Current research in neurobiology最新文献

Cognitive theories of consciousness, such as global workspace theory and higher-order theories, posit that frontoparietal circuits play a crucial role in conscious access. However, recent studies using no-report paradigms have posed a challenge to cognitive theories by demonstrating conscious accessibility in the apparent absence of prefrontal cortex (PFC) activation. To address this challenge, this paper presents a computational model of conscious access, based upon active inference, that treats working memory gating as a cognitive action. We simulate a visual masking task and show that late P3b-like event-related potentials (ERPs), and increased PFC activity, are induced by the working memory demands of self-report generation. When reporting demands are removed, these late ERPs vanish and PFC activity is reduced. These results therefore reproduce, and potentially explain, results from no-report paradigms. However, even without reporting demands, our model shows that simulated PFC activity on visible stimulus trials still crosses the threshold for reportability – maintaining the link between PFC and conscious access. Therefore, our simulations show that evidence provided by no-report paradigms does not necessarily contradict cognitive theories of consciousness.

Value-based decisions depend on different forms of memory. However, the respective roles of memory and valuation processes that give rise to these decisions are often vaguely described and have rarely been investigated jointly. In this review article, we address the problem of memory-based decision making from a neuroeconomic perspective. We first describe the neural and cognitive processes involved in decisions requiring memory processes, with a focus on episodic memory. Based on the results of a systematic research program, we then spotlight the phenomenon of the memory bias, a general preference for choice options that can be retrieved from episodic memory more successfully. Our findings indicate that failed memory recall biases neural valuation processes as indicated by altered effective connectivity between the hippocampus and ventromedial prefrontal cortex. This bias can be attributed to meta-cognitive beliefs about the relationship between subjective value and memory as well as to uncertainty aversion. After summarizing the findings, we outline potential future research endeavors to integrate the two research traditions of memory and decision making.

Repetitive transcranial magnetic stimulation (rTMS) is a widespread technique in neuroscience and medicine, however its mechanisms are not well known. In this review, we consider intensity as a key therapeutic parameter of rTMS, and review the studies that have examined the biological effects of rTMS using magnetic fields that are orders of magnitude lower that those currently used in the clinic. We discuss how extensive characterisation of “low intensity” rTMS has set the stage for translation of new rTMS parameters from a mechanistic evidence base, with potential for innovative and effective therapeutic applications. Low-intensity rTMS demonstrates neurobiological effects across healthy and disease models, which include depression, injury and regeneration, abnormal circuit organisation, tinnitus etc. Various short and long-term changes to metabolism, neurotransmitter release, functional connectivity, genetic changes, cell survival and behaviour have been investigated and we summarise these key changes and the possible mechanisms behind them. Mechanisms at genetic, molecular, cellular and system levels have been identified with evidence that low-intensity rTMS and potentially rTMS in general acts through several key pathways to induce changes in the brain with modulation of internal calcium signalling identified as a major mechanism. We discuss the role that preclinical models can play to inform current clinical research as well as uncover new pathways for investigation.

The firing maps of grid cells in the entorhinal cortex are thought to provide an efficient metric system capable of supporting spatial inference in all environments. However, whether spatial representations of grid cells are determined by local environment cues or are organized into globally coherent patterns remains undetermined. We propose a navigation model containing a path integration system in the entorhinal cortex and a cognitive map system in the hippocampus. In the path integration system, grid cell network and head direction (HD) cell network integrate movement and visual information, and form attractor states to represent the positions and head directions of the animal. In the cognitive map system, a topological map is constructed capturing the attractor states of the path integration system as nodes and the transitions between attractor states as links. On loop closure, when the animal revisits a familiar place, the topological map is calibrated to minimize odometry errors. The change of the topological map is mapped back to the path integration system, to correct the states of the grid cells and the HD cells. The proposed model was tested on iRat, a rat-like miniature robot, in a realistic maze. Experimental results showed that, after familiarization of the environment, both grid cells and HD cells develop globally coherent firing maps by map calibration and activity correction. These results demonstrate that the hippocampus and the entorhinal cortex work together to form globally coherent metric representations of the environment. The underlying mechanisms of the hippocampal-entorhinal circuit in capturing the structure of the environment from sequences of experience are critical for understanding episodic memory.

Cognitive impairment, particularly deficits in executive function (EF) is common in Parkinson's disease (PD) and may lead to dementia. There are currently no effective treatments for cognitive impairment. Work from our lab and others has shown that physical exercise may improve motor performance in PD but its role in cognitive function remains poorly eludicated. In this study in a rodent model of PD, we sought to examine whether exercise improves cognitive processing and flexibility, important features of EF. Rats received 6-hydroxydopamine lesions of the bilateral striatum (caudate-putamen, CPu), specifically the dorsomedial CPu, a brain region central to EF. Rats were exercised on motorized running wheels or horizontal treadmills for 6–12 weeks. EF-related behaviors including attention and processing, as well as flexibility (inhibition) were evaluated using either an operant 3-choice serial reaction time task (3-CSRT) with rule reversal (3-CSRT-R), or a T-maze task with reversal. Changes in striatal transcript expression of dopamine receptors (Drd1-4) and synaptic proteins (Synaptophysin, PSD-95) were separately examined following 4 weeks of exercise in a subset of rats. Exercise/Lesion rats showed a modest, yet significant improvement in processing-related response accuracy in the 3-CSRT-R and T-maze, as well as a significant improvement in cognitive flexibility as assessed by inhibitory aptitude in the 3-CSRT-R. By four weeks, exercise also elicited increased expression of Drd1, Drd3, Drd4, synaptophysin, and PSD-95 in the dorsomedial and dorsolateral CPu. Our results underscore the observation that exercise, in addition to improving motor function may benefit cognitive performance, specifically EF, and that early changes (by 4 weeks) in CPu dopamine modulation and synaptic connectivity may underlie these benefits.

The mechanism of the active cochlea relies on a complex interaction between microstructures in the organ of Corti. A significant longitudinal vibration “hotspot” was recently observed in the high-frequency region of the living gerbil cochlea between the Deiters cells and the outer hair cells. A similar phenomenon was also found in guinea pigs with a relatively smaller magnitude. The cause is unknown, but one hypothesis is that this phenomenon is due to the structural constraints between different microstructures. It is not easy to explain the mechanism of hotspots directly from experimental observations. It may also be difficult to image or test if the hotspot will occur in the low-frequency region in the cochlea. We built two three-dimensional finite element models corresponding to the high- and low-frequency regions in the guinea pig cochlea. Responses of the organ of Corti to passive acoustic and outer hair cell electrical excitation were calculated. The two excitations were then superimposed to predict the active response of the organ of Corti. The hotspot phenomenon in the experiment was reproduced and analyzed in-depth about influencing factors. Our results indicate that hotspots appear in the low-frequency region of the cochlea as well. We hypothesize that the hotspot is a locally originated phenomenon in the cochlea, and the traveling wave further enhances the response to low-frequency excitation. The movement of outer hair cells inclined in the longitudinal direction is the leading cause of the hotspot.

Hearing with a cochlear implant (CI) is limited compared to natural hearing. Although CI users may develop compensatory strategies, it is currently unknown whether these extend from auditory to visual functions, and whether compensatory strategies vary between different CI user groups. To better understand the experience-dependent contributions to multisensory plasticity in audiovisual speech perception, the current event-related potential (ERP) study presented syllables in auditory, visual, and audiovisual conditions to CI users with unilateral or bilateral hearing loss, as well as to normal-hearing (NH) controls. Behavioural results revealed shorter audiovisual response times compared to unisensory conditions for all groups. Multisensory integration was confirmed by electrical neuroimaging, including topographic and ERP source analysis, showing a visual modulation of the auditory-cortex response at N1 and P2 latency. However, CI users with bilateral hearing loss showed a distinct pattern of N1 topography, indicating a stronger visual impact on auditory speech processing compared to CI users with unilateral hearing loss and NH listeners. Furthermore, both CI user groups showed a delayed auditory-cortex activation and an additional recruitment of the visual cortex, and a better lip-reading ability compared to NH listeners. In sum, these results extend previous findings by showing distinct multisensory processes not only between NH listeners and CI users in general, but even between CI users with unilateral and bilateral hearing loss. However, the comparably enhanced lip-reading ability and visual-cortex activation in both CI user groups suggest that these visual improvements are evident regardless of the hearing status of the contralateral ear.

IGF-1 and GLP-1 receptors are essential in all tissues, facilitating defense by upregulating anabolic processes. They are abundantly distributed throughout the central nervous system, promoting neuronal proliferation, survival, and differentiation. IGF-1/GLP-1 is a growth factor that stimulates neurons' development, reorganization, myelination, and survival. In primary and secondary brain injury, the IGF-1/GLP-1 receptors are impaired, resulting in further neuro complications such as cerebral tissue degradation, neuroinflammation, oxidative stress, and atrophy. Intracerebral hemorrhage (ICH) is a severe condition caused by a stroke for which there is currently no effective treatment. While some pre-clinical studies and medications are being developed as symptomatic therapies in clinical trials, there are specific pharmacological implications for improving post-operative conditions in patients with intensive treatment. Identifying the underlying molecular process and recognizing the worsening situation can assist researchers in developing effective therapeutic solutions to prevent post-hemorrhagic symptoms and the associated neural dysfunctions. As a result, in the current review, we have addressed the manifestations of the disease that are aggravated by the downregulation of IGF-1 and GLP-1 receptors, which can lead to ICH or other neurodegenerative disorders. Our review summarizes that IGF-1/GLP-1 activators may be useful for treating ICH and its related neurodegeneration.

The current study examined the neural mechanisms for mental effort and its correlation to speech perception using functional near-infrared spectroscopy (fNIRS) in listeners with normal hearing (NH). Data were collected while participants listened and responded to unprocessed and degraded sentences, where words were presented in grammatically correct or shuffled order. Effortful listening and task difficulty due to stimulus manipulations was confirmed using a subjective questionnaire and a well-established objective measure of mental effort – pupillometry. fNIRS measures focused on cortical responses in two a priori regions of interest, the left auditory cortex (AC) and lateral frontal cortex (LFC), which are closely related to auditory speech perception and listening effort, respectively. We examined the relations between the two objective measures and behavioral measures of speech perception (task performance) and task difficulty.

Results

demonstrated that changes in pupil dilation were positively correlated with the self-reported task difficulty levels and negatively correlated with the task performance scores. A significant and negative correlation between the two behavioral measures was also found. That is, as perceived task demands increased and task performance scores decreased, pupils dilated more. fNIRS measures (cerebral oxygenation) in the left AC and LFC were both negatively correlated with the self-reported task difficulty levels and positively correlated with task performance scores. These results suggest that pupillometry measures can indicate task demands and listening effort; whereas, fNIRS measures using a similar paradigm seem to reflect speech processing, but not effort.

Studying higher brain function presents fundamental scientific challenges but has great potential for impactful translation to the clinic, supporting the needs of many patients suffering from conditions that relate to neuronal dysfunction. For many key questions relevant to human neurological conditions and clinical interventions, non-human primates (NHPs) remain the only suitable model organism and the only effective way to study the relationship between brain structure and function with the knowledge and tools currently available. Here we present three exemplary studies of current research yielding important findings that are directly translational to human clinical patients but which would be impossible without NHP studies. Our first example shows how studies of the NHP prefrontal cortex are leading to clinically relevant advances and potential new treatments for human neuropsychiatric disorders such as depression and anxiety. Our second example looks at the relevance of NHP research to our understanding of visual pathways and the visual cortex, leading to visual prostheses that offer treatments for otherwise blind patients. Finally, we consider recent advances in treatments leading to improved recovery of movement and motor control in stroke patients, resulting from our improved understanding of brain stem parallel pathways involved in movement in NHPs. The case for using NHPs in neuroscience research, and the direct benefits to human patients, is strong but has rarely been set out directly. This paper reviews three very different areas of neuroscience research, expressly highlighting the unique insights offered to each by NHP studies and their direct applicability to human clinical conditions.