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Journal of Affective Disorders Reports Jan 2023Bipolar disorder (BD) is a chronic multifactorial disorder that presents with cognitive impairment as one of its main features, in patients as well as in their...
BACKGROUND
Bipolar disorder (BD) is a chronic multifactorial disorder that presents with cognitive impairment as one of its main features, in patients as well as in their first-degree relatives. However, the profile of cognitive dysfunction in BD patients and their relatives is not yet well defined. Various neurocognitive deficits have been proposed as endophenotypes for BD. In the present study, we explored the susceptibility to neurocognitive deficits in BD patients and their siblings compared to healthy controls.
METHOD
A sample consisting of patients diagnosed with BD (=37), their unaffected siblings (=30) and a healthy control group (=39) was assessed using the Brief Assessment of Cognition for Affective Disorders (BAC-A) battery of tests in various cognitive domains: memory, processing speed, working memory, reasoning and problem solving, and affective processing.
RESULTS
Compared to healthy controls, BD patients and their unaffected siblings showed deficits in attention and motor speed, or processing speed as measured by the Symbol coding task ( = 0.008), as well as a similar degree of impairment ( = 1.000).
LIMITATIONS
The lack of statistically significant findings in the other cognitive domains could be related to differences in task difficulty. Most patients were taking psychotropic medication with varying effects on cognition and being treated as outpatients, implying a currently higher level of functioning, which may limit extrapolation of the sample to the general population of BD patients.
CONCLUSIONS
These results support the view of considering processing speed as an endophenotype for bipolar disorder.
PubMed: 36844417
DOI: 10.1016/j.jadr.2022.100459 -
Neurobiology of Disease Apr 2023Neuromodulation (neurostimulation) is a relatively new and rapidly growing treatment for refractory epilepsy. Three varieties are approved in the US: vagus nerve... (Review)
Review
Neuromodulation (neurostimulation) is a relatively new and rapidly growing treatment for refractory epilepsy. Three varieties are approved in the US: vagus nerve stimulation (VNS), deep brain stimulation (DBS) and responsive neurostimulation (RNS). This article reviews thalamic DBS for epilepsy. Among many thalamic sub-nuclei, DBS for epilepsy has been targeted to the anterior nucleus (ANT), centromedian nucleus (CM), dorsomedial nucleus (DM) and pulvinar (PULV). Only ANT is FDA-approved, based upon a controlled clinical trial. Bilateral stimulation of ANT reduced seizures by 40.5% at three months in the controlled phase (p = .038) and 75% by 5 years in the uncontrolled phase. Side effects related to paresthesias, acute hemorrhage, infection, occasional increased seizures, and usually transient effects on mood and memory. Efficacy was best documented for focal onset seizures in temporal or frontal lobe. CM stimulation may be useful for generalized or multifocal seizures and PULV for posterior limbic seizures. Mechanisms of DBS for epilepsy are largely unknown, but animal work points to changes in receptors, channels, neurotransmitters, synapses, network connectivity and neurogenesis. Personalization of therapies, in terms of connectivity of the seizure onset zone to the thalamic sub- nucleus and individual characteristics of the seizures, might lead to improved efficacy. Many questions remain about DBS, including the best candidates for different types of neuromodulation, the best targets, the best stimulation parameters, how to minimize side effects and how to deliver current noninvasively. Despite the questions, neuromodulation provides useful new opportunities to treat people with refractory seizures not responding to medicines and not amenable to resective surgery.
Topics: Animals; Deep Brain Stimulation; Epilepsy; Thalamus; Seizures; Drug Resistant Epilepsy
PubMed: 36809846
DOI: 10.1016/j.nbd.2023.106045 -
Current Opinion in Neurology Apr 2023Neurostimulation is a quickly growing treatment approach for epilepsy patients. We summarize recent approaches to provide a perspective on the future of neurostimulation. (Review)
Review
PURPOSE OF REVIEW
Neurostimulation is a quickly growing treatment approach for epilepsy patients. We summarize recent approaches to provide a perspective on the future of neurostimulation.
RECENT FINDINGS
Invasive stimulation for treatment of focal epilepsy includes vagus nerve stimulation, responsive neurostimulation of the cortex and deep brain stimulation of the anterior nucleus of the thalamus. A wide range of other targets have been considered, including centromedian, central lateral and pulvinar thalamic nuclei; medial septum, nucleus accumbens, subthalamic nucleus, cerebellum, fornicodorsocommissure and piriform cortex. Stimulation for generalized onset seizures and mixed epilepsies as well as increased efforts focusing on paediatric populations have emerged. Hardware with more permanently implanted lead options and sensing capabilities is emerging. A wider variety of programming approaches than typically used may improve patient outcomes. Finally, noninvasive brain stimulation with its favourable risk profile offers the potential to treat increasingly diverse epilepsy patients.
SUMMARY
Neurostimulation for the treatment of epilepsy is surprisingly varied. Flexibility and reversibility of neurostimulation allows for rapid innovation. There remains a continued need for excitability biomarkers to guide treatment and innovation. Neurostimulation, a part of bioelectronic medicine, offers distinctive benefits as well as unique challenges.
Topics: Child; Humans; Deep Brain Stimulation; Epilepsy; Seizures; Cerebral Cortex; Thalamus
PubMed: 36762660
DOI: 10.1097/WCO.0000000000001138 -
ELife Jan 2023Even during sustained attention, enhanced processing of attended stimuli waxes and wanes rhythmically, with periods of enhanced and relatively diminished visual...
Even during sustained attention, enhanced processing of attended stimuli waxes and wanes rhythmically, with periods of enhanced and relatively diminished visual processing (and subsequent target detection) alternating at 4 or 8 Hz in a sustained visual attention task. These alternating attentional states occur alongside alternating dynamical states, in which lateral intraparietal cortex (LIP), the frontal eye field (FEF), and the mediodorsal pulvinar (mdPul) exhibit different activity and functional connectivity at α, β, and γ frequencies-rhythms associated with visual processing, working memory, and motor suppression. To assess whether and how these multiple interacting rhythms contribute to periodicity in attention, we propose a detailed computational model of FEF and LIP. When driven by θ-rhythmic inputs simulating experimentally-observed mdPul activity, this model reproduced the rhythmic dynamics and behavioral consequences of observed attentional states, revealing that the frequencies and mechanisms of the observed rhythms allow for peak sensitivity in visual target detection while maintaining functional flexibility.
Topics: Visual Perception; Cerebral Cortex; Frontal Lobe; Theta Rhythm; Periodicity; Photic Stimulation
PubMed: 36718998
DOI: 10.7554/eLife.67684 -
BioRxiv : the Preprint Server For... Apr 2023Investigators in neuroscience have turned to Big Data to address replication and reliability issues by increasing sample sizes, statistical power, and representativeness...
Investigators in neuroscience have turned to Big Data to address replication and reliability issues by increasing sample sizes, statistical power, and representativeness of data. These efforts unveil new questions about integrating data arising from distinct sources and instruments. We focus on the most frequently assessed cognitive domain - memory testing - and demonstrate a process for reliable data harmonization across three common measures. We aggregated global raw data from 53 studies totaling N = 10,505 individuals. A mega-analysis was conducted using empirical bayes harmonization to remove site effects, followed by linear models adjusting for common covariates. A continuous item response theory (IRT) model estimated each individual's latent verbal learning ability while accounting for item difficulties. Harmonization significantly reduced inter-site variance while preserving covariate effects, and our conversion tool is freely available online. This demonstrates that large-scale data sharing and harmonization initiatives can address reproducibility and integration challenges across the behavioral sciences.
PubMed: 36712107
DOI: 10.1101/2023.01.16.524331 -
Human Brain Mapping Apr 2023Cross-modal plasticity in blind individuals has been reported over the past decades showing that nonvisual information is carried and processed by "visual" brain...
Cross-modal plasticity in blind individuals has been reported over the past decades showing that nonvisual information is carried and processed by "visual" brain structures. However, despite multiple efforts, the structural underpinnings of cross-modal plasticity in congenitally blind individuals remain unclear. We mapped thalamocortical connectivity and assessed the integrity of white matter of 10 congenitally blind individuals and 10 sighted controls. We hypothesized an aberrant thalamocortical pattern of connectivity taking place in the absence of visual stimuli from birth as a potential mechanism of cross-modal plasticity. In addition to the impaired microstructure of visual white matter bundles, we observed structural connectivity changes between the thalamus and occipital and temporal cortices. Specifically, the thalamic territory dedicated to connections with the occipital cortex was smaller and displayed weaker connectivity in congenitally blind individuals, whereas those connecting with the temporal cortex showed greater volume and increased connectivity. The abnormal pattern of thalamocortical connectivity included the lateral and medial geniculate nuclei and the pulvinar nucleus. For the first time in humans, a remapping of structural thalamocortical connections involving both unimodal and multimodal thalamic nuclei has been demonstrated, shedding light on the possible mechanisms of cross-modal plasticity in humans. The present findings may help understand the functional adaptations commonly observed in congenitally blind individuals.
Topics: Humans; Blindness; Occipital Lobe; Thalamus; Temporal Lobe; Geniculate Bodies
PubMed: 36661404
DOI: 10.1002/hbm.26192 -
The Journal of Neuroscience : the... Feb 2023Distributed cortical regions show differential responses to visual objects belonging to different domains varying by animacy (e.g., animals vs tools), yet it remains...
Distributed cortical regions show differential responses to visual objects belonging to different domains varying by animacy (e.g., animals vs tools), yet it remains unclear whether this is an organization principle also applying to the subcortical structures. Combining multiple fMRI activation experiments (two main experiments and six validation datasets; 12 females and 9 males in the main Experiment 1; 10 females and 10 males in the main Experiment 2), resting-state functional connectivity, and task-based dynamic causal modeling analysis in human subjects, we found that visual processing of images of animals and tools elicited different patterns of response in the pulvinar, with robust left lateralization for tools, and distinct, bilateral (with rightward tendency) clusters for animals. Such domain-preferring activity distribution in the pulvinar was associated with the magnitude with which the voxels were intrinsically connected with the corresponding domain-preferring regions in the cortex. The pulvinar-to-right-amygdala path showed a one-way shortcut supporting the perception of animals, and the modulation connection from pulvinar to parietal showed an advantage to the perception of tools. These results incorporate the subcortical regions into the object processing network and highlight that domain organization appears to be an overarching principle across various processing stages in the brain. Viewing objects belonging to different domains elicited different cortical regions, but whether the domain organization applied to the subcortical structures (e.g., pulvinar) was unknown. Multiple fMRI activation experiments revealed that object pictures belonging to different domains elicited differential patterns of response in the pulvinar, with robust left lateralization for tool pictures, and distinct, bilateral (with rightward tendency) clusters for animals. Combining the resting-state functional connectivity and dynamic causal modeling analysis on task-based fMRI data, we found domain-preferring activity distribution in the pulvinar aligned with that in cortical regions. These results highlight the need for coherent visual theories that explain the mechanisms underlying the domain organization across various processing stages.
Topics: Male; Female; Animals; Humans; Pulvinar; Magnetic Resonance Imaging; Brain; Brain Mapping; Amygdala
PubMed: 36596697
DOI: 10.1523/JNEUROSCI.0613-22.2022 -
NeuroImage Feb 2023Selective attention mechanisms operate across large-scale cortical networks by amplifying behaviorally relevant sensory information while suppressing interference from...
Selective attention mechanisms operate across large-scale cortical networks by amplifying behaviorally relevant sensory information while suppressing interference from distractors. Although it is known that fronto-parietal regions convey information about attentional priorities, it is unclear how such cortical communication is orchestrated. Based on its unique connectivity pattern with the cortex, we hypothesized that the pulvinar, a nucleus of the thalamus, may play a key role in coordinating and modulating remote cortical activity during selective attention. By using a visual task that orthogonally manipulated top-down selection and bottom-up competition during functional MRI, we investigated the modulations induced by task-relevant (spatial cue) and task-irrelevant but salient (distractor) stimuli on functional interactions between the pulvinar, occipito-temporal cortex, and frontoparietal areas involved in selective attention. Pulvinar activity and connectivity were distinctively modulated during the co-occurrence of the cue and salient distractor stimuli, as opposed to the presence of one of these factors alone. Causal modelling analysis further indicated that the pulvinar acted by weighting excitatory signals to cortical areas, predominantly in the presence of both the cue and the distractor. These results converge to support a pivotal role of the pulvinar in integrating top-down and bottom-up signals among distributed networks when confronted with conflicting visual stimuli, and thus contributing to shape priority maps for the guidance of attention.
Topics: Humans; Pulvinar; Thalamus; Parietal Lobe; Frontal Lobe; Magnetic Resonance Imaging
PubMed: 36572132
DOI: 10.1016/j.neuroimage.2022.119832 -
Current Biology : CB Dec 2022Eye movements cause rapid motion of the retinal image, potentially confusable with external motion. A recent study shows that neurons in mouse primary visual cortex...
Eye movements cause rapid motion of the retinal image, potentially confusable with external motion. A recent study shows that neurons in mouse primary visual cortex distinguish self-generated from external motion by combining sensory input with saccade-related signals from the thalamic pulvinar nucleus.
Topics: Animals; Mice; Eye Movements; Saccades; Neurons; Perception; Motion Perception; Photic Stimulation; Visual Perception
PubMed: 36538882
DOI: 10.1016/j.cub.2022.11.003 -
Communications Biology Dec 2022Attention is a core cognitive function that filters and selects behaviourally relevant information in the environment. The cortical mapping of attentional systems...
Attention is a core cognitive function that filters and selects behaviourally relevant information in the environment. The cortical mapping of attentional systems identified two segregated networks that mediate stimulus-driven and goal-driven processes, the Ventral and the Dorsal Attention Networks (VAN, DAN). Deep brain electrophysiological recordings, behavioral data from phylogenetic distant species, and observations from human brain pathologies challenge purely corticocentric models. Here, we used advanced methods of functional alignment applied to resting-state functional connectivity analyses to map the subcortical architecture of the Ventral and Dorsal Attention Networks. Our investigations revealed the involvement of the pulvinar, the superior colliculi, the head of caudate nuclei, and a cluster of brainstem nuclei relevant to both networks. These nuclei are densely connected structural network hubs, as revealed by diffusion-weighted imaging tractography. Their projections establish interrelations with the acetylcholine nicotinic receptor as well as dopamine and serotonin transporters, as demonstrated in a spatial correlation analysis with a normative atlas of neurotransmitter systems. This convergence of functional, structural, and neurochemical evidence provides a comprehensive framework to understand the neural basis of attention across different species and brain diseases.
Topics: Humans; Phylogeny
PubMed: 36477440
DOI: 10.1038/s42003-022-04281-0