fibers project to any of the intralaminar thalamic nuclei.

Thalamic and hippocampal volume associated with memory functions in multiple sclerosis.

PubMed

Tremblay, Alexandra; Jobin, Céline; Demers, Mélanie; Dagenais, Emmanuelle; Narayanan, Sridar; Araújo, David; Douglas, Arnold L; Roger, Elaine; Chamelian, Laury; Duquette, Pierre; Rouleau, Isabelle

2018-06-08

Although multiple sclerosis (MS) has long been considered to primarily affect white matter, it is now recognized that cognitive deficits in MS are also related to neocortical, thalamic and hippocampal damage. However, the association between damage to these structures and memory deficits in MS is unclear. This study examines whether MS patients with cognitive impairment have a reduction of hippocampal and/or thalamic volumes compared to cognitively intact patients, and whether these volume reductions correlate with various aspects of memory function. Volumetric MRI measures of thalamus and hippocampus of forty-one patients with MS were performed. The patients were divided in two groups depending on the presence or absence of cognitive impairment, based on their neuropsychological tests scores. Right hippocampal volume was found to be associated with learning, and the left thalamic volume was found to predict performance in verbal memory. Cognitively impaired patients had a tendency to have a reduced left thalamic volume compared to cognitively intact patients. This study does not support a direct relationship between hippocampal atrophy and verbal memory. These results add to the growing evidence of the involvement of thalamus in cognitive impairment in MS and its association with verbal memory deficits. Copyright © 2018. Published by Elsevier Inc.

Thalamic synchrony and dynamic regulation of global forebrain oscillations.

PubMed

Huguenard, John R; McCormick, David A

2007-07-01

The circuitry within the thalamus creates an intrinsic oscillatory unit whose function depends critically on reciprocal synaptic connectivity between excitatory thalamocortical relay neurons and inhibitory thalamic reticular neurons along with a robust post-inhibitory rebound mechanism in relay neurons. Feedforward and feedback connections between cortex and thalamus reinforce the thalamic oscillatory activity into larger thalamocortical networks to generate sleep spindles and spike-wave discharge of generalized absence epilepsy. The degree of synchrony within the thalamic network seems to be crucial in determining whether normal (spindle) or pathological (spike-wave) oscillations occur, and recent studies show that regulation of excitability in the reticular nucleus leads to dynamical modulation of the state of the thalamic circuit and provide a basis for explaining how a variety of unrelated genetic alterations might lead to the spike-wave phenotype. In addition, given the central role of the reticular nucleus in generating spike-wave discharge, these studies have suggested specific interventions that would prevent seizures while still allowing normal spindle generation to occur. This review is part of the INMED/TINS special issue Physiogenic and pathogenic oscillations: the beauty and the beast, based on presentations at the annual INMED/TINS symposium (http://inmednet.com).

[Pure Amnesia].

PubMed

Tagawa, Koichi; Tokida, Haruki

2017-06-01

Pure amnesia (amnesic syndrome) is an organic brain syndrome characterized by impairment in episodic memory, with either an anterograde or sometimes retrograde loss of memories. Although episodic memory is impaired, semantic memory, immediate memory, and procedural memory are preserved. The Papez circuit is a network of nerve fibers and nerve centers that starts and ends in the hippocampus travelling by way of the fornix, mammillary bodies, anterior thalamic nuclei, cingulate gyrus, and parahippocampal gyrus. A lesion restricted to this circuit often produces pure amnesia. Regions concerned with the Yakovlev circuit also have an important role in memory. Clinical cases of pure amnesia caused by cerebrovascular disease presented following brain imaging and resulted from various different lesions. The cases identified were predominantly thalamic amnesia and hippocampal amnesia. Thalamic amnesia often resulted from an infarction in the territory of the thalamotuberal artery and paramedian thalamic artery although thalamic hemorrhage in medial portion of thalamus also produced pure amnesia. Hippocampal amnesia usually occurred following an infarction in the temporal branches of posterior cerebral artery. Cases of retrosplenial amnesia caused by subcortical hematoma and infarction in the retrosplenial region are also described. In addition, cases of pure amnesia resulting from an infarction in the fornix, mammillary body hemorrhage, and caudate hemorrhage are also shown.

Post-Thalamic Stroke Movement Disorders: A Systematic Review.

PubMed

Gupta, Navnika; Pandey, Sanjay

2018-06-05

After a stroke, movement disorders are rare manifestations mainly affecting the deep structures of the brain like the basal ganglia (44%) and thalamus (37%), although there have been case studies of movement disorders in strokes affecting the cerebral cortex also. This review aims to delineate the various movement disorders seen in association with thalamic strokes and tries to identify the location of the nuclei affected in each of the described movement disorders. Cases were identified through a search of PubMed database using different search terms related to post-thalamic stroke movement disorders and a secondary search of references of identified articles. We reviewed 2,520 research articles and only 86 papers met the inclusion criteria. Cases were included if they met criteria for post-thalamic stroke movement disorders. Case-cohort studies were also reviewed and will be discussed further. Key Messages: The most common post-stroke abnormal movement disorder reported in our review was dystonia followed by hemiataxia. There was a higher association between ischaemic stroke and movement disorder. Acute onset movement disorders were more common than delayed. The posterolateral thalamus was most commonly involved in post-thalamic stroke movement disorders. © 2018 S. Karger AG, Basel.

Thalamic alexia with agraphia

PubMed Central

de Gobbi Porto, Fábio Henrique; d'Ávila Freitas, Maria Isabel; de Oliveira, Maira Okada; Lucato, Leandro Tavares; Orsini, Marco; de Menezes, Sara Lúcia Silveira; Magaldi, Regina Miksian; Porto, Cláudia Sellitto; Dozzi Brucki, Sonia Maria; Nitrini, Ricardo

2012-01-01

Alexia with agraphia is defined as an acquired impairment affecting reading and writing ability. It can be associated with aphasia, but can also occur as an isolated entity. This impairment has classically been associated with a left angular gyrus lesion In the present study, we describe a case involving a patient who developed alexia with agraphia and other cognitive deficits after a thalamic hemorrhage. In addition, we discuss potential mechanisms of this cortical dysfunction syndrome caused by subcortical injury. We examined a patient who presented with alexia with agraphia and other cognitive deficits due to a hemorrhage in the left thalamus. Neuropsychological evaluation showed attention, executive function, arithmetic and memory impairments. In addition, language tests revealed severe alexia with agraphia in the absence of aphasia. Imaging studies disclosed an old thalamic hemorrhage involving the anterior, dorsomedial and pulvinar nuclei. Tractography revealed asymmetric thalamocortical radiations in the parietal region (left

Measurement of frontal lobe volume and thalamic volume in fetuses with congenital heart disease at different gestational weeks using three dimensional ultra sonography and its clinical value.

PubMed

Li-Fei, Zhu; Hong-Xiong, Liu; Ying, H E

2016-11-01

Our study aimed to investigate the measurement of frontal lobe volume and thalamic volume in fetuses with congenital heart disease (CHD) at different gestational weeks using three dimensional (3-D) ultrasonography and its clinical value. Then, 238 pregnant women who received obstetric ultrasonography in ultrasound department of Internal Medicine of our hospital were enrolled between March 2013 to April 2014. In this study, 85 fetuses were diagnosed to develop CHD by prenatal fetal echocardiography, and the other 153 fetuses were normal. Frontal lobe volume, thalamic volume and cerebral blood flow was determined by color Doppler ultrasonic diagnostic apparatus (type: GE Voluson E8). The level of MCA-PI and CPR in CHD fetus group performed significantly lower than that in normal fetus group (P<0.05), but the level of UA-PI performed significantly higher than that in normal fetus group (P<0.05). When gestational age <30 weeks, there was no significant difference in thalamic volume and frontal lobe volume between the two groups (P<0.05); when gestational age <30 weeks, the level of CHD fetus group performed significantly lower thalamic volume and frontal lobe volume than that in normal fetus group (P<0.05). When gestational age <30 weeks, there was no significant difference in BPD, HC, and GA between the two groups (P<0.05); when gestational age <30 weeks, the level of BPD, HC and GA in CHD fetus group performed significantly lower than that in normal fetus group (P<0.05). If gestational age <30 weeks, CHD performed a small impact on fetal frontal lobe volume and thalamic volume; if gestational age <30 weeks, the level of frontal lobe volume and thalamic volume in fetuses with CHD performed significantly lower than that in normal fetuses.

Thalamic modulation of aggression.

PubMed

Andy, O J; Giurintano, L; Giurintano, S; McDonald, T

1975-01-01

This experiment extends Pavlov's method of contrasts for 8 components of aggression were quantitatively evaluated in 11 freely moving adult cats. Aggression was elicited from the perifornix septohypothalamic areas by a series of progressively increasing and decreasing stimulation parameters. Three levels of thalamic stimulation (low, medium, and high) were combined with the perifornix stimulations. High level thalamic stimulation tended to facilitate the aggressive response elicited by low level perifornix stimulation. Thalamic lesions attenuated the aggression response, especially those elicited during high level perifornix stimulation. It was suggested that within the hypothalamic induced aggression circuitry the center median nucleus modulates the excitatory state of the system. The discussion concerns anatomic and physiologic pathways through which the center median nucleus may modulate the sensory, motor, and affective-autonomic subsystems into a well integrated aggressive state. These experimental findings are supported by the clinically established treatment of aggression by stereotaxic lesions placed in the center median nucleus.

What does a comparison of the alcoholic Korsakoff syndrome and thalamic infarction tell us about thalamic amnesia?

PubMed

Kopelman, Michael D

2015-07-01

In this review, the clinical, neuropsychological, and neuroimaging findings in the alcoholic Korsakoff syndrome and in thalamic amnesia, resulting from focal infarction, are compared. In both disorders, there is controversy over what is the critical site for anterograde amnesia to occur-damage to the anterior thalamus/mammillo-thalamic tract has most commonly been cited, but damage to the medio-dorsal nuclei has also been advocated. Both syndromes show 'core' features of an anterograde amnesic syndrome; but retrograde amnesia is generally much more extensive (going back many years or decades) in the Korsakoff syndrome. Likewise, spontaneous confabulation occurs more commonly in the Korsakoff syndrome, although seen in only a minority of chronic cases. These differences are attributed to the greater prevalence of frontal atrophy and frontal damage in Korsakoff cases. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

Remote thalamic microstructural abnormalities related to cognitive function in ischemic stroke patients.

PubMed

Fernández-Andújar, Marina; Doornink, Fleur; Dacosta-Aguayo, Rosalía; Soriano-Raya, Juan José; Miralbell, Júlia; Bargalló, Núria; López-Cancio, Elena; Pérez de la Ossa, Natalia; Gomis, Meritxell; Millán, Mònica; Barrios, Maite; Cáceres, Cynthia; Pera, Guillem; Forés, Rosa; Clemente, Imma; Dávalos, Antoni; Mataró, Maria

2014-11-01

Ischemic stroke can lead to a continuum of cognitive sequelae, ranging from mild vascular cognitive impairment to vascular dementia. These cognitive deficits can be influenced by the disruption of cortico-subcortical circuits. We sought to explore remote thalamic microstructural abnormalities and their association with cognitive function after ischemic stroke. Seventeen patients with right hemispheric ischemic stroke and 17 controls matched for age, sex, and years of education were included. All participants underwent neurological, neuropsychological, and diffusion tensor image examination. Patients were assessed 3 months poststroke. Voxel-wise analysis was used to study thalamic diffusion differences between groups. Mean fractional anisotropy (FA) and mean diffusivity (MD) values in significant thalamic areas were calculated for each subject and correlated with cognitive performance. Stroke patients showed lower FA values and higher MD values in specific areas of both the left and right thalamus compared with controls. In patients, decreased FA values were associated with lower verbal fluency performance in the right thalamus (R(2) = 0.45, β = 0.74) and the left thalamus (R(2) = 0.57, β = 0.77) after adjusting for diabetes mellitus. Moreover, increased MD values were associated with lower verbal fluency performance in the right thalamus (R(2) = 0.27, β = -0.54) after adjusting for diabetes mellitus. In controls, thalamic FA and MD values were not related to any cognitive function. Our findings support the hypothesis that ischemic stroke lesions are associated with remote thalamic diffusion abnormalities, and that these abnormalities can contribute to cognitive dysfunction 3 months after a cerebrovascular event. PsycINFO Database Record (c) 2014 APA, all rights reserved.

High frequency stimulation abolishes thalamic network oscillations: an electrophysiological and computational analysis

NASA Astrophysics Data System (ADS)

Lee, Kendall H.; Hitti, Frederick L.; Chang, Su-Youne; Lee, Dongchul C.; Roberts, David W.; McIntyre, Cameron C.; Leiter, James C.

2011-08-01

Deep brain stimulation (DBS) of the thalamus has been demonstrated to be effective for the treatment of epilepsy. To investigate the mechanism of action of thalamic DBS, we examined the effects of high frequency stimulation (HFS) on spindle oscillations in thalamic brain slices from ferrets. We recorded intracellular and extracellular electrophysiological activity in the nucleus reticularis thalami (nRt) and in thalamocortical relay (TC) neurons in the lateral geniculate nucleus, stimulated the slice using a concentric bipolar electrode, and recorded the level of glutamate within the slice. HFS (100 Hz) of TC neurons generated excitatory post-synaptic potentials, increased the number of action potentials in both TC and nRt neurons, reduced the input resistance, increased the extracellular glutamate concentration, and abolished spindle wave oscillations. HFS of the nRt also suppressed spindle oscillations. In both locations, HFS was associated with significant and persistent elevation in extracellular glutamate levels and suppressed spindle oscillations for many seconds after the cessation of stimulation. We simulated HFS within a computational model of the thalamic network, and HFS also disrupted spindle wave activity, but the suppression of spindle activity was short-lived. Simulated HFS disrupted spindle activity for prolonged periods of time only after glutamate release and glutamate-mediated activation of a hyperpolarization-activated current (Ih) was incorporated into the model. Our results suggest that the mechanism of action of thalamic DBS as used in epilepsy may involve the prolonged release of glutamate, which in turn modulates specific ion channels such as Ih, decreases neuronal input resistance, and abolishes thalamic network oscillatory activity.

The sensory thalamus and cerebral motor cortex are affected concurrently during induction of anesthesia with propofol: a case series with intracranial electroencephalogram recordings.

PubMed

Verdonck, Olivier; Reed, Sean J; Hall, Jeffery; Gotman, Jean; Plourde, Gilles

2014-03-01

Brain imaging studies suggest that loss of consciousness induced by general anesthetics is associated with impairment of thalamic function. There is, however, limited information on the time course of these changes. We recently obtained intracranial electroencephalogram (EEG) recordings from the ventroposterolateral (VPL) nucleus of the thalamus and from the motor cortex during induction of anesthesia in three patients to study the time course of the alterations of cortical and thalamic function. The patients were American Society of Anesthesiologists physical status I-II males aged 33-57 yr with intractable central pain caused by brachial plexus injury (patient 1 and 2) or insular infarct (patient 3). Anesthesia was induced with propofol (2.5-3.1 mg·kg(-1) over 30-45 sec) followed, after loss of consciousness, by rocuronium for tracheal intubation. The data retained for analysis are from one minute before the start of propofol to 110 sec later during ventilation of the patients' lungs before tracheal intubation. Spectral analysis was used to measure absolute EEG power. Propofol caused significant increases of cortical and thalamic power in the delta to beta frequency bands (1-30 Hz). These increases of cortical and thalamic power occurred either concomitantly or within seconds of each other. Propofol also caused a decrease in cortical and thalamic high-gamma (62-200 Hz) power that also followed a similar time course. We conclude that induction of anesthesia with propofol in these patients was associated with concurrent alterations of cortical and sensory thalamic activity.

Activity propagation in an avian basal ganglia-thalamo-cortical circuit essential for vocal learning

PubMed Central

Kojima, Satoshi; Doupe, Allison J.

2009-01-01

In mammalian basal ganglia-thalamo-cortical circuits, GABAergic pallidal neurons are thought to ‘gate’ or modulate excitation in thalamus with their strong inhibitory inputs, and thus signal to cortex by pausing and permitting thalamic neurons to fire in response to excitatory drive. In contrast, in a homologous circuit specialized for vocal learning in songbirds, evidence suggests that pallidal neurons signal by eliciting postinhibitory rebound spikes in thalamus, which could occur even without any excitatory drive to thalamic neurons. To test whether songbird pallidal neurons can also communicate with thalamus by gating excitatory drive, as well as by postinhibitory rebound, we examined the activity of thalamic relay neurons in response to acute inactivation of the basal ganglia structure Area X; Area X contains the pallidal neurons that project to thalamus. Although inactivation of Area X should eliminate rebound-mediated spiking in thalamus, this manipulation tonically increases the firing rate of thalamic relay neurons, providing evidence that songbird pallidal neurons can gate tonic thalamic excitatory drive. We also found that the increased thalamic activity was fed forward to its target in the avian equivalent of cortex, which includes neurons that project to the vocal premotor area. These data raise the possibility that basal ganglia circuits can signal to cortex through thalamus both by generating postinhibitory rebound and by gating excitatory drive, and may switch between these modes depending on the statistics of pallidal firing. Moreover, these findings provide insight into the strikingly different disruptive effects of basal ganglia and ‘cortical’ lesions on songbird vocal learning. PMID:19369547

Quantifying interictal metabolic activity in human temporal lobe epilepsy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Henry, T.R.; Mazziotta, J.C.; Engel, J. Jr.

1990-09-01

The majority of patients with complex partial seizures of unilateral temporal lobe origin have interictal temporal hypometabolism on (18F)fluorodeoxyglucose positron emission tomography (FDG PET) studies. Often, this hypometabolism extends to ipsilateral extratemporal sites. The use of accurately quantified metabolic data has been limited by the absence of an equally reliable method of anatomical analysis of PET images. We developed a standardized method for visual placement of anatomically configured regions of interest on FDG PET studies, which is particularly adapted to the widespread, asymmetric, and often severe interictal metabolic alterations of temporal lobe epilepsy. This method was applied by a singlemore » investigator, who was blind to the identity of subjects, to 10 normal control and 25 interictal temporal lobe epilepsy studies. All subjects had normal brain anatomical volumes on structural neuroimaging studies. The results demonstrate ipsilateral thalamic and temporal lobe involvement in the interictal hypometabolism of unilateral temporal lobe epilepsy. Ipsilateral frontal, parietal, and basal ganglial metabolism is also reduced, although not as markedly as is temporal and thalamic metabolism.« less

Autoradiographic evidence for two classes of mu opioid binding sites in rat brain using (/sup 125/I)FK33824

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rothman, R.B.; Jacobson, A.E.; Rice, K.C.

1987-11-01

Previous studies demonstrated that pretreatment of brain membranes with the irreversible mu antagonist, beta-funaltrexamine (beta-FNA), partially eliminated mu binding sites (25,35), consistent with the existence of two mu binding sites distinguished by beta-FNA. This paper tests the hypothesis that the FNA-sensitive and FNA-insensitive mu binding sites have different anatomical distributions in rat brain. Prior to autoradiographic visualization of mu binding sites, (/sup 3/H)oxymorphone, (/sup 3/H)D-ala2-MePhe4, Gly-ol5-enkephalin (DAGO), and (/sup 125/I)D-ala2-Me-Phe4-met(o)-ol)enkephalin (FK33824) were shown to selectively label mu binding sites using slide mounted sections of molded minced rat brain. As found using membranes, beta-FNA eliminated only a portion of mu bindingmore » sites. Autoradiographic visualization of mu binding sites using the mu-selective ligand (/sup 125/I)FK33824 in control and FNA-treated sections of rat brain demonstrated that the proportion of mu binding sites sensitive to beta-FNA varied across regions of the brain, particularly the dorsal thalamus, ventrobasal complex and the hypothalamus, providing anatomical data supporting the existence of two classes of mu binding sites in rat brain.« less

Thalamic control of sensory selection in divided attention.

PubMed

Wimmer, Ralf D; Schmitt, L Ian; Davidson, Thomas J; Nakajima, Miho; Deisseroth, Karl; Halassa, Michael M

2015-10-29

How the brain selects appropriate sensory inputs and suppresses distractors is unknown. Given the well-established role of the prefrontal cortex (PFC) in executive function, its interactions with sensory cortical areas during attention have been hypothesized to control sensory selection. To test this idea and, more generally, dissect the circuits underlying sensory selection, we developed a cross-modal divided-attention task in mice that allowed genetic access to this cognitive process. By optogenetically perturbing PFC function in a temporally precise window, the ability of mice to select appropriately between conflicting visual and auditory stimuli was diminished. Equivalent sensory thalamocortical manipulations showed that behaviour was causally dependent on PFC interactions with the sensory thalamus, not sensory cortex. Consistent with this notion, we found neurons of the visual thalamic reticular nucleus (visTRN) to exhibit PFC-dependent changes in firing rate predictive of the modality selected. visTRN activity was causal to performance as confirmed by bidirectional optogenetic manipulations of this subnetwork. Using a combination of electrophysiology and intracellular chloride photometry, we demonstrated that visTRN dynamically controls visual thalamic gain through feedforward inhibition. Our experiments introduce a new subcortical model of sensory selection, in which the PFC biases thalamic reticular subnetworks to control thalamic sensory gain, selecting appropriate inputs for further processing.

Thalamic pain alleviated by stellate ganglion block: A case report.

PubMed

Liao, Chenlong; Yang, Min; Liu, Pengfei; Zhong, Wenxiang; Zhang, Wenchuan

2017-02-01

Thalamic pain is a distressing and treatment-resistant type of central post-stroke pain. Although stellate ganglion block is an established intervention used in pain management, its use in the treatment of thalamic pain has never been reported. A 66-year-old woman presented with a 3-year history of severe intermittent lancinating pain on the right side of the face and the right hand. The pain started from the ulnar side of the right forearm after a mild ischemic stroke in bilateral basal ganglia and left thalamus. Weeks later, the pain extended to the dorsum of the finger tips and the whole palmar surface, becoming more severe. Meanwhile, there was also pain with similar characteristics emerging on her right face, resembling atypical trigeminal neuralgia. Thalamic pain was diagnosed. After refusing the further invasive treatment, she was suggested to try stellate ganglion block. After a 3-day period of pain free (numerical rating scale: 0) postoperatively, she reported moderate to good pain relief with a numerical rating scale of about 3 to 4 lasting 1 month after the first injection. Pain as well as the quality of life was markedly improved with less dose of analgesic agents. Stellate ganglion block may be an optional treatment for thalamic pain.

Aphasia and unilateral spatial neglect due to acute thalamic hemorrhage: clinical correlations and outcomes.

PubMed

Osawa, Aiko; Maeshima, Shinichiro

2016-04-01

Thalamic hemorrhages are associated with a variety of cognitive dysfunctions, and it is well known that such cognitive changes constitute a limiting factor of recovery of the activities of daily living (ADL). The relationship between cognitive dysfunction and hematomas is unclear. In this study, we investigated the relationship between aphasia/neglect and hematoma volume, hematoma type, and the ADL. One hundred fifteen patients with thalamic hemorrhage (70 men and 45 women) were studied. Their mean age was 68.9 ± 10.3 years, and patients with both left and right lesions were included. We calculated hematoma volume and examined the presence or absence of aphasia/neglect and the relationships between these dysfunctions and hematoma volume, hematoma type, and the ADL. Fifty-nine patients were found to have aphasia and 35 were found to have neglect. Although there was no relationship between hematoma type and cognitive dysfunction, hematoma volume showed a correlation with the severity of cognitive dysfunction. The ADL score and ratio of patient discharge for patients with aphasia/neglect were lower than those for patients without aphasia/neglect. We observed a correlation between the hematoma volume in thalamic hemorrhage and cognitive dysfunction. Aphasia/neglect is found frequently in patients with acute thalamic hemorrhage and may influence the ADL.

Short pauses in thalamic deep brain stimulation promote tremor and neuronal bursting.

PubMed

Swan, Brandon D; Brocker, David T; Hilliard, Justin D; Tatter, Stephen B; Gross, Robert E; Turner, Dennis A; Grill, Warren M

2016-02-01

We conducted intraoperative measurements of tremor during DBS containing short pauses (⩽50 ms) to determine if there is a minimum pause duration that preserves tremor suppression. Nine subjects with ET and thalamic DBS participated during IPG replacement surgery. Patterns of DBS included regular 130 Hz stimulation interrupted by 0, 15, 25 or 50 ms pauses. The same patterns were applied to a model of the thalamic network to quantify effects of pauses on activity of model neurons. All patterns of DBS decreased tremor relative to 'off'. Patterns with pauses generated less tremor reduction than regular high frequency DBS. The model revealed that rhythmic burst-driver inputs to thalamus were masked during DBS, but pauses in stimulation allowed propagation of bursting activity. The mean firing rate of bursting-type model neurons as well as the firing pattern entropy of model neurons were both strongly correlated with tremor power across stimulation conditions. The temporal pattern of stimulation influences the efficacy of thalamic DBS. Pauses in stimulation resulted in decreased tremor suppression indicating that masking of pathological bursting is a mechanism of thalamic DBS for tremor. Pauses in stimulation decreased the efficacy of open-loop DBS for suppression of tremor. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Thalamic Activation in the Kleine-Levin Syndrome

PubMed Central

Engström, Maria; Karlsson, Thomas; Landtblom, Anne-Marie

2014-01-01

Study Objectives: The objective of this study was to investigate if combined measures of activation in the thalamus and working memory capacity could guide the diagnosis of Kleine-Levin Syndrome (KLS). A second objective was to obtain more insight into the neurobiological causes of KLS. Design: Matched group and consecutive recruitment. Setting: University hospital neurology department and imaging center. Patients or Participants: Eighteen patients with KLS diagnosed according to the International Classification of Sleep Disorders and 26 healthy controls were included. Interventions: N/A. Measurements and Results: Working memory capacity was assessed by the listening span task. A version of this task (reading span) was presented to the participants during functional magnetic resonance imaging (fMRI). Activation in the thalamus was measured in a region of interest analysis. A combination of the working memory capacity and the thalamic activation measures resulted in 80% prediction accuracy, 81% sensitivity, and 78% specificity regarding the ability to separate KLS patients from healthy controls. The controls had an inverse relation between working memory capacity and thalamic activation; higher performing participants had lower thalamic activation (r = -0.41). KLS patients showed the opposite relationship; higher performing participants had a tendency to higher thalamic activation (r = -0.35). Conclusions: This study shows that functional neuroimaging of the thalamus combined with neuropsychological assessment of working memory function provides a means to guide diagnosis of Kleine-Levin Syndrome. Results in this study also indicate that imaging of brain function and evaluation of cognitive capacity can give insights into the neurobiological mechanisms of Kleine-Levin Syndrome. Citation: Engström M; Karlsson T; Landtblom AM. Thalamic activation in the Kleine-Levin Syndrome. SLEEP 2014;37(2):379-386. PMID:24497666

Successive neuron loss in the thalamus and cortex in a mouse model of infantile neuronal ceroid lipofuscinosis.

PubMed

Kielar, Catherine; Maddox, Lucy; Bible, Ellen; Pontikis, Charlie C; Macauley, Shannon L; Griffey, Megan A; Wong, Michael; Sands, Mark S; Cooper, Jonathan D

2007-01-01

Infantile neuronal ceroid lipofuscinosis (INCL) is caused by deficiency of the lysosomal enzyme, palmitoyl protein thioesterase 1 (PPT1). We have investigated the onset and progression of pathological changes in Ppt1 deficient mice (Ppt1-/-) and the development of their seizure phenotype. Surprisingly, cortical atrophy and neuron loss occurred only late in disease progression but were preceded by localized astrocytosis within individual thalamic nuclei and the progressive loss of thalamic neurons that relay different sensory modalities to the cortex. This thalamic neuron loss occurred first within the visual system and only subsequently in auditory and somatosensory relay nuclei or the inhibitory reticular thalamic nucleus. The loss of granule neurons and GABAergic interneurons followed in each corresponding cortical region, before the onset of seizure activity. These findings provide novel evidence for successive neuron loss within the thalamus and cortex in Ppt1-/- mice, revealing the thalamus as an important early focus of INCL pathogenesis.

Effects of thalamic deep brain stimulation on spontaneous language production.

PubMed

Ehlen, Felicitas; Vonberg, Isabelle; Kühn, Andrea A; Klostermann, Fabian

2016-08-01

The thalamus is thought to contribute to language-related processing, but specifications of this notion remain vague. An assessment of potential effects of thalamic deep brain stimulation (DBS) on spontaneous language may help to delineate respective functions. For this purpose, we analyzed spontaneous language samples from thirteen (six female / seven male) patients with essential tremor treated with DBS of the thalamic ventral intermediate nucleus (VIM) in their respective ON vs. OFF conditions. Samples were obtained from semi-structured interviews and examined on multidimensional linguistic levels. In the VIM-DBS ON condition, participants used a significantly higher proportion of paratactic as opposed to hypotactic sentence structures. This increase correlated negatively with the change in the more global cognitive score, which in itself did not change significantly. In conclusion, VIM-DBS appears to induce the use of a simplified syntactic structure. The findings are discussed in relation to concepts of thalamic roles in language-related cognitive behavior. Copyright © 2016 Elsevier Ltd. All rights reserved.

Successive neuron loss in the thalamus and cortex in a mouse model of infantile neuronal ceroid lipofuscinosis

PubMed Central

Kielar, Catherine; Maddox, Lucy; Bible, Ellen; Pontikis, Charlie C; Macauley, Shannon L; Griffey, Megan A; Wong, Michael; Sands, Mark S; Cooper, Jonathan D

2007-01-01

Infantile neuronal ceroid lipofuscinosis (INCL) is caused by deficiency of the lysosomal enzyme, palmitoyl protein thioesterase 1 (PPT1). We have investigated the onset and progression of pathological changes in Ppt1-deficient mice (Ppt1−/−) and the development of their seizure phenotype. Surprisingly, cortical atrophy and neuron loss occurred only late in disease progression, but were preceded by localized astrocytosis within individual thalamic nuclei and the progressive loss of thalamic neurons that relay different sensory modalities to the cortex. This thalamic neuron loss occurred first within the visual system and only subsequently in auditory and somatosensory relay nuclei or the inhibitory reticular thalamic nucleus. The loss of granule neurons and GABAergic interneurons followed in each corresponding cortical region, before the onset of seizure activity. These findings provide novel evidence for successive neuron loss within the thalamus and cortex in Ppt1−/− mice, revealing the thalamus as an important early focus of INCL pathogenesis. PMID:17046272

External pallidal stimulation improves parkinsonian motor signs and modulates neuronal activity throughout the basal ganglia thalamic network.

PubMed

Vitek, Jerrold L; Zhang, Jianyu; Hashimoto, Takao; Russo, Gary S; Baker, Kenneth B

2012-01-01

Deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) and the subthalamic nucleus (STN) are effective for the treatment of advanced Parkinson's disease (PD). We have shown previously that DBS of the external segment of the globus pallidus (GPe) is associated with improvements in parkinsonian motor signs; however, the mechanism of this effect is not known. In this study, we extend our findings on the effect of STN and GPi DBS on neuronal activity in the basal ganglia thalamic network to include GPe DBS using the 1-methyl-4-phenyl-1.2.3.6-tetrahydropyridine (MPTP) monkey model. Stimulation parameters that improved bradykinesia were associated with changes in the pattern and mean discharge rate of neuronal activity in the GPi, STN, and the pallidal [ventralis lateralis pars oralis (VLo) and ventralis anterior (VA)] and cerebellar [ventralis lateralis posterior pars oralis (VPLo)] receiving areas of the motor thalamus. Population post-stimulation time histograms revealed a complex pattern of stimulation-related inhibition and excitation for the GPi and VA/VLo, with a more consistent pattern of inhibition in STN and excitation in VPLo. Mean discharge rate was reduced in the GPi and STN and increased in the VPLo. Effective GPe DBS also reduced bursting in the STN and GPi. These data support the hypothesis that therapeutic DBS activates output from the stimulated structure and changes the temporal pattern of neuronal activity throughout the basal ganglia thalamic network and provide further support for GPe as a potential therapeutic target for DBS in the treatment of PD. Copyright © 2011 Elsevier Inc. All rights reserved.

Advanced fiber tracking in early acquired brain injury causing cerebral palsy.

PubMed

Lennartsson, F; Holmström, L; Eliasson, A-C; Flodmark, O; Forssberg, H; Tournier, J-D; Vollmer, B

2015-01-01

Diffusion-weighted MR imaging and fiber tractography can be used to investigate alterations in white matter tracts in patients with early acquired brain lesions and cerebral palsy. Most existing studies have used diffusion tensor tractography, which is limited in areas of complex fiber structures or pathologic processes. We explored a combined normalization and probabilistic fiber-tracking method for more realistic fiber tractography in this patient group. This cross-sectional study included 17 children with unilateral cerebral palsy and 24 typically developing controls. DWI data were collected at 1.5T (45 directions, b=1000 s/mm(2)). Regions of interest were defined on a study-specific fractional anisotropy template and mapped onto subjects for fiber tracking. Probabilistic fiber tracking of the corticospinal tract and thalamic projections to the somatosensory cortex was performed by using constrained spherical deconvolution. Tracts were qualitatively assessed, and DTI parameters were extracted close to and distant from lesions and compared between groups. The corticospinal tract and thalamic projections to the somatosensory cortex were realistically reconstructed in both groups. Structural changes to tracts were seen in the cerebral palsy group and included splits, dislocations, compaction of the tracts, or failure to delineate the tract and were associated with underlying pathology seen on conventional MR imaging. Comparisons of DTI parameters indicated primary and secondary neurodegeneration along the corticospinal tract. Corticospinal tract and thalamic projections to the somatosensory cortex showed dissimilarities in both structural changes and DTI parameters. Our proposed method offers a sensitive means to explore alterations in WM tracts to further understand pathophysiologic changes following early acquired brain injury. © 2015 by American Journal of Neuroradiology.

Lucid dreams, an atypical sleep disturbance in anterior and mediodorsal thalamic strokes.

PubMed

Sagnier, S; Coulon, P; Chaufton, C; Poli, M; Debruxelles, S; Renou, P; Rouanet, F; Olindo, S; Sibon, I

2015-11-01

Cognitive, affective, and behavioural disturbances are commonly reported following thalamic strokes. Conversely, sleep disorders are rarely reported in this context. Herein, we report the cases of two young patients admitted for an ischemic stroke located in the territories of the left pre-mammillary and paramedian arteries. Together with aphasia, memory complaint, impaired attention and executive functions, they reported lucid dreams with catastrophic content or conflicting situations. Lucid dreams are an atypical presentation in thalamic strokes. These cases enlarge the clinical spectrum of sleep-wake disturbances potentially observed after an acute cerebrovascular event. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Persistent anterograde amnesia due to the artery of Percheron occlusion: a case report.

PubMed

Ince, Birsen; Asan, Furkan

2018-04-01

Bilateral thalamic infarction involving the artery of Percheron (AOP) can cause diagnostic difficulties due to the varying clinical presentations. AOP infarcts presented with isolated memory impairment are not common and the factors affecting the persistence of memory disorders are still unknown. A 41-year-old male patient was hospitalized with acute unconsciousness. MRI disclosed bilateral paramedian thalamic infarction The patient had isolated memory deficit and his anterograde amnesia continued without any change in the past decade. More cases might answer the questions concerning the intra- and extra-thalamic structures responsible for the amnesic syndrome and the factors affecting the persistence of the symptoms.

Thalamic inflammation after brain trauma is associated with thalamo-cortical white matter damage.

PubMed

Scott, Gregory; Hellyer, Peter J; Ramlackhansingh, Anil F; Brooks, David J; Matthews, Paul M; Sharp, David J

2015-12-01

Traumatic brain injury can trigger chronic neuroinflammation, which may predispose to neurodegeneration. Animal models and human pathological studies demonstrate persistent inflammation in the thalamus associated with axonal injury, but this relationship has never been shown in vivo. Using [(11)C]-PK11195 positron emission tomography, a marker of microglial activation, we previously demonstrated thalamic inflammation up to 17 years after traumatic brain injury. Here, we use diffusion MRI to estimate axonal injury and show that thalamic inflammation is correlated with thalamo-cortical tract damage. These findings support a link between axonal damage and persistent inflammation after brain injury.

Thalamocortical Dysfunction and Thalamic Injury after Asphyxial Cardiac Arrest in Developing Rats

PubMed Central

Shoykhet, Michael; Simons, Daniel J.; Alexander, Henry; Hosler, Christina; Kochanek, Patrick M.; Clark, Robert S. B.

2012-01-01

Global hypoxia-ischemia interrupts oxygen delivery and blood flow to the entire brain. Previous studies of global brain hypoxia ischemia have primarily focused on injury to the cerebral cortex and to the hippocampus. Susceptible neuronal populations also include inhibitory neurons in the thalamic Reticular Nucleus. We therefore investigated the impact of global brain hypoxia-ischemia on the thalamic circuit function in the somatosensory system of young rats. We used single neuron recordings and controlled whisker deflections to examine responses of thalamocortical neurons to sensory stimulation in rat survivors of 9 min of asphyxial cardiac arrest incurred on post-natal day 17. We found that 48–72 hours after cardiac arrest, thalamocortical neurons demonstrate significantly elevated firing rates both during spontaneous activity and in response to whisker deflections. The elevated evoked firing rates persist for at least 6–8 weeks after injury. Despite the overall increase in firing, by 6 weeks, thalamocortical neurons display degraded receptive fields, with decreased responses to adjacent whiskers. Nine min of asphyxial cardiac arrest was associated with extensive degeneration of neurites in the somatosensory nucleus as well as activation of microglia in the Reticular Nucleus. Global brain hypoxia-ischemia during cardiac arrest has a long-term impact on processing and transfer of sensory information by thalamic circuitry. Thalamic circuitry and normalization of its function may represent a distinct therapeutic target after cardiac arrest. PMID:22492052

Simultaneous Top-down Modulation of the Primary Somatosensory Cortex and Thalamic Nuclei during Active Tactile Discrimination

PubMed Central

Pais-Vieira, Miguel; Lebedev, Mikhail A.; Wiest, Michael C.; Nicolelis, Miguel A.L.

2013-01-01

The rat somatosensory system contains multiple thalamocortical loops (TCL) that altogether process, in fundamentally different ways, tactile stimuli delivered passively or actively sampled. To elucidate potential top-down mechanisms that govern TCL processing in awake, behaving animals, we simultaneously recorded neuronal ensemble activity across multiple cortical and thalamic areas while rats performed an active aperture discrimination task. Single neurons located in the primary somatosensory cortex (S1), the ventroposterior medial (VPM) and the posterior medial (POM) thalamic nuclei of the trigeminal somatosensory pathways exhibited prominent anticipatory firing modulations prior to the whiskers touching the aperture edges. This cortical and thalamic anticipatory firing could not be explained by whisker movements or whisker stimulation, because neither trigeminal ganglion sensory-evoked responses nor EMG activity were detected during the same period. Both thalamic and S1 anticipatory activity were predictive of the animal’s discrimination accuracy. Inactivation of the primary motor cortex (M1) with muscimol affected anticipatory patterns in S1 and the thalamus, and impaired the ability to predict the animal’s performance accuracy based on thalamocortical anticipatory activity. These findings suggest that neural processing in TCLs is launched in anticipation of whisker contact with objects, depends on top-down effects generated in part by M1 activity, and cannot be explained by the classical feedforward model of the rat trigeminal system. PMID:23447616

Increased responses in the somatosensory thalamus immediately after spinal cord injury.

PubMed

Alonso-Calviño, E; Martínez-Camero, I; Fernández-López, E; Humanes-Valera, D; Foffani, G; Aguilar, J

2016-03-01

Spinal cord injury (SCI) involves large-scale deafferentation of supraspinal structures in the somatosensory system, producing well-known long-term effects at the thalamo-cortical level. We recently showed that SCI provokes immediate changes in cortical spontaneous and evoked responses and here, we have performed a similar study to define the immediate changes produced in the thalamic ventro-postero-lateral nucleus (VPL) that are associated with the forepaw and hindpaw circuits. Extracellular electrophysiological recordings from the VPL reflected the spontaneous activity and the responses to peripheral electrical stimulation applied to the paws. Accordingly, the activity of the neuronal populations recorded at specific thalamic locations that correspond to the forepaw and hindpaw circuits was recorded under control conditions and immediately after thoracic SCI. The results demonstrate that peripheral inputs from both extremities overlap on neuronal populations in the somatosensory thalamus. In addition, they show that the responses of thalamic neurons to forepaw and hindpaw stimuli are increased immediately after SCI, in association with a specific decrease in spontaneous activity in the hindpaw locations. Finally, the increased thalamic responses after SCI have a state-dependent component in relation with cortical activity. Together, our results indicate that the thalamic changes occurring immediately after SCI could contribute to the cortical changes also detected immediately after such spinal lesions. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Thalamic morphology in schizophrenia and schizoaffective disorder.

PubMed

Smith, Matthew J; Wang, Lei; Cronenwett, Will; Mamah, Daniel; Barch, Deanna M; Csernansky, John G

2011-03-01

Biomarkers are needed that can distinguish between schizophrenia and schizoaffective disorder to inform the ongoing debate over the diagnostic boundary between these two disorders. Neuromorphometric abnormalities of the thalamus have been reported in individuals with schizophrenia and linked to core features of the disorder, but have not been similarly investigated in individuals with schizoaffective disorder. In this study, we examine whether individuals with schizoaffective disorder have a pattern of thalamic deformation that is similar or different to the pattern found in individuals with schizophrenia. T1-weighted magnetic resonance images were collected from individuals with schizophrenia (n = 47), individuals with schizoaffective disorder (n = 15), and controls (n = 42). Large-deformation, high-dimensional brain mapping was used to obtain three-dimensional surfaces of the thalamus. Multiple analyses of variance were used to test for group differences in volume and measures of surface shape. Individuals with schizophrenia or schizoaffective disorder have similar thalamic volumes. Thalamic surface shape deformation associated with schizophrenia suggests selective involvement of the anterior and posterior thalamus, while deformations in mediodorsal and ventrolateral regions were observed in both groups. Schizoaffective disorder had distinct deformations in medial and lateral thalamic regions. Abnormalities distinct to schizoaffective disorder suggest involvement of the central and ventroposterior medial thalamus which may be involved in mood circuitry, dorsolateral nucleus which is involved in recall processing, and the lateral geniculate nucleus which is involved in visual processing. Copyright © 2010 Elsevier Ltd. All rights reserved.

Thalamic Morphology in Schizophrenia and Schizoaffective Disorder

PubMed Central

Smith, Matthew J.; Wang, Lei; Cronenwett, Will; Mamah, Daniel; Barch, Deanna M.; Csernansky, John G.

2010-01-01

Background Biomarkers are needed that can distinguish between schizophrenia and schizoaffective disorder to inform the ongoing debate over the diagnostic boundary between these two disorders. Neuromorphometric abnormalities of the thalamus have been reported in individuals with schizophrenia and linked to core features of the disorder, but have not been similarly investigated in individuals with schizoaffective disorder. In this study, we examine whether individuals with schizoaffective disorder have a pattern of thalamic deformation that is similar or different to the pattern found in individuals with schizophrenia. Method T1-weighted magnetic resonance images were collected from individuals with schizophrenia (n=47), individuals with schizoaffective disorder (n=15), and controls (n=42). Large-deformation, high-dimensional brain mapping was used to obtain three-dimensional surfaces of the thalamus. Multiple analyses of variance were used to test for group differences in volume and measures of surface shape. Results Individuals with schizophrenia or schizoaffective disorder have similar thalamic volumes. Thalamic surface shape deformation associated with schizophrenia suggests selective involvement of the anterior and posterior thalamus, while deformations in mediodorsal and ventrolateral regions were observed in both groups. Schizoaffective disorder had distinct deformations in medial and lateral thalamic regions. Conclusions Abnormalities distinct to schizoaffective disorder suggest involvement of the central and ventroposterior medial thalamus which may be involved in mood circuitry, dorsolateral nucleus which is involved in recall processing, and the lateral geniculate nucleus which is involved in visual processing. PMID:20797731

Communication skills and thalamic lesion: Strategies of rehabilitation.

PubMed

Amaddii, Luisa; Centorrino, Santi; Cambi, Jacopo; Passali, Desiderio

2014-01-01

To describe the speech rehabilitation history of patients with thalamic lesions. Thalamic lesions can affect speech and language according to diverse thalamic nuclei involved. Because of the strategic functional position of the thalamus within the cognitive networks, its lesion can also interfere with other cognitive processes, such as attention, memory and executive functions. Alterations of these cognitive domains contribute significantly to language deficits, leading to communicative inefficacy. This fact must be considered in the rehabilitation efforts. Whereas evaluation of cognitive functions and communicative efficiency is different from that of aphasic disorder, treatment should also be different. The treatment must be focused on specific cognitive deficits with belief in the regaining of communicative ability, as well as it occurs in therapy of pragmatic disorder in traumatic brain injury: attention process training, mnemotechnics and prospective memory training. According to our experience: (a) there is a close correlation between cognitive processes and communication skills; (b) alterations of attention, memory and executive functions cause a loss of efficiency in the language use; and (c) appropriate cognitive treatment improves pragmatic competence and therefore the linguistic disorder. For planning a speech-therapy it is important to consider the relationship between cognitive functions and communication. The cognitive/behavioral treatment confirms its therapeutic efficiency for thalamic lesions. Copyright © 2014 Polish Otorhinolaryngology - Head and Neck Surgery Society. Published by Elsevier Urban & Partner Sp. z.o.o. All rights reserved.

Thalamic modulation of cingulate seizure activity via the regulation of gap junctions in mice thalamocingulate slice.

PubMed

Chang, Wei-Pang; Wu, José Jiun-Shian; Shyu, Bai-Chuang

2013-01-01

The thalamus is an important target for deep brain stimulation in the treatment of seizures. However, whether the modulatory effect of thalamic inputs on cortical seizures occurs through the modulation of gap junctions has not been previously studied. Therefore, we tested the effects of different gap junction blockers and couplers in a drug-resistant seizure model and studied the role of gap junctions in the thalamic modulation on cortical seizures. Multielectrode array and calcium imaging were used to record the cortical seizures induced by 4-aminopyridine (250 µM) and bicuculline (5-50 µM) in a novel thalamocingulate slice preparation. Seizure-like activity was significantly attenuated by the pan-gap junction blockers carbenoxolone and octanol and specific neuronal gap junction blocker mefloquine. The gap junction coupler trimethylamine significantly enhanced seizure-like activity. Gap junction blockers did not influence the initial phase of seizure-like activity, but they significantly decreased the amplitude and duration of the maintenance phase. The development of seizures is regulated by extracellular potassium concentration. Carbenoxolone partially restored the amplitude and duration after removing the thalamic inputs. A two-dimensional current source density analysis showed that the sink and source signals shifted to deeper layers after removing the thalamic inputs during the clonic phase. These results indicate that the regulatory mechanism of deep brain stimulation in the thalamus occurs partially though gap junctions.

Medial posterior choroidal artery territory infarction associated with tumor removal in the pineal/tectum/thalamus region through the occipital transtentorial approach.

PubMed

Saito, Ryuta; Kumabe, Toshihiro; Kanamori, Masayuki; Sonoda, Yukihiko; Mugikura, Shunji; Takahashi, Shoki; Tominaga, Teiji

2013-08-01

Damage to the deep venous system, occipital lobe, and/or corpus callosum is well known to cause complications associated with the occipital transtentorial approach (OTA), but ischemic complications are not well documented. The authors investigated the high incidences of ischemic complications associated with removal of pineal/tectal/thalamic tumors through the OTA. Clinical records of 29 patients who underwent 31 surgeries using the OTA from December 2001 to May 2011 were retrospectively studied. Tumor locations were the pineal/tectal/thalamic region for 19, cerebellum for 7, and medial temporal lobe for 3. Postoperative diffusion-weighted magnetic resonance images obtained within 72 h after surgery detected infarction in the tectal/splenial/thalamic region, presumably representing the medial posterior choroidal artery (MPChA) territory, in 10 patients. All these patients had tumor in the pineal/tectal/thalamic region. Deteriorated or newly developed eye symptoms including vertical gaze palsy tended to persist in these patients compared to those without ischemic complications. A relatively high incidence of MPChA territory infarction was associated with removal of tumors in the pineal/tectal/thalamic region through the OTA. Eye symptoms often occurred post-surgery and tended to persist in these patients. Neurosurgeons must be aware of the possibility of MPChA territory infarction to further increase the safety of the OTA. Copyright © 2012 Elsevier B.V. All rights reserved.

Drivers from the deep: the contribution of collicular input to thalamocortical processing.

PubMed

Wurtz, Robert H; Sommer, Marc A; Cavanaugh, James

2005-01-01

A traditional view of the thalamus is that it is a relay station which receives sensory input and conveys this information to cortex. This sensory input determines most of the properties of first order thalamic neurons, and so is said to drive, rather than modulate, these neurons. This holds as a rule for first order thalamic nuclei, but in contrast, higher order thalamic nuclei receive much of their driver input back from cerebral cortex. In addition, higher order thalamic neurons receive inputs from subcortical movement-related centers. In the terminology popularized from studies of the sensory system, can we consider these ascending motor inputs to thalamus from subcortical structures to be modulators, subtly influencing the activity of their target neurons, or drivers, dictating the activity of their target neurons? This chapter summarizes relevant evidence from neuronal recording, inactivation, and stimulation of pathways projecting from the superior colliculus through thalamus to cerebral cortex. The study concludes that many inputs to the higher order nuclei of the thalamus from subcortical oculomotor areas - from the superior colliculus and probably other midbrain and pontine regions - should be regarded as motor drivers analogous to the sensory drivers at the first order thalamic nuclei. These motor drivers at the thalamus are viewed as being at the top of a series of feedback loops that provide information on impending actions, just as sensory drivers provide information about the external environment.

Thalamic Modulation of Cingulate Seizure Activity Via the Regulation of Gap Junctions in Mice Thalamocingulate Slice

PubMed Central

Chang, Wei-Pang; Wu, José Jiun-Shian; Shyu, Bai-Chuang

2013-01-01

The thalamus is an important target for deep brain stimulation in the treatment of seizures. However, whether the modulatory effect of thalamic inputs on cortical seizures occurs through the modulation of gap junctions has not been previously studied. Therefore, we tested the effects of different gap junction blockers and couplers in a drug-resistant seizure model and studied the role of gap junctions in the thalamic modulation on cortical seizures. Multielectrode array and calcium imaging were used to record the cortical seizures induced by 4-aminopyridine (250 µM) and bicuculline (5–50 µM) in a novel thalamocingulate slice preparation. Seizure-like activity was significantly attenuated by the pan-gap junction blockers carbenoxolone and octanol and specific neuronal gap junction blocker mefloquine. The gap junction coupler trimethylamine significantly enhanced seizure-like activity. Gap junction blockers did not influence the initial phase of seizure-like activity, but they significantly decreased the amplitude and duration of the maintenance phase. The development of seizures is regulated by extracellular potassium concentration. Carbenoxolone partially restored the amplitude and duration after removing the thalamic inputs. A two-dimensional current source density analysis showed that the sink and source signals shifted to deeper layers after removing the thalamic inputs during the clonic phase. These results indicate that the regulatory mechanism of deep brain stimulation in the thalamus occurs partially though gap junctions. PMID:23690968

Effects of Intralaminar Thalamic Stimulation on Language Functions

ERIC Educational Resources Information Center

Bhatnagar, Subhash C.; Mandybur, George T.

2005-01-01

Fifteen neurosurgical subjects, who were undergoing thalamic chronic electrode implants as a treatment for dyskinesia and chronic pain, were evaluated on a series of neurolinguistic functions to determine if the stimulation of the centromedianum nucleus of the thalamus affected language and cognitive processing. Analysis of the data revealed that…

Thalamocortical Projection Neuron and Interneuron Numbers in the Visual Thalamic Nuclei of the Adult C57BL/6 Mouse.

PubMed

Evangelio, Marian; García-Amado, María; Clascá, Francisco

2018-01-01

A key parameter to constrain predictive, bottom-up circuit models of a given brain domain is the number and position of the neuronal populations involved. These include not only the neurons whose bodies reside within the domain, but also the neurons in distant regions that innervate the domain. The mouse visual cortex receives its main subcortical input from the dorsal lateral geniculate nucleus (dLGN) and the lateral posterior (LP) complex of the thalamus. The latter consists of three different nuclei: lateral posterior lateral (LPL), lateral posterior medial rostral (LPMR), and lateral posterior medial caudal (LPMC), each exhibiting specific patterns of connections with the various visual cortical areas. Here, we have determined the number of thalamocortical projection neurons and interneurons in the LP complex and dLGN of the adult C57BL/6 male mouse. We combined Nissl staining and histochemical and immunolabeling methods for consistently delineating nuclei borders, and applied unbiased stereological cell counting methods. Thalamic interneurons were identified using GABA immunolabeling. The C57BL/6 dLGN contains ∼21,200 neurons, while LP complex contains ∼31,000 total neurons. The dLGN and LP are the only nuclei of the mouse dorsal thalamus containing substantial numbers GABA-immunoreactive interneurons. These interneurons, however, are scarcer than previously estimated; they are 5.6% of dLGN neurons and just 1.9% of the LP neurons. It can be thus inferred that the dLGN contains ∼20,000 and the LP complex ∼30,400 thalamocortical projection neurons (∼12,000 in LPL, 15,200 in LPMR, and 4,200 in LPMC). The present dataset is relevant for constraining models of mouse visual thalamocortical circuits, as well as for quantitative comparisons between genetically modified mouse strains, or across species.

Thalamocortical Projection Neuron and Interneuron Numbers in the Visual Thalamic Nuclei of the Adult C57BL/6 Mouse

PubMed Central

Evangelio, Marian; García-Amado, María; Clascá, Francisco

2018-01-01

A key parameter to constrain predictive, bottom-up circuit models of a given brain domain is the number and position of the neuronal populations involved. These include not only the neurons whose bodies reside within the domain, but also the neurons in distant regions that innervate the domain. The mouse visual cortex receives its main subcortical input from the dorsal lateral geniculate nucleus (dLGN) and the lateral posterior (LP) complex of the thalamus. The latter consists of three different nuclei: lateral posterior lateral (LPL), lateral posterior medial rostral (LPMR), and lateral posterior medial caudal (LPMC), each exhibiting specific patterns of connections with the various visual cortical areas. Here, we have determined the number of thalamocortical projection neurons and interneurons in the LP complex and dLGN of the adult C57BL/6 male mouse. We combined Nissl staining and histochemical and immunolabeling methods for consistently delineating nuclei borders, and applied unbiased stereological cell counting methods. Thalamic interneurons were identified using GABA immunolabeling. The C57BL/6 dLGN contains ∼21,200 neurons, while LP complex contains ∼31,000 total neurons. The dLGN and LP are the only nuclei of the mouse dorsal thalamus containing substantial numbers GABA-immunoreactive interneurons. These interneurons, however, are scarcer than previously estimated; they are 5.6% of dLGN neurons and just 1.9% of the LP neurons. It can be thus inferred that the dLGN contains ∼20,000 and the LP complex ∼30,400 thalamocortical projection neurons (∼12,000 in LPL, 15,200 in LPMR, and 4,200 in LPMC). The present dataset is relevant for constraining models of mouse visual thalamocortical circuits, as well as for quantitative comparisons between genetically modified mouse strains, or across species. PMID:29706872

Impairment of Syntax and Lexical Semantics in a Patient with Bilateral Paramedian Thalamic Infarction

ERIC Educational Resources Information Center

De Witte, Lieve; Wilssens, Ineke; Engelborghs, Sebastian; De Deyn, Peter P.; Marien, Peter

2006-01-01

Bilateral vascular thalamic lesions are rare. Although a variety of neurobehavioral manifestations have been described, the literature is less documented with regard to accompanying linguistic disturbances. This article presents an in-depth neurolinguistic analysis of the language symptoms of a patient who incurred bilateral paramedian ischemic…

Symmetrical infantile thalamic degeneration in two sibs

PubMed Central

Abuelo, Dianne N; Barsel-Bowers, Gail; Tutschka, Barbara G; Ambler, Mary; Singer, Don B

1981-01-01

This is the first observation of two cases of symmetrical infantile thalamic degeneration with cell mineralisation in a family. Although it cannot be established at present, autosomal recessive inheritance of a metabolic error causing or predisposing to damage to specific areas of the central nervous system is a possible aetiology for this condition. Images PMID:7334503

Rhythmic syllable-related activity in a songbird motor thalamic nucleus necessary for learned vocalizations

PubMed Central

Danish, Husain H.; Aronov, Dmitriy; Fee, Michale S.

2017-01-01

Birdsong is a complex behavior that exhibits hierarchical organization. While the representation of singing behavior and its hierarchical organization has been studied in some detail in avian cortical premotor circuits, our understanding of the role of the thalamus in adult birdsong is incomplete. Using a combination of behavioral and electrophysiological studies, we seek to expand on earlier work showing that the thalamic nucleus Uvaeformis (Uva) is necessary for the production of stereotyped, adult song in zebra finch (Taeniopygia guttata). We confirm that complete bilateral lesions of Uva abolish singing in the ‘directed’ social context, but find that in the ‘undirected’ social context, such lesions result in highly variable vocalizations similar to early babbling song in juvenile birds. Recordings of neural activity in Uva reveal strong syllable-related modulation, maximally active prior to syllable onsets and minimally active prior to syllable offsets. Furthermore, both song and Uva activity exhibit a pronounced coherent modulation at 10Hz—a pattern observed in downstream premotor areas in adult and, even more prominently, in juvenile birds. These findings are broadly consistent with the idea that Uva is critical in the sequential activation of behavioral modules in HVC. PMID:28617829

Schizophrenia-Related Microdeletion Impairs Emotional Memory through MicroRNA-Dependent Disruption of Thalamic Inputs to the Amygdala.

PubMed

Eom, Tae-Yeon; Bayazitov, Ildar T; Anderson, Kara; Yu, Jing; Zakharenko, Stanislav S

2017-05-23

Individuals with 22q11.2 deletion syndrome (22q11DS) are at high risk of developing psychiatric diseases such as schizophrenia. Individuals with 22q11DS and schizophrenia are impaired in emotional memory, anticipating, recalling, and assigning a correct context to emotions. The neuronal circuits responsible for these emotional memory deficits are unknown. Here, we show that 22q11DS mouse models have disrupted synaptic transmission at thalamic inputs to the lateral amygdala (thalamo-LA projections). This synaptic deficit is caused by haploinsufficiency of the 22q11DS gene Dgcr8, which is involved in microRNA processing, and is mediated by the increased dopamine receptor Drd2 levels in the thalamus and by reduced probability of glutamate release from thalamic inputs. This deficit in thalamo-LA synaptic transmission is sufficient to cause fear memory deficits. Our results suggest that dysregulation of the Dgcr8-Drd2 mechanism at thalamic inputs to the amygdala underlies emotional memory deficits in 22q11DS. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Anticipatory activity in the human thalamus is predictive of reaction times.

PubMed

Nikulin, V V; Marzinzik, F; Wahl, M; Schneider, G-H; Kupsch, A; Curio, G; Klostermann, F

2008-09-09

Responding to environmental stimuli in a fast manner is a fundamental behavioral capacity. The pace at which one responds is known to be predetermined by cortical areas, but it remains to be shown if subcortical structures also take part in defining motor swiftness. As the thalamus has previously been implicated in behavioral control, we tested if neuronal activity at this level could also predict the reaction time of upcoming movements. To this end we simultaneously recorded electrical brain activity from the scalp and the ventral intermediate nucleus (VIM) of the thalamus in patients undergoing thalamic deep brain stimulation. Based on trial-to-trial analysis of a Go/NoGo task, we demonstrate that both cortical and thalamic neuronal activity prior to the delivery of upcoming Go stimulus correlates with the reaction time. This result goes beyond the demonstration of thalamic activity being associated with but potentially staying invariant to motor performance. In contrast, it indicates that the latencies at which we respond to environmental stimuli are not exclusively related to cortical pre-movement states but are also correlated with anticipatory thalamic activity.

Development of involuntary movements after ventriculoperitoneal shunting for normal pressure hydrocephalus in a patient with chronic-phase thalamic haemorrhage.

PubMed

Shindo, Keiichiro; Kondo, Takeo; Sugiyama, Ken; Nishijima, Kazunori; Furusawa, Yoshihito; Mori, Takayuki; Izumi, Shin-Ichi

2007-10-01

Delayed-onset involuntary movements have been described after thalamic stroke. We treated a patient with involuntary movements that increased after ventriculoperitoneal shunting (VPS) for normal pressure hydrocephalus (NPH) following thalamic haemorrage. One and one-half years after right thalamic and intraventricular haemorrhage, NPH suggested clinical evaluation and neuroimaging studies in a 56-year-old man. Hemidystonia and pseudochoreoathetosis were evident in the left arm, leg and trunk. Proprioceptive impairment and mild cerebellar dysfunction affected the left upper and lower extremity. Yet the patient could walk unassisted and carry out activities of daily living (ADL) rated as 90 points according to the Barthel Index (BI). Lumbar puncture lessened both gait disturbance and cognitive impairment. After VPS, cognition and urinary continence improved, but involuntary movements worsened, precluding unaided ambulation and decreasing the BI score to 65 points. Computed tomography after VPS showed resolution of NPH, while single-photon emission computed tomography showed increased cerebral blood flow after VPS. Increased cerebral blood flow after VPS is suspected to have promoted development of abnormal neuronal circuitry.

Recall deficits in stroke patients with thalamic lesions covary with damage to the parvocellular mediodorsal nucleus of the thalamus.

PubMed

Pergola, Giulio; Güntürkün, Onur; Koch, Benno; Schwarz, Michael; Daum, Irene; Suchan, Boris

2012-08-01

The functional role of the mediodorsal thalamic nucleus (MD) and its cortical network in memory processes is discussed controversially. While Aggleton and Brown (1999) suggested a role for recognition and not recall, Van der Werf et al. (2003) suggested that this nucleus is functionally related to executive function and strategic retrieval, based on its connections to the prefrontal cortices (PFC). The present study used a lesion approach including patients with focal thalamic lesions to examine the functions of the MD, the intralaminar nuclei and the midline nuclei in memory processing. A newly designed pair association task was used, which allowed the assessment of recognition and cued recall performance. Volume loss in thalamic nuclei was estimated as a predictor for alterations in memory performance. Patients performed poorer than healthy controls on recognition accuracy and cued recall. Furthermore, patients responded slower than controls specifically on recognition trials followed by successful cued recall of the paired associate. Reduced recall of picture pairs and increased response times during recognition followed by cued recall covaried with the volume loss in the parvocellular MD. This pattern suggests a role of this thalamic region in recall and thus recollection, which does not fit the framework proposed by Aggleton and Brown (1999). The functional specialization of the parvocellular MD accords with its connectivity to the dorsolateral PFC, highlighting the role of this thalamocortical network in explicit memory (Van der Werf et al., 2003). Copyright © 2012 Elsevier Ltd. All rights reserved.

Specific thalamic nuclei function as novel 'nociceptive discriminators' in the endogenous control of nociception in rats.

PubMed

You, H-J; Lei, J; Niu, N; Yang, L; Fan, X-L; Tjølsen, A; Li, Q

2013-03-01

Recently, we hypothesized that supraspinal structures may have important functions in discriminating between noxious mechanically and heat mediated nociception through distinct functions: facilitation and inhibition. In this study, conducted in conscious rats, we explored the role of different thalamic nuclei: the mediodorsal (MD) nucleus, the central medial (CM) nucleus, the submedius (SM) nucleus, the ventralmedial (VM) nucleus and the ventral posterolateral (VPL) nucleus, in the descending control of secondary and contralateral mechanical hyperalgesia and heat hypoalgesia occurring in intramuscularly hypertonic (HT, 5.8%) saline-induced muscle nociception. We found that the MD nuclei participated in the descending facilitation of mechanical hyperalgesia, and that the VM nuclei were specifically involved in the descending inhibition of heat hypoalgesia. Neither descending facilitation nor descending inhibition was affected after electrolytic lesion of the thalamic CM, SM, and VPL nuclei. This descending facilitatory and inhibitory modulation of nociception was strengthened by glutamate, and weakened by GABA, microinjected into the thalamic MD and VM nuclei. It is suggested that (1) thalamic MD nucleus and VM nucleus form two distinct endogenous systems in the control of noxious mechanically and heat evoked responses, and (2) the strengthening of descending inhibition and the weakening of descending facilitation by means of up regulation and down regulation of appropriate receptor expression in the VM and MD nuclei may provide a new strategic policy in treating pathological pain. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Global Intracellular Slow-Wave Dynamics of the Thalamocortical System

PubMed Central

Sheroziya, Maxim

2014-01-01

It is widely accepted that corticothalamic neurons recruit the thalamus in slow oscillation, but global slow-wave thalamocortical dynamics have never been experimentally shown. We analyzed intracellular activities of neurons either from different cortical areas or from a variety of specific and nonspecific thalamic nuclei in relation to the phase of global EEG signal in ketamine-xylazine anesthetized mice. We found that, on average, slow-wave active states started off within frontal cortical areas as well as higher-order and intralaminar thalamus (posterior and parafascicular nuclei) simultaneously. Then, the leading edge of active states propagated in the anteroposterior/lateral direction over the cortex at ∼40 mm/s. The latest structure we recorded within the slow-wave cycle was the anterior thalamus, which followed active states of the retrosplenial cortex. Active states from different cortical areas tended to terminate simultaneously. Sensory thalamic ventral posterior medial and lateral geniculate nuclei followed cortical active states with major inhibitory and weak tonic-like “modulator” EPSPs. In these nuclei, sharp-rising, large-amplitude EPSPs (“drivers”) were not modulated by cortical slow waves, suggesting their origin in ascending pathways. The thalamic active states in other investigated nuclei were composed of depolarization: some revealing “driver”- and “modulator”-like EPSPs, others showing “modulator”-like EPSPs only. We conclude that sensory thalamic nuclei follow the propagating cortical waves, whereas neurons from higher-order thalamic nuclei display “hub dynamics” and thus may contribute to the generation of cortical slow waves. PMID:24966387

Third Ventricular Cerebrospinal Fluid Cysts of Thalamic Origin: Review of Embryologic Origin, Presentation, and Management Strategies with a Case Series.

PubMed

Vasquez, Ciro A; Casey, Michael; Folzenlogen, Zach; Ormond, David R; Lillehei, Kevin; Youssef, A Samy

2017-07-01

Third ventricular cerebrospinal fluid (CSF) cysts of thalamic origin are rare. The objective of this study is to review their possible pathogenesis, clinical presentation, and management strategies with a case series describing management via an endoscopic approach with fenestration using a single burr-hole technique. A systematic literature review of reported cases of thalamic cysts was conducted with further meta-analysis of CSF cysts that involve the third ventricle. The mode of presentation, pathologic analysis, surgical management, and outcomes were analyzed. Twenty-two studies reported between 1990 and 2013 described 42 cases of thalamic cyst. Of those cases, 13 were consistent with CSF cyst that originated in the thalamus and involved the third ventricle. Eight cases (61.5%) were treated via endoscopic fenestration, 2 cases (15.4%) were surgically drained, 2 cases (15.4%) were stereotactically aspirated, and 1 case (7.69%) was observed. The most common presenting symptoms were gait disturbance (26.3%) and headaches (26.3%) followed by tremors (15.8%) and weakness (15.8%). In our series, a single burr-hole technique was a successful definitive treatment, with an average period of 23 months. Third ventricular CSF cysts of thalamic origin most commonly present with hydrocephalus. They can be safely definitively treated via endoscopic fenestration to the CSF circulation using a single burr-hole technique. Long-term follow-up shows lasting improvement in symptoms without reaccumulation of the cyst. Copyright © 2017 Elsevier Inc. All rights reserved.

Tremor cells in the human thalamus: differences among neurological disorders.

PubMed

Brodkey, Jason A; Tasker, Ronald R; Hamani, Clement; McAndrews, Mary Pat; Dostrovsky, Jonathan O; Lozano, Andres M

2004-07-01

Thalamic neurons firing at frequencies synchronous with tremor are thought to play a critical role in the generation and maintenance of tremor. The authors studied the incidence and locations of neurons with tremor-related activity (TRA) in the thalamus of patients with varied pathological conditions-including Parkinson disease (PD), essential tremor (ET), multiple sclerosis (MS), and cerebellar disorders--to determine whether known differences in the effectiveness of thalamic stereotactic procedures for these tremors could be correlated to differences in the incidence or locations of TRA cells. Seventy-five operations were performed in 61 patients during which 686 TRA cells were recorded from 440 microelectrode trajectories in the thalamus. The locations of the TRA cells in relation to electrophysiologically defined thalamic nuclei and the commissural coordinates were compared among patient groups. The authors found that TRA cells are present in patients with each of these disorders and that these cells populate several nuclei in the ventral lateral tier of the thalamus. There were no large differences in the locations of TRA cells among the different diagnostic classes, although there was a difference in the incidence of TRA cells in patients with PD, who had greater than 3.8 times more cells per thalamic trajectory than patients with ET and approximately five times more cells than patients with MS or cerebellar disorders. There was an increased incidence of TRA in the thalamus of patients with PD. The location of thalamic TRA cells in patients with basal ganglia and other tremor disorders was similar.

Accelerated Echo Planer J-resolved Spectroscopic Imaging of Putamen and Thalamus in Obstructive Sleep Apnea.

PubMed

Sarma, Manoj K; Macey, Paul M; Nagarajan, Rajakumar; Aysola, Ravi; Harper, Ronald M; Thomas, M Albert

2016-09-06

Obstructive sleep apnea syndrome (OSAS) leads to neurocognitive and autonomic deficits that are partially mediated by thalamic and putamen pathology. We examined the underlying neurochemistry of those structures using compressed sensing-based 4D echo-planar J-resolved spectroscopic imaging (JRESI), and quantified values with prior knowledge fitting. Bilaterally increased thalamic mI/Cr, putamen Glx/Cr, and Glu/Cr, and bilaterally decreased thalamic and putamen tCho/Cr and GABA/Cr occurred in OSAS vs healthy subjects (p < 0.05). Increased right thalamic Glx/Cr, Glu/Cr, Gln/Cr, Asc/Cr, and decreased GPC/Cr and decreased left thalamic tNAA/Cr, NAA/Cr were detected. The right putamen showed increased mI/Cr and decreased tCho/Cr, and the left, decreased PE/Cr ratio. ROC curve analyses demonstrated 60-100% sensitivity and specificity for the metabolite ratios in differentiating OSAS vs. Positive correlations were found between: left thalamus mI/Cr and baseline oxygen saturation (SaO2); right putamen tCho/Cr and apnea hypopnea index; right putamen GABA/Cr and baseline SaO2; left putamen PE/Cr and baseline SaO2; and left putamen NAA/Cr and SaO2 nadir (all p < 0.05). Negative correlations were found between left putamen PE/Cr and SaO2 nadir. These findings suggest underlying inflammation or glial activation, with greater alterations accompanying lower oxygen saturation. These metabolite levels may provide biomarkers for future neurochemical interventions by pharmacologic or other means.

Thalamic neuron models encode stimulus information by burst-size modulation

PubMed Central

Elijah, Daniel H.; Samengo, Inés; Montemurro, Marcelo A.

2015-01-01

Thalamic neurons have been long assumed to fire in tonic mode during perceptive states, and in burst mode during sleep and unconsciousness. However, recent evidence suggests that bursts may also be relevant in the encoding of sensory information. Here, we explore the neural code of such thalamic bursts. In order to assess whether the burst code is generic or whether it depends on the detailed properties of each bursting neuron, we analyzed two neuron models incorporating different levels of biological detail. One of the models contained no information of the biophysical processes entailed in spike generation, and described neuron activity at a phenomenological level. The second model represented the evolution of the individual ionic conductances involved in spiking and bursting, and required a large number of parameters. We analyzed the models' input selectivity using reverse correlation methods and information theory. We found that n-spike bursts from both models transmit information by modulating their spike count in response to changes to instantaneous input features, such as slope, phase, amplitude, etc. The stimulus feature that is most efficiently encoded by bursts, however, need not coincide with one of such classical features. We therefore searched for the optimal feature among all those that could be expressed as a linear transformation of the time-dependent input current. We found that bursting neurons transmitted 6 times more information about such more general features. The relevant events in the stimulus were located in a time window spanning ~100 ms before and ~20 ms after burst onset. Most importantly, the neural code employed by the simple and the biologically realistic models was largely the same, implying that the simple thalamic neuron model contains the essential ingredients that account for the computational properties of the thalamic burst code. Thus, our results suggest the n-spike burst code is a general property of thalamic neurons. PMID:26441623

Altered Cortico-Striatal–Thalamic Connectivity in Relation to Spatial Working Memory Capacity in Children with ADHD

PubMed Central

Mills, Kathryn L.; Bathula, Deepti; Dias, Taciana G. Costa; Iyer, Swathi P.; Fenesy, Michelle C.; Musser, Erica D.; Stevens, Corinne A.; Thurlow, Bria L.; Carpenter, Samuel D.; Nagel, Bonnie J.; Nigg, Joel T.; Fair, Damien A.

2012-01-01

Introduction: Attention deficit hyperactivity disorder (ADHD) captures a heterogeneous group of children, who are characterized by a range of cognitive and behavioral symptoms. Previous resting-state functional connectivity MRI (rs-fcMRI) studies have sought to understand the neural correlates of ADHD by comparing connectivity measurements between those with and without the disorder, focusing primarily on cortical–striatal circuits mediated by the thalamus. To integrate the multiple phenotypic features associated with ADHD and help resolve its heterogeneity, it is helpful to determine how specific circuits relate to unique cognitive domains of the ADHD syndrome. Spatial working memory has been proposed as a key mechanism in the pathophysiology of ADHD. Methods: We correlated the rs-fcMRI of five thalamic regions of interest (ROIs) with spatial span working memory scores in a sample of 67 children aged 7–11 years [ADHD and typically developing children (TDC)]. In an independent dataset, we then examined group differences in thalamo-striatal functional connectivity between 70 ADHD and 89 TDC (7–11 years) from the ADHD-200 dataset. Thalamic ROIs were created based on previous methods that utilize known thalamo-cortical loops and rs-fcMRI to identify functional boundaries in the thalamus. Results/Conclusion: Using these thalamic regions, we found atypical rs-fcMRI between specific thalamic groupings with the basal ganglia. To identify the thalamic connections that relate to spatial working memory in ADHD, only connections identified in both the correlational and comparative analyses were considered. Multiple connections between the thalamus and basal ganglia, particularly between medial and anterior dorsal thalamus and the putamen, were related to spatial working memory and also altered in ADHD. These thalamo-striatal disruptions may be one of multiple atypical neural and cognitive mechanisms that relate to the ADHD clinical phenotype. PMID:22291667

Flexible Use of Predictive Cues beyond the Orbitofrontal Cortex: Role of the Submedius Thalamic Nucleus.

PubMed

Alcaraz, Fabien; Marchand, Alain R; Vidal, Elisa; Guillou, Alexandre; Faugère, Angélique; Coutureau, Etienne; Wolff, Mathieu

2015-09-23

The orbitofrontal cortex (OFC) is known to play a crucial role in learning the consequences of specific events. However, the contribution of OFC thalamic inputs to these processes is largely unknown. Using a tract-tracing approach, we first demonstrated that the submedius nucleus (Sub) shares extensive reciprocal connections with the OFC. We then compared the effects of excitotoxic lesions of the Sub or the OFC on the ability of rats to use outcome identity to direct responding. We found that neither OFC nor Sub lesions interfered with the basic differential outcomes effect. However, more specific tests revealed that OFC rats, but not Sub rats, were disproportionally relying on the outcome, rather than on the discriminative stimulus, to guide behavior, which is consistent with the view that the OFC integrates information about predictive cues. In subsequent experiments using a Pavlovian contingency degradation procedure, we found that both OFC and Sub lesions produced a severe deficit in the ability to update Pavlovian associations. Altogether, the submedius therefore appears as a functionally relevant thalamic component in a circuit dedicated to the integration of predictive cues to guide behavior, previously conceived as essentially dependent on orbitofrontal functions. Significance statement: In the present study, we identify a largely unknown thalamic region, the submedius nucleus, as a new functionally relevant component in a circuit supporting the flexible use of predictive cues. Such abilities were previously conceived as largely dependent on the orbitofrontal cortex. Interestingly, this echoes recent findings in the field showing, in research involving an instrumental setup, an additional involvement of another thalamic nuclei, the parafascicular nucleus, when correct responding requires an element of flexibility (Bradfield et al., 2013a). Therefore, the present contribution supports the emerging view that limbic thalamic nuclei may contribute critically to adaptive responding when an element of flexibility is required after the establishment of initial learning. Copyright © 2015 the authors 0270-6474/15/3513183-11$15.00/0.

Thalamic neuron models encode stimulus information by burst-size modulation.

PubMed

Elijah, Daniel H; Samengo, Inés; Montemurro, Marcelo A

2015-01-01

Thalamic neurons have been long assumed to fire in tonic mode during perceptive states, and in burst mode during sleep and unconsciousness. However, recent evidence suggests that bursts may also be relevant in the encoding of sensory information. Here, we explore the neural code of such thalamic bursts. In order to assess whether the burst code is generic or whether it depends on the detailed properties of each bursting neuron, we analyzed two neuron models incorporating different levels of biological detail. One of the models contained no information of the biophysical processes entailed in spike generation, and described neuron activity at a phenomenological level. The second model represented the evolution of the individual ionic conductances involved in spiking and bursting, and required a large number of parameters. We analyzed the models' input selectivity using reverse correlation methods and information theory. We found that n-spike bursts from both models transmit information by modulating their spike count in response to changes to instantaneous input features, such as slope, phase, amplitude, etc. The stimulus feature that is most efficiently encoded by bursts, however, need not coincide with one of such classical features. We therefore searched for the optimal feature among all those that could be expressed as a linear transformation of the time-dependent input current. We found that bursting neurons transmitted 6 times more information about such more general features. The relevant events in the stimulus were located in a time window spanning ~100 ms before and ~20 ms after burst onset. Most importantly, the neural code employed by the simple and the biologically realistic models was largely the same, implying that the simple thalamic neuron model contains the essential ingredients that account for the computational properties of the thalamic burst code. Thus, our results suggest the n-spike burst code is a general property of thalamic neurons.

A subset of thalamocortical projections to the retrosplenial cortex possesses two vesicular glutamate transporter isoforms, VGluT1 and VGluT2, in axon terminals and somata.

PubMed

Oda, Satoko; Funato, Hiromasa; Sato, Fumi; Adachi-Akahane, Satomi; Ito, Masanori; Takase, Kenkichi; Kuroda, Masaru

2014-06-15

Vesicular glutamate transporter isoforms, VGluT1-VGluT3, accumulate glutamate into synaptic vesicles and are considered to be important molecules in glutamatergic transmission. Among them, VGluT2 mRNA is expressed predominantly throughout the dorsal thalamus, whereas VGluT1 mRNA is expressed in a few thalamic nuclei. In the thalamic nuclei that project to the retrosplenial cortex (RSC), VGluT1 mRNA is expressed strongly in the anterodorsal thalamic nucleus (AD), is expressed moderately in the anteroventral and laterodorsal thalamic nuclei, and is not expressed in the anteromedial thalamic nucleus. Thus, it has been strongly suggested that a subset of thalamocortical projections to RSC possesses both VGluT1 and VGluT2. In this study, double-labeled neuronal somata showing both VGluT1 and VGluT2 immunolabelings were found exclusively in the ventral region of AD (vAD). Many double-labeled axon terminals were also found in two major targets of vAD, the rostral part of the reticular thalamic nucleus and layers Ia and III-IV of the retrosplenial granular b cortex (RSGb). Some were also found in layer Ia of the retrosplenial granular a cortex (RSGa). These axon terminals contain significant amounts of both VGluTs. Because the subset of thalamocortical projections to RSC has a unique molecular basis in the glutamatergic transmission system, it might play an important role in the higher cognitive functions processed in the RSC. Furthermore, double-labeled axon terminals of a different type were distributed in RSGb and RSGa. Because they are small and the immunoreactivity of VGluT2 is significantly weaker than that of VGluT1, they seemed to be a subset of corticocortical terminals. Copyright © 2013 Wiley Periodicals, Inc.

Method of analysis of local neuronal circuits in the vertebrate central nervous system.

PubMed

Reinis, S; Weiss, D S; McGaraughty, S; Tsoukatos, J

1992-06-01

Although a considerable amount of knowledge has been accumulated about the activity of individual nerve cells in the brain, little is known about their mutual interactions at the local level. The method presented in this paper allows the reconstruction of functional relations within a group of neurons as recorded by a single microelectrode. Data are sampled at 10 or 13 kHz. Prominent spikes produced by one or more single cells are selected and sorted by K-means cluster analysis. The activities of single cells are then related to the background firing of neurons in their vicinity. Auto-correlograms of the leading cells, auto-correlograms of the background cells (mass correlograms) and cross-correlograms between these two levels of firing are computed and evaluated. The statistical probability of mutual interactions is determined, and the statistically significant, most common interspike intervals are stored and attributed to real pairs of spikes in the original record. Selected pairs of spikes, characterized by statistically significant intervals between them, are then assembled into a working model of the system. This method has revealed substantial differences between the information processing in the visual cortex, the inferior colliculus, the rostral ventromedial medulla and the ventrobasal complex of the thalamus. Even short 1-s records of the multiple neuronal activity may provide meaningful and statistically significant results.

Anterior Thalamic Lesions Alter Both Hippocampal-Dependent Behavior and Hippocampal Acetylcholine Release in the Rat

ERIC Educational Resources Information Center

Savage, Lisa M.; Hall, Joseph M.; Vetreno, Ryan P.

2011-01-01

The anterior thalamic nuclei (ATN) are important for learning and memory as damage to this region produces a persistent amnestic syndrome. Dense connections between the ATN and the hippocampus exist, and importantly, damage to the ATN can impair hippocampal functioning. Acetylcholine (ACh) is a key neurotransmitter in the hippocampus, and in vivo…

Mechanisms Contributing to the Induction and Storage of Pavlovian Fear Memories in the Lateral Amygdala

ERIC Educational Resources Information Center

Kim, Dongbeom; Pare, Denis; Nair, Satish S.

2013-01-01

The relative contributions of plasticity in the amygdala vs. its afferent pathways to conditioned fear remain controversial. Some believe that thalamic and cortical neurons transmitting information about the conditioned stimulus (CS) to the lateral amygdala (LA) serve a relay function. Others maintain that thalamic and/or cortical plasticity is…

Lateral and Anterior Thalamic Lesions Impair Independent Memory Systems

ERIC Educational Resources Information Center

Mitchell, Anna S.; Dalrymple-Alford, John C.

2006-01-01

Damage to the medial region of the thalamus, both in clinical cases (e.g., patients with infarcts or the Korsakoff's syndrome) and animal lesion models, is associated with variable amnesic deficits. Some studies suggest that many of these memory deficits rely on the presence of lateral thalamic lesions (LT) that include the intralaminar nuclei,…

Thalamus surface shape deformity in obsessive-compulsive disorder and schizophrenia.

PubMed

Kang, Do-Hyung; Kim, Sun Hyung; Kim, Chi-Won; Choi, Jung-Seok; Jang, Joon Hwan; Jung, Myung Hun; Lee, Jong-Min; Kim, Sun I; Kwon, Jun Soo

2008-04-16

The authors performed a three-dimensional shape deformation analysis to clarify the various patterns of specific thalamic nuclei abnormality using three age-matched and sex-matched groups of 22 patients with obsessive-compulsive disorder (OCD), 22 patients with schizophrenia and 22 control participants. Compared with the healthy volunteers, the anterior, lateral outward surface deformities of the thalamus were significant in OCD patients, whereas the posterior, medial outward deformities of the thalamus were prominent in schizophrenia patients. In terms of thalamic asymmetry, both OCD and schizophrenia patients exhibited the loss of a leftward pattern of asymmetry on the posterior, medial surface of the thalamus. Different patterns of shape abnormality of specific thalamic nuclei may be related to the different phenomenology of OCD and schizophrenia.

Transition to subthreshold activity with the use of phase shifting in a model thalamic network

NASA Astrophysics Data System (ADS)

Thomas, Elizabeth; Grisar, Thierry

1997-05-01

Absence epilepsy involves a state of low frequency synchronous oscillations by the involved neuronal networks. These oscillations may be either above or subthreshold. In this investigation, we studied the methods which could be utilized to transform the threshold activity of neurons in the network to a subthreshold state. A model thalamic network was constructed using the Hodgkin Huxley framework. Subthreshold activity was achieved by the application of stimuli to the network which caused phase shifts in the oscillatory activity of selected neurons in the network. In some instances the stimulus was a periodic pulse train of low frequency to the reticular thalamic neurons of the network while in others, it was a constant hyperpolarizing current applied to the thalamocortical neurons.

The impact of fornix lesions in rats on spatial learning tasks sensitive to anterior thalamic and hippocampal damage

PubMed Central

Dumont, Julie R.; Amin, Eman; Wright, Nicholas F.; Dillingham, Christopher M.; Aggleton, John P.

2015-01-01

The present study sought to understand how the hippocampus and anterior thalamic nuclei are conjointly required for spatial learning by examining the impact of cutting a major tract (the fornix) that interconnects these two sites. The initial experiments examined the consequences of fornix lesions in rats on spatial biconditional discrimination learning. The rationale arose from previous findings showing that fornix lesions spare the learning of spatial biconditional tasks, despite the same task being highly sensitive to both hippocampal and anterior thalamic nuclei lesions. In the present study, fornix lesions only delayed acquisition of the spatial biconditional task, pointing to additional contributions from non-fornical routes linking the hippocampus with the anterior thalamic nuclei. The same fornix lesions spared the learning of an analogous nonspatial biconditional task that used local contextual cues. Subsequent tests, including T-maze place alternation, place learning in a cross-maze, and a go/no-go place discrimination, highlighted the impact of fornix lesions when distal spatial information is used flexibly to guide behaviour. The final experiment examined the ability to learn incidentally the spatial features of a square water-maze that had differently patterned walls. Fornix lesions disrupted performance but did not stop the rats from distinguishing the various corners of the maze. Overall, the results indicate that interconnections between the hippocampus and anterior thalamus, via the fornix, help to resolve problems with flexible spatial and temporal cues, but the results also signal the importance of additional, non-fornical contributions to hippocampal-anterior thalamic spatial processing, particularly for problems with more stable spatial solutions. PMID:25453745

Thalamic atrophy in antero-medial and dorsal nuclei correlates with six-month outcome after severe brain injury☆

PubMed Central

Lutkenhoff, Evan S.; McArthur, David L.; Hua, Xue; Thompson, Paul M.; Vespa, Paul M.; Monti, Martin M.

2013-01-01

The primary and secondary damage to neural tissue inflicted by traumatic brain injury is a leading cause of death and disability. The secondary processes, in particular, are of great clinical interest because of their potential susceptibility to intervention. We address the dynamics of tissue degeneration in cortico-subcortical circuits after severe brain injury by assessing volume change in individual thalamic nuclei over the first six-months post-injury in a sample of 25 moderate to severe traumatic brain injury patients. Using tensor-based morphometry, we observed significant localized thalamic atrophy over the six-month period in antero-dorsal limbic nuclei as well as in medio-dorsal association nuclei. Importantly, the degree of atrophy in these nuclei was predictive, even after controlling for full-brain volume change, of behavioral outcome at six-months post-injury. Furthermore, employing a data-driven decision tree model, we found that physiological measures, namely the extent of atrophy in the anterior thalamic nucleus, were the most predictive variables of whether patients had regained consciousness by six-months, followed by behavioral measures. Overall, these findings suggest that the secondary non-mechanical degenerative processes triggered by severe brain injury are still ongoing after the first week post-trauma and target specifically antero-medial and dorsal thalamic nuclei. This result therefore offers a potential window of intervention, and a specific target region, in agreement with the view that specific cortico-thalamo-cortical circuits are crucial to the maintenance of large-scale network neural activity and thereby the restoration of cognitive function after severe brain injury. PMID:24273723

The Activity of Thalamic Nucleus Reuniens Is Critical for Memory Retrieval, but Not Essential for the Early Phase of "Off-Line" Consolidation

ERIC Educational Resources Information Center

Mei, Hao; Logothetis, Nikos K.; Eschenko, Oxana

2018-01-01

Spatial navigation depends on the hippocampal function, but also requires bidirectional interactions between the hippocampus (HPC) and the prefrontal cortex (PFC). The cross-regional communication is typically regulated by critical nodes of a distributed brain network. The thalamic nucleus reuniens (RE) is reciprocally connected to both HPC and…

Simulation of thalamic prosthetic vision: reading accuracy, speed, and acuity in sighted humans.

PubMed

Vurro, Milena; Crowell, Anne Marie; Pezaris, John S

2014-01-01

The psychophysics of reading with artificial sight has received increasing attention as visual prostheses are becoming a real possibility to restore useful function to the blind through the coarse, pseudo-pixelized vision they generate. Studies to date have focused on simulating retinal and cortical prostheses; here we extend that work to report on thalamic designs. This study examined the reading performance of normally sighted human subjects using a simulation of three thalamic visual prostheses that varied in phosphene count, to help understand the level of functional ability afforded by thalamic designs in a task of daily living. Reading accuracy, reading speed, and reading acuity of 20 subjects were measured as a function of letter size, using a task based on the MNREAD chart. Results showed that fluid reading was feasible with appropriate combinations of letter size and phosphene count, and performance degraded smoothly as font size was decreased, with an approximate doubling of phosphene count resulting in an increase of 0.2 logMAR in acuity. Results here were consistent with previous results from our laboratory. Results were also consistent with those from the literature, despite using naive subjects who were not trained on the simulator, in contrast to other reports.

Newly observed thalamic involvement and mutations of the HEXA gene in a Korean patient with juvenile GM2 gangliosidosis.

PubMed

Lee, Soon Min; Lee, Min Jung; Lee, Joon Soo; Kim, Heung Dong; Lee, Jin Sung; Kim, Jinna; Lee, Seung Koo; Lee, Young Mock

2008-09-01

Neuroimaging studies of patients with GM2 gangliosidosis are rare. The thalamus and basal ganglia are principally involved in patients affected by the infantile form of GM2 gangliosidosis. Unlike in the infantile form, in juvenile or adult type GM2 gangliosidosis, progressive cortical and cerebellar atrophy is the main abnormality seen on conventional magnetic resonance imaging (MRI); no basal ganglial or thalamic impairment were observed. This report is of a Korean girl with subacute onset, severe deficiency of hexosaminidase A activity and mutations (Arg137Term, Ala246Thr) of the HEXA gene. A 3.5-year-old girl who was previously in good health was evaluated for hypotonia and ataxia 3 months ago and showed progressive developmental deterioration, including cognitive decline. Serial brain MRI showed progressive overall volume decrease of the entire brain and thalamic atrophy. Fluorine-18 FDG PET scan showed severe decreased uptake in bilateral thalamus and diffuse cerebral cortex. We suggest, through our experience, that the thalamic involvement in MR imaging and FDG-PET can be observed in the juvenile form of GM2 gangliosidosis, and we suspect the association of mutations in the HEXA gene.

Physiological and morphological characterization of organotypic cocultures of the chick forebrain area MNH and its main input area DMA/DMP.

PubMed

Endepols, H; Jungnickel, J; Braun, K

2001-01-01

Cocultures of the learning-relevant forebrain region mediorostral neostriatum and hyperstriatum ventrale (MNH) and its main glutamatergic input area nucleus dorsomedialis anterior thalami/posterior thalami were morphologically and physiologically characterized. Synaptic contacts of thalamic fibers were light- and electron-microscopically detected on MNH neurons by applying the fluorescence tracer DiI-C18(3) into the thalamus part of the coculture. Most thalamic synapses on MNH neurons were symmetric and located on dendritic shafts, but no correlation between Gray-type ultrastructure and dendritic localization was found. Using intracellular current clamp recordings, we found that the electrophysiological properties, such as input resistance, time constant, action potential threshold, amplitude, and duration of MNH neurons, remain stable for over 30 days in vitro. Pharmacological blockade experiments revealed glutamate as the main neurotransmitter of thalamic synapses on MNH neurons, which were also found on inhibitory neurons. High frequency stimulation of thalamic inputs evoked synaptic potentiation in 22% of MNH neurons. The results indicate that DMA/DMP-MNH cocultures, which can be maintained under stable conditions for at least 4 weeks, provide an attractive in vitro model for investigating synaptic plasticity in the avian brain.

White Matter Connectivity of the Thalamus Delineates the Functional Architecture of Competing Thalamocortical Systems

PubMed Central

O'Muircheartaigh, Jonathan; Keller, Simon S.; Barker, Gareth J.; Richardson, Mark P.

2015-01-01

There is an increasing awareness of the involvement of thalamic connectivity on higher level cortical functioning in the human brain. This is reflected by the influence of thalamic stimulation on cortical activity and behavior as well as apparently cortical lesion syndromes occurring as a function of small thalamic insults. Here, we attempt to noninvasively test the correspondence of structural and functional connectivity of the human thalamus using diffusion-weighted and resting-state functional MRI. Using a large sample of 102 adults, we apply tensor independent component analysis to diffusion MRI tractography data to blindly parcellate bilateral thalamus according to diffusion tractography-defined structural connectivity. Using resting-state functional MRI collected in the same subjects, we show that the resulting structurally defined thalamic regions map to spatially distinct, and anatomically predictable, whole-brain functional networks in the same subjects. Although there was significant variability in the functional connectivity patterns, the resulting 51 structural and functional patterns could broadly be reduced to a subset of 7 similar core network types. These networks were distinct from typical cortical resting-state networks. Importantly, these networks were distributed across the brain and, in a subset, map extremely well to known thalamocortico-basal-ganglial loops. PMID:25899706

Physiological and Morphological Characterization of Organotypic Cocultures of the Chick Forebrain Area MNH and its Main Input Area DMA/DMP

PubMed Central

Endepols, Heike; Jungnickel, Julia; Braun, Katharina

2001-01-01

Cocultures of the learning-relevant forebrain region mediorostrai neostriatum and hyperstriatum ventrale (MNH) and its main glutamatergic input area nucleus dorsomedialis anterior thalami/posterior thalami were morphologically and physiologically characterized. Synaptic contacts of thalamic fibers were lightand electron-microscopically detected on MNH neurons by applying the fluorescence tracer DiI-C18(3) into the thalamus part of the coculture. Most thalamic synapses on MNH neurons were symmetric and located on dendritic shafts, but no correlation between Gray-type ultrastructure and dendritic localization was found. Using intraceilular current clamp recordings, we found that the electrophysiological properties, such as input resistance, time constant, action potential threshold, amplitude, and duration of MNH neurons, remain stable for over 30 days in vitro. Pharmacological blockade experiments revealed glutamate as the main neurotransmitter of thalamic synapses on MNH neurons, which were also found on inhibitory neurons. High frequency stimulation of thalamic inputs evoked synaptic potentiation in 22% of MNH neurons. The results indicate that DMA/DMP-MNH cocultures, which can be maintained under stable conditions for at least 4 weeks, provide an attractive in vitro model for investigating synaptic plasticity in the avian brain. PMID:12018771

Lesions of the fornix and anterior thalamic nuclei dissociate different aspects of hippocampal-dependent spatial learning: implications for the neural basis of scene learning.

PubMed

Aggleton, John P; Poirier, Guillaume L; Aggleton, Hugh S; Vann, Seralynne D; Pearce, John M

2009-06-01

The present study used 2 different discrimination tasks designed to isolate distinct components of visuospatial learning: structural learning and geometric learning. Structural learning refers to the ability to learn the precise combination of stimulus identity with stimulus location. Rats with anterior thalamic lesions and fornix lesions were unimpaired on a configural learning task in which the rats learned 3 concurrent mirror-image discriminations (structural learning). Indeed, both lesions led to facilitated learning. In contrast, anterior thalamic lesions impaired the geometric discrimination (e.g., swim to the corner with the short wall to the right of the long wall). Finally, both the fornix and anterior thalamic lesions severely impaired T-maze alternation, a task that taxes an array of spatial strategies including allocentric learning. This pattern of dissociations and double dissociations highlights how distinct classes of spatial learning rely on different systems, even though they may converge on the hippocampus. Consequently, the findings suggest that structural learning is heavily dependent on cortico-hippocampal interactions. In contrast, subcortical inputs (such as those from the anterior thalamus) contribute to geometric learning. Copyright (c) 2009 APA, all rights reserved.

COMMUNICATION Designing a somatosensory neural prosthesis: percepts evoked by different patterns of thalamic stimulation

NASA Astrophysics Data System (ADS)

Heming, Ethan; Sanden, Andrew; Kiss, Zelma H. T.

2010-12-01

Although major advances have been made in the development of motor prostheses, fine motor control requires intuitive somatosensory feedback. Here we explored whether a thalamic site for a somatosensory neural prosthetic could provide natural somatic sensation to humans. Different patterns of electrical stimulation (obtained from thalamic spike trains) were applied in patients undergoing deep brain stimulation surgery. Changes in pattern produced different sensations, while preserving somatotopic representation. While most percepts were reported as 'unnatural', some stimulations produced more 'natural' sensations than others. However, the additional patterns did not elicit more 'natural' percepts than high-frequency (333 Hz) electrical stimulation. These features suggest that despite some limitations, the thalamus may be a feasible site for a somatosensory neural prosthesis and different stimulation patterns may be useful in its development.

Thalamic deactivation at sleep onset precedes that of the cerebral cortex in humans

PubMed Central

Magnin, Michel; Rey, Marc; Bastuji, Hélène; Guillemant, Philippe; Mauguière, François; Garcia-Larrea, Luis

2010-01-01

Thalamic and cortical activities are assumed to be time-locked throughout all vigilance states. Using simultaneous intracortical and intrathalamic recordings, we demonstrate here that the thalamic deactivation occurring at sleep onset most often precedes that of the cortex by several minutes, whereas reactivation of both structures during awakening is synchronized. Delays between thalamus and cortex deactivations can vary from one subject to another when a similar cortical region is considered. In addition, heterogeneity in activity levels throughout the cortical mantle is larger than previously thought during the descent into sleep. Thus, asynchronous thalamo-cortical deactivation while falling asleep probably explains the production of hypnagogic hallucinations by a still-activated cortex and the common self-overestimation of the time needed to fall asleep. PMID:20142493

The Medial Dorsal Thalamic Nucleus and the Medial Prefrontal Cortex of the Rat Function Together to Support Associative Recognition and Recency but Not Item Recognition

ERIC Educational Resources Information Center

Cross, Laura; Brown, Malcolm W.; Aggleton, John P.; Warburton, E. Clea

2013-01-01

In humans recognition memory deficits, a typical feature of diencephalic amnesia, have been tentatively linked to mediodorsal thalamic nucleus (MD) damage. Animal studies have occasionally investigated the role of the MD in single-item recognition, but have not systematically analyzed its involvement in other recognition memory processes. In…

Acute Korsakoff-like amnestic syndrome resulting from left thalamic infarction following a right hippocampal hemorrhage.

PubMed

Rahme, R; Moussa, R; Awada, A; Ibrahim, I; Ali, Y; Maarrawi, J; Rizk, T; Nohra, G; Okais, N; Samaha, E

2007-04-01

Korsakoff-like amnestic syndromes have been rarely described following structural lesions of the central nervous system. In this report, we describe a case of acute Korsakoff-like syndrome resulting from the combination of a left anteromedian thalamic infarct and a right hippocampal hemorrhage. We also review the literature relevant to the neuropathology and pathophysiology of Korsakoff syndrome and anterograde amnesia.

Cerebral oxidative metabolism mapping in four genetic mouse models of anxiety and mood disorders.

PubMed

Matrov, Denis; Kaart, Tanel; Lanfumey, Laurence; Maldonado, Rafael; Sharp, Trevor; Tordera, Rosa M; Kelly, Paul A; Deakin, Bill; Harro, Jaanus

2018-06-07

The psychopathology of depression is highly complex and the outcome of studies on animal models is divergent. In order to find brain regions that could be metabolically distinctively active across a variety of mouse depression models and to compare the interconnectivity of brain regions of wild-type and such genetically modified mice, histochemical mapping of oxidative metabolism was performed by the measurement of cytochrome oxidase activity. We included mice with the heterozygous knockout of the vesicular glutamate transporter (VGLUT 1 -/+ ), full knockout of the cannabinoid 1 receptor (CB1 -/- ), an anti-sense knockdown of the glucocorticoid receptor (GRi) and overexpression of the human 5-hydroxytryptamine transporter (h5-HTT). Altogether 76 mouse brains were studied to measure oxidative metabolism in one hundred brain regions, and the obtained dataset was submitted to a variety of machine learning algorithms and multidimensional scaling. Overall, the top brain regions having the largest contribution to classification into depression model were the lateroanterior hypothalamic nucleus, the anterior part of the basomedial amygdaloid nucleus, claustrum, the suprachiasmatic nucleus, the ventromedial hypothalamic nucleus, and the anterior hypothalamic area. In terms of the patterns of inter-regional relationship between wild-type and genetically modified mice there was little overall difference, while the most deviating brain regions were cortical amygdala and ventrolateral and ventral posteromedial thalamic nuclei. The GRi mice that most clearly differed from their controls exhibited deviation of connectivity for a number of brain regions, such as ventrolateral thalamic nucleus, the intermediate part of the lateral septal nucleus, the anteriodorsal part of the medial amygdaloid nucleus, the medial division of the central amygdaloid nucleus, ventral pallidum, nucleus of the vertical limb of the diagonal band, anteroventral parts of the thalamic nucleus and parts of the bed nucleus of the stria terminalis. Conclusively, the GRi mouse model was characterized by changes in the functional connectivity of the extended amygdala and stress response circuits. Copyright © 2018 Elsevier B.V. All rights reserved.

The activity of thalamic nucleus reuniens is critical for memory retrieval, but not essential for the early phase of "off-line" consolidation.

PubMed

Mei, Hao; Logothetis, Nikos K; Eschenko, Oxana

2018-03-01

Spatial navigation depends on the hippocampal function, but also requires bidirectional interactions between the hippocampus (HPC) and the prefrontal cortex (PFC). The cross-regional communication is typically regulated by critical nodes of a distributed brain network. The thalamic nucleus reuniens (RE) is reciprocally connected to both HPC and PFC and may coordinate the information flow within the HPC-PFC pathway. Here we examined if RE activity contributes to the spatial memory consolidation. Rats were trained to find reward following a complex trajectory on a crossword-like maze. Immediately after each of the five daily learning sessions the RE was reversibly inactivated by local injection of muscimol. The post-training RE inactivation affected neither the spatial task acquisition nor the memory retention, which was tested after a 20-d "forgetting" period. In contrast, the RE inactivation in well-trained rats prior to the maze exposure impaired the task performance without affecting locomotion or appetitive motivation. Our results support the role of the RE in memory retrieval and/or "online" processing of spatial information, but do not provide evidence for its engagement in "off-line" processing, at least within a time window immediately following learning experience. © 2018 Mei et al.; Published by Cold Spring Harbor Laboratory Press.

Thalamic Amnesia Mimicking Transient Global Amnesia.

PubMed

Giannantoni, Nadia M; Lacidogna, Giordano; Broccolini, Aldobrando; Pilato, Fabio; Profice, Paolo; Morosetti, Roberta; Caliandro, Pietro; Gambassi, Giovanni; Della Marca, Giacomo; Frisullo, Giovanni

2015-06-01

Transient global amnesia is a benign syndrome and one of the most frequent discharges from the emergency department that can hardly be distinguished from other mimicking diseases. No consensus in the evaluation of transient global amnesia has yet been found in the emergency setting. We describe a 69-year-old woman who presented to our emergency department with an abrupt onset of anterograde amnesia, preceded by a similar amnesic episode misinterpreted as transient global amnesia. Neuroradiologic, neuropsychological, and neurophysiological evaluations supported the diagnosis of vascular thalamic amnesia. We report a patient who clinically fulfilled transient global amnesia's criteria and in whom nevertheless was disclosed a thalamic ischemic lesion on neuroimaging.This case report highlights the importance of performing neuroradiologic screening in the emergency department even when clinical history and physical findings are highly suggestive for transient global amnesia.

Examining Intrinsic Thalamic Resting State Networks Using Graph Theory Analysis : Implications for mTBI detection

DTIC Science & Technology

2012-08-01

disruptions in the resting state networks and neurocognitive pathologies such as schizophrenia, Alzheimer’s disease and attention deficit hyperactive ... deficits associated with TBI [8,9,10]. However, there is a growing body of evidence suggesting that TBI could induce thalamic injury, classically...Inventory (NBSI), Post Traumatic Stress Disorder (PCL-C) and the Automated Neuropsychological Assessment Metrics (ANAM). C. Data Acquisition and

Thalamofrontal neurodevelopment in new-onset pediatric idiopathic generalized epilepsy

PubMed Central

Dabbs, K.; Tuchsherer, V.; Sheth, R.D.; Koehn, M.A.; Hermann, B.P.; Seidenberg, M.

2011-01-01

Background: Quantitative MRI techniques have demonstrated thalamocortical abnormalities in idiopathic generalized epilepsy (IGE). However, there are few studies examining IGE early in its course and the neurodevelopmental course of this region is not adequately defined. Objective: We examined the 2-year developmental course of the thalamus and frontal lobes in pediatric new-onset IGE (i.e., within 12 months of diagnosis). Methods: We performed whole-brain MRI in 22 patients with new-onset IGE and 36 age-matched healthy controls. MRI was repeated 24 months after baseline MRI. Quantitative volumetrics were used to examine thalamic and frontal lobe volumes. Results: The IGE group showed significant differences in thalamic volume within 1 year of seizure onset (baseline) and went on to show thalamic volume loss at a significantly faster rate than healthy control children over the 2-year interval. The control group also showed a significantly greater increase in frontal white matter expansion than the IGE group. In contrast, frontal lobe gray matter volume differences were moderate at baseline and persisted over time, indicating similar developmental trajectories with differences early in the disease process that are maintained. Conclusions: Brain tissue abnormalities in thalamic and frontal regions can be identified very early in the course of IGE and an abnormal trajectory of growth continues over a 2-year interval. PMID:21205692

Genes in the GABA pathway increase in the lateral thalamus of Sprague Dawley rats during the proestrus/estrus phase

PubMed Central

Umorin, Mikhail; Stinson, Crystal; Bellinger, Larry L.; Kramer, Phillip

2015-01-01

Pain can vary over the estrous cycle as a result of changes in estradiol concentration but the mechanism causing this variation is unclear. Because the thalamus is important in pain control, gene expression in the lateral thalamus (ventral posteromedial, ventral posterolateral, reticular thalamic nuclei) was screened at different phases of the estrous cycle. Gene expression changes in Sprague-Dawley rats were further analyzed by real-time PCR and ELISA and plasma estradiol levels were measured by RIAs at different phases of the estrous cycle. Our results indicated that both the RNA and protein expression of glutamate decarboxylase 1 and 2 (GAD1, GAD2), GABA(A) receptor-associated protein like 1 (GABARAPL1) and vesicular GABA transporter (VGAT) significantly increased in the lateral thalamus when plasma estradiol levels were elevated. Estradiol levels were elevated during the proestrus and estrus phases of the estrous cycle. Estrogen receptor α (ERα) was observed to be co-localized in thalamic cells and thalamic infusion of an ERα antagonist significantly reduced GAD1 and VGAT transcript. GAD1, GAD2 GABARAPL1 and VGAT have been shown to effect neuronal responses suggesting that modulation of pain during the estrous cycle can be dependent, in part, through estradiol induced changes in thalamic gene expression. PMID:26388520

Thalamofrontal neurodevelopment in new-onset pediatric idiopathic generalized epilepsy.

PubMed

Pulsipher, D T; Dabbs, K; Tuchsherer, V; Sheth, R D; Koehn, M A; Hermann, B P; Seidenberg, M

2011-01-04

Quantitative MRI techniques have demonstrated thalamocortical abnormalities in idiopathic generalized epilepsy (IGE). However, there are few studies examining IGE early in its course and the neurodevelopmental course of this region is not adequately defined. We examined the 2-year developmental course of the thalamus and frontal lobes in pediatric new-onset IGE (i.e., within 12 months of diagnosis). We performed whole-brain MRI in 22 patients with new-onset IGE and 36 age-matched healthy controls. MRI was repeated 24 months after baseline MRI. Quantitative volumetrics were used to examine thalamic and frontal lobe volumes. The IGE group showed significant differences in thalamic volume within 1 year of seizure onset (baseline) and went on to show thalamic volume loss at a significantly faster rate than healthy control children over the 2-year interval. The control group also showed a significantly greater increase in frontal white matter expansion than the IGE group. In contrast, frontal lobe gray matter volume differences were moderate at baseline and persisted over time, indicating similar developmental trajectories with differences early in the disease process that are maintained. Brain tissue abnormalities in thalamic and frontal regions can be identified very early in the course of IGE and an abnormal trajectory of growth continues over a 2-year interval.

Intracortical multiplication of thalamocortical signals in mouse auditory cortex.

PubMed

Li, Ling-yun; Li, Ya-tang; Zhou, Mu; Tao, Huizhong W; Zhang, Li I

2013-09-01

Cortical processing of sensory information begins with the transformation of thalamically relayed signals. We optogenetically silenced intracortical circuits to isolate thalamic inputs to layer 4 neurons and found that intracortical excitation linearly amplified thalamocortical responses underlying frequency and direction selectivity, with spectral range and tuning preserved, and prolonged the response duration. This signal pre-amplification and prolongation enhanced the salience of thalamocortically relayed information and ensured its robust, faithful and more persistent representation.

Thalamic input to auditory cortex is locally heterogeneous but globally tonotopic

PubMed Central

Vasquez-Lopez, Sebastian A; Weissenberger, Yves; Lohse, Michael; Keating, Peter; King, Andrew J

2017-01-01

Topographic representation of the receptor surface is a fundamental feature of sensory cortical organization. This is imparted by the thalamus, which relays information from the periphery to the cortex. To better understand the rules governing thalamocortical connectivity and the origin of cortical maps, we used in vivo two-photon calcium imaging to characterize the properties of thalamic axons innervating different layers of mouse auditory cortex. Although tonotopically organized at a global level, we found that the frequency selectivity of individual thalamocortical axons is surprisingly heterogeneous, even in layers 3b/4 of the primary cortical areas, where the thalamic input is dominated by the lemniscal projection. We also show that thalamocortical input to layer 1 includes collaterals from axons innervating layers 3b/4 and is largely in register with the main input targeting those layers. Such locally varied thalamocortical projections may be useful in enabling rapid contextual modulation of cortical frequency representations. PMID:28891466

[Motor neglect of thalamic origin: report on two cases (author's transl)].

PubMed

Laplane, D; Escourolle, R; Degos, J D; Sauron, B; Massiou, H

1982-01-01

Two cases of thalamic lesions with motor neglect are presented. The syndrome of motor neglect was complete in those cases with a) underutilization of left limbs, but good utilization upon verbal orders, b) loss of placement reaction, c) weakness of movement when hand was approaching the target, d) weakness of motor reaction to nociceptive stimuli. Those cases confirm that motor neglect exists after thalamic lesions and bring pathologic clues for topographic discussion. Motor neglect seems to be a particular case of partial unilateral neglect throwing some doubt on the hypothesis of a global trouble of hemispheric activation. Prevalence of left motor neglects suggests some linkage between propositional motility and language. One may suppose that in the right hemisphere language is able to have a vicarious action when spontaneous activation is lost; at the opposite, in the left hemisphere language and motility would be too linked to let this dissociation be generally possible.

Thalamic structures and associated cognitive functions: Relations with age and aging.

PubMed

Fama, Rosemary; Sullivan, Edith V

2015-07-01

The thalamus, with its cortical, subcortical, and cerebellar connections, is a critical node in networks supporting cognitive functions known to decline in normal aging, including component processes of memory and executive functions of attention and information processing. The macrostructure, microstructure, and neural connectivity of the thalamus changes across the adult lifespan. Structural and functional magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) have demonstrated, regional thalamic volume shrinkage and microstructural degradation, with anterior regions generally more compromised than posterior regions. The integrity of selective thalamic nuclei and projections decline with advancing age, particularly those in thalamofrontal, thalamoparietal, and thalamolimbic networks. This review presents studies that assess the relations between age and aging and the structure, function, and connectivity of the thalamus and associated neural networks and focuses on their relations with processes of attention, speed of information processing, and working and episodic memory. Copyright © 2015 Elsevier Ltd. All rights reserved.

Thalamic amplification of cortical connectivity sustains attentional control

PubMed Central

Schmitt, L. Ian; Wimmer, Ralf D.; Nakajima, Miho; Happ, Michael; Mofakham, Sima; Halassa, Michael M.

2017-01-01

While interactions between the thalamus and cortex are critical for cognitive function1–3, the exact contribution of the thalamus to these interactions is often unclear. Recent studies have shown diverse connectivity patterns across the thalamus 4,5, but whether this diversity translates to thalamic functions beyond relaying information to or between cortical regions6 is unknown. Here, by investigating prefrontal cortical (PFC) representation of two rules used to guide attention, we find that the mediodorsal thalamus (MD) sustains these representations without relaying categorical information. Specifically, MD input amplifies local PFC connectivity, enabling rule-specific neural sequences to emerge and thereby maintain rule representations. Consistent with this notion, broadly enhancing PFC excitability diminishes rule specificity and behavioral performance, while enhancing MD excitability improves both. Overall, our results define a previously unknown principle in neuroscience; thalamic control of functional cortical connectivity. This function indicates that the thalamus plays much more central roles in cognition than previously thought. PMID:28467827

Thalamic abnormalities are a cardinal feature of alcohol-related brain dysfunction.

PubMed

Pitel, Anne Lise; Segobin, Shailendra H; Ritz, Ludivine; Eustache, Francis; Beaunieux, Hélène

2015-07-01

Two brain networks are particularly affected by the harmful effect of chronic and excessive alcohol consumption: the circuit of Papez and the frontocerebellar circuit, in both of which the thalamus plays a key role. Shrinkage of the thalamus is more severe in alcoholics with Korsakoff's syndrome (KS) than in those without neurological complication (AL). In accordance with the gradient effect of thalamic abnormalities between AL and KS, the pattern of brain dysfunction in the Papez's circuit results in anterograde amnesia in KS and only mild-to-moderate episodic memory disorders in AL. On the opposite, dysfunction of the frontocerebellar circuit results in a similar pattern of working memory and executive deficits in the AL and KS. Several hypotheses, mutually compatible, can be drawn to explain that the severe thalamic shrinkage observed in KS has different consequences in the neuropsychological profile associated with the two brain networks. Copyright © 2014. Published by Elsevier Ltd.

Crossed cerebellar and uncrossed basal ganglia and thalamic diaschisis in Alzheimer's disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akiyama, H.; Harrop, R.; McGeer, P.L.

1989-04-01

We detected crossed cerebellar as well as uncrossed basal ganglia and thalamic diaschisis in Alzheimer's disease by positron emission tomography (PET) using /sup 18/F-fluorodeoxyglucose. We studied a series of 26 consecutive, clinically diagnosed Alzheimer cases, including 6 proven by later autopsy, and compared them with 9 age-matched controls. We calculated asymmetry indices (AIs) of cerebral metabolic rate for matched left-right regions of interest (ROIs) and determined the extent of diaschisis by correlative analyses. For the Alzheimer group, we found cerebellar AIs correlated negatively, and thalamic AIs positively, with those of the cerebral hemisphere and frontal, temporal, parietal, and angular cortices,more » while basal ganglia AIs correlated positively with frontal cortical AIs. The only significant correlation of AIs for normal subjects was between the thalamus and cerebral hemisphere. These data indicate that PET is a sensitive technique for detecting diaschisis.« less

Interactions between thalamic and cortical rhythms during semantic memory recall in human

NASA Astrophysics Data System (ADS)

Slotnick, Scott D.; Moo, Lauren R.; Kraut, Michael A.; Lesser, Ronald P.; Hart, John, Jr.

2002-04-01

Human scalp electroencephalographic rhythms, indicative of cortical population synchrony, have long been posited to reflect cognitive processing. Although numerous studies employing simultaneous thalamic and cortical electrode recording in nonhuman animals have explored the role of the thalamus in the modulation of cortical rhythms, direct evidence for thalamocortical modulation in human has not, to our knowledge, been obtained. We simultaneously recorded from thalamic and scalp electrodes in one human during performance of a cognitive task and found a spatially widespread, phase-locked, low-frequency rhythm (7-8 Hz) power decrease at thalamus and scalp during semantic memory recall. This low-frequency rhythm power decrease was followed by a spatially specific, phase-locked, fast-rhythm (21-34 Hz) power increase at thalamus and occipital scalp. Such a pattern of thalamocortical activity reflects a plausible neural mechanism underlying semantic memory recall that may underlie other cognitive processes as well.

CACNA1H missense mutations associated with amyotrophic lateral sclerosis alter Cav3.2 T-type calcium channel activity and reticular thalamic neuron firing.

PubMed

Rzhepetskyy, Yuriy; Lazniewska, Joanna; Blesneac, Iulia; Pamphlett, Roger; Weiss, Norbert

2016-11-01

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. In a recent study by Steinberg and colleagues, 2 recessive missense mutations were identified in the Cav3.2 T-type calcium channel gene (CACNA1H), in a family with an affected proband (early onset, long duration ALS) and 2 unaffected parents. We have introduced and functionally characterized these mutations using transiently expressed human Cav3.2 channels in tsA-201 cells. Both of these mutations produced mild but significant changes on T-type channel activity that are consistent with a loss of channel function. Computer modeling in thalamic reticular neurons suggested that these mutations result in decreased neuronal excitability of thalamic structures. Taken together, these findings implicate CACNA1H as a susceptibility gene in amyotrophic lateral sclerosis.

The thalamus as a monitor of motor outputs.

PubMed Central

Guillery, R W; Sherman, S M

2002-01-01

Many of the ascending pathways to the thalamus have branches involved in movement control. In addition, the recently defined, rich innervation of 'higher' thalamic nuclei (such as the pulvinar) from pyramidal cells in layer five of the neocortex also comes from branches of long descending axons that supply motor structures. For many higher thalamic nuclei the clue to understanding the messages that are relayed to the cortex will depend on knowing the nature of these layer five motor outputs and on defining how messages from groups of functionally distinct output types are combined as inputs to higher cortical areas. Current evidence indicates that many and possibly all thalamic relays to the neocortex are about instructions that cortical and subcortical neurons are contributing to movement control. The perceptual functions of the cortex can thus be seen to represent abstractions from ongoing motor instructions. PMID:12626014

A cortical motor nucleus drives the basal ganglia-recipient thalamus in singing birds

PubMed Central

Goldberg, Jesse H.

2012-01-01

The pallido-recipient thalamus transmits information from the basal ganglia (BG) to the cortex and plays a critical role motor initiation and learning. Thalamic activity is strongly inhibited by pallidal inputs from the BG, but the role of non-pallidal inputs, such as excitatory inputs from cortex, is unclear. We have recorded simultaneously from presynaptic pallidal axon terminals and postsynaptic thalamocortical neurons in a BG-recipient thalamic nucleus necessary for vocal variability and learning in zebra finches. We found that song-locked rate modulations in the thalamus could not be explained by pallidal inputs alone, and persisted following pallidal lesion. Instead, thalamic activity was likely driven by inputs from a motor ‘cortical’ nucleus also necessary for singing. These findings suggest a role for cortical inputs to the pallido-recipient thalamus in driving premotor signals important for exploratory behavior and learning. PMID:22327474

Control of Absence Seizures by the Thalamic Feed-Forward Inhibition

PubMed Central

Chen, Mingming; Guo, Daqing; Xia, Yang; Yao, Dezhong

2017-01-01

As a subtype of idiopathic generalized epilepsies, absence epilepsy is believed to be caused by pathological interactions within the corticothalamic (CT) system. Using a biophysical mean-field model of the CT system, we demonstrate here that the feed-forward inhibition (FFI) in thalamus, i.e., the pathway from the cerebral cortex (Ctx) to the thalamic reticular nucleus (TRN) and then to the specific relay nuclei (SRN) of thalamus that are also directly driven by the Ctx, may participate in controlling absence seizures. In particular, we show that increasing the excitatory Ctx-TRN coupling strength can significantly suppress typical electrical activities during absence seizures. Further, investigation demonstrates that the GABAA- and GABAB-mediated inhibitions in the TRN-SRN pathway perform combination roles in the regulation of absence seizures. Overall, these results may provide an insightful mechanistic understanding of how the thalamic FFI serves as an intrinsic regulator contributing to the control of absence seizures. PMID:28491031

Decoding thalamic afferent input using microcircuit spiking activity

PubMed Central

Sederberg, Audrey J.; Palmer, Stephanie E.

2015-01-01

A behavioral response appropriate to a sensory stimulus depends on the collective activity of thousands of interconnected neurons. The majority of cortical connections arise from neighboring neurons, and thus understanding the cortical code requires characterizing information representation at the scale of the cortical microcircuit. Using two-photon calcium imaging, we densely sampled the thalamically evoked response of hundreds of neurons spanning multiple layers and columns in thalamocortical slices of mouse somatosensory cortex. We then used a biologically plausible decoder to characterize the representation of two distinct thalamic inputs, at the level of the microcircuit, to reveal those aspects of the activity pattern that are likely relevant to downstream neurons. Our data suggest a sparse code, distributed across lamina, in which a small population of cells carries stimulus-relevant information. Furthermore, we find that, within this subset of neurons, decoder performance improves when noise correlations are taken into account. PMID:25695647

Decoding thalamic afferent input using microcircuit spiking activity.

PubMed

Sederberg, Audrey J; Palmer, Stephanie E; MacLean, Jason N

2015-04-01

A behavioral response appropriate to a sensory stimulus depends on the collective activity of thousands of interconnected neurons. The majority of cortical connections arise from neighboring neurons, and thus understanding the cortical code requires characterizing information representation at the scale of the cortical microcircuit. Using two-photon calcium imaging, we densely sampled the thalamically evoked response of hundreds of neurons spanning multiple layers and columns in thalamocortical slices of mouse somatosensory cortex. We then used a biologically plausible decoder to characterize the representation of two distinct thalamic inputs, at the level of the microcircuit, to reveal those aspects of the activity pattern that are likely relevant to downstream neurons. Our data suggest a sparse code, distributed across lamina, in which a small population of cells carries stimulus-relevant information. Furthermore, we find that, within this subset of neurons, decoder performance improves when noise correlations are taken into account. Copyright © 2015 the American Physiological Society.

The effect of unilateral thalamic deep brain stimulation on the vocal dysfunction in a patient with spasmodic dysphonia: interrogating cerebellar and pallidal neural circuits.

PubMed

Poologaindran, Anujan; Ivanishvili, Zurab; Morrison, Murray D; Rammage, Linda A; Sandhu, Mini K; Polyhronopoulos, Nancy E; Honey, Christopher R

2018-02-01

Spasmodic dysphonia (SD) is a neurological disorder of the voice where a patient's ability to speak is compromised due to involuntary contractions of the intrinsic laryngeal muscles. Since the 1980s, SD has been treated with botulinum toxin A (BTX) injections into the throat. This therapy is limited by the delayed-onset of benefits, wearing-off effects, and repeated injections required every 3 months. In a patient with essential tremor (ET) and coincident SD, the authors set out to quantify the effects of thalamic deep brain stimulation (DBS) on vocal function while investigating the underlying motor thalamic circuitry. A 79-year-old right-handed woman with ET and coincident adductor SD was referred to our neurosurgical team. While primarily treating her limb tremor, the authors studied the effects of unilateral, thalamic DBS on vocal function using the Unified Spasmodic Dysphonia Rating Scale (USDRS) and voice-related quality of life (VRQOL). Since dystonia is increasingly being considered a multinodal network disorder, an anterior trajectory into the left thalamus was deliberately chosen such that the proximal contacts of the electrode were in the ventral oralis anterior (Voa) nucleus (pallidal outflow) and the distal contacts were in the ventral intermediate (Vim) nucleus (cerebellar outflow). In addition to assessing on/off unilateral thalamic Vim stimulation on voice, the authors experimentally assessed low-voltage unilateral Vim, Voa, or multitarget stimulation in a prospective, randomized, doubled-blinded manner. The evaluators were experienced at rating SD and were familiar with the vocal tremor of ET. A Wilcoxon signed-rank test was used to study the pre- and posttreatment effect of DBS on voice. Unilateral left thalamic Vim stimulation (DBS on) significantly improved SD vocal dysfunction compared with no stimulation (DBS off), as measured by the USDRS (p < 0.01) and VRQOL (p < 0.01). In the experimental interrogation, both low-voltage Vim (p < 0.01) and multitarget Vim + Voa (p < 0.01) stimulation were significantly superior to low-voltage Voa stimulation. For the first time, the effects of high-frequency stimulation of different neural circuits in SD have been quantified. Unexpectedly, focused Voa (pallidal outflow) stimulation was inferior to Vim (cerebellar outflow) stimulation despite the classification of SD as a dystonia. While only a single case, scattered reports exist on the positive effects of thalamic DBS on dysphonia. A Phase 1 pilot trial (DEBUSSY; clinical trial no. NCT02558634, clinicaltrials.gov) is underway at the authors' center to evaluate the safety and preliminary efficacy of DBS in SD. The authors hope that this current report stimulates neurosurgeons to investigate this new indication for DBS.

[Acute bilateral thalamic infarcts in a young man with patent foramen ovale].

PubMed

Chávez-Valencia, Venice; Soto-Cabrera, Elizabeth

2010-01-01

Patent foramen ovale (PFO) has been associated with cryptogenic stroke in young patients. A 27-year-old man presented with acute confusional syndrome, altered language, bradypsychia and somnolence. Brain MRI showed symmetrical bilateral thalamic infarctions probably due to occlusion of Percheron's artery type 2b. Echocardiography showed patent foramen ovale. Cerebrovascular disease is a frequent cause of disability and even death in young patients, and thus its medical approach should be emphasized.

[Effects of transcranial magnetotherapy on electroencephalographic parameters in females with overactive urinary bladder].

PubMed

Neĭmark, A I; Klyzhina, E A; Neĭmark, B A; Mel'nik, M A

2007-01-01

Urodynamic parameters and bioelectric brain activity were studied in 30 females aged 24-66 years with overactive bladder (OAB) before and after transcranial magnetotherapy. It was found that OAB patients have disorders of bioelectric brain activity by two types of EEG patterns (I.A. Svyatogor classification)--thalamic and stem, Patients with thalamic type EEG benefit more from magnetotherapy higher efficacy of which manifests with regress of clinical symptoms and urodynamic improvement.

The Impact of Cortical Deafferentation on the Neocortical Slow Oscillation

PubMed Central

Lemieux, Maxime; Chen, Jen-Yung; Lonjers, Peter; Bazhenov, Maxim

2014-01-01

Slow oscillation is the main brain rhythm observed during deep sleep in mammals. Although several studies have demonstrated its neocortical origin, the extent of the thalamic contribution is still a matter of discussion. Using electrophysiological recordings in vivo on cats and computational modeling, we found that the local thalamic inactivation or the complete isolation of the neocortical slabs maintained within the brain dramatically reduced the expression of slow and fast oscillations in affected cortical areas. The slow oscillation began to recover 12 h after thalamic inactivation. The slow oscillation, but not faster activities, nearly recovered after 30 h and persisted for weeks in the isolated slabs. We also observed an increase of the membrane potential fluctuations recorded in vivo several hours after thalamic inactivation. Mimicking this enhancement in a network computational model with an increased postsynaptic activity of long-range intracortical afferents or scaling K+ leak current, but not several other Na+ and K+ intrinsic currents was sufficient for recovering the slow oscillation. We conclude that, in the intact brain, the thalamus contributes to the generation of cortical active states of the slow oscillation and mediates its large-scale synchronization. Our study also suggests that the deafferentation-induced alterations of the sleep slow oscillation can be counteracted by compensatory intracortical mechanisms and that the sleep slow oscillation is a fundamental and intrinsic state of the neocortex. PMID:24741059

Increased thalamic resting-state connectivity as a core driver of LSD-induced hallucinations.

PubMed

Müller, F; Lenz, C; Dolder, P; Lang, U; Schmidt, A; Liechti, M; Borgwardt, S

2017-12-01

It has been proposed that the thalamocortical system is an important site of action of hallucinogenic drugs and an essential component of the neural correlates of consciousness. Hallucinogenic drugs such as LSD can be used to induce profoundly altered states of consciousness, and it is thus of interest to test the effects of these drugs on this system. 100 μg LSD was administrated orally to 20 healthy participants prior to fMRI assessment. Whole brain thalamic functional connectivity was measured using ROI-to-ROI and ROI-to-voxel approaches. Correlation analyses were used to explore relationships between thalamic connectivity to regions involved in auditory and visual hallucinations and subjective ratings on auditory and visual drug effects. LSD caused significant alterations in all dimensions of the 5D-ASC scale and significantly increased thalamic functional connectivity to various cortical regions. Furthermore, LSD-induced functional connectivity measures between the thalamus and the right fusiform gyrus and insula correlated significantly with subjective auditory and visual drug effects. Hallucinogenic drug effects might be provoked by facilitations of cortical excitability via thalamocortical interactions. Our findings have implications for the understanding of the mechanism of action of hallucinogenic drugs and provide further insight into the role of the 5-HT 2A -receptor in altered states of consciousness. © 2017 The Authors Acta Psychiatrica Scandinavica Published by John Wiley & Sons Ltd.

Thalamic pathology and memory loss in early Alzheimer’s disease: moving the focus from the medial temporal lobe to Papez circuit

PubMed Central

Pralus, Agathe; Nelson, Andrew J. D.; Hornberger, Michael

2016-01-01

Abstract It is widely assumed that incipient protein pathology in the medial temporal lobe instigates the loss of episodic memory in Alzheimer’s disease, one of the earliest cognitive deficits in this type of dementia. Within this region, the hippocampus is seen as the most vital for episodic memory. Consequently, research into the causes of memory loss in Alzheimer’s disease continues to centre on hippocampal dysfunction and how disease-modifying therapies in this region can potentially alleviate memory symptomology. The present review questions this entrenched notion by bringing together findings from post-mortem studies, non-invasive imaging (including studies of presymptomatic, at-risk cases) and genetically modified animal models. The combined evidence indicates that the loss of episodic memory in early Alzheimer’s disease reflects much wider neurodegeneration in an extended mnemonic system (Papez circuit), which critically involves the limbic thalamus. Within this system, the anterior thalamic nuclei are prominent, both for their vital contributions to episodic memory and for how these same nuclei appear vulnerable in prodromal Alzheimer’s disease. As thalamic abnormalities occur in some of the earliest stages of the disease, the idea that such changes are merely secondary to medial temporal lobe dysfunctions is challenged. This alternate view is further strengthened by the interdependent relationship between the anterior thalamic nuclei and retrosplenial cortex, given how dysfunctions in the latter cortical area provide some of the earliest in vivo imaging evidence of prodromal Alzheimer’s disease. Appreciating the importance of the anterior thalamic nuclei for memory and attention provides a more balanced understanding of Alzheimer’s disease. Furthermore, this refocus on the limbic thalamus, as well as the rest of Papez circuit, would have significant implications for the diagnostics, modelling, and experimental treatment of cognitive symptoms in Alzheimer’s disease. PMID:27190025

Phase-amplitude coupling within the anterior thalamic nuclei during seizures.

PubMed

Ibrahim, George M; Wong, Simeon; Morgan, Benjamin R; Lipsman, Nir; Fallah, Aria; Weil, Alexander G; Krishna, Vibhor; Wennberg, Richard A; Lozano, Andres A

2018-04-01

Cross-frequency phase-amplitude coupling (cfPAC) subserves an integral role in the hierarchical organization of interregional neuronal communication and is also expressed by epileptogenic cortex during seizures. Here, we sought to characterize patterns of cfPAC expression in the anterior thalamic nuclei during seizures by studying extra-operative recordings in patients implanted with deep brain stimulation electrodes for intractable epilepsy. Nine seizures from two patients were analyzed in the peri-ictal period. CfPAC was calculated using the modulation index and interregional functional connectivity was indexed using the phase-locking value. Statistical analysis was performed within subjects on the basis of nonparametric permutation and corrected with Gaussian field theory. Five of the nine analyzed seizures demonstrated significant cfPAC. Significant cfPAC occurred during the pre-ictal and ictal periods in three seizures, as well as the postictal windows in four seizures. The preferred phase at which cfPAC occurred differed 1) in space, between the thalami of the epileptogenic and nonepileptogenic hemispheres; and 2) in time, at seizure termination. The anterior thalamic nucleus of the epileptogenic hemisphere also exhibited altered interregional phase-locking synchrony concurrent with the expression of cfPAC. By analyzing extraoperative recordings from the anterior thalamic nuclei, we show that cfPAC associated with altered interregional phase synchrony is lateralized to the thalamus of the epileptogenic hemisphere during seizures. Electrophysiological differences in cfPAC, including preferred phase of oscillatory interactions may be further investigated as putative targets for individualized neuromodulation paradigms in patients with drug-resistant epilepsy. NEW & NOTEWORTHY The association between fast brain activity and slower oscillations is an integral mechanism for hierarchical neuronal communication, which is also manifested in epileptogenic cortex. Our data suggest that the same phenomenon occurs in the anterior thalamic nuclei during seizures. Further, the preferred phase of modulation shows differences in space, between the epileptogenic and nonepileptogenic hemispheres and time, as seizures terminate. Our data encourage the study of cross-frequency coupling for targeted, individualized closed-loop stimulation paradigms.

Increased thalamic centrality and putamen-thalamic connectivity in patients with parkinsonian resting tremor.

PubMed

Gu, Quanquan; Cao, Hengyi; Xuan, Min; Luo, Wei; Guan, Xiaojun; Xu, Jingjing; Huang, Peiyu; Zhang, Minming; Xu, Xiaojun

2017-01-01

Evidence has indicated a strong association between hyperactivity in the cerebello-thalamo-motor cortical loop and resting tremor in Parkinson's disease (PD). Within this loop, the thalamus serves as a central hub based on its structural centrality in the generation of resting tremor. To study whether this thalamic abnormality leads to an alteration at the whole-brain level, our study investigated the role of the thalamus in patients with parkinsonian resting tremor in a large-scale brain network context. Forty-one patients with PD (22 with resting tremor, TP and 19 without resting tremor, NTP) and 45 healthy controls (HC) were included in this resting-state functional MRI study. Graph theory-based network analysis was performed to examine the centrality measures of bilateral thalami across the three groups. To further provide evidence to the central role of the thalamus in parkinsonian resting tremor, the seed-based functional connectivity analysis was then used to quantify the functional interactions between the basal ganglia and the thalamus. Compared with the HC group, patients with the TP group exhibited increased degree centrality ( p  < .04), betweenness centrality ( p  < .01), and participation coefficient ( p  < .01) in the bilateral thalami. Two of these alterations (degree centrality and participation coefficient) were significantly correlated with tremor severity, especially in the left hemisphere ( p  < .02). The modular analysis showed that the TP group had more intermodular connections between the thalamus and the regions within the cerebello-thalamo-motor cortical loop. Furthermore, the data revealed significantly enhanced functional connectivity between the putamen and the thalamus in the TP group ( p  = .027 corrected for family-wise error). These findings suggest increased thalamic centrality as a potential tremor-specific imaging measure for PD, and provide evidence for the altered putamen-thalamic interaction in patients with resting tremor.

NORADRENERGIC CONTROL OF CORTICO-STRIATO-THALAMIC AND MESOLIMBIC CROSS-STRUCTURAL SYNCHRONY

PubMed Central

Dzirasa, Kafui; Phillips, H. Westley; Sotnikova, Tatyana D.; Salahpour, Ali; Kumar, Sunil; Gainetdinov, Raul R.; Caron, Marc G.; Nicolelis, Miguel A. L.

2010-01-01

While normal dopaminergic tone has been shown to be essential for the induction of cortico-striatal and mesolimbic theta oscillatory activity, the influence of norepinephrine on these brain networks remains relatively unknown. To address this question, we simultaneously recorded local field potentials (LFPs) and single neuron activity across ten interconnected brain areas (ventral striatum, frontal association cortex hippocampus, primary motor cortex, orbital frontal cortex, prelimbic cortex, dorsal lateral striatum, medial dorsal nucleus of thalamus, substantia nigra pars reticularis, and ventral tegmental area) in a combined genetically and pharmacologically induced mouse model of hyponoradrenergia. Our results show that norepinephrine (NE) depletion induces a novel state in male mice characterized by a profound disruption of coherence across multiple cortico-striatal circuits, and an increase in mesolimbic cross-structural coherence. Moreover, this brain state is accompanied by a complex behavioral phenotype consisting of transient hyperactivity, stereotypic behaviors, and an acute twelve-fold increase in grooming. Notably, treatment with a norepinephrine precursors (L-DOPA 100mg/kg or L-DOPS 5mg/kg), or a selective serotonin reuptake inhibitor (fluoxetine 20mg/kg) attenuates the abnormal behaviors and selectively reverses the circuit changes observed in NE depleted mice. Together, our results demonstrate that norepinephrine modulates the dynamic tuning of coherence across cortico-striatal-thalamic circuits, and they suggest that changes in coherence across these circuits mediate the abnormal generation of hyperactivity and repetitive behaviors. PMID:20445065

Noradrenergic control of cortico-striato-thalamic and mesolimbic cross-structural synchrony.

PubMed

Dzirasa, Kafui; Phillips, H Westley; Sotnikova, Tatyana D; Salahpour, Ali; Kumar, Sunil; Gainetdinov, Raul R; Caron, Marc G; Nicolelis, Miguel A L

2010-05-05

Although normal dopaminergic tone has been shown to be essential for the induction of cortico-striatal and mesolimbic theta oscillatory activity, the influence of norepinephrine on these brain networks remains relatively unknown. To address this question, we simultaneously recorded local field potentials and single-neuron activity across 10 interconnected brain areas (ventral striatum, frontal association cortex, hippocampus, primary motor cortex, orbital frontal cortex, prelimbic cortex, dorsal lateral striatum, medial dorsal nucleus of thalamus, substantia nigra pars reticularis, and ventral tegmental area) in a combined genetically and pharmacologically induced mouse model of hyponoradrenergia. Our results show that norepinephrine (NE) depletion induces a novel state in male mice characterized by a profound disruption of coherence across multiple cortico-striatal circuits and an increase in mesolimbic cross-structural coherence. Moreover, this brain state is accompanied by a complex behavioral phenotype consisting of transient hyperactivity, stereotypic behaviors, and an acute 12-fold increase in grooming. Notably, treatment with a norepinephrine precursors (l-3,4-dihydroxyphenylalanine at 100 mg/kg or l-threo-dihydroxyphenylserine at 5 mg/kg) or a selective serotonin reuptake inhibitor (fluoxetine at 20 mg/kg) attenuates the abnormal behaviors and selectively reverses the circuit changes observed in NE-depleted mice. Together, our results demonstrate that norepinephrine modulates the dynamic tuning of coherence across cortico-striato-thalamic circuits, and they suggest that changes in coherence across these circuits mediate the abnormal generation of hyperactivity and repetitive behaviors.

Synaptic changes in the thalamocortical system of cathepsin D-deficient mice: a model of human congenital neuronal ceroid-lipofuscinosis.

PubMed

Partanen, Sanna; Haapanen, Aleksi; Kielar, Catherine; Pontikis, Charles; Alexander, Noreen; Inkinen, Teija; Saftig, Paul; Gillingwater, Thomas H; Cooper, Jonathan D; Tyynelä, Jaana

2008-01-01

Cathepsin D (CTSD; EC 3.4.23.5) is a lysosomal aspartic protease, the deficiency of which causes early-onset and particularly aggressive forms of neuronal ceroid-lipofuscinosis in infants, sheep, and mice. Cathepsin D deficiencies are characterized by severe neurodegeneration, but the molecular mechanisms behind the neuronal death remain poorly understood. In this study, we have systematically mapped the distribution of neuropathologic changes in CTSD-deficient mouse brains by stereologic, immunologic, and electron microscopic methods. We report highly accentuated neuropathologic changes within the ventral posterior nucleus (ventral posteromedial [VPM]/ventral posterolateral [VPL]) of thalamus and in neuronal laminae IV and VI of the somatosensory cortex (S1BF), which receive and send information to the thalamic VPM/VPL. These changes included pronounced astrocytosis and microglial activation that begin in the VPM/VPL thalamic nucleus of CTSD-deficient mice and are associated with reduced neuronal number and redistribution of presynaptic markers. In addition, loss of synapses, axonal pathology, and aggregation of synaptophysin and synaptobrevin were observed in the VPM/VPL. These synaptic alterations are accompanied by changes in the amount of synaptophysin/synaptobrevin heterodimer, which regulates formation of the SNARE complex at the synapse. Taken together, these data reveal the somatosensory thalamocortical circuitry as a particular focus of pathologic changes and provide the first evidence for synaptic alterations at the molecular and ultrastructural levels in CTSD deficiency.

Thalamic and parietal brain morphology predicts auditory category learning.

PubMed

Scharinger, Mathias; Henry, Molly J; Erb, Julia; Meyer, Lars; Obleser, Jonas

2014-01-01

Auditory categorization is a vital skill involving the attribution of meaning to acoustic events, engaging domain-specific (i.e., auditory) as well as domain-general (e.g., executive) brain networks. A listener's ability to categorize novel acoustic stimuli should therefore depend on both, with the domain-general network being particularly relevant for adaptively changing listening strategies and directing attention to relevant acoustic cues. Here we assessed adaptive listening behavior, using complex acoustic stimuli with an initially salient (but later degraded) spectral cue and a secondary, duration cue that remained nondegraded. We employed voxel-based morphometry (VBM) to identify cortical and subcortical brain structures whose individual neuroanatomy predicted task performance and the ability to optimally switch to making use of temporal cues after spectral degradation. Behavioral listening strategies were assessed by logistic regression and revealed mainly strategy switches in the expected direction, with considerable individual differences. Gray-matter probability in the left inferior parietal lobule (BA 40) and left precentral gyrus was predictive of "optimal" strategy switch, while gray-matter probability in thalamic areas, comprising the medial geniculate body, co-varied with overall performance. Taken together, our findings suggest that successful auditory categorization relies on domain-specific neural circuits in the ascending auditory pathway, while adaptive listening behavior depends more on brain structure in parietal cortex, enabling the (re)direction of attention to salient stimulus properties. © 2013 Published by Elsevier Ltd.

Pondering the Pulvinar.

PubMed

Lakatos, Peter; O'Connell, Monica N; Barczak, Annamaria

2016-01-06

While the function of the pulvinar remains one of the least explored among the thalamic nuclei despite occupying the most thalamic volume in primates, it has long been suspected to play a crucial role in attentive stimulus processing. In this issue of Neuron, Zhou et al. (2016) use simultaneous pulvinar-visual cortex recordings and pulvinar inactivation to provide evidence that the pulvinar is essential for intact stimulus processing, maintenance of neuronal oscillatory dynamics, and mediating the effects of attention. Copyright © 2016 Elsevier Inc. All rights reserved.

Neuropsychiatry of complex visual hallucinations.

PubMed

Mocellin, Ramon; Walterfang, Mark; Velakoulis, Dennis

2006-09-01

To describe the phenomenology and pathophysiology of complex visual hallucinations (CVH) in various organic states, in particular Charles Bonnet syndrome and peduncular hallucinosis. Three cases of CVH in the setting of pontine infarction, thalamic infarction and temporoparietal epileptiform activity are presented and the available psychiatric, neurological and biological literature on the structures of the central nervous system involved in producing hallucinatory states is reviewed. Complex visual hallucinations can arise from a variety of processes involving the retinogeniculocalcarine tract, or ascending brainstem modulatory structures. The cortical activity responsible for hallucinations results from altered or reduced input into these regions, or a loss of ascending inhibition of their afferent pathways. A significant degree of overlaps exists between the concepts of Charles Bonnet syndrome and peduncular hallucinosis. The fluidity of these eponymous syndromes reduces their validity and meaning, and may result in an inappropriate attribution of the underlying pathology. An understanding of how differing pathologies may produce CVH allows for the appropriate tailoring of treatment, depending on the site and nature of the lesion and content of perceptual disturbance.

Nonlinear predictive control for adaptive adjustments of deep brain stimulation parameters in basal ganglia-thalamic network.

PubMed

Su, Fei; Wang, Jiang; Niu, Shuangxia; Li, Huiyan; Deng, Bin; Liu, Chen; Wei, Xile

2018-02-01

The efficacy of deep brain stimulation (DBS) for Parkinson's disease (PD) depends in part on the post-operative programming of stimulation parameters. Closed-loop stimulation is one method to realize the frequent adjustment of stimulation parameters. This paper introduced the nonlinear predictive control method into the online adjustment of DBS amplitude and frequency. This approach was tested in a computational model of basal ganglia-thalamic network. The autoregressive Volterra model was used to identify the process model based on physiological data. Simulation results illustrated the efficiency of closed-loop stimulation methods (amplitude adjustment and frequency adjustment) in improving the relay reliability of thalamic neurons compared with the PD state. Besides, compared with the 130Hz constant DBS the closed-loop stimulation methods can significantly reduce the energy consumption. Through the analysis of inter-spike-intervals (ISIs) distribution of basal ganglia neurons, the evoked network activity by the closed-loop frequency adjustment stimulation was closer to the normal state. Copyright © 2017 Elsevier Ltd. All rights reserved.

Motor cortex stimulation for movement disorders.

PubMed

Cioni, Beatrice; Tufo, Tommaso; Bentivoglio, Annarita; Trevisi, Gianluca; Piano, Carla

2016-06-01

Motor cortex stimulation (MCS) was introduced by Tsubokawa in 1991 1 for the treatment of thalamic pain, after coming to the conclusion that the hyperactivity of thalamic neurons after spino-thalamic tractotomy was inhibited by stimulation of the motor cortex. MCS has been reported not only to be effective on pain, but also to improve movement disorders such as Parkinson's disease, tremor, dystonia, poststroke movement disorders and hemiparesis. Most of these publications are case reports or small series, and the real impact of MCS on movement disorders remains to be determined. In order to clarify this point, we conducted a PubMed search from 1991 to 2016 using established MeSH words. A total of 40 papers were selected and examined. Furthermore, personal experience with MCS for Parkinson's disease and akinesia, is reported. Only four studies were randomized controlled clinical trials: three out of four failed to demonstrate the efficacy of MCS at short term. At long term, MCS seems to show a clinical positive effect in the studies prolonged in an open observational trial.

Differentiating Cerebellar Impact on Thalamic Nuclei.

PubMed

Gornati, Simona V; Schäfer, Carmen B; Eelkman Rooda, Oscar H J; Nigg, Alex L; De Zeeuw, Chris I; Hoebeek, Freek E

2018-05-29

The cerebellum plays a role in coordination of movements and non-motor functions. Cerebellar nuclei (CN) axons connect to various parts of the thalamo-cortical network, but detailed information on the characteristics of cerebello-thalamic connections is lacking. Here, we assessed the cerebellar input to the ventrolateral (VL), ventromedial (VM), and centrolateral (CL) thalamus. Confocal and electron microscopy showed an increased density and size of CN axon terminals in VL compared to VM or CL. Electrophysiological recordings in vitro revealed that optogenetic CN stimulation resulted in enhanced charge transfer and action potential firing in VL neurons compared to VM or CL neurons, despite that the paired-pulse ratio was not significantly different. Together, these findings indicate that the impact of CN input onto neurons of different thalamic nuclei varies substantially, which highlights the possibility that cerebellar output differentially controls various parts of the thalamo-cortical network. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Persistence of disturbed thalamic glucose metabolism in a case of Wernicke-Korsakoff syndrome.

PubMed

Fellgiebel, Andreas; Scheurich, Armin; Siessmeier, Thomas; Schmidt, Lutz G; Bartenstein, Peter

2003-10-30

We report the case of a 40-year-old alcoholic male patient, hospitalized with an acute ataxia of stance and gait, ocular muscle weakness with nystagmus and a global apathetic-confusional state. After admission, an amnestic syndrome with confabulation was also observed and diagnosis of Wernicke-Korsakoff syndrome was made. Under treatment with intravenous thiamine, the patient recovered completely from gaze weakness and ataxia, whereas a severe amnestic syndrome persisted. Fluorodeoxyglucose (FDG) positron emission tomography (PET) showed bilateral thalamic and severe bilateral temporal-parietal hypometabolism resembling a pattern typical for Alzheimer's disease. Longitudinal assessment of the alcohol-abstinent and thiamine-substituted patient revealed improvements of clinical state and neuropsychological performance that were paralleled by recovered cerebral glucose metabolism. In contrast to metabolic rates that increased between 7.1% (anterior cingulate, left) and 23.5% (parietal, left) in cortical areas during a 9-month remission period, thalamic glucose metabolism remained severely disturbed over time (change: left +0.2%, right +0.3%).

mu-Opioid receptor-independent fashion of the suppression of sodium currents by mu-opioid analgesics in thalamic neurons.

PubMed

Hashimoto, Keisuke; Amano, Taku; Kasakura, Akiko; Uhl, George R; Sora, Ichiro; Sakai, Norio; Kuzumaki, Naoko; Suzuki, Tsutomu; Narita, Minoru

2009-03-27

Most reports in the literature have shown that the effects of opioid analgesics are primarily mediated by mu-opioid receptor (MOR), whereas other potential targets of opioid analgesics have not been thoroughly characterized. In this study, we found that extracellular application of morphine, fentanyl or oxycodone, which are all considered to be MOR agonists, at relatively high concentrations, but not endogenous mu-opioid peptides, produced a concentration-dependent suppression of sodium currents in cultured thalamic neurons. These effects of opioids were not affected by either a MOR antagonist naloxone or a deletion of MOR gene. Among these opioids, fentanyl strongly suppressed sodium currents to the same degree as lidocaine, and both morphine and oxycodone slightly but significantly reduced sodium currents when they were present extracellularly. In contrast, the intracellular application of morphine, but not oxycodone, fentanyl or lidocaine, reduced sodium currents. These results suggest that morphine, fentanyl and oxycodone each produce the MOR-independent suppression of sodium currents by distinct mechanisms in thalamic neurons.

Contralateral Supracerebellar-Infratentorial Approach for Resection of Thalamic Cavernous Malformations.

PubMed

Mascitelli, Justin; Burkhardt, Jan-Karl; Gandhi, Sirin; Lawton, Michael T

2018-02-26

Surgical resection of cavernous malformations (CM) in the posterior thalamus, pineal region, and midbrain tectum is technically challenging owing to the presence of adjacent eloquent cortex and critical neurovascular structures. Various supracerebellar infratentorial (SCIT) approaches have been used in the surgical armamentarium targeting lesions in this region, including the median, paramedian, and extreme lateral variants. Surgical view of a posterior thalamic CM from the traditional ipsilateral vantage point may be obscured by occipital lobe and tentorium. To describe a novel surgical approach via a contralateral SCIT (cSCIT) trajectory for resecting posterior thalamic CMs. From 1997 to 2017, 75 patients underwent the SCIT approach for cerebrovascular/oncologic pathology by the senior author. Of these, 30 patients underwent the SCIT approach for CM resection, and 3 patients underwent the cSCIT approach. Historical patient data, radiographic features, surgical technique, and postoperative neurological outcomes were evaluated in each patient. All 3 patients presented with symptomatic CMs within the right posterior thalamus with radiographic evidence of hemorrhage. All surgeries were performed in the sitting position. There were no intraoperative complications. Neuroimaging demonstrated complete CM resection in all cases. There were no new or worsening neurological deficits or evidence of rebleeding/recurrence noted postoperatively. This study establishes the surgical feasibility of a contralateral SCIT approach in resection of symptomatic thalamic CMs It demonstrates the application for this procedure in extending the surgical trajectory superiorly and laterally and maximizing safe resectability of these deep CMs with gravity-assisted brain retraction.

[Ultrasonic measurements of fetal thalamus, caudate nucleus and lenticular nucleus in prenatal diagnosis].

PubMed

Yang, Ruiqi; Wang, Fei; Zhang, Jialing; Zhu, Chonglei; Fan, Limei

2015-05-19

To establish the reference values of thalamus, caudate nucleus and lenticular nucleus diameters through fetal thalamic transverse section. A total of 265 fetuses at our hospital were randomly selected from November 2012 to August 2014. And the transverse and length diameters of thalamus, caudate nucleus and lenticular nucleus were measured. SPSS 19.0 statistical software was used to calculate the regression curve of fetal diameter changes and gestational weeks of pregnancy. P < 0.05 was considered as having statistical significance. The linear regression equation of fetal thalamic length diameter and gestational week was: Y = 0.051X+0.201, R = 0.876, linear regression equation of thalamic transverse diameter and fetal gestational week was: Y = 0.031X+0.229, R = 0.817, linear regression equation of fetal head of caudate nucleus length diameter and gestational age was: Y = 0.033X+0.101, R = 0.722, linear regression equation of fetal head of caudate nucleus transverse diameter and gestational week was: R = 0.025 - 0.046, R = 0.711, linear regression equation of fetal lentiform nucleus length diameter and gestational week was: Y = 0.046+0.229, R = 0.765, linear regression equation of fetal lentiform nucleus diameter and gestational week was: Y = 0.025 - 0.05, R = 0.772. Ultrasonic measurement of diameter of fetal thalamus caudate nucleus, and lenticular nucleus through thalamic transverse section is simple and convenient. And measurements increase with fetal gestational weeks and there is linear regression relationship between them.

Increased error-related thalamic activity during early compared to late cocaine abstinence.

PubMed

Li, Chiang-Shan R; Luo, Xi; Sinha, Rajita; Rounsaville, Bruce J; Carroll, Kathleen M; Malison, Robert T; Ding, Yu-Shin; Zhang, Sheng; Ide, Jaime S

2010-06-01

Altered cognitive control is implicated in the shaping of cocaine dependence. One of the key component processes of cognitive control is error monitoring. Our previous imaging work highlighted greater activity in distinct cortical and subcortical regions including the dorsal anterior cingulate cortex (dACC), thalamus and insula when participants committed an error during the stop signal task (Li et al., 2008b). Importantly, dACC, thalamic and insular activity has been associated with drug craving. One hypothesis is that the intense interoceptive activity during craving prevents these cerebral structures from adequately registering error and/or monitoring performance. Alternatively, the dACC, thalamus and insula show abnormally heightened responses to performance errors, suggesting that excessive responses to salient stimuli such as drug cues could precipitate craving. The two hypotheses would each predict decreased and increased activity during stop error (SE) as compared to stop success (SS) trials in the SST. Here we showed that cocaine dependent patients (PCD) experienced greater subjective feeling of loss of control and cocaine craving during early (average of day 6) compared to late (average of day 18) abstinence. Furthermore, compared to PCD during late abstinence, PCD scanned during early abstinence showed increased thalamic as well as insular but not dACC responses to errors (SE>SS). These findings support the hypothesis that heightened thalamic reactivity to salient stimuli co-occur with cocaine craving and loss of self control. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Thalamic functional connectivity predicts seizure laterality in individual TLE patients: application of a biomarker development strategy.

PubMed

Barron, Daniel S; Fox, Peter T; Pardoe, Heath; Lancaster, Jack; Price, Larry R; Blackmon, Karen; Berry, Kristen; Cavazos, Jose E; Kuzniecky, Ruben; Devinsky, Orrin; Thesen, Thomas

2015-01-01

Noninvasive markers of brain function could yield biomarkers in many neurological disorders. Disease models constrained by coordinate-based meta-analysis are likely to increase this yield. Here, we evaluate a thalamic model of temporal lobe epilepsy that we proposed in a coordinate-based meta-analysis and extended in a diffusion tractography study of an independent patient population. Specifically, we evaluated whether thalamic functional connectivity (resting-state fMRI-BOLD) with temporal lobe areas can predict seizure onset laterality, as established with intracranial EEG. Twenty-four lesional and non-lesional temporal lobe epilepsy patients were studied. No significant differences in functional connection strength in patient and control groups were observed with Mann-Whitney Tests (corrected for multiple comparisons). Notwithstanding the lack of group differences, individual patient difference scores (from control mean connection strength) successfully predicted seizure onset zone as shown in ROC curves: discriminant analysis (two-dimensional) predicted seizure onset zone with 85% sensitivity and 91% specificity; logistic regression (four-dimensional) achieved 86% sensitivity and 100% specificity. The strongest markers in both analyses were left thalamo-hippocampal and right thalamo-entorhinal cortex functional connection strength. Thus, this study shows that thalamic functional connections are sensitive and specific markers of seizure onset laterality in individual temporal lobe epilepsy patients. This study also advances an overall strategy for the programmatic development of neuroimaging biomarkers in clinical and genetic populations: a disease model informed by coordinate-based meta-analysis was used to anatomically constrain individual patient analyses.

Long-term outcome of thalamic deep brain stimulation in two patients with Tourette syndrome.

PubMed

Ackermans, Linda; Duits, Annelien; Temel, Yasin; Winogrodzka, Ania; Peeters, Frenk; Beuls, Emile A M; Visser-Vandewalle, Veerle

2010-10-01

Thalamic deep brain stimulation for intractable Tourette Syndrome was introduced in 1999 by Vandewalle et al. In this follow-up study, the authors report on the long-term (6 and 10 years) outcome in terms of tic reduction, cognition, mood and side effects of medial thalamic deep brain stimulation in two previously described Tourette patients. The authors compared the outcome of two patients at 6 and 10 years after surgery with their preoperative status and after 8 months and 5 years of treatment, respectively. Standardised video recordings were scored by three independent investigators. Both patients underwent (neuro)psychological assessment at all time points of follow-up. Tic improvement observed at 5 years in patient 1 (90.1%) was maintained at 10 years (92.6%). In patient 2, the tic improvement at 8 months (82%) was slightly decreased at 6 years (78%). During follow-up, case 1 revealed no changes in cognition, but case 2 showed a decrease in verbal fluency and learning which was in line with his subjective reports. Case 2 showed a slight decrease in depression, but overall psychopathology was still high at 6 years after surgery with an increase in anger and aggression together with difficulties in social adaptation. Besides temporary hardware-related complications, no distressing adverse effects were observed. Bilateral thalamic stimulation may provide sustained tic benefit after at least 6 years, but to maximise overall outcome, attention is needed for postoperative psychosocial adaptation, already prior to surgery.

Thalamic alterations in preterm neonates and its relation to ventral striatum disturbances revealed by a combined shape and pose analysis

PubMed Central

Lao, Yi; Wang, Yalin; Shi, Jie; Ceschin, Rafael; Nelson, Marvin D.; Panigrahy, Ashok; Leporé, Natasha

2015-01-01

Finding the neuroanatomical correlates of prematurity is vital to understanding which structures are affected, and design efficient prevention andtreatment strategy. Converging results reveal that thalamic abnormalities are important indicators of prematurity. However, little is known about the localization of the disturbance within the subnuclei of the thalamus, or on the association of altered thalamic development with other deep gray matter disturbances. Here, using brain structural magnetic resonance imaging (MRI), we perform a novel combined shape and pose analysis of the thalamus and ventral striatum between 17 preterm and 19 term-born neonates. We detect statistically significant surface deformations and pose changes on the thalamus andventral striatum, successfully locating the alterations on specific regions such as the anterior and ventral-anterior thalamic nuclei, and for the first time, demonstrating the feasibility of using relative pose parameters as indicators for prematurity in neonates. We also perform a set of correlation analyses between the thalamus and the ventral striatum, based on the surface and pose results. Our methods show that regional abnormalities of the thalamus are associated with alterations of the ventral striatum, possibly due to disturbed development of sharedpre-frontal connectivity. More specifically, the significantly correlated regions in these two structures point to frontal-subcortical pathways including the dorsolateral prefrontal-subcortical circuit, the lateral orbitofrontal-subcortical circuit, the motor circuit, and the oculomotor circuit. These findings reveal new insight into potential subcortical structural covariatesfor poor neurodevelopmental outcomes in the preterm population. PMID:25366970

The origins of thalamic inputs to grasp zones in frontal cortex of macaque monkeys

PubMed Central

Stepniewska, Iwona; Kaas, Jon H.

2015-01-01

The hand representation in primary motor cortex (M1) is instrumental to manual dexterity in primates. In Old World monkeys, rostral and caudal aspects of the hand representation are located in the precentral gyrus and the anterior bank of the central sulcus, respectively. We previously reported the organization of the cortico-cortical connections of the grasp zone in rostral M1. Here we describe the organization of thalamocortical connections that were labeled from the same tracer injections. Thalamocortical connections of a grasp zone in ventral premotor cortex (PMv) and the M1 orofacial representation are included for direct comparison. The M1 grasp zone was primarily connected with ventral lateral divisions of motor thalamus. The largest proportion of inputs originated in the posterior division (VLp) followed by the medial and the anterior divisions. Thalamic inputs to the M1 grasp zone originated in more lateral aspects of VLp as compared to the origins of thalamic inputs to the M1 orofacial representation. Inputs to M1 from thalamic divisions connected with cerebellum constituted three fold the density of inputs from divisions connected with basal ganglia, whereas the ratio of inputs was more balanced for the grasp zone in PMv. Privileged access of the cerebellothalamic pathway to the grasp zone in rostral M1 is consistent with the connection patterns previously reported for the precentral gyrus. Thus, cerebellar nuclei are likely more involved than basal ganglia nuclei with the contributions of rostral M1 to manual dexterity. PMID:26254903

Subset of Cortical Layer 6b Neurons Selectively Innervates Higher Order Thalamic Nuclei in Mice.

PubMed

Hoerder-Suabedissen, Anna; Hayashi, Shuichi; Upton, Louise; Nolan, Zachary; Casas-Torremocha, Diana; Grant, Eleanor; Viswanathan, Sarada; Kanold, Patrick O; Clasca, Francisco; Kim, Yongsoo; Molnár, Zoltán

2018-05-01

The thalamus receives input from 3 distinct cortical layers, but input from only 2 of these has been well characterized. We therefore investigated whether the third input, derived from layer 6b, is more similar to the projections from layer 6a or layer 5. We studied the projections of a restricted population of deep layer 6 cells ("layer 6b cells") taking advantage of the transgenic mouse Tg(Drd1a-cre)FK164Gsat/Mmucd (Drd1a-Cre), that selectively expresses Cre-recombinase in a subpopulation of layer 6b neurons across the entire cortical mantle. At P8, 18% of layer 6b neurons are labeled with Drd1a-Cre::tdTomato in somatosensory cortex (SS), and some co-express known layer 6b markers. Using Cre-dependent viral tracing, we identified topographical projections to higher order thalamic nuclei. VGluT1+ synapses formed by labeled layer 6b projections were found in posterior thalamic nucleus (Po) but not in the (pre)thalamic reticular nucleus (TRN). The lack of TRN collaterals was confirmed with single-cell tracing from SS. Transmission electron microscopy comparison of terminal varicosities from layer 5 and layer 6b axons in Po showed that L6b varicosities are markedly smaller and simpler than the majority from L5. Our results suggest that L6b projections to the thalamus are distinct from both L5 and L6a projections.

The origins of thalamic inputs to grasp zones in frontal cortex of macaque monkeys.

PubMed

Gharbawie, Omar A; Stepniewska, Iwona; Kaas, Jon H

2016-07-01

The hand representation in primary motor cortex (M1) is instrumental to manual dexterity in primates. In Old World monkeys, rostral and caudal aspects of the hand representation are located in the precentral gyrus and the anterior bank of the central sulcus, respectively. We previously reported the organization of the cortico-cortical connections of the grasp zone in rostral M1. Here we describe the organization of thalamocortical connections that were labeled from the same tracer injections. Thalamocortical connections of a grasp zone in ventral premotor cortex (PMv) and the M1 orofacial representation are included for direct comparison. The M1 grasp zone was primarily connected with ventral lateral divisions of motor thalamus. The largest proportion of inputs originated in the posterior division (VLp) followed by the medial and the anterior divisions. Thalamic inputs to the M1 grasp zone originated in more lateral aspects of VLp as compared to the origins of thalamic inputs to the M1 orofacial representation. Inputs to M1 from thalamic divisions connected with cerebellum constituted three fold the density of inputs from divisions connected with basal ganglia, whereas the ratio of inputs was more balanced for the grasp zone in PMv. Privileged access of the cerebellothalamic pathway to the grasp zone in rostral M1 is consistent with the connection patterns previously reported for the precentral gyrus. Thus, cerebellar nuclei are likely more involved than basal ganglia nuclei with the contributions of rostral M1 to manual dexterity.

Thalamocortical dysconnectivity in schizophrenia

PubMed Central

Woodward, Neil D.; Karbasforoushan, Haleh; Heckers, Stephan

2013-01-01

Objective The thalamus and cerebral cortex are connected via topographically organized, reciprocal connections. Previous studies revealed thalamic abnormalities in schizophrenia; however, it is not known if thalamocortical networks are differentially affected in the disorder. To explore this possibility, we examined functional connectivity in intrinsic low frequency blood-oxygen-level-dependent (BOLD) signal fluctuations between major divisions of the cortex and thalamus using resting-state functional magnetic resonance imaging. Method 77 healthy subjects and 62 patients with schizophrenia underwent resting-state fMRI. To identify functional subdivisions of the thalamus, we parceled the cortex into six regions-of-interest; prefrontal, motor, somatosensory, temporal, posterior parietal, and occipital cortex. Mean BOLD time-series was extracted from each of the regions-of-interest and entered into a seed-based functional connectivity analysis. Results Consistent with prior reports, activity in distinct cortical areas correlated with specific, largely non-overlapping regions of the thalamus in both healthy subjects and schizophrenia patients. Direct comparison between groups revealed reduced prefrontal-thalamic connectivity and increased motor/somatosensory-thalamic connectivity in schizophrenia. The changes in connectivity were unrelated to local grey matter content within the thalamus and antipsychotic medication dosage. No differences were observed in temporal, posterior parietal, and occipital cortex connectivity with the thalamus. Conclusions This study establishes differential abnormalities of thalamocortical networks in schizophrenia. The etiology of schizophrenia may disrupt the development of prefrontal-thalamic connectivity and refinement of somatomotor connectivity with the thalamus that occurs during brain maturation. PMID:23032387

Mesothalamic discharge in a chronic pain, allergy and fluid retention syndrome (case report).

PubMed

Andy, O J; Nicholas, W; Dearman, C

1995-01-01

A 32-year-old woman was bedridden for a year because of chronic pain and headaches. She had insomnia, depression, suicidal thoughts and a severe chemical allergy. She had been on steroid therapy for two years and became Cushingoid with striae in the arm pits, groins and abdomen. However, she had no hypertension, nor the buffalo fat and hirsutism. She was very edematous, with a weight gain from 112 to 180 lbs. The fluid retention did not conform to the syndrome of inappropriate antidiuretic hormone. Studies revealed abnormal scalp EEG discharges and high-voltage seizure discharges in the posterior thalamus. Electrothalamic stimulation suppressed the thalamic discharges and relieved the patient's pelvic pain and headaches. After one month of several thalamic stimulations per day, she was able to get out of bed and ambulate. In addition, the patient no longer was edematous and was tolerating perfumes and floor detergents. Steroids were progressively reduced without complications of withdrawal. She went from a completely steroid dependent state to independent during the first 1-1/2 yrs of thalamic stimulation. With continued thalamic stimulation she has done well for 8-1/2 yrs, weighs 112 lbs, keeps house and drives a car. It's speculated the illness is a chronic pain multiple syndrome predominantly due to mesothalamic discharges and body infirmities. The mesothalamic discharge implicated neural networks, which represent biologic systems, i.e. pain, sleep, fluid retention, etc. Therapeutic stimulation attenuates the discharges and the neural networks return to their normal set points of homeostasis.

Cyto- and chemoarchitecture of the dorsal thalamus of the monotreme Tachyglossus aculeatus, the short beaked echidna.

PubMed

Ashwell, Ken W S; Paxinos, George

2005-12-01

We have examined the cyto- and chemoarchitecture of the dorsal thalamus of the short beaked echidna (Tachyglossus aculeatus), using Nissl and myelin staining, immunoreactivity for parvalbumin, calbindin, calretinin and non-phosphorylated neurofilament protein (SMI-32 antibody), and histochemistry for acetylcholinesterase and NADPH diaphorase. Immunohistochemical methods revealed many nuclear boundaries, which were difficult to discern with Nissl staining. Parvalbumin immunoreactive somata were concentrated in the ventral posterior, reticular, posterior, lateral and medial geniculate nuclei, while parvalbumin immunoreactivity of the neuropil was present throughout all but the midline nuclei. Large numbers of calbindin immunoreactive somata were also found within the midline thalamic nuclei, and thalamic sensory relay nuclei. Immunoreactivity for calretinin was found in many small somata within the lateral geniculate "a" nucleus, with other labelled somata found in the lateral geniculate "b" nucleus, ventral posterior medial and ventral posterior lateral nuclei. Immunoreactivity with the SMI-32 antibody was largely confined to somata and neuropil within the thalamocortical relay nuclei (ventral posterior medial and lateral nuclei, lateral and medial geniculate nuclei and the posterior thalamic nucleus). In broad terms there were many similarities between the thalamus of this monotreme and that of eutheria (e.g. disposition of somatosensory thalamus, complementarity of parvalbumin and calbindin immunoreactive structures), but there were some unique features of the thalamus of the echidna. These include the relatively small size of the thalamic reticular nucleus and the preponderance of calbindin immunoreactive neurons over parvalbumin immunoreactive neurons in the ventral posterior nucleus.

The nature of tremor circuits in parkinsonian and essential tremor

PubMed Central

Cagnan, Hayriye; Little, Simon; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Cheeran, Binith; Fitzgerald, James; Green, Alexander L.; Aziz, Tipu

2014-01-01

Tremor is a cardinal feature of Parkinson’s disease and essential tremor, the two most common movement disorders. Yet, the mechanisms underlying tremor generation remain largely unknown. We hypothesized that driving deep brain stimulation electrodes at a frequency closely matching the patient’s own tremor frequency should interact with neural activity responsible for tremor, and that the effect of stimulation on tremor should reveal the role of different deep brain stimulation targets in tremor generation. Moreover, tremor responses to stimulation might reveal pathophysiological differences between parkinsonian and essential tremor circuits. Accordingly, we stimulated 15 patients with Parkinson’s disease with either thalamic or subthalamic electrodes (13 male and two female patients, age: 50–77 years) and 10 patients with essential tremor with thalamic electrodes (nine male and one female patients, age: 34–74 years). Stimulation at near-to tremor frequency entrained tremor in all three patient groups (ventrolateral thalamic stimulation in Parkinson’s disease, P = 0.0078, subthalamic stimulation in Parkinson’s disease, P = 0.0312; ventrolateral thalamic stimulation in essential tremor, P = 0.0137; two-tailed paired Wilcoxon signed-rank tests). However, only ventrolateral thalamic stimulation in essential tremor modulated postural tremor amplitude according to the timing of stimulation pulses with respect to the tremor cycle (e.g. P = 0.0002 for tremor amplification, two-tailed Wilcoxon rank sum test). Parkinsonian rest and essential postural tremor severity (i.e. tremor amplitude) differed in their relative tolerance to spontaneous changes in tremor frequency when stimulation was not applied. Specifically, the amplitude of parkinsonian rest tremor remained unchanged despite spontaneous changes in tremor frequency, whereas that of essential postural tremor reduced when tremor frequency departed from median values. Based on these results we conclude that parkinsonian rest tremor is driven by a neural network, which includes the subthalamic nucleus and ventrolateral thalamus and has broad frequency-amplitude tolerance. We propose that it is this tolerance to changes in tremor frequency that dictates that parkinsonian rest tremor may be significantly entrained by low frequency stimulation without stimulation timing-dependent amplitude modulation. In contrast, the circuit influenced by low frequency thalamic stimulation in essential tremor has a narrower frequency-amplitude tolerance so that tremor entrainment through extrinsic driving is necessarily accompanied by amplitude modulation. Such differences in parkinsonian rest and essential tremor will be important in selecting future strategies for closed loop deep brain stimulation for tremor control. PMID:25200741

Association of Thalamic Dysconnectivity and Conversion to Psychosis in Youth and Young Adults at Elevated Clinical Risk

PubMed Central

Anticevic, Alan; Haut, Kristen; Murray, John D.; Repovs, Grega; Yang, Genevieve J.; Diehl, Caroline; McEwen, Sarah C.; Bearden, Carrie E.; Addington, Jean; Goodyear, Bradley; Cadenhead, Kristin S.; Mirzakhanian, Heline; Cornblatt, Barbara A.; Olvet, Doreen; Mathalon, Daniel H.; McGlashan, Thomas H.; Perkins, Diana O.; Belger, Aysenil; Seidman, Larry J.; Tsuang, Ming T.; van Erp, Theo G. M.; Walker, Elaine F; Hamann, Stephan; Woods, Scott W; Qiu, Maolin; Cannon, Tyrone D.

2016-01-01

IMPORTANCE Severe neuropsychiatric conditions, such as schizophrenia, affect distributed neural computations. One candidate system profoundly altered in chronic schizophrenia involves the thalamocortical networks. It is widely acknowledged that schizophrenia is a neurodevelopmental disorder that likely affects the brain before onset of clinical symptoms. However, no investigation has tested whether thalamocortical connectivity is altered in individuals at risk for psychosis or whether this pattern is more severe in individuals who later develop full-blown illness. OBJECTIVES To determine whether baseline thalamocortical connectivity differs between individuals at clinical high risk for psychosis and healthy controls, whether this pattern is more severe in those who later convert to full-blown illness, and whether magnitude of thalamocortical dysconnectivity is associated with baseline prodromal symptom severity. DESIGN, SETTING, AND PARTICIPANTS In this multicenter, 2-year follow-up, case-control study, we examined 397 participants aged 12–35 years of age (243 individuals at clinical high risk of psychosis, of whom 21 converted to full-blown illness, and 154 healthy controls). The baseline scan dates were January 15, 2010, to April 30, 2012. MAIN OUTCOMES AND MEASURES Whole-brain thalamic functional connectivity maps were generated using individuals’ anatomically defined thalamic seeds, measured using resting-state functional connectivity magnetic resonance imaging. RESULTS Using baseline magnetic resonance images, we identified thalamocortical dysconnectivity in the 243 individuals at clinical high risk for psychosis, which was particularly pronounced in the 21 participants who converted to full-blown illness. The pattern involved widespread hypoconnectivity between the thalamus and prefrontal and cerebellar areas, which was more prominent in those who converted to full-blown illness (t173 = 3.77, P < .001, Hedge g = 0.88). Conversely, there was marked thalamic hyperconnectivity with sensory motor areas, again most pronounced in those who converted to full-blown illness (t173 = 2.85, P < .001, Hedge g = 0.66). Both patterns were significantly correlated with concurrent prodromal symptom severity (r = 0.27, P < 3.6 × 10−8, Spearman ρ = 0.27, P < 4.75 × 10−5, 2-tailed). CONCLUSIONS AND RELEVANCE Thalamic dysconnectivity, resembling that seen in schizophrenia, was evident in individuals at clinical high risk for psychosis and more prominently in those who later converted to psychosis. Dysconnectivity correlated with symptom severity, supporting the idea that thalamic connectivity may have prognostic implications for risk of conversion to full-blown illness. PMID:26267151

Thalamic Massa Intermedia Duplication in a Dysmorphic 14 month-old Toddler.

PubMed

Whitehead, Matthew T

2015-06-01

The massa intermedia is an inconstant parenchymal band connecting the medial thalami. It may be thickened in various disease processes such as Chiari II malformation or absent in other disease states. However, the massa intermedia may also be absent in up to 30% of normal human brains. To the best of my knowledge, detailed imaging findings of massa intermedia duplication have only been described in a single case report. An additional case of thalamic massa intermedia duplication discovered on a routine brain MR performed for dysmorphic facial features is reported herein.

Motor and cortico-striatal-thalamic connectivity alterations in intrauterine growth restriction.

PubMed

Eixarch, Elisenda; Muñoz-Moreno, Emma; Bargallo, Nuria; Batalle, Dafnis; Gratacos, Eduard

2016-06-01

Intrauterine growth restriction is associated with short- and long-term neurodevelopmental problems. Structural brain changes underlying these alterations have been described with the use of different magnetic resonance-based methods that include changes in whole structural brain networks. However, evaluation of specific brain circuits and its correlation with related functions has not been investigated in intrauterine growth restriction. In this study, we aimed to investigate differences in tractography-related metrics in cortico-striatal-thalamic and motor networks in intrauterine growth restricted children and whether these parameters were related with their specific function in order to explore its potential use as an imaging biomarker of altered neurodevelopment. We included a group of 24 intrauterine growth restriction subjects and 27 control subjects that were scanned at 1 year old; we acquired T1-weighted and 30 directions diffusion magnetic resonance images. Each subject brain was segmented in 93 regions with the use of anatomical automatic labeling atlas, and deterministic tractography was performed. Brain regions included in motor and cortico-striatal-thalamic networks were defined based in functional and anatomic criteria. Within the streamlines that resulted from the whole brain tractography, those belonging to each specific circuit were selected and tractography-related metrics that included number of streamlines, fractional anisotropy, and integrity were calculated for each network. We evaluated differences between both groups and further explored the correlation of these parameters with the results of socioemotional, cognitive, and motor scales from Bayley Scale at 2 years of age. Reduced fractional anisotropy (cortico-striatal-thalamic, 0.319 ± 0.018 vs 0.315 ± 0.015; P = .010; motor, 0.322 ± 0.019 vs 0.319 ± 0.020; P = .019) and integrity cortico-striatal-thalamic (0.407 ± 0.040 vs 0.399 ± 0.034; P = .018; motor, 0.417 ± 0.044 vs 0.409 ± 0.046; P = .016) in both networks were observed in the intrauterine growth restriction group, with no differences in number of streamlines. More importantly, strong specific correlation was found between tractography-related metrics and its relative function in both networks in intrauterine growth restricted children. Motor network metrics were correlated specifically with motor scale results (fractional anisotropy: rho = 0.857; integrity: rho = 0.740); cortico-striatal-thalamic network metrics were correlated with cognitive (fractional anisotropy: rho = 0.793; integrity, rho = 0.762) and socioemotional scale (fractional anisotropy: rho = 0.850; integrity: rho = 0.877). These results support the existence of altered brain connectivity in intrauterine growth restriction demonstrated by altered connectivity in motor and cortico-striatal-thalamic networks, with reduced fractional anisotropy and integrity. The specific correlation between tractography-related metrics and neurodevelopmental outcomes in intrauterine growth restriction shows the potential to use this approach to develop imaging biomarkers to predict specific neurodevelopmental outcome in infants who are at risk because of intrauterine growth restriction and other prenatal diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

Heterogeneity of cell firing properties and opioid sensitivity in the thalamic reticular nucleus.

PubMed

Brunton, J; Charpak, S

1997-05-01

The thalamic reticular nucleus receives afferents from the dorsal thalamus, cortex and brainstem, and projects back onto most cortically projecting thalamic nuclei thus playing a key role in the synchronization of the thalamocortical network. Although this nucleus was initially thought to consist of a homogeneous population of cells using GABA as a transmitter, and sharing identical intrinsic membrane properties, some heterogeneity was subsequently reported. The morphological diversity is generally acknowledged, but only two studies have shown functional differences between two classes of cells which vary in their ability to discharge in bursts. However, the location of the non-bursting cells was not characterized with anatomical techniques. Our recent work on the action of mu-opioid agonists in the thalamus revealed a widespread K+-mediated inhibition of most, if not all, thalamic relay and diffuse projection neurons. However, in the reticular nucleus, preliminary experiments suggested that the opioid sensitivity was variable. Based on these results and on observations of a discrete localization of mu-opioid receptors in the reticular nucleus, we investigated cellular heterogeneity within the nucleus using opioid agonists as markers. Using the whole cell patch clamp technique in young rat thalamic slices, we tested the responses of 28 neurons to opioids, the intrinsic membrane properties of each cell, and their relative location within the nucleus. Two types of intrinsic membrane properties underlying distinct discharge behaviours were seen in neurobiotin-labelled cells clearly located in the reticular nucleus: type I with the typical bursting behaviour previously reported in reticularis neurons, and type II in which bursting was greatly reduced or absent. Each class of cell could be further divided into subpopulations based on their opioid sensitivity. About half of both bursting (20) and non-bursting or tonic (8) cells were strongly inhibited by the mu-opioid receptor agonist D-Ala2,N-Me-Phe4,glycinol5-enkephalin, an effect mediated by an increase in K+ conductance. At no time was inhibition by delta- or kappa-receptor agonists seen. Our work therefore further demonstrates that the reticular nucleus is functionally heterogeneous, although the role of such cell diversity has still to be determined.

Thalamic and extrathalamic mechanisms of consciousness after severe brain injury.

PubMed

Lutkenhoff, Evan S; Chiang, Jeffrey; Tshibanda, Luaba; Kamau, Evelyn; Kirsch, Murielle; Pickard, John D; Laureys, Steven; Owen, Adrian M; Monti, Martin M

2015-07-01

What mechanisms underlie the loss and recovery of consciousness after severe brain injury? We sought to establish, in the largest cohort of patients with disorders of consciousness (DOC) to date, the link between gold standard clinical measures of awareness and wakefulness, and specific patterns of local brain pathology-thereby possibly providing a mechanistic framework for patient diagnosis, prognosis, and treatment development. Structural T1-weighted magnetic resonance images were collected, in a continuous sample of 143 severely brain-injured patients with DOC (and 96 volunteers), across 2 tertiary expert centers. Brain atrophy in subcortical regions (bilateral thalamus, basal ganglia, hippocampus, basal forebrain, and brainstem) was assessed across (1) healthy volunteers and patients, (2) clinical entities (eg, vegetative state, minimally conscious state), (3) clinical measures of consciousness (Coma Recovery Scale-Revised), and (4) injury etiology. Compared to volunteers, patients exhibited significant atrophy across all structures (p < 0.05, corrected). Strikingly, we found almost no significant differences across clinical entities. Nonetheless, the clinical measures of awareness and wakefulness upon which differential diagnosis rely were systematically associated with tissue atrophy within thalamic and basal ganglia nuclei, respectively; the basal forebrain was atrophied in proportion to patients' response to sensory stimulation. In addition, nontraumatic injuries exhibited more extensive thalamic atrophy. These findings provide, for the first time, a grounding in pathology for gold standard behavior-based clinical measures of consciousness, and reframe our current models of DOC by stressing the different links tying thalamic mechanisms to willful behavior and extrathalamic mechanisms to behavioral (and electrocortical) arousal. © 2015 American Neurological Association.

Asymmetric top-down modulation of ascending visual pathways in pigeons.

PubMed

Freund, Nadja; Valencia-Alfonso, Carlos E; Kirsch, Janina; Brodmann, Katja; Manns, Martina; Güntürkün, Onur

2016-03-01

Cerebral asymmetries are a ubiquitous phenomenon evident in many species, incl. humans, and they display some similarities in their organization across vertebrates. In many species the left hemisphere is associated with the ability to categorize objects based on abstract or experience-based behaviors. Using the asymmetrically organized visual system of pigeons as an animal model, we show that descending forebrain pathways asymmetrically modulate visually evoked responses of single thalamic units. Activity patterns of neurons within the nucleus rotundus, the largest thalamic visual relay structure in birds, were differently modulated by left and right hemispheric descending systems. Thus, visual information ascending towards the left hemisphere was modulated by forebrain top-down systems at thalamic level, while right thalamic units were strikingly less modulated. This asymmetry of top-down control could promote experience-based processes within the left hemisphere, while biasing the right side towards stimulus-bound response patterns. In a subsequent behavioral task we tested the possible functional impact of this asymmetry. Under monocular conditions, pigeons learned to discriminate color pairs, so that each hemisphere was trained on one specific discrimination. Afterwards the animals were presented with stimuli that put the hemispheres in conflict. Response patterns on the conflicting stimuli revealed a clear dominance of the left hemisphere. Transient inactivation of left hemispheric top-down control reduced this dominance while inactivation of right hemispheric top-down control had no effect on response patterns. Functional asymmetries of descending systems that modify visual ascending pathways seem to play an important role in the superiority of the left hemisphere in experience-based visual tasks. Copyright © 2015. Published by Elsevier Ltd.

Category specific dysnomia after thalamic infarction: a case-control study.

PubMed

Levin, Netta; Ben-Hur, Tamir; Biran, Iftah; Wertman, Eli

2005-01-01

Category specific naming impairment was described mainly after cortical lesions. It is thought to result from a lesion in a specific network, reflecting the organization of our semantic knowledge. The deficit usually involves multiple semantic categories whose profile of naming deficit generally obeys the animate/inanimate dichotomy. Thalamic lesions cause general semantic naming deficit, and only rarely a category specific semantic deficit for very limited and highly specific categories. We performed a case-control study on a 56-year-old right-handed man who presented with language impairment following a left anterior thalamic infarction. His naming ability and semantic knowledge were evaluated in the visual, tactile and auditory modalities for stimuli from 11 different categories, and compared to that of five controls. In naming to visual stimuli the patient performed poorly (error rate>50%) in four categories: vegetables, toys, animals and body parts (average 70.31+/-15%). In each category there was a different dominating error type. He performed better in the other seven categories (tools, clothes, transportation, fruits, electric, furniture, kitchen utensils), averaging 14.28+/-9% errors. Further analysis revealed a dichotomy between naming in animate and inanimate categories in the visual and tactile modalities but not in response to auditory stimuli. Thus, a unique category specific profile of response and naming errors to visual and tactile, but not auditory stimuli was found after a left anterior thalamic infarction. This might reflect the role of the thalamus not only as a relay station but further as a central integrator of different stages of perceptual and semantic processing.

Mental arithmetic leads to multiple discrete changes from baseline in the firing patterns of human thalamic neurons.

PubMed

Kim, J H; Ohara, S; Lenz, F A

2009-04-01

Primate thalamic action potential bursts associated with low-threshold spikes (LTS) occur during waking sensory and motor activity. We now test the hypothesis that different firing and LTS burst characteristics occur during quiet wakefulness (spontaneous condition) versus mental arithmetic (counting condition). This hypothesis was tested by thalamic recordings during the surgical treatment of tremor. Across all neurons and epochs, preburst interspike intervals (ISIs) were bimodal at median values, consistent with the duration of type A and type B gamma-aminobutyric acid inhibitory postsynaptic potentials. Neuronal spike trains (117 neurons) were categorized by joint ISI distributions into those firing as LTS bursts (G, grouped), firing as single spikes (NG, nongrouped), or firing as single spikes with sporadic LTS bursting (I, intermediate). During the spontaneous condition (46 neurons) only I spike trains changed category. Overall, burst rates (BRs) were lower and firing rates (FRs) were higher during the counting versus the spontaneous condition. Spike trains in the G category sometimes changed to I and NG categories at the transition from the spontaneous to the counting condition, whereas those in the I category often changed to NG. Among spike trains that did not change category by condition, G spike trains had lower BRs during counting, whereas NG spike trains had higher FRs. BRs were significantly greater than zero for G and I categories during wakefulness (both conditions). The changes between the spontaneous and counting conditions are most pronounced for the I category, which may be a transitional firing pattern between the bursting (G) and relay modes of thalamic firing (NG).

At the centre of neuronal, synaptic and axonal pathology in murine prion disease: degeneration of neuroanatomically linked thalamic and brainstem nuclei

PubMed Central

Reis, Renata; Hennessy, Edel; Murray, Caoimhe; Griffin, Éadaoin W.

2015-01-01

Aims The processes by which neurons degenerate in chronic neurodegenerative diseases remain unclear. Synaptic loss and axonal pathology frequently precede neuronal loss and protein aggregation demonstrably spreads along neuroanatomical pathways in many neurodegenerative diseases. The spread of neuronal pathology is less studied. Methods We previously demonstrated severe neurodegeneration in the posterior thalamus of multiple prion disease strains. Here we used the ME7 model of prion disease to examine the nature of this degeneration in the posterior thalamus and the major brainstem projections into this region. Results We objectively quantified neurological decline between 16 and 18 weeks post‐inoculation and observed thalamic subregion‐selective neuronal, synaptic and axonal pathology while demonstrating relatively uniform protease‐resistant prion protein (PrP) aggregation and microgliosis across the posterior thalamus. Novel amyloid precursor protein (APP) pathology was particularly prominent in the thalamic posterior (PO) and ventroposterior lateral (VPL) nuclei. The brainstem nuclei forming the major projections to these thalamic nuclei were examined. Massive neuronal loss in the PO was not matched by significant neuronal loss in the interpolaris (Sp5I), while massive synaptic loss in the ventral posteromedial nucleus (VPM) did correspond with significant neuronal loss in the principal trigeminal nucleus. Likewise, significant VPL synaptic loss was matched by significant neuronal loss in the gracile and cuneate nuclei. Conclusion These findings demonstrate significant spread of neuronal pathology from the thalamus to the brainstem in prion disease. The divergent neuropathological features in adjacent neuronal populations demonstrates that there are discrete pathways to neurodegeneration in different neuronal populations. PMID:25727649

Right medial thalamic lesion causes isolated retrograde amnesia.

PubMed

Miller, L A; Caine, D; Harding, A; Thompson, E J; Large, M; Watson, J D

2001-01-01

Pervasive retrograde amnesia without anterograde memory impairment has rarely been described as a consequence of circumscribed brain damage. We report this phenomenon in a 33 yr-old, right-handed man (JG) in association with the extension in the right thalamus of a previously small, bilateral thalamic lesion. JG presented with a dense amnesia for autobiographical material more than a few years old, with some sparing of recent memories. Furthermore, he was completely unable to recognise famous people or world events. Many other aspects of semantic knowledge were intact and there was no evidence of general intellectual impairment, executive dysfunction or loss of visual imagery. Magnetic resonance imaging revealed an acute lesion in the right thalamus and two small, symmetrical, bilateral non-acute thalamic lesions. Follow-up neuropsychological assessment indicated a stable pattern of impaired retrograde and spared anterograde memory over 18 months and psychiatric assessments yielded no evidence of confabulation, malingering or other symptoms to suggest psychogenic amnesia. JG's profile indicates that the division of declarative memory into just two categories - episodic and semantic - is inadequate. Rather, his case adds to the growing body evidence to suggest that world knowledge pertaining to people and events is stored or accessed similarly to autobiographical information and differently from other types of more general factual knowledge. We hypothesize that the right mediodorsal thalamic nucleus and immediately surrounding regions comprise the central processing mechanism referred to by McClelland (Revue Neurologique, 150 (1994) 570) and Markowitsch (Brain Research Review, 21 (1995) 117) as responsible for inducing and co-ordinating the recall of these sorts of cortically stored memory engrams.

Pre-stimulus thalamic theta power predicts human memory formation.

PubMed

Sweeney-Reed, Catherine M; Zaehle, Tino; Voges, Jürgen; Schmitt, Friedhelm C; Buentjen, Lars; Kopitzki, Klaus; Richardson-Klavehn, Alan; Hinrichs, Hermann; Heinze, Hans-Jochen; Knight, Robert T; Rugg, Michael D

2016-09-01

Pre-stimulus theta (4-8Hz) power in the hippocampus and neocortex predicts whether a memory for a subsequent event will be formed. Anatomical studies reveal thalamus-hippocampal connectivity, and lesion, neuroimaging, and electrophysiological studies show that memory processing involves the dorsomedial (DMTN) and anterior thalamic nuclei (ATN). The small size and deep location of these nuclei have limited real-time study of their activity, however, and it is unknown whether pre-stimulus theta power predictive of successful memory formation is also found in these subcortical structures. We recorded human electrophysiological data from the DMTN and ATN of 7 patients receiving deep brain stimulation for refractory epilepsy. We found that greater pre-stimulus theta power in the right DMTN was associated with successful memory encoding, predicting both behavioral outcome and post-stimulus correlates of successful memory formation. In particular, significant correlations were observed between right DMTN theta power and both frontal theta and right ATN gamma (32-50Hz) phase alignment, and frontal-ATN theta-gamma cross-frequency coupling. We draw the following primary conclusions. Our results provide direct electrophysiological evidence in humans of a role for the DMTN as well as the ATN in memory formation. Furthermore, prediction of subsequent memory performance by pre-stimulus thalamic oscillations provides evidence that post-stimulus differences in thalamic activity that index successful and unsuccessful encoding reflect brain processes specifically underpinning memory formation. Finally, the findings broaden the understanding of brain states that facilitate memory encoding to include subcortical as well as cortical structures. Copyright © 2016 Elsevier Inc. All rights reserved.

The role of the first postmitotic cortical cells in the development of thalamocortical innervation in the reeler mouse.

PubMed

Molnár, Z; Adams, R; Goffinet, A M; Blakemore, C

1998-08-01

In the mutant mouse reeler, the tangential distribution of thalamocortical fibers is essentially normal, even though neurons of the cortical plate accumulate below the entire early-born preplate population (Caviness et al., 1998). This seems incompatible with the hypothesis that cells of the subplate (the lower component of the preplate in normal mammals) form an axonal scaffold that guides thalamic fibers and act as temporary targets for them (Blakemore and Molnár, 1990, Shatz et al., 1990). We used carbocyanine dyes to trace projections in wild-type and reeler mice between embryonic day 13 and postnatal day 3. Preplate formation and early extension of corticofugal fibers to form a topographic array are indistinguishable in the two phenotypes. So too are the emergence of thalamic axons in topographic order through the primitive internal capsule, their meeting with preplate axons, and their distribution over the preplate scaffold. Distinctive differences appear after the cortical plate begins to accumulate below the preplate of reeler, causing the preplate axons to form oblique fascicles, running through the cortical plate. Thalamic axons then pass through the plate within the same fascicles and accumulate in the "superplate" layer for approximately 2-3 d, before defasciculating and plunging down to terminate deep in the cortical plate, creating the curious "looping" pattern seen in the adult. Thus, thalamocortical innervation in reeler follows the same algorithm of development but in relation to the misplaced population of early-born neurons. Far from challenging the theory that preplate fibers guide thalamic axons, reeler provides strong evidence for it.

Network and neuronal membrane properties in hybrid networks reciprocally regulate selectivity to rapid thalamocortical inputs.

PubMed

Pesavento, Michael J; Pinto, David J

2012-11-01

Rapidly changing environments require rapid processing from sensory inputs. Varying deflection velocities of a rodent's primary facial vibrissa cause varying temporal neuronal activity profiles within the ventral posteromedial thalamic nucleus. Local neuron populations in a single somatosensory layer 4 barrel transform sparsely coded input into a spike count based on the input's temporal profile. We investigate this transformation by creating a barrel-like hybrid network with whole cell recordings of in vitro neurons from a cortical slice preparation, embedding the biological neuron in the simulated network by presenting virtual synaptic conductances via a conductance clamp. Utilizing the hybrid network, we examine the reciprocal network properties (local excitatory and inhibitory synaptic convergence) and neuronal membrane properties (input resistance) by altering the barrel population response to diverse thalamic input. In the presence of local network input, neurons are more selective to thalamic input timing; this arises from strong feedforward inhibition. Strongly inhibitory (damping) network regimes are more selective to timing and less selective to the magnitude of input but require stronger initial input. Input selectivity relies heavily on the different membrane properties of excitatory and inhibitory neurons. When inhibitory and excitatory neurons had identical membrane properties, the sensitivity of in vitro neurons to temporal vs. magnitude features of input was substantially reduced. Increasing the mean leak conductance of the inhibitory cells decreased the network's temporal sensitivity, whereas increasing excitatory leak conductance enhanced magnitude sensitivity. Local network synapses are essential in shaping thalamic input, and differing membrane properties of functional classes reciprocally modulate this effect.

Sleep Spindles Are Related to Schizotypal Personality Traits and Thalamic Glutamine/Glutamate in Healthy Subjects

PubMed Central

Lustenberger, Caroline; O’Gorman, Ruth L.; Pugin, Fiona; Tüshaus, Laura; Wehrle, Flavia; Achermann, Peter; Huber, Reto

2015-01-01

Background: Schizophrenia is a severe mental disorder affecting approximately 1% of the worldwide population. Yet, schizophrenia-like experiences (schizotypy) are very common in the healthy population, indicating a continuum between normal mental functioning and the psychosis found in schizophrenic patients. A continuum between schizotypy and schizophrenia would be supported if they share the same neurobiological origin. Two such neurobiological markers of schizophrenia are: (1) a reduction of sleep spindles (12–15 Hz oscillations during nonrapid eye movement sleep), likely reflecting deficits in thalamo-cortical circuits and (2) increased glutamine and glutamate (Glx) levels in the thalamus. Thus, this study aimed to investigate whether sleep spindles and Glx levels are related to schizotypal personality traits in healthy subjects. Methods: Twenty young male subjects underwent 2 all-night sleep electroencephalography recordings (128 electrodes). Sleep spindles were detected automatically. After those 2 nights, thalamic Glx levels were measured by magnetic resonance spectroscopy. Subjects completed a magical ideation scale to assess schizotypy. Results: Sleep spindle density was negatively correlated with magical ideation (r = −.64, P < .01) and thalamic Glx levels (r = −.70, P < .005). No correlation was found between Glx levels in the thalamus and magical ideation (r = .12, P > .1). Conclusions: The common relationship of sleep spindle density with schizotypy and thalamic Glx levels indicates a neurobiological overlap between nonclinical schizotypy and schizophrenia. Thus, sleep spindle density and magical ideation may reflect the anatomy and efficiency of the thalamo-cortical system that shows pronounced impairment in patients with schizophrenia. PMID:25074975

Diffusion tensor imaging in children with tuberous sclerosis complex: tract-based spatial statistics assessment of brain microstructural changes.

PubMed

Zikou, Anastasia K; Xydis, Vasileios G; Astrakas, Loukas G; Nakou, Iliada; Tzarouchi, Loukia C; Tzoufi, Meropi; Argyropoulou, Maria I

2016-07-01

There is evidence of microstructural changes in normal-appearing white matter of patients with tuberous sclerosis complex. To evaluate major white matter tracts in children with tuberous sclerosis complex using tract-based spatial statistics diffusion tensor imaging (DTI) analysis. Eight children (mean age ± standard deviation: 8.5 ± 5.5 years) with an established diagnosis of tuberous sclerosis complex and 8 age-matched controls were studied. The imaging protocol consisted of T1-weighted high-resolution 3-D spoiled gradient-echo sequence and a spin-echo, echo-planar diffusion-weighted sequence. Differences in the diffusion indices were evaluated using tract-based spatial statistics. Tract-based spatial statistics showed increased axial diffusivity in the children with tuberous sclerosis complex in the superior and anterior corona radiata, the superior longitudinal fascicle, the inferior fronto-occipital fascicle, the uncinate fascicle and the anterior thalamic radiation. No significant differences were observed in fractional anisotropy, mean diffusivity and radial diffusivity between patients and control subjects. No difference was found in the diffusion indices between the baseline and follow-up examination in the patient group. Patients with tuberous sclerosis complex have increased axial diffusivity in major white matter tracts, probably related to reduced axonal integrity.

Lesion of the Centromedian Thalamic Nucleus in MPTP-Treated Monkeys

PubMed Central

Lanciego, Jose L.; Rodríguez-Oroz, Maria C.; Blesa, Francisco J.; Alvarez-Erviti, Lydia; Guridi, Jorge; Barroso-Chinea, Pedro; Smith, Yoland; Obeso, Jose A.

2015-01-01

The caudal intralaminar nuclei are a major source of glutamatergic afferents to the basal ganglia. Experiments in the 6-hydroxydopamine rat model have shown that the parafascicular nucleus is overactive and its lesion alleviates basal ganglia neurochemical abnormalities associated with dopamine depletion. Accordingly, removal of this excitatory innervation of the basal ganglia could have a beneficial value in the parkinsonian state. To test this hypothesis, unilateral kainate-induced chemical ablation of the centromedian thalamic nucleus (CM) has been performed in MPTP-treated monkeys. Successful lesions restricted to the CM boundaries (n = 2) without spreading over other neighboring thalamic nuclei showed an initial, short-lasting, and mild change in the parkinsonian motor scale but no effect against levodopa-induced dyskinesias. The lack of significant and persistent motor improvement leads us to conclude that unilateral selective lesion of the CM alone cannot be considered as a suitable surgical approach for the treatment of PD or levo-dopa-induced dyskinesias. The role of the caudal intralaminar nuclei in the pathophysiology of movement disorders of basal ganglia origin remains to be clarified. PMID:18175345

Multisensory connections of monkey auditory cerebral cortex

PubMed Central

Smiley, John F.; Falchier, Arnaud

2009-01-01

Functional studies have demonstrated multisensory responses in auditory cortex, even in the primary and early auditory association areas. The features of somatosensory and visual responses in auditory cortex suggest that they are involved in multiple processes including spatial, temporal and object-related perception. Tract tracing studies in monkeys have demonstrated several potential sources of somatosensory and visual inputs to auditory cortex. These include potential somatosensory inputs from the retroinsular (RI) and granular insula (Ig) cortical areas, and from the thalamic posterior (PO) nucleus. Potential sources of visual responses include peripheral field representations of areas V2 and prostriata, as well as the superior temporal polysensory area (STP) in the superior temporal sulcus, and the magnocellular medial geniculate thalamic nucleus (MGm). Besides these sources, there are several other thalamic, limbic and cortical association structures that have multisensory responses and may contribute cross-modal inputs to auditory cortex. These connections demonstrated by tract tracing provide a list of potential inputs, but in most cases their significance has not been confirmed by functional experiments. It is possible that the somatosensory and visual modulation of auditory cortex are each mediated by multiple extrinsic sources. PMID:19619628

The relation between persistent coma and brain ischemia after severe brain injury.

PubMed

Cheng, Quan; Jiang, Bing; Xi, Jian; Li, Zhen Yan; Liu, Jin Fang; Wang, Jun Yu

2013-12-01

To investigate the relation between brain ischemia and persistent vegetative state after severe traumatic brain injury. The 66 patients with severe brain injury were divided into two groups: The persistent coma group (coma duration ≥10 d) included 51 patients who had an admission Glasgow Coma Scale (GCS) of 5-8 and were unconscious for more than 10 d. There were 15 patients in the control group, their admission GCS was 5-8, and were unconscious for less than 10 d. The brain areas, including frontal, parietal, temporal, occipital lobes and thalamus, were measured by Single Photon Emission Computed Tomography (SPECT). In the first SPECT scan, multiple areas of cerebral ischemia were documented in all patients in both groups, whereas bilateral thalamic ischemia were presented in all patients in the persistent coma group and were absented in the control group. In the second SPECT scan taken during the period of analepsia, with an indication that unilateral thalamic ischemia were persisted in 28 of 41 patients in persistent coma group(28/41,68.29%). Persistent coma after severe brain injury is associated with bilateral thalamic ischemia.

Central thalamic deep brain stimulation for support of forebrain arousal regulation in the minimally conscious state.

PubMed

Schiff, Nicholas D

2013-01-01

This chapter considers the use of central thalamic deep brain stimulation (CT/DBS) to support arousal regulation mechanisms in the minimally conscious state (MCS). CT/DBS for selected patients in a MCS is first placed in the historical context of prior efforts to use thalamic electrical brain stimulation to treat the unconscious clinical conditions of coma and vegetative state. These previous studies and a proof of concept result from a single-subject study of a patient in a MCS are reviewed against the background of new population data providing benchmarks of the natural history of vegetative and MCSs. The conceptual foundations for CT/DBS in selected patients in a MCS are then presented with consideration of both circuit and cellular mechanisms underlying recovery of consciousness identified from empirical studies. Directions for developing future generalizable criteria for CT/DBS that focus on the integrity of necessary brain systems and behavioral profiles in patients in a MCS that may optimally response to support of arousal regulation mechanisms are proposed. © 2013 Elsevier B.V. All rights reserved.

Olfactory mechanisms in the control of maternal aggression, appetite, and fearfulness: effects of lesions to olfactory receptors, mediodorsal thalamic nucleus, and insular prefrontal cortex.

PubMed

Ferreira, A; Dahlöf, L G; Hansen, S

1987-10-01

During lactation the female rat is hyperphagic, aggressive toward adult conspecifics, and less fearful than usual. In the first experiment the importance of olfactory receptors was investigated by surgically removing the olfactory epithelium of the nasal cavity. Mother rats subjected to this treatment consumed significantly less food and weighed less than sham-operated females. Moreover, experimental subjects displayed a dramatic decrease in maternal aggression. Fear behavior (sound-elicited freezing), on the other hand, was not affected by the lesions. The mediodorsal thalamic nucleus and the prefrontal insular cortex form part of the central olfactory system. The second experiment assessed the involvement of this olfactory-related thalamocortical system and the behavioral profile of mother rats. It was found that whereas the thalamic and cortical lesions left food intake and fear behavior unaffected, they significantly decreased the frequency with which the mother would attack an intruder male placed into her home cage. The sense of smell appears, according to the present experiments, to play a crucial role in maternal aggression.

Thalamic nuclei convey diverse contextual information to layer 1 of visual cortex

PubMed Central

Imhof, Fabia; Martini, Francisco J.; Hofer, Sonja B.

2017-01-01

Sensory perception depends on the context within which a stimulus occurs. Prevailing models emphasize cortical feedback as the source of contextual modulation. However, higher-order thalamic nuclei, such as the pulvinar, interconnect with many cortical and subcortical areas, suggesting a role for the thalamus in providing sensory and behavioral context – yet the nature of the signals conveyed to cortex by higher-order thalamus remains poorly understood. Here we use axonal calcium imaging to measure information provided to visual cortex by the pulvinar equivalent in mice, the lateral posterior nucleus (LP), as well as the dorsolateral geniculate nucleus (dLGN). We found that dLGN conveys retinotopically precise visual signals, while LP provides distributed information from the visual scene. Both LP and dLGN projections carry locomotion signals. However, while dLGN inputs often respond to positive combinations of running and visual flow speed, LP signals discrepancies between self-generated and external visual motion. This higher-order thalamic nucleus therefore conveys diverse contextual signals that inform visual cortex about visual scene changes not predicted by the animal’s own actions. PMID:26691828

The Emotional Gatekeeper: A Computational Model of Attentional Selection and Suppression through the Pathway from the Amygdala to the Inhibitory Thalamic Reticular Nucleus

PubMed Central

Bullock, Daniel; Barbas, Helen

2016-01-01

In a complex environment that contains both opportunities and threats, it is important for an organism to flexibly direct attention based on current events and prior plans. The amygdala, the hub of the brain's emotional system, is involved in forming and signaling affective associations between stimuli and their consequences. The inhibitory thalamic reticular nucleus (TRN) is a hub of the attentional system that gates thalamo-cortical signaling. In the primate brain, a recently discovered pathway from the amygdala sends robust projections to TRN. Here we used computational modeling to demonstrate how the amygdala-TRN pathway, embedded in a wider neural circuit, can mediate selective attention guided by emotions. Our Emotional Gatekeeper model demonstrates how this circuit enables focused top-down, and flexible bottom-up, allocation of attention. The model suggests that the amygdala-TRN projection can serve as a unique mechanism for emotion-guided selection of signals sent to cortex for further processing. This inhibitory selection mechanism can mediate a powerful affective ‘framing’ effect that may lead to biased decision-making in highly charged emotional situations. The model also supports the idea that the amygdala can serve as a relevance detection system. Further, the model demonstrates how abnormal top-down drive and dysregulated local inhibition in the amygdala and in the cortex can contribute to the attentional symptoms that accompany several neuropsychiatric disorders. PMID:26828203

Targeting brain-derived neurotrophic factor in the medial thalamus for the treatment of central poststroke pain in a rodent model.

PubMed

Shih, Hsi-Chien; Kuan, Yung-Hui; Shyu, Bai-Chung

2017-07-01

Approximately 7% to 10% of patients develop a chronic pain syndrome after stroke. This chronic pain condition is called central poststroke pain (CPSP). Recent studies have observed an abnormal increase in the secretion of brain-derived neurotrophic factor (BDNF) in spinal cord tissue after spinal cord injury. An animal model of CPSP was established by an intrathalamus injection of collagenase. Mechanical and thermal allodynia was induced after lesions of the thalamic ventral basal complex in rats. Four weeks after the injection, the number of neurons decreased, the number of astrocytes, microglia, and P2X4 receptors increased, and BDNF mRNA expression increased in the brain lesion area. Nociceptive activity in the medial thalamus (MT) and the coherence coefficient of spontaneous field potential oscillations in the anterior cingulate cortex were enhanced in CPSP animals, and these enhancements were blocked by an acute injection of TrkB-Fc and TrkB antagonist Tat Cyclotraxin-B. Instead of being inhibited by the γ-aminobutyric acid (GABA) system in normal rats, multiunit activity in the MT was enhanced after a microinjection of muscimol, a GABAA receptor agonist, in CPSP animals. After CPSP, BDNF expression was enhanced in the MT, whereas the expression of GABAA channels and the cotransporter KCC2 decreased in the same area. These findings suggest that neuronal plasticity in the MT that was induced by BDNF overexpression after the thalamic lesion was a key factor in CPSP.

Frequency organization and responses to complex sounds in the medial geniculate body of the mustached bat.

PubMed

Wenstrup, J J

1999-11-01

The auditory cortex of the mustached bat (Pteronotus parnellii) displays some of the most highly developed physiological and organizational features described in mammalian auditory cortex. This study examines response properties and organization in the medial geniculate body (MGB) that may contribute to these features of auditory cortex. About 25% of 427 auditory responses had simple frequency tuning with single excitatory tuning curves. The remainder displayed more complex frequency tuning using two-tone or noise stimuli. Most of these were combination-sensitive, responsive to combinations of different frequency bands within sonar or social vocalizations. They included FM-FM neurons, responsive to different harmonic elements of the frequency modulated (FM) sweep in the sonar signal, and H1-CF neurons, responsive to combinations of the bat's first sonar harmonic (H1) and a higher harmonic of the constant frequency (CF) sonar signal. Most combination-sensitive neurons (86%) showed facilitatory interactions. Neurons tuned to frequencies outside the biosonar range also displayed combination-sensitive responses, perhaps related to analyses of social vocalizations. Complex spectral responses were distributed throughout dorsal and ventral divisions of the MGB, forming a major feature of this bat's analysis of complex sounds. The auditory sector of the thalamic reticular nucleus also was dominated by complex spectral responses to sounds. The ventral division was organized tonotopically, based on best frequencies of singly tuned neurons and higher best frequencies of combination-sensitive neurons. Best frequencies were lowest ventrolaterally, increasing dorsally and then ventromedially. However, representations of frequencies associated with higher harmonics of the FM sonar signal were reduced greatly. Frequency organization in the dorsal division was not tonotopic; within the middle one-third of MGB, combination-sensitive responses to second and third harmonic CF sonar signals (60-63 and 90-94 kHz) occurred in adjacent regions. In the rostral one-third, combination-sensitive responses to second, third, and fourth harmonic FM frequency bands predominated. These FM-FM neurons, thought to be selective for delay between an emitted pulse and echo, showed some organization of delay selectivity. The organization of frequency sensitivity in the MGB suggests a major rewiring of the output of the central nucleus of the inferior colliculus, by which collicular neurons tuned to the bat's FM sonar signals mostly project to the dorsal, not the ventral, division. Because physiological differences between collicular and MGB neurons are minor, a major role of the tecto-thalamic projection in the mustached bat may be the reorganization of responses to provide for cortical representations of sonar target features.

Thalamic Ventral Intermediate Nucleus Deep Brain Stimulation for Orthostatic Tremor.

PubMed

Lehn, Alexander C; O'Gorman, Cullen; Olson, Sarah; Salari, Mehri

2017-01-01

Orthostatic tremor (OT) was first described in 1977. It is characterized by rapid tremor of 13-18 Hz and can be recorded in the lower limbs and trunk muscles. OT remains difficult to treat, although some success has been reported with deep brain stimulation (DBS). We report a 68-year-old male with OT who did not improve significantly after bilateral thalamic stimulation. Although some patients were described who improved after DBS surgery, more information is needed about the effect of these treatment modalities on OT, ideally in the form of randomized trial data.

The role of the parafascicular complex (CM-Pf) of the human thalamus in the neuronal mechanisms of selective attention.

PubMed

Raeva, S N

2006-03-01

The reactions of 93 neurons in the parafascicular complex (CM-Pf) of the human thalamus were studied by microelectrode recording during stereotaxic neurosurgical operations in patients with spastic torticollis. High reactivity was demonstrated for two previously classified types of neurons with identical irregular (type A) and bursting Ca2+ -dependent (type B) activities in response to presentation of relevant verbal stimuli evoking selective attention in humans. Concordant changes in the network activity of A and B neurons were observed, in the form of linked activatory-inhibitory patterns of responses and the appearance, at the moment of presentation of an imperative morpheme of the command stimulus, of rapidly occurring intercellular interactions consisting of local synchronization with simultaneously developing rhythmic oscillatory (3-4 Hz) activity. Data are presented on the existence of a direct connection between these neuronal rearrangements and activation of selective attention, providing evidence for the involvement of the thalamic parafascicular complex (CM-Pf) in the mechanisms of selective attention and processing of relevant verbal information during the preparative period of voluntary actions.

Differential Impact of Multiple Sclerosis on Cortical and Deep Gray Matter Structures in African Americans and Caucasian Americans.

PubMed

Al-Kawaz, Mais; Monohan, Elizabeth; Morris, Eric; Perumal, Jai S; Nealon, Nancy; Vartanian, Timothy; Gauthier, Susan A

2017-05-01

African Americans with multiple sclerosis (AAwMS) have different disease phenotypes when compared to Caucasians Americans with MS (CAwMS). The pathologic basis of this difference in disease presentation is unknown. Fifty-Four AAwMS and 54 CAwMS were appropriately matched for age, gender, treatment duration, and disease duration. FreeSurfer was used to segment brain white matter and gray matter from T1 images and compute thalamic volume. Regional cortical thickness was calculated using QDEC. The 2 matched cohorts differed in disability, with AAwMS demonstrating significantly higher EDSS scores (2.3±2.2 vs. 1.3±1.5, P < .009), yet the 2 populations had similar T2 hyperintense lesion volumes (P = .35). AAwMS had a significantly lower total global cortical thickness when compared to CAwMS (P = .03). Controlling for EDSS, AAwMS showed multiple cortical regions to be significantly thinner than CAwMS; these included areas within the temporal, parietal and occipital lobes, as well as the precentral and postcentral gyrus. Middletemporal cortex was most affected in AAwMS in the left hemisphere (P = .009), while the superiortemporal cortex was most affected in the right hemisphere (P = .0001). In contrast, thalamic volume was significantly reduced in CAwMS when compared to AAwMS (P = .01). In both groups, worse disability was associated with lower total thalamic volume percentage. AAwMS and CAwMS patients differ with regard to global and regional cortical thickness and thalamic volume. This diverging pattern of gray matter volumetrics among otherwise matched patients suggests that racial-specific disease differences may exist. Copyright © 2016 by the American Society of Neuroimaging.

The role of the thalamic nuclei in recognition memory accompanied by recall during encoding and retrieval: an fMRI study.

PubMed

Pergola, Giulio; Ranft, Alexander; Mathias, Klaus; Suchan, Boris

2013-07-01

The present functional imaging study aimed at investigating the contribution of the mediodorsal nucleus and the anterior nuclei of the thalamus with their related cortical networks to recognition memory and recall. Eighteen subjects performed associative picture encoding followed by a single item recognition test during the functional magnetic resonance imaging session. After scanning, subjects performed a cued recall test using the formerly recognized pictures as cues. This post-scanning test served to classify recognition trials according to subsequent recall performance. In general, single item recognition accompanied by successful recall of the associations elicited stronger activation in the mediodorsal nucleus of the thalamus and in the prefrontal cortices both during encoding and retrieval compared to recognition without recall. In contrast, the anterior nuclei of the thalamus were selectively active during the retrieval phase of recognition followed by recall. A correlational analysis showed that activation of the anterior thalamus during retrieval as assessed by measuring the percent signal changes predicted lower rates of recognition without recall. These findings show that the thalamus is critical for recognition accompanied by recall, and provide the first evidence of a functional segregation of the thalamic nuclei with respect to the memory retrieval phase. In particular, the mediodorsal thalamic-prefrontal cortical network is activated during successful encoding and retrieval of associations, which suggests a role of this system in recall and recollection. The activity of the anterior thalamic-temporal network selectively during retrieval predicts better memory performances across subjects and this confirms the paramount role of this network in recall and recollection. Copyright © 2013 Elsevier Inc. All rights reserved.

Intrinsic development of choroidal and thalamic collaterals in hemorrhagic-onset moyamoya disease: case-control study of the Japan Adult Moyamoya Trial.

PubMed

Fujimura, Miki; Funaki, Takeshi; Houkin, Kiyohiro; Takahashi, Jun C; Kuroda, Satoshi; Tomata, Yasutake; Tominaga, Teiji; Miyamoto, Susumu

2018-05-04

OBJECTIVE This study was performed to identify the angiographic features of hemorrhagic-onset moyamoya disease (MMD) in comparison with those of patients with ischemic-onset MMD. METHODS This case-control study compared the data set of the Japan Adult Moyamoya (JAM) Trial with the angiographic data of adult patients with ischemic-onset MMD. The authors analyzed angiograms obtained at onset, classifying the collaterals into 3 subtypes: lenticulostriate anastomosis, thalamic anastomosis, and choroidal anastomosis. They then compared the extent of these collaterals, as indicated by the collateral development grade from 0 to 2 in each subtype, between the JAM Trial group and the ischemic-onset group. They also compared the involvement of the posterior cerebral artery (PCA) and Suzuki's angiographic staging between each group. RESULTS Among 89 ischemic-onset patients, 103 symptomatic hemispheres in 80 patients were analyzed and compared with 75 hemorrhagic hemispheres from the JAM Trial. The hemorrhagic-onset patients showed a significantly higher proportion of thalamic anastomosis (p = 0.043) and choroidal anastomosis (< 0.001), as indicated by grade 2 in each subtype, compared with ischemic-onset patients. Suzuki's angiographic staging was significantly higher in the hemorrhagic group (< 0.038). There was no difference in the extent of lenticulostriate anastomosis and PCA involvement between the groups. CONCLUSIONS In adult MMD, the characteristic pattern of the abnormal vascular networks at the base of the brain is different between each onset type. In light of the more prominent development of thalamic and choroidal anastomosis in the JAM Trial group in the present study, development of these collaterals, especially the choroidal collateral extending beyond the lateral ventricle, may play a critical role in hemorrhagic presentation in MMD. Clinical trial registration no. C000000166 ( http://www.umin.ac.jp/ctr/index.htm ).

Low thalamic NAA-concentration corresponds to strong neural activation in working memory in Kleine-Levin syndrome.

PubMed

Vigren, Patrick; Tisell, Anders; Engström, Maria; Karlsson, Thomas; Leinhard Dahlqvist, Olof; Lundberg, Peter; Landtblom, Anne-Marie

2013-01-01

Kleine Levin Syndrome (KLS) is a rare disorder of periodic hypersomnia and behavioural disturbances in young individuals. It has previously been shown to be associated with disturbances of working memory (WM), which, in turn, was associated with higher activation of the thalamus with increasing WM load, demonstrated with functional magnetic resonance imaging (fMRI). In this study we aimed to further elucidate how these findings are related to the metabolism of the thalamus. fMRI and magnetic resonance spectroscopy were applied while performing a WM task. Standard metabolites were examined: n-acetylaspartate (NAA), myo-inositol, choline, creatine and glutamate-glutamine. Fourteen KLS-patients and 15 healthy controls participated in the study. The patients with active disease were examined in asymptomatic periods. There was a statistically significant negative correlation between thalamic fMRI-activation and thalamic NAA, i.e., high fMRI-activation corresponded to low NAA-levels. This correlation was not seen in healthy controls. Thalamic levels of NAA in patients and controls showed no significant differences between the groups. None of the other metabolites showed any co-variation with fMRI-activation. This study shows negative correlation between NAA-levels and fMRI-activity in the left thalamus of KLS-patients while performing a WM task. This correlation could not be found in healthy control subjects, primarily interpreted as an effect of increased effort in the patient group upon performing the task. It might indicate a disturbance in the neuronal networks responsible for WM in KLS patients, resulting in higher effort at lower WM load, compared with healthy subjects. The general relationship between NAA and BOLD-signal is also discussed in the article.

Abnormal functional integration of thalamic low frequency oscillation in the BOLD signal after acute heroin treatment.

PubMed

Denier, Niklaus; Schmidt, André; Gerber, Hana; Vogel, Marc; Huber, Christian G; Lang, Undine E; Riecher-Rossler, Anita; Wiesbeck, Gerhard A; Radue, Ernst-Wilhelm; Walter, Marc; Borgwardt, Stefan

2015-12-01

Heroin addiction is a severe relapsing brain disorder associated with impaired cognitive control, including deficits in attention allocation. The thalamus has a high density of opiate receptors and is critically involved in orchestrating cortical activity during cognitive control. However, there have been no studies on how acute heroin treatment modulates thalamic activity. In a cross-over, double-blind, vehicle-controlled study, 29 heroin-maintained outpatients were studied after heroin and placebo administration, while 20 healthy controls were included for the placebo condition only. Resting-state functional magnetic resonance imaging was used to analyze functional integration of the thalamus by three different resting state analysis techniques. Thalamocortical functional connectivity (FC) was analyzed by seed-based correlation, while intrinsic thalamic oscillation was assessed by analysis of regional homogeneity (ReHo) and the fractional amplitude of low frequency fluctuations (fALFF). Relative to the placebo treatment and healthy controls, acute heroin administration reduced thalamocortical FC to cortical regions, including the frontal cortex, while the reductions in FC to the mediofrontal cortex, orbitofrontal cortex, and frontal pole were positively correlated with the plasma level of morphine, the main psychoactive metabolite of heroin. Furthermore, heroin treatment was associated with increased thalamic ReHo and fALFF values, whereas fALFF following heroin exposure correlated negatively with scores of attentional control. The heroin-associated increase in fALFF was mainly dominated by slow-4 (0.027-0.073 Hz) oscillations. Our findings show that there are acute effects of heroin within the thalamocortical system and may shed new light on the role of the thalamus in cognitive control in heroin addiction. Future research is needed to determine the underlying physiological mechanisms and their role in heroin addiction. © 2015 Wiley Periodicals, Inc.

Cortical thinness and volume differences associated with marijuana abuse in emerging adults.

PubMed

Mashhoon, Y; Sava, S; Sneider, J T; Nickerson, L D; Silveri, M M

2015-10-01

The prevalence of marijuana (MJ) use among youth and its legalization for medical or recreational use has intensified public health endeavors of understanding MJ effects on brain structure and function. Studies indicate that MJ use is related to impaired cognitive performance, and altered functional brain activation and chemistry in adolescents and adults, but MJ effects on brain morphology in emerging adults are less understood. Fifteen MJ users (age 21.8±3.6, 2 females) and 15 non-user (NU) participants (age 22.3±3.5, 2 females) were included, demographically matched on age, education and alcohol use. High-resolution structural MR images were acquired at 3Tesla. Cortical thickness (CT) and volumetric analyses were performed using Freesurfer. A priori regions of interest (ROI) included orbitofrontal and cingulate cortices, amygdala, hippocampus and thalamus. Whole brain CT analysis did not result in significant group differences in a priori ROIs but revealed MJ users had significantly less CT (i.e., thinness) in right fusiform gyrus (rFG) compared to NU (p<0.05). Thalamic volume was significantly smaller in MJ users compared to NU (right, p=0.05; left, p=0.01) and associated with greater non-planning (p<0.01) and overall impulsivity (p=0.04). There were no other group differences. RFG cortical thinness and smaller thalamic volume in emerging adults is associated with MJ abuse. Furthermore, smaller thalamic volume associated with greater impulsivity contributes to growing evidence that the thalamus is neurobiologically perturbed by MJ use. Collectively, altered thalamic and rFG structural integrity may interfere with their known roles in regulating visuoperceptual and object information processing. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Thalamic volume and related visual recognition are associated with freezing of gait in non-demented patients with Parkinson's disease.

PubMed

Sunwoo, Mun Kyung; Cho, Kyoo H; Hong, Jin Yong; Lee, Ji E; Sohn, Young H; Lee, Phil Hyu

2013-12-01

The pathophysiology of freezing of gait (FOG) in non-demented Parkinson's disease (PD) patients remains poorly understood. Recent studies have suggested that neurochemical alterations in the cholinergic systems play a role in the development of FOG. Here, we evaluated the association between subcortical cholinergic structures and FOG in patients with non-demented PD. We recruited 46 non-demented patients with PD, categorized into PD with (n = 16) and without FOG (n = 30) groups. We performed neuropsychological test, region-of-interest-based volumetric analysis of the substantia innominata (SI) and automatic analysis of subcortical brain structures using a computerized segmentation procedure. The comprehensive neuropsychological assessment showed that PD patients with FOG had lower cognitive performance in the frontal executive and visual-related functions compared with those without freezing of gait. The normalized SI volume did not differ significantly between the two groups (1.65 ± 0.18 vs. 1.68 ± 0.31). The automatic analysis of subcortical structures revealed that the thalamic volumes were significantly reduced in PD patients with FOG compared with those without FOG after adjusting for age, sex, disease duration, the Unified PD Rating Scale scores and total intracranial volume (left: 6.71 vs. 7.16 cm3, p = 0.029, right: 6.47 vs. 6.91 cm3, p = 0.026). Multiple linear regression analysis revealed that thalamic volume showed significant positive correlations with visual recognition memory (left: β = 0.441, p = 0.037, right: β = 0.498, p = 0.04). These data suggest that thalamic volume and related visual recognition, rather than the cortical cholinergic system arising from the SI, may be a major contributor to the development of freezing of gait in non-demented patients with PD. Copyright © 2013. Published by Elsevier Ltd.

The dusp1 Immediate Early Gene is Regulated by Natural Stimuli Predominantly in Sensory Input Neurons

PubMed Central

Horita, Haruhito; Wada, Kazuhiro; Rivas, Miriam V.; Hara, Erina; Jarvis, Erich D.

2010-01-01

Many immediate early genes (IEGs) have activity-dependent induction in a subset of brain subdivisions or neuron types. However, none have been reported yet with regulation specific to thalamic-recipient sensory neurons of the telencephalon or in the thalamic sensory input neurons themselves. Here, we report the first such gene, dual specificity phosphatase 1 (dusp1). Dusp1 is an inactivator of mitogen-activated protein kinase (MAPK), and MAPK activates expression of egr1, one of the most commonly studied IEGs, as determined in cultured cells. We found that in the brain of naturally behaving songbirds and other avian species, hearing song, seeing visual stimuli, or performing motor behavior caused high dusp1 upregulation, respectively, in auditory, visual, and somatosensory input cell populations of the thalamus and thalamic-recipient sensory neurons of the telencephalic pallium, whereas high egr1 upregulation occurred only in subsequently connected secondary and tertiary sensory neuronal populations of these same pathways. Motor behavior did not induce high levels of dusp1 expression in the motor-associated areas adjacent to song nuclei, where egr1 is upregulated in response to movement. Our analysis of dusp1 expression in mouse brain suggests similar regulation in the sensory input neurons of the thalamus and thalamic-recipient layer IV and VI neurons of the cortex. These findings suggest that dusp1 has specialized regulation to sensory input neurons of the thalamus and telencephalon; they further suggest that this regulation may serve to attenuate stimulus-induced expression of egr1 and other IEGs, leading to unique molecular properties of forebrain sensory input neurons. PMID:20506480

Intra- and interobserver agreement for fetal cerebral measurements in 3D-ultrasonography.

PubMed

Albers, Maria E W A; Buisman, Erato T I A; Kahn, René S; Franx, Arie; Onland-Moret, N Charlotte; de Heus, Roel

2018-04-10

The aim of this study is to evaluate intra- and interobserver agreement for measurement of intracranial, cerebellar, and thalamic volume with the Virtual Organ Computer-aided AnaLysis (VOCAL) technique in three-dimensional ultrasound images, in comparison to two-dimensional measurements of these brain structures. Three-dimensional ultrasound images of the brains of 80 fetuses at 20-24 weeks' gestational age were obtained from YOUth, a Dutch prospective cohort study. Two observers performed offline measurement of the occipitofrontal diameter, intracranial volume, transcerebellar diameter, cerebellar volume, and thalamic width, area, and volume, independently. VOCAL was used for calculation of the volumes. The two-way random, single measures intraclass correlation coefficient (ICC) was used for analysis of agreement and Bland-Altman plots were configured. Intra- and interobserver agreement was almost perfect for occipitofrontal diameter (intra ICC 0.88, 95% CI 0.82-0.92; inter ICC 0.91, 95% CI 0.85-0.94), intracranial volume (intra ICC 0.96, 95% CI 0.91-0.98; inter ICC 0.97, 95% CI 0.96-0.98) and transcerebellar diameter (intra ICC 0.91, 95% CI 0.86-0.94; inter ICC 0.86, 95% CI 0.78-0.910). For cerebellar volume, the intraobserver agreement was almost perfect (0.85, 95% CI 0.76-0.90), whereas the interobserver agreement was substantial (0.75, 95% CI 0.44-0.88). Agreement was only moderate for thalamic measurements. Bland-Altman plots for the volume measurements are normally distributed with acceptable mean differences and 95% limits of agreement. The intra- and interobserver agreement of the measurement of intracranial and cerebellar volume with VOCAL was almost perfect. These measurements are therefore reliable, and can be used to investigate fetal brain development. Thalamic measurements are not reliable enough. © 2018 Wiley Periodicals, Inc.

A computational relationship between thalamic sensory neural responses and contrast perception.

PubMed

Jiang, Yaoguang; Purushothaman, Gopathy; Casagrande, Vivien A

2015-01-01

Uncovering the relationship between sensory neural responses and perceptual decisions remains a fundamental problem in neuroscience. Decades of experimental and modeling work in the sensory cortex have demonstrated that a perceptual decision pool is usually composed of tens to hundreds of neurons, the responses of which are significantly correlated not only with each other, but also with the behavioral choices of an animal. Few studies, however, have measured neural activity in the sensory thalamus of awake, behaving animals. Therefore, it remains unclear how many thalamic neurons are recruited and how the information from these neurons is pooled at subsequent cortical stages to form a perceptual decision. In a previous study we measured neural activity in the macaque lateral geniculate nucleus (LGN) during a two alternative forced choice (2AFC) contrast detection task, and found that single LGN neurons were significantly correlated with the monkeys' behavioral choices, despite their relatively poor contrast sensitivity and a lack of overall interneuronal correlations. We have now computationally tested a number of specific hypotheses relating these measured LGN neural responses to the contrast detection behavior of the animals. We modeled the perceptual decisions with different numbers of neurons and using a variety of pooling/readout strategies, and found that the most successful model consisted of about 50-200 LGN neurons, with individual neurons weighted differentially according to their signal-to-noise ratios (quantified as d-primes). These results supported the hypothesis that in contrast detection the perceptual decision pool consists of multiple thalamic neurons, and that the response fluctuations in these neurons can influence contrast perception, with the more sensitive thalamic neurons likely to exert a greater influence.

Estimation of Thalamocortical and Intracortical Network Models from Joint Thalamic Single-Electrode and Cortical Laminar-Electrode Recordings in the Rat Barrel System

PubMed Central

Blomquist, Patrick; Devor, Anna; Indahl, Ulf G.; Ulbert, Istvan; Einevoll, Gaute T.; Dale, Anders M.

2009-01-01

A new method is presented for extraction of population firing-rate models for both thalamocortical and intracortical signal transfer based on stimulus-evoked data from simultaneous thalamic single-electrode and cortical recordings using linear (laminar) multielectrodes in the rat barrel system. Time-dependent population firing rates for granular (layer 4), supragranular (layer 2/3), and infragranular (layer 5) populations in a barrel column and the thalamic population in the homologous barreloid are extracted from the high-frequency portion (multi-unit activity; MUA) of the recorded extracellular signals. These extracted firing rates are in turn used to identify population firing-rate models formulated as integral equations with exponentially decaying coupling kernels, allowing for straightforward transformation to the more common firing-rate formulation in terms of differential equations. Optimal model structures and model parameters are identified by minimizing the deviation between model firing rates and the experimentally extracted population firing rates. For the thalamocortical transfer, the experimental data favor a model with fast feedforward excitation from thalamus to the layer-4 laminar population combined with a slower inhibitory process due to feedforward and/or recurrent connections and mixed linear-parabolic activation functions. The extracted firing rates of the various cortical laminar populations are found to exhibit strong temporal correlations for the present experimental paradigm, and simple feedforward population firing-rate models combined with linear or mixed linear-parabolic activation function are found to provide excellent fits to the data. The identified thalamocortical and intracortical network models are thus found to be qualitatively very different. While the thalamocortical circuit is optimally stimulated by rapid changes in the thalamic firing rate, the intracortical circuits are low-pass and respond most strongly to slowly varying inputs from the cortical layer-4 population. PMID:19325875

Organization of projections from the anterior pole of the nucleus reticularis thalami (NRT) to subdivisions of the motor thalamus: light and electron microscopic studies in the rhesus monkey.

PubMed

Ilinsky, I A; Ambardekar, A V; Kultas-Ilinsky, K

1999-07-05

Projections to the motor-related thalamic nuclei from the anterior pole of the reticular thalamic nucleus (NRT) were studied after injections of biotinylated dextran amine and wheat germ agglutinin conjugated horseradish peroxidase at light and electron microscopic levels, respectively. Each injection resulted in anterograde labeling in the three subdivisions of the ventral anterior nucleus (pars parvicellularis, VApc; pars densicellularis, VAdc; and pars magnocellularis, VAmc) and in the ventral lateral nucleus (VL). NRT fibers had beaded shapes and coursed in a posterior direction giving rise to relatively diffuse terminal plexuses. The average size of the beads (0.7 microm2) and their density per 100 microm of fiber length (23.7-25.7) were similar between the nuclei studied. At the electron microscopic level, anterogradely labeled boutons displayed positive immunoreactivity for gamma-aminobutyric acid (GABA), contained pleomorphic synaptic vesicles, and formed relatively long (approximately 0.4 microm) symmetric synaptic contacts. Usually, a single terminal formed synapses on more than one postsynaptic structure. Synaptic contacts were on projection and local circuit neurons and targeted mainly their distal dendrites. In the VAmc, synapses on local circuit neurons composed 48% of the total sample, in the VAdc/VApc and in the VL the proportion was higher, 65% and 62%, respectively. The results suggest that the input from the anterior pole of the monkey reticular nucleus to the motor-related thalamic nuclei is organized differently from what is known on the organization of connections of NRT with sensory thalamic nuclei in other species in that the terminal fields of individual fibers are diffuse rather than focal and that at least 50% of synapses are established on GABAergic local circuit neurons.

Prepatterning and patterning of the thalamus along embryonic development of Xenopus laevis

PubMed Central

Bandín, Sandra; Morona, Ruth; González, Agustín

2015-01-01

Previous developmental studies of the thalamus (alar part of the diencephalic prosomere p2) have defined the molecular basis for the acquisition of the thalamic competence (preparttening), the subsequent formation of the secondary organizer in the zona limitans intrathalamica, and the early specification of two anteroposterior domains (rostral and caudal progenitor domains) in response to inducing activities and that are shared in birds and mammals. In the present study we have analyzed the embryonic development of the thalamus in the anuran Xenopus laevis to determine conserved or specific features in the amphibian diencephalon. From early embryonic stages to the beginning of the larval period, the expression patterns of 22 markers were analyzed by means of combined In situ hybridization (ISH) and immunohistochemical techniques. The early genoarchitecture observed in the diencephalon allowed us to discern the boundaries of the thalamus with the prethalamus, pretectum, and epithalamus. Common molecular features were observed in the thalamic prepatterning among vertebrates in which Wnt3a, Fez, Pax6 and Xiro1 expression were of particular importance in Xenopus. The formation of the zona limitans intrathalamica was observed, as in other vertebrates, by the progressive expression of Shh. The largely conserved expressions of Nkx2.2 in the rostral thalamic domain vs. Gbx2 and Ngn2 (among others) in the caudal domain strongly suggest the role of Shh as morphogen in the amphibian thalamus. All these data showed that the molecular characteristics observed during preparttening and patterning in the thalamus of the anuran Xenopus (anamniote) share many features with those described during thalamic development in amniotes (common patterns in tetrapods) but also with zebrafish, strengthening the idea of a basic organization of this diencephalic region across vertebrates. PMID:26321920

Visuomotor signals for reaching movements in the rostro-dorsal sector of the monkey thalamic reticular nucleus.

PubMed

Saga, Yosuke; Nakayama, Yoshihisa; Inoue, Ken-Ichi; Yamagata, Tomoko; Hashimoto, Masashi; Tremblay, Léon; Takada, Masahiko; Hoshi, Eiji

2017-05-01

The thalamic reticular nucleus (TRN) collects inputs from the cerebral cortex and thalamus and, in turn, sends inhibitory outputs to the thalamic relay nuclei. This unique connectivity suggests that the TRN plays a pivotal role in regulating information flow through the thalamus. Here, we analyzed the roles of TRN neurons in visually guided reaching movements. We first used retrograde transneuronal labeling with rabies virus, and showed that the rostro-dorsal sector of the TRN (TRNrd) projected disynaptically to the ventral premotor cortex (PMv). In other experiments, we recorded neurons from the TRNrd or PMv while monkeys performed a visuomotor task. We found that neurons in the TRNrd and PMv showed visual-, set-, and movement-related activity modulation. These results indicate that the TRNrd, as well as the PMv, is involved in the reception of visual signals and in the preparation and execution of reaching movements. The fraction of neurons that were non-selective for the location of visual signals or the direction of reaching movements was greater in the TRNrd than in the PMv. Furthermore, the fraction of neurons whose activity increased from the baseline was greater in the TRNrd than in the PMv. The timing of activity modulation of visual-related and movement-related neurons was similar in TRNrd and PMv neurons. Overall, our data suggest that TRNrd neurons provide motor thalamic nuclei with inhibitory inputs that are predominantly devoid of spatial selectivity, and that these signals modulate how these nuclei engage in both sensory processing and motor output during visually guided reaching behavior. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Reduced thalamic volume in men with antisocial personality disorder or schizophrenia and a history of serious violence and childhood abuse.

PubMed

Kumari, V; Gudjonsson, G H; Raghuvanshi, S; Barkataki, I; Taylor, P; Sumich, A; Das, K; Kuipers, E; Ffytche, D H; Das, M

2013-05-01

Violent behaviour has been associated with presence of certain mental disorders, most notably antisocial personality disorder (ASPD) and schizophrenia, childhood abuse, and multiple brain abnormalities. This study examined for the first time, to the authors' knowledge, the role of psychosocial deprivation (PSD), including childhood physical and sexual abuse, in structural brain volumes of violent individuals with ASPD or schizophrenia. Fifty-six men (26 with ASPD or schizophrenia and a history of serious violence, 30 non-violent) underwent magnetic resonance imaging and were assessed on PSD. Stereological volumetric brain ratings were examined for group differences and their association with PSD ratings. PSD-brain associations were examined further using voxel-based-morphometry. The findings revealed: reduced thalamic volume in psychosocially-deprived violent individuals, relative to non-deprived violent individuals and healthy controls; negative association between thalamic volume and abuse ratings (physical and sexual) in violent individuals; and trend-level negative associations between PSD and hippocampal and prefrontal volumes in non-violent individuals. The voxel-based-morphometry analysis detected a negative association between PSD and localised grey matter volumes in the left inferior frontal region across all individuals, and additionally in the left middle frontal and precentral gyri in non-violent individuals. Violent mentally-disordered individuals with PSD, relative to those with no or minimal PSD, suffer from an additional brain deficit, i.e., reduced thalamic volume; this may affect sensory information processing, and have implications for management, of these individuals. PSD may have a stronger relationship with volumetric loss of stress-linked regions, namely the frontal cortex, in non-violent individuals. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Acupuncture as adjuvant therapy in thalamic syndrome: case report.

PubMed

Santos, Alysson Bruno Oliveira; Gozzani, Judymara Lauzi

2011-01-01

Cerebrovascular diseases are responsible for a large proportion of deaths in the world. Among survivors, the majority of limiting sequelae observed is motor in origin; but when sensorial pathways or centers are affected patients can evolve with sensorial changes in the body region represented by the area of the brain affected. When the affected area is related to the thalamus the patient might develop thalamic syndrome. The objective of this report was to demonstrate the use of electroacupuncture as adjuvant in the treatment of central pain, diagnosed as thalamic syndrome difficult to control with pharmacologic therapy. This is a 46 year-old female with history of ischemic stroke in the left temporoparietal region in April 2003 that evolved to right hemiparesis and hemitaxia. One year later, the patient developed continuous, insidious pain on the right side of the body with allodynia and hyperalgia, diagnosed as thalamic syndrome. In January 2006, she was admitted to the department of pain therapy and palliative care of Santa Casa de Misericórdia de São Paulo where pharmacologic treatment was instituted with poor response; she was scheduled for neurofunctional surgery. In July 2009, electroacupuncture, in an attempt to obtain better pain control, was proposed to the patient. Electroacupuncture was done on points in the scalp. After the 11(th) session, her pain was controlled, with no use of opioids or topical amitriptyline, her well-being had increased, her motor coordination improved, she presented global pain reduction, complete in hand and face. The efficacy of electroacupuncture in pain control and well-being are in agreement with modern studies which demonstrated activation of antinociceptive pathways in the brain. Controlled prospective studies are required to reaffirm and consolidate electroacupuncture as an important technique in controlling central pain. Copyright © 2011 Elsevier Editora Ltda. All rights reserved.

Spatial Hyperschematia without Spatial Neglect after Insulo-Thalamic Disconnection

PubMed Central

Saj, Arnaud; Wilcke, Juliane C.; Gschwind, Markus; Emond, Héloïse; Assal, Frédéric

2013-01-01

Different spatial representations are not stored as a single multipurpose map in the brain. Right brain-damaged patients can show a distortion, a compression of peripersonal and extrapersonal space. Here we report the case of a patient with a right insulo-thalamic disconnection without spatial neglect. The patient, compared with 10 healthy control subjects, showed a constant and reliable increase of her peripersonal and extrapersonal egocentric space representations - that we named spatial hyperschematia - yet left her allocentric space representations intact. This striking dissociation shows that our interactions with the surrounding world are represented and processed modularly in the human brain, depending on their frame of reference. PMID:24302992

Do the anterior and lateral thalamic nuclei make distinct contributions to spatial representation and memory?

PubMed

Clark, Benjamin J; Harvey, Ryan E

2016-09-01

The anterior and lateral thalamus has long been considered to play an important role in spatial and mnemonic cognitive functions; however, it remains unclear whether each region makes a unique contribution to spatial information processing. We begin by reviewing evidence from anatomical studies and electrophysiological recordings which suggest that at least one of the functions of the anterior thalamus is to guide spatial orientation in relation to a global or distal spatial framework, while the lateral thalamus serves to guide behavior in relation to a local or proximal framework. We conclude by reviewing experimental work using targeted manipulations (lesion or neuronal silencing) of thalamic nuclei during spatial behavior and single-unit recordings from neuronal representations of space. Our summary of this literature suggests that although the evidence strongly supports a working model of spatial information processing involving the anterior thalamus, research regarding the role of the lateral thalamus is limited and requires further attention. We therefore identify a number of major gaps in this research and suggest avenues of future study that could potentially solidify our understanding of the relative roles of anterior and lateral thalamic regions in spatial representation and memory. Copyright © 2016 Elsevier Inc. All rights reserved.

Vestibular thalamus: Two distinct graviceptive pathways.

PubMed

Baier, Bernhard; Conrad, Julian; Stephan, Thomas; Kirsch, Valerie; Vogt, Thomas; Wilting, Janine; Müller-Forell, Wibke; Dieterich, Marianne

2016-01-12

To determine whether there are distinct thalamic regions statistically associated with either contraversive or ipsiversive disturbance of verticality perception measured by subjective visual vertical (SVV). We used modern statistical lesion behavior mapping on a sample of 37 stroke patients with isolated thalamic lesions to clarify which thalamic regions are involved in graviceptive otolith processing and whether there are distinct regions associated with contraversive or ipsiversive SVV deviation. We found 2 distinct systems of graviceptive processing within the thalamus. Contraversive tilt of SVV was associated with lesions to the nuclei dorsomedialis, intralamellaris, centrales thalami, posterior thalami, ventrooralis internus, ventrointermedii, ventrocaudales and superior parts of the nuclei parafascicularis thalami. The regions associated with ipsiversive tilt of SVV were located in more inferior regions, involving structures such as the nuclei endymalis thalami, inferior parts of the nuclei parafascicularis thalami, and also small parts of the junction zone of the nuclei ruber tegmenti and brachium conjunctivum. Our data indicate that there are 2 anatomically distinct graviceptive signal processing mechanisms within the vestibular network in humans that lead, when damaged, to a vestibular tone imbalance either to the contraversive or to the ipsiversive side. © 2015 American Academy of Neurology.

Continuous and lurching traveling pulses in neuronal networks with delay and spatially decaying connectivity

PubMed Central

Golomb, David; Ermentrout, G. Bard

1999-01-01

Propagation of discharges in cortical and thalamic systems, which is used as a probe for examining network circuitry, is studied by constructing a one-dimensional model of integrate-and-fire neurons that are coupled by excitatory synapses with delay. Each neuron fires only one spike. The velocity and stability of propagating continuous pulses are calculated analytically. Above a certain critical value of the constant delay, these pulses lose stability. Instead, lurching pulses propagate with discontinuous and periodic spatio-temporal characteristics. The parameter regime for which lurching occurs is strongly affected by the footprint (connectivity) shape; bistability may occur with a square footprint shape but not with an exponential footprint shape. For strong synaptic coupling, the velocity of both continuous and lurching pulses increases logarithmically with the synaptic coupling strength gsyn for an exponential footprint shape, and it is bounded for a step footprint shape. We conclude that the differences in velocity and shape between the front of thalamic spindle waves in vitro and cortical paroxysmal discharges stem from their different effective delay; in thalamic networks, large effective delay between inhibitory neurons arises from their effective interaction via the excitatory cells which display postinhibitory rebound. PMID:10557346

Thalamic Atrophy Contributes to Low Slow Wave Sleep in Neuromyelitis Optica Spectrum Disorder.

PubMed

Su, Lei; Han, Yujuan; Xue, Rong; Wood, Kristofer; Shi, Fu-Dong; Liu, Yaou; Fu, Ying

2016-12-01

Slow wave sleep abnormality has been reported in neuromyelitis optica spectrum disorder (NMOSD), but mechanism for such abnormality is unknown. To determine the structural defects in the brain that account for the decrease of slow wave sleep in NMOSD patients. Thirty-three NMOSD patients and 18 matched healthy controls (HC) were enrolled. Polysomnography was used to monitor slow wave sleep and three-dimensional T1-weighted MRIs were obtained to assess the alterations of grey matter volume. The percentage of deep slow wave sleep decreased in 93% NMOSD patients. Compared to HC, a reduction of grey matter volume was found in the bilateral thalamus of patients with a lower percentage of slow wave sleep (FWE corrected at cluster-level, p < 0.05, cluster size > 400 voxels). Furthermore, the right thalamic fraction was positively correlated with the decrease in the percentage of slow wave sleep in NMOSD patients (p < 0.05, FDR corrected, cluster size > 200 voxels). Our study identified that thalamic atrophy is associated with the decrease of slow wave sleep in NMOSD patients. Further studies should evaluate whether neurotransmitters or hormones which stem from thalamus are involved in the decrease of slow wave sleep.

Regional thalamic neuropathology in patients with hippocampal sclerosis and epilepsy: A postmortem study

PubMed Central

Sinjab, Barah; Martinian, Lillian; Sisodiya, Sanjay M; Thom, Maria

2013-01-01

Purpose Clinical, experimental, and neuroimaging data all indicate that the thalamus is involved in the network of changes associated with temporal lobe epilepsy (TLE), particularly in association with hippocampal sclerosis (HS), with potential roles in seizure initiation and propagation. Pathologic changes in the thalamus may be a result of an initial insult, ongoing seizures, or retrograde degeneration through reciprocal connections between thalamic and limbic regions. Our aim was to carry out a neuropathologic analysis of the thalamus in a postmortem (PM) epilepsy series, to assess the distribution, severity, and nature of pathologic changes and its association with HS. Methods Twenty-four epilepsy PM cases (age range 25–87 years) and eight controls (age range 38–85 years) were studied. HS was classified as unilateral (UHS, 11 cases), bilateral (BHS, 4 cases) or absent (No-HS, 9 cases). Samples from the left and right sides of the thalamus were stained with cresyl violet (CV), and for glial firbillary acidic protein (GFAP) and synaptophysin. Using image analysis, neuronal densities (NDs) or field fraction staining values (GFAP, synaptophysin) were measured in four thalamic nuclei: anteroventral nucleus (AV), lateral dorsal nucleus (LD), mediodorsal nucleus (MD), and ventrolateral nucleus (VL). The results were compared within and between cases. Key Findings The severity, nature, and distribution of thalamic pathology varied between cases. A pattern that emerged was a preferential involvement of the MD in UHS cases with a reduction in mean ND ipsilateral to the side of HS (p = 0.05). In UHS cases, greater field fraction values for GFAP and lower values for synaptophysin and ND were seen in the majority of cases in the MD ipsilateral to the side of sclerosis compared to other thalamic nuclei. In addition, differences in the mean ND between classical HS, atypical HS, and No-HS cases were noted in the ipsilateral MD (p < 0.05), with lower values observed in HS. Significance Our study demonstrates that stereotypical pathologic changes, as seen in HS, are not clearly defined in the thalamus. This may be partly explained by the heterogeneity of our PM study group. With quantitation, there is some evidence for preferential involvement of the MD, suggesting a potential role in TLE, which requires further investigation. PMID:24138281

Novel β-catenin target genes identified in thalamic neurons encode modulators of neuronal excitability

PubMed Central

2012-01-01

Background LEF1/TCF transcription factors and their activator β-catenin are effectors of the canonical Wnt pathway. Although Wnt/β-catenin signaling has been implicated in neurodegenerative and psychiatric disorders, its possible role in the adult brain remains enigmatic. To address this issue, we sought to identify the genetic program activated by β-catenin in neurons. We recently showed that β-catenin accumulates specifically in thalamic neurons where it activates Cacna1g gene expression. In the present study, we combined bioinformatics and experimental approaches to find new β-catenin targets in the adult thalamus. Results We first selected the genes with at least two conserved LEF/TCF motifs within the regulatory elements. The resulting list of 428 putative LEF1/TCF targets was significantly enriched in known Wnt targets, validating our approach. Functional annotation of the presumed targets also revealed a group of 41 genes, heretofore not associated with Wnt pathway activity, that encode proteins involved in neuronal signal transmission. Using custom polymerase chain reaction arrays, we profiled the expression of these genes in the rat forebrain. We found that nine of the analyzed genes were highly expressed in the thalamus compared with the cortex and hippocampus. Removal of nuclear β-catenin from thalamic neurons in vitro by introducing its negative regulator Axin2 reduced the expression of six of the nine genes. Immunoprecipitation of chromatin from the brain tissues confirmed the interaction between β-catenin and some of the predicted LEF1/TCF motifs. The results of these experiments validated four genes as authentic and direct targets of β-catenin: Gabra3 for the receptor of GABA neurotransmitter, Calb2 for the Ca2+-binding protein calretinin, and the Cacna1g and Kcna6 genes for voltage-gated ion channels. Two other genes from the latter cluster, Cacna2d2 and Kcnh8, appeared to be regulated by β-catenin, although the binding of β-catenin to the regulatory sequences of these genes could not be confirmed. Conclusions In the thalamus, β-catenin regulates the expression of a novel group of genes that encode proteins involved in neuronal excitation. This implies that the transcriptional activity of β-catenin is necessary for the proper excitability of thalamic neurons, may influence activity in the thalamocortical circuit, and may contribute to thalamic pathologies. PMID:23157480

From functional architecture to functional connectomics.

PubMed

Reid, R Clay

2012-07-26

"Receptive Fields, Binocular Interaction and Functional Architecture in the Cat's Visual Cortex" by Hubel and Wiesel (1962) reported several important discoveries: orientation columns, the distinct structures of simple and complex receptive fields, and binocular integration. But perhaps the paper's greatest influence came from the concept of functional architecture (the complex relationship between in vivo physiology and the spatial arrangement of neurons) and several models of functionally specific connectivity. They thus identified two distinct concepts, topographic specificity and functional specificity, which together with cell-type specificity constitute the major determinants of nonrandom cortical connectivity. Orientation columns are iconic examples of topographic specificity, whereby axons within a column connect with cells of a single orientation preference. Hubel and Wiesel also saw the need for functional specificity at a finer scale in their model of thalamic inputs to simple cells, verified in the 1990s. The difficult but potentially more important question of functional specificity between cortical neurons is only now becoming tractable with new experimental techniques. Copyright © 2012 Elsevier Inc. All rights reserved.

Model-based rational feedback controller design for closed-loop deep brain stimulation of Parkinson's disease

NASA Astrophysics Data System (ADS)

Gorzelic, P.; Schiff, S. J.; Sinha, A.

2013-04-01

Objective. To explore the use of classical feedback control methods to achieve an improved deep brain stimulation (DBS) algorithm for application to Parkinson's disease (PD). Approach. A computational model of PD dynamics was employed to develop model-based rational feedback controller design. The restoration of thalamocortical relay capabilities to patients suffering from PD is formulated as a feedback control problem with the DBS waveform serving as the control input. Two high-level control strategies are tested: one that is driven by an online estimate of thalamic reliability, and another that acts to eliminate substantial decreases in the inhibition from the globus pallidus interna (GPi) to the thalamus. Control laws inspired by traditional proportional-integral-derivative (PID) methodology are prescribed for each strategy and simulated on this computational model of the basal ganglia network. Main Results. For control based upon thalamic reliability, a strategy of frequency proportional control with proportional bias delivered the optimal control achieved for a given energy expenditure. In comparison, control based upon synaptic inhibitory output from the GPi performed very well in comparison with those of reliability-based control, with considerable further reduction in energy expenditure relative to that of open-loop DBS. The best controller performance was amplitude proportional with derivative control and integral bias, which is full PID control. We demonstrated how optimizing the three components of PID control is feasible in this setting, although the complexity of these optimization functions argues for adaptive methods in implementation. Significance. Our findings point to the potential value of model-based rational design of feedback controllers for Parkinson's disease.

How acute total sleep loss affects the attending brain: a meta-analysis of neuroimaging studies.

PubMed

Ma, Ning; Dinges, David F; Basner, Mathias; Rao, Hengyi

2015-02-01

Attention is a cognitive domain that can be severely affected by sleep deprivation. Previous neuroimaging studies have used different attention paradigms and reported both increased and reduced brain activation after sleep deprivation. However, due to large variability in sleep deprivation protocols, task paradigms, experimental designs, characteristics of subject populations, and imaging techniques, there is no consensus regarding the effects of sleep loss on the attending brain. The aim of this meta-analysis was to identify brain activations that are commonly altered by acute total sleep deprivation across different attention tasks. Coordinate-based meta-analysis of neuroimaging studies of performance on attention tasks during experimental sleep deprivation. The current version of the activation likelihood estimation (ALE) approach was used for meta-analysis. The authors searched published articles and identified 11 sleep deprivation neuroimaging studies using different attention tasks with a total of 185 participants, equaling 81 foci for ALE analysis. The meta-analysis revealed significantly reduced brain activation in multiple regions following sleep deprivation compared to rested wakefulness, including bilateral intraparietal sulcus, bilateral insula, right prefrontal cortex, medial frontal cortex, and right parahippocampal gyrus. Increased activation was found only in bilateral thalamus after sleep deprivation compared to rested wakefulness. Acute total sleep deprivation decreases brain activation in the fronto-parietal attention network (prefrontal cortex and intraparietal sulcus) and in the salience network (insula and medial frontal cortex). Increased thalamic activation after sleep deprivation may reflect a complex interaction between the de-arousing effects of sleep loss and the arousing effects of task performance on thalamic activity. © 2015 Associated Professional Sleep Societies, LLC.

Electrocortical and behavioral responses elicited by acute electrical stimulation of inferior thalamic peduncle and nucleus reticularis thalami in a patient with major depression disorder.

PubMed

Velasco, Marcos; Velasco, Francisco; Jiménez, Fiacro; Carrillo-Ruiz, José D; Velasco, Ana Luisa; Salín-Pascual, Rafael

2006-02-01

Our aim was to study electrocortical and behavioral responses elicited by 6, 60 and 3/s stimulation of the inferior thalamic peduncle (ITP) and nucleus reticularis thalami (Re) in a patient with of major depression disorder resistant to psychotherapy, pharmacotherapy and electroconvulsive therapy and candidate to be treated by electrical stimulation of the ITP. In this patient, two multicontact electrodes were implanted bilaterally through frontal coronal parasagittal burr-holes with oblique trajectories aiming ITP and Re. Stimulation was performed through externalized systems. Referential scalp electroencephalographic (EEG) recordings were performed and subjective sensations and clinical symptoms reported by patient and changes in responsiveness in single response tasks during stimulation trials were systematically recorded. Unilateral, low (6/s) and high (60/s) frequency stimulation of either ITP or Re produced identical recruiting-like responses or desynchronization-DC shift changes predominant at frontopolar region, bilaterally. Billateral, high intensity 3/s stimulation or either ITP or Re produced electrocortical responses that consisted in generalized 3/s spike-wave complexes predominant at frontopolar, frontocentral and frontotemporal regions. However, while ITP responses were accompanied by all symptoms described for a spontaneous absence attack, Re responses were behaviorly accompanied only by delayed reaction time. These data suggests that in humans as in cats, ITP and Re are both part of a non-specific thalamo-orbitofrontal system normally engaged in cortical synchronization, selective attention and sleep. Under abnormal conditions, ITP and RE may play a role in the physiopathology of typical absence attacks and depression disorders.

Anatomy of the Limbic White Matter Tracts as Revealed by Fiber Dissection and Tractography.

PubMed

Pascalau, Raluca; Popa Stănilă, Roxana; Sfrângeu, Silviu; Szabo, Bianca

2018-05-01

The limbic tracts are involved in crucial cerebral functions such as memory, emotion, and behavior. The complex architecture of the limbic circuit makes it harder to approach compared with other white matter networks. Our study aims to describe the 3-dimensional anatomy of the limbic white matter by the use of 2 complementary study methods, namely ex vivo fiber dissection and in vivo magnetic resonance imaging-based tractography. Three fiber dissection protocols were performed using blunt wooden instruments and a surgical microscope on formalin-fixed brains prepared according to the Klingler method. Diffusion tensor imaging acquisitions were done with a 3-Tesla magnetic resonance scanner on patients with head and neck pathology that did not involve the brain. Fiber tracking was performed with manually selected regions of interest. Cingulum, fornix, the anterior thalamic peduncle, the accumbofrontal bundle, medial forebrain bundle, the uncinate fasciculus, the mammillothalamic tract, ansa peduncularis, and stria terminalis were dissected and fiber tracked. For each tract, location, configuration, segmentation, dimensions, dissection and tractography particularities, anatomical relations, and terminations are described. The limbic white matter tracts were systematized as 2 concentric rings around the thalamus. The inner ring is formed by fornix, mammillothalamic tract, ansa peduncularis, stria terminalis, accumbofrontal fasciculus, and medial forebrain bundle and anterior thalamic peduncle, and the outer ring is formed by the cingulum and uncinate fasciculus. This paper proposes a fiber-tracking protocol for the limbic tracts inspired and validated by fiber dissection findings that can be used routinely in the clinical practice. Copyright © 2018 Elsevier Inc. All rights reserved.

Development of the dorsal and ventral thalamus in platypus (Ornithorhynchus anatinus) and short-beaked echidna (Tachyglossus aculeatus).

PubMed

Ashwell, Ken W S

2012-04-01

The living monotremes (platypus and echidnas) are distinguished from therians as well as each other in part by the unusual structure of the thalamus in each. In particular, the platypus has an enlarged ventral posterior (VP) nucleus reflecting the great behavioural importance of trigeminosensation and electroreception. The embryological collections of the Museum für Naturkunde in Berlin were used to analyse the development of the dorsal thalamus and ventral thalamus (prethalamus) in both species. Prosomeric organization of the forebrain emerged at 6 mm crown-rump length (CRL), but thalamic neurogenesis did not commence until about 8-9 mm CRL. Distinctive features of the dorsal thalamus in the two species began to emerge after hatching (about 14-15 mm CRL). During the first post-hatching week, dense clusters of granular cells aggregated to form the VP of the platypus, whereas the VP complex of the echidna remained smaller and divided into distinct medial and lateral divisions. At the end of the first post-hatching week, the thalamocortical tract was much larger in the platypus than the echidna. The dorsal thalamus of the platypus is essentially adult-like by the sixth week of post-hatching life. The similar appearance of the dorsal thalamus in the two species until the time of hatching, followed by the rapid expansion of the VP in the platypus, is most consistent with ancestral platypuses having undergone changes in the genetic control of thalamic neurogenesis to produce a large VP for trigeminal electroreception after the divergence of the two lineages of monotreme.

Model-based rational feedback controller design for closed-loop deep brain stimulation of Parkinson's disease.

PubMed

Gorzelic, P; Schiff, S J; Sinha, A

2013-04-01

To explore the use of classical feedback control methods to achieve an improved deep brain stimulation (DBS) algorithm for application to Parkinson's disease (PD). A computational model of PD dynamics was employed to develop model-based rational feedback controller design. The restoration of thalamocortical relay capabilities to patients suffering from PD is formulated as a feedback control problem with the DBS waveform serving as the control input. Two high-level control strategies are tested: one that is driven by an online estimate of thalamic reliability, and another that acts to eliminate substantial decreases in the inhibition from the globus pallidus interna (GPi) to the thalamus. Control laws inspired by traditional proportional-integral-derivative (PID) methodology are prescribed for each strategy and simulated on this computational model of the basal ganglia network. For control based upon thalamic reliability, a strategy of frequency proportional control with proportional bias delivered the optimal control achieved for a given energy expenditure. In comparison, control based upon synaptic inhibitory output from the GPi performed very well in comparison with those of reliability-based control, with considerable further reduction in energy expenditure relative to that of open-loop DBS. The best controller performance was amplitude proportional with derivative control and integral bias, which is full PID control. We demonstrated how optimizing the three components of PID control is feasible in this setting, although the complexity of these optimization functions argues for adaptive methods in implementation. Our findings point to the potential value of model-based rational design of feedback controllers for Parkinson's disease.

Efferent projections of the septum in the Tegu lizard, Tupinambis nigropunctatus.

PubMed

Sligar, C M; Voneida, T J

1981-09-01

A H3 proline or H3 leucine mixture was injected into the septal region of the Tegu lizard in order to determine its efferent projections. The brains were processed according to standard autoradiographic technique and counterstained with cresyl violet. Septal projections were limited to either telencephalic or diencephalic areas. Intratelencephalic projections consisted of efferents to medial pallium, nucleus accumbens, bed nucleus of the anterior commissure, preoptic area and septum itself. Fibers entering the diencephalon projected to medial habenular nucleus, dorsomedial thalamic nucleus, dorsolateral thalamic area, periventricular nucleus of the hypothalamus, lateral hypothalamic area and mammillary nucleus. The results are discussed in relation to the efferent projections of the septum in other vertebrates.

Deep brain stimulation for the treatment of uncommon tremor syndromes.

PubMed

Ramirez-Zamora, Adolfo; Okun, Michael S

2016-08-01

Deep brain stimulation (DBS) has become a standard therapy for the treatment of select cases of medication refractory essential tremor and Parkinson's disease however the effectiveness and long-term outcomes of DBS in other uncommon and complex tremor syndromes has not been well established. Traditionally, the ventralis intermedius nucleus (VIM) of the thalamus has been considered the main target for medically intractable tremors; however alternative brain regions and improvements in stereotactic techniques and hardware may soon change the horizon for treatment of complex tremors. In this article, we conducted a PubMed search using different combinations between the terms 'Uncommon tremors', 'Dystonic tremor', 'Holmes tremor' 'Midbrain tremor', 'Rubral tremor', 'Cerebellar tremor', 'outflow tremor', 'Multiple Sclerosis tremor', 'Post-traumatic tremor', 'Neuropathic tremor', and 'Deep Brain Stimulation/DBS'. Additionally, we examined and summarized the current state of evolving interventions for treatment of complex tremor syndromes. Expert commentary: Recently reported interventions for rare tremors include stimulation of the posterior subthalamic area, globus pallidus internus, ventralis oralis anterior/posterior thalamic subnuclei, and the use of dual lead stimulation in one or more of these targets. Treatment should be individualized and dictated by tremor phenomenology and associated clinical features.

Dynamics of action potential initiation in the GABAergic thalamic reticular nucleus in vivo.

PubMed

Muñoz, Fabián; Fuentealba, Pablo

2012-01-01

Understanding the neural mechanisms of action potential generation is critical to establish the way neural circuits generate and coordinate activity. Accordingly, we investigated the dynamics of action potential initiation in the GABAergic thalamic reticular nucleus (TRN) using in vivo intracellular recordings in cats in order to preserve anatomically-intact axo-dendritic distributions and naturally-occurring spatiotemporal patterns of synaptic activity in this structure that regulates the thalamic relay to neocortex. We found a wide operational range of voltage thresholds for action potentials, mostly due to intrinsic voltage-gated conductances and not synaptic activity driven by network oscillations. Varying levels of synchronous synaptic inputs produced fast rates of membrane potential depolarization preceding the action potential onset that were associated with lower thresholds and increased excitability, consistent with TRN neurons performing as coincidence detectors. On the other hand the presence of action potentials preceding any given spike was associated with more depolarized thresholds. The phase-plane trajectory of the action potential showed somato-dendritic propagation, but no obvious axon initial segment component, prominent in other neuronal classes and allegedly responsible for the high onset speed. Overall, our results suggest that TRN neurons could flexibly integrate synaptic inputs to discharge action potentials over wide voltage ranges, and perform as coincidence detectors and temporal integrators, supported by a dynamic action potential threshold.

Chronic hyperperfusion and angiogenesis follow subacute hypoperfusion in the thalamus of rats with focal cerebral ischemia

PubMed Central

Hayward, Nick MEA; Yanev, Pavel; Haapasalo, Annakaisa; Miettinen, Riitta; Hiltunen, Mikko; Gröhn, Olli; Jolkkonen, Jukka

2011-01-01

Cerebral blood flow (CBF) is disrupted after focal ischemia in rats. We examined long-term hemodynamic and cerebrovascular changes in the rat thalamus after focal cerebral ischemia. Cerebral blood flow quantified by arterial spin labeling magnetic resonance imaging was decreased in the ipsilateral and contralateral thalamus 2 days after cerebral ischemia. Partial thalamic CBF recovery occurred by day 7, then the ipsilateral thalamus was chronically hyperperfused at 30 days and 3 months compared with its contralateral side. This contrasted with permanent hypoperfusion in the ipsilateral cortex. Angiogenesis was indicated by endothelial cell (RECA-1) immunohistochemistry that showed increased blood vessel branching in the ipsilateral thalamus at the end of the 3-month follow-up. Only transient thalamic IgG extravasation was observed, indicating that the blood–brain barrier was intact after day 2. Angiogenesis was preceded by transiently altered expression levels of cadherin family adhesion molecules, cadherin-7, protocadherin-1, and protocadherin-17. In conclusion, thalamic pathology after focal cerebral ischemia involved long-term hemodynamic changes and angiogenesis preceded by altered expression of vascular adhesion factors. Postischemic angiogenesis in the thalamus represents a novel type of remote plasticity, which may support removal of necrotic brain tissue and aid functional recovery. PMID:21081957

Repetition reveals ups and downs of hippocampal, thalamic, and neocortical engagement during mnemonic decisions

PubMed Central

Reagh, Zachariah M.; Murray, Elizabeth A.; Yassa, Michael A.

2017-01-01

The extent to which current information is consistent with past experiences and our capacity to recognize or discriminate accordingly are key factors in flexible memory-guided behavior. Despite a wealth of evidence linking hippocampal and neocortical computations to these phenomena, many important factors remain poorly understood. One such factor is repeated encoding of learned information. In this experiment, participants completed a task in which study stimuli were incidentally encoded either once or three separate times during high-resolution fMRI scanning. We asked how repetition influenced recognition and discrimination memory judgments, and how this affects engagement of hippocampal and neocortical regions. Repetition revealed shifts in engagement in an anterior (ventral) CA1-thalamic-medial prefrontal network related to true and false recognition. Conversely, repetition revealed shifts in a posterior (dorsal) dentate/CA3-parahippocampal-restrosplenial network related to accurate discrimination. These differences in engagement were accompanied by task-related correlations in respective anterior and posterior networks. In particular, the anterior thalamic region observed during recognition judgments is functionally and anatomically consistent with nucleus reuniens in humans, and was found to mediate correlations between the anterior CA1 and medial prefrontal cortex. These findings offer new insights into how repeated experience affects memory and its neural substrates in hippocampal-neocortical networks. PMID:27859884

The Mediodorsal Thalamus Drives Feedforward Inhibition in the Anterior Cingulate Cortex via Parvalbumin Interneurons

PubMed Central

Delevich, Kristen; Tucciarone, Jason; Huang, Z. Josh

2015-01-01

Although the medial prefrontal cortex (mPFC) is classically defined by its reciprocal connections with the mediodorsal thalamic nucleus (MD), the nature of information transfer between MD and mPFC is poorly understood. In sensory thalamocortical pathways, thalamic recruitment of feedforward inhibition mediated by fast-spiking, putative parvalbumin-expressing (PV) interneurons is a key feature that enables cortical neurons to represent sensory stimuli with high temporal fidelity. Whether a similar circuit mechanism is in place for the projection from the MD (a higher-order thalamic nucleus that does not receive direct input from the periphery) to the mPFC is unknown. Here we show in mice that inputs from the MD drive disynaptic feedforward inhibition in the dorsal anterior cingulate cortex (dACC) subregion of the mPFC. In particular, we demonstrate that axons arising from MD neurons directly synapse onto and excite PV interneurons that in turn mediate feedforward inhibition of pyramidal neurons in layer 3 of the dACC. This feedforward inhibition in the dACC limits the time window during which pyramidal neurons integrate excitatory synaptic inputs and fire action potentials, but in a manner that allows for greater flexibility than in sensory cortex. These findings provide a foundation for understanding the role of MD-PFC circuit function in cognition. PMID:25855185

Feedforward inhibitory control of sensory information in higher-order thalamic nuclei.

PubMed

Lavallée, Philippe; Urbain, Nadia; Dufresne, Caroline; Bokor, Hajnalka; Acsády, László; Deschênes, Martin

2005-08-17

Sensory stimuli evoke strong responses in thalamic relay cells, which ensure a faithful relay of information to the neocortex. However, relay cells of the posterior thalamic nuclear group in rodents, despite receiving significant trigeminal input, respond poorly to vibrissa deflection. Here we show that sensory transmission in this nucleus is impeded by fast feedforward inhibition mediated by GABAergic neurons of the zona incerta. Intracellular recordings of posterior group neurons revealed that the first synaptic event after whisker deflection is a prominent inhibition. Whisker-evoked EPSPs with fast rise time and longer onset latency are unveiled only after lesioning the zona incerta. Excitation survives barrel cortex lesion, demonstrating its peripheral origin. Electron microscopic data confirm that trigeminal axons make large synaptic terminals on the proximal dendrites of posterior group cells and on the somata of incertal neurons. Thus, the connectivity of the system allows an unusual situation in which inhibition precedes ascending excitation resulting in efficient shunting of the responses. The dominance of inhibition over excitation strongly suggests that the paralemniscal pathway is not designed to relay inputs triggered by passive whisker deflection. Instead, we propose that this pathway operates through disinhibition, and that the posterior group forwards to the cerebral cortex sensory information that is contingent on motor instructions.

Thalamic synaptic transmission of sensory information modulated by synergistic interaction of adenosine and serotonin.

PubMed

Yang, Ya-Chin; Hu, Chun-Chang; Huang, Chen-Syuan; Chou, Pei-Yu

2014-03-01

The thalamic synapses relay peripheral sensory information to the cortex, and constitute an important part of the thalamocortical network that generates oscillatory activities responsible for different vigilance (sleep and wakefulness) states. However, the modulation of thalamic synaptic transmission by potential sleep regulators, especially by combination of regulators in physiological scenarios, is not fully characterized. We found that somnogen adenosine itself acts similar to wake-promoting serotonin, both decreasing synaptic strength as well as short-term depression, at the retinothalamic synapse. We then combined the two modulators considering the coexistence of them in the hypnagogic (sleep-onset) state. Adenosine plus serotonin results in robust synergistic inhibition of synaptic strength and dramatic transformation of short-term synaptic depression to facilitation. These synaptic effects are not achievable with a single modulator, and are consistent with a high signal-to-noise ratio but a low level of signal transmission through the thalamus appropriate for slow-wave sleep. This study for the first time demonstrates that the sleep-regulatory modulators may work differently when present in combination than present singly in terms of shaping information flow in the thalamocortical network. The major synaptic characters such as the strength and short-term plasticity can be profoundly altered by combination of modulators based on physiological considerations. © 2013 International Society for Neurochemistry.

Preparation, Characterization, and Pharmacological Activity of Cymbopogon winterianus Jowitt ex Bor (Poaceae) Leaf Essential Oil of β-Cyclodextrin Inclusion Complexes

PubMed Central

Santos, Priscila L.; Araújo, Adriano A. S.; Quintans, Jullyana S. S.; Oliveira, Makson G. B.; Brito, Renan G.; Serafini, Mairim R.; Menezes, Paula P.; Santos, Marcio R. V.; Alves, Pericles B.; de Lucca Júnior, Waldecy; Blank, Arie F.; La Rocca, Viviana; Almeida, Reinaldo N.; Quintans-Júnior, Lucindo J.

2015-01-01

This study aimed to evaluate the orofacial antinociceptive effect of the Cymbopogon winterianus essential oil (LEO) complexed in β-cyclodextrin (LEO-CD) and to assess the possible involvement of the central nervous system (CNS). The LEO was extracted, chromatographed, and complexed in β-cyclodextrin. The complex was characterized by differential scanning calorimetry (DSC) and thermogravimetry derivative (TG/DTG). Male Swiss mice (2-3 months) were treated with LEO-CD (50–200 mg/kg, p.o.), vehicle (distilled water, p.o.), or standard drug (i.p.) and subjected to the orofacial nociception formalin-, capsaicin-, and glutamate-induced. After the formalin test, the animals were perfused and the brains subjected to immunofluorescence for Fos. The rota-rod test (7 rpm/min) was carried out. Geraniol (37.57%) was the main compound of LEO. DSC and TG/DTG proved the complexation. The orofacial nociceptive behavior was significantly (p < 0.05) reduced. The number of Fos-positive cells was significantly changed in the dorsal raphe nucleus (p < 0.01), locus coeruleus (p < 0.001), trigeminal nucleus (p < 0.05), and trigeminal thalamic tract (p < 0.05). LEO-CD did not cause changes in motor coordination in the rota-rod test. Thus, our results suggested that LEO-CD has an orofacial antinociceptive profile, probably mediated by the activation of the CNS without changing the motor coordination. PMID:26246838

Longitudinal changes in white matter integrity among adolescent substance users.

PubMed

Bava, Sunita; Jacobus, Joanna; Thayer, Rachel E; Tapert, Susan F

2013-01-01

The influence of repeated substance use during adolescent neurodevelopment remains unclear as there have been few prospective investigations. The aims of this study were to identify longitudinal changes in fiber tract integrity associated with alcohol- and marijuana-use severity over the course of 1.5 years. Adolescents with extensive marijuana- and alcohol-use histories by mid-adolescence (n = 41) and youth with consistently minimal if any substance use (n = 51) were followed over 18 months. Teens received diffusion tensor imaging and detailed substance-use assessments with toxicology screening at baseline and 18-month follow-ups (i.e., 182 scans in all), as well as interim substance-use interviews each 6 months. At an 18-month follow-up, substance users showed poorer white matter integrity in 7 tracts: (i) right superior longitudinal fasciculus, (ii) left superior longitudinal fasciculus, (iii) right posterior thalamic radiations, (iv) right prefrontal thalamic fibers, (v) right superior temporal gyrus white matter, (vi) right inferior longitudinal fasciculus, and (vii) left posterior corona radiata (ps < 0.01). More alcohol use during the interscan interval predicted higher mean diffusivity (i.e., worsened integrity) in right (p < 0.05) and left (p = 0.06) superior longitudinal fasciculi, above and beyond baseline values in these bundles. Marijuana use during the interscan interval did not predict change over time. More externalizing behaviors at Time 1 predicted lower fractional anisotropy and higher radial diffusivity (i.e., poorer integrity) of the right prefrontal thalamic fibers (p < 0.025). Findings add to previous cross-sectional studies reporting white matter disadvantages in youth with substance-use histories. In particular, alcohol use during adolescent neurodevelopment may be linked to reductions in white matter quality in association fiber tracts with frontal connections. In contrast, youth who engage in a variety of risk-taking behaviors may have unique neurodevelopmental trajectories characterized by truncated development in fronto-thalamic tracts, which could have functional and clinical consequences in young adulthood. Copyright © 2012 by the Research Society on Alcoholism.

Longitudinal thalamic diffusion changes after middle cerebral artery infarcts

PubMed Central

Herve, D; Molko, N; Pappata, S; Buffon, F; LeBihan, D; Bousser, M; Chabriat, H

2005-01-01

Background: Cerebral infarcts are responsible for functional alterations and microscopic tissue damage at distance from the ischaemic area. Such remote effects have been involved in stroke recovery. Thalamic hypometabolism is related to motor recovery in middle cerebral artery (MCA) infarcts but little is known concerning the tissue changes underlying these metabolic changes. Diffusion tensor imaging (DTI) is highly sensitive to microstructural tissue alterations and can be used to quantify in vivo the longitudinal microscopic tissue changes occurring in the thalamus after MCA infarcts in humans. Methods: Nine patients underwent DTI after an isolated MCA infarct. Mean diffusivity (MD), fractional anisotropy (FA), and thalamic region volume were measured from the first week to the sixth month after stroke onset in these patients and in 10 age matched controls. Results: MD significantly increased in the ipsilateral thalamus between the first and the sixth month (0.766x10–3 mm2/s first month; 0.792x10–3 mm2/s third month; 0.806x10–3 mm2/s sixth month). No significant modification of FA was detected. In six patients, the ipsilateral/contralateral index of MD was higher than the upper limit of the 95% CI calculated in 10 age matched controls. An early decrease of MD preceded the increase of ipsilateral thalamic diffusion in one patient at the first week and in two other patients at the first month. Conclusion: After MCA infarcts, an increase in diffusion is observed with DTI in the ipsilateral thalamus later than 1 month after the stroke onset. This is presumably because of the progressive loss of neurons and/or glial cells. In some patients, this increase is preceded by a transient decrease in diffusion possibly related to an early swelling of these cells or to microglial activation. Further studies in larger series are needed to assess the clinical correlates of these findings. PMID:15654032

Tremor-related activity of neurons in the 'motor' thalamus: changes in firing rate and pattern in the MPTP vervet model of parkinsonism.

PubMed

Guehl, D; Pessiglione, M; François, C; Yelnik, J; Hirsch, E C; Féger, J; Tremblay, L

2003-06-01

The pathophysiology of parkinsonian tremor remains a matter of debate with two opposing hypotheses proposing a peripheral and a central origin, respectively. A central origin of tremor could arise either from a rhythmic activity of the internal segment of the globus pallidus (GPi) or from a structure such as the thalamus, outside the basal ganglia. In this study, single-unit recordings were performed in three 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated monkeys within the GPi and within three territories of the motor thalamus (delimited by their afferent inputs from the GPi, the substantia nigra and the cerebellum, respectively). For each recorded neuron, we compared the variations in firing rate and pattern in tremor and no tremor periods. Tremor either occurred spontaneously or was induced by external stimulation. When the animals entered into a tremor period we observed: (i) an increase in the mean firing rate in about half of the recorded neurons of the motor thalamus; and (ii), a change from an irregular to a rhythmic discharge within the range of tremor frequency (5-7 Hz) in about 10% of the recorded neurons of the motor thalamus (pallidal and cerebellar territories) and the GPi. Most of the thalamic neurons that exhibited a rhythmic discharge during tremor were found to be sensitive to external stimulation. Because the changes in firing rate occurred predominantly in the motor thalamus and not in the GPi, and because a fast rhythmic discharge of 10-15 Hz was frequently observed in the GPi and not in the motor thalamus, we conclude that thalamic activity is not a simple reproduction of basal ganglia output. Moreover, we suggest that thalamic processing of basal ganglia outputs could participate in the genesis of tremor, and that this thalamic processing could be influenced by sensory inputs and/or changes in attentional level elicited by external stimulation.

Confocal Laser Scanning Microscopy and Ultrastructural Study of VGLUT2 Thalamic Input to Striatal Projection Neurons in Rats

PubMed Central

Lei, Wanlong; Deng, Yunping; Liu, Bingbing; Mu, Shuhua; Guley, Natalie M.; Wong, Ting; Reiner, Anton

2014-01-01

We examined thalamic input to striatum in rats using immunolabeling for the vesicular glutamate transporter (VGLUT2). Double immunofluorescence viewed with confocal laser scanning microscopy (CLSM) revealed that VGLUT2+ terminals are distinct from VGLUT1+ terminals. CLSM of Phaseolus vulgaris-leucoagglutinin (PHAL)-labeled cortical or thalamic terminals revealed that VGLUT2 is rare in corticostriatal terminals but nearly always present in thalamostriatal terminals. Electron microscopy revealed that VGLUT2+ terminals made up 39.4% of excitatory terminals in striatum (with VGLUT1+ corticostriatal terminals constituting the rest), and 66.8% of VGLUT2+ terminals synapsed on spines and the remainder on dendrites. VGLUT2+ axo-spinous terminals had a mean diameter of 0.624 lm, while VGLUT2+ axodendritic terminals a mean diameter of 0.698 µm. In tissue in which we simultaneously immunolabeled thalamostriatal terminals for VGLUT2 and striatal neurons for D1 (with about half of spines immunolabeled for D1), 54.6% of VGLUT2+ terminals targeted D1+ spines (i.e., direct pathway striatal neurons), and 37.3% of D1+ spines received VGLUT2+ synaptic contacts. By contrast, 45.4% of VGLUT2+ terminals targeted D1-negative spines (i.e., indirect pathway striatal neurons), and only 25.8% of D1-negative spines received VGLUT2+ synaptic contacts. Similarly, among VGLUT2+ axodendritic synaptic terminals, 59.1% contacted D1+ dendrites, and 40.9% contacted D1-negative dendrites. VGLUT2+ terminals on D1+ spines and dendrites tended to be slightly smaller than those on D1-negative spines and dendrites. Thus, thala-mostriatal terminals contact both direct and indirect pathway striatal neurons, with a slight preference for direct. These results are consistent with physiological studies indicating slightly different effects of thalamic input on the two types of striatal projection neurons. PMID:23047588

Confocal laser scanning microscopy and ultrastructural study of VGLUT2 thalamic input to striatal projection neurons in rats.

PubMed

Lei, Wanlong; Deng, Yunping; Liu, Bingbing; Mu, Shuhua; Guley, Natalie M; Wong, Ting; Reiner, Anton

2013-04-15

We examined thalamic input to striatum in rats using immunolabeling for the vesicular glutamate transporter (VGLUT2). Double immunofluorescence viewed with confocal laser scanning microscopy (CLSM) revealed that VGLUT2+ terminals are distinct from VGLUT1+ terminals. CLSM of Phaseolus vulgaris-leucoagglutinin (PHAL)-labeled cortical or thalamic terminals revealed that VGLUT2 is rare in corticostriatal terminals but nearly always present in thalamostriatal terminals. Electron microscopy revealed that VGLUT2+ terminals made up 39.4% of excitatory terminals in striatum (with VGLUT1+ corticostriatal terminals constituting the rest), and 66.8% of VGLUT2+ terminals synapsed on spines and the remainder on dendrites. VGLUT2+ axospinous terminals had a mean diameter of 0.624 μm, while VGLUT2+ axodendritic terminals a mean diameter of 0.698 μm. In tissue in which we simultaneously immunolabeled thalamostriatal terminals for VGLUT2 and striatal neurons for D1 (with about half of spines immunolabeled for D1), 54.6% of VGLUT2+ terminals targeted D1+ spines (i.e., direct pathway striatal neurons), and 37.3% of D1+ spines received VGLUT2+ synaptic contacts. By contrast, 45.4% of VGLUT2+ terminals targeted D1-negative spines (i.e., indirect pathway striatal neurons), and only 25.8% of D1-negative spines received VGLUT2+ synaptic contacts. Similarly, among VGLUT2+ axodendritic synaptic terminals, 59.1% contacted D1+ dendrites, and 40.9% contacted D1-negative dendrites. VGLUT2+ terminals on D1+ spines and dendrites tended to be slightly smaller than those on D1-negative spines and dendrites. Thus, thalamostriatal terminals contact both direct and indirect pathway striatal neurons, with a slight preference for direct. These results are consistent with physiological studies indicating slightly different effects of thalamic input on the two types of striatal projection neurons. Copyright © 2012 Wiley Periodicals, Inc.

Differential synaptology of vGluT2-containing thalamostriatal afferents between the patch and matrix compartments in rats.

PubMed

Raju, Dinesh V; Shah, Deep J; Wright, Terrence M; Hall, Randy A; Smith, Yoland

2006-11-10

The striatum is divided into two compartments named the patch (or striosome) and the matrix. Although these two compartments can be differentiated by their neurochemical content or afferent and efferent projections, the synaptology of inputs to these striatal regions remains poorly characterized. By using the vesicular glutamate transporters vGluT1 and vGluT2, as markers of corticostriatal and thalamostriatal projections, respectively, we demonstrate a differential pattern of synaptic connections of these two pathways between the patch and the matrix compartments. We also demonstrate that the majority of vGluT2-immunolabeled axon terminals form axospinous synapses, suggesting that thalamic afferents, like corticostriatal inputs, terminate preferentially onto spines in the striatum. Within both compartments, more than 90% of vGluT1-containing terminals formed axospinous synapses, whereas 87% of vGluT2-positive terminals within the patch innervated dendritic spines, but only 55% did so in the matrix. To characterize further the source of thalamic inputs that could account for the increase in axodendritic synapses in the matrix, we undertook an electron microscopic analysis of the synaptology of thalamostriatal afferents to the matrix compartments from specific intralaminar, midline, relay, and associative thalamic nuclei in rats. Approximately 95% of PHA-L-labeled terminals from the central lateral, midline, mediodorsal, lateral dorsal, anteroventral, and ventral anterior/ventral lateral nuclei formed axospinous synapses, a pattern reminiscent of corticostriatal afferents but strikingly different from thalamostriatal projections arising from the parafascicular nucleus (PF), which terminated onto dendritic shafts. These findings provide the first evidence for a differential pattern of synaptic organization of thalamostriatal glutamatergic inputs to the patch and matrix compartments. Furthermore, they demonstrate that the PF is the sole source of significant axodendritic thalamic inputs to striatal projection neurons. These observations pave the way for understanding differential regulatory mechanisms of striatal outflow from the patch and matrix compartments by thalamostriatal afferents. 2006 Wiley-Liss, Inc.

Parvalbumin-producing cortical interneurons receive inhibitory inputs on proximal portions and cortical excitatory inputs on distal dendrites.

PubMed

Kameda, Hiroshi; Hioki, Hiroyuki; Tanaka, Yasuyo H; Tanaka, Takuma; Sohn, Jaerin; Sonomura, Takahiro; Furuta, Takahiro; Fujiyama, Fumino; Kaneko, Takeshi

2012-03-01

To examine inputs to parvalbumin (PV)-producing interneurons, we generated transgenic mice expressing somatodendritic membrane-targeted green fluorescent protein specifically in the interneurons, and completely visualized their dendrites and somata. Using immunolabeling for vesicular glutamate transporter (VGluT)1, VGluT2, and vesicular GABA transporter, we found that VGluT1-positive terminals made contacts 4- and 3.1-fold more frequently with PV-producing interneurons than VGluT2-positive and GABAergic terminals, respectively, in the primary somatosensory cortex. Even in layer 4, where VGluT2-positive terminals were most densely distributed, VGluT1-positive inputs to PV-producing interneurons were 2.4-fold more frequent than VGluT2-positive inputs. Furthermore, although GABAergic inputs to PV-producing interneurons were as numerous as VGluT2-positive inputs in most cortical layers, GABAergic inputs clearly preferred the proximal dendrites and somata of the interneurons, indicating that the sites of GABAergic inputs were more optimized than those of VGluT2-positive inputs. Simulation analysis with a PV-producing interneuron model compatible with the present morphological data revealed a plausible reason for this observation, by showing that GABAergic and glutamatergic postsynaptic potentials evoked by inputs to distal dendrites were attenuated to 60 and 87%, respectively, of those evoked by somatic inputs. As VGluT1-positive and VGluT2-positive axon terminals were presumed to be cortical and thalamic glutamatergic inputs, respectively, cortical excitatory inputs to PV-producing interneurons outnumbered the thalamic excitatory and intrinsic inhibitory inputs more than two-fold in any cortical layer. Although thalamic inputs are known to evoke about two-fold larger unitary excitatory postsynaptic potentials than cortical ones, the present results suggest that cortical inputs control PV-producing interneurons at least as strongly as thalamic inputs. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Thalamic Functional Connectivity in Mild Traumatic Brain Injury: Longitudinal Associations With Patient-Reported Outcomes and Neuropsychological Tests.

PubMed

Banks, Sarah D; Coronado, Rogelio A; Clemons, Lori R; Abraham, Christine M; Pruthi, Sumit; Conrad, Benjamin N; Morgan, Victoria L; Guillamondegui, Oscar D; Archer, Kristin R

2016-08-01

(1) To examine differences in patient-reported outcomes, neuropsychological tests, and thalamic functional connectivity (FC) between patients with mild traumatic brain injury (mTBI) and individuals without mTBI and (2) to determine longitudinal associations between changes in these measures. Prospective observational case-control study. Academic medical center. A sample (N=24) of 13 patients with mTBI (mean age, 39.3±14.0y; 4 women [31%]) and 11 age- and sex-matched controls without mTBI (mean age, 37.6±13.3y; 4 women [36%]). Not applicable. Resting state FC (3T magnetic resonance imaging scanner) was examined between the thalamus and the default mode network, dorsal attention network, and frontoparietal control network. Patient-reported outcomes included pain (Brief Pain Inventory), depressive symptoms (Patient Health Questionnaire-9), posttraumatic stress disorder ([PTSD] Checklist - Civilian Version), and postconcussive symptoms (Rivermead Post-Concussion Symptoms Questionnaire). Neuropsychological tests included the Delis-Kaplan Executive Function System Tower test, Trails B, and Hotel Task. Assessments occurred at 6 weeks and 4 months after hospitalization in patients with mTBI and at a single visit for controls. Student t tests found increased pain, depressive symptoms, PTSD symptoms, and postconcussive symptoms; decreased performance on Trails B; increased FC between the thalamus and the default mode network; and decreased FC between the thalamus and the dorsal attention network and between the thalamus and the frontoparietal control network in patients with mTBI as compared with controls. The Spearman correlation coefficient indicated that increased FC between the thalamus and the dorsal attention network from baseline to 4 months was associated with decreased pain and postconcussive symptoms (corrected P<.05). Findings suggest that alterations in thalamic FC occur after mTBI, and improvements in pain and postconcussive symptoms are correlated with normalization of thalamic FC over time. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Progressive gait ataxia following deep brain stimulation for essential tremor: adverse effect or lack of efficacy?

PubMed

Reich, Martin M; Brumberg, Joachim; Pozzi, Nicolò G; Marotta, Giorgio; Roothans, Jonas; Åström, Mattias; Musacchio, Thomas; Lopiano, Leonardo; Lanotte, Michele; Lehrke, Ralph; Buck, Andreas K; Volkmann, Jens; Isaias, Ioannis U

2016-11-01

Thalamic deep brain stimulation is a mainstay treatment for severe and drug-refractory essential tremor, but postoperative management may be complicated in some patients by a progressive cerebellar syndrome including gait ataxia, dysmetria, worsening of intention tremor and dysarthria. Typically, this syndrome manifests several months after an initially effective therapy and necessitates frequent adjustments in stimulation parameters. There is an ongoing debate as to whether progressive ataxia reflects a delayed therapeutic failure due to disease progression or an adverse effect related to repeated increases of stimulation intensity. In this study we used a multimodal approach comparing clinical stimulation responses, modelling of volume of tissue activated and metabolic brain maps in essential tremor patients with and without progressive ataxia to disentangle a disease-related from a stimulation-induced aetiology. Ten subjects with stable and effective bilateral thalamic stimulation were stratified according to the presence (five subjects) of severe chronic-progressive gait ataxia. We quantified stimulated brain areas and identified the stimulation-induced brain metabolic changes by multiple 18 F-fluorodeoxyglucose positron emission tomography performed with and without active neurostimulation. Three days after deactivating thalamic stimulation and following an initial rebound of symptom severity, gait ataxia had dramatically improved in all affected patients, while tremor had worsened to the presurgical severity, thus indicating a stimulation rather than disease-related phenomenon. Models of the volume of tissue activated revealed a more ventrocaudal stimulation in the (sub)thalamic area of patients with progressive gait ataxia. Metabolic maps of both patient groups differed by an increased glucose uptake in the cerebellar nodule of patients with gait ataxia. Our data suggest that chronic progressive gait ataxia in essential tremor is a reversible cerebellar syndrome caused by a maladaptive response to neurostimulation of the (sub)thalamic area. The metabolic signature of progressive gait ataxia is an activation of the cerebellar nodule, which may be caused by inadvertent current spread and antidromic stimulation of a cerebellar outflow pathway originating in the vermis. An anatomical candidate could be the ascending limb of the uncinate tract in the subthalamic area. Adjustments in programming and precise placement of the electrode may prevent this adverse effect and help fine-tuning deep brain stimulation to ameliorate tremor without negative cerebellar signs. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Analysis of correlation between white matter changes and functional responses in thalamic stroke: a DTI & EEG study.

PubMed

Duru, Adil Deniz; Duru, Dilek Göksel; Yumerhodzha, Sami; Bebek, Nerses

2016-06-01

Diffusion tensor imaging (DTI) allows in vivo structural brain mapping and detection of microstructural disruption of white matter (WM). One of the commonly used parameters for grading the anisotropic diffusivity in WM is fractional anisotropy (FA). FA value helps to quantify the directionality of the local tract bundle. Therefore, FA images are being used in voxelwise statistical analyses (VSA). The present study used Tract-Based Spatial Statistics (TBSS) of FA images across subjects, and computes the mean skeleton map to detect voxelwise knowledge of the tracts yielding to groupwise comparison. The skeleton image illustrates WM structure and shows any changes caused by brain damage. The microstructure of WM in thalamic stroke is investigated, and the VSA results of healthy control and thalamic stroke patients are reported. It has been shown that several skeleton regions were affected subject to the presence of thalamic stroke (FWE, p < 0.05). Furthermore the correlation of quantitative EEG (qEEG) scores and neurophysiological tests with the FA skeleton for the entire test group is also investigated. We compared measurements that are related to the same fibers across subjects, and discussed implications for VSA of WM in thalamic stroke cases, for the relationship between behavioral tests and FA skeletons, and for the correlation between the FA maps and qEEG scores.Results obtained through the regression analyses did not exceed the corrected statistical threshold values for multiple comparisons (uncorrected, p < 0.05). However, in the regression analysis of FA values and the theta band activity of EEG, cingulum bundle and corpus callosum were found to be related. These areas are parts of the Default Mode Network (DMN) where DMN is known to be involved in resting state EEG theta activity. The relation between the EEG alpha band power values and FA values of the skeleton was found to support the cortico-thalamocortical cycles for both subject groups. Further, the neurophysiological tests including Benton Face Recognition (BFR), Digit Span test (DST), Warrington Topographic Memory test (WTMT), California Verbal Learning test (CVLT) has been regressed with the FA skeleton maps for both subject groups. Our results corresponding to DST task were found to be similar with previously reported findings for working memory and episodic memory tasks. For the WTMT, FA values of the cingulum (right) that plays a role in memory process was found to be related with the behavioral responses. Splenium of corpus callosum was found to be correlated for both subject groups for the BFR.

Patterns of developmental expression of the RNA editing enzyme rADAR2.

PubMed

Paupard M-C; O'Connell, M A; Gerber, A P; Zukin, R S

2000-01-01

To date, two structurally related RNA-editing enzymes with adenosine deaminase activity have been identified in mammalian tissue: ADAR1 and ADAR2 [Bass B. I. et al. (1997) RNA 3, 947-949]. In rodents, ADAR2 undergoes alternative RNA splicing, giving rise to two splice variants that differ by the presence or absence of a 10-amino-acid insert in the carboxy-terminal catalytic domain. However, the physiological significance of the splicing and its regional and developmental regulation are as yet unknown. The present study examined spatial and temporal patterns of ADAR2 gene transcripts within specific neuronal populations of rat brain. The two rodent ADAR2 isoforms were expressed at comparable levels at all ages examined. rADAR2 messenger RNA expression was first detectable in the thalamic nuclei formation at embryonic day E19. The rADAR2b insert and rADAR2a splice probes produced images similar to that of the rADAR2 pan probe. At birth, rADAR2a messenger RNA splice variants were abundantly expressed in the thalamic nuclei. No signal for any probe was detectable in other brain regions, including neocortex, hippocampus, striatum and cerebellum at this stage of development. During the first week of postnatal life, rADAR2 messenger RNA expression (detected with the pan probe) increased gradually in several brain regions, with low expression detected at postnatal day P7 in the olfactory bulb, inferior colliculus, and within the pyramidal and granule cell layers of the hippocampus. Hybridization patterns of the rADAR2a variant probe reached peak expression at about the second week of life, while peak expression of the rADAR2b probe was reached at about the third week of life. At the end of the first week of life (P7), expression of both splice variants was strongest in the thalamic nuclei. By P14, rADAR2 messenger RNA expression was more consolidated in the deeper structures, including the thalamic nuclei and the granule cell layer of the cerebellum. By P21, maximal levels of rADARb expression were observed in the thalamic nuclei, inferior colliculus, cerebellum and pontine nuclei. In the adult, rADAR2 messenger RNA expression was of highest intensity in the thalamic nuclei, with high levels of expression in the olfactory bulb, inferior colliculus, cerebellum and pontine nuclei. At the level of the hippocampus, positive labelling was restricted to the CA3 region of the Ammon's horn and the dentate gyrus, with weak signals in the CA1 subfield. rADAR2 pan expression was at near background levels throughout the neocortex and caudate putamen. In summary, our study shows that ADAR2 messenger RNA expression is regulated in a cell-specific manner throughout development. At early ages, ADAR2 messenger RNA is expressed only within (and restricted to) the thalamic nuclei. By the third postnatal week, expression of the editase enzyme is more widely distributed throughout the olfactory bulb, CA3 and dentate gyrus of the hippocampus, thalamus, inferior colliculus and the molecular cell layer of the cerebellum. ADAR2 is thought to act at specific nucleotide positions in primary transcripts encoding glutamate receptor subunits, thereby altering gating and ionic permeability properties of AMPA- and kainate-activated channels. ADAR2 also acts at pre-messenger RNA encoding the serotonin 5HT-2C receptor to alter G-protein coupling. Thus, RNA editing may be an important mechanism for fine-tuning of the physiological and pharmacological properties of transmitter receptors of the central nervous system.

Functional neural networks underlying response inhibition in adolescents and adults.

PubMed

Stevens, Michael C; Kiehl, Kent A; Pearlson, Godfrey D; Calhoun, Vince D

2007-07-19

This study provides the first description of neural network dynamics associated with response inhibition in healthy adolescents and adults. Functional and effective connectivity analyses of whole brain hemodynamic activity elicited during performance of a Go/No-Go task were used to identify functionally integrated neural networks and characterize their causal interactions. Three response inhibition circuits formed a hierarchical, inter-dependent system wherein thalamic modulation of input to premotor cortex by fronto-striatal regions led to response suppression. Adolescents differed from adults in the degree of network engagement, regional fronto-striatal-thalamic connectivity, and network dynamics. We identify and characterize several age-related differences in the function of neural circuits that are associated with behavioral performance changes across adolescent development.

Preserved memory abilities in thalamic amnesia.

PubMed

Nichelli, P; Bahmanian-Behbahani, G; Gentilini, M; Vecchi, A

1988-12-01

The pattern of preserved learning abilities is described in a severely amnesic patient after bilateral thalamic infarction. Experimental findings cannot be accounted for both by the view that only episodic memory is impaired in amnesia, while semantic memory is spared, and by the theory that what is spared in amnesia is procedural learning contrasted with impaired declarative memory. In agreement with Warrington and Weiskrantz (1982), diencephalic amnesia is considered to be a disconnection syndrome between the frontal and temporal lobes. The conditions for showing spared and impaired memory in amnesics are specified on the basis of the performance of the patient and of the data available in the literature. This allows us to derive practical suggestions for programmes aimed at remediation of memory defects.

Functional neural networks underlying response inhibition in adolescents and adults

PubMed Central

Stevens, Michael C.; Kiehl, Kent A.; Pearlson, Godfrey D.; Calhoun, Vince D.

2008-01-01

This study provides the first description of neural network dynamics associated with response inhibition in healthy adolescents and adults. Functional and effective connectivity analyses of whole brain hemodynamic activity elicited during performance of a Go/No-Go task were used to identify functionally-integrated neural networks and characterize their causal interactions. Three response inhibition circuits formed a hierarchical, inter-dependent system wherein thalamic modulation of input to premotor cortex by frontostriatal regions led to response suppression. Adolescents differed from adults in the degree of network engagement, regional fronto-striatal-thalamic connectivity, and network dynamics. We identify and characterize several age-related differences in the function of neural circuits that are associated with behavioral performance changes across adolescent development. PMID:17467816

Intracortical circuits amplify sound-evoked activity in primary auditory cortex following systemic injection of salicylate in the rat

PubMed Central

Chrostowski, Michael; Salvi, Richard J.; Allman, Brian L.

2012-01-01

A high dose of sodium salicylate temporarily induces tinnitus, mild hearing loss, and possibly hyperacusis in humans and other animals. Salicylate has well-established effects on cochlear function, primarily resulting in the moderate reduction of auditory input to the brain. Despite decreased peripheral sensitivity and output, salicylate induces a paradoxical enhancement of the sound-evoked field potential at the level of the primary auditory cortex (A1). Previous electrophysiologic studies have begun to characterize changes in thalamorecipient layers of A1; however, A1 is a complex neural circuit with recurrent intracortical connections. To describe the effects of acute systemic salicylate treatment on both thalamic and intracortical sound-driven activity across layers of A1, we applied current-source density (CSD) analysis to field potentials sampled across cortical layers in the anesthetized rat. CSD maps were normally characterized by a large, short-latency, monosynaptic, thalamically driven sink in granular layers followed by a lower amplitude, longer latency, polysynaptic, intracortically driven sink in supragranular layers. Following systemic administration of salicylate, there was a near doubling of both granular and supragranular sink amplitudes at higher sound levels. The supragranular sink amplitude input/output function changed from becoming asymptotic at approximately 50 dB to sharply nonasymptotic, often dominating the granular sink amplitude at higher sound levels. The supragranular sink also exhibited a significant decrease in peak latency, reflecting an acceleration of intracortical processing of the sound-evoked response. Additionally, multiunit (MU) activity was altered by salicylate; the normally onset/sustained MU response type was transformed into a primarily onset response type in granular and infragranular layers. The results from CSD analysis indicate that salicylate significantly enhances sound-driven response via intracortical circuits. PMID:22496535

Hierarchical Distribution of the Tau Cytoskeletal Pathology in the Thalamus of Alzheimer's Disease Patients.

PubMed

Rüb, Udo; Stratmann, Katharina; Heinsen, Helmut; Del Turco, Domenico; Ghebremedhin, Estifanos; Seidel, Kay; den Dunnen, Wilfred; Korf, Horst-Werner

2016-01-01

In spite of considerable progress in neuropathological research on Alzheimer's disease (AD), knowledge regarding the exact pathoanatomical distribution of the tau cytoskeletal pathology in the thalamus of AD patients in the advanced Braak and Braak AD stages V or VI of the cortical cytoskeletal pathology is still fragmentary. Investigation of serial 100 μm-thick brain tissue sections through the thalamus of clinically diagnosed AD patients with Braak and Braak AD stage V or VI cytoskeletal pathologies immunostained with the anti-tau AT8 antibody, along with the affection of the extraterritorial reticular nucleus of the thalamus, reveals a consistent and severe tau immunoreactive cytoskeletal pathology in the limbic nuclei of the thalamus (e.g., paraventricular, anterodorsal and laterodorsal nuclei, limitans-suprageniculate complex). The thalamic nuclei integrated into the associative networks of the human brain (e.g., ventral anterior and mediodorsal nuclei) are only mildly affected, while its motor precerebellar (ventral lateral nucleus) and sensory nuclei (e.g., lateral and medial geniculate bodies, ventral posterior medial and lateral nuclei, parvocellular part of the ventral posterior medial nucleus) are more or less spared. The highly stereotypical and characteristic thalamic distribution pattern of the AD-related tau cytoskeletal pathology represents an anatomical mirror of the hierarchical topographic distribution of the cytoskeletal pathology in the interconnected regions of the cerebral cortex of AD patients. These pathoanatomical parallels support the pathophysiological concept of a transneuronal spread of the disease process of AD along anatomical pathways. The AD-related tau cytoskeletal pathology in the thalamus most likely contributes substantially to the neuropsychiatric disease symptoms (e.g., dementia), attention deficits, oculomotor dysfunctions, altered non-discriminative aspects of pain experience of AD patients, and the disruption of their waking and sleeping patterns.

How Acute Total Sleep Loss Affects the Attending Brain: A Meta-Analysis of Neuroimaging Studies

PubMed Central

Ma, Ning; Dinges, David F.; Basner, Mathias; Rao, Hengyi

2015-01-01

Study Objectives: Attention is a cognitive domain that can be severely affected by sleep deprivation. Previous neuroimaging studies have used different attention paradigms and reported both increased and reduced brain activation after sleep deprivation. However, due to large variability in sleep deprivation protocols, task paradigms, experimental designs, characteristics of subject populations, and imaging techniques, there is no consensus regarding the effects of sleep loss on the attending brain. The aim of this meta-analysis was to identify brain activations that are commonly altered by acute total sleep deprivation across different attention tasks. Design: Coordinate-based meta-analysis of neuroimaging studies of performance on attention tasks during experimental sleep deprivation. Methods: The current version of the activation likelihood estimation (ALE) approach was used for meta-analysis. The authors searched published articles and identified 11 sleep deprivation neuroimaging studies using different attention tasks with a total of 185 participants, equaling 81 foci for ALE analysis. Results: The meta-analysis revealed significantly reduced brain activation in multiple regions following sleep deprivation compared to rested wakefulness, including bilateral intraparietal sulcus, bilateral insula, right prefrontal cortex, medial frontal cortex, and right parahippocampal gyrus. Increased activation was found only in bilateral thalamus after sleep deprivation compared to rested wakefulness. Conclusion: Acute total sleep deprivation decreases brain activation in the fronto-parietal attention network (prefrontal cortex and intraparietal sulcus) and in the salience network (insula and medial frontal cortex). Increased thalamic activation after sleep deprivation may reflect a complex interaction between the de-arousing effects of sleep loss and the arousing effects of task performance on thalamic activity. Citation: Ma N, Dinges DF, Basner M, Rao H. How acute total sleep loss affects the attending brain: a meta-analysis of neuroimaging studies. SLEEP 2015;38(2):233–240. PMID:25409102

Antinociceptive effect of chlorphenesin carbamate in adjuvant arthritic rats.

PubMed

Okuyama, S; Aihara, H

1987-02-01

The antinociceptive effect of chlorphenesin carbamate (CPC) and mephenesin were examined in adjuvant arthritic rats. In the behavioral study, CPC (100-400 mg/kg, p.o.) but not mephenesin (100-400 mg/kg, p.o.) had a dose-dependent antinociceptive effect, determined using the flexion test. In the electrophysiological study, CPC (25-50 mg/kg, i.v.) but not mephenesin (50 mg/kg, i.v.) depressed the evoked neuronal responses of nociceptive neurons in the ventrobasal thalamus (VB), while the evoked responses of non-nociceptive neurons were not depressed by either CPC (50 mg/kg, i.v.) or mephenesin (50 mg/kg, i.v.). The spontaneous firings of the VB nociceptive neurons were depressed by both CPC (50 mg/kg, i.v.) and mephenesin (50 mg/kg, i.v.). However, mephenesin (50 mg/kg, i.v.) but not CPC (50 mg/kg, i.v.) also depressed the spontaneous firings of the mesencephalic reticular formation (RF), in these adjuvant arthritic rats. These results indicate that CPC but not mephenesin, has an antinociceptive action in adjuvant arthritic rats.

The Human Thalamus Is an Integrative Hub for Functional Brain Networks

PubMed Central

Bertolero, Maxwell A.

2017-01-01

The thalamus is globally connected with distributed cortical regions, yet the functional significance of this extensive thalamocortical connectivity remains largely unknown. By performing graph-theoretic analyses on thalamocortical functional connectivity data collected from human participants, we found that most thalamic subdivisions display network properties that are capable of integrating multimodal information across diverse cortical functional networks. From a meta-analysis of a large dataset of functional brain-imaging experiments, we further found that the thalamus is involved in multiple cognitive functions. Finally, we found that focal thalamic lesions in humans have widespread distal effects, disrupting the modular organization of cortical functional networks. This converging evidence suggests that the human thalamus is a critical hub region that could integrate diverse information being processed throughout the cerebral cortex as well as maintain the modular structure of cortical functional networks. SIGNIFICANCE STATEMENT The thalamus is traditionally viewed as a passive relay station of information from sensory organs or subcortical structures to the cortex. However, the thalamus has extensive connections with the entire cerebral cortex, which can also serve to integrate information processing between cortical regions. In this study, we demonstrate that multiple thalamic subdivisions display network properties that are capable of integrating information across multiple functional brain networks. Moreover, the thalamus is engaged by tasks requiring multiple cognitive functions. These findings support the idea that the thalamus is involved in integrating information across cortical networks. PMID:28450543

Deafferentation in thalamic and pontine areas in severe traumatic brain injury.

PubMed

Laouchedi, M; Galanaud, D; Delmaire, C; Fernandez-Vidal, S; Messé, A; Mesmoudi, S; Oulebsir Boumghar, F; Pélégrini-Issac, M; Puybasset, L; Benali, H; Perlbarg, V

2015-07-01

Severe traumatic brain injury (TBI) is characterized mainly by diffuse axonal injuries (DAI). The cortico-subcortical disconnections induced by such fiber disruption play a central role in consciousness recovery. We hypothesized that these cortico-subcortical deafferentations inferred from diffusion MRI data could differentiate between TBI patients with favorable or unfavorable (death, vegetative state, or minimally conscious state) outcome one year after injury. Cortico-subcortical fiber density maps were derived by using probabilistic tractography from diffusion tensor imaging data acquired in 24 severe TBI patients and 9 healthy controls. These maps were compared between patients and controls as well as between patients with favorable (FO) and unfavorable (UFO) 1-year outcome to identify the thalamo-cortical and ponto-thalamo-cortical pathways involved in the maintenance of consciousness. Thalamo-cortical and ponto-thalamo-cortical fiber density was significantly lower in TBI patients than in healthy controls. Comparing FO and UFO TBI patients showed thalamo-cortical deafferentation associated with unfavorable outcome for projections from ventral posterior and intermediate thalamic nuclei to the associative frontal, sensorimotor and associative temporal cortices. Specific ponto-thalamic deafferentation in projections from the upper dorsal pons (including the reticular formation) was also associated with unfavorable outcome. Fiber density of cortico-subcortical pathways as measured from diffusion MRI tractography is a relevant candidate biomarker for early prediction of one-year favorable outcome in severe TBI. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Dynamics of Action Potential Initiation in the GABAergic Thalamic Reticular Nucleus In Vivo

PubMed Central

Muñoz, Fabián; Fuentealba, Pablo

2012-01-01

Understanding the neural mechanisms of action potential generation is critical to establish the way neural circuits generate and coordinate activity. Accordingly, we investigated the dynamics of action potential initiation in the GABAergic thalamic reticular nucleus (TRN) using in vivo intracellular recordings in cats in order to preserve anatomically-intact axo-dendritic distributions and naturally-occurring spatiotemporal patterns of synaptic activity in this structure that regulates the thalamic relay to neocortex. We found a wide operational range of voltage thresholds for action potentials, mostly due to intrinsic voltage-gated conductances and not synaptic activity driven by network oscillations. Varying levels of synchronous synaptic inputs produced fast rates of membrane potential depolarization preceding the action potential onset that were associated with lower thresholds and increased excitability, consistent with TRN neurons performing as coincidence detectors. On the other hand the presence of action potentials preceding any given spike was associated with more depolarized thresholds. The phase-plane trajectory of the action potential showed somato-dendritic propagation, but no obvious axon initial segment component, prominent in other neuronal classes and allegedly responsible for the high onset speed. Overall, our results suggest that TRN neurons could flexibly integrate synaptic inputs to discharge action potentials over wide voltage ranges, and perform as coincidence detectors and temporal integrators, supported by a dynamic action potential threshold. PMID:22279567

Early life stress predicts thalamic hyperconnectivity: A transdiagnostic study of global connectivity.

PubMed

Philip, Noah S; Tyrka, Audrey R; Albright, Sarah E; Sweet, Lawrence H; Almeida, Jorge; Price, Lawrence H; Carpenter, Linda L

2016-08-01

Early life stress (ELS) is an established risk factor for psychiatric illness and is associated with altered functional connectivity within- and between intrinsic neural networks. The widespread nature of these disruptions suggests that broad imaging measures of neural connectivity, such as global based connectivity (GBC), may be particularly appropriate for studies of this population. GBC is designed to identify brain regions having maximal functional connectedness with the rest of the brain, and alterations in GBC may reflect a restriction or broadening of network synchronization. We evaluated whether ELS severity predicted GBC in a sample (N = 46) with a spectrum of ELS exposure. Participants included healthy controls without ELS, those with at least moderate ELS but without psychiatric disorders, and a group of patients with ELS- related psychiatric disorders. The spatial distribution of GBC peaked in regions of the salience and default mode networks, and ELS severity predicted increased GBC of the left thalamus (corrected p < 0.005, r = 0.498). Thalamic connectivity was subsequently evaluated and revealed reduced connectivity with the salience network, particularly the dorsal anterior cingulate cortex (corrected p < 0.005), only in the patient group. These findings support a model of disrupted thalamic connectivity in ELS and trauma-related negative affect states, and underscore the importance of a transdiagnostic, dimensional neuroimaging approach to understanding the sequelae of trauma exposure. Published by Elsevier Ltd.

The thalamus and multiple sclerosis

PubMed Central

Minagar, Alireza; Barnett, Michael H.; Benedict, Ralph H.B.; Pelletier, Daniel; Pirko, Istvan; Sahraian, Mohamad Ali; Frohman, Elliott

2013-01-01

The paired thalamic nuclei are gray matter (GM) structures on both sides of the third ventricle that play major roles in cortical activation, relaying sensory information to the higher cortical centers that influence cognition. Multiple sclerosis (MS) is an immune-mediated disease of the human CNS that affects both the white matter (WM) and GM. A number of clinical observations as well as recent neuropathologic and neuroimaging studies have clearly demonstrated extensive involvement of the thalamus, basal ganglia, and neocortex in patients with MS. Modern MRI techniques permit visualization of GM lesions and measurement of atrophy. These contemporary methods have fundamentally altered our understanding of the pathophysiologic nature of MS. Evidence confirms the contention that GM injury can be detected in the earliest phases of MS, and that iron deposition and atrophy of deep gray nuclei are closely related to the magnitude of inflammation. Extensive involvement of GM, and particularly of the thalamus, is associated with a wide range of clinical manifestations including cognitive decline, motor deficits, fatigue, painful syndromes, and ocular motility disturbances in patients with MS. In this review, we characterize the neuropathologic, neuroimaging, and clinical features of thalamic involvement in MS. Further, we underscore the contention that neuropathologic and neuroimaging correlative investigations of thalamic derangements in MS may elucidate not heretofore considered pathobiological underpinnings germane to understanding the ontogeny, magnitude, and progression of the disease process. PMID:23296131

The thalamus and multiple sclerosis: modern views on pathologic, imaging, and clinical aspects.

PubMed

Minagar, Alireza; Barnett, Michael H; Benedict, Ralph H B; Pelletier, Daniel; Pirko, Istvan; Sahraian, Mohamad Ali; Frohman, Elliott; Zivadinov, Robert

2013-01-08

The paired thalamic nuclei are gray matter (GM) structures on both sides of the third ventricle that play major roles in cortical activation, relaying sensory information to the higher cortical centers that influence cognition. Multiple sclerosis (MS) is an immune-mediated disease of the human CNS that affects both the white matter (WM) and GM. A number of clinical observations as well as recent neuropathologic and neuroimaging studies have clearly demonstrated extensive involvement of the thalamus, basal ganglia, and neocortex in patients with MS. Modern MRI techniques permit visualization of GM lesions and measurement of atrophy. These contemporary methods have fundamentally altered our understanding of the pathophysiologic nature of MS. Evidence confirms the contention that GM injury can be detected in the earliest phases of MS, and that iron deposition and atrophy of deep gray nuclei are closely related to the magnitude of inflammation. Extensive involvement of GM, and particularly of the thalamus, is associated with a wide range of clinical manifestations including cognitive decline, motor deficits, fatigue, painful syndromes, and ocular motility disturbances in patients with MS. In this review, we characterize the neuropathologic, neuroimaging, and clinical features of thalamic involvement in MS. Further, we underscore the contention that neuropathologic and neuroimaging correlative investigations of thalamic derangements in MS may elucidate not heretofore considered pathobiological underpinnings germane to understanding the ontogeny, magnitude, and progression of the disease process.

Subcortical roles in lexical task processing: Inferences from thalamic and subthalamic event-related potentials.

PubMed

Tiedt, Hannes O; Ehlen, Felicitas; Krugel, Lea K; Horn, Andreas; Kühn, Andrea A; Klostermann, Fabian

2017-01-01

Subcortical functions for language capacities are poorly defined, but may be investigated in the context of deep brain stimulation. Here, we studied event-related potentials recorded from electrodes in the subthalamic nucleus (STN) and the thalamic ventral intermediate nucleus (VIM) together with surface-EEG. Participants completed a lexical decision task (LDT), which required the differentiation of acoustically presented words from pseudo-words by button press. Target stimuli were preceded by prime-words. In recordings from VIM, a slow potential shift apparent at the lower electrode contacts persisted during target stimulus presentation (equally for words and pseudo-words). In contrast, recordings from STN electrodes showed a short local activation on prime-words but not target-stimuli. In both depth-recording regions, further components related to contralateral motor responses to target words were evident. On scalp level, mid-central activations on (pseudo)lexical stimuli were obtained, in line with the expression of N400 potentials. The prolonged activity recorded from VIM, exclusively accompanying the relevant LDT phase, is in line with the idea of thalamic "selective engagement" for supporting the realization of the behavioral focus demanded by the task. In contrast, the phasic prime related activity rather indicates "procedural" STN functions, for example, for trial sequencing or readiness inhibition of prepared target reactions. Hum Brain Mapp 38:370-383, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Post-Traumatic Tremor and Thalamic Deep Brain Stimulation: Evidence for Use of Diffusion Tensor Imaging.

PubMed

Boccard, Sandra G J; Rebelo, Pedro; Cheeran, Binith; Green, Alexander; FitzGerald, James J; Aziz, Tipu Z

2016-12-01

Deep brain stimulation (DBS) is a well-established treatment to reduce tremor, notably in Parkinson disease. DBS may also be effective in post-traumatic tremor, one of the most common movement disorders caused by head injury. However, the cohorts of patients often have multiple lesions that may impact the outcome depending on which fiber tracts are affected. A 20-year-old man presented after road traffic accident with severe closed head injury and polytrauma. Computed tomography scan showed left frontal and basal ganglia hemorrhagic contusions and intraventricular hemorrhage. A disabling tremor evolved in step with motor recovery. Despite high-intensity signals in the intended thalamic target, a visual analysis of the preoperative diffusion tensor imaging revealed preservation of connectivity of the intended target, ventralis oralis posterior thalamic nucleus (VOP). This was confirmed by the postoperative tractography study presented here. DBS of the VOP/zona incerta was performed. Six months postimplant, marked improvement of action (postural, kinetic, and intention) tremor was achieved. We demonstrated a strong connectivity between the VOP and the superior frontal gyrus containing the premotor cortex and other central brain areas responsible for movement control. In spite of an existing lesion in the target, the preservation of these tracts may be relevant to the improvement of the patient's symptoms by DBS. Copyright © 2016 Elsevier Inc. All rights reserved.

General and specific consciousness: a first-order representationalist approach

PubMed Central

Mehta, Neil; Mashour, George A.

2013-01-01

It is widely acknowledged that a complete theory of consciousness should explain general consciousness (what makes a state conscious at all) and specific consciousness (what gives a conscious state its particular phenomenal quality). We defend first-order representationalism, which argues that consciousness consists of sensory representations directly available to the subject for action selection, belief formation, planning, etc. We provide a neuroscientific framework for this primarily philosophical theory, according to which neural correlates of general consciousness include prefrontal cortex, posterior parietal cortex, and non-specific thalamic nuclei, while neural correlates of specific consciousness include sensory cortex and specific thalamic nuclei. We suggest that recent data support first-order representationalism over biological theory, higher-order representationalism, recurrent processing theory, information integration theory, and global workspace theory. PMID:23882231

Intraoperative neurophysiological responses in epileptic patients submitted to hippocampal and thalamic deep brain stimulation.

PubMed

Cukiert, Arthur; Cukiert, Cristine Mella; Argentoni-Baldochi, Meire; Baise, Carla; Forster, Cássio Roberto; Mello, Valeria Antakli; Burattini, José Augusto; Lima, Alessandra Moura

2011-12-01

Deep brain stimulation (DBS) has been used in an increasing frequency for treatment of refractory epilepsy. Acute deep brain macrostimulation intraoperative findings were sparsely published in the literature. We report on our intraoperative macrostimulation findings during thalamic and hippocampal DBS implantation. Eighteen patients were studied. All patients underwent routine pre-operative evaluation that included clinical history, neurological examination, interictal and ictal EEG, high resolution 1.5T MRI and neuropsychological testing. Six patients with temporal lobe epilepsy were submitted to hippocampal DBS (Hip-DBS); 6 patients with focal epilepsy were submitted to anterior thalamic nucleus DBS (AN-DBS) and 6 patients with generalized epilepsy were submitted to centro-median thalamic nucleus DBS (CM-DBS). Age ranged from 9 to 40 years (11 males). All patients were submitted to bilateral quadripolar DBS electrode implantation in a single procedure, under general anesthesia, and intraoperative scalp EEG monitoring. Final electrode's position was checked postoperatively using volumetric CT scanning. Bipolar stimulation using the more proximal and distal electrodes was performed. Final standard stimulation parameters were 6Hz, 4V, 300μs (low frequency range: LF) or 130Hz, 4V, 300μs (high frequency range: HF). Bilateral recruiting response (RR) was obtained after unilateral stimulation in all patients submitted to AN and CM-DBS using LF stimulation. RR was widespread but prevailed over the fronto-temporal region bilaterally, and over the stimulated hemisphere. HF stimulation led to background slowing and a DC shift. The mean voltage for the appearance of RR was 4V (CM) and 3V (AN). CM and AN-DBS did not alter inter-ictal spiking frequency or morphology. RR obtained after LF Hip-DBS was restricted to the stimulated temporal lobe and no contralateral activation was noted. HF stimulation yielded no visually recognizable EEG modification. Mean intensity for initial appearance of RR was 3V. In 5 of the 6 patients submitted to Hip-DBS, an increase in inter-ictal spiking was noted unilaterally immediately after electrode insertion. Intraoperative LF stimulation did not modify temporal lobe spiking; on the other hand, HF was effective in abolishing inter-ictal spiking in 4 of the 6 patients studied. There was no immediate morbidity or mortality in this series. Macrostimulation might be used to confirm that the hardware was working properly. There was no typical RR derived from each studied thalamic nuclei after LF stimulation. On the other hand, absence of such RRs was highly suggestive of hardware malfunction or inadequate targeting. Thalamic-DBS (Th-DBS) RR was always bilateral after unilateral stimulation, although they somehow prevailed over the stimulated hemisphere. Contrary to Th-DBS, Hip-DBS gave rise to localized RR over the ipsolateral temporal neocortex, and absence of this response might very likely be related to inadequate targeting or hardware failure. Increased spiking was seen over temporal neocortex during hippocampal electrode insertion; this might point to the more epileptogenic hippocampal region in each individual patient. We did not notice any intraoperative response difference among patients with temporal lobe epilepsy with or without MTS. The relationship between these intraoperative findings and seizure outcome is not yet clear and should be further evaluated. 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Deep brain stimulation for the treatment of uncommon tremor syndromes

PubMed Central

Ramirez-Zamora, Adolfo; Okun, Michael S.

2016-01-01

ABSTRACT Introduction: Deep brain stimulation (DBS) has become a standard therapy for the treatment of select cases of medication refractory essential tremor and Parkinson’s disease however the effectiveness and long-term outcomes of DBS in other uncommon and complex tremor syndromes has not been well established. Traditionally, the ventralis intermedius nucleus (VIM) of the thalamus has been considered the main target for medically intractable tremors; however alternative brain regions and improvements in stereotactic techniques and hardware may soon change the horizon for treatment of complex tremors. Areas covered: In this article, we conducted a PubMed search using different combinations between the terms ‘Uncommon tremors’, ‘Dystonic tremor’, ‘Holmes tremor’ ‘Midbrain tremor’, ‘Rubral tremor’, ‘Cerebellar tremor’, ‘outflow tremor’, ‘Multiple Sclerosis tremor’, ‘Post-traumatic tremor’, ‘Neuropathic tremor’, and ‘Deep Brain Stimulation/DBS’. Additionally, we examined and summarized the current state of evolving interventions for treatment of complex tremor syndromes. Expert c ommentary: Recently reported interventions for rare tremors include stimulation of the posterior subthalamic area, globus pallidus internus, ventralis oralis anterior/posterior thalamic subnuclei, and the use of dual lead stimulation in one or more of these targets. Treatment should be individualized and dictated by tremor phenomenology and associated clinical features. PMID:27228280

Brain Imaging in Pediatric Obsessive-Compulsive Disorder

ERIC Educational Resources Information Center

MacMaster, Frank P.; O'Neill, Joseph; Rosenberg, David R.

2008-01-01

Neuroimaging findings support the frontal-striatal-thalamic model of pediatric obsessive-compulsive disorder. Glutamate is also implicated in the pathological finding of the disease. Implications for pediatric OCD treatments are discussed.

Speech and language adverse effects after thalamotomy and deep brain stimulation in patients with movement disorders: A meta-analysis.

PubMed

Alomar, Soha; King, Nicolas K K; Tam, Joseph; Bari, Ausaf A; Hamani, Clement; Lozano, Andres M

2017-01-01

The thalamus has been a surgical target for the treatment of various movement disorders. Commonly used therapeutic modalities include ablative and nonablative procedures. A major clinical side effect of thalamic surgery is the appearance of speech problems. This review summarizes the data on the development of speech problems after thalamic surgery. A systematic review and meta-analysis was performed using nine databases, including Medline, Web of Science, and Cochrane Library. We also checked for articles by searching citing and cited articles. We retrieved studies between 1960 and September 2014. Of a total of 2,320 patients, 19.8% (confidence interval: 14.8-25.9) had speech difficulty after thalamotomy. Speech difficulty occurred in 15% (confidence interval: 9.8-22.2) of those treated with a unilaterally and 40.6% (confidence interval: 29.5-52.8) of those treated bilaterally. Speech impairment was noticed 2- to 3-fold more commonly after left-sided procedures (40.7% vs. 15.2%). Of the 572 patients that underwent DBS, 19.4% (confidence interval: 13.1-27.8) experienced speech difficulty. Subgroup analysis revealed that this complication occurs in 10.2% (confidence interval: 7.4-13.9) of patients treated unilaterally and 34.6% (confidence interval: 21.6-50.4) treated bilaterally. After thalamotomy, the risk was higher in Parkinson's patients compared to patients with essential tremor: 19.8% versus 4.5% in the unilateral group and 42.5% versus 13.9% in the bilateral group. After DBS, this rate was higher in essential tremor patients. Both lesioning and stimulation thalamic surgery produce adverse effects on speech. Left-sided and bilateral procedures are approximately 3-fold more likely to cause speech difficulty. This effect was higher after thalamotomy compared to DBS. In the thalamotomy group, the risk was higher in Parkinson's patients, whereas in the DBS group it was higher in patients with essential tremor. Understanding the pathophysiology of speech disturbance after thalamic procedures is a priority. © 2017 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Serotonin gating of cortical and thalamic glutamate inputs onto principal neurons of the basolateral amygdala.

PubMed

Guo, Ji-Dong; O'Flaherty, Brendan M; Rainnie, Donald G

2017-11-01

The basolateral amygdala (BLA) is a key site for crossmodal association of sensory stimuli and an important relay in the neural circuitry of emotion. Indeed, the BLA receives substantial glutamatergic inputs from multiple brain regions including the prefrontal cortex and thalamic nuclei. Modulation of glutamatergic transmission in the BLA regulates stress- and anxiety-related behaviors. Serotonin (5-HT) also plays an important role in regulating stress-related behavior through activation of both pre- and postsynaptic 5-HT receptors. Multiple 5-HT receptors are expressed in the BLA, where 5-HT has been reported to modulate glutamatergic transmission. However, the 5-HT receptor subtype mediating this effect is not yet clear. The aim of this study was to use patch-clamp recordings from BLA neurons in an ex vivo slice preparation to examine 1) the effect of 5-HT on extrinsic sensory inputs, and 2) to determine if any pathway specificity exists in 5-HT regulation of glutamatergic transmission. Two independent input pathways into the BLA were stimulated: the external capsule to mimic cortical input, and the internal capsule to mimic thalamic input. Bath application of 5-HT reversibly reduced the amplitude of evoked excitatory postsynaptic currents (eEPSCs) induced by stimulation of both pathways. The decrease was associated with an increase in the paired-pulse ratio and coefficient of variation of eEPSC amplitude, suggesting 5-HT acts presynaptically. Moreover, the effect of 5-HT in both pathways was mimicked by the selective 5-HT 1B receptor agonist CP93129, but not by the 5-HT 1A receptor agonist 8-OH DPAT. Similarly the effect of exogenous 5-HT was blocked by the 5-HT 1B receptor antagonist GR55562, but not affected by the 5-HT 1A receptor antagonist WAY 100635 or the 5-HT 2 receptor antagonists pirenperone and MDL 100907. Together these data suggest 5-HT gates cortical and thalamic glutamatergic inputs into the BLA by activating presynaptic 5-HT 1B receptors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Functional correlates of the therapeutic and adverse effects evoked by thalamic stimulation for essential tremor

PubMed Central

Gibson, William S.; Jo, Hang Joon; Testini, Paola; Cho, Shinho; Felmlee, Joel P.; Welker, Kirk M.; Klassen, Bryan T.; Min, Hoon-Ki

2016-01-01

Deep brain stimulation is an established neurosurgical therapy for movement disorders including essential tremor and Parkinson’s disease. While typically highly effective, deep brain stimulation can sometimes yield suboptimal therapeutic benefit and can cause adverse effects. In this study, we tested the hypothesis that intraoperative functional magnetic resonance imaging could be used to detect deep brain stimulation-evoked changes in functional and effective connectivity that would correlate with the therapeutic and adverse effects of stimulation. Ten patients receiving deep brain stimulation of the ventralis intermedius thalamic nucleus for essential tremor underwent functional magnetic resonance imaging during stimulation applied at a series of stimulation localizations, followed by evaluation of deep brain stimulation-evoked therapeutic and adverse effects. Correlations between the therapeutic effectiveness of deep brain stimulation (3 months postoperatively) and deep brain stimulation-evoked changes in functional and effective connectivity were assessed using region of interest-based correlation analysis and dynamic causal modelling, respectively. Further, we investigated whether brain regions might exist in which activation resulting from deep brain stimulation might correlate with the presence of paraesthesias, the most common deep brain stimulation-evoked adverse effect. Thalamic deep brain stimulation resulted in activation within established nodes of the tremor circuit: sensorimotor cortex, thalamus, contralateral cerebellar cortex and deep cerebellar nuclei (FDR q < 0.05). Stimulation-evoked activation in all these regions of interest, as well as activation within the supplementary motor area, brainstem, and inferior frontal gyrus, exhibited significant correlations with the long-term therapeutic effectiveness of deep brain stimulation (P < 0.05), with the strongest correlation (P < 0.001) observed within the contralateral cerebellum. Dynamic causal modelling revealed a correlation between therapeutic effectiveness and attenuated within-region inhibitory connectivity in cerebellum. Finally, specific subregions of sensorimotor cortex were identified in which deep brain stimulation-evoked activation correlated with the presence of unwanted paraesthesias. These results suggest that thalamic deep brain stimulation in tremor likely exerts its effects through modulation of both olivocerebellar and thalamocortical circuits. In addition, our findings indicate that deep brain stimulation-evoked functional activation maps obtained intraoperatively may contain predictive information pertaining to the therapeutic and adverse effects induced by deep brain stimulation. PMID:27329768

Unconditioned stimulus pathways to the amygdala: effects of lesions of the posterior intralaminar thalamus on foot-shock-induced c-Fos expression in the subdivisions of the lateral amygdala.

PubMed

Lanuza, E; Moncho-Bogani, J; Ledoux, J E

2008-08-26

The lateral nucleus of the amygdala (LA) is a site of convergence for auditory (conditioned stimulus) and foot-shock (unconditioned stimulus) inputs during fear conditioning. The auditory pathways to LA are well characterized, but less is known about the pathways through which foot shock is transmitted. Anatomical tracing and physiological recording studies suggest that the posterior intralaminar thalamic nucleus, which projects to LA, receives both auditory and somatosensory inputs. In the present study we examined the expression of the immediate-early gene c-fos in the LA in rats in response to foot-shock stimulation. We then determined the effects of posterior intralaminar thalamic lesions on foot-shock-induced c-Fos expression in the LA. Foot-shock stimulation led to an increase in the density of c-Fos-positive cells in all LA subnuclei in comparison to controls exposed to the conditioning box but not shocked. However, some differences among the dorsolateral, ventrolateral and ventromedial subnuclei were observed. The ventrolateral subnucleus showed a homogeneous activation throughout its antero-posterior extension. In contrast, only the rostral aspect of the ventromedial subnucleus and the central aspect of the dorsolateral subnucleus showed a significant increment in c-Fos expression. The density of c-Fos-labeled cells in all LA subnuclei was also increased in animals placed in the box in comparison to untreated animals. Unilateral electrolytic lesions of the posterior intralaminar thalamic nucleus and the medial division of the medial geniculate body reduced foot-shock-induced c-Fos activation in the LA ipsilateral to the lesion. The number of c-Fos labeled cells on the lesioned side was reduced to the levels observed in the animals exposed only to the box. These results indicate that the LA is involved in processing information about the foot-shock unconditioned stimulus and receives this kind of somatosensory information from the posterior intralaminar thalamic nucleus and the medial division of the medial geniculate body.

Degeneration of paramedian nuclei in the thalamus induces Holmes tremor in a case of artery of Percheron infarction.

PubMed

Wei, Tz-Shiang; Hsu, Chun-Sheng; Lee, Yu-Chun; Chang, Shin-Tsu

2017-11-01

Holmes' tremor is an uncommon neurologic disorder following brain insults, and its pathogenesis is undefined. The interruption of the dento-rubro-thalamic tract and secondary deterioration of the nigrostriatal pathway are both required to initiate Holmes' tremor. We used nuclear medicine imaging tools to analyze a patient with concurrent infarction in different zones of each side of the thalamus. Finding whether the paramedian nuclear groups of the thalamus were injured was a decisive element for developing Holmes' tremor. A 36-year-old woman was admitted to our department due to a bilateral paramedian thalamic infarction. Seven months after the stroke, a unilaterally involuntary trembling with irregularly wavering motions occurring in both her left hand and forearm. Based on the distinct features of the unilateral coarse tremor and the locations of the lesions on the magnetic resonance imaging (MRI), the patient was diagnosed with bilateral paramedian thalamic infarction complicated with a unilateral Holmes' tremor. The patient refused our recommendation of pharmacological treatment with levodopa and other dopamine agonists based on personal reasons and was only willing to accept physical and occupational training programs at our outpatient clinic. We utilized serial anatomic and functional neuroimaging of the brain to survey the neurologic deficit. A brain magnetic resonance imaging showed unequal recovery on each side of the thalamus. The residual lesion appeared larger in the right-side thalamus and had gathered in the paramedian area. A brain perfusion single-photon emission computed tomography (SPECT) revealed that the post-stroke hypometabolic changes were not only in the right-side thalamus but also in the right basal ganglion, which was anatomically intact. Furthermore, the brain Technetium-99m-labeled tropanes as a dopamine transporter imaging agents scan ( Tc-TRODAT-1) displayed a secondary reduction of dopamine transporters in the right nigrostriatal pathway which had resulted from the damage on the paramedian nuclear groups of the right-side thalamus. Based on the functional images, we illustrated that a retrograde degeneration originating from the thalamic paramedian nuclear groups, and extending forward along the direct innervating fibers of the mesothalamic pathway, played an essential role towards initiating Holmes' tremor.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Girard, P.; Tommasi, M.; Francois, B.

The case history is described of a patient with thalamic glioma, which was treated with a 12600-r dose of x rays. Complete hemiplegia developed 21 months later and autopsy showed cerebral scarring and necrosis attributable to radiotherapy. (H.H.D.)

An experimental approach towards the development of an in vitro cortical-thalamic co-culture model.

PubMed

Kanagasabapathi, Thirukumaran T; Massobrio, Paolo; Tedesco, Mariateresa; Martinoia, Sergio; Wadman, Wytse J; Decré, Michel M J

2011-01-01

In this paper, we propose an experimental approach to develop an in vitro dissociated cortical-thalamic co-culture model using a dual compartment neurofluidic device. The device has two compartments separated by 10 μm wide and 3 μm high microchannels. The microchannels provide a physical isolation of neurons allowing only neurites to grow between the compartments. Long-term viable co-culture was maintained in the compartmented device, neurite growth through the microchannels was verified using immunofluorescence staining, and electrophysiological recordings from the co-culture system was investigated. Preliminary analysis of spontaneous activities from the co-culture shows a distinctively different firing pattern associated with cultures of individual cell types and further analysis is proposed for a deeper understanding of the dynamics involved in the network connectivity in such a co-culture system.

Bilingual language processing after a lesion in the left thalamic and temporal regions. A case report with early childhood onset

DOE Office of Scientific and Technical Information (OSTI.GOV)

van Lieshout, P.; Renier, W.; Eling, P.

1990-02-01

This case study concerns an 18-year-old bilingual girl who suffered a radiation lesion in the left (dominant) thalamic and temporal region when she was 4 years old. Language and memory assessment revealed deficits in auditory short-term memory, auditory word comprehension, nonword repetition, syntactic processing, word fluency, and confrontation naming tasks. Both languages (English and Dutch) were found to be affected in a similar manner, despite the fact that one language (English) was acquired before and the other (Dutch) after the period of lesion onset. Most of the deficits appear to be related to verbal (short-term) memory dysfunction. Several hypotheses ofmore » subcortical involvement in memory processes are discussed with reference to existing theories in this area.« less

[Thalamic Stroke and Associated Behavior Disorders. Possibilities for Integral Management: Case Report].

PubMed

Camargo, Loida Camargo; Sánchez, Katherine Parra

2012-06-01

Since ancient Greece, cerebrovascular accidents have been described with no variation. Even today, they are still a catastrophic event in the lives of patients with a high risk of disabling sequelae. Case report of a 56-year male patient with thalamic ischemia. The intervention with integral strategies involving pharmacological management and cognitive interventions was decisive for the satisfactory evolution of the patient. The management of patients with cerebrovascular accidents cannot be limited to the emergency room. Pharmacological advances in programs and cognitive intervention methods provide intervention tools from the very beginning of the stroke thus reducing the impact of long-term sequelae, and consequently enabling a better reintegration of the patient to his family. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

The effects of Thalamic Deep Brain Stimulation on speech dynamics in patients with Essential Tremor: An articulographic study.

PubMed

Mücke, Doris; Hermes, Anne; Roettger, Timo B; Becker, Johannes; Niemann, Henrik; Dembek, Till A; Timmermann, Lars; Visser-Vandewalle, Veerle; Fink, Gereon R; Grice, Martine; Barbe, Michael T

2018-01-01

Acoustic studies have revealed that patients with Essential Tremor treated with thalamic Deep Brain Stimulation (DBS) may suffer from speech deterioration in terms of imprecise oral articulation and reduced voicing control. Based on the acoustic signal one cannot infer, however, whether this deterioration is due to a general slowing down of the speech motor system (e.g., a target undershoot of a desired articulatory goal resulting from being too slow) or disturbed coordination (e.g., a target undershoot caused by problems with the relative phasing of articulatory movements). To elucidate this issue further, we here investigated both acoustics and articulatory patterns of the labial and lingual system using Electromagnetic Articulography (EMA) in twelve Essential Tremor patients treated with thalamic DBS and twelve age- and sex-matched controls. By comparing patients with activated (DBS-ON) and inactivated stimulation (DBS-OFF) with control speakers, we show that critical changes in speech dynamics occur on two levels: With inactivated stimulation (DBS-OFF), patients showed coordination problems of the labial and lingual system in terms of articulatory imprecision and slowness. These effects of articulatory discoordination worsened under activated stimulation, accompanied by an additional overall slowing down of the speech motor system. This leads to a poor performance of syllables on the acoustic surface, reflecting an aggravation either of pre-existing cerebellar deficits and/or the affection of the upper motor fibers of the internal capsule.

Alterations of neocortico-limbic association fibers and correlation with diet in prediabetes diagnosed by impaired fasting glucose.

PubMed

Hou, Yi-Cheng; Yang, Shwu-Huey; Wu, Yu-Te; Lai, Chien-Han

2016-06-01

To assess the existence of alterations in the micro-integrity of the fasciculus in prediabetic subjects. The issue of micro-integrity in white matter tracts has not been adequately addressed in prediabetes. Sixty-four prediabetic subjects and 54 controls were enrolled. All participants completed 24-hour diet records and 3-day diet records and received diffusion tensor imaging at 3T. The data for white matter micro-integrity were analyzed and compared between prediabetic subjects and controls with age and gender as covariates. In addition, voxel-wise regression between white matter micro-integrity, diet, and preprandial glucose levels were used to explore the relationship between white matter micro-integrity and diet or serum glucose levels. We found that prediabetic subjects had significant reductions in the micro-integrity of bilateral anterior thalamic radiation, left inferior longitudinal fasciculus, and left superior longitudinal fasciculus (corrected P < 0.05). In addition, total carbohydrate intake amount and preprandial serum glucose levels were negatively correlated with the micro-integrity in the left inferior longitudinal fasciculus and left anterior thalamic radiation (r: -0.47, corrected P < 0.05). Restrictive alterations in the white matter micro-integrity of the anterior thalamic radiation and inferior and superior longitudinal fasciculi might represent the initial "hot spots" for white matter tract alterations, which might play a role in the development of prediabetes. J. Magn. Reson. Imaging 2016;43:1500-1506. © 2016 Wiley Periodicals, Inc.

Two whisker motor areas in the rat cortex: evidence from thalamocortical connections.

PubMed

Mohammed, Hisham; Jain, Neeraj

2014-02-15

In primates, the motor cortex consists of at least seven different areas, which are involved in movement planning, coordination, initiation, and execution. However, for rats, only the primary motor cortex has been well described. A rostrally located second motor area has been proposed, but its extent, organization, and even definitive existence remain uncertain. Only a rostral forelimb area (RFA) has been definitively described, besides few reports of a rostral hindlimb area. We have previously proposed existence of a second whisker area, which we termed the rostral whisker area (RWA), based on its differential response to intracortical microstimulation compared with the caudal whisker area (CWA) in animals under deep anesthesia (Tandon et al. [2008] Eur J Neurosci 27:228). To establish that RWA is distinct from the caudally contiguous CWA, we determined sources of thalamic inputs to the two proposed whisker areas. Sources of inputs to RFA, caudal forelimb area (CFA), and caudal hindlimb region were determined for comparison. The results show that RWA and CWA can be distinguished based on differences in their thalamic inputs. RWA receives major projections from mediodorsal and ventromedial nuclei, whereas the major projections to CWA are from the ventral anterior, ventrolateral, and posterior nuclei. Moreover, the thalamic nuclei that provide major inputs to RWA are the same as for RFA, and the nuclei projecting to CWA are same as for CFA. The results suggest that rats have a second rostrally located motor area with RWA and RFA as its constituents. Copyright © 2013 Wiley Periodicals, Inc.

Structural and functional connectivity mapping of the vestibular circuitry from human brainstem to cortex.

PubMed

Kirsch, V; Keeser, D; Hergenroeder, T; Erat, O; Ertl-Wagner, B; Brandt, T; Dieterich, M

2016-04-01

Structural and functional interconnections of the bilateral central vestibular network have not yet been completely delineated. This includes both ipsilateral and contralateral pathways and crossing sites on the way from the vestibular nuclei via the thalamic relay stations to multiple "vestibular cortex" areas. This study investigated "vestibular" connectivity in the living human brain in between the vestibular nuclei and the parieto-insular vestibular cortex (PIVC) by combined structural and functional connectivity mapping using diffusion tensor imaging and functional connectivity magnetic resonance imaging in 24 healthy right-handed volunteers. We observed a congruent functional and structural link between the vestibular nuclei and the ipsilateral and contralateral PIVC. Five separate and distinct vestibular pathways were identified: three run ipsilaterally, while the two others cross either in the pons or the midbrain. Two of the ipsilateral projections run through the posterolateral or paramedian thalamic subnuclei, while the third bypasses the thalamus to reach the inferior part of the insular cortex directly. Both contralateral pathways travel through the posterolateral thalamus. At the cortical level, the PIVC regions of both hemispheres with a right hemispherical dominance are interconnected transcallosally through the antero-caudal splenium. The above-described bilateral vestibular circuitry in its entirety takes the form of a structure of a rope ladder extending from the brainstem to the cortex with three crossings in the brainstem (vestibular nuclei, pons, midbrain), none at thalamic level and a fourth cortical crossing through the splenium of the corpus callosum.

Right-sided dominance of the bilateral vestibular system in the upper brainstem and thalamus.

PubMed

Dieterich, Marianne; Kirsch, V; Brandt, T

2017-10-01

MRI diffusion tensor imaging tractography was performed on the bilateral vestibular brainstem pathways, which run from the vestibular nuclei via the paramedian and posterolateral thalamic subnuclei to the parieto-insular vestibular cortex. Twenty-one right-handed healthy subjects participated. Quantitative analysis revealed a rope-ladder-like system of vestibular pathways in the brainstem with crossings at pontine and mesencephalic levels. Three structural types of right-left fiber distributions could be delineated: (1) evenly distributed pathways at the lower pontine level from the vestibular nuclei to the pontine crossing, (2) a moderate, pontomesencephalic right-sided lateralization between the pontine and mesencephalic crossings, and (3) a further increase of the right-sided lateralization above the mesencephalic crossing leading to the thalamic vestibular subnuclei. The increasing lateralization along the brainstem was the result of an asymmetric number of pontine and mesencephalic crossing fibers which was higher for left-to-right crossings. The dominance of the right vestibular meso-diencephalic circuitry in right-handers corresponds to the right-hemispheric dominance of the vestibular cortical network. The structural asymmetry apparent in the upper brainstem might be interpreted in relation to the different functions of the vestibular system depending on their anatomical level: a symmetrical sensorimotor reflex control of eye, head, and body mediated by the lower brainstem; a lateralized right-sided upper brainstem-thalamic function as part of the dominant right-sided cortical/subcortical vestibular system that enables a global percept of body motion and orientation in space.

Direct visualization of anatomic subfields within the superior aspect of the human lateral thalamus by MRI at 7T.

PubMed

Kanowski, M; Voges, J; Buentjen, L; Stadler, J; Heinze, H-J; Tempelmann, C

2014-09-01

The morphology of the human thalamus shows high interindividual variability. Therefore, direct visualization of landmarks within the thalamus is essential for an improved definition of electrode positions for deep brain stimulation. The aim of this study was to provide anatomic detail in the thalamus by using inversion recovery TSE imaging at 7T. The MR imaging protocol was optimized on 1 healthy subject to segment thalamic nuclei from one another. Final images, acquired with 0.5(2)-mm2 in-plane resolution and 3-mm section thickness, were compared with stereotactic brain atlases to assign visualized details to known anatomy. The robustness of the visualization of thalamic nuclei was assessed with 4 healthy subjects at lower image resolution. Thalamic subfields were successfully delineated in the dorsal aspect of the lateral thalamus. T1-weighting was essential. MR images had an appearance very similar to that of myelin-stained sections seen in brain atlases. Visualized intrathalamic structures were, among others, the lamella medialis, the external medullary lamina, the reticulatum thalami, the nucleus centre médian, the boundary between the nuclei dorso-oralis internus and externus, and the boundary between the nuclei dorso-oralis internus and zentrolateralis intermedius internus. Inversion recovery-prepared TSE imaging at 7T has a high potential to reveal fine anatomic detail in the thalamus, which may be helpful in enhancing the planning of stereotactic neurosurgery in the future. © 2014 by American Journal of Neuroradiology.

Characterization of thalamocortical association using amplitude and connectivity of fMRI in mild traumatic brain injury

PubMed Central

Zhou, Yongxia; Lui, Yvonne W; Zuo, Xi-Nian; Milham, Michael P.; Reaume, Joseph; Grossman, Robert I.; Ge, Yulin

2013-01-01

Purpose To examine thalamic and cortical injuries using fractional amplitude of low-frequency fluctuations (fALFF) and functional connectivity MRI (fcMRI) based on resting state (RS) and task-related fMRI in patients with mild traumatic brain injury (MTBI). Materials and Methods Twenty-seven patients and 27 age-matched controls were recruited. 3T fMRI at RS and finger tapping task were used to assess fALFF and fcMRI patterns. fALFF was computed with filtering (0.01-0.08Hz) and scaling after preprocessing. fcMRI was performed using a standard seed-based correlation method, and delayed fcMRI (coherence) in frequency domain were also performed between thalamus and cortex. Results In comparison with controls, MTBI patients exhibited significantly decreased fALFF in the thalamus (and frontal/temporal sub segments) and cortical frontal and temporal lobes; as well as decreased thalamo-thalamo and thalamo-frontal/thalamo-temporal fcMRI at rest based on RS-fMRI (corrected P<0.05). This thalamic and cortical disruption also existed at task-related condition in patients. Conclusion The decreased fALFF (i.e. lower neuronal activity) in the thalamus and its segments provides additional evidence of thalamic injury in patients with MTBI. Our findings of fALFF and fcMRI changes during motor task and resting state may offer insights into the underlying cause and primary location of disrupted thalamo-cortical networks after MTBI. PMID:24014176

Postmortem structural studies of the thalamus in schizophrenia

PubMed Central

Dorph-Petersen, Karl-Anton; Lewis, David A.

2017-01-01

In this review, we seek to answer the following question: Do findings in the current literature support the idea that thalamo-cortical dysfunction in schizophrenia is due to structural abnormalities in the thalamus? We base our review on the existing literature of design-unbiased stereological studies of the postmortem thalamus from subjects with schizophrenia. Thus, all reported results are based upon the use of unbiased principles of sampling to determine volume and/or total cell numbers of thalamus or its constituent nuclei. We found 28 such papers covering 26 studies. In a series of tables we list all positive and negative findings from the total thalamus, the mediodorsal, pulvinar and anterior nuclei, as well as less frequently studied thalamic regions. Only four studies examined the entire thalamus and the results were inconsistent. We found largely consistent evidence for structural changes (reduced volume and cell numbers) in the pulvinar located in the posterior thalamus. In contrast, findings in the mediodorsal thalamic nucleus are inconsistent, with the largest and most recent studies generally failing to support earlier reports of a lower number of neurons in schizophrenia. Thus, the current findings of stereological studies of the thalamus in schizophrenia support the idea that thalamo-cortical dysfunction in schizophrenia might be attributable, at least in part, to structural alterations in the pulvinar that could impair thalamic inputs to higher order cortical association areas in the frontal and parietal lobes. However, more studies are needed before robust conclusions can be drawn. PMID:27567291

Impaired thalamocortical connectivity in autism spectrum disorder: a study of functional and anatomical connectivity.

PubMed

Nair, Aarti; Treiber, Jeffrey M; Shukla, Dinesh K; Shih, Patricia; Müller, Ralph-Axel

2013-06-01

The thalamus plays crucial roles in the development and mature functioning of numerous sensorimotor, cognitive and attentional circuits. Currently limited evidence suggests that autism spectrum disorder may be associated with thalamic abnormalities, potentially related to sociocommunicative and other impairments in this disorder. We used functional connectivity magnetic resonance imaging and diffusion tensor imaging probabilistic tractography to study the functional and anatomical integrity of thalamo-cortical connectivity in children and adolescents with autism spectrum disorder and matched typically developing children. For connectivity with five cortical seeds (prefontal, parieto-occipital, motor, somatosensory and temporal), we found evidence of both anatomical and functional underconnectivity. The only exception was functional connectivity with the temporal lobe, which was increased in the autism spectrum disorders group, especially in the right hemisphere. However, this effect was robust only in partial correlation analyses (partialling out time series from other cortical seeds), whereas findings from total correlation analyses suggest that temporo-thalamic overconnectivity in the autism group was only relative to the underconnectivity found for other cortical seeds. We also found evidence of microstructural compromise within the thalamic motor parcel, associated with compromise in tracts between thalamus and motor cortex, suggesting that the thalamus may play a role in motor abnormalities reported in previous autism studies. More generally, a number of correlations of diffusion tensor imaging and functional connectivity magnetic resonance imaging measures with diagnostic and neuropsychological scores indicate involvement of abnormal thalamocortical connectivity in sociocommunicative and cognitive impairments in autism spectrum disorder.

Discontinuous Galerkin finite element method for solving population density functions of cortical pyramidal and thalamic neuronal populations.

PubMed

Huang, Chih-Hsu; Lin, Chou-Ching K; Ju, Ming-Shaung

2015-02-01

Compared with the Monte Carlo method, the population density method is efficient for modeling collective dynamics of neuronal populations in human brain. In this method, a population density function describes the probabilistic distribution of states of all neurons in the population and it is governed by a hyperbolic partial differential equation. In the past, the problem was mainly solved by using the finite difference method. In a previous study, a continuous Galerkin finite element method was found better than the finite difference method for solving the hyperbolic partial differential equation; however, the population density function often has discontinuity and both methods suffer from a numerical stability problem. The goal of this study is to improve the numerical stability of the solution using discontinuous Galerkin finite element method. To test the performance of the new approach, interaction of a population of cortical pyramidal neurons and a population of thalamic neurons was simulated. The numerical results showed good agreement between results of discontinuous Galerkin finite element and Monte Carlo methods. The convergence and accuracy of the solutions are excellent. The numerical stability problem could be resolved using the discontinuous Galerkin finite element method which has total-variation-diminishing property. The efficient approach will be employed to simulate the electroencephalogram or dynamics of thalamocortical network which involves three populations, namely, thalamic reticular neurons, thalamocortical neurons and cortical pyramidal neurons. Copyright © 2014 Elsevier Ltd. All rights reserved.

Peak firing rates of rat anterodorsal thalamic head direction cells are higher during faster passive rotations.

PubMed

Zugaro, Michaël B; Berthoz, Alain; Wiener, Sidney I

2002-01-01

Head direction cells discharge selectively when the head of the animal is oriented in a specific direction. The goal of this study was to determine how sensory signals arising from passive rotations (e.g., triggered by vestibular stimulation and dynamic visual inputs) influence the responses of anterodorsal thalamic head direction cells in the absence of voluntary movement cues (e.g., motor command, efference copy, and associated kinesthetic signals). Three unrestrained rats consumed water from a reservoir at the center of a circular platform while passively subjected to sinusoidal rotatory oscillations at fast (153 +/- 27 degrees/s, sd) and slow (38 +/- 15 degrees/s) peak velocities. In 14 anterodorsal thalamic head direction cells, the preferred directions, angular response ranges and baseline firing rates remained stable, but the peak firing rates were, on average, 36% higher during the fast rotations (Wilcoxon matched-pairs test, p < 0.001; variation range: +11% to approximately +100%). No cell changed its peak firing rate by less than 10%, while three cells (21%) increased their peak firing rates by more than 50%. The velocity-dependent increase in peak firing rates was similar for left and right rotations, and the skewness of the directional response curves were not significantly different between left and right turns (Wilcoxon matched-pairs tests, n = 14, ns). These results show that sensory signals concerning self-movements modulate the responses of the head direction cells in the absence of active locomotion.

The thalamus as the generator and modulator of EEG alpha rhythm: a combined PET/EEG study with lorazepam challenge in humans.

PubMed

Schreckenberger, Mathias; Lange-Asschenfeldt, Christian; Lange-Asschenfeld, Christian; Lochmann, Matthias; Mann, Klaus; Siessmeier, Thomas; Buchholz, Hans-Georg; Bartenstein, Peter; Gründer, Gerhard

2004-06-01

Purpose of this study was to investigate the functional relationship between electroencephalographic (EEG) alpha power and cerebral glucose metabolism before and after pharmacological alpha suppression by lorazepam. Ten healthy male volunteers were examined undergoing two F18-fluorodeoxyglucose (18-FDG) positron emission tomography (PET) scans with simultaneous EEG recording: 1x placebo, 1x lorazepam. EEG power spectra were computed by means of Fourier analysis. The PET data were analyzed using SPM99, and the correlations between metabolism and alpha power were calculated for both conditions. The comparison lorazepam versus placebo revealed reduced glucose metabolism of the bilateral thalamus and adjacent subthalamic areas, the occipital cortex and temporo-insular areas (P < 0.001). EEG alpha power was reduced in all derivations (P < 0.001). Under placebo, there was a positive correlation between alpha power and metabolism of the bilateral thalamus and the occipital and adjacent parietal cortex (P < 0.001). Under lorazepam, the thalamic and parietal correlations were maintained, whereas the occipital correlation was no longer detectable (P < 0.001). The correlation analysis of the difference lorazepam-placebo showed the alpha power exclusively correlated with the thalamic activity (P < 0.0001). These results support the hypothesis of a close functional relationship between thalamic activity and alpha rhythm in humans mediated by corticothalamic loops which are independent of sensory afferences. The study paradigm could be a promising approach for the investigation of cortico-thalamo-cortical feedback loops in neuropsychiatric diseases.

Thalamic deep brain stimulation decelerates automatic lexical activation.

PubMed

Ehlen, Felicitas; Vonberg, Isabelle; Tiedt, Hannes O; Horn, Andreas; Fromm, Ortwin; Kühn, Andrea A; Klostermann, Fabian

2017-02-01

Deep Brain Stimulation (DBS) of the thalamic ventral intermediate nucleus (VIM) is a therapeutic option for patients with essential tremor. Despite a generally low risk of side effects, declines in verbal fluency (VF) have previously been reported. We aimed to specify effects of VIM-DBS on major cognitive operations needed for VF task performance, represented by clusters and switches. Clusters are word production spurts, thought to arise from automatic activation of associated information pertaining to a given lexical field. Switches are slow word-to-word transitions, presumed to indicate controlled operations for stepping from one lexical field to another. Thirteen essential tremor patients with VIM-DBS performed verbal fluency tasks in their VIM-DBS ON and OFF conditions. Clusters and switches were formally defined by mathematical criteria. All results were compared to those of fifteen healthy control subjects, and significant OFF-ON-change scores were correlated to stimulation parameters. Patients produced fewer words than healthy controls. DBS ON compared to DBS OFF aggravated this deficit by prolonging the intervals between words within clusters, whereas switches remained unaffected. This stimulation effect correlated with more anterior electrode positions. VIM-DBS seems to influence word output dynamics during verbal fluency tasks on the level of word clustering. This suggests a perturbation of automatic lexical co-activation by thalamic stimulation, particularly if delivered relatively anteriorly. The findings are discussed in the context of the hypothesized role of the thalamus in lexical processing. Copyright © 2016 Elsevier Inc. All rights reserved.

Developmental synchrony of thalamocortical circuits in the neonatal brain.

PubMed

Poh, Joann S; Li, Yue; Ratnarajah, Nagulan; Fortier, Marielle V; Chong, Yap-Seng; Kwek, Kenneth; Saw, Seang-Mei; Gluckman, Peter D; Meaney, Michael J; Qiu, Anqi

2015-08-01

The thalamus is a deep gray matter structure and consists of axonal fibers projecting to the entire cortex, which provide the anatomical support for its sensorimotor and higher-level cognitive functions. There is limited in vivo evidence on the normal thalamocortical development, especially in early life. In this study, we aimed to investigate the developmental patterns of the cerebral cortex, the thalamic substructures, and their connectivity with the cortex in the first few weeks of the postnatal brain. We hypothesized that there is developmental synchrony of the thalamus, its cortical projections, and corresponding target cortical structures. We employed diffusion tensor imaging (DTI) and divided the thalamus into five substructures respectively connecting to the frontal, precentral, postcentral, temporal, and parietal and occipital cortex. T2-weighted magnetic resonance imaging (MRI) was used to measure cortical thickness. We found age-related increases in cortical thickness of bilateral frontal cortex and left temporal cortex in the early postnatal brain. We also found that the development of the thalamic substructures was synchronized with that of their respective thalamocortical connectivity in the first few weeks of the postnatal life. In particular, the right thalamo-frontal substructure had the fastest growth in the early postnatal brain. Our study suggests that the distinct growth patterns of the thalamic substructures are in synchrony with those of the cortex in early life, which may be critical for the development of the cortical and subcortical functional specialization. Copyright © 2015 Elsevier Inc. All rights reserved.

Mirror therapy for an adult with central post-stroke pain: a case report.

PubMed

Corbetta, Davide; Sarasso, Elisabetta; Agosta, Federica; Filippi, Massimo; Gatti, Roberto

2018-01-01

Treatment of central post-stroke pain (CPSP) after a thalamic-capsular stroke is generally based on pharmacological approach as it is low responsive to physiotherapy. In this case report, the use of mirror therapy (MT) for the reduction of CPSP in a subject after a stroke involving thalamus is presented. Five years after a right lenticular-capsular thalamic stroke, despite a good recovery of voluntary movement that guaranteed independence in daily life activities, a 50-year-old woman presented with mild weakness and spasticity, an important sensory loss and a burning pain in the left upper limb. MT for reducing arm pain was administered in 45-min sessions, five days a week, for two consecutive weeks. MT consisted in performing symmetrical movements of both forearms and hands while watching the image of the sound limb reflected by a parasagittal mirror superimposed to the affected limb. Pain severity was assessed using visual analogue scale (VAS) before and after the intervention and at one-year follow-up. After the two weeks of MT, the patient demonstrated 4.5 points reduction in VAS pain score of the hand at rest and 3.9 points during a maximal squeeze left hand contraction. At one-year follow-up, pain reduction was maintained and also extended to the shoulder. This case report shows the successful application of a motor training with a sensory confounding condition (MT) in reducing CPSP in a patient with a chronic thalamic stroke.

Intracellular activity of cortical and thalamic neurones during high-voltage rhythmic spike discharge in Long-Evans rats in vivo

PubMed Central

Polack, Pierre-Olivier; Charpier, Stéphane

2006-01-01

Spontaneous high-voltage rhythmic spike (HVRS) discharges at 6–12 Hz have been widely described in the electrocorticogram (EcoG) of Long-Evans rats. These ECoG oscillations have been proposed to reflect a state of attentive immobility allowing the optimization of sensory integration within the corticothalamic pathway. This hypothesis has been challenged by recent studies emphasizing similarities between HVRS discharges and spike-and-wave discharges (SWDs) in well-established rat genetic models of absence epilepsy. Here, we made in vivo intracellular recordings to determine, for the first time, the cellular mechanisms responsible for the synchronized oscillations in the corticothalamic loop during HVRS discharges in the Long-Evans rats. We show that HVRS discharges are associated in corticothalamic neurones with rhythmic suprathreshold synaptic depolarizations superimposed on a tonic hyperpolarization, likely due to a process of synaptic disfacilitation. Simultaneously, thalamocortical neurones exhibit a large-amplitude ‘croissant’-shaped membrane hyperpolarization with a voltage sensitivity suggesting a potassium-dependent mechanism. This thalamic hyperpolarizing envelope was associated with a membrane oscillation resulting from interactions between excitatory synaptic inputs, a chloride-dependent inhibitory conductance and voltage-gated intrinsic currents. These cortical and thalamic cellular mechanisms underlying HVRS activity in Long-Evans rats are remarkably similar to those previously described in the thalamocortical networks during SWDs. Thus, the present study provides an additional support to the hypothesis that HVRS activity in Long-Evans rats is an absence-like seizure activity. PMID:16410284

Speech disorders of Parkinsonism: a review.

PubMed Central

Critchley, E M

1981-01-01

Study of the speech disorders of Parkinsonism provides a paradigm of the integration of phonation, articulation and language in the production of speech. The initial defect in the untreated patient is a failure to control respiration for the purpose of speech and there follows a forward progression of articulatory symptoms involving larynx, pharynx, tongue and finally lips. There is evidence that the integration of speech production is organised asymmetrically at thalamic level. Experimental or therapeutic lesions in the region of the inferior medial portion of ventro-lateral thalamus may influence the initiation, respiratory control, rate and prosody of speech. Higher language functions may also be involved in thalamic integration: different forms of anomia are reported with pulvinar and ventrolateral thalamic lesions and transient aphasia may follow stereotaxis. The results of treatment with levodopa indicates that neurotransmitter substances enhance the clarity, volume and persistence of phonation and the latency and smoothness of articulation. The improvement of speech performance is not necessarily in phase with locomotor changes. The dose-related dyskinetic effects of levodopa, which appear to have a physiological basis in observations previously made in post-encephalitic Parkinsonism, not only influence the prosody of speech with near-mutism, hesitancy and dysfluency but may affect work-finding ability and in instances of excitement (erethism) even involve the association of long-term memory with speech. In future, neurologists will need to examine more closely the role of neurotransmitters in speech production and formulation. PMID:7031185

Transient visual pathway critical for normal development of primate grasping behavior.

PubMed

Mundinano, Inaki-Carril; Fox, Dylan M; Kwan, William C; Vidaurre, Diego; Teo, Leon; Homman-Ludiye, Jihane; Goodale, Melvyn A; Leopold, David A; Bourne, James A

2018-02-06

An evolutionary hallmark of anthropoid primates, including humans, is the use of vision to guide precise manual movements. These behaviors are reliant on a specialized visual input to the posterior parietal cortex. Here, we show that normal primate reaching-and-grasping behavior depends critically on a visual pathway through the thalamic pulvinar, which is thought to relay information to the middle temporal (MT) area during early life and then swiftly withdraws. Small MRI-guided lesions to a subdivision of the inferior pulvinar subnucleus (PIm) in the infant marmoset monkey led to permanent deficits in reaching-and-grasping behavior in the adult. This functional loss coincided with the abnormal anatomical development of multiple cortical areas responsible for the guidance of actions. Our study reveals that the transient retino-pulvinar-MT pathway underpins the development of visually guided manual behaviors in primates that are crucial for interacting with complex features in the environment.

Flexible timing by temporal scaling of cortical responses

PubMed Central

Wang, Jing; Narain, Devika; Hosseini, Eghbal A.; Jazayeri, Mehrdad

2017-01-01

Musicians can perform at different tempos, speakers can control the cadence of their speech, and children can flexibly vary their temporal expectations of events. To understand the neural basis of such flexibility, we recorded from the medial frontal cortex of nonhuman primates trained to produce different time intervals with different effectors. Neural responses were heterogeneous, nonlinear and complex, and exhibited a remarkable form of temporal invariance: firing rate profiles were temporally scaled to match the produced intervals. Recording from downstream neurons in the caudate and thalamic neurons projecting to the medial frontal cortex indicated that this phenomenon originates within cortical networks. Recurrent neural network models trained to perform the task revealed that temporal scaling emerges from nonlinearities in the network and degree of scaling is controlled by the strength of external input. These findings demonstrate a simple and general mechanism for conferring temporal flexibility upon sensorimotor and cognitive functions. PMID:29203897

Mechanisms of Neuronal Computation in Mammalian Visual Cortex

PubMed Central

Priebe, Nicholas J.; Ferster, David

2012-01-01

Orientation selectivity in the primary visual cortex (V1) is a receptive field property that is at once simple enough to make it amenable to experimental and theoretical approaches and yet complex enough to represent a significant transformation in the representation of the visual image. As a result, V1 has become an area of choice for studying cortical computation and its underlying mechanisms. Here we consider the receptive field properties of the simple cells in cat V1—the cells that receive direct input from thalamic relay cells—and explore how these properties, many of which are highly nonlinear, arise. We have found that many receptive field properties of V1 simple cells fall directly out of Hubel and Wiesel’s feedforward model when the model incorporates realistic neuronal and synaptic mechanisms, including threshold, synaptic depression, response variability, and the membrane time constant. PMID:22841306

Morphological elucidation of basal ganglia circuits contributing reward prediction

PubMed Central

Fujiyama, Fumino; Takahashi, Susumu; Karube, Fuyuki

2015-01-01

Electrophysiological studies in monkeys have shown that dopaminergic neurons respond to the reward prediction error. In addition, striatal neurons alter their responsiveness to cortical or thalamic inputs in response to the dopamine signal, via the mechanism of dopamine-regulated synaptic plasticity. These findings have led to the hypothesis that the striatum exhibits synaptic plasticity under the influence of the reward prediction error and conduct reinforcement learning throughout the basal ganglia circuits. The reinforcement learning model is useful; however, the mechanism by which such a process emerges in the basal ganglia needs to be anatomically explained. The actor–critic model has been previously proposed and extended by the existence of role sharing within the striatum, focusing on the striosome/matrix compartments. However, this hypothesis has been difficult to confirm morphologically, partly because of the complex structure of the striosome/matrix compartments. Here, we review recent morphological studies that elucidate the input/output organization of the striatal compartments. PMID:25698913

Effects of ethanol on visual unit activity in the thalamus.

DOT National Transportation Integrated Search

1978-01-01

The investigator studied the effects of ethanol on the spontaneous activity of single neurons in functionally differentiated subnuclei of a posterior thalamic visual projection area, nucleus rotundus, in the anesthetized pigeon. Low doses of ethanol,...

Thalamocortical NMDA conductances and intracortical inhibition can explain cortical temporal tuning

NASA Technical Reports Server (NTRS)

Krukowski, A. E.; Miller, K. D.

2001-01-01

Cells in cerebral cortex fail to respond to fast-moving stimuli that evoke strong responses in the thalamic nuclei innervating the cortex. The reason for this behavior has remained a mystery. We study an experimentally motivated model of the thalamic input-recipient layer of cat primary visual cortex that accounts for many aspects of cortical orientation tuning. In this circuit, inhibition dominates over excitation, but temporal modulations of excitation and inhibition occur out of phase with one another, allowing excitation to transiently drive cells. We show that this circuit provides a natural explanation of cortical low-pass temporal frequency tuning, provided N-methyl-D-aspartate (NMDA) receptors are present in thalamocortical synapses in proportions measured experimentally. This suggests a new and unanticipated role for NMDA conductances in shaping the temporal response properties of cortical cells, and suggests that common cortical circuit mechanisms underlie both spatial and temporal response tuning.

Fornix and retrosplenial contribution to a hippocampo-thalamic circuit underlying conditional learning.

PubMed

Dumont, Julie R; Petrides, Michael; Sziklas, Viviane

2010-05-01

Rats with combined bilateral lesions of the retrosplenial cortex and the fornix or rats with unilateral lesions to the anterior thalamus and the hippocampus, made in opposite hemispheres (disconnection preparation), and combined with unilateral damage of the retrosplenial cortex in either hemisphere, were tested on a spatial-visual conditional learning task in which they learned arbitrary associations between stimuli and the scene in which they were embedded. All experimental groups were impaired in comparison with normal animals. The more severe deficits occurred when (1) both the fornix and the retrosplenial cortex were damaged bilaterally thus depriving the hippocampus both from subcortical interactions via the fornix and retrosplenial-mediated interactions and (2) when, in the crossed lesion preparation, the unilateral retrosplenial lesion was made in the hemisphere with the intact hippocampus, again because this lesion would be maximally disconnecting the hippocampus from functional interaction with the anterior thalamic nucleus and retrosplenial-mediated input.

5-HT2 receptor distribution shown by [18F] setoperone PET in high-functioning autistic adults.

PubMed

Beversdorf, David Q; Nordgren, Richard E; Bonab, Ali A; Fischman, Alan J; Weise, Steven B; Dougherty, Darin D; Felopulos, Gretchen J; Zhou, Feng C; Bauman, Margaret L

2012-01-01

The serotonergic system is implicated in disordered emotional behavior. Autism is characterized by impaired processing of emotional information. The serotonergic (5-HT) system is also critically involved in brain development, and abnormal brain synthesis of serotonin is observed in autism. Furthermore, whole blood and platelet serotonin have been reported to be elevated in autism. The authors examined the CNS serotonin system in autism in vivo. 5-HT2 receptors were visualized by PET imaging of [18F]setoperone-binding in this pilot study of 6 high-functioning autistic adults and 10 matched-control participants. Autism subjects had less thalamic [18F]setoperone binding than controls, when covaried for age, but no difference reached significance in other areas. A negative relationship between thalamic binding and history of language impairment was also observed. Further studies will be needed to gain a clearer picture of the role of the 5-HT system in autism.

Fatal thalamic abscess secondary to dental infection.

PubMed

Basyuni, Shadi; Sharma, Valmiki; Santhanam, Vijay; Ferro, Ashley

2015-12-17

We present the case of poor neurological recovery and subsequent death secondary to a thalamic abscess in a 53-year-old man. This patient initially presented with sudden dysarthria and left hemiparesis while driving. Neuroimaging showed a multilobular abscess involving the right thalamus with oedema extending to the basal ganglionic region and brainstem. The source of the abscess was initially unknown and it required draining multiple times while the different causes were being explored. The patient's neurological state along with intubation made for a difficult and inconclusive oral examination. It was only after neuroimaging included tooth-bearing areas that it became evident that this patient had extensive periodontal disease with multiple areas of periapical radiolucencies. The patient underwent complete dental clearance alongside repeated drainage of the abscess. Despite initial postoperative improvement, the patient never recovered from the neurological damage and died 3 weeks later. 2015 BMJ Publishing Group Ltd.

Stereotaxic gamma knife surgery in treatment of critically located pilocytic astrocytoma: preliminary result

PubMed Central

Hafez, Raef FA

2007-01-01

Background Low-grade gliomas are uncommon primary brain tumors, located more often in the posterior fossa, optic pathway, and brain stem and less commonly in the cerebral hemispheres. Case presentations Two patients with diagnosed recurrent cystic pilocytic astrocytoma critically located within the brain (thalamic and brain stem) were treated with gamma knife surgery. Gamma knife surgery (GKS) did improve the patient's clinical condition very much which remained stable later on. Progressive reduction on the magnetic resonance imaging (MRI) studies of the solid part of the tumor and almost disappearance of the cystic component was achieved within the follow-up period of 36 months in the first case with the (thalamic located lesion) and 22 months in the second case with the (brain stem located lesion). Conclusion Gamma knife surgery represents an alternate tool in the treatment of recurrent and/or small postoperative residual pilocytic astrocytoma especially if they are critically located PMID:17394660

A corticothalamic switch: controlling the thalamus with dynamic synapses

PubMed Central

Crandall, Shane R.; Cruikshank, Scott J.; Connors, Barry W.

2015-01-01

SUMMARY Corticothalamic neurons provide massive input to the thalamus. This top-down projection may allow cortex to regulate sensory processing by modulating the excitability of thalamic cells. Layer 6 corticothalamic neurons monosynaptically excite thalamocortical cells, but also indirectly inhibit them by driving inhibitory cells of the thalamic reticular nucleus. Whether corticothalamic activity generally suppresses or excites the thalamus remains unclear. Here we show that the corticothalamic influence is dynamic, with the excitatory-inhibitory balance shifting in an activity-dependent fashion. During low-frequency activity corticothalamic effects are mainly suppressive, whereas higher frequency activity (even a short bout of gamma frequency oscillations) converts the corticothalamic influence to enhancement. The mechanism of this switching depends upon distinct forms of short-term synaptic plasticity across multiple corticothalamic circuit components. Our results reveal an activity-dependent mechanism by which corticothalamic neurons can bidirectionally switch the excitability and sensory throughput of the thalamus, possibly to meet changing behavioral demands. PMID:25913856

Vocal babbling in songbirds requires the basal ganglia-recipient motor thalamus but not the basal ganglia

PubMed Central

Goldberg, Jesse H.

2011-01-01

Young songbirds produce vocal “babbling,” and the variability of their songs is thought to underlie a process of trial-and-error vocal learning. It is known that this exploratory variability requires the “cortical” component of a basal ganglia (BG) thalamocortical loop, but less understood is the role of the BG and thalamic components in this behavior. We found that large bilateral lesions to the songbird BG homolog Area X had little or no effect on song variability during vocal babbling. In contrast, lesions to the BG-recipient thalamic nucleus DLM (medial portion of the dorsolateral thalamus) largely abolished normal vocal babbling in young birds and caused a dramatic increase in song stereotypy. These findings support the idea that the motor thalamus plays a key role in the expression of exploratory juvenile behaviors during learning. PMID:21430276

Fluctuating drowsiness following cardiac catheterisation: artery of Percheron ischaemic stroke causing bilateral thalamic infarcts.

PubMed

Hammersley, Daniel; Arora, Ankur; Dissanayake, Madhava; Sengupta, Nabarun

2017-01-02

An 81-year-old man underwent cardiac catheterisation to investigate breathlessness and left ventricular impairment of unknown cause. He had unobstructed coronary arteries. Immediately following the procedure, he became suddenly unresponsive with vertical gaze palsy, anisocoria and bilateral upgoing plantar responses. He made a rapid recovery to his premorbid state 25 min later with no residual focal neurological signs. He then had multiple unresponsive episodes, interspaced with complete resolution of symptoms and neurological signs. MRI of the brain identified bilateral medial thalamic infarcts and midbrain infarcts, consistent with an artery of Percheron territory infarction. By the time the diagnosis was reached, the thrombolysis window had elapsed. The unresponsive episodes diminished with time and the patient was discharged to inpatient rehabilitation. At 6-month review after the episode, the patient has a degree of progressive cognitive impairment. 2017 BMJ Publishing Group Ltd.

Resection of a Pediatric Thalamic Juvenile Pilocytic Astrocytoma with Whole Brain Tractography

PubMed Central

Weiner, Howard L

2017-01-01

The resection of deep-seated brain tumors has been associated with morbidity due to injury to critical neural structures during the approach. Recent technological advancements in navigation and stereotaxy, surgical planning, brain tractography and minimal-access brain ports present the opportunity to overcome such limitations. Here, we present the case of a pediatric patient with a left thalamic/midbrain juvenile pilocytic astrocytoma (JPA). The tumor displaced the corticospinal fibers posteriorly and resulted in hemiparesis. Using whole brain tractography to plan a corridor for the approach, neuronavigation, a tubular retractor and an exoscope for visualization, we obtained gross total resection of the tumor, while minimizing injury to white matter bundles, including the corticospinal fibers. We propose that surgical planning with whole brain tractography is essential for reducing morbidity while accessing deep-lying brain lesions via retractor tubes, by means of sparing critical fiber tracts. PMID:29234572

A Chinese patient with pusher syndrome and unilateral spatial neglect syndrome.

PubMed

Chen, Xiao-Wei; Lin, Cheng-He; Zheng, Hua; Lin, Zhen-Lan

2014-07-01

To observe clinical manifestations, behavioral characteristics, and effects of rehabilitation on a patient with pusher syndrome and unilateral spatial neglect caused by right thalamic hemorrhage. Assessment of pusher syndrome was made by the Scale for Contraversive pushing (SCP), and unilateral spatial neglect syndrome was diagnosed using line cancellation, letter and star cancellation, line bisection tests and copy and continuation of graphic sequence test. Behavioral therapy, occupational therapy, reading training and traditional Chinese medicine methods were adopted for treatment of pusher syndrome and unilateral spatial neglect. The patient showed typical pusher syndrome and unilateral spatial neglect symptoms. The pusher syndrome and unilateral spatial neglect symptoms were significantly improved following rehabilitation treatments. Pusher syndrome and unilateral spatial neglect syndrome occurred simultaneously after right thalamic hemorrhage. Early rehabilitation therapy can reduce the symptoms of pusher syndrome and unilateral spatial neglect syndrome and improve motor function.

Differential effects of deep brain stimulation on verbal fluency.

PubMed

Ehlen, Felicitas; Schoenecker, Thomas; Kühn, Andrea A; Klostermann, Fabian

2014-07-01

We aimed at gaining insights into principles of subcortical lexical processing. Therefore, effects of deep brain stimulation (DBS) in different target structures on verbal fluency (VF) were tested. VF was assessed with active vs. inactivated DBS in 13 and 14 patients with DBS in the vicinity of the thalamic ventral intermediate nucleus (VIM) and, respectively, of the subthalamic nucleus (STN). Results were correlated to electrode localizations in postoperative MRI, and compared to those of 12 age-matched healthy controls. Patients' VF performance was generally below normal. However, while activation of DBS in the vicinity of VIM provoked marked VF decline, it induced subtle phonemic VF enhancement in the vicinity of STN. The effects correlated with electrode localizations in left hemispheric stimulation sites. The results show distinct dependencies of VF on DBS in the vicinity of VIM vs. STN. Particular risks for deterioration occur in patients with relatively ventromedial thalamic electrodes. Copyright © 2014 Elsevier Inc. All rights reserved.

Isolated thalamic tuberculoma presenting as ataxic hemiparesis

PubMed Central

Sahu, Ritesh; Patil, Tushar B; Kori, Prakash; Shukla, Rakesh

2013-01-01

Lacunar syndrome is a neurodeficit secondary to a deep cerebral lesion, usually because of microatheroma of small arteries. Ataxic hemiparesis (AH) is a lacunar syndrome with unilateral pyramidal weakness and ipsilateral ataxia. Thalamic tuberculoma, as a cause of AH, has not been previously described in the literature. We describe an elderly man who presented with left hemiparesis and ipsilateral ataxia. Clinical examination revealed upper motor neuron left facial paresis and left-sided hemiparesis. The patient had incoordination in left upper and lower limbs. Mantoux test was positive and erythrocyte sedimentation rate was elevated. MRI of brain showed a conglomerated hypointense lesion in the right thalamus with a peripheral hyperintensity on T1-weighted imaging and a hyperintense lesion in T2-weighted imaging with significant perilesional oedema, suggesting a tuberculoma. The patient was treated with antitubercular therapy and was symptomatically better at the 9 months follow-up. PMID:23580686

A unique combination of anatomy and physiology in cells of the rat paralaminar thalamic nuclei adjacent to the medial geniculate body

PubMed Central

Smith, Philip H.; Bartlett, Edward L.; Kowalkowski, Anna

2010-01-01

The medial geniculate body (MGB) has three major subdivisions - ventral (MGV), dorsal (MGD) and medial (MGM). MGM is linked with paralaminar nuclei that are situated medial and ventral to MGV/MGD. Paralaminar nuclei have unique inputs and outputs when compared with MGV and MGD and have been linked to circuitry underlying some important functional roles. We recorded intracellularly from cells in the paralaminar nuclei in vitro. We found that they possess an unusual combination of anatomical and physiological features when compared to those reported for “standard” thalamic neurons seen in the MGV/MGD and elsewhere in the thalamus. Compared to MGV/MGD neurons, anatomically, 1) paralaminar cell dendrites can be long, branch sparingly and encompass a much larger area. 2) their dendrites may be smooth but can have well defined spines and 3) their axons can have collaterals that branch locally within the same or nearby paralaminar nuclei. When compared to MGV/MGD neurons physiologically 1) their spikes are larger in amplitude and can be shorter in duration and 2) can have dual afterhyperpolarizations with fast and slow components and 3) they can have a reduction or complete absence of the low threshold, voltage-sensitive calcium conductance that reduces or eliminates the voltage-dependent burst response. We also recorded from cells in the parafascicular nucleus, a nucleus of the posterior intralaminar nuclear group, because they have unusual anatomical features that are similar to some of our paralaminar cells. Like the labeled paralaminar cells, parafascicular cells had physiological features distinguishing them from typical thalamic neurons. PMID:16566009

Thalamic connections of the core auditory cortex and rostral supratemporal plane in the macaque monkey.

PubMed

Scott, Brian H; Saleem, Kadharbatcha S; Kikuchi, Yukiko; Fukushima, Makoto; Mishkin, Mortimer; Saunders, Richard C

2017-11-01

In the primate auditory cortex, information flows serially in the mediolateral dimension from core, to belt, to parabelt. In the caudorostral dimension, stepwise serial projections convey information through the primary, rostral, and rostrotemporal (AI, R, and RT) core areas on the supratemporal plane, continuing to the rostrotemporal polar area (RTp) and adjacent auditory-related areas of the rostral superior temporal gyrus (STGr) and temporal pole. In addition to this cascade of corticocortical connections, the auditory cortex receives parallel thalamocortical projections from the medial geniculate nucleus (MGN). Previous studies have examined the projections from MGN to auditory cortex, but most have focused on the caudal core areas AI and R. In this study, we investigated the full extent of connections between MGN and AI, R, RT, RTp, and STGr using retrograde and anterograde anatomical tracers. Both AI and R received nearly 90% of their thalamic inputs from the ventral subdivision of the MGN (MGv; the primary/lemniscal auditory pathway). By contrast, RT received only ∼45% from MGv, and an equal share from the dorsal subdivision (MGd). Area RTp received ∼25% of its inputs from MGv, but received additional inputs from multisensory areas outside the MGN (30% in RTp vs. 1-5% in core areas). The MGN input to RTp distinguished this rostral extension of auditory cortex from the adjacent auditory-related cortex of the STGr, which received 80% of its thalamic input from multisensory nuclei (primarily medial pulvinar). Anterograde tracers identified complementary descending connections by which highly processed auditory information may modulate thalamocortical inputs. © 2017 Wiley Periodicals, Inc.

Differential Modulation of Spontaneous and Evoked Thalamocortical Network Activity by Acetylcholine Level In Vitro

PubMed Central

Wester, Jason C.

2013-01-01

Different levels of cholinergic neuromodulatory tone have been hypothesized to set the state of cortical circuits either to one dominated by local cortical recurrent activity (low ACh) or to one dependent on thalamic input (high ACh). High ACh levels depress intracortical but facilitate thalamocortical synapses, whereas low levels potentiate intracortical synapses. Furthermore, recent work has implicated the thalamus in controlling cortical network state during waking and attention, when ACh levels are highest. To test this hypothesis, we used rat thalamocortical slices maintained in medium to generate spontaneous up- and down-states and applied different ACh concentrations to slices in which thalamocortical connections were either maintained or severed. The effects on spontaneous and evoked up-states were measured using voltage-sensitive dye imaging, intracellular recordings, local field potentials, and single/multiunit activity. We found that high ACh can increase the frequency of spontaneous up-states, but reduces their duration in slices with intact thalamocortical connections. Strikingly, when thalamic connections are severed, high ACh instead greatly reduces or abolishes spontaneous up-states. Furthermore, high ACh reduces the spatial propagation, velocity, and depolarization amplitude of evoked up-states. In contrast, low ACh dramatically increases up-state frequency regardless of the presence or absence of intact thalamocortical connections and does not reduce the duration, spatial propagation, or velocity of evoked up-states. Therefore, our data support the hypothesis that strong cholinergic modulation increases the influence, and thus the signal-to-noise ratio, of afferent input over local cortical activity and that lower cholinergic tone enhances recurrent cortical activity regardless of thalamic input. PMID:24198382

Maturing Thalamocortical Functional Connectivity Across Development

PubMed Central

Fair, Damien A.; Bathula, Deepti; Mills, Kathryn L.; Dias, Taciana G. Costa; Blythe, Michael S.; Zhang, Dongyang; Snyder, Abraham Z.; Raichle, Marcus E.; Stevens, Alexander A.; Nigg, Joel T.; Nagel, Bonnie J.

2010-01-01

Recent years have witnessed a surge of investigations examining functional brain organization using resting-state functional connectivity MRI (rs-fcMRI). To date, this method has been used to examine systems organization in typical and atypical developing populations. While the majority of these investigations have focused on cortical–cortical interactions, cortical–subcortical interactions also mature into adulthood. Innovative work by Zhang et al. (2008) in adults have identified methods that utilize rs-fcMRI and known thalamo-cortical topographic segregation to identify functional boundaries in the thalamus that are remarkably similar to known thalamic nuclear grouping. However, despite thalamic nuclei being well formed early in development, the developmental trajectory of functional thalamo-cortical relations remains unexplored. Thalamic maps generated by rs-fcMRI are based on functional relationships, and should modify with the dynamic thalamo-cortical changes that occur throughout maturation. To examine this possibility, we employed a strategy as previously described by Zhang et al. to a sample of healthy children, adolescents, and adults. We found strengthening functional connectivity of the cortex with dorsal/anterior subdivisions of the thalamus, with greater connectivity observed in adults versus children. Temporal lobe connectivity with ventral/midline/posterior subdivisions of the thalamus weakened with age. Changes in sensory and motor thalamo-cortical interactions were also identified but were limited. These findings are consistent with known anatomical and physiological cortical–subcortical changes over development. The methods and developmental context provided here will be important for understanding how cortical–subcortical interactions relate to models of typically developing behavior and developmental neuropsychiatric disorders. PMID:20514143

Thalamic inputs to dorsomedial striatum are involved in inhibitory control: evidence from the five-choice serial reaction time task in rats.

PubMed

Saund, Jasjot; Dautan, Daniel; Rostron, Claire; Urcelay, Gonzalo P; Gerdjikov, Todor V

2017-08-01

Corticostriatal circuits are widely implicated in the top-down control of attention including inhibitory control and behavioural flexibility. However, recent neurophysiological evidence also suggests a role for thalamic inputs to striatum in behaviours related to salient, reward-paired cues. Here, we used designer receptors exclusively activated by designer drugs (DREADDs) to investigate the role of parafascicular (Pf) thalamic inputs to the dorsomedial striatum (DMS) using the five-choice serial reaction time task (5CSRTT) in rats. The 5CSRTT requires sustained attention in order to detect spatially and temporally distributed visual cues and provides measures of inhibitory control related to impulsivity (premature responses) and compulsivity (perseverative responses). Rats underwent bilateral Pf injections of the DREADD vector, AAV2-CaMKIIa-HA-hM4D(Gi)-IRES-mCitrine. The DREADD agonist, clozapine N-oxide (CNO; 1 μl bilateral; 3 μM) or vehicle, was injected into DMS 1 h before behavioural testing. Task parameters were manipulated to increase attention load or reduce stimulus predictability respectively. We found that inhibition of the Pf-DMS projection significantly increased perseverative responses when stimulus predictability was reduced but had no effect on premature responses or response accuracy, even under increased attentional load. Control experiments showed no effects on locomotor activity in an open field. These results complement previous lesion work in which the DMS and orbitofrontal cortex were similarly implicated in perseverative responses and suggest a specific role for thalamostriatal inputs in inhibitory control.

Thalamic Proteome Changes and Behavioral Impairments in Thiamine-deficient Rats.

PubMed

Nunes, Polliana Toledo; Gómez-Mendoza, Diana Paola; Rezende, Cristiana Perdigão; Figueiredo, Henrique César Pereira; Ribeiro, Angela Maria

2018-06-09

Thiamine deficiency (TD) has been used as an experimental model in rodents to study the molecular mechanisms of neurodegeneration and its association with behavioral changes. The aims of the present study were to investigate the spatial cognitive performance of pyrithiamine-induced thiamine deficiency (PTD) in adult male rats and disclose the thalamic proteome alterations caused by a severe TD episode. After the onset of the neurological signs, such as seizure and/or loss of righting reflex, the TD treatment was interrupted. Following 15 days of recovery, all rats were submitted to the spatial cognitive tasks in the Morris Water Maze (MWM). The results show that the PTD rats exhibited deficits during the learning process, which was reverted by repeated training. However, despite the spatial cognitive recovery, some protein changes were not reversible. The proteomic analysis, using label-free quantification, revealed deregulation of 183 thalamic proteins. Using bioinformatic tools, these proteins were categorized according to Gene Ontology functional annotation and metabolic pathways. We show that a severe TD affects proteins involved in different biological processes, such as, oxidative stress, neurotransmitter synthesis and synaptic vesicle cycle. These could explain the outcome in neurotransmitter release changes caused by TD, previously observed by our group and by other authors. These findings disclose the role of key proteins and metabolic pathways probably involved in the neurodegeneration process induced by TD. These proteins represent relevant molecular targets for future studies focusing also on the molecular basis of selective vulnerability of some brain areas to TD insult. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Golgi-type I and Golgi-type II neurons in the ventral anterior thalamic nucleus of the adult human: morphological features and quantitative analysis.

PubMed

Al-Hussain Bani Hani, Saleh M; El-Dwairi, Qasim A; Bataineh, Ziad M; Al-Haidari, Mohammad S; Al-Alami, Jamil

2008-05-01

The morphological and quantitative features of neurons in the adult human ventral anterior thalamic nucleus were studied in Golgi preparations. Two neuronal types were found and their quantitative features were studied. Golgi-type I neurons were medium to large cells with dense dendritic trees and dendritic protrusions and short hair-like appendages. They have somatic mean diameter of 30.8 microm (+/-9.4, n = 85). They have an average 100.3 dendritic branches, 48.97 dendritic branching points, and 58.85 dendritic tips. The mean diameters of their primary, secondary, and tertiary dendrites were 3.1 microm (+/-1, n = 80), 1.85 microm (+/-0.8, n = 145), and 1.5 microm (+/-0.4, n = 160), respectively. Golgi-type II neurons were small to medium cells with few sparsely branching dendrites and dendritic stalked appendages with or without terminal swellings. They have somatic mean diameters of 22.2 microm (+/-5.8, n = 120). They have an average 33.76 dendritic branches, 16.49 dendritic branching points, and 21.97 dendritic tips. The mean diameters of their primary, secondary, and tertiary dendrites were 1.6 microm (+/-0.86, n = 70), 1.15 microm (+/-0.55, n = 118), and 1 microm (+/-0.70, n = 95), respectively. These quantitative data may form the basis for further quantitative studies involving aging or some degenerative diseases that may affect cell bodies and/or dendritic trees of the Golgi-type I and/or Golgi-type II thalamic neurons.

Changes in the thalamus in atypical parkinsonism detected using shape analysis and diffusion tensor imaging.

PubMed

Hess, C P; Christine, C W; Apple, A C; Dillon, W P; Aminoff, M J

2014-05-01

The thalamus is interconnected with the nigrostriatal system and cerebral cortex and has a major role in cognitive function and sensorimotor integration. The purpose of this study was to determine how regional involvement of the thalamus differs among Parkinson disease, progressive supranuclear palsy, and corticobasal syndrome. Nine patients with Parkinson disease, 5 with progressive supranuclear palsy, and 6 with corticobasal syndrome underwent 3T MR imaging along with 12 matched, asymptomatic volunteers by using a protocol that included volumetric T1 and diffusion tensor imaging. Acquired data were automatically processed to delineate the margins of the motor and nonmotor thalamic nuclear groups, and measurements of ADC were calculated from the DTI data within these regions. Thalamic volume, shape, and ADC were compared across groups. Thalamic volume was smaller in the progressive supranuclear palsy and corticobasal syndrome groups compared with the Parkinson disease and control groups. Shape analysis revealed that this was mainly due to the diminished size of the lateral thalamus. Overall, ADC measurements were higher in the progressive supranuclear palsy group compared with both the Parkinson disease and control groups, and anatomic subgroup analysis demonstrated that these changes were greater within the motor regions of the thalamus in progressive supranuclear palsy and corticobasal degeneration. Reduced size and increased ADC disproportionately involve the lateral thalamus in progressive supranuclear palsy and corticobasal syndrome, consistent with selective neurodegeneration and atrophy in this region. Because these findings were not observed in Parkinson disease, they may be more specific markers of tau-related neurodegeneration. © 2014 by American Journal of Neuroradiology.

Hyper-connectivity of the Thalamus in during Early Stages following Mild Traumatic Brain Injury

PubMed Central

Sours, Chandler; George, Elijah O.; Zhuo, Jiachen; Roys, Steven; Gullapalli, Rao P.

2015-01-01

The thalamo-cortical resting state functional connectivity of 7 sub-thalamic regions were examined in a prospectively recruited population of 77 acute mild TBI (mTBI) patients within the first 10 days (mean 6±3 days) of injury and 35 neurologically intact control subjects using the Oxford thalamic connectivity atlas. Neuropsychological assessments were conducted using the Automated Neuropsychological Assessment Metrics (ANAM). A subset of participants received a magentic resonance spectroscopy (MRS) exam to determine metabolite concentrations in the thalamus and posterior cingulate cortex. Results show that patients performed worse than the control group on various subtests of ANAM and the weighted throughput score, suggesting reduced cognitive performance at this early stage of injury. Both voxel and region of interest based analysis of the resting state fMRI data demonstrated that acute mTBI patients have increased functional connectivity between the various sub-thalamic regions and cortical regions associated with sensory processing and the default mode network (DMN). In addition, a significant reduction in NAA/Cr was observed in the thalamus in the mTBI patients. Furthermore, an increase in Cho/Cr ratio specific to mTBI patients with self-reported sensory symptoms was observed compared to those without self-reported sensory symptoms. These results provide novel insights into the neural mechanisms of the brain state related to internal rumination and arousal, which have implications for new interventions for mTBI patients with persistent symptoms. Furthermore, an understanding of heightened sensitivity to sensory related inputs during early stages of injury may facilitate enhanced prediction of safe return to work. PMID:26153468

Assessing Quantitative Changes in Intrinsic Thalamic Networks in Blast and Nonblast Mild Traumatic Brain Injury: Implications for Mechanisms of Injury.

PubMed

Nathan, Dominic E; Bellgowan, Julie F; Oakes, Terrence R; French, Louis M; Nadar, Sreenivasan R; Sham, Elyssa B; Liu, Wei; Riedy, Gerard

2016-06-01

In the global war on terror, the increased use of improvised explosive devices has resulted in increased incidence of blast-related mild traumatic brain injury (mTBI). Diagnosing mTBI is both challenging and controversial due to heterogeneity of injury location, trauma intensity, transient symptoms, and absence of focal biomarkers on standard clinical imaging modalities. The goal of this study is to identify a brain biomarker that is sensitive to mTBI injury. Research suggests the thalamus may be sensitive to changes induced by mTBI. A significant number of connections to and from various brain regions converge at the thalamus. In addition, the thalamus is involved in information processing, integration, and regulation of specific behaviors and mood. In this study, changes in task-free thalamic networks as quantified by graph theory measures in mTBI blast (N = 186), mTBI nonblast (N = 80), and controls (N = 21) were compared. Results show that the blast mTBI group had significant hyper-connectivity compared with the controls and nonblast mTBI group. However, after controlling for post-traumatic stress symptoms (PTSS), the blast mTBI group was not different from the controls, but the nonblast mTBI group showed significant hypo-connectivity. The results suggest that there are differences in the mechanisms of injury related to mTBI as reflected in the architecture of the thalamic networks. However, the effect of PTSS and its relationship to mTBI is difficult to distinguish and warrants more research.

A role for the anteromedial thalamic nucleus in the acquisition of contextual fear memory to predatory threats.

PubMed

de Lima, Miguel Antonio Xavier; Baldo, Marcus Vinicius C; Canteras, Newton Sabino

2017-01-01

Previous studies from our group have shown that cytotoxic lesions in the ventral portion of the anteromedial thalamic nucleus (AMv), one of the main targets of the hypothalamic predator-responsive circuit, strongly impairs contextual fear responses to an environment previously associated with a predator. The AMv is in a position to convey information to cortico-hippocampal-amygdalar circuits involved in the processing of fear memory. However, it remains to be determined whether the nucleus is involved in the acquisition or subsequent expression of contextual fear. In the present investigation, we addressed this question by inactivating the rat AMv with muscimol either prior to cat exposure or prior to exposure to the cat-related context. Accordingly, AMv pharmacological inactivation prior to cat exposure did not interfere with innate fear responses, but it drastically reduced contextual conditioning to the predator-associated environment. On the other hand, AMv inactivation prior to exposure to the environment associated with the predator threat did not affect contextual fear responses. The behavioral results were further supported by the demonstration that AMv inactivation prior to cat exposure also blocked the activation of sites critically involved in the expression of anti-predatory contextual defensive responses (i.e., the dorsal premammillary nucleus and the dorsolateral periaqueductal gray) in animals exposed to the predator-associated context. The AMv projections were also examined, and the results of this investigation outline important paths that can influence hippocampal circuitry and raise new ideas for anterior thalamic-hippocampal paths involved in emotional learning.

Tuning Shifts of the Auditory System By Corticocortical and Corticofugal Projections and Conditioning

PubMed Central

Suga, Nobuo

2011-01-01

The central auditory system consists of the lemniscal and nonlemniscal systems. The thalamic lemniscal and non-lemniscal auditory nuclei are different from each other in response properties and neural connectivities. The cortical auditory areas receiving the projections from these thalamic nuclei interact with each other through corticocortical projections and project down to the subcortical auditory nuclei. This corticofugal (descending) system forms multiple feedback loops with the ascending system. The corticocortical and corticofugal projections modulate auditory signal processing and play an essential role in the plasticity of the auditory system. Focal electric stimulation -- comparable to repetitive tonal stimulation -- of the lemniscal system evokes three major types of changes in the physiological properties, such as the tuning to specific values of acoustic parameters of cortical and subcortical auditory neurons through different combinations of facilitation and inhibition. For such changes, a neuromodulator, acetylcholine, plays an essential role. Electric stimulation of the nonlemniscal system evokes changes in the lemniscal system that is different from those evoked by the lemniscal stimulation. Auditory signals ascending from the lemniscal and nonlemniscal thalamic nuclei to the cortical auditory areas appear to be selected or adjusted by a “differential” gating mechanism. Conditioning for associative learning and pseudo-conditioning for nonassociative learning respectively elicit tone-specific and nonspecific plastic changes. The lemniscal, corticofugal and cholinergic systems are involved in eliciting the former, but not the latter. The current article reviews the recent progress in the research of corticocortical and corticofugal modulations of the auditory system and its plasticity elicited by conditioning and pseudo-conditioning. PMID:22155273

A Preliminary Experience with Use of Intraoperative Magnetic Resonance Imaging in Thalamic Glioma Surgery: A Case Series of 38 Patients.

PubMed

Zheng, Xuan; Xu, Xinghua; Zhang, Hui; Wang, Qun; Ma, Xiaodong; Chen, Xiaolei; Sun, Guochen; Zhang, Jiashu; Jiang, Jinli; Xu, Bainan; Zhang, Jun

2016-05-01

Thalamic gliomas are rare tumors that constitute 1%-5% of all central nervous system tumors. Despite advanced techniques and equipment, surgical resection remains challenging because of the vital structures adjacent to the tumor. Intraoperative magnetic resonance imaging (MRI) might play an active role during brain tumor surgery because it compensates for brain shift or operation-induced hemorrhage, which are challenging issues for neurosurgeons. We reviewed 38 patients treated surgically under intraoperative MRI guidance between January 2008 and July 2015 at our center. Preoperative, intraoperative, and postoperative MRI scans were reviewed. Preoperative and postoperative motor power, morbidity and mortality, resection rate, surgical approach, pathologic results, and patient demographics were also reviewed. Mean patient age was 37 years ± 18; 12 patients were included in the low-grade group, and 26 patients were included in the high-grade group. Under intraoperative MRI guidance, the gross total resection rate was increased from 16 (42.1%) to 26 (68.4%), and the near-total or subtotal resection rate was increased from 5 (13.2%) to 9 (23.7%). Hematoma formation was discovered in 3 patients on intraoperative MRI scan; each patient underwent a hemostatic operation immediately. With improvements in neurosurgical techniques and equipment, surgical resection is considered feasible in patients with thalamic gliomas. Intraoperative MRI may be helpful in achieving the maximal resection rate with minimal surgical-related morbidity. However, because of severe disease progression, the overall prognosis is unfavorable. Copyright © 2016 Elsevier Inc. All rights reserved.

Characterization of Topographically Specific Sleep Spindles in Mice

PubMed Central

Kim, Dongwook; Hwang, Eunjin; Lee, Mina; Sung, Hokun; Choi, Jee Hyun

2015-01-01

Study Objective: Sleep spindles in humans have been classified as slow anterior and fast posterior spindles; recent findings indicate that their profiles differ according to pharmacology, pathology, and function. However, little is known about the generation mechanisms within the thalamocortical system for different types of spindles. In this study, we aim to investigate the electrophysiological behaviors of the topographically distinctive spindles within the thalamocortical system by applying high-density EEG and simultaneous thalamic LFP recordings in mice. Design: 32-channel extracranial EEG and 2-channel thalamic LFP were recorded simultaneously in freely behaving mice to acquire spindles during spontaneous sleep. Subjects: Hybrid F1 male mice of C57BL/6J and 129S4/svJae. Measurements and Results: Spindle events in each channel were detected by spindle detection algorithm, and then a cluster analysis was applied to classify the topographically distinctive spindles. All sleep spindles were successfully classified into 3 groups: anterior, posterior, and global spindles. Each spindle type showed distinct thalamocortical activity patterns regarding the extent of similarity, phase synchrony, and time lags between cortical and thalamic areas during spindle oscillation. We also found that sleep slow waves were likely to associate with all types of sleep spindles, but also that the ongoing cortical decruitment/recruitment dynamics before the onset of spindles and their relationship with spindle generation were also variable, depending on the spindle types. Conclusion: Topographically specific sleep spindles show distinctive thalamocortical network behaviors. Citation: Kim D, Hwang E, Lee M, Sung H, Choi JH. Characterization of topographically specific sleep spindles in mice. SLEEP 2015;38(1):85–96. PMID:25325451

Variable Action Potential Backpropagation during Tonic Firing and Low-Threshold Spike Bursts in Thalamocortical But Not Thalamic Reticular Nucleus Neurons.

PubMed

Connelly, William M; Crunelli, Vincenzo; Errington, Adam C

2017-05-24

Backpropagating action potentials (bAPs) are indispensable in dendritic signaling. Conflicting Ca 2+ -imaging data and an absence of dendritic recording data means that the extent of backpropagation in thalamocortical (TC) and thalamic reticular nucleus (TRN) neurons remains unknown. Because TRN neurons signal electrically through dendrodendritic gap junctions and possibly via chemical dendritic GABAergic synapses, as well as classical axonal GABA release, this lack of knowledge is problematic. To address this issue, we made two-photon targeted patch-clamp recordings from rat TC and TRN neuron dendrites to measure bAPs directly. These recordings reveal that "tonic"' and low-threshold-spike (LTS) "burst" APs in both cell types are always recorded first at the soma before backpropagating into the dendrites while undergoing substantial distance-dependent dendritic amplitude attenuation. In TC neurons, bAP attenuation strength varies according to firing mode. During LTS bursts, somatic AP half-width increases progressively with increasing spike number, allowing late-burst spikes to propagate more efficiently into the dendritic tree compared with spikes occurring at burst onset. Tonic spikes have similar somatic half-widths to late burst spikes and undergo similar dendritic attenuation. In contrast, in TRN neurons, AP properties are unchanged between LTS bursts and tonic firing and, as a result, distance-dependent dendritic attenuation remains consistent across different firing modes. Therefore, unlike LTS-associated global electrical and calcium signals, the spatial influence of bAP signaling in TC and TRN neurons is more restricted, with potentially important behavioral-state-dependent consequences for synaptic integration and plasticity in thalamic neurons. SIGNIFICANCE STATEMENT In most neurons, action potentials (APs) initiate in the axosomatic region and propagate into the dendritic tree to provide a retrograde signal that conveys information about the level of cellular output to the locations that receive most input: the dendrites. In thalamocortical and thalamic reticular nucleus neurons, the site of AP generation and the true extent of backpropagation remain unknown. Using patch-clamp recordings, this study measures dendritic propagation of APs directly in these neurons. In either cell type, high-frequency low-threshold spike burst or lower-frequency tonic APs undergo substantial voltage attenuation as they spread into the dendritic tree. Therefore, backpropagating spikes in these cells can only influence signaling in the proximal part of the dendritic tree. Copyright © 2017 Connelly et al.

The CaV2.3 R-type voltage-gated Ca2+ channel in mouse sleep architecture.

PubMed

Siwek, Magdalena Elisabeth; Müller, Ralf; Henseler, Christina; Broich, Karl; Papazoglou, Anna; Weiergräber, Marco

2014-05-01

Voltage-gated Ca(2+) channels (VGCCs) are key elements in mediating thalamocortical rhythmicity. Low-voltage activated (LVA) CaV 3 T-type Ca(2+) channels have been related to thalamic rebound burst firing and to generation of non-rapid eye movement (NREM) sleep. High-voltage activated (HVA) CaV 1 L-type Ca(2+) channels, on the opposite, favor the tonic mode of action associated with higher levels of vigilance. However, the role of the HVA Non-L-type CaV2.3 Ca(2+) channels, which are predominantly expressed in the reticular thalamic nucleus (RTN), still remains unclear. Recently, CaV2.3(-/-) mice were reported to exhibit altered spike-wave discharge (SWD)/absence seizure susceptibility supported by the observation that CaV2.3 mediated Ca(2+) influx into RTN neurons can trigger small-conductance Ca(2+)-activated K(+)-channel type 2 (SK2) currents capable of maintaining thalamic burst activity. Based on these studies we investigated the role of CaV2.3 R-type Ca(2+) channels in rodent sleep. The role of CaV2.3 Ca(2+) channels was analyzed in CaV2.3(-/-) mice and controls in both spontaneous and artificial urethane-induced sleep, using implantable video-EEG radiotelemetry. Data were analyzed for alterations in sleep architecture using sleep staging software and time-frequency analysis. CaV2.3 deficient mice exhibited reduced wake duration and increased slow-wave sleep (SWS). Whereas mean sleep stage durations remained unchanged, the total number of SWS epochs was increased in CaV2.3(-/-) mice. Additional changes were observed for sleep stage transitions and EEG amplitudes. Furthermore, urethane-induced SWS mimicked spontaneous sleep results obtained from CaV2.3 deficient mice. Quantitative Real-time PCR did not reveal changes in thalamic CaV3 T-type Ca(2+) channel expression. The detailed mechanisms of SWS increase in CaV2.3(-/-) mice remain to be determined. Low-voltage activated CaV2.3 R-type Ca(2+) channels in the thalamocortical loop and extra-thalamocortical circuitries substantially regulate rodent sleep architecture thus representing a novel potential target for pharmacological treatment of sleep disorders in the future.

Self-sustained asynchronous irregular states and Up-Down states in thalamic, cortical and thalamocortical networks of nonlinear integrate-and-fire neurons.

PubMed

Destexhe, Alain

2009-12-01

Randomly-connected networks of integrate-and-fire (IF) neurons are known to display asynchronous irregular (AI) activity states, which resemble the discharge activity recorded in the cerebral cortex of awake animals. However, it is not clear whether such activity states are specific to simple IF models, or if they also exist in networks where neurons are endowed with complex intrinsic properties similar to electrophysiological measurements. Here, we investigate the occurrence of AI states in networks of nonlinear IF neurons, such as the adaptive exponential IF (Brette-Gerstner-Izhikevich) model. This model can display intrinsic properties such as low-threshold spike (LTS), regular spiking (RS) or fast-spiking (FS). We successively investigate the oscillatory and AI dynamics of thalamic, cortical and thalamocortical networks using such models. AI states can be found in each case, sometimes with surprisingly small network size of the order of a few tens of neurons. We show that the presence of LTS neurons in cortex or in thalamus, explains the robust emergence of AI states for relatively small network sizes. Finally, we investigate the role of spike-frequency adaptation (SFA). In cortical networks with strong SFA in RS cells, the AI state is transient, but when SFA is reduced, AI states can be self-sustained for long times. In thalamocortical networks, AI states are found when the cortex is itself in an AI state, but with strong SFA, the thalamocortical network displays Up and Down state transitions, similar to intracellular recordings during slow-wave sleep or anesthesia. Self-sustained Up and Down states could also be generated by two-layer cortical networks with LTS cells. These models suggest that intrinsic properties such as adaptation and low-threshold bursting activity are crucial for the genesis and control of AI states in thalamocortical networks.

Stimulation of the nervous system for the management of seizures: current and future developments.

PubMed

Murphy, Jerome V; Patil, Arunangelo

2003-01-01

Vagal nerve stimulation (VNS) for the treatment of refractory epilepsy appears to have started from the theory that since VNS can alter the EEG, it may influence epilepsy. It proved effective in several models of epilepsy and was then tried in short-term, open-label and double-blind trials, leading to approval in Canada, Europe and the US. Follow-up observations in these patients demonstrated continued improvement in seizure control for up to 2 years. Close to 50% of treated patients have achieved at least a 50% reduction in seizure frequency. This therapy was also useful as rescue therapy for ongoing seizures in some patients; many patients are more alert. The initial trials were completed in patients >/=12 years of age with refractory partial seizures. Subsequently, similar benefits were shown in patients with tuberous sclerosis complex, Lennox-Gastaut syndrome, hypothalamic hamartomas and primary generalised seizures. Implanting the generator and leads is technically easy, and complications are few. The method of action is largely unknown, although VNS appears to alter metabolic activity in specific brain nuclei. Considering that improvement in mood is frequently found in patients using VNS, it has undergone trials in patients with depression. Other illnesses deserving exploration with this unusual therapy are Alzheimer's disease and autism. Some aspects of VNS have proven disappointing. Although patients have fewer seizures, the number of antiepileptic drugs they take is not significantly reduced. In addition, there is no way to accurately predict the end of life of the generator. Optimal stimulation parameters, if they exist, are unknown. Deep brain stimulation is a new method for controlling medically refractory seizures. It is based on the observation that thalamic stimulation can influence the EEG over a wide area. Several thalamic nuclei have been the object of stimulation in different groups of patients. Intraoperative brain imaging is essential for electrode placement. The procedure is done under local anaesthesia. Experience with this therapy is currently limited, but growing.

Expression of GABA receptor subunits in the hippocampus and thalamus after experimental traumatic brain injury

PubMed Central

Drexel, Meinrad; Puhakka, Noora; Kirchmair, Elke; Hörtnagl, Heide; Pitkänen, Asla; Sperk, Günther

2015-01-01

Traumatic brain injury is a major cause of death and disability worldwide and often associated with post-traumatic epilepsy. We recently demonstrated that TBI induces acquired GABAA receptors channelopathy that associates with hyperexcitability in granule cell layer (GCL). We now assessed the expression of GABAA and GABAB receptor subunit mRNAs between 6 h and 6 months post-TBI in the hippocampus and thalamus. The expression of major GABAA receptor subunit mRNAs (α1, α2, α5, β2, β3, γ2 and δ) was, often bilaterally, down-regulated in the GCL and in the CA3 pyramidal cells. Instead, expression of α4 (GCL, CA3, CA1), α5 (CA1) and γ2 (GCL, CA3, CA1) mRNA was up-regulated after 10 d and/or 4 months. Many of these changes were reversible. In the thalamus, we found decreases in α1, α4, β2, γ2 and δ mRNAs in the laterodorsal thalamus and in the area combining the posterior thalamic nuclear group, ventroposterolateral and ventroposteromedial complex at 6 h to 4 months post-TBI. Unlike in the hippocampus, thalamic subunit down-regulations were irreversible and limited to the ipsilateral side. However, contralaterally there was up-regulation of the subunits δ and α4 6 h and 4 months after TBI, respectively. PCR array analysis suggested a mild long-lasting GABAA receptor channelopathy in the GCL and thalamus after TBI. Whereas TBI induces transient changes in the expression of GABAA receptor subunits in the hippocampus (presumably representing compensatory mechanisms), alterations of GABAA receptor subunit mRNAs in the thalamus are long-lasting and related to degeneration of receptor-containing neurons in thalamo-cortical relay nuclei. This article is part of the Special Issue entitled ‘GABAergic Signaling in Health and Disease’. PMID:25229716

Expression of GABA receptor subunits in the hippocampus and thalamus after experimental traumatic brain injury.

PubMed

Drexel, Meinrad; Puhakka, Noora; Kirchmair, Elke; Hörtnagl, Heide; Pitkänen, Asla; Sperk, Günther

2015-01-01

Traumatic brain injury is a major cause of death and disability worldwide and often associated with post-traumatic epilepsy. We recently demonstrated that TBI induces acquired GABAA receptors channelopathy that associates with hyperexcitability in granule cell layer (GCL). We now assessed the expression of GABAA and GABAB receptor subunit mRNAs between 6 h and 6 months post-TBI in the hippocampus and thalamus. The expression of major GABAA receptor subunit mRNAs (α1, α2, α5, β2, β3, γ2 and δ) was, often bilaterally, down-regulated in the GCL and in the CA3 pyramidal cells. Instead, expression of α4 (GCL, CA3, CA1), α5 (CA1) and γ2 (GCL, CA3, CA1) mRNA was up-regulated after 10 d and/or 4 months. Many of these changes were reversible. In the thalamus, we found decreases in α1, α4, β2, γ2 and δ mRNAs in the laterodorsal thalamus and in the area combining the posterior thalamic nuclear group, ventroposterolateral and ventroposteromedial complex at 6 h to 4 months post-TBI. Unlike in the hippocampus, thalamic subunit down-regulations were irreversible and limited to the ipsilateral side. However, contralaterally there was up-regulation of the subunits δ and α4 6 h and 4 months after TBI, respectively. PCR array analysis suggested a mild long-lasting GABAA receptor channelopathy in the GCL and thalamus after TBI. Whereas TBI induces transient changes in the expression of GABAA receptor subunits in the hippocampus (presumably representing compensatory mechanisms), alterations of GABAA receptor subunit mRNAs in the thalamus are long-lasting and related to degeneration of receptor-containing neurons in thalamo-cortical relay nuclei. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Mean-field thalamocortical modeling of longitudinal EEG acquired during intensive meditation training.

PubMed

Saggar, Manish; Zanesco, Anthony P; King, Brandon G; Bridwell, David A; MacLean, Katherine A; Aichele, Stephen R; Jacobs, Tonya L; Wallace, B Alan; Saron, Clifford D; Miikkulainen, Risto

2015-07-01

Meditation training has been shown to enhance attention and improve emotion regulation. However, the brain processes associated with such training are poorly understood and a computational modeling framework is lacking. Modeling approaches that can realistically simulate neurophysiological data while conforming to basic anatomical and physiological constraints can provide a unique opportunity to generate concrete and testable hypotheses about the mechanisms supporting complex cognitive tasks such as meditation. Here we applied the mean-field computational modeling approach using the scalp-recorded electroencephalogram (EEG) collected at three assessment points from meditating participants during two separate 3-month-long shamatha meditation retreats. We modeled cortical, corticothalamic, and intrathalamic interactions to generate a simulation of EEG signals recorded across the scalp. We also present two novel extensions to the mean-field approach that allow for: (a) non-parametric analysis of changes in model parameter values across all channels and assessments; and (b) examination of variation in modeled thalamic reticular nucleus (TRN) connectivity over the retreat period. After successfully fitting whole-brain EEG data across three assessment points within each retreat, two model parameters were found to replicably change across both meditation retreats. First, after training, we observed an increased temporal delay between modeled cortical and thalamic cells. This increase provides a putative neural mechanism for a previously observed reduction in individual alpha frequency in these same participants. Second, we found decreased inhibitory connection strength between the TRN and secondary relay nuclei (SRN) of the modeled thalamus after training. This reduction in inhibitory strength was found to be associated with increased dynamical stability of the model. Altogether, this paper presents the first computational approach, taking core aspects of physiology and anatomy into account, to formally model brain processes associated with intensive meditation training. The observed changes in model parameters inform theoretical accounts of attention training through meditation, and may motivate future study on the use of meditation in a variety of clinical populations. Copyright © 2015 Elsevier Inc. All rights reserved.

VGLUT1 mRNA and protein expression in the visual system of prosimian galagos (Otolemur garnetti)

PubMed Central

Balaram, Pooja; Hackett, Troy A; Kaas, Jon H

2011-01-01

The presynaptic storage and release of glutamate, an excitatory neurotransmitter, is modulated by a family of transport proteins known as vesicular glutamate transporters. Vesicular glutamate transporter 1 (VGLUT1) is widely distributed in the central nervous system of most mammalian and nonmammalian species, and regulates the uptake of glutamate into synaptic vesicles as well as the transport of filled glutamatergic vesicles to the terminal membrane during excitatory transmission. In rodents, VGLUT1 mRNA is primarily found in the neocortex, cerebellum, and hippocampus, and the VGLUT1 transport protein is involved in intercortical and corticothalamic projections that remain distinct from projections involving other VGLUT isoforms. With the exception of a few thalamic sensory nuclei, VGLUT1 mRNA is absent from subcortical areas and does not colocalize with other VGLUT mRNAs. VGLUT1 is similarly restricted to a few thalamic association nuclei and does not colocalize with other VGLUT proteins. However, recent work in primates has shown that VGLUT1 mRNA is also found in several subcortical nuclei as well as cortical areas, and that VGLUT1 may overlap with other VGLUT isoforms in glutamatergic projections. In order to expand current knowledge of VGLUT1 distributions in primates and gain insight on glutamatergic transmission in the visual system of primate species, we examined VGLUT1 mRNA and protein distributions in the lateral geniculate nucleus, pulvinar complex, superior colliculus, V1, V2, and the middle temporal area (MT) of prosimian galagos. We found that, similar to other studies in primates, VGLUT1 mRNA and protein are widely distributed in both subcortical and cortical areas. However, glutamatergic projections involving VGLUT1 are largely limited to intrinsic connections within subcortical and cortical areas, as well as the expected intercortical and corticothalamic projections. Additionally, VGLUT1 expression in galagos allowed us to identify laminar subdivisions of the superior colliculus, V1, V2, and MT. PMID:22912561

Functional Anatomy of Non-REM Sleep

PubMed Central

de Andrés, Isabel; Garzón, Miguel; Reinoso-Suárez, Fernando

2011-01-01

The state of non-REM sleep (NREM), or slow wave sleep, is associated with a synchronized EEG pattern in which sleep spindles and/or K complexes and high-voltage slow wave activity (SWA) can be recorded over the entire cortical surface. In humans, NREM is subdivided into stages 2 and 3–4 (presently named N3) depending on the proportions of each of these polygraphic events. NREM is necessary for normal physical and intellectual performance and behavior. An overview of the brain structures involved in NREM generation shows that the thalamus and the cerebral cortex are absolutely necessary for the most significant bioelectric and behavioral events of NREM to be expressed; other structures like the basal forebrain, anterior hypothalamus, cerebellum, caudal brain stem, spinal cord and peripheral nerves contribute to NREM regulation and modulation. In NREM stage 2, sustained hyperpolarized membrane potential levels resulting from interaction between thalamic reticular and projection neurons gives rise to spindle oscillations in the membrane potential; the initiation and termination of individual spindle sequences depends on corticothalamic activities. Cortical and thalamic mechanisms are also involved in the generation of EEG delta SWA that appears in deep stage 3–4 (N3) NREM; the cortex has classically been considered to be the structure that generates this activity, but delta oscillations can also be generated in thalamocortical neurons. NREM is probably necessary to normalize synapses to a sustainable basal condition that can ensure cellular homeostasis. Sleep homeostasis depends not only on the duration of prior wakefulness but also on its intensity, and sleep need increases when wakefulness is associated with learning. NREM seems to ensure cell homeostasis by reducing the number of synaptic connections to a basic level; based on simple energy demands, cerebral energy economizing during NREM sleep is one of the prevalent hypotheses to explain NREM homeostasis. PMID:22110467

Strategic Lesions in the Anterior Thalamic Radiation and Apathy in Early Alzheimer's Disease

PubMed Central

Torso, Mario; Serra, Laura; Giulietti, Giovanni; Spanò, Barbara; Tuzzi, Elisa; Koch, Giacomo; Caltagirone, Carlo; Cercignani, Mara; Bozzali, Marco

2015-01-01

Background Behavioural disorders and psychological symptoms of Dementia (BPSD) are commonly observed in Alzheimer’s disease (AD), and strongly contribute to increasing patients' disability. Using voxel-lesion-symptom mapping (VLSM), we investigated the impact of white matter lesions (WMLs) on the severity of BPSD in patients with amnestic mild cognitive impairment (a-MCI). Methods Thirty-one a-MCI patients (with a conversion rate to AD of 32% at 2 year follow-up) and 26 healthy controls underwent magnetic resonance imaging (MRI) examination at 3T, including T2-weighted and fluid-attenuated-inversion-recovery images, and T1-weighted volumes. In the patient group, BPSD was assessed using the Neuropsychiatric Inventory-12. After quantitative definition of WMLs, their distribution was investigated, without an a priori anatomical hypothesis, against patients’ behavioural symptoms. Unbiased regional grey matter volumetrics was also used to assess the contribution of grey matter atrophy to BPSD. Results Apathy, irritability, depression/dysphoria, anxiety and agitation were shown to be the most common symptoms in the patient sample. Despite a more widespread anatomical distribution, a-MCI patients did not differ from controls in WML volumes. VLSM revealed a strict association between the presence of lesions in the anterior thalamic radiations (ATRs) and the severity of apathy. Regional grey matter atrophy did not account for any BPSD. Conclusions This study indicates that damage to the ATRs is strategic for the occurrence of apathy in patients with a-MCI. Disconnection between the prefrontal cortex and the mediodorsal and anterior thalamic nuclei might represent the pathophysiological substrate for apathy, which is one of the most common psychopathological symptoms observed in dementia. PMID:25932637

Impact of Strategically Located White Matter Hyperintensities on Cognition in Memory Clinic Patients with Small Vessel Disease.

PubMed

Biesbroek, J Matthijs; Weaver, Nick A; Hilal, Saima; Kuijf, Hugo J; Ikram, Mohammad Kamran; Xu, Xin; Tan, Boon Yeow; Venketasubramanian, Narayanaswamy; Postma, Albert; Biessels, Geert Jan; Chen, Christopher P L H

2016-01-01

Studies on the impact of small vessel disease (SVD) on cognition generally focus on white matter hyperintensity (WMH) volume. The extent to which WMH location relates to cognitive performance has received less attention, but is likely to be functionally important. We examined the relation between WMH location and cognition in a memory clinic cohort of patients with sporadic SVD. A total of 167 patients with SVD were recruited from memory clinics. Assumption-free region of interest-based analyses based on major white matter tracts and voxel-wise analyses were used to determine the association between WMH location and executive functioning, visuomotor speed and memory. Region of interest-based analyses showed that WMHs located particularly within the anterior thalamic radiation and forceps minor were inversely associated with both executive functioning and visuomotor speed, independent of total WMH volume. Memory was significantly associated with WMH volume in the forceps minor, independent of total WMH volume. An independent assumption-free voxel-wise analysis identified strategic voxels in these same tracts. Region of interest-based analyses showed that WMH volume within the anterior thalamic radiation explained 6.8% of variance in executive functioning, compared to 3.9% for total WMH volume; WMH volume within the forceps minor explained 4.6% of variance in visuomotor speed and 4.2% of variance in memory, compared to 1.8% and 1.3% respectively for total WMH volume. Our findings identify the anterior thalamic radiation and forceps minor as strategic white matter tracts in which WMHs are most strongly associated with cognitive impairment in memory clinic patients with SVD. WMH volumes in individual tracts explained more variance in cognition than total WMH burden, emphasizing the importance of lesion location when addressing the functional consequences of WMHs.

Real-time fMRI neurofeedback of the mediodorsal and anterior thalamus enhances correlation between thalamic BOLD activity and alpha EEG rhythm.

PubMed

Zotev, Vadim; Misaki, Masaya; Phillips, Raquel; Wong, Chung Ki; Bodurka, Jerzy

2018-02-01

Real-time fMRI neurofeedback (rtfMRI-nf) with simultaneous EEG allows volitional modulation of BOLD activity of target brain regions and investigation of related electrophysiological activity. We applied this approach to study correlations between thalamic BOLD activity and alpha EEG rhythm. Healthy volunteers in the experimental group (EG, n = 15) learned to upregulate BOLD activity of the target region consisting of the mediodorsal (MD) and anterior (AN) thalamic nuclei using rtfMRI-nf during retrieval of happy autobiographical memories. Healthy subjects in the control group (CG, n = 14) were provided with a sham feedback. The EG participants were able to significantly increase BOLD activities of the MD and AN. Functional connectivity between the MD and the inferior precuneus was significantly enhanced during the rtfMRI-nf task. Average individual changes in the occipital alpha EEG power significantly correlated with the average MD BOLD activity levels for the EG. Temporal correlations between the occipital alpha EEG power and BOLD activities of the MD and AN were significantly enhanced, during the rtfMRI-nf task, for the EG compared to the CG. Temporal correlations with the alpha power were also significantly enhanced for the posterior nodes of the default mode network, including the precuneus/posterior cingulate, and for the dorsal striatum. Our findings suggest that the temporal correlation between the MD BOLD activity and posterior alpha EEG power is modulated by the interaction between the MD and the inferior precuneus, reflected in their functional connectivity. Our results demonstrate the potential of the rtfMRI-nf with simultaneous EEG for noninvasive neuromodulation studies of human brain function. © 2017 Wiley Periodicals, Inc.

Control of Somatosensory Cortical Processing by Thalamic Posterior Medial Nucleus: A New Role of Thalamus in Cortical Function

PubMed Central

Castejon, Carlos; Barros-Zulaica, Natali; Nuñez, Angel

2016-01-01

Current knowledge of thalamocortical interaction comes mainly from studying lemniscal thalamic systems. Less is known about paralemniscal thalamic nuclei function. In the vibrissae system, the posterior medial nucleus (POm) is the corresponding paralemniscal nucleus. POm neurons project to L1 and L5A of the primary somatosensory cortex (S1) in the rat brain. It is known that L1 modifies sensory-evoked responses through control of intracortical excitability suggesting that L1 exerts an influence on whisker responses. Therefore, thalamocortical pathways targeting L1 could modulate cortical firing. Here, using a combination of electrophysiology and pharmacology in vivo, we have sought to determine how POm influences cortical processing. In our experiments, single unit recordings performed in urethane-anesthetized rats showed that POm imposes precise control on the magnitude and duration of supra- and infragranular barrel cortex whisker responses. Our findings demonstrated that L1 inputs from POm imposed a time and intensity dependent regulation on cortical sensory processing. Moreover, we found that blocking L1 GABAergic inhibition or blocking P/Q-type Ca2+ channels in L1 prevents POm adjustment of whisker responses in the barrel cortex. Additionally, we found that POm was also controlling the sensory processing in S2 and this regulation was modulated by corticofugal activity from L5 in S1. Taken together, our data demonstrate the determinant role exerted by the POm in the adjustment of somatosensory cortical processing and in the regulation of cortical processing between S1 and S2. We propose that this adjustment could be a thalamocortical gain regulation mechanism also present in the processing of information between cortical areas. PMID:26820514

Reduced thalamic N-acetylaspartate in idiopathic normal pressure hydrocephalus: a controlled 1H-magnetic resonance spectroscopy study of frontal deep white matter and the thalamus using absolute quantification.

PubMed

Lundin, F; Tisell, A; Dahlqvist Leinhard, O; Tullberg, M; Wikkelsö, C; Lundberg, P; Leijon, G

2011-07-01

Patients with idiopathic normal pressure hydrocephalus (INPH) frequently have a reduction in cerebral blood flow in the subcortical frontal lobe/basal ganglia/thalamic areas. With magnetic resonance spectroscopy, the metabolism in the brain can be examined. The aim of this study was to investigate if there was a compromised metabolism in the thalamus and in the subcortical frontal areas in INPH patients. This was done by measuring total creatine, myo-inositol, total choline, N-acetylaspartate (NAA), total N-acetylaspartate (tNA), glutamate and lactate levels. A comparison was made with healthy individuals (HI). 16 patients (nine males, seven females, mean age 74 years, range 49-83) diagnosed as INPH and 15 HI (nine males, six females, mean age 74 years, range 62-89) were examined. (1)H magnetic resonance spectroscopy (1.5 T, point-resolved spectroscopy, echo time/relaxation time 30/3000 ms, volume of interest 2.5-3 ml) was performed in frontal deep white matter and in the thalamus. Absolute quantification with internal water as a reference was used. INPH patients had lower NAA (p=0.02) and lower tNA (p=0.05) concentrations in the thalamus compared with HI. NAA and tNA in the frontal deep white matter did not differ between patients and HI. The absolute metabolic concentrations of total creatine, myo-inositol total choline, tNA, lactate and Cr ratios in frontal deep white matter and in the thalamus were similar in INPH patients and HI. Reduced thalamic NAA and tNA in INPH patients suggest a compromised metabolic neuronal function in these regions. Thus, the thalamus might have an important role in the pathogenesis of INPH.

Effect of novel atypical antipsychotic, blonanserin, on extracellular neurotransmitter level in rat prefrontal cortex.

PubMed

Ohoyama, Keiko; Yamamura, Satoshi; Hamaguchi, Tatsuya; Nakagawa, Masanori; Motomura, Eishi; Shiroyama, Takashi; Tanii, Hisashi; Okada, Motohiro

2011-02-25

To clarify the mechanisms of action of blonanserin, an atypical antipsychotic drug, we studied the effects of systemic administration of blonanserin and risperidone on extracellular levels of norepinephrine, dopamine, serotonin, GABA and glutamate in the medial prefrontal cortex using microdialysis, and neuronal firing in the ventral tegmental area, locus coeruleus, dorsal raphe nucleus and mediodorsal thalamic nucleus using radiotelemetry. The binding affinities of blonanserin to D(2) and 5-HT(2A) receptors in the rat brain were confirmed and found to be similar. Blonanserin transiently increased neuronal firing in locus coeruleus and ventral tegmental area but not in dorsal raphe nucleus or mediodorsal thalamic nucleus, whereas risperidone increased the firing in locus coeruleus, ventral tegmental area and dorsal raphe nucleus but not in mediodorsal thalamic nucleus. Blonanserin persistently increased frontal extracellular levels of norepinephrine and dopamine but not serotonin, GABA or glutamate, whereas risperidone persistently increased those of norepinephrine, dopamine and serotonin but not GABA or glutamate. These results suggest a pharmacological correlation between the stimulatory effects of these antipsychotics on frontal monoamine release and neuronal activity in monoaminergic nuclei. Inhibition of the α(2) adrenoceptor increased extracellular monoamine levels and enhanced blonanserin-induced increase in extracellular serotonin level. These results indicated that the combination of antagonism of D(2) and 5-HT(2A) receptors contribute to the rise in extracellular levels of norepinephrine and dopamine, and that α(2) adrenoceptors play important roles in frontal serotonin release. They also suggest that blonanserin-induced activation of monoaminergic transmission could be, at least partially, involved in atypical antipsychotic properties of blonanserin. Copyright © 2010 Elsevier B.V. All rights reserved.

Five-months-postoperative neuropsychological outcome from a pilot prospective randomized clinical trial of thalamic deep brain stimulation for Tourette syndrome.

PubMed

Schoenberg, Mike R; Maddux, Brian N; Riley, David E; Whitney, Christina M; Ogrocki, Paula K; Gould, Deborah; Maciunas, Robert J

2015-02-01

Tourette syndrome (TS) is a neuropsychiatric disorder presenting with motor and/or sonic tics associated with frontostriatal dysfunction. This study provided pilot data of the neuropsychological safety of bilateral thalamic deep brain stimulation (DBS) to treat medication-refractory TS in adults. This study used a repeated-measures design with pretest and 3-month follow-up from start of continuous bilateral DBS. Five male patients underwent DBS surgery for medically refractory TS. Repeated-measures ANOVA was used to evaluate for any change in neuropsychological test scores, employing a false discovery rate. Outcome measures included 14 neuropsychological tests assessing psychomotor speed, attention, memory, language, visuoconstructional, and executive functions, as well as subjective mood ratings of depression and anxiety. Average age was 28.2 years (SD = 7.5) with 12-17 years of education. Participants were disabled by tics, with a tic frequency of 50-80 per minute before surgery. At baseline, subjects' cognitive function was generally average, although mild deficits in sequencing and verbal fluency were present, as were clinically mild obsessive-compulsive symptoms. At 3 months of continuous DBS (5 months after implantation), 3 of 5 participants had clinical reductions in motor and sonic tics. Cognitive scores generally remained stable, but declines of moderate to large effect size (Cohen's d > 0.6) in verbal fluency, visual immediate memory, and reaction time were observed. Fewer symptoms of depression and anxiety, as well as fewer obsessions and compulsions, were reported after 3 months of continuous high-frequency DBS. Bilateral centromedian-parafascicular thalamic DBS for medically refractory TS shows promise for treatment of medically refractory TS without marked neuropsychological morbidity. Symptoms of depression and anxiety improved. © 2014 International Neuromodulation Society.

Postural imbalance and falls in PSP correlate with functional pathology of the thalamus.

PubMed

Zwergal, A; la Fougère, C; Lorenzl, S; Rominger, A; Xiong, G; Deutschenbaur, L; Linn, J; Krafczyk, S; Dieterich, M; Brandt, T; Strupp, M; Bartenstein, P; Jahn, K

2011-07-12

To determine how postural imbalance and falls are related to regional cerebral glucose metabolism (PET) and functional activation of the cerebral postural network (fMRI) in patients with progressive supranuclear palsy (PSP). Sixteen patients with PSP, who had self-monitored their frequency of falls, underwent a standardized clinical assessment, posturographic measurement of balance during modified sensory input, and a resting [¹⁸F]FDG-PET. In addition, patients performed an fMRI paradigm using mental imagery of standing. Results were compared to healthy controls (n = 16). The frequency of falls/month in patients (range 1-40) correlated with total PSP rating score (r = 0.90). Total sway path in PSP significantly correlated with frequency of falls, especially during modulated sensory input (eyes open: r = 0.62, eyes closed: r = 0.67, eyes open/head extended: r = 0.84, eyes open/foam-padded platform: r = 0.87). Higher sway path values and frequency of falls were associated with decreased regional glucose metabolism (rCGM) in the thalamus (sway path: r = -0.80, falls: r = -0.64) and increased rCGM in the precentral gyrus (sway path: r = 0.79, falls: r = 0.64). Mental imagery of standing during fMRI revealed a reduced activation of the mesencephalic brainstem tegmentum and the thalamus in patients with postural imbalance and falls. The new and clinically relevant finding of this study is that imbalance and falls in PSP are closely associated with thalamic dysfunction. Deficits in thalamic postural control get most evident when balance is assessed during modified sensory input. The results are consistent with the hypothesis that reduced thalamic activation via the ascending brainstem projections may cause postural imbalance in PSP.

Moving Forward: Advances in the Treatment of Movement Disorders with Deep Brain Stimulation

PubMed Central

Schiefer, Terry K.; Matsumoto, Joseph Y.; Lee, Kendall H.

2011-01-01

The modern era of stereotactic and functional neurosurgery has ushered in state of the art technologies for the treatment of movement disorders, particularly Parkinson’s disease (PD), tremor, and dystonia. After years of experience with various surgical therapies, the eventual shortcomings of both medical and surgical treatments, and several serendipitous discoveries, deep brain stimulation (DBS) has risen to the forefront as a highly effective, safe, and reversible treatment for these conditions. Idiopathic advanced PD can be treated with thalamic, globus pallidus internus (GPi), or subthalamic nucleus (STN) DBS. Thalamic DBS primarily relieves tremor while GPi and STN DBS alleviate a wide range of Parkinsonian symptoms. Thalamic DBS is also used in the treatment of other types of tremor, particularly essential tremor, with excellent results. Both primary and various types of secondary dystonia can be treated very effectively with GPi DBS. The variety of anatomical targets for these movement disorders is indicative of the network-level dysfunction mediating these movement disturbances. Despite an increasing understanding of the clinical benefits of DBS, little is known about how DBS can create such wide sweeping neuromodulatory effects. The key to improving this therapeutic modality and discovering new ways to treat these and other neurologic conditions lies in better understanding the intricacies of DBS. Here we review the history and pertinent clinical data for DBS treatment of PD, tremor, and dystonia. While multiple regions of the brain have been targeted for DBS in the treatment of these movement disorders, this review article focuses on those that are most commonly used in current clinical practice. Our search criteria for PubMed included combinations of the following terms: DBS, neuromodulation, movement disorders, PD, tremor, dystonia, and history. Dates were not restricted. PMID:22084629

The effect of pharmacological inactivation of the mammillary body and anterior thalamic nuclei on hippocampal theta rhythm in urethane-anesthetized rats.

PubMed

Żakowski, Witold; Zawistowski, Piotr; Braszka, Łukasz; Jurkowlaniec, Edyta

2017-10-24

The mammillary body (MB) and the anterior thalamic nuclei (ATN) are closely related structures, which take part in learning and memory processes. However, the exact role of these structures has remained unclear. In both structures neurons firing according to hippocampal theta rhythm have been found, mainly in the medial mammillary nucleus (MM) and anteroventral thalamic nucleus (AV). These neurons are driven by descending projections from the hippocampal formation and are thought to convey theta rhythm back to the hippocampus (HP). We argue that the MB-ATN axis not only relays theta signal, but may also modulate it. To examine it, we performed a pharmacological inactivation of the MM and AV by local infusion of procaine, and measured changes in theta activity in selected structures of the extended hippocampal system in urethane-anesthetized rats. The inactivation of the MM resulted in decrease in EEG power in the HP and AV, the most evidently in the lower theta frequency bands, i.e. 3-5Hz in the HP (down to 9.2% in 3- to 4-Hz band and 37.6% in 4- to 5-Hz band, in comparison to the power in the control conditions) and 3-4Hz in the AV (down to 24.9%). After the AV inactivation, hippocampal EEG power decreased in theta frequency bands of 3-8Hz (down to 61.6% in 6- to 7-Hz band and 69.4% in 7- to 8-Hz band). Our results suggest that the role of the MB-ATN axis in regulating theta rhythm signaling may be much more important than has been speculated so far. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Directional responding of C57BL/6J mice in the Morris water maze is influenced by visual and vestibular cues and is dependent upon the anterior thalamic nuclei

PubMed Central

Stackman, Robert W.; Lora, Joan C.; Williams, Sidney B.

2012-01-01

Recent findings indicate that rats navigate in spatial tasks such as the Morris water maze (MWM) using a local cue-based reference frame rather than a distal cue-based reference frame. Specifically, rats swim in a particular direction to a location relative to pool-based cues, rather than to an absolute location defined by room-based cues. Neural mechanisms supporting this bias in rodents for relative responding in spatial tasks are not yet understood. Anterior thalamic neurons discharge according to the current directional heading of the animal. The contribution of head direction (HD) cell activity to navigation has been difficult to elucidate. We found that male C57BL/6J mice trained for 4 or 7 days in the MWM exhibited an overwhelming preference for swimming in a direction relative to pool-based cues over absolute responding during a platform-less probe test. Rotation of extra-maze cues caused a corresponding rotation of the direction mice swam during probe test, suggesting that both pool- and room-based reference frames guide platform search. However, disorienting the mice before the probe test disturbed relative responding. Therefore, relative responding is guided by both internal and external cue sources. Selective inactivation of anterior thalamic nuclei (ATN) by microinfusion of muscimol or fluorophore-conjugated muscimol caused a near complete shift in preference from relative to absolute responding. Interestingly, inactivation of the dorsal CA1 region of the hippocampus did not affect relative responding. These data suggest that ATN, and HD cells therein, may guide relative responding in the MWM, a task considered by most to reflect hippocampal processing. PMID:22836256

Different cortical projections from three subdivisions of the rat lateral posterior thalamic nucleus: a single-neuron tracing study with viral vectors.

PubMed

Nakamura, Hisashi; Hioki, Hiroyuki; Furuta, Takahiro; Kaneko, Takeshi

2015-05-01

The lateral posterior thalamic nucleus (LP) is one of the components of the extrageniculate pathway in the rat visual system, and is cytoarchitecturally divided into three subdivisions--lateral (LPl), rostromedial (LPrm), and caudomedial (LPcm) portions. To clarify the differences in the dendritic fields and axonal arborisations among the three subdivisions, we applied a single-neuron labeling technique with viral vectors to LP neurons. The proximal dendrites of LPl neurons were more numerous than those of LPrm and LPcm neurons, and LPrm neurons tended to have wider dendritic fields than LPl neurons. We then analysed the axonal arborisations of LP neurons by reconstructing the axon fibers in the cortex. The LPl, LPrm and LPcm were different from one another in terms of the projection targets--the main target cortical regions of LPl and LPrm neurons were the secondary and primary visual areas, whereas those of LPcm neurons were the postrhinal and temporal association areas. Furthermore, the principal target cortical layers of LPl neurons in the visual areas were middle layers, but that of LPrm neurons was layer 1. This indicates that LPl and LPrm neurons can be categorised into the core and matrix types of thalamic neurons, respectively, in the visual areas. In addition, LPl neurons formed multiple axonal clusters within the visual areas, whereas the fibers of LPrm neurons were widely and diffusely distributed. It is therefore presumed that these two types of neurons play different roles in visual information processing by dual thalamocortical innervation of the visual areas. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Probabilistic vs. deterministic fiber tracking and the influence of different seed regions to delineate cerebellar-thalamic fibers in deep brain stimulation.

PubMed

Schlaier, Juergen R; Beer, Anton L; Faltermeier, Rupert; Fellner, Claudia; Steib, Kathrin; Lange, Max; Greenlee, Mark W; Brawanski, Alexander T; Anthofer, Judith M

2017-06-01

This study compared tractography approaches for identifying cerebellar-thalamic fiber bundles relevant to planning target sites for deep brain stimulation (DBS). In particular, probabilistic and deterministic tracking of the dentate-rubro-thalamic tract (DRTT) and differences between the spatial courses of the DRTT and the cerebello-thalamo-cortical (CTC) tract were compared. Six patients with movement disorders were examined by magnetic resonance imaging (MRI), including two sets of diffusion-weighted images (12 and 64 directions). Probabilistic and deterministic tractography was applied on each diffusion-weighted dataset to delineate the DRTT. Results were compared with regard to their sensitivity in revealing the DRTT and additional fiber tracts and processing time. Two sets of regions-of-interests (ROIs) guided deterministic tractography of the DRTT or the CTC, respectively. Tract distances to an atlas-based reference target were compared. Probabilistic fiber tracking with 64 orientations detected the DRTT in all twelve hemispheres. Deterministic tracking detected the DRTT in nine (12 directions) and in only two (64 directions) hemispheres. Probabilistic tracking was more sensitive in detecting additional fibers (e.g. ansa lenticularis and medial forebrain bundle) than deterministic tracking. Probabilistic tracking lasted substantially longer than deterministic. Deterministic tracking was more sensitive in detecting the CTC than the DRTT. CTC tracts were located adjacent but consistently more posterior to DRTT tracts. These results suggest that probabilistic tracking is more sensitive and robust in detecting the DRTT but harder to implement than deterministic approaches. Although sensitivity of deterministic tracking is higher for the CTC than the DRTT, targets for DBS based on these tracts likely differ. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Robust modulation of arousal regulation, performance, and frontostriatal activity through central thalamic deep brain stimulation in healthy nonhuman primates

PubMed Central

Ryou, Jae-Wook; Wei, Xuefeng F.; Butson, Christopher R.; Schiff, Nicholas D.; Purpura, Keith P.

2016-01-01

The central thalamus (CT) is a key component of the brain-wide network underlying arousal regulation and sensory-motor integration during wakefulness in the mammalian brain. Dysfunction of the CT, typically a result of severe brain injury (SBI), leads to long-lasting impairments in arousal regulation and subsequent deficits in cognition. Central thalamic deep brain stimulation (CT-DBS) is proposed as a therapy to reestablish and maintain arousal regulation to improve cognition in select SBI patients. However, a mechanistic understanding of CT-DBS and an optimal method of implementing this promising therapy are unknown. Here we demonstrate in two healthy nonhuman primates (NHPs), Macaca mulatta, that location-specific CT-DBS improves performance in visuomotor tasks and is associated with physiological effects consistent with enhancement of endogenous arousal. Specifically, CT-DBS within the lateral wing of the central lateral nucleus and the surrounding medial dorsal thalamic tegmental tract (DTTm) produces a rapid and robust modulation of performance and arousal, as measured by neuronal activity in the frontal cortex and striatum. Notably, the most robust and reliable behavioral and physiological responses resulted when we implemented a novel method of CT-DBS that orients and shapes the electric field within the DTTm using spatially separated DBS leads. Collectively, our results demonstrate that selective activation within the DTTm of the CT robustly regulates endogenous arousal and enhances cognitive performance in the intact NHP; these findings provide insights into the mechanism of CT-DBS and further support the development of CT-DBS as a therapy for reestablishing arousal regulation to support cognition in SBI patients. PMID:27582298

Phencyclidine inhibits the activity of thalamic reticular gamma-aminobutyric acidergic neurons in rat brain.

PubMed

Troyano-Rodriguez, Eva; Lladó-Pelfort, Laia; Santana, Noemi; Teruel-Martí, Vicent; Celada, Pau; Artigas, Francesc

2014-12-15

The neurobiological basis of action of noncompetitive N-methyl-D-aspartate acid receptor (NMDA-R) antagonists is poorly understood. Electrophysiological studies indicate that phencyclidine (PCP) markedly disrupts neuronal activity with an overall excitatory effect and reduces the power of low-frequency oscillations (LFO; <4 Hz) in thalamocortical networks. Because the reticular nucleus of the thalamus (RtN) provides tonic feed-forward inhibition to the rest of the thalamic nuclei, we examined the effect of PCP on RtN activity, under the working hypothesis that NMDA-R blockade in RtN would disinhibit thalamocortical networks. Drug effects (PCP followed by clozapine) on the activity of RtN (single unit and local field potential recordings) and prefrontal cortex (PFC; electrocorticogram) in anesthetized rats were assessed. PCP (.25-.5 mg/kg, intravenous) reduced the discharge rate of 19 of 21 RtN neurons to 37% of baseline (p < .000001) and the power of LFO in RtN and PFC to ~20% of baseline (p < .001). PCP also reduced the coherence between PFC and RtN in the LFO range. A low clozapine dose (1 mg/kg intravenous) significantly countered the effect of PCP on LFO in PFC but not in RtN and further reduced the discharge rate of RtN neurons. However, clozapine administration partly antagonized the fall in coherence and phase-locking values produced by PCP. PCP activates thalamocortical circuits in a bottom-up manner by reducing the activity of RtN neurons, which tonically inhibit thalamic relay neurons. However, clozapine reversal of PCP effects is not driven by restoring RtN activity and may involve a cortical action. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Functional integration changes in regional brain glucose metabolism from childhood to adulthood.

PubMed

Trotta, Nicola; Archambaud, Frédérique; Goldman, Serge; Baete, Kristof; Van Laere, Koen; Wens, Vincent; Van Bogaert, Patrick; Chiron, Catherine; De Tiège, Xavier

2016-08-01

The aim of this study was to investigate the age-related changes in resting-state neurometabolic connectivity from childhood to adulthood (6-50 years old). Fifty-four healthy adult subjects and twenty-three pseudo-healthy children underwent [(18) F]-fluorodeoxyglucose positron emission tomography at rest. Using statistical parametric mapping (SPM8), age and age squared were first used as covariate of interest to identify linear and non-linear age effects on the regional distribution of glucose metabolism throughout the brain. Then, by selecting voxels of interest (VOI) within the regions showing significant age-related metabolic changes, a psychophysiological interaction (PPI) analysis was used to search for age-induced changes in the contribution of VOIs to the metabolic activity in other brain areas. Significant linear or non-linear age-related changes in regional glucose metabolism were found in prefrontal cortices (DMPFC/ACC), cerebellar lobules, and thalamo-hippocampal areas bilaterally. Decreases were found in the contribution of thalamic, hippocampal, and cerebellar regions to DMPFC/ACC metabolic activity as well as in the contribution of hippocampi to preSMA and right IFG metabolic activities. Increases were found in the contribution of the right hippocampus to insular cortex and of the cerebellar lobule IX to superior parietal cortex metabolic activities. This study evidences significant linear or non-linear age-related changes in regional glucose metabolism of mesial prefrontal, thalamic, mesiotemporal, and cerebellar areas, associated with significant modifications in neurometabolic connectivity involving fronto-thalamic, fronto-hippocampal, and fronto-cerebellar networks. These changes in functional brain integration likely represent a metabolic correlate of age-dependent effects on sensory, motor, and high-level cognitive functional networks. Hum Brain Mapp 37:3017-3030, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Crossed Cerebellar Tracer Uptake on Acute-Stage 123I-Iomazenil SPECT Imaging Predicts 3-Month Functional Outcome in Patients With Nonfatal Hypertensive Putaminal or Thalamic Hemorrhage.

PubMed

Kojima, Daigo; Komoribayashi, Nobukazu; Omama, Shinichi; Oikawa, Kohki; Fujiwara, Shunrou; Kobayashi, Masakazu; Kubo, Yoshitaka; Terasaki, Kazunori; Ogasawara, Kuniaki

2018-06-01

Whereas SPECT images obtained 180 minutes after administration of I-iomazenil (IMZ) (late images) are proportional to the distribution of central benzodiazepine receptor-binding potential, SPECT images obtained within 30 minutes after I-IMZ administration (early images) correlate with regional brain perfusion. The aim of the present study was to determine whether crossed cerebellar tracer uptake on acute-stage I-IMZ SPECT imaging predicts 3-month functional outcome in patients with nonfatal hypertensive putaminal or thalamic hemorrhage. Forty-six patients underwent early and late SPECT imaging with I-IMZ within 7 days after the onset of hemorrhage. A region of interest was automatically placed in the bilateral cerebellar hemispheres using a 3-dimensional stereotaxic region-of-interest template, and the ratio of the value in the cerebellar hemisphere contralateral to the affected side to that in the ipsilateral cerebellar hemisphere (ARcbl) was calculated in each patient. Each patient's physical function was measured using the modified Rankin scale (mRS) score 3 months after onset. The ARcbl on early (ρ = -0.511, P = 0.0003) and late (ρ = -0.714, P < 0.0001) images correlated with the mRS 3 months after the onset of hemorrhage. Multivariate analysis showed that only a low ARcbl in late images was significantly associated with a poor functional outcome (mRS score ≥3 at 3 months after onset) (95% confidence interval, 0.001-0.003; P = 0.0212). Crossed cerebellar tracer uptake on acute-stage I-IMZ SPECT imaging predicts 3-month functional outcome in patients with nonfatal hypertensive putaminal or thalamic hemorrhage.

Regional gray matter atrophy in relapsing remitting multiple sclerosis: baseline analysis of multi-center data.

PubMed

Datta, Sushmita; Staewen, Terrell D; Cofield, Stacy S; Cutter, Gary R; Lublin, Fred D; Wolinsky, Jerry S; Narayana, Ponnada A

2015-03-01

Regional gray matter (GM) atrophy in multiple sclerosis (MS) at disease onset and its temporal variation can provide objective information regarding disease evolution. An automated pipeline for estimating atrophy of various GM structures was developed using tensor based morphometry (TBM) and implemented on a multi-center sub-cohort of 1008 relapsing remitting MS (RRMS) patients enrolled in a Phase 3 clinical trial. Four hundred age and gender matched healthy controls were used for comparison. Using the analysis of covariance, atrophy differences between MS patients and healthy controls were assessed on a voxel-by-voxel analysis. Regional GM atrophy was observed in a number of deep GM structures that included thalamus, caudate nucleus, putamen, and cortical GM regions. General linear regression analysis was performed to analyze the effects of age, gender, and scanner field strength, and imaging sequence on the regional atrophy. Correlations between regional GM volumes and expanded disability status scale (EDSS) scores, disease duration (DD), T2 lesion load (T2 LL), T1 lesion load (T1 LL), and normalized cerebrospinal fluid (nCSF) were analyzed using Pearson׳s correlation coefficient. Thalamic atrophy observed in MS patients compared to healthy controls remained consistent within subgroups based on gender and scanner field strength. Weak correlations between thalamic volume and EDSS (r=-0.133; p<0.001) and DD (r=-0.098; p=0.003) were observed. Of all the structures, thalamic volume moderately correlated with T2 LL (r=-0.492; P-value<0.001), T1 LL (r=-0.473; P-value<0.001) and nCSF (r=-0.367; P-value<0.001). Copyright © 2015 Elsevier B.V. All rights reserved.

Acute bithalamic infarct manifesting as sleep-like coma: A diagnostic challenge.

PubMed

Honig, Asaf; Eliahou, Ruth; Eichel, Roni; Shemesh, Ari Aharon; Ben-Hur, Tamir; Auriel, Eitan

2016-12-01

Bilateral thalamic infarction (BTI) typically presents as a sleep-like coma (SLC) without localizing signs, posing a diagnostic challenge that may lead the treating physician to search for toxic or metabolic causes and delay treatment. We review our experience with BTI of different etiologies, and emphasize the critical role of timely imaging, diagnosis, and management in a series of 12 patients with a presentation of SLC and acute BTI who were managed in our Medical Centers from 2006-2015. In 11/12, urgent head CT scans showed normal brain tissue, while diffusion-weighted (DWI) MRI revealed symmetric bilateral thalamic hyperintense lesions with variable degrees of brainstem involvement. In 1/12, CT scans revealed a contralateral subacute stroke from a thalamic infarct 1month earlier with a unilateral hyperintense lesion on DWI-MRI. From clinical and imaging findings (DWI-MRI, CT angiography and venography), etiology was attributed to embolic causes (cardio-embolism, artery-to-artery mechanism), small vessel disease, or deep sinus vein thrombosis secondary to dural arteriovenous (AV) fistula. Three patients had good outcomes after prompt diagnosis and optimal treatment in <3hours (intravenous tissue plasminogen activator in two patients cardio-embolic etiology and neuro-endovascular repair in one patient with venous infarction due to a dural AV fistula). The diagnosis was made beyond the therapeutic window in seven patients, who were left with significant neurological sequelae. Higher awareness of BTI presenting as SLC is warranted. Optimal patient management includes urgent DWI-MRI. In cases of BTI, further imaging workup is indicated to provide a comprehensive assessment for etiology. Early diagnosis and prompt, targeted intervention are crucial. Copyright © 2016 Elsevier Ltd. All rights reserved.

Different mechanisms of secondary neuronal damage in thalamic nuclei after focal cerebral ischemia in rats.

PubMed

Dihné, Marcel; Grommes, Christian; Lutzenburg, Michael; Witte, Otto W; Block, Frank

2002-12-01

After focal cerebral ischemia, depending on its localization and extent, secondary neuronal damage may occur that is remote from the initial lesion. In this study differences in secondary damage of the ventroposterior thalamic nucleus (VPN) and the reticular thalamic nucleus (RTN) were investigated with the use of different ischemia models. Transient middle cerebral artery occlusion (MCAO) leads to cortical infarction, including parts of the basal ganglia such as the globus pallidus, and to widespread edema. Photothrombotic ischemia generates pure cortical infarcts sparing the basal ganglia and with only minor edema. Neuronal degeneration was quantified within the ipsilateral RTN and VPN 14 days after ischemia. Glial reactions were studied with the use of immunohistochemistry. MCAO resulted in delayed neuronal cell loss of the ipsilateral VPN and RTN. Glial activation occurred in both nuclei beginning after 24 hours. Photothrombotic ischemia resulted in delayed neuronal cell loss only within the VPN. Even 2 weeks after photothrombotic ischemia, glial activation could only be seen within the VPN. Pure cortical infarcts after photothrombotic ischemia, without major edema and without effects on the globus pallidus of the basal ganglia, only lead to secondary VPN damage that is possibly due to retrograde degeneration. MCAO, which results in infarction of cortex and globus pallidus and which causes widespread edema, leads to secondary damage in the VPN and RTN. Thus, additional RTN damage may be due to loss of protective GABAergic input from the globus pallidus to the RTN or due to the extensive edema. Retrograde degeneration is not possible because the RTN, in contrast to the VPN, has no efferents to the cortex.

The thalamus in drug addiction: from rodents to humans.

PubMed

Huang, Anna S; Mitchell, Jameson A; Haber, Suzanne N; Alia-Klein, Nelly; Goldstein, Rita Z

2018-03-19

Impairments in response inhibition and salience attribution (iRISA) have been proposed to underlie the clinical symptoms of drug addiction as mediated by cortico-striatal-thalamo-cortical networks. The bulk of evidence supporting the iRISA model comes from neuroimaging research that has focused on cortical and striatal influences with less emphasis on the role of the thalamus. Here, we highlight the importance of the thalamus in drug addiction, focusing on animal literature findings on thalamic nuclei in the context of drug-seeking, structural and functional changes of the thalamus as measured by imaging studies in human drug addiction, particularly during drug cue and non-drug reward processing, and response inhibition tasks. Findings from the animal literature suggest that the paraventricular nucleus of the thalamus, the lateral habenula and the mediodorsal nucleus may be involved in the reinstatement, extinction and expression of drug-seeking behaviours. In support of the iRISA model, the human addiction imaging literature demonstrates enhanced thalamus activation when reacting to drug cues and reduced thalamus activation during response inhibition. This pattern of response was further associated with the severity of, and relapse in, drug addiction. Future animal studies could widen their field of focus by investigating the specific role(s) of different thalamic nuclei in different phases of the addiction cycle. Similarly, future human imaging studies should aim to specifically delineate the structure and function of different thalamic nuclei, for example, through the application of advanced imaging protocols at higher magnetic fields (7 Tesla).This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'. © 2018 The Author(s).

Fear conditioning leads to alteration in specific genes expression in cortical and thalamic neurons that project to the lateral amygdala.

PubMed

Katz, Ira K; Lamprecht, Raphael

2015-02-01

RNA transcription is needed for memory formation. However, the ability to identify genes whose expression is altered by learning is greatly impaired because of methodological difficulties in profiling gene expression in specific neurons involved in memory formation. Here, we report a novel approach to monitor the expression of genes after learning in neurons in specific brain pathways needed for memory formation. In this study, we aimed to monitor gene expression after fear learning. We retrogradely labeled discrete thalamic neurons that project to the lateral amygdala (LA) of rats. The labeled neurons were dissected, using laser microdissection microscopy, after fear conditioning learning or unpaired training. The RNAs from the dissected neurons were subjected to microarray analysis. The levels of selected RNAs detected by the microarray analysis to be altered by fear conditioning were also assessed by nanostring analysis. We observed that the expression of genes involved in the regulation of translation, maturation and degradation of proteins was increased 6 h after fear conditioning compared to unpaired or naïve trained rats. These genes were not expressed 24 h after training or in cortical neurons that project to the LA. The expression of genes involved in transcription regulation and neuronal development was altered after fear conditioning learning in the cortical-LA pathway. The present study provides key information on the identity of genes expressed in discrete thalamic and cortical neurons that project to the LA after fear conditioning. Such an approach could also serve to identify gene products as targets for the development of a new generation of therapeutic agents that could be aimed to functionally identified brain circuits to treat memory-related disorders. © 2014 International Society for Neurochemistry.

Looking for a precursor of spontaneous Sleep Slow Oscillations in human sleep: The role of the sigma activity

PubMed Central

Allegrini, Paolo; Bedini, Remo; Bergamasco, Massimo; Laurino, Marco; Sebastiani, Laura; Gemignani, Angelo

2016-01-01

Sleep Slow Oscillations (SSOs), paradigmatic EEG markers of cortical bistability (alternation between cellular downstates and upstates), and sleep spindles, paradigmatic EEG markers of thalamic rhythm, are two hallmarks of sleeping brain. Selective thalamic lesions are reportedly associated to reductions of spindle activity and its spectrum ~14 Hz (sigma), and to alterations of SSO features. This apparent, parallel behavior suggests that thalamo-cortical entrainment favors cortical bistability. Here we investigate temporally-causal associations between thalamic sigma activity and shape, topology, and dynamics of SSOs. We recorded sleep EEG and studied whether spatio-temporal variability of SSO amplitude, negative slope (synchronization in downstate falling) and detection rate are driven by cortical-sigma-activity expression (12–18 Hz), in 3 consecutive 1 s-EEG-epochs preceding each SSO event (Baselines). We analyzed: (i) spatial variability, comparing maps of baseline sigma power and of SSO features, averaged over the first sleep cycle; (ii) event-by-event shape variability, computing for each electrode correlations between baseline sigma power and amplitude/slope of related SSOs; (iii) event-by-event spreading variability, comparing baseline sigma power in electrodes showing an SSO event with the homologous ones, spared by the event. The scalp distribution of baseline sigma power mirrored those of SSO amplitude and slope; event-by-event variability in baseline sigma power was associated with that in SSO amplitude in fronto-central areas; within each SSO event, electrodes involved in cortical bistability presented higher baseline sigma activity than those free of SSO. In conclusion, spatio-temporal variability of thalamocortical entrainment, measured by background sigma activity, is a reliable estimate of the cortical proneness to bistability. PMID:26003553

Prenatal enrichment and recovery from perinatal cortical damage: effects of maternal complex housing

PubMed Central

Gibb, Robbin L.; Gonzalez, Claudia L. R.; Kolb, Bryan

2014-01-01

Birth is a particularly vulnerable time for acquiring brain injury. Unfortunately, very few treatments are available for those affected. Here we explore the effectiveness of prenatal intervention in an animal model of early brain damage. We used a complex housing paradigm as a form of prenatal enrichment. Six nulliparous dams and one male rat were placed in complex housing (condomom group) for 12 h per day until the dams' delivered their pups. At parturition the dams were left in their home (standard) cages with their pups. Four dams were housed in standard cages (cagemom group) throughout pregnancy and with their pups until weaning. At postnatal day 3 (P3) infants of both groups received frontal cortex removals or sham surgery. Behavioral testing began on P60 and included the Morris water task and a skilled reaching task. Brains were processed for Golgi analyses. Complex housing of the mother had a significant effect on the behavior of their pups. Control animals from the condomom group outperformed those of the cagemom group in the water task. Condomom animals with lesions performed better than their cagemom cohorts in both the water task and in skilled reaching. Condomom animals showed an increase in cortical thickness at anterior planes and thalamic area at both anterior and posterior regions. Golgi analyses revealed an increase in spine density. These results suggest that prenatal enrichment alters brain organization in manner that is prophylactic for perinatal brain injury. This result could have significant implications for the prenatal management of infants expected to be at risk for difficult birth. PMID:25009478

An Atypical Presentation of Subacute Encephalopathy with Seizures in Chronic Alcoholism Syndrome.

PubMed

Kim, Tae-Kyoung; Jung, Eui Sung; Park, Jong-Moo; Kang, Kyusik; Lee, Woong-Woo; Lee, Jung-Ju

2016-06-01

Subacute encephalopathy with seizures in chronic alcoholism syndrome is a rare clinical manifestation in patients with chronic alcohol abuse. We report the case of a patient with chronic alcoholism who presented with partial nonconvulsive status epilepticus associated with a thalamic lesion.

Hippocampal and diencephalic pathology in developmental amnesia.

PubMed

Dzieciol, Anna M; Bachevalier, Jocelyne; Saleem, Kadharbatcha S; Gadian, David G; Saunders, Richard; Chong, W K Kling; Banks, Tina; Mishkin, Mortimer; Vargha-Khadem, Faraneh

2017-01-01

Developmental amnesia (DA) is a selective episodic memory disorder associated with hypoxia-induced bilateral hippocampal atrophy of early onset. Despite the systemic impact of hypoxia-ischaemia, the resulting brain damage was previously reported to be largely limited to the hippocampus. However, the thalamus and the mammillary bodies are parts of the hippocampal-diencephalic network and are therefore also at risk of injury following hypoxic-ischaemic events. Here, we report a neuroimaging investigation of diencephalic damage in a group of 18 patients with DA (age range 11-35 years), and an equal number of controls. Importantly, we uncovered a marked degree of atrophy in the mammillary bodies in two thirds of our patients. In addition, as a group, patients had mildly reduced thalamic volumes. The size of the anterior-mid thalamic (AMT) segment was correlated with patients' visual memory performance. Thus, in addition to the hippocampus, the diencephalic structures also appear to play a role in the patients' memory deficit. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Selectively driving cholinergic fibers optically in the thalamic reticular nucleus promotes sleep

PubMed Central

Ni, Kun-Ming; Hou, Xiao-Jun; Yang, Ci-Hang; Dong, Ping; Li, Yue; Zhang, Ying; Jiang, Ping; Berg, Darwin K; Duan, Shumin; Li, Xiao-Ming

2016-01-01

Cholinergic projections from the basal forebrain and brainstem are thought to play important roles in rapid eye movement (REM) sleep and arousal. Using transgenic mice in which channelrhdopsin-2 is selectively expressed in cholinergic neurons, we show that optical stimulation of cholinergic inputs to the thalamic reticular nucleus (TRN) activates local GABAergic neurons to promote sleep and protect non-rapid eye movement (NREM) sleep. It does not affect REM sleep. Instead, direct activation of cholinergic input to the TRN shortens the time to sleep onset and generates spindle oscillations that correlate with NREM sleep. It does so by evoking excitatory postsynaptic currents via α7-containing nicotinic acetylcholine receptors and inducing bursts of action potentials in local GABAergic neurons. These findings stand in sharp contrast to previous reports of cholinergic activity driving arousal. Our results provide new insight into the mechanisms controlling sleep. DOI: http://dx.doi.org/10.7554/eLife.10382.001 PMID:26880556

[Deficit of verbal recall caused by left dorso-lateral thalamic infarction].

PubMed

Rousseaux, M; Cabaret, M; Benaim, C; Steinling, M

1995-01-01

A case of amnesia with preferential disorder of verbal recall, associated to a limited infarct of the left superior, external and anterior thalamus, is reported. This lesion involved the anterior and middle dorso-lateral nuclei and the centrolateral nucleus, sparing most of the structures classically incriminated in diencephalic amnesia. At the initial stage, the patient presented discrete language impairment and severe deficit of semantic processing, which later recovered. At the late stage, the anterograde and retrograde amnesia principally concerned the recall of verbal information used in daily life, verbal learning using short-term and long-term recall, questionnaires evaluating retrograde memory and requiring the evocation of proper names. Verbal priming was also affected. Verbal recognition was preserved. Evocation of the most recent events of the personal life was also impaired. Confrontation of this case with others previously reported suggests that various thalamic amnesias may be described, associated to different cognitive deficits, in relation with the preferential situation of lesions.

Thalamic reticular nucleus induces fast and local modulation of arousal state

PubMed Central

Lewis, Laura D; Voigts, Jakob; Flores, Francisco J; Schmitt, L Ian; Wilson, Matthew A

2015-01-01

During low arousal states such as drowsiness and sleep, cortical neurons exhibit rhythmic slow wave activity associated with periods of neuronal silence. Slow waves are locally regulated, and local slow wave dynamics are important for memory, cognition, and behaviour. While several brainstem structures for controlling global sleep states have now been well characterized, a mechanism underlying fast and local modulation of cortical slow waves has not been identified. Here, using optogenetics and whole cortex electrophysiology, we show that local tonic activation of thalamic reticular nucleus (TRN) rapidly induces slow wave activity in a spatially restricted region of cortex. These slow waves resemble those seen in sleep, as cortical units undergo periods of silence phase-locked to the slow wave. Furthermore, animals exhibit behavioural changes consistent with a decrease in arousal state during TRN stimulation. We conclude that TRN can induce rapid modulation of local cortical state. DOI: http://dx.doi.org/10.7554/eLife.08760.001 PMID:26460547

Tangential migration of corridor guidepost neurons contributes to anxiety circuits.

PubMed

Tinterri, Andrea; Deck, Marie; Keita, Maryama; Mailhes, Caroline; Rubin, Anna Noren; Kessaris, Nicoletta; Lokmane, Ludmilla; Bielle, Franck; Garel, Sonia

2018-02-15

In mammals, thalamic axons are guided internally toward their neocortical target by corridor (Co) neurons that act as axonal guideposts. The existence of Co-like neurons in non-mammalian species, in which thalamic axons do not grow internally, raised the possibility that Co cells might have an ancestral role. Here, we investigated the contribution of corridor (Co) cells to mature brain circuits using a combination of genetic fate-mapping and assays in mice. We unexpectedly found that Co neurons contribute to striatal-like projection neurons in the central extended amygdala. In particular, Co-like neurons participate in specific nuclei of the bed nucleus of the stria terminalis, which plays essential roles in anxiety circuits. Our study shows that Co neurons possess an evolutionary conserved role in anxiety circuits independently from an acquired guidepost function. It furthermore highlights that neurons can have multiple sequential functions during brain wiring and supports a general role of tangential migration in the building of subpallial circuits. © 2017 Wiley Periodicals, Inc.

Getting signals into the brain: visual prosthetics through thalamic microstimulation.

PubMed

Pezaris, John S; Eskandar, Emad N

2009-07-01

Common causes of blindness are diseases that affect the ocular structures, such as glaucoma, retinitis pigmentosa, and macular degeneration, rendering the eyes no longer sensitive to light. The visual pathway, however, as a predominantly central structure, is largely spared in these cases. It is thus widely thought that a device-based prosthetic approach to restoration of visual function will be effective and will enjoy similar success as cochlear implants have for restoration of auditory function. In this article the authors review the potential locations for stimulation electrode placement for visual prostheses, assessing the anatomical and functional advantages and disadvantages of each. Of particular interest to the neurosurgical community is placement of deep brain stimulating electrodes in thalamic structures that has shown substantial promise in an animal model. The theory of operation of visual prostheses is discussed, along with a review of the current state of knowledge. Finally, the visual prosthesis is proposed as a model for a general high-fidelity machine-brain interface.

Comparative study on the electrophysiological responses at thalamic level to different analgesic peptides.

PubMed

Braga, P C; Biella, G; Tiengo, M; Guidobono, F; Pecile, A; Fraschini, F

1985-01-01

Using electrophysiological methods to detect the extracellular activity of single neurons in the thalamus of anaesthetized rats, their response to mechanical and thermal noxious stimuli were assessed before and after administration of 4 analgesic peptides of various types. Dermophin, a peptide extracted from frog's skin, was found to have an opioid-like antinociceptive activity antagonized by naloxone. Caerulein, which has a similar origin, failed to suppress the nociceptive responses of thalamic neurons evoked by peripheral stimuli. Calcitonin, a peptide found at brain level, induced an alteration of the increased firing characteristic of noxious stimuli, and its action was not reversed by naloxone. FK 33-824, a synthetic peptide, induced a morphine-like action when injected i.c.v. at a dosage 1000 times lower than that of morphine on a molar basis. It is concluded that electrophysiological investigations on peptides endowed with analgesic activity contribute greatly to a more precise profile of the peptides as candidate drugs in pain control.

Generation and characterization of Lhx9 – GFPCreERT2 knock-in mouse line

PubMed Central

Xie, Xiaoling; Deng, Min; Gan, Lin

2014-01-01

Summary LHX9 is a LIM-homeodomain transcription factor essential for the development of gonads, spinal cord interneurons, and thalamic neurons to name a few. We recently reported the expression of LHX9 in retinal amacrine cells during development. In this study, we generated an Lhx9 - GFPCreERT2 (GCE) knock-in mouse line by knocking-in a GCE cassette at the Lhx9 locus, thus inactivating endogenous Lhx9. Lhx9GCE/+ mice were viable, fertile, and displayed no overt phenotypical characteristics. Lhx9GCE/GCE mice were all phenotypically female, smaller in size, viable, but infertile. The specificity and efficacy of the Lhx9-GCE mouse line was verified by crossing it to a Rosa26 - tdTomato reporter mouse line, which reveals the Cre recombinase activities in retinal amacrine cells, developing limbs, testis, hippocampal neurons, thalamic neurons, and cerebellar neurons. Taken together, the Lhx9-GCE mouse line could serve as a beneficial tool for lineage tracing and gene manipulation experiments. PMID:25112520

Site-specific effects of the nonsteroidal anti-inflammatory drug lysine clonixinate on rat brain opioid receptors.

PubMed

Ortí, E; Coirini, H; Pico, J C

1999-04-01

In addition to effects in the periphery through inhibition of prostaglandin synthesis, several lines of evidence suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) act in the central nervous system. The possibility that the central action of NSAIDs involves regulation of opioid receptors was investigated by quantitative autoradiography of mu, delta, and kappa sites in rat brain slices. Increased (p < 0.05) labeling of mu receptors was observed in thalamic nuclei, gyrus dentate, and layers of the parietal cortex of rats treated for 10 days with lysine clonixinate. Labeling of delta receptors was lower in the lateral septum, and kappa sites decreased in thalamic nuclei. These effects were not mediated through direct interaction with opioid-binding sites, since receptor-binding assays using rat brain membranes confirmed that clonixinate up to 1 x 10(-4) mol/l does not inhibit mu, delta, and kappa receptor specific binding. Central effects of NSAIDs might, therefore, involve interaction with the opioid receptor system through indirect mechanisms.

Distinct Thalamic Reticular Cell Types Differentially Modulate Normal and Pathological Cortical Rhythms.

PubMed

Clemente-Perez, Alexandra; Makinson, Stefanie Ritter; Higashikubo, Bryan; Brovarney, Scott; Cho, Frances S; Urry, Alexander; Holden, Stephanie S; Wimer, Matthew; Dávid, Csaba; Fenno, Lief E; Acsády, László; Deisseroth, Karl; Paz, Jeanne T

2017-06-06

Integrative brain functions depend on widely distributed, rhythmically coordinated computations. Through its long-ranging connections with cortex and most senses, the thalamus orchestrates the flow of cognitive and sensory information. Essential in this process, the nucleus reticularis thalami (nRT) gates different information streams through its extensive inhibition onto other thalamic nuclei, however, we lack an understanding of how different inhibitory neuron subpopulations in nRT function as gatekeepers. We dissociated the connectivity, physiology, and circuit functions of neurons within rodent nRT, based on parvalbumin (PV) and somatostatin (SOM) expression, and validated the existence of such populations in human nRT. We found that PV, but not SOM, cells are rhythmogenic, and that PV and SOM neurons are connected to and modulate distinct thalamocortical circuits. Notably, PV, but not SOM, neurons modulate somatosensory behavior and disrupt seizures. These results provide a conceptual framework for how nRT may gate incoming information to modulate brain-wide rhythms. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Differences in cortical vs. subcortical GABAergic signaling: a candidate mechanism of electroclinical dissociation of neonatal seizures

PubMed Central

Glykys, J.; Dzhala, V.I.; Kuchibhotla, K.V.; Feng, G.; Kuner, T.; Augustine, G.; Bacskai, BJ.; Staley, KJ.

2010-01-01

Electroclinical dissociation of neonatal seizures refers to electrographic seizure activity that is not clinically manifest. Dissociation increases after treatment with Phenobarbital, which increases the GABAA receptor (GABAAR) conductance. The effects of GABAAR activation depend on the intracellular Cl− concentration ([Cl−]i) that is determined by the inward Cl− transporter NKCC1 and the outward Cl− transporter KCC2. Differential maturation of Cl− transport observed in cortical vs. subcortical regions should alter the efficacy of GABA-mediated inhibition. In perinatal rat pups, most thalamic neurons maintained low [Cl−]i, and were inhibited by GABA. Phenobarbital suppressed thalamic seizure activity. Most neocortical neurons maintained higher [Cl−]i, and were excited by GABAAR activation. Phenobarbital had insignificant anticonvulsant responses in the neocortex until NKCC1 was blocked. Regional differences in the ontogeny of Cl− transport may thus explain why seizure activity in the cortex is not suppressed by anticonvulsants that block the transmission of seizure activity through subcortical networks. PMID:19755108

The effect of different anesthetics on neurovascular coupling

PubMed Central

Franceschini, Maria Angela; Radhakrishnan, Harsha; Thakur, Kiran; Wu, Weicheng; Ruvinskaya, Svetlana; Carp, Stefan; Boas, David A.

2010-01-01

To date, the majority of neurovascular coupling studies focused on the thalamic afferents' activity in layer IV and the corresponding large spiking activity as responsible for functional hyperemia. This paper highlights the role of the secondary and late cortico-cortical transmission in neurovascular coupling. Simultaneous scalp electroencephalography (EEG) and diffuse optical imaging (DOI) measurements were obtained during multiple conditions of event-related electrical forepaw stimulation in 33 male Sprague-Dawley rats divided into 6 groups depending on the maintaining anesthetic - alpha-chloralose, pentobarbital, ketamine-xylazine, fentanyl-droperidol, isoflurane, or propofol. The somatosensory evoked potentials (SEP) were decomposed into four components and the question of which best predicts the hemodynamic responses was investigated. Results of the linear regression analysis show that the hemodynamic response is best correlated with the secondary and late cortico-cortical transmissions and not with the initial thalamic input activity in layer IV. Baseline cerebral blood flow (CBF) interacts with neural activity and influences the evoked hemodynamic responses. Finally, neurovascular coupling appears to be the same across all anesthetics used. PMID:20350606

Expression of the Diabetes-Associated Gene TCF7L2 in Adult Mouse Brain

PubMed Central

LEE, SYANN; LEE, CHARLOTTE E.; ELIAS, CAROL F.; ELMQUIST, JOEL K.

2014-01-01

Polymorphisms of the gene TCF7L2 (transcription factor 7-like 2) are strongly associated with the development and progression of type 2 diabetes. TCF7L2 is important in the development of peripheral organs such as adipocytes, pancreas, and the intestine. However, very little is known about its expression elsewhere. In this study we used in situ hybridization histochemistry to show that TCF7L2 has a unique expression pattern in the mouse brain. TCF7L2 is expressed in two distinct populations. First, it is highly ex pressed in thalamic and tectal structures. Additionally, TCF7L2 mRNA is expressed at moderate to low levels in specific cells of the hypothalamus, preoptic nucleus, and circumventricular organs. Collectively, these patterns of expression suggest that TCF7L2 has distinct functions within the brain, with a general role in the development and maintenance of thalamic and midbrain neurons, and then a distinct role in autonomic homeostasis. PMID:19845015

Brain mechanisms of hallucinogens and entactogens

PubMed Central

Vollenweider, Franz X.

2001-01-01

This review focuses on recent brain imaging and behavioral studies of sensory gating functions, which assess similarities between the effects of classic hallucinogens (eg, psilocybin), dissociative anesthetics (eg, ketamine), and entactogens (eg, 3,4-methylenedioxymethamphetamine [MDMA]) in humans. Serotonergic hallucinogens and psychotomimetic anesthetics produce overlapping psychotic syndromes associated with a marked activation of the prefrontal cortex (hyperfrontality) and other overlapping changes in temporoparietal, striatal, and thalamic regions, suggesting that both classes of drugs act upon a common final pathway. Together with the observation that both hallucinogens and N-methyl-oaspartate (NMDA) antagonists disrupt sensory gating in rats by acting on 5-hydroxytryptamine (serotonin) 5-HT2 receptors located in cortico-striato-thalamic circuitry these findings suggest that disruption of cortico-subcortical processing leading to sensory overload of the cortex is a communality of these psychoses. In contrast to hallucinogens, the entactogen MDMA produces an emotional state of positive mood, concomitant with an activation of prefrontolimbiclparalimbic structures and a deactivation of amygdala and thalamus. PMID:22033605

Astrocytes refine cortical connectivity at dendritic spines

PubMed Central

Risher, W Christopher; Patel, Sagar; Kim, Il Hwan; Uezu, Akiyoshi; Bhagat, Srishti; Wilton, Daniel K; Pilaz, Louis-Jan; Singh Alvarado, Jonnathan; Calhan, Osman Y; Silver, Debra L; Stevens, Beth; Calakos, Nicole; Soderling, Scott H; Eroglu, Cagla

2014-01-01

During cortical synaptic development, thalamic axons must establish synaptic connections despite the presence of the more abundant intracortical projections. How thalamocortical synapses are formed and maintained in this competitive environment is unknown. Here, we show that astrocyte-secreted protein hevin is required for normal thalamocortical synaptic connectivity in the mouse cortex. Absence of hevin results in a profound, long-lasting reduction in thalamocortical synapses accompanied by a transient increase in intracortical excitatory connections. Three-dimensional reconstructions of cortical neurons from serial section electron microscopy (ssEM) revealed that, during early postnatal development, dendritic spines often receive multiple excitatory inputs. Immuno-EM and confocal analyses revealed that majority of the spines with multiple excitatory contacts (SMECs) receive simultaneous thalamic and cortical inputs. Proportion of SMECs diminishes as the brain develops, but SMECs remain abundant in Hevin-null mice. These findings reveal that, through secretion of hevin, astrocytes control an important developmental synaptic refinement process at dendritic spines. DOI: http://dx.doi.org/10.7554/eLife.04047.001 PMID:25517933

Perturbation of Serotonin Homeostasis during Adulthood Affects Serotonergic Neuronal Circuitry.

PubMed

Pratelli, Marta; Migliarini, Sara; Pelosi, Barbara; Napolitano, Francesco; Usiello, Alessandro; Pasqualetti, Massimo

2017-01-01

Growing evidence shows that the neurotransmitter serotonin (5-HT) modulates the fine-tuning of neuron development and the establishment of wiring patterns in the brain. However, whether serotonin is involved in the maintenance of neuronal circuitry in the adult brain remains elusive. Here, we use a Tph2 fl ° x conditional knockout (cKO) mouse line to assess the impact of serotonin depletion during adulthood on serotonergic system organization. Data show that the density of serotonergic fibers is increased in the hippocampus and decreased in the thalamic paraventricular nucleus (PVN) as a consequence of brain serotonin depletion. Strikingly, these defects are rescued following reestablishment of brain 5-HT signaling via administration of the serotonin precursor 5-hydroxytryptophan (5-HTP). Finally, 3D reconstruction of serotonergic fibers reveals that changes in serotonin homeostasis affect axonal branching complexity. These data demonstrate that maintaining proper serotonin homeostasis in the adult brain is crucial to preserve the correct serotonergic axonal wiring.

Corticofugal modulation of peripheral auditory responses

PubMed Central

Terreros, Gonzalo; Delano, Paul H.

2015-01-01

The auditory efferent system originates in the auditory cortex and projects to the medial geniculate body (MGB), inferior colliculus (IC), cochlear nucleus (CN) and superior olivary complex (SOC) reaching the cochlea through olivocochlear (OC) fibers. This unique neuronal network is organized in several afferent-efferent feedback loops including: the (i) colliculo-thalamic-cortico-collicular; (ii) cortico-(collicular)-OC; and (iii) cortico-(collicular)-CN pathways. Recent experiments demonstrate that blocking ongoing auditory-cortex activity with pharmacological and physical methods modulates the amplitude of cochlear potentials. In addition, auditory-cortex microstimulation independently modulates cochlear sensitivity and the strength of the OC reflex. In this mini-review, anatomical and physiological evidence supporting the presence of a functional efferent network from the auditory cortex to the cochlear receptor is presented. Special emphasis is given to the corticofugal effects on initial auditory processing, that is, on CN, auditory nerve and cochlear responses. A working model of three parallel pathways from the auditory cortex to the cochlea and auditory nerve is proposed. PMID:26483647

Thalamocortical and corticothalamic pathways differentially contribute to goal-directed behaviors in the rat

PubMed Central

Alcaraz, Fabien; Fresno, Virginie; Marchand, Alain R; Kremer, Eric J; Coutureau, Etienne

2018-01-01

Highly distributed neural circuits are thought to support adaptive decision-making in volatile and complex environments. Notably, the functional interactions between prefrontal and reciprocally connected thalamic nuclei areas may be important when choices are guided by current goal value or action-outcome contingency. We examined the functional involvement of selected thalamocortical and corticothalamic pathways connecting the dorsomedial prefrontal cortex (dmPFC) and the mediodorsal thalamus (MD) in the behaving rat. Using a chemogenetic approach to inhibit projection-defined dmPFC and MD neurons during an instrumental learning task, we show that thalamocortical and corticothalamic pathways differentially support goal attributes. Both pathways participate in adaptation to the current goal value, but only thalamocortical neurons are required to integrate current causal relationships. These data indicate that antiparallel flow of information within thalamocortical circuits may convey qualitatively distinct aspects of adaptive decision-making and highlight the importance of the direction of information flow within neural circuits. PMID:29405119

Consciousness, cognition and brain networks: New perspectives.

PubMed

Aldana, E M; Valverde, J L; Fábregas, N

2016-10-01

A detailed analysis of the literature on consciousness and cognition mechanisms based on the neural networks theory is presented. The immune and inflammatory response to the anesthetic-surgical procedure induces modulation of neuronal plasticity by influencing higher cognitive functions. Anesthetic drugs can cause unconsciousness, producing a functional disruption of cortical and thalamic cortical integration complex. The external and internal perceptions are processed through an intricate network of neural connections, involving the higher nervous activity centers, especially the cerebral cortex. This requires an integrated model, formed by neural networks and their interactions with highly specialized regions, through large-scale networks, which are distributed throughout the brain collecting information flow of these perceptions. Functional and effective connectivity between large-scale networks, are essential for consciousness, unconsciousness and cognition. It is what is called the "human connectome" or map neural networks. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Repeated administration of CGP 46381, a gamma-aminobutyric acidB antagonist, and ethosuximide suppresses seizure-associated cyclic adenosine 3'5' monophosphate response element- and activator protein-1 DNA-binding activities in lethargic (lh/lh) mice.

PubMed

Ishige, K; Endo, H; Saito, H; Ito, Y

2001-01-19

To characterize seizure-associated increases in cerebral cortical and thalamic cyclic AMP responsive element (CRE)- and activator protein 1 (AP-1) DNA-binding activities in lethargic (lh/lh) mice, a genetic model of absence seizures, we examined the effects of ethosuximide and CGP 46381 on these DNA-binding activities. Repeated administration (twice a day for 5 days) of ethosuximide (200 mg/kg) or CGP 46381 (60 mg/kg) attenuated both seizure behavior and the increased DNA-binding activities, and was more effective than a single administration of these drugs. These treatments did not affect either normal behavior or basal DNA-binding activities in non-epileptic control (+/+) mice. Gel supershift assays revealed that the increased CRE-binding activity was attributable to activation of the binding activity of CREB, and that the c-Fos-c-Jun complex was a component of the increased AP-1 DNA-binding activity.

Juvenile Leigh syndrome, optic atrophy, ataxia, dystonia, and epilepsy due to T14487C mutation in the mtDNA-ND6 gene: a mitochondrial syndrome presenting from birth to adolescence.

PubMed

Leshinsky-Silver, Esther; Shuvalov, Ruslan; Inbar, Shani; Cohen, Sarit; Lev, Dorit; Lerman-Sagie, Tally

2011-04-01

An increasing number of reports describe mutations in mitochondrial DNA coding regions, especially in mitochondrial DNA- encoded nicotinamide adenine dinucleotide dehydrogenase subunit genes of the respiratory chain complex I, as causing early-onset Leigh syndrome. The authors report the molecular findings in a 24-year-old patient with juvenile-onset Leigh syndrome presenting with optic atrophy, ataxia dystonia, and epilepsy. A brain magnetic resonance imaging revealed bilateral basal ganglia and thalamic hypointensities, and a magnetic resonance spectroscopy revealed an increased lactate peak. The authors identified a T14487C change causing M63V substitution in the mitochondrial ND6 gene. The mutation was heteroplasmic in muscle and blood samples, with different mutation loads, and was absent in the patient's mother's urine and blood samples. They suggest that the T14487C mtDNA mutation should be analyzed in Leigh syndrome, presenting with optic atrophy, ataxia, dystonia, and epilepsy, regardless of age.

The CaV2.3 R-Type Voltage-Gated Ca2+ Channel in Mouse Sleep Architecture

PubMed Central

Siwek, Magdalena Elisabeth; Müller, Ralf; Henseler, Christina; Broich, Karl; Papazoglou, Anna; Weiergräber, Marco

2014-01-01

Study Objectives: Voltage-gated Ca2+ channels (VGCCs) are key elements in mediating thalamocortical rhythmicity. Low-voltage activated (LVA) CaV 3 T-type Ca2+ channels have been related to thalamic rebound burst firing and to generation of non-rapid eye movement (NREM) sleep. High-voltage activated (HVA) CaV 1 L-type Ca2+ channels, on the opposite, favor the tonic mode of action associated with higher levels of vigilance. However, the role of the HVA Non-L-type CaV2.3 Ca2+ channels, which are predominantly expressed in the reticular thalamic nucleus (RTN), still remains unclear. Recently, CaV2.3−/− mice were reported to exhibit altered spike-wave discharge (SWD)/absence seizure susceptibility supported by the observation that CaV2.3 mediated Ca2+ influx into RTN neurons can trigger small-conductance Ca2+-activated K+-channel type 2 (SK2) currents capable of maintaining thalamic burst activity. Based on these studies we investigated the role of CaV2.3 R-type Ca2+ channels in rodent sleep. Methods: The role of CaV2.3 Ca2+ channels was analyzed in CaV2.3−/− mice and controls in both spontaneous and artificial urethane-induced sleep, using implantable video-EEG radiotelemetry. Data were analyzed for alterations in sleep architecture using sleep staging software and time-frequency analysis. Results: CaV2.3 deficient mice exhibited reduced wake duration and increased slow-wave sleep (SWS). Whereas mean sleep stage durations remained unchanged, the total number of SWS epochs was increased in CaV2.3−/− mice. Additional changes were observed for sleep stage transitions and EEG amplitudes. Furthermore, urethane-induced SWS mimicked spontaneous sleep results obtained from CaV2.3 deficient mice. Quantitative Real-time PCR did not reveal changes in thalamic CaV3 T-type Ca2+ channel expression. The detailed mechanisms of SWS increase in CaV2.3−/− mice remain to be determined. Conclusions: Low-voltage activated CaV2.3 R-type Ca2+ channels in the thalamocortical loop and extra-thalamocortical circuitries substantially regulate rodent sleep architecture thus representing a novel potential target for pharmacological treatment of sleep disorders in the future. Citation: Siwek ME, Müller R, Henseler C, Broich K, Papazoglou A, Weiergräber M. The CaV2.3 R-type voltage-gated Ca2+ channel in mouse sleep architecture. SLEEP 2014;37(5):881-892. PMID:24790266

Development of Maps of Simple and Complex Cells in the Primary Visual Cortex

PubMed Central

Antolík, Ján; Bednar, James A.

2011-01-01

Hubel and Wiesel (1962) classified primary visual cortex (V1) neurons as either simple, with responses modulated by the spatial phase of a sine grating, or complex, i.e., largely phase invariant. Much progress has been made in understanding how simple-cells develop, and there are now detailed computational models establishing how they can form topographic maps ordered by orientation preference. There are also models of how complex cells can develop using outputs from simple cells with different phase preferences, but no model of how a topographic orientation map of complex cells could be formed based on the actual connectivity patterns found in V1. Addressing this question is important, because the majority of existing developmental models of simple-cell maps group neurons selective to similar spatial phases together, which is contrary to experimental evidence, and makes it difficult to construct complex cells. Overcoming this limitation is not trivial, because mechanisms responsible for map development drive receptive fields (RF) of nearby neurons to be highly correlated, while co-oriented RFs of opposite phases are anti-correlated. In this work, we model V1 as two topographically organized sheets representing cortical layer 4 and 2/3. Only layer 4 receives direct thalamic input. Both sheets are connected with narrow feed-forward and feedback connectivity. Only layer 2/3 contains strong long-range lateral connectivity, in line with current anatomical findings. Initially all weights in the model are random, and each is modified via a Hebbian learning rule. The model develops smooth, matching, orientation preference maps in both sheets. Layer 4 units become simple cells, with phase preference arranged randomly, while those in layer 2/3 are primarily complex cells. To our knowledge this model is the first explaining how simple cells can develop with random phase preference, and how maps of complex cells can develop, using only realistic patterns of connectivity. PMID:21559067

Medial Auditory Thalamus Inactivation Prevents Acquisition and Retention of Eyeblink Conditioning

ERIC Educational Resources Information Center

Halverson, Hunter E.; Poremba, Amy; Freeman, John H.

2008-01-01

The auditory conditioned stimulus (CS) pathway that is necessary for delay eyeblink conditioning was investigated using reversible inactivation of the medial auditory thalamic nuclei (MATN) consisting of the medial division of the medial geniculate (MGm), suprageniculate (SG), and posterior intralaminar nucleus (PIN). Rats were given saline or…

Cognitive Inflexibility and Frontal-Cortical Activation in Pediatric Obsessive-Compulsive Disorder

ERIC Educational Resources Information Center

Britton, Jennifer C.; Rauch, Scott L.; Rosso, Isabelle M.; Killgore, William D. S.; Price, Lauren M.; Ragan, Jennifer; Chosak, Anne; Hezel, Dianne M.; Pine, Daniel S.; Leibenluft, Ellen; Pauls, David L.; Jenike, Michael A.; Stewart, S. Evelyn

2010-01-01

Objective: Deficits in cognitive flexibility and response inhibition have been linked to perturbations in cortico-striatal-thalamic circuitry in adult obsessive-compulsive disorder (OCD). Although similar cognitive deficits have been identified in pediatric OCD, few neuroimaging studies have been conducted to examine its neural correlates in the…

The Differential Effects of Thalamus and Basal Ganglia on Facial Emotion Recognition

ERIC Educational Resources Information Center

Cheung, Crystal C. Y.; Lee, Tatia M. C.; Yip, James T. H.; King, Kristin E.; Li, Leonard S. W.

2006-01-01

This study examined if subcortical stroke was associated with impaired facial emotion recognition. Furthermore, the lateralization of the impairment and the differential profiles of facial emotion recognition deficits with localized thalamic or basal ganglia damage were also studied. Thirty-eight patients with subcortical strokes and 19 matched…

Medial Auditory Thalamic Stimulation as a Conditioned Stimulus for Eyeblink Conditioning in Rats

ERIC Educational Resources Information Center

Campolattaro, Matthew M.; Halverson, Hunter E.; Freeman, John H.

2007-01-01

The neural pathways that convey conditioned stimulus (CS) information to the cerebellum during eyeblink conditioning have not been fully delineated. It is well established that pontine mossy fiber inputs to the cerebellum convey CS-related stimulation for different sensory modalities (e.g., auditory, visual, tactile). Less is known about the…

Functional Magnetic Resonance Imaging during Planning before and after Cognitive-Behavioral Therapy in Pediatric Obsessive-Compulsive Disorder

ERIC Educational Resources Information Center

Huyser, Chaim; Veltman, Dick J.; Wolters, Lidewij H.; de Haan, Else; Boer, Frits

2010-01-01

Objective: Pediatric obsessive compulsive disorder (OCD) has been associated with cognitive abnormalities, in particular executive impairments, and dysfunction of frontal-striatal-thalamic circuitry. The aim of this study was to investigate if planning as an executive function is compromised in pediatric OCD and is associated with…

Vascular Thalamic Amnesia: A Reappraisal

ERIC Educational Resources Information Center

Carlesimo, Giovanni Augusto; Lombardi, Maria Giovanna; Caltagirone, Carlo

2011-01-01

In humans lacunar infarcts in the mesial and anterior regions of the thalami are frequently associated with amnesic syndromes. In this review paper, we scrutinized 41 papers published between 1983 and 2009 that provided data on a total of 83 patients with the critical ischemic lesions (i.e. 17 patients with right-sided lesions, 25 with left-sided…

Cholinergic Receptor Substrates of Neuronal Plasticity and Learning

DTIC Science & Technology

1992-01-29

cortical binding of 3H- oxotremorine (OXO), a ligand having high affinity for M2 muscarinic receptors, are described in a manuscript by Vogt, Gabriel...of 1H Oxotremorine co-incubated with Pirenzepine (OXO-M/PZ) throughout the course of training in three thalamic nudei. -L As in the case of training

Hemodynamic monitoring in different cortical layers with a single fiber optical system

NASA Astrophysics Data System (ADS)

Yu, Linhui; Noor, M. Sohail; Kiss, Zelma H. T.; Murari, Kartikeya

2018-02-01

Functional monitoring of highly-localized deep brain structures is of great interest. However, due to light scattering, optical methods have limited depth penetration or can only measure from a large volume. In this research, we demonstrate continuous measurement of hemodynamics in different cortical layers in response to thalamic deep brain stimulation (DBS) using a single fiber optical system. A 200-μm-core-diameter multimode fiber is used to deliver and collect light from tissue. The fiber probe can be stereotaxically implanted into the brain region of interest at any depth to measure the di use reflectance spectra from a tissue volume of 0.02-0.03 mm3 near the fiber tip. Oxygenation is then extracted from the reflectance spectra using an algorithm based on Monte Carlo simulations. Measurements were performed on the surface (cortical layer I) and at 1.5 mm depth (cortical layer VI) of the motor cortex in anesthetized rats with thalamic DBS. Preliminary results revealed the oxygenation changes in response to DBS. Moreover, the baseline as well as the stimulus-evoked change in oxygenation were different at the two depths of cortex.

Development of the Thalamocortical Interactions: Past, Present and Future.

PubMed

López-Bendito, Guillermina

2018-06-20

For the past two decades, we have advanced in our understanding of the mechanisms implicated in the formation of brain circuits. The connection between the cortex and thalamus has deserved much attention, as thalamocortical connectivity is crucial for sensory processing and motor learning. Classical dye tracing studies in wild-type and knockout mice initially helped to characterize the developmental progression of this connectivity and revealed key transcription factors involved. With the recent advances in technical tools to specifically label subsets of projecting neurons, knock-down genes individually and/or modify their activity, the field has gained further understanding on the rules operating in thalamocortical circuit formation and plasticity. In this review, I will summarize the most relevant discoveries that have been made in this field, from development to early plasticity processes covering three major aspects: axon guidance, thalamic influence on sensory cortical specification, and the role of spontaneous thalamic activity. I will emphasize how the implementation of new tools has helped the field to progress and what I consider to be open questions and the perspective for the future. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Transition dynamics of generalized multiple epileptic seizures associated with thalamic reticular nucleus excitability: A computational study

NASA Astrophysics Data System (ADS)

Liu, Suyu; Wang, Qingyun

2017-11-01

Presently, we improve a computational framework of thalamocortical circuits related to the Taylor's model to investigate the relationship between thalamic reticular nucleus (RE) excitability and epilepsy. By using bifurcation analysis, we explore the RE's excitability dynamics mechanism in the processes of seizure generation, development and transition. Results show that the seizure-free state, absence seizures, clonic seizures and tonic seizures can be formed as the RE excitability is changed in this established model. Importantly, it is verified that physiological changing GABAA inhibition in RE can elicit absence seizures and clonic seizures and the pathological transitions between these two seizures. Furthermore, when the level of AMPA connection is decreased or increased, this proposed model embraces absence seizures and clonic seizures, and tonic seizures, respectively. Except that, bifurcation mechanisms of dynamical transition of different seizures are analyzed in detail. In addition, hybrid regulations of the reticular nucleus excitability for epileptic seizures are proven to be valid within the suitable levels of AMPA and GABAA connection. Hopefully, the obtained results could be helpful for effective control of epileptic activities with additional pharmacological interference.

The intralaminar thalamus—an expressway linking visual stimuli to circuits determining agency and action selection

PubMed Central

Fisher, Simon D.; Reynolds, John N. J.

2014-01-01

Anatomical investigations have revealed connections between the intralaminar thalamic nuclei and areas such as the superior colliculus (SC) that receive short latency input from visual and auditory primary sensory areas. The intralaminar nuclei in turn project to the major input nucleus of the basal ganglia, the striatum, providing this nucleus with a source of subcortical excitatory input. Together with a converging input from the cerebral cortex, and a neuromodulatory dopaminergic input from the midbrain, the components previously found necessary for reinforcement learning in the basal ganglia are present. With this intralaminar sensory input, the basal ganglia are thought to play a primary role in determining what aspect of an organism’s own behavior has caused salient environmental changes. Additionally, subcortical loops through thalamic and basal ganglia nuclei are proposed to play a critical role in action selection. In this mini review we will consider the anatomical and physiological evidence underlying the existence of these circuits. We will propose how the circuits interact to modulate basal ganglia output and solve common behavioral learning problems of agency determination and action selection. PMID:24765070

Unilateral Postoperative Deep Cerebral Venous Thrombosis with Complete Recovery: A Report of 2 Cases.

PubMed

Benifla, Mony; Laughlin, Suzzanne; Tovar-Spinoza, Zulma S; Rutka, James T; Dirks, Peter B

2017-01-01

Postsurgical deep brain venous thrombosis has not been well described in children before. When approaching thalamic or intraventricular lesions, extra care should be taken to prevent injury to the internal cerebral veins (ICVs) and the vein of Galen. However, even when they are well preserved during surgery, postoperative hemodynamic changes, mainly in the first 24 h, or surgical manipulation can cause thrombosis of these veins. We report 2 children with unilateral postoperative ICV thrombosis; in 1 of the patients the vein of Galen was also thrombosed. Although both patients had altered sensorium initially, no anticoagulation therapy was given, and they both recovered well. When approaching thalamic or intraventricular lesions, extra care should be taken to prevent injury to the ICV and the vein of Galen. The surgeon should respect the deep brain venous system when approaching midline structures. Both the neurosurgeon and the neuroradiologist should be aware of this possible complication in order to make a prompt diagnosis and to offer proper treatment if needed. © 2017 S. Karger AG, Basel.

Multiple anatomical systems embedded within the primate medial temporal lobe: implications for hippocampal function.

PubMed

Aggleton, John P

2012-08-01

A review of medial temporal lobe connections reveals three distinct groupings of hippocampal efferents. These efferent systems and their putative memory functions are: (1) The 'extended-hippocampal system' for episodic memory, which involves the anterior thalamic nuclei, mammillary bodies and retrosplenial cortex, originates in the subicular cortices, and has a largely laminar organisation; (2) The 'rostral hippocampal system' for affective and social learning, which involves prefrontal cortex, amygdala and nucleus accumbens, has a columnar organisation, and originates from rostral CA1 and subiculum; (3) The 'reciprocal hippocampal-parahippocampal system' for sensory processing and integration, which originates from the length of CA1 and the subiculum, and is characterised by columnar, connections with reciprocal topographies. A fourth system, the 'parahippocampal-prefrontal system' that supports familiarity signalling and retrieval processing, has more widespread prefrontal connections than those of the hippocampus, along with different thalamic inputs. Despite many interactions between these four systems, they may retain different roles in memory which when combined explain the importance of the medial temporal lobe for the formation of declarative memories. Copyright © 2011 Elsevier Ltd. All rights reserved.

Cellular organization of cortical barrel columns is whisker-specific

PubMed Central

Meyer, Hanno S.; Egger, Robert; Guest, Jason M.; Foerster, Rita; Reissl, Stefan; Oberlaender, Marcel

2013-01-01

The cellular organization of the cortex is of fundamental importance for elucidating the structural principles that underlie its functions. It has been suggested that reconstructing the structure and synaptic wiring of the elementary functional building block of mammalian cortices, the cortical column, might suffice to reverse engineer and simulate the functions of entire cortices. In the vibrissal area of rodent somatosensory cortex, whisker-related “barrel” columns have been referred to as potential cytoarchitectonic equivalents of functional cortical columns. Here, we investigated the structural stereotypy of cortical barrel columns by measuring the 3D neuronal composition of the entire vibrissal area in rat somatosensory cortex and thalamus. We found that the number of neurons per cortical barrel column and thalamic “barreloid” varied substantially within individual animals, increasing by ∼2.5-fold from dorsal to ventral whiskers. As a result, the ratio between whisker-specific thalamic and cortical neurons was remarkably constant. Thus, we hypothesize that the cellular architecture of sensory cortices reflects the degree of similarity in sensory input and not columnar and/or cortical uniformity principles. PMID:24101458

Spatial cognitive deficits in an animal model of Wernicke-Korsakoff syndrome are related to changes in thalamic VDAC protein concentrations.

PubMed

Bueno, K O; de Souza Resende, L; Ribeiro, A F; Dos Santos, D M; Gonçalves, E C; Vigil, F A B; de Oliveira Silva, I F; Ferreira, L F; de Castro Pimenta, A M; Ribeiro, A M

2015-05-21

Proteomic profiles of the thalamus and the correlation between the rats' performance on a spatial learning task and differential protein expression were assessed in the thiamine deficiency (TD) rat model of Wernicke-Korsakoff syndrome. Two-dimensional gel-electrophoresis detected 320 spots and a significant increase or decrease in seven proteins. Four proteins were correlated to rat behavioral performance in the Morris Water Maze. One of the four proteins was identified by mass spectrometry as Voltage-Dependent Anion Channels (VDACs). The association of VDAC is evident in trials in which the rats' performance was worst, in which the VDAC protein was reduced, as confirmed by Western blot. No difference was observed on the mRNA of Vdac genes, indicating that the decreased VDAC expression may be related to a post-transcriptional process. The results show that TD neurodegeneration involves changes in thalamic proteins and suggest that VDAC protein activity might play an important role in an initial stage of the spatial learning process. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Molecular imaging of the dopaminergic system and its association with human cognitive function.

PubMed

Cropley, Vanessa L; Fujita, Masahiro; Innis, Robert B; Nathan, Pradeep J

2006-05-15

Molecular imaging with positron emission tomography (PET) and single photon emission computed tomography (SPECT) has recently been used to examine dopamine (DA) function and its relationship with cognition in human subjects. This article will review PET and SPECT studies that have explored the relationship between cognitive processes and components of the DA system (pre-, intra-, and postsynaptic) in healthy and patient populations such as Parkinson's disease (PD), schizophrenia, Huntington's disease, and aging. It is demonstrated that DA activity modulates a range of frontal executive-type cognitive processes such as working memory, attentional functioning, and sequential organization, and alterations of DA within the fronto-striato-thalamic circuits might contribute to the cognitive impairments observed in PD, schizophrenia, and normal aging. Although associations between DA and cognitive measures need to be considered within the context of fronto-striato-thalamic circuitry, it is suggested that striatal (especially caudate) DA activity, particularly via D2 receptors, might be important for response inhibition, temporal organization of material, and motor performance, whereas cortical DA transmission via D1 receptors might be important for maintaining and representing on-going behavior.

[Effect of non-selective alpha-adrenergic receptor antagonist nicergoline on the activity of neurons in the ventral lateral thalamic nucleus].

PubMed

Lukhanina, O P; Pil'kevych, N A

2005-01-01

In experiments on rats microionophoretic administration of nicergoline mainly showed the dual effect on the background activity of the ventrolateral thalamic nucleus (VL) neurons and their reactions evoked by the superior cerebellum peduncle stimulation: inhibitory under weak (2-10 nA) and excitatory under stronger (20-40 nA) currents. Microionophoresis (25 nA) of nicergoline led to decrease of the postexcitatory inhibitory processes during paired stimulation of the cerebellum fibers. Paired-pulse ratio (number of spikes in the short-latency neuronal responses elicited by the second pulse/number of spikes by the first pulse) increased, which support a presynaptic mode of drug action. Hence excitatory effect of nicergoline may be related to the blockade of the presynaptic alpha2-receptors, while inhibitory effect by the blockade of the postsynaptic alphal-receptors. Present data reveal the essential participation of the alpha-adrenoreceptor system in the modulation of background and evoked neuronal activity of the motor thalamus. The possible role of noradrenergic denervation in the development of movement disorders accompanying Parkinson's disease is discussed.

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

PubMed

Fan, Denggui; Liao, Fucheng; Wang, Qingyun

2017-07-01

Absence epilepsy, characterized by 2-4 Hz spike-wave discharges (SWDs), can be caused by pathological interactions within the thalamocortical system. Cortical spindling oscillations are also demonstrated to involve the oscillatory thalamocortical rhythms generated by the synaptic circuitry of the thalamus and cortex. This implies that SWDs and spindling oscillations can share the common thalamocortical mechanism. Additionally, the thalamic reticular nucleus (RE) is hypothesized to regulate the onsets and propagations of both the epileptic SWDs and sleep spindles. Based on the proposed single-compartment thalamocortical neural field model, we firstly investigate the stimulation effect of RE on the initiations, terminations, and transitions of SWDs. It is shown that the activations and deactivations of RE triggered by single-pulse stimuli can drive the cortical subsystem to behave as the experimentally observed onsets and self-abatements of SWDs, as well as the transitions from 2-spike and wave discharges (2-SWDs) to SWDs. In particular, with increasing inhibition from RE to the specific relay nucleus (TC), rich transition behaviors in cortex can be obtained through the upstream projection path, RE→TC→Cortex. Although some of the complex dynamical patterns can be expected from the earlier single compartment thalamocortical model, the effect of brain network topology on the emergence of SWDs and spindles, as well as the transitions between them, has not been fully investigated. We thereby develop a spatially extended 3-compartment coupled network model with open-/closed-end connective configurations, to investigate the spatiotemporal effect of RE on the SWDs and spindles. Results show that the degrees of activations of RE 1 can induce the rich spatiotemporal evolution properties including the propagations from SWDs to spindles within different compartments and the transitions between them, through the RE 1 →TC 1 →Cortex 1 and Cortex 1 →Cortex 2 →Cortex 3 projecting paths, respectively. Overall, those results imply that RE possesses the pacemaker function in controlling SWDs and spindling oscillations, which computationally provide causal support for the involvement of RE in absence seizures and sleep spindles.

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

NASA Astrophysics Data System (ADS)

Fan, Denggui; Liao, Fucheng; Wang, Qingyun

2017-07-01

Absence epilepsy, characterized by 2-4 Hz spike-wave discharges (SWDs), can be caused by pathological interactions within the thalamocortical system. Cortical spindling oscillations are also demonstrated to involve the oscillatory thalamocortical rhythms generated by the synaptic circuitry of the thalamus and cortex. This implies that SWDs and spindling oscillations can share the common thalamocortical mechanism. Additionally, the thalamic reticular nucleus (RE) is hypothesized to regulate the onsets and propagations of both the epileptic SWDs and sleep spindles. Based on the proposed single-compartment thalamocortical neural field model, we firstly investigate the stimulation effect of RE on the initiations, terminations, and transitions of SWDs. It is shown that the activations and deactivations of RE triggered by single-pulse stimuli can drive the cortical subsystem to behave as the experimentally observed onsets and self-abatements of SWDs, as well as the transitions from 2-spike and wave discharges (2-SWDs) to SWDs. In particular, with increasing inhibition from RE to the specific relay nucleus (TC), rich transition behaviors in cortex can be obtained through the upstream projection path, RE → TC → Cortex . Although some of the complex dynamical patterns can be expected from the earlier single compartment thalamocortical model, the effect of brain network topology on the emergence of SWDs and spindles, as well as the transitions between them, has not been fully investigated. We thereby develop a spatially extended 3-compartment coupled network model with open-/closed-end connective configurations, to investigate the spatiotemporal effect of RE on the SWDs and spindles. Results show that the degrees of activations of RE 1 can induce the rich spatiotemporal evolution properties including the propagations from SWDs to spindles within different compartments and the transitions between them, through the RE 1 → TC 1 → Cortex 1 and Cortex 1 → Cortex 2 → Cortex 3 projecting paths, respectively. Overall, those results imply that RE possesses the pacemaker function in controlling SWDs and spindling oscillations, which computationally provide causal support for the involvement of RE in absence seizures and sleep spindles.

Impact of Strategically Located White Matter Hyperintensities on Cognition in Memory Clinic Patients with Small Vessel Disease

PubMed Central

Hilal, Saima; Kuijf, Hugo J.; Ikram, Mohammad Kamran; Xu, Xin; Tan, Boon Yeow; Venketasubramanian, Narayanaswamy; Postma, Albert; Biessels, Geert Jan; Chen, Christopher P. L. H.

2016-01-01

Background and Purpose Studies on the impact of small vessel disease (SVD) on cognition generally focus on white matter hyperintensity (WMH) volume. The extent to which WMH location relates to cognitive performance has received less attention, but is likely to be functionally important. We examined the relation between WMH location and cognition in a memory clinic cohort of patients with sporadic SVD. Methods A total of 167 patients with SVD were recruited from memory clinics. Assumption-free region of interest-based analyses based on major white matter tracts and voxel-wise analyses were used to determine the association between WMH location and executive functioning, visuomotor speed and memory. Results Region of interest-based analyses showed that WMHs located particularly within the anterior thalamic radiation and forceps minor were inversely associated with both executive functioning and visuomotor speed, independent of total WMH volume. Memory was significantly associated with WMH volume in the forceps minor, independent of total WMH volume. An independent assumption-free voxel-wise analysis identified strategic voxels in these same tracts. Region of interest-based analyses showed that WMH volume within the anterior thalamic radiation explained 6.8% of variance in executive functioning, compared to 3.9% for total WMH volume; WMH volume within the forceps minor explained 4.6% of variance in visuomotor speed and 4.2% of variance in memory, compared to 1.8% and 1.3% respectively for total WMH volume. Conclusions Our findings identify the anterior thalamic radiation and forceps minor as strategic white matter tracts in which WMHs are most strongly associated with cognitive impairment in memory clinic patients with SVD. WMH volumes in individual tracts explained more variance in cognition than total WMH burden, emphasizing the importance of lesion location when addressing the functional consequences of WMHs. PMID:27824925

Fast voltage-sensitive dye imaging of excitatory and inhibitory synaptic transmission in the rat granular retrosplenial cortex.

PubMed

Nixima, Ken'ichi; Okanoya, Kazuo; Ichinohe, Noritaka; Kurotani, Tohru

2017-09-01

Rodent granular retrosplenial cortex (GRS) has dense connections between the anterior thalamic nuclei (ATN) and hippocampal formation. GRS superficial pyramidal neurons exhibit distinctive late spiking (LS) firing property and form patchy clusters with prominent apical dendritic bundles. The aim of this study was to investigate spatiotemporal dynamics of signal transduction in the GRS induced by ATN afferent stimulation by using fast voltage-sensitive dye imaging in rat brain slices. In coronal slices, layer 1a stimulation, which presumably activated thalamic fibers, evoked propagation of excitatory synaptic signals from layers 2-4 to layers 5-6 in a direction perpendicular to the layer axis, followed by transverse signal propagation within each layer. In the presence of ionotropic glutamate receptor antagonists, inhibitory responses were observed in superficial layers, induced by direct activation of inhibitory interneurons in layer 1. In horizontal slices, excitatory signals in deep layers propagated transversely mainly from posterior to anterior via superficial layers. Cortical inhibitory responses upon layer 1a stimulation in horizontal slices were weaker than those in the coronal slices. Observed differences between coronal and horizontal planes suggest anisotropy of the intracortical circuitry. In conclusion, ATN inputs are processed differently in coronal and horizontal planes of the GRS and then conveyed to other cortical areas. In both planes, GRS superficial layers play an important role in signal propagation, which suggests that superficial neuronal cascade is crucial in the integration of multiple information sources. NEW & NOTEWORTHY Superficial neurons in the rat granular retrosplenial cortex (GRS) show distinctive late-spiking (LS) firing property. However, little is known about spatiotemporal dynamics of signal transduction in the GRS. We demonstrated LS neuron network relaying thalamic inputs to deep layers and anisotropic distribution of inhibition between coronal and horizontal planes. Since deep layers of the GRS receive inputs from the subiculum, GRS circuits may work as an integrator of multiple sources such as sensory and memory information. Copyright © 2017 the American Physiological Society.

Mind the Gap: Two Dissociable Mechanisms of Temporal Processing in the Auditory System

PubMed Central

Anderson, Lucy A.

2016-01-01

High temporal acuity of auditory processing underlies perception of speech and other rapidly varying sounds. A common measure of auditory temporal acuity in humans is the threshold for detection of brief gaps in noise. Gap-detection deficits, observed in developmental disorders, are considered evidence for “sluggish” auditory processing. Here we show, in a mouse model of gap-detection deficits, that auditory brain sensitivity to brief gaps in noise can be impaired even without a general loss of central auditory temporal acuity. Extracellular recordings in three different subdivisions of the auditory thalamus in anesthetized mice revealed a stimulus-specific, subdivision-specific deficit in thalamic sensitivity to brief gaps in noise in experimental animals relative to controls. Neural responses to brief gaps in noise were reduced, but responses to other rapidly changing stimuli unaffected, in lemniscal and nonlemniscal (but not polysensory) subdivisions of the medial geniculate body. Through experiments and modeling, we demonstrate that the observed deficits in thalamic sensitivity to brief gaps in noise arise from reduced neural population activity following noise offsets, but not onsets. These results reveal dissociable sound-onset-sensitive and sound-offset-sensitive channels underlying auditory temporal processing, and suggest that gap-detection deficits can arise from specific impairment of the sound-offset-sensitive channel. SIGNIFICANCE STATEMENT The experimental and modeling results reported here suggest a new hypothesis regarding the mechanisms of temporal processing in the auditory system. Using a mouse model of auditory temporal processing deficits, we demonstrate the existence of specific abnormalities in auditory thalamic activity following sound offsets, but not sound onsets. These results reveal dissociable sound-onset-sensitive and sound-offset-sensitive mechanisms underlying auditory processing of temporally varying sounds. Furthermore, the findings suggest that auditory temporal processing deficits, such as impairments in gap-in-noise detection, could arise from reduced brain sensitivity to sound offsets alone. PMID:26865621

TCF7L2 mediates the cellular and behavioral response to chronic lithium treatment in animal models.

PubMed

Misztal, Katarzyna; Brozko, Nikola; Nagalski, Andrzej; Szewczyk, Lukasz M; Krolak, Marta; Brzozowska, Katarzyna; Kuznicki, Jacek; Wisniewska, Marta B

2017-02-01

The mechanism of lithium's therapeutic action remains obscure, hindering the discovery of safer treatments for bipolar disorder. Lithium can act as an inhibitor of the kinase GSK3α/β, which in turn negatively regulates β-catenin, a co-activator of LEF1/TCF transcription factors. However, unclear is whether therapeutic levels of lithium activate β-catenin in the brain, and whether this activation could have a therapeutic significance. To address this issue we chronically treated mice with lithium. Although the level of non-phospho-β-catenin increased in all of the brain areas examined, β-catenin translocated into cellular nuclei only in the thalamus. Similar results were obtained when thalamic and cortical neurons were treated with a therapeutically relevant concentration of lithium in vitro. We tested if TCF7L2, a member of LEF1/TCF family that is highly expressed in the thalamus, facilitated the activation of β-catenin. Silencing of Tcf7l2 in thalamic neurons prevented β-catenin from entering the nucleus, even when the cells were treated with lithium. Conversely, when Tcf7l2 was ectopically expressed in cortical neurons, β-catenin shifted to the nucleus, and lithium augmented this process. Lastly, we silenced tcf7l2 in zebrafish and exposed them to lithium for 3 days, to evaluate whether TCF7L2 is involved in the behavioral response. Lithium decreased the dark-induced activity of control zebrafish, whereas the activity of zebrafish with tcf7l2 knockdown was unaltered. We conclude that therapeutic levels of lithium activate β-catenin selectively in thalamic neurons. This effect is determined by the presence of TCF7L2, and potentially contributes to the therapeutic response. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Neuroprotective changes of thalamic degeneration-related gene expression by acupuncture in an MPTP mouse model of parkinsonism: microarray analysis.

PubMed

Yeo, Sujung; Choi, Yeong-Gon; Hong, Yeon-Mi; Lim, Sabina

2013-02-25

Acupuncture stimulations at GB34 and LR3 inhibit the reduction of tyrosine hydroxylase in the nigrostriatal dopaminergic neurons in the parkinsonism animal models. Especially, behavioral tests showed that acupuncture stimulations improved the motor dysfunction in a previous study by almost 87.7%. The thalamus is a crucial area for the motor circuit and has been identified as one of the most markedly damaged areas in Parkinson's disease (PD), so acupuncture stimulations might also have an effect on the thalamic damage. In this study, gene expression changes following acupuncture at the acupoints were investigated in the thalamus of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism model using a whole transcript array. It was confirmed that acupuncture at these acupoints could inhibit the decrease of tyrosine hydroxylase in the thalamic regions of the MPTP model, while acupuncture at the non-acupoints could not suppress this decrease by its level shown in the acupoints. GeneChip gene array analysis showed that 18 (5 annotated genes: Dnase1l2, Dusp4, Mafg, Ndph and Pgm5) of the probes down-regulated in MPTP, as compared to the control, were exclusively up-regulated by acupuncture at the acupoints, but not at the non-acupoints. In addition, 14 (3 annotated genes; Serinc2, Sp2 and Ucp2) of the probes up-regulated in MPTP, as compared to the control, were exclusively down-regulated by acupuncture at the acupoints, but not at the non-acupoints. The expression levels of the representative genes in the microarray were validated by real-time RT-PCR. These results suggest that the 32 probes (8 annotated genes) which are affected by MPTP and acupuncture may be responsible for exerting the inhibitory effect of acupuncture in the thalamus which can be damaged by MPTP intoxication. Copyright © 2012 Elsevier B.V. All rights reserved.

Beta oscillatory neurons in the motor thalamus of movement disorder and pain patients.

PubMed

Basha, Diellor; Dostrovsky, Jonathan O; Lopez Rios, Adriana L; Hodaie, Mojgan; Lozano, Andres M; Hutchison, William D

2014-11-01

Excessive beta oscillations (15-25Hz) in the basal ganglia have been linked to the akineto-rigid symptoms of Parkinson's disease (PD) although it remains unclear whether the underlying mechanism is causative or associative. While a number of studies have reported beta activity in the subthalamic nucleus and globus pallidus internus, relatively little is known about the beta rhythm of the motor thalamus and its relation to movement disorders. To test whether thalamic beta oscillations are related to parkinsonian symptoms, we examined the spectral properties of neuronal activity in the ventral thalamic nuclei of five Parkinson's disease patients (two female, age range 50-72years) and compared them to five essential tremor (three female, aged 41-75) and four central pain patients (one female, aged 38-60). Spike and local field potential recordings were obtained during microelectrode-guided localization of thalamic nuclei prior to the implantation of deep brain stimulating electrodes. A total of 118 movement-related neurons in the region of the ventral intermediate nucleus (Vim) were analyzed across all patient groups. Eighty of these neurons (68%) displayed significant oscillatory firing in the beta range with the limbs at rest. In contrast, only 5.7% of the ventral oral posterior (Vop) (χ(2) test, p<0.05) and only 7.2% of the ventral caudal (Vc) neurons fired rhythmically at beta frequency (χ(2) test, p<0.05). Beta power was significantly decreased during limb movements (ANOVA, p<0.05) and was inversely related to tremor-frequency power during tremor epochs in ET and PD (r(2)=0.44). Comparison between patient groups showed that Vim beta power was significantly higher in ET patients versus pain and PD groups (ANOVA, p<0.05). The findings suggest that beta oscillations are found predominantly in Vim and are involved in movement but are not enhanced in tremor-dominant Parkinson's patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of yoga versus walking on mood, anxiety, and brain GABA levels: a randomized controlled MRS study.

PubMed

Streeter, Chris C; Whitfield, Theodore H; Owen, Liz; Rein, Tasha; Karri, Surya K; Yakhkind, Aleksandra; Perlmutter, Ruth; Prescot, Andrew; Renshaw, Perry F; Ciraulo, Domenic A; Jensen, J Eric

2010-11-01

Yoga and exercise have beneficial effects on mood and anxiety. γ-Aminobutyric acid (GABA)-ergic activity is reduced in mood and anxiety disorders. The practice of yoga postures is associated with increased brain GABA levels. This study addresses the question of whether changes in mood, anxiety, and GABA levels are specific to yoga or related to physical activity. Healthy subjects with no significant medical/psychiatric disorders were randomized to yoga or a metabolically matched walking intervention for 60 minutes 3 times a week for 12 weeks. Mood and anxiety scales were taken at weeks 0, 4, 8, 12, and before each magnetic resonance spectroscopy scan. Scan 1 was at baseline. Scan 2, obtained after the 12-week intervention, was followed by a 60-minute yoga or walking intervention, which was immediately followed by Scan 3. The yoga subjects (n = 19) reported greater improvement in mood and greater decreases in anxiety than the walking group (n = 15). There were positive correlations between improved mood and decreased anxiety and thalamic GABA levels. The yoga group had positive correlations between changes in mood scales and changes in GABA levels. The 12-week yoga intervention was associated with greater improvements in mood and anxiety than a metabolically matched walking exercise. This is the first study to demonstrate that increased thalamic GABA levels are associated with improved mood and decreased anxiety. It is also the first time that a behavioral intervention (i.e., yoga postures) has been associated with a positive correlation between acute increases in thalamic GABA levels and improvements in mood and anxiety scales. Given that pharmacologic agents that increase the activity of the GABA system are prescribed to improve mood and decrease anxiety, the reported correlations are in the expected direction. The possible role of GABA in mediating the beneficial effects of yoga on mood and anxiety warrants further study.

Sleep, consciousness and the spontaneous and evoked electrical activity of the brain. Is there a cortical integrating mechanism?

PubMed

Evans, B M

2003-02-01

The physiological mechanisms that underlie consciousness and unconsciousness are the sleep/wake mechanisms. Deep sleep is a state of physiological reversible unconsciousness. The change from that state to wakefulness is mediated by the reticular activating mechanism. The reverse change from wakefulness to sleep is also an active process effected by an arousal inhibitory mechanism based on a partial blockade of the thalamus and upper brain stem, associated with thalamic sleep spindles and also with cortical sub-delta activity (<1 Hz). The deactivation of the thalamus has been demonstrated both electrically and by positron emission tomography during deep sleep. Normally, wakefulness is associated with instant awareness (defined as the ability to integrate all sensory information from the external environment and the internal environment of the body). Awareness may be a function of the thalamo-cortical network in the cerebral hemispheres, which forms the final path of the sleep/wake mechanism. Anatomical and physiological studies suggest that there may be a double thalamo-cortical network; one relating to cortical and thalamic areas with specific functions and the other global, involving all cortical areas and so-called 'non-specific' thalamic nuclei. The global system might function as a cortical integrating mechanism permitting the spread of information between the specific cortical areas and thus underlying awareness. The global system may also be responsible for much of the spontaneous and evoked electrical activity of the brain. The cognitive change between sleep and wakefulness is accompanied by changes in the autonomic system, the cerebral blood flow and cerebral metabolism. Awareness is an essential component of total consciousness (defined as continuous awareness of the external and internal environment, both past and present, together with the emotions arising from it). In addition to awareness, full consciousness requires short-term and explicit memory and intact emotional responses.

The serotonin hallucinogen 5-MeO-DMT alters cortico-thalamic activity in freely moving mice: Regionally-selective involvement of 5-HT1A and 5-HT2A receptors.

PubMed

Riga, Maurizio S; Lladó-Pelfort, Laia; Artigas, Francesc; Celada, Pau

2017-12-06

5-MeO-DMT is a natural hallucinogen acting as serotonin 5-HT 1A /5-HT 2A receptor agonist. Its ability to evoke hallucinations could be used to study the neurobiology of psychotic symptoms and to identify new treatment targets. Moreover, recent studies revealed the therapeutic potential of serotonin hallucinogens in treating mood and anxiety disorders. Our previous results in anesthetized animals show that 5-MeO-DMT alters cortical activity via 5-HT 1A and 5-HT 2A receptors. Here, we examined 5-MeO-DMT effects on oscillatory activity in prefrontal (PFC) and visual (V1) cortices, and in mediodorsal thalamus (MD) of freely-moving wild-type (WT) and 5-HT 2A -R knockout (KO2A) mice. We performed local field potential multi-recordings evaluating the power at different frequency bands and coherence between areas. We also examined the prevention of 5-MeO-DMT effects by the 5-HT 1A -R antagonist WAY-100635. 5-MeO-DMT affected oscillatory activity more in cortical than in thalamic areas. More marked effects were observed in delta power in V1 of KO2A mice. 5-MeO-DMT increased beta band coherence between all examined areas. In KO2A mice, WAY100635 prevented most of 5-MeO-DMT effects on oscillatory activity. The present results indicate that hallucinatory activity of 5-MeO-DMT is likely mediated by simultaneous alteration of prefrontal and visual activities. The prevention of these effects by WAY-100635 in KO2A mice supports the potential usefulness of 5-HT 1A receptor antagonists to treat visual hallucinations. 5-MeO-DMT effects on PFC theta activity and cortico-thalamic coherence may be related to its antidepressant activity. Copyright © 2017. Published by Elsevier Ltd.

Phase dependent modulation of tremor amplitude in essential tremor through thalamic stimulation

PubMed Central

Cagnan, Hayriye; Brittain, John-Stuart; Little, Simon; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Joint, Carole; Fitzgerald, James; Green, Alexander L.; Aziz, Tipu

2013-01-01

High frequency deep brain stimulation of the thalamus can help ameliorate severe essential tremor. Here we explore how the efficacy, efficiency and selectivity of thalamic deep brain stimulation might be improved in this condition. We started from the hypothesis that the effects of electrical stimulation on essential tremor may be phase dependent, and that, in particular, there are tremor phases at which stimuli preferentially lead to a reduction in the amplitude of tremor. The latter could be exploited to improve deep brain stimulation, particularly if tremor suppression could be reinforced by cumulative effects. Accordingly, we stimulated 10 patients with essential tremor and thalamic electrodes, while recording tremor amplitude and phase. Stimulation near the postural tremor frequency entrained tremor. Tremor amplitude was also modulated depending on the phase at which stimulation pulses were delivered in the tremor cycle. Stimuli in one half of the tremor cycle reduced median tremor amplitude by ∼10%, while those in the opposite half of the tremor cycle increased tremor amplitude by a similar amount. At optimal phase alignment tremor suppression reached 27%. Moreover, tremor amplitude showed a non-linear increase in the degree of suppression with successive stimuli; tremor suppression was increased threefold if a stimulus was preceded by four stimuli with a similar phase relationship with respect to the tremor, suggesting cumulative, possibly plastic, effects. The present results pave the way for a stimulation system that tracks tremor phase to control when deep brain stimulation pulses are delivered to treat essential tremor. This would allow treatment effects to be maximized by focussing stimulation on the optimal phase for suppression and by ensuring that this is repeated over many cycles so as to harness cumulative effects. Such a system might potentially achieve tremor control with far less power demand and greater specificity than current high frequency stimulation approaches, and may lower the risk for tolerance and rebound. PMID:24038075

Medial thalamic 18-FDG uptake following inescapable shock correlates with subsequent learned helpless behavior

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mirrione,M.M.; Mirrione, M.M.; Schulz, D.

2009-12-06

The learned helplessness paradigm has been repeatedly shown to correlate with neurobiological aspects of depression in humans. In this model, rodents are exposed inescapable foot-shock in order to reveal susceptibility to escape deficit, defined as 'learned helplessness' (LH). Few methods are available to probe the neurobiological aspects underlying the differences in susceptibility in the living animal, thus far being limited to studies examining regional neurochemical changes with microdialysis. With the widespread implementation of small animal neuroimaging methods, including positron emission tomography (PET), it is now possible to explore the living brain on a systems level to define regional changes thatmore » may correlate with vulnerability to stress. In this study, 12 wild type Sprague-Dawley rats were exposed to 40 minutes of inescapable foot-shock followed by metabolic imaging using 2-deoxy-2[{sup 18}F]fluoro-D-glucose (18-FDG) 1 hour later. The escape test was performed on these rats 48 hours later (to accommodate radiotracer decay), where they were given the opportunity to press a lever to shut off the shock. A region of interest (ROI) analysis was used to investigate potential correlations (Pearson Regression Coefficients) between regional 18-FDG uptake following inescapable shock and subsequent learned helpless behavior (time to finish the test; number of successful lever presses within 20 seconds of shock onset). ROI analysis revealed a significant positive correlation between time to finish and 18-FDG uptake, and a negative correlation between lever presses and uptake, in the medial thalamic area (p=0.033, p=0.036). This ROI included the paraventricular thalamus, mediodorsal thalamus, and the habenula. In an effort to account for possible spillover artifact, the posterior thalamic area (including ventral medial and lateral portions) was also evaluated but did not reveal significant correlations (p=0.870, p=0.897). No other significant correlations were found in additional regions analyzed including the nucleus accumbens, caudate putamen, substantia nigra, and amygdala. These data suggest that medial thalamic 18-FDG uptake during inescapable shock may contribute to subsequent escape deficits, and are not confounded by shock effects per se, since all animals received the same treatment prior to scanning. We have previously explored 18-FDG differences following the escape test session which also showed hyperactivity in the medial thalamus of learned helpless animals compared to non-learned helpless, and included additional cortical-limbic changes. Given the neuroanatomical connections between the medial thalamus (and habenula) with the prefrontal cortex and monoaminergic brain stem, one possible speculation is that abnormal neuronal activity in these areas during stress may set in motion circuitry changes that correlate with learned helpless behavior.« less

Spatiotemporal profiles of receptive fields of neurons in the lateral posterior nucleus of the cat LP-pulvinar complex.

PubMed

Piché, Marilyse; Thomas, Sébastien; Casanova, Christian

2015-10-01

The pulvinar is the largest extrageniculate thalamic visual nucleus in mammals. It establishes reciprocal connections with virtually all visual cortexes and likely plays a role in transthalamic cortico-cortical communication. In cats, the lateral posterior nucleus (LP) of the LP-pulvinar complex can be subdivided in two subregions, the lateral (LPl) and medial (LPm) parts, which receive a predominant input from the striate cortex and the superior colliculus, respectively. Here, we revisit the receptive field structure of LPl and LPm cells in anesthetized cats by determining their first-order spatiotemporal profiles through reverse correlation analysis following sparse noise stimulation. Our data reveal the existence of previously unidentified receptive field profiles in the LP nucleus both in space and time domains. While some cells responded to only one stimulus polarity, the majority of neurons had receptive fields comprised of bright and dark responsive subfields. For these neurons, dark subfields' size was larger than that of bright subfields. A variety of receptive field spatial organization types were identified, ranging from totally overlapped to segregated bright and dark subfields. In the time domain, a large spectrum of activity overlap was found, from cells with temporally coinciding subfield activity to neurons with distinct, time-dissociated subfield peak activity windows. We also found LP neurons with space-time inseparable receptive fields and neurons with multiple activity periods. Finally, a substantial degree of homology was found between LPl and LPm first-order receptive field spatiotemporal profiles, suggesting a high integration of cortical and subcortical inputs within the LP-pulvinar complex. Copyright © 2015 the American Physiological Society.

Brain network dysfunction in youth with obsessive-compulsive disorder induced by simple uni-manual behavior: The role of the dorsal anterior cingulate cortex

PubMed Central

Friedman, Amy L.; Burgess, Ashley; Ramaseshan, Karthik; Easter, Phil; Khatib, Dalal; Chowdury, Asadur; Arnold, Paul D.; Hanna, Gregory L.; Rosenberg, David R.; Diwadkar, Vaibhav A.

2017-01-01

In an effort to elucidate differences in functioning brain networks between youth with obsessive-compulsive disorder and controls, we used fMRI signals to analyze brain network interactions of the dorsal anterior cingulate cortex (dACC) during visually coordinated motor responses. Subjects made a uni-manual response to briefly presented probes, at periodic (allowing participants to maintain a “motor set”) or random intervals (demanding reactive responses). Network interactions were assessed using psycho-physiological interaction (PPI), a basic model of functional connectivity evaluating modulatory effects of the dACC in the context of each task condition. Across conditions, OCD were characterized by hyper-modulation by the dACC, with loci alternatively observed as both condition-general and condition-specific. Thus, dynamically driven task demands during simple uni-manual motor control induce compensatory network interactions in cortical-thalamic regions in OCD. These findings support previous research in OCD showing compensatory network interactions during complex memory tasks, but establish that these network effects are observed during basic sensorimotor processing. Thus, these patterns of network dysfunction may in fact be independent of the complexity of tasks used to induce brain network activity. Hypothesis-driven approaches coupled with sophisticated network analyses are a highly valuable approach in using fMRI to uncover mechanisms in disorders like OCD. PMID:27992792

Linking Essential Tremor to the Cerebellum: Physiological Evidence.

PubMed

Filip, Pavel; Lungu, Ovidiu V; Manto, Mario-Ubaldo; Bareš, Martin

2016-12-01

Essential tremor (ET), clinically characterized by postural and kinetic tremors, predominantly in the upper extremities, originates from pathological activity in the dynamic oscillatory network comprising the majority of nodes in the central motor network. Evidence indicates dysfunction in the thalamus, the olivocerebellar loops, and intermittent cortical engagement. Pathology of the cerebellum, a structure with architecture intrinsically predisposed to oscillatory activity, has also been implicated in ET as shown by clinical, neuroimaging, and pathological studies. Despite electrophysiological studies assessing cerebellar impairment in ET being scarce, their impact is tangible, as summarized in this review. The electromyography-magnetoencephalography combination provided the first direct evidence of pathological alteration in cortico-subcortical communication, with a significant emphasis on the cerebellum. Furthermore, complex electromyography studies showed disruptions in the timing of agonist and antagonist muscle activation, a process generally attributed to the cerebellum. Evidence pointing to cerebellar engagement in ET has also been found in electrooculography measurements, cerebellar repetitive transcranial magnetic stimulation studies, and, indirectly, in complex analyses of the activity of the ventral intermediate thalamic nucleus (an area primarily receiving inputs from the cerebellum), which is also used in the advanced treatment of ET. In summary, further progress in therapy will require comprehensive electrophysiological and physiological analyses to elucidate the precise mechanisms leading to disease symptoms. The cerebellum, as a major node of this dynamic oscillatory network, requires further study to aid this endeavor.

Receptor-Selective Agonists Induce Emesis and Fos Expression in the Brain and Enteric Nervous System of the Least Shrew (Cryptotis parva)

PubMed Central

Ray, Andrew P.; Chebolu, Seetha; Darmani, Nissar A.

2009-01-01

Research on the mechanisms of emesis has implicated multiple neurotransmitters via both central (dorsal vagal complex) and peripheral (enteric neurons and enterochromaffin cells) anatomical substrates. Taking advantage of advances in receptor-specific agonists, and utilizing Fos expression as a functional activity marker, this study demonstrates a strong, but incomplete, overlap in anatomical substrates for a variety of emetogens. We used cisplatin and specific agonists to 5-HT3 serotonergic, D2/D3 dopaminergic, and NK1 tachykininergic receptors to induce vomiting in the least shrew (Cryptotis parva), and quantified the resulting Fos expression. The least shrew is a small mammal whose responses to emetic challenges are very similar to its human counterparts. In all cases, the enteric nervous system, nucleus of the solitary tract, and dorsal motor nucleus of the vagus demonstrated significantly increased Fos immunoreactivity (Fos-IR). However, Fos-IR induction was notably absent from the area postrema following the dopaminergic and NK1 receptor-specific agents. Two brain nuclei not usually discussed regarding emesis, the dorsal raphe nucleus and paraventricular thalamic nucleus, also demonstrated increased emesis-related Fos-IR. Taken together, these data suggest the dorsal vagal complex is part of a common pathway for a variety of distinct emetogens, but there are central emetic substrates, both medullary and diencephalic, that can be accessed without directly stimulating the area postrema. PMID:19699757

Systems-theory of psychosis--the relevance of "internal censorship".

PubMed

Emrich, H M; Leweke, F M; Schneider, U

2006-02-01

The different aspects of the neurobiology of psychotic disorders are presently discussed under the perspective of Arvid Calssons neurochemical theory of mesolimbic/cortico-thalamic loops. In this regard the question as to whether--neuropsychologically--a "filter-defect" or a disturbance of "internal censorship" is causative for psychoses. This topic is discussed in the present paper.

Evaluation of nonlinear properties of epileptic activity using largest Lyapunov exponent

NASA Astrophysics Data System (ADS)

Medvedeva, Tatiana M.; Lüttjohann, Annika; van Luijtelaar, Gilles; Sysoev, Ilya V.

2016-04-01

Absence seizures are known to be highly non-linear large amplitude oscillations with a well pronounced main time scale. Whilst the appearance of the main frequency is usually considered as a transition from noisy complex dynamics of baseline EEG to more regular absence activity, the dynamical properties of this type of epileptiformic activity in genetic absence models was not studied precisely. Here, the estimation of the largest Lyapunov exponent from intracranial EEGs of 10 WAG/Rij rats (genetic model of absence epilepsy) was performed. Fragments of 10 seizures and 10 episodes of on-going EEG each of 4 s length were used for each animal, 3 cortical and 2 thalamic channels were analysed. The method adapted for short noisy data was implemented. The positive values of the largest Lyapunov exponent were found as for baseline as for spike wave discharges (SWDs), with values for SWDs being significantly less than for on-going activity. Current findings may indicate that SWD is a chaotic process with a well pronounced main timescale rather than a periodic regime. Also, the absence activity was shown to be less chaotic than the baseline one.

Levodopa-induced Dyskinesia: Clinical Features, Pathophysiology, and Medical Management

PubMed Central

Pandey, Sanjay; Srivanitchapoom, Prachaya

2017-01-01

Levodopa-induced dyskinesia (LID) is commonly seen in Parkinson's disease patients treated with levodopa. This side effect is usually encountered after long duration of treatment, but occasionally, this may be seen even after few days or months of treatment. LID is broadly classified as peak-dose dyskinesia, wearing-off or off-period dyskinesia, and diphasic dyskinesia. Pathogenesis of LID is complex, and different neurotransmitters such as dopamine, glutamine, adenosine, and gamma-aminobutyric acid play important role altering the normal physiology of direct and indirect pathway of cortico-basal ganglia-thalamic loop responsible for fine motor control. Treatment of LID requires careful history taking and clinical examination to find the type of dyskinesia as different approach is required for different types. Changes in dopaminergic medication including continuous dopaminergic stimulation are very helpful in the management of peak-dose dyskinesia. Different types of surgical approaches including unilateral pallidotomy and deep brain stimulation have given very good result in patients, who cannot be managed by medications alone. The surgical management of LID is dealt with in detail in another review in this series. PMID:28904447

Neurobehavioral and neurometabolic (SPECT) correlates of paranormal information: involvement of the right hemisphere and its sensitivity to weak complex magnetic fields.

PubMed

Roll, W G; Persinger, M A; Webster, D L; Tiller, S G; Cook, C M

2002-02-01

Experiments were designed to help elucidate the neurophysiological correlates for the experiences reported by Sean Harribance. For most of his life he has routinely experienced "flashes of images" of objects that were hidden and of accurate personal information concerning people with whom he was not familiar. The specificity of details for target pictures of people was correlated positively with the proportion of occipital alpha activity. Results from a complete neuropsychological assessment, Single Photon Emission Computed Tomography (SPECT), and screening electroencephalography suggested that his experiences were associated with increased activity within the parietal lobe and occipital regions of the right hemisphere. Sensed presences (subjectively localized to his left side) were evoked when weak, magnetic fields, whose temporal structure simulated long-term potentiation in the hippocampus, were applied over his right temporoparietal lobes. These results suggest that the phenomena attributed to paranormal or "extrasensory" processes are correlated quantitatively with morphological and functional anomalies involving the right parietotemporal cortices (or its thalamic inputs) and the hippocampal formation.

Reticular influences on primary and augmenting responses in the somatosensory cortex.

PubMed

Steriade, M; Morin, D

1981-01-26

The effects of brief, conditioning trains of high-frequency pulses to the midbrain reticular formation (RF) on primary and augmenting responses of somatosensory (SI) cortex were investigated. Testing stimulation was applied to the ventrobasal (VB) thalamus or to the white matter (WM) beneath SI in VB-lesioned animals. The RF-elicited EEG activation was associated with increased firing rates of SI neurons, enhanced probability of early synaptic discharges to VB or WM stimuli, and significantly reduced duration of the suppressed firing period following an afferent VB or WM volley. The diminished latency of the postinhibitory rebound under RF stimulation had the consequence that, within 10/sec shock-train, the second stimulus was delivered following completion of the rebound component and, instead of an augmented potential, generated a field response of primary-type. The dependence of the RF-induced change in augmenting potentials upon the sharpening effect exerted on the preceding inhibitory-rebound sequence was corroborated by analyzing the RF influence on neurons with different time-course of recovery from inhibition. The replacement of augmenting potentials by primary responses under RF stimulation is advanced as the mechanism behind the obliteration of spontaneously developing 'type I' spindle-waves during EEG arousal. The demonstration of RF influences on SI responses to WM stimulation in VB-lesioned animals points out the cortical level of the effects. The reticulo-thalamo-cortical pathways underlying these influences are discussed.