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Acta Neurobiologiae Experimentalis 2016Fear-conditioning is one of the most widely used paradigms in attempts to unravel the processes and mechanisms underlying learning and plasticity. In most of the... (Review)
Review
Fear-conditioning is one of the most widely used paradigms in attempts to unravel the processes and mechanisms underlying learning and plasticity. In most of the Pavlovian conditioning paradigms auditory stimulus is used as a conditioned stimulus (CS), but conditioning can be accomplished also to tactile CS. The whisker-to-barrel tactile system in mice offers convenient way to investigate the brain pathways and mechanisms of learning, and plasticity of the brain cortex. To support a claim that an animal learns during conditioning session and that the plastic changes are associative in nature, objective measures of behavior are necessary. Multiple types of conditioned responses can develop, depending on the training situation, CS and unconditioned stimulus (UCS) characteristics. These include physiological responses, such as salivation, heart rate, galvanic skin reaction, and also behavioral responses, such as startle reflex potentiation or suppression of the ongoing behavior. When studying learning with the whisker system in behaving mice, stimulation of individual whiskers in a well-controlled manner may require animal restrain with a disadvantage of only limited behavioral responses observed. Stimulation of whiskers in the neck-restraining apparatus evokes head movements. When whiskers stimulation (CS) is paired with an aversive UCS during conditioning, the head movements decrease in the course of the training. This reaction, called minifreezing, resembles freezing response, frequently used behavioral measure, however applicable only in freely moving animals. This article will review experimental evidences confirming that minifreezing is a relevant index of association formation between the neutral CS and the and the aversive UCS.
Topics: Animals; Association Learning; Conditioning, Classical; Fear; Mice; Vibrissae
PubMed: 27373946
DOI: 10.21307/ane-2017-008 -
The Journal of Neuroscience : the... Mar 2020Memories for past experiences can range from vague recognition to full-blown recall of associated details. Electroencephalography has shown that recall signals unfold a...
Memories for past experiences can range from vague recognition to full-blown recall of associated details. Electroencephalography has shown that recall signals unfold a few hundred milliseconds after simple recognition, but has only provided limited insights into the underlying brain networks. Functional magnetic resonance imaging (fMRI) has revealed a "core recollection network" (CRN) centered on posterior parietal and medial temporal lobe regions, but the temporal dynamics of these regions during retrieval remain largely unknown. Here we used Magnetoencephalography in a memory paradigm assessing correct rejection (CR) of lures, item recognition (IR) and associative recall (AR) in human participants of both sexes. We found that power decreases in the alpha frequency band (10-12 Hz) systematically track different mnemonic outcomes in both time and space: Over left posterior sensors, alpha power decreased in a stepwise fashion from 500 ms onward, first from CR to IR and then from IR to AR. When projecting alpha power into source space, the CRN known from fMRI studies emerged, including posterior parietal cortex (PPC) and hippocampus. While PPC showed a monotonic change across conditions, hippocampal effects were specific to recall. These region-specific effects were corroborated by a separate fMRI dataset. Importantly, alpha power time courses revealed a temporal dissociation between item and associative memory in hippocampus and PPC, with earlier AR effects in hippocampus. Our data thus link engagement of the CRN to the temporal dynamics of episodic memory and highlight the role of alpha rhythms in revealing when and where different types of memories are retrieved. Our ability to remember ranges from the vague feeling of familiarity to vivid recollection of associated details. Scientific understanding of episodic memory thus far relied upon separate lines of research focusing on either temporal (via electroencephalography) or spatial (via functional magnetic resonance imaging) dimensions. However, both techniques have limitations that have hindered understanding of when and where memories are retrieved. Capitalizing on the enhanced temporal and spatial resolution of magnetoencephalography, we show that changes in alpha power reveal both when and where different types of memory are retrieved. Having access to the temporal and spatial characteristics of successful retrieval provided new insights into the cross-regional dynamics in the hippocampus and parietal cortex.
Topics: Adolescent; Adult; Alpha Rhythm; Association Learning; Brain Mapping; Female; Hippocampus; Humans; Magnetoencephalography; Male; Mental Recall; Nerve Net; Parietal Lobe; Psychomotor Performance; Recognition, Psychology; Young Adult
PubMed: 32034067
DOI: 10.1523/JNEUROSCI.1982-19.2020 -
The Journal of Physiology Oct 2014Acetylcholine is a crucial neuromodulator for attention, learning and memory. Release of acetylcholine in primary sensory cortex enhances processing of sensory stimuli,... (Review)
Review
Acetylcholine is a crucial neuromodulator for attention, learning and memory. Release of acetylcholine in primary sensory cortex enhances processing of sensory stimuli, and many in vitro studies have pinpointed cellular mechanisms that could mediate this effect. In contrast, how cholinergic modulation shapes the function of intact circuits during behaviour is only beginning to emerge. Here we review recent data on the recruitment of identified interneuron types in neocortex by cholinergic signalling, obtained with a combination of genetic targeting of cell types, two-photon imaging and optogenetics. These results suggest that acetylcholine release during basal forebrain stimulation, and during physiological recruitment of the basal forebrain, can strongly and rapidly influence the firing of neocortical interneurons. In contrast to the traditional view of neuromodulation as a relatively slow process, cholinergic signalling can thus rapidly convey time-locked information to neocortex about the behavioural state of the animal and the occurrence of salient sensory stimuli. Importantly, these effects strongly depend on interneuron type, and different interneuron types in turn control distinct aspects of circuit function. One prominent effect of phasic acetylcholine release is disinhibition of pyramidal neurons, which can facilitate sensory processing and associative learning.
Topics: Acetylcholine; Animals; Association Learning; Interneurons; Neocortex
PubMed: 24879871
DOI: 10.1113/jphysiol.2014.273862 -
NeuroImage Nov 2019Functional magnetic resonance imaging (MRI) studies have demonstrated a critical role of hippocampus and inferior frontal gyrus (IFG) in associative memory. Similarly,...
Functional magnetic resonance imaging (MRI) studies have demonstrated a critical role of hippocampus and inferior frontal gyrus (IFG) in associative memory. Similarly, evidence from structural MRI studies suggests a relationship between gray-matter volume in these regions and associative memory. However, how brain volume and activity relate to each other during associative-memory formation remains unclear. Here, we used joint independent component analysis (jICA) to examine how gray-matter volume and brain activity would be associated during associative encoding, especially in medial-temporal lobe (MTL) and IFG. T1-weighted images were collected from 27 young adults, and functional MRI was employed during intentional encoding of object pairs. A subsequent recognition task tested participants' memory performance. Unimodal analyses using voxel-based morphometry revealed that participants with better associative memory showed larger gray-matter volume in left anterior hippocampus. Results from the jICA revealed one component that comprised a covariance pattern between gray-matter volume in anterior and posterior MTL and encoding-related activity in IFG. Our findings suggest that gray matter within the MTL modulates distally distinct parts of the associative encoding circuit, and extend previous studies that demonstrated MTL-IFG functional connectivity during associative memory tasks.
Topics: Adult; Association; Female; Gray Matter; Humans; Magnetic Resonance Imaging; Male; Memory; Organ Size; Prefrontal Cortex; Temporal Lobe; Young Adult
PubMed: 31323259
DOI: 10.1016/j.neuroimage.2019.116020 -
Hippocampus Dec 2017Adaptive behavior frequently depends on inference from past experience. Recent studies suggest that the underlying process of integrating related memories may depend on...
Adaptive behavior frequently depends on inference from past experience. Recent studies suggest that the underlying process of integrating related memories may depend on interaction between hippocampus and prefrontal cortex. Here, we investigated how hippocampal damage affects memory integration. Subjects with mediotemporal lesions and healthy controls learned a set of overlapping AB- and BC-associations (object-face- and face-object pairs) and were then tested for memory of these associations ("direct" trials) and of inferential AC-associations ("indirect" trials). The experiment consisted of four encoding/retrieval cycles. In direct trials, performance of patients and controls was similar and stable across cycles. By contrast, in indirect trials, patients and controls showed distinct patterns of behavior. Whereas patients and controls initially showed only minor differences, controls increased performance across subsequent cycles, while patient performance decreased to chance level. Further analysis suggested that this deficit was not merely a consequence of impaired associative memory but rather resulted from an additional hippocampal contribution to memory integration. Our findings further suggest that contextual factors modulate this contribution. Patient deficits in more complex memory-guided behavior may depend on the flexible interaction of hippocampus-dependent and -independent mechanisms of memory integration.
Topics: Adult; Association Learning; Brain Neoplasms; Female; Hippocampus; Humans; Male; Memory; Memory Disorders; Middle Aged; Neuropsychological Tests; Pattern Recognition, Visual; Young Adult
PubMed: 28768057
DOI: 10.1002/hipo.22766 -
The Journal of Neuroscience : the... Sep 2015Rewards obtained from specific behaviors can and do change across time. To adapt to such conditions, humans need to represent and update associations between behaviors...
Rewards obtained from specific behaviors can and do change across time. To adapt to such conditions, humans need to represent and update associations between behaviors and their outcomes. Much previous work focused on how rewards affect the processing of specific tasks. However, abstract associations between multiple potential behaviors and multiple rewards are an important basis for adaptation as well. In this experiment, we directly investigated which brain areas represent associations between multiple tasks and rewards, using time-resolved multivariate pattern analysis of functional magnetic resonance imaging data. Importantly, we were able to dissociate neural signals reflecting task-reward associations from those related to task preparation and reward expectation processes, variables that were often correlated in previous research. We hypothesized that brain regions involved in processing tasks and/or rewards will be involved in processing associations between them. Candidate areas included the dorsal anterior cingulate cortex, which is involved in associating simple actions and rewards, and the parietal cortex, which has been shown to represent task rules and action values. Our results indicate that local spatial activation patterns in the inferior parietal cortex indeed represent task-reward associations. Interestingly, the parietal cortex flexibly changes its content of representation within trials. It first represents task-reward associations, later switching to process tasks and rewards directly. These findings highlight the importance of the inferior parietal cortex in associating behaviors with their outcomes and further show that it can flexibly reconfigure its function within single trials. Significance statement: Rewards obtained from specific behaviors rarely remain constant over time. To adapt to changing conditions, humans need to continuously update and represent the current association between behavior and its outcomes. However, little is known about the neural representation of behavior-outcome associations. Here, we used multivariate pattern analysis of functional magnetic resonance imaging data to investigate the neural correlates of such associations. Our results demonstrate that the parietal cortex plays a central role in representing associations between multiple behaviors and their outcomes. They further highlight the flexibility of the parietal cortex, because we find it to adapt its function to changing task demands within trials on relatively short timescales.
Topics: Adult; Association Learning; Female; Humans; Male; Parietal Lobe; Reward
PubMed: 26354905
DOI: 10.1523/JNEUROSCI.4882-14.2015 -
The Journal of Neuroscience : the... Aug 2018Perception can be cast as a process of inference, in which bottom-up signals are combined with top-down predictions in sensory systems. In line with this, neural...
Perception can be cast as a process of inference, in which bottom-up signals are combined with top-down predictions in sensory systems. In line with this, neural activity in sensory cortex is strongly modulated by prior expectations. Such top-down predictions often arise from cross-modal associations, such as when a sound (e.g., bell or bark) leads to an expectation of the visual appearance of the corresponding object (e.g., bicycle or dog). We hypothesized that the hippocampus, which rapidly learns arbitrary relationships between stimuli over space and time, may be involved in forming such associative predictions. We exposed male and female human participants to auditory cues predicting visual shapes, while measuring high-resolution fMRI signals in visual cortex and the hippocampus. Using multivariate reconstruction methods, we discovered a dissociation between these regions: representations in visual cortex were dominated by whichever shape was presented, whereas representations in the hippocampus reflected only which shape was predicted by the cue. The strength of hippocampal predictions correlated across participants with the amount of expectation-related facilitation in visual cortex. These findings help bridge the gap between memory and sensory systems in the human brain. The way we perceive the world is to a great extent determined by our prior knowledge. Despite this intimate link between perception and memory, these two aspects of cognition have mostly been studied in isolation. Here we investigate their interaction by asking how memory systems that encode and retrieve associations can inform perception. We find that upon hearing a familiar auditory cue, the hippocampus represents visual information that had previously co-occurred with the cue, even when this expectation differs from what is currently visible. Furthermore, the strength of this hippocampal expectation correlates with facilitation of perceptual processing in visual cortex. These findings help bridge the gap between memory and sensory systems in the human brain.
Topics: Adult; Association; Association Learning; Cues; Female; Form Perception; Hippocampus; Humans; Magnetic Resonance Imaging; Male; Neuroimaging; Pattern Recognition, Physiological; Visual Cortex
PubMed: 29986875
DOI: 10.1523/JNEUROSCI.0163-18.2018 -
Clinical Neurophysiology : Official... Nov 2017The original protocol of Paired Associative Stimulation (PAS) in humans implies repetitive cortical and peripheral nerve stimuli, delivered at specific inter-stimulus... (Review)
Review
The original protocol of Paired Associative Stimulation (PAS) in humans implies repetitive cortical and peripheral nerve stimuli, delivered at specific inter-stimulus intervals, able to elicit non-invasively long-term potentiation (LTP)- and long-term depression (LTD)-like plasticity in the human motor cortex. PAS has been designed to drive cortical LTP/LTD according to the Hebbian rule of associative plasticity. Over the last two decades, a growing number of researchers have increasingly used the PAS technique to assess cortical associative plasticity in healthy humans and in patients with movement disorders and other neuropsychiatric diseases. The present review covers the physiology, pharmacology, pathology and motor effects of PAS. Further sections of the review focus on new protocols of "modified PAS" and possible future application of PAS in neuromorphic circuits designed for brain-computer interface.
Topics: Association; Brain; Electric Stimulation; Humans; Neuronal Plasticity
PubMed: 28938144
DOI: 10.1016/j.clinph.2017.08.003 -
The Journal of Neuroscience : the... Jan 2016Parents have large genetic and environmental influences on offspring's cognition, behavior, and brain. These intergenerational effects are observed in mood disorders,...
UNLABELLED
Parents have large genetic and environmental influences on offspring's cognition, behavior, and brain. These intergenerational effects are observed in mood disorders, with particularly robust association in depression between mothers and daughters. No studies have thus far examined the neural bases of these intergenerational effects in humans. Corticolimbic circuitry is known to be highly relevant in a wide range of processes, including mood regulation and depression. These findings suggest that corticolimbic circuitry may also show matrilineal transmission patterns. Therefore, we examined human parent-offspring association in this neurocircuitry and investigated the degree of association in gray matter volume between parent and offspring. We used voxelwise correlation analysis in a total of 35 healthy families, consisting of parents and their biological offspring. We found positive associations of regional gray matter volume in the corticolimbic circuit, including the amygdala, hippocampus, anterior cingulate cortex, and ventromedial prefrontal cortex between biological mothers and daughters. This association was significantly greater than mother-son, father-daughter, and father-son associations. The current study suggests that the corticolimbic circuitry, which has been implicated in mood regulation, shows a matrilineal-specific transmission patterns. Our preliminary findings are consistent with what has been found behaviorally in depression and may have clinical implications for disorders known to have dysfunction in mood regulation such as depression. Studies such as ours will likely bridge animal work examining gene expression in the brains and clinical symptom-based observations and provide promising ways to investigate intergenerational transmission patterns in the human brain.
SIGNIFICANCE STATEMENT
Parents have large genetic and environmental influences on the offspring, known as intergenerational effects. Specifically, depression has been shown to exhibit strong matrilineal transmission patterns. Although intergenerational transmission patterns in the human brain are virtually unknown, this would suggest that the corticolimbic circuitry relevant to a wide range of processes including mood regulation may also show matrilineal transmission patterns. Therefore, we examined the degree of association in corticolimbic gray matter volume (GMV) between parent and offspring in 35 healthy families. We found that positive correlations in maternal corticolimbic GMV with daughters were significantly greater than other parent-offspring dyads. Our findings provide new insight into the potential neuroanatomical basis of circuit-based female-specific intergenerational transmission patterns in depression.
Topics: Adolescent; Adult; Analysis of Variance; Association; Cerebral Cortex; Child; Child, Preschool; Cognition; Female; Humans; Image Processing, Computer-Assisted; Intergenerational Relations; Limbic System; Magnetic Resonance Imaging; Middle Aged; Mother-Child Relations; Neural Pathways; Statistics as Topic
PubMed: 26818513
DOI: 10.1523/JNEUROSCI.4974-14.2016 -
Nature Communications Sep 2019When an action is familiar, we are able to anticipate how it will change the state of the world. These expectations can result from retrieval of action-outcome...
When an action is familiar, we are able to anticipate how it will change the state of the world. These expectations can result from retrieval of action-outcome associations in the hippocampus and the reinstatement of anticipated outcomes in visual cortex. How does this role for the hippocampus in action-based prediction change over time? We use high-resolution fMRI and a dual-training behavioral paradigm to examine how the hippocampus interacts with visual cortex during predictive and nonpredictive actions learned either three days earlier or immediately before the scan. Just-learned associations led to comparable background connectivity between the hippocampus and V1/V2, regardless of whether actions predicted outcomes. However, three-day-old associations led to stronger background connectivity and greater differentiation between neural patterns for predictive vs. nonpredictive actions. Hippocampal prediction may initially reflect indiscriminate binding of co-occurring events, with action information pruning weaker associations and leading to more selective and accurate predictions over time.
Topics: Adolescent; Adult; Association Learning; Brain Mapping; Female; Hippocampus; Humans; Learning; Magnetic Resonance Imaging; Male; Memory; Neocortex; Temporal Lobe; Time Factors; Visual Cortex; Young Adult
PubMed: 31488845
DOI: 10.1038/s41467-019-12016-9