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Journal of Movement Disorders Jan 2017Here we argue functional neuroanatomy for posture-gait control. Multi-sensory information such as somatosensory, visual and vestibular sensation act on various areas of... (Review)
Review
Here we argue functional neuroanatomy for posture-gait control. Multi-sensory information such as somatosensory, visual and vestibular sensation act on various areas of the brain so that adaptable posture-gait control can be achieved. Automatic process of gait, which is steady-state stepping movements associating with postural reflexes including headeye coordination accompanied by appropriate alignment of body segments and optimal level of postural muscle tone, is mediated by the descending pathways from the brainstem to the spinal cord. Particularly, reticulospinal pathways arising from the lateral part of the mesopontine tegmentum and spinal locomotor network contribute to this process. On the other hand, walking in unfamiliar circumstance requires cognitive process of postural control, which depends on knowledges of self-body, such as body schema and body motion in space. The cognitive information is produced at the temporoparietal association cortex, and is fundamental to sustention of vertical posture and construction of motor programs. The programs in the motor cortical areas run to execute anticipatory postural adjustment that is optimal for achievement of goal-directed movements. The basal ganglia and cerebellum may affect both the automatic and cognitive processes of posturegait control through reciprocal connections with the brainstem and cerebral cortex, respectively. Consequently, impairments in cognitive function by damages in the cerebral cortex, basal ganglia and cerebellum may disturb posture-gait control, resulting in falling.
PubMed: 28122432
DOI: 10.14802/jmd.16062 -
Nature Neuroscience Jan 2020Theories stipulate that memories are encoded within networks of cortical projection neurons. Conversely, GABAergic interneurons are thought to function primarily to...
Theories stipulate that memories are encoded within networks of cortical projection neurons. Conversely, GABAergic interneurons are thought to function primarily to inhibit projection neurons and thereby impose network gain control, an important but purely modulatory role. Here we show in male mice that associative fear learning potentiates synaptic transmission and cue-specific activity of medial prefrontal cortex somatostatin (SST) interneurons and that activation of these cells controls both memory encoding and expression. Furthermore, the synaptic organization of SST and parvalbumin interneurons provides a potential circuit basis for SST interneuron-evoked disinhibition of medial prefrontal cortex output neurons and recruitment of remote brain regions associated with defensive behavior. These data suggest that, rather than constrain mnemonic processing, potentiation of SST interneuron activity represents an important causal mechanism for conditioned fear.
Topics: Animals; Association Learning; Fear; Interneurons; Male; Memory; Mice; Mice, Inbred C57BL; Prefrontal Cortex; Somatostatin; Synaptic Transmission
PubMed: 31844314
DOI: 10.1038/s41593-019-0552-7 -
Frontiers in Neuroscience 2023Accumulating evidence of clinical and neuroimaging studies indicated that migraine is related to brain structural alterations. However, it is still not clear whether the...
BACKGROUND
Accumulating evidence of clinical and neuroimaging studies indicated that migraine is related to brain structural alterations. However, it is still not clear whether the associations of brain structural alterations with migraine are likely to be causal, or could be explained by reverse causality confounding.
METHODS
We carried on a bidirectional Mendelian randomization analysis in order to identify the causal relationship between brain structures and migraine risk. Summary-level data and independent variants used as instruments came from large genome-wide association studies of total surface area and average thickness of cortex (33,992 participants), gray matter volume (8,428 participants), white matter hyperintensities (50,970 participants), hippocampal volume (33,536 participants), and migraine (102,084 cases and 771,257 controls).
RESULTS
We identified suggestive associations of the decreased surface area (OR = 0.85; 95% CI, 0.75-0.96; = 0.007), and decreased hippocampal volume (OR = 0.74; 95% CI, 0.55-1.00; = 0.047) with higher migraine risk. We did not find any significant association of gray matter volume, cortical thickness, or white matter hyperintensities with migraine. No evidence supporting the significant association was found in the reverse MR analysis.
CONCLUSION
We provided suggestive evidence that surface area and hippocampal volume are causally associated with migraine risk.
PubMed: 36937660
DOI: 10.3389/fnins.2023.1148458 -
Behavioral Neuroscience Apr 2019Occasion setting refers to the ability of 1 stimulus, an occasion setter, to modulate the efficacy of the association between another, conditioned stimulus (CS) and an... (Review)
Review
Occasion setting refers to the ability of 1 stimulus, an occasion setter, to modulate the efficacy of the association between another, conditioned stimulus (CS) and an unconditioned stimulus (US) or reinforcer. Occasion setters and simple CSs are readily distinguished. For example, occasion setters are relatively immune to extinction and counterconditioning, and their combination and transfer functions differ substantially from those of simple CSs. Similarly, the acquisition of occasion setting is favored when stimuli are separated by longer intervals, by empty trace intervals, and are of different modalities, whereas the opposite conditions typically favor the acquisition of simple associations. Furthermore, the simple conditioning and occasion setting properties of a single stimulus can be independent, for example, that stimulus may simultaneously predict the occurrence of a reinforcer and indicate that another stimulus will not be reinforced. Many behavioral phenomena that are intractable to simple associative analysis are better understood within an occasion setting framework. Besides capturing the distinction between direct and modulatory control common to many arenas in neuroscience, occasion setting provides a model for the hierarchical organization of memory for events and event relations, and for contextual control more broadly. Although early lesion studies further differentiated between occasion setting and simple conditioning functions, little is known about the neurobiology of occasion setting. Modern techniques for precise manipulation and monitoring of neuronal activity in multiple brain regions are ideally suited for disentangling contributions of simple conditioning and occasion setting in associative learning. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Topics: Animals; Association Learning; Basolateral Nuclear Complex; Brain; Conditioning, Psychological; Cues; Discrimination Learning; Extinction, Psychological; Humans; Models, Neurological; Models, Psychological; Motivation; Neural Pathways; Nucleus Accumbens; Prefrontal Cortex; Transfer, Psychology
PubMed: 30907616
DOI: 10.1037/bne0000306 -
Neuropsychopharmacology : Official... Jan 2016Fear conditioning has been commonly used as a model of emotional learning in animals and, with the introduction of functional neuroimaging techniques, has proven useful... (Review)
Review
Fear conditioning has been commonly used as a model of emotional learning in animals and, with the introduction of functional neuroimaging techniques, has proven useful in establishing the neurocircuitry of emotional learning in humans. Studies of fear acquisition suggest that regions such as amygdala, insula, anterior cingulate cortex, and hippocampus play an important role in acquisition of fear, whereas studies of fear extinction suggest that the amygdala is also crucial for safety learning. Extinction retention testing points to the ventromedial prefrontal cortex as an essential region in the recall of the safety trace, and explicit learning of fear and safety associations recruits additional cortical and subcortical regions. Importantly, many of these findings have implications in our understanding of the pathophysiology of psychiatric disease. Recent studies using clinical populations have lent insight into the changes in regional activity in specific disorders, and treatment studies have shown how pharmaceutical and other therapeutic interventions modulate brain activation during emotional learning. Finally, research investigating individual differences in neurotransmitter receptor genotypes has highlighted the contribution of these systems in fear-associated learning.
Topics: Amygdala; Animals; Association Learning; Brain; Brain Mapping; Extinction, Psychological; Fear; Gyrus Cinguli; Hippocampus; Humans; Nerve Net; Neuroimaging; Panic Disorder; Prefrontal Cortex
PubMed: 26294108
DOI: 10.1038/npp.2015.255 -
Frontiers in Systems Neuroscience 2020The traditional cerebellum's role has been linked to the high computational demands for sensorimotor control. However, several findings have pointed to its involvement... (Review)
Review
The traditional cerebellum's role has been linked to the high computational demands for sensorimotor control. However, several findings have pointed to its involvement in executive and emotional functions in the last decades. First in 2009 and then, in 2016, we raised why we should consider the cerebellum when thinking about drug addiction. A decade later, mounting evidence strongly suggests the cerebellar involvement in this disorder. Nevertheless, direct evidence is still partial and related mainly to drug-induced reward memory, but recent results about cerebellar functions may provide new insights into its role in addiction. The present review does not intend to be a compelling revision on available findings, as we did in the two previous reviews. This minireview focuses on specific findings of the cerebellum's role in drug-related reward memories and the way ahead for future research. The results discussed here provide grounds for involving the cerebellar cortex's apical region in regulating behavior driven by drug-cue associations. They also suggest that the cerebellar cortex dysfunction may facilitate drug-induced learning by increasing glutamatergic output from the deep cerebellar nucleus (DCN) to the ventral tegmental area (VTA) and neural activity in its projecting areas.
PubMed: 33192350
DOI: 10.3389/fnsys.2020.586574 -
Neuron Aug 2019The paraventricular thalamus (PVT) is an interface for brain reward circuits, with input signals arising from structures, such as prefrontal cortex and hypothalamus,...
The paraventricular thalamus (PVT) is an interface for brain reward circuits, with input signals arising from structures, such as prefrontal cortex and hypothalamus, that are broadcast to downstream limbic targets. However, the precise synaptic connectivity, activity, and function of PVT circuitry for reward processing are unclear. Here, using in vivo two-photon calcium imaging, we find that PVT neurons projecting to the nucleus accumbens (PVT-NAc) develop inhibitory responses to reward-predictive cues coding for both cue-reward associative information and behavior. The multiplexed activity in PVT-NAc neurons is directed by opposing activity patterns in prefrontal and lateral hypothalamic afferent axons. Further, we find that prefrontal cue encoding may maintain accurate cue-reward processing, as optogenetic disruption of this encoding induced long-lasting effects on downstream PVT-NAc cue responses and behavioral cue discrimination. Together, these data reveal that PVT-NAc neurons act as an interface for reward processing by integrating relevant inputs to accurately inform reward-seeking behavior.
Topics: Animals; Association Learning; Conditioning, Classical; Craving; Cues; Glutamic Acid; Hypothalamic Area, Lateral; Mice; Midline Thalamic Nuclei; Neural Pathways; Neurons; Optogenetics; Patch-Clamp Techniques; Prefrontal Cortex; Reward; gamma-Aminobutyric Acid
PubMed: 31196673
DOI: 10.1016/j.neuron.2019.05.018 -
Complex Psychiatry Sep 2022Genome-wide association studies (GWAS) have played a critical role in identifying many thousands of loci associated with complex phenotypes and diseases. This has led to...
INTRODUCTION
Genome-wide association studies (GWAS) have played a critical role in identifying many thousands of loci associated with complex phenotypes and diseases. This has led to several translations of novel disease susceptibility genes into drug targets and care. This however has not been the case for analyses where sample sizes are small, which suffer from multiple comparisons testing. The present study examined the statistical impact of combining a burden test methodology, PrediXcan, with a multimodel meta-analysis, cross phenotype association (CPASSOC).
METHODS
The analysis was conducted on 5 addiction traits: family alcoholism, cannabis craving, alcohol, nicotine, and cannabis dependence and 10 brain tissues: anterior cingulate cortex BA24, cerebellar hemisphere, cortex, hippocampus, nucleus accumbens basal ganglia, caudate basal ganglia, cerebellum, frontal cortex BA9, hypothalamus, and putamen basal ganglia. Our sample consisted of 1,640 participants from the University of California, San Francisco (UCSF) Family Alcoholism Study. Genotypes were obtained through low pass whole genome sequencing and the use of Thunder, a linkage disequilibrium variant caller.
RESULTS
The post-PrediXcan, gene-phenotype association without aggregation resulted in 2 significant results, and . Aggregating across phenotypes resulted no significant findings. Aggregating across tissues resulted in 15 significant and 5 suggestive associations: and ; , and respectively.
DISCUSSION
Given the relatively small size of the cohort, this multimodel approach was able to find over a dozen significant associations between predicted gene expression and addiction traits. Of our findings, 8 had prior associations with similar phenotypes through investigation of the GWAS Atlas. With the onset of improved transcriptome data, this approach should increase in efficacy.
PubMed: 36407771
DOI: 10.1159/000523748 -
Trends in Neurosciences Mar 2015The study of neurobiological mechanisms underlying anxiety disorders has been shaped by learning models that frame anxiety as maladaptive learning. Pavlovian... (Review)
Review
The study of neurobiological mechanisms underlying anxiety disorders has been shaped by learning models that frame anxiety as maladaptive learning. Pavlovian conditioning and extinction are particularly influential in defining learning stages that can account for symptoms of anxiety disorders. Recently, dynamic and task related communication between the basolateral complex of the amygdala (BLA) and the medial prefrontal cortex (mPFC) has emerged as a crucial aspect of successful evaluation of threat and safety. Ongoing patterns of neural signaling within the mPFC-BLA circuit during encoding, expression and extinction of adaptive learning are reviewed. The mechanisms whereby deficient mPFC-BLA interactions can lead to generalized fear and anxiety are discussed in learned and innate anxiety. Findings with cross-species validity are emphasized.
Topics: Amygdala; Animals; Association Learning; Humans; Mental Recall; Neural Pathways; Prefrontal Cortex
PubMed: 25583269
DOI: 10.1016/j.tins.2014.12.007