Thalamocortical Spectral Transmission Relies on Balanced Input Strengths

The thalamus is a key element of sensory transmission in the brain, as it gates and selects sensory streams through a modulation of its internal activity. A preponderant role in these functions is played by its internal activity in the alpha range ([8–14] Hz), but the mechanism underlying this process is not completely understood. In particular, how do thalamocortical connections convey stimulus driven information selectively over the back-ground of thalamic internally generated activity? Here we investigate this issue with a spiking network model of feedforward connectivity between thalamus and primary sensory cortex reproducing the local field potential of both areas. We found that in a feedforward network, thalamic oscillations in the alpha range do not entrain cortical activity for two reasons: (i) alpha range oscillations are weaker in neurons projecting to the cortex, (ii) the gamma resonance dynamics of cortical networks hampers oscillations over the 10–20 Hz range thus weakening alpha range oscillations. This latter mechanism depends on the balance of the strength of thalamocortical connections toward excitatory and inhibitory neurons in the cortex. Our results highlight the relevance of corticothalamic feedback to sustain alpha range oscillations and pave the way toward an integrated understanding of the sensory streams traveling between the periphery and the cortex.

Individualized Thalamic Parcellation Reveals Alterations in Shape and Microstructure of Thalamic Nuclei in Patients with Disorder of Consciousness

The thalamus plays crucial roles in consciousness generation and information processing. Previous evidence suggests that disorder of consciousness (DOC) caused by severe brain injury, is potentially related to thalamic abnormalities. However, how the morphology and microstructure change in thalamic subfields and thalamocortical fiber pathways in patients with DOC, and the relationships between these changes and the consciousness status remain unclear. Here, we generated the individual-specific thalamic parcellation in 10 DOC patients and 10 healthy controls (HC) via a novel thalamic segmentation framework based on the fiber orientation distribution (FOD) derived from 7-Tesla diffusion MRI, and investigated the shape deformation of thalamic nuclei as well as the microstructural changes associated with thalamic nuclei and thalamocortical pathways in patients with DOC. Enlargement of dorsal posterior nucleus and atrophy of anterior nucleus in the right thalamus were observed in DOC cohort relative to the HCs, and the former was closely linked to the consciousness level of the patients. We also found significant reductions of fiber density, but not fiber bundle cross-section, within several thalamic nuclei and most of the thalamocortical fiber pathways, suggesting that loss of axons might take primary responsibility for the impaired thalamocortical connections in patients with DOC rather than the change in fiber-bundle morphology. Furthermore, the individual-specific thalamic parcellation achieved 80% accuracy in classifying patients at the minimally conscious state from the vegetative state, compared to around 60% accuracy based on group-level parcellations. Our findings provide the first evidence for the shape deformation of thalamic nuclei in DOC patients and the microstructural basis of the disrupted thalamocortical connections.

Thalamocortical spectral transmission relies on balanced input strengths

The thalamus is a key element of sensory transmission in the brain, as all sensory information is processed by the thalamus before reaching the cortex. The thalamus is known to gate and select sensory streams through a modulation of its internal activity in which spindle oscillations play a preponderant role, but the mechanism underlying this process is not completely understood. In particular, how do thalamocortical connections convey stimulus-driven information selectively over the background of thalamic internally generated activity (such as spindle oscillations)? Here we investigate this issue with a spiking network model of connectivity between thalamus and primary sensory cortex reproducing the local field potential of both areas. We found two features of the thalamocortical dynamics that filter out spindle oscillations: i) spindle oscillations are weaker in neurons projecting to the cortex, ii) the resonance dynamics of cortical networks selectively blocks frequency in the range encompassing spindle oscillations. This latter mechanism depends on the balance of the strength of thalamocortical connections toward excitatory and inhibitory neurons in the cortex. Our results pave the way toward an integrated understanding of the sensory streams traveling between the periphery and the cortex.

Disrupted basal ganglia–thalamocortical loops in focal to bilateral tonic-clonic seizures

Focal to bilateral tonic-clonic seizures are associated with lower quality of life, higher risk of seizure-related injuries, increased chance of sudden unexpected death, and unfavourable treatment outcomes. Achieving greater understanding of their underlying circuitry offers better opportunity to control these seizures. Towards this goal, we provide a network science perspective of the interactive pathways among basal ganglia, thalamus and cortex, to explore the imprinting of secondary seizure generalization on the mesoscale brain network in temporal lobe epilepsy. Specifically, we parameterized the functional organization of both the thalamocortical network and the basal ganglia–thalamus network with resting state functional MRI in three groups of patients with different focal to bilateral tonic-clonic seizure histories. Using the participation coefficient to describe the pattern of thalamocortical connections among different cortical networks, we showed that, compared to patients with no previous history, those with positive histories of focal to bilateral tonic-clonic seizures, including both remote (none for >1 year) and current (within the past year) histories, presented more uniform distribution patterns of thalamocortical connections in the ipsilateral medial-dorsal thalamic nuclei. As a sign of greater thalamus-mediated cortico-cortical communication, this result comports with greater susceptibility to secondary seizure generalization from the epileptogenic temporal lobe to broader brain networks in these patients. Using interregional integration to characterize the functional interaction between basal ganglia and thalamus, we demonstrated that patients with current history presented increased interaction between putamen and globus pallidus internus, and decreased interaction between the latter and the thalamus, compared to the other two patient groups. Importantly, through a series of ‘disconnection’ simulations, we showed that these changes in interactive profiles of the basal ganglia–thalamus network in the current history group mainly depended upon the direct but not the indirect basal ganglia pathway. It is intuitively plausible that such disruption in the striatum-modulated tonic inhibition of the thalamus from the globus pallidus internus could lead to an under-suppressed thalamus, which in turn may account for their greater vulnerability to secondary seizure generalization. Collectively, these findings suggest that the broken balance between basal ganglia inhibition and thalamus synchronization can inform the presence and effective control of focal to bilateral tonic-clonic seizures. The mechanistic underpinnings we uncover may shed light on the development of new treatment strategies for patients with temporal lobe epilepsy.

Disrupted basal ganglia—thalamocortical loops in focal to bilateral tonic-clonic seizures

Focal to bilateral tonic-clonic seizures are associated with lower quality of life, higher risk of seizure-related injuries, increased chance of sudden unexpected death, as well as unfavorable treatment outcomes. Achieving greater understanding of its underlying circuitry offers better opportunity to control these particularly serious seizures. Towards this goal, we provide a network science perspective of the interactive pathways among basal ganglia, thalamus and the cortex, to explore the imprinting of secondary seizure generalization on the mesoscale brain network in temporal lobe epilepsy. Specifically, we parameterized the functional organization of both the thalamocortical network and the basal ganglia—thalamus network with resting-state functional magnetic resonance imaging in three groups of patients with different focal to bilateral tonic-clonic seizure histories. Using the participation coefficient to describe the pattern of thalamocortical connections among different cortical networks, we showed that, compared to patients with no previous history, those with positive histories of focal to bilateral tonic-clonic seizures, including both remote (none for over one year) and current (within the past year) histories, presented more uniform distribution patterns of thalamocortical connections in the ipsilateral medial-dorsal thalamic nuclei. As a sign of greater thalamus mediated cortico-cortical communication, this result comports with greater susceptibility to secondary seizure generalization from the epileptogenic temporal lobe to broader brain networks in these patients. Using interregional integration to characterize the functional interaction between basal ganglia and thalamus, we demonstrated that patients with current history presented increased interaction between putamen and globus pallidus internus, and decreased interaction between the latter and the thalamus, compared to the other two patient groups. Importantly, through a series of “disconnection” simulations, we showed that these changes in interactive profiles of the basal ganglia—thalamus network in the current history group mainly depended upon the direct but not the indirect basal ganglia pathway. It is intuitively plausible that such disruption in the striatum modulated tonic inhibition of the thalamus from the globus pallidus internus could lead to an under-suppressed thalamus, which in turn may account for their greater vulnerability to secondary seizure generalization. Collectively, these findings suggest that the broken balance between the basal ganglia inhibition and thalamus synchronization can inform the presence and effective control of focal to bilateral tonic-clonic seizures. The mechanistic underpinnings we uncover may shed light on the development of new treatment strategies for patients with temporal lobe epilepsy.