Cortical Pathways Research Articles

Unilateral resection of both cortical visual pathways in a pediatric patient alters action but not perception

The human cortical visual system consists of two major pathways, a ventral pathway which subserves perception and a dorsal pathway which primarily subserves visuomotor control. Previous studies have found that children with cortical resections of the ventral visual pathway retain largely normal visuoperceptual abilities. Whether visually guided actions, supported by computations carried out by the dorsal pathway, follow a similar pattern of preservation remains unknown. To address this question, we examined visuoperceptual and visuomotor behaviors in a pediatric patient, TC, who underwent a cortical resection that included portions of the left ventral and dorsal pathways. We collected kinematic data when TC used her right and left hands to perceptually estimate the width of blocks that varied in width and length, and, separately, to grasp the same blocks. TC's perceptual estimation performance was comparable to that of controls, independent of the hand used. In contrast, relative to controls, she showed reduced visuomotor sensitivity to object shape and this was more evident when she grasped the objects with her contralesional right hand. These results provide novel evidence for a striking difference in the competence of the two visual pathways to cortical injuries acquired in childhood.

BTN: Neuroanatomical aligning between visual object tracking in deep neural network and smooth pursuit in brain

Inspired by neuroanatomy, deep neural networks (DNNs) have recently developed from shallow network structures to exceedingly deep structures, providing excellent visual tracking results. However, standard DNNs usually do not easily connect with brain areas on account of their excessive network depth and absent biological constraints, such as recurrent connections. We propose a brain-like tracking network (BTN) with four neuroanatomically mapped regions and recurrence, guided by the brain-like tracking score (BTS), a novel benchmark to measure the model similarity of the human smooth pursuit pathway. In addition, we propose that the middle temporal (MT) and medial superior temporal (MST) areas in the cerebral cortex are equivalent to the designed network structure on the basis of the continuous motion perception of the tracking pathway, and indicate that the metrics between the neuroanatomical similarity in the cerebral cortex and visual tracking of the DNN are compatible. Despite having significant tracking performance on the Tracking-Gump dataset, the BTN has achieved a high BTS. In summary, this research builds a BTN, a brain-like and recurrent DNN, as the first model of the cortical pathway of smooth pursuit.

Overt Oculomotor Behavior Reveals Covert Temporal Predictions.

Our eyes move in response to stimulus statistics, reacting to surprising events, and adapting to predictable ones. Cortical and subcortical pathways contribute to generating context-specific eye-movement dynamics, and oculomotor dysfunction is recognized as one the early clinical markers of Parkinson's disease (PD). We asked if covert computations of environmental statistics generating temporal expectations for a potential target are registered by eye movements, and if so, assuming that temporal expectations rely on motor system efficiency, whether they are impaired in PD. We used a repeating tone sequence, which generates a hazard rate distribution of target probability, and analyzed the distribution of blinks when participants were waiting for the target, but the target did not appear. Results show that, although PD participants tend to produce fewer and less temporally organized blink events relative to healthy controls, in both groups blinks became more suppressed with increasing target probability, leading to a hazard rate of oculomotor inhibition effects. The covert generation of temporal predictions may reflect a key feature of cognitive resilience in Parkinson's Disease.

Dual projecting cells linking thalamic and cortical communication routes between the medial prefrontal cortex and hippocampus

The interactions between the medial prefrontal cortex (mPFC) and the hippocampus (HC) are critical for memory and decision making and have been specifically implicated in several neurological disorders including schizophrenia, epilepsy, frontotemporal dementia, and Alzheimer’s disease. The ventral midline thalamus (vmThal), and lateral entorhinal cortex and perirhinal cortex (LEC/PER) constitute major communication pathways that facilitate mPFC-HC interactions in memory. Although vmThal and LEC/PER circuits have been delineated separately we sought to determine whether these two regions share cell-specific inputs that could influence both routes simultaneously. To do this we used a dual fluorescent retrograde tracing approach using cholera toxin subunit-B (CTB-488 and CTB-594) with injections targeting vmThal and the LEC/PER in rats. Retrograde cell body labeling was examined in key regions of interest within the mPFC-HC system including: (1) mPFC, specifically anterior cingulate cortex (ACC), dorsal and ventral prelimbic cortex (dPL, vPL), and infralimbic cortex (IL); (2) medial and lateral septum (MS, LS); (3) subiculum (Sub) along the dorsal–ventral and proximal–distal axes; and (4) LEC and medial entorhinal cortex (MEC). Results showed that dual vmThal-LEC/PER-projecting cell populations are found in MS, vSub, and the shallow layers II/III of LEC and MEC. We did not find any dual projecting cells in mPFC or in the cornu ammonis (CA) subfields of the HC. Thus, mPFC and HC activity is sent to vmThal and LEC/PER via non-overlapping projection cell populations. Importantly, the dual projecting cell populations in MS, vSub, and EC are in a unique position to simultaneously influence both cortical and thalamic mPFC-HC pathways critical to memory. Significance statementThe interactions between mPFC and HC are critical for learning and memory, and dysfunction within this circuit is implicated in various neurodegenerative and psychiatric diseases. mPFC-HC interactions are mediated through multiple communication pathways including a thalamic hub through the vmThal and a cortical hub through lateral entorhinal cortex and perirhinal cortex. Our data highlight newly identified dual projecting cell populations in the septum, Sub, and EC of the rat brain. These dual projecting cells may have the ability to modify the information flow within the mPFC-HC circuit through synchronous activity, and thus offer new cell-specific circuit targets for basic and translational studies in memory.

Modeling the Ventral and Dorsal Cortical Visual Pathways Using Artificial Neural Networks.

Although in conventional models of cortical processing, object recognition and spatial properties are processed separately in ventral and dorsal cortical visual pathways respectively, some recent studies have shown that representations associated with both objects' identity (of shape) and space are present in both visual pathways. However, it is still unclear whether the presence of identity and spatial properties in both pathways have functional roles. In our study, we have tried to answer this question through computational modeling. Our simulation results show that both a model ventral and dorsal pathway, separately trained to do object and spatial recognition, respectively, each actively retained information about both identity and space. In addition, we show that these networks retained different amounts and kinds of identity and spatial information. As a result, our modeling suggests that two separate cortical visual pathways for identity and space (1) actively retain information about both identity and space (2) retain information about identity and space differently and (3) that this differently retained information about identity and space in the two pathways may be necessary to accurately and optimally recognize and localize objects. Further, modeling results suggests these findings are robust and do not strongly depend on the specific structures of the neural networks.

Cortical Pathways During Postural Control: New Insights From Functional EEG Source Connectivity.

Postural control is a complex feedback system that relies on vast array of sensory inputs in order to maintain a stable upright stance. The brain cortex plays a crucial role in the processing of this information and in the elaboration of a successful adaptive strategy to external stimulation preventing loss of balance and falls. In the present work, the participants postural control system was challenged by disrupting the upright stance via a mechanical skeletal muscle vibration applied to the calves. The EEG source connectivity method was used to investigate the cortical response to the external stimulation and highlight the brain network primarily involved in high-level coordination of the postural control system. The cortical network reconfiguration was assessed during two experimental conditions of eyes open and eyes closed and the network flexibility (i.e. its dynamic reconfiguration over time) was correlated with the sample entropy of the stabilogram sway. The results highlight two different cortical strategies in the alpha band: the predominance of frontal lobe connections during open eyes and the strengthening of temporal-parietal network connections in the absence of visual cues. Furthermore, a high correlation emerges between the flexibility in the regions surrounding the right temporo-parietal junction and the sample entropy of the CoP sway, suggesting their centrality in the postural control system. These results open the possibility to employ network-based flexibility metrics as markers of a healthy postural control system, with implications in the diagnosis and treatment of postural impairing diseases.

Multisensory responses in a belt region of the dorsal auditory cortical pathway

A basic function of the cerebral cortex is to receive and integrate information from different sensory modalities into a comprehensive percept of the environment. Neurons that demonstrate multisensory convergence occur across the necortex but are especially prevalent in higher order association areas. However, a recent study of a cat higher order auditory area, the dorsal zone (DZ) of auditory cortex, did not observe any multisensory features. Therefore, the goal of the present investigation was to address this conflict using recording and testing methodologies that are established for exposing and studying multisensory neuronal processing. Among the 482 neurons studied, we found that 76.6% were influenced by non-auditory stimuli. Of these neurons, 99% were affected by visual stimulation, but only 11% by somatosensory. Furthermore, a large proportion of the multisensory neurons showed integrated responses to multisensory stimulation, constituted a majority of the excitatory and inhibitory neurons encountered (as identified by the duration of their waveshape) and exhibited a distinct spatial distribution within DZ. These findings demonstrate that the DZ of auditory cortex robustly exhibits multisensory properties and that the proportions of multisensory neurons encountered are consistent with those identified in other higher order cortices.

Visual field differences in temporal synchrony processing for audio-visual stimuli.

Audio-visual integration relies on temporal synchrony between visual and auditory inputs. However, differences in traveling and transmitting speeds between visual and auditory stimuli exist; therefore, audio-visual synchrony perception exhibits flexible functions. The processing speed of visual stimuli affects the perception of audio-visual synchrony. The present study examined the effects of visual fields, in which visual stimuli are presented, for the processing of audio-visual temporal synchrony. The point of subjective simultaneity, the temporal binding window, and the rapid recalibration effect were measured using temporal order judgment, simultaneity judgment, and stream/bounce perception, because different mechanisms of temporal processing have been suggested among these three paradigms. The results indicate that auditory stimuli should be presented earlier for visual stimuli in the central visual field than in the peripheral visual field condition in order to perceive subjective simultaneity in the temporal order judgment task conducted in this study. Meanwhile, the subjective simultaneity bandwidth was broader in the central visual field than in the peripheral visual field during the simultaneity judgment task. In the stream/bounce perception task, neither the point of subjective simultaneity nor the temporal binding window differed between the two types of visual fields. Moreover, rapid recalibration occurred in both visual fields during the simultaneity judgment tasks. However, during the temporal order judgment task and stream/bounce perception, rapid recalibration occurred only in the central visual field. These results suggest that differences in visual processing speed based on the visual field modulate the temporal processing of audio-visual stimuli. Furthermore, these three tasks, temporal order judgment, simultaneity judgment, and stream/bounce perception, each have distinct functional characteristics for audio-visual synchrony perception. Future studies are necessary to confirm the effects of compensation regarding differences in the temporal resolution of the visual field in later cortical visual pathways on visual field differences in audio-visual temporal synchrony.

Bilateral Asymmetry in Ocular Counter-Rolling Reflex Is Associated With Individual Motion Sickness Susceptibility.

Accumulating evidence suggests that individual variations in vestibular functions are associated with motion sickness (MS) susceptibility. We investigated whether vestibular functions in the reflex and cortical pathways could predict the susceptibility of individuals to MS. MS-susceptible and control adults were recruited according to the Motion Sickness Susceptibility Questionnaire (MSSQ) score. Otolith reflex and cortical functions were assessed using the ocular counter rolling test and the head-tilt subjective visual vertical (HT-SVV) test, respectively. The bilateral asymmetry of each function was compared between the MS-susceptible and the control groups. Although the two tests for otolith functions were conducted using the same stimulation (lateral head tilt), bilateral asymmetry of otolith reflex rather than cortical function was significantly associated with MS susceptibility. Our data suggests that bilateral asymmetry in the otolith reflex pathway is capable of predicting susceptibility to MS to some extent. Our data also suggest that the association between vestibular function and MS susceptibility can vary based on the vehicle types. Future vehicles, such as self-driving cars, will make us aware of other vestibular functions associated with MS susceptibility.

A Cortico-Cortical Pathway Targets Inhibitory Interneurons and Modulates Paw Movement during Locomotion in Mice

The primary somatosensory cortex (S1) is important for the control of movement as it encodes sensory input from the body periphery and external environment during ongoing movement. Mouse S1 consists of several distinct sensorimotor subnetworks that receive topographically organized corticocortical inputs from distant sensorimotor areas, including the secondary somatosensory cortex (S2) and primary motor cortex (M1). The role of the vibrissal S1 area and associated cortical connections during active sensing is well documented, but whether (and if so, how) non-whisker S1 areas are involved in movement control remains relatively unexplored. Here, we demonstrate that unilateral silencing of the non-whisker S1 area in both male and female mice disrupts hind paw movement during locomotion on a rotarod and a runway. S2 and M1 provide major long-range inputs to this S1 area. Silencing S2→non-whisker S1 projections alters the hind paw orientation during locomotion, whereas manipulation of the M1 projection has little effect. Using patch-clamp recordings in brain slices from male and female mice, we show that S2 projection preferentially innervates inhibitory interneuron subtypes. We conclude that interneuron-mediated S2-S1 corticocortical interactions are critical for efficient locomotion.SIGNIFICANCE STATEMENT Somatosensory cortex participates in controlling rhythmic movements, such as whisking and walking, but the neural circuitry underlying movement control by somatosensory cortex remains relatively unexplored. We uncover a corticocortical circuit in primary somatosensory cortex that regulates paw orientation during locomotion in mice. We identify neuronal elements that comprise these cortical pathways using pharmacology, behavioral assays, and circuit-mapping methods.

Characterizing the cortical pathways underlying visual trigger induced urinary urgency incontinence by functional MRI.

Visual triggers have long been recognized clinically to stimulate urgency urinary incontinence (UUI). Current pathophysiology recognizes the importance of cortical control over micturition but there is no standardized methodology for clinicians to study the impact of visual triggers. Our aim was to develop an imaging protocol able to characterize the brain's response to personalized visual triggers, providing a methodology for evaluation on connectivity within the brain in patients with visually triggered urinary urgency. A magnetic resonance imaging (MRI) methodology specific for urologic use was developed. A 3T-Elition Scanner was first used to acquire static structural images. These images were then used to define approximately 200 brain regions of interest (ROI) using a validated brain atlas. Then, real-time functional MRI (fMRI) scans were conducted during natural bladder filling, where study subjects were shown randomized block sequences of visual stimuli comprised of both subject-specific trigger images and neutral images. The fMRI scan data were merged to identify key ROI underlying UUI. Dynamic fMRI scans were conducted in 10 subjects, 4 with trigger-induced UUI, 2 with trigger-induced urgency, and 4 with no urgency or leakage to visual triggers. No subjects with UUI history lost continence during imaging, but all four subjects reported sensations of urgency in response to their own subject-specific trigger images. The ROI identified were the periaqueductal gray, anterior cingulate gyrus, pons, and prefrontal cortex. We found increased activity in the prefrontal cortex and limbic system ROI in response to subject-specific visual triggers of UUI. This information provides proof of principle for further exploration of subject-specific trigger image evaluation using fMRI to explore causation in patients with UUI.

The Efficacy and Safety of Pridopidine on Treatment of Patients with Huntington's Disease: A Systematic Review and Meta-Analysis.

Pridopidine is a novel drug that helps stabilize psychomotor function in patients with Huntington's disease (HD) by activating the cortical glutamate pathway. It promises to achieve the unmet needs of current therapies of HD without worsening other symptoms. To review the literature discussing the efficacy of pridopidine in alleviating motor symptoms and its safety in patients with HD. We searched Scopus, Web of Science, the Cochrane Library, Wiley, and PubMed for randomized controlled trials (RCTs) of pridopidine on HD. Data from eligible studies were extracted and pooled as mean differences for efficacy and risk ratios (RRs) for safety using RevMan software version 5.3. A total of 4 relevant RCTs with 1130 patients were selected (816 in the pridopidine group and 314 in the placebo group). The pooled effect size favored pridopidine over placebo insignificantly in the Unified Huntington's Disease Rating Scale Total Motor Score (mean difference [MD], -0.93; 95% confidence interval [CI], -2.01 to 0.14; P= 0.09), whereas the effect size of 3 studies significantly favored pridopidine over placebo in the Unified Huntington's Disease Rating Scale Modified Motor Score (MD, -0.81; 95% CI, -1.48 to -0.13; P= 0.02). Pridopidine generally was well tolerated. None of the adverse effects were considerably higher in the case of pridopidine compared with placebo in overall adverse events (RR, 1.03; 95% CI, 0.94-1.13; P= 0.49) and serious adverse events (RR, 1.62; 95% CI, 0.88-2.99; P= 0.12). The effects of pridopidine on motor functions (especially voluntary movements) in patients with HD are encouraging and provide a good safety profile that motivates further clinical trials on patients to confirm its effectiveness and safety.

Modulation of tactile feedback for the execution of dexterous movement.

Although dexterity relies on the constant transmission of sensory information, unchecked feedback can be disruptive. Yet how somatosensory feedback from the hands is regulated and whether this modulation influences movement remain unclear. We found that mouse tactile afferents recruit neurons in the brainstem cuneate nucleus, whose activity is modulated by distinct classes of local inhibitory neurons. Manipulation of these inhibitory circuits suppresses or enhances the transmission of tactile information, which affects manual behaviors. Top-down cortical pathways innervate cuneate in a complementary pattern, with somatosensory cortical neurons targeting the core tactile region of cuneate and a large rostral cortical population driving feed-forward inhibition of tactile transmission through an inhibitory shell. These findings identify a circuit basis for tactile feedback modulation that enables the effective execution of dexterous movement.

Attention along the cortical hierarchy: Development matters.

We build on the existing biased competition view to argue that attention is an emergent property of neural computations within and across hierarchically embedded and structurally connected cortical pathways. Critically then, one must ask, what is attention emergent from? Within this framework, developmental changes in the quality of sensory input and feedforward-feedback information flow shape the emergence and efficiency of attention. Several gradients of developing structural and functional cortical architecture across the caudal-to-rostral axis provide the substrate for attention to emerge. Neural activity within visual areas depends on neuronal density, receptive field size, tuning properties of neurons, and the location of and competition between features and objects in the visual field. These visual cortical properties highlight the information processing bottleneck attention needs to resolve. Recurrent feedforward and feedback connections convey sensory information through a series of steps at each level of the cortical hierarchy, integrating sensory information across the entire extent of the cortical hierarchy and linking sensory processing to higher-order brain regions. Higher-order regions concurrently provide input conveying behavioral context and goals. Thus, attention reflects the output of a series of complex biased competition neural computations that occur within and across hierarchically embedded cortical regions. Cortical development proceeds along the caudal-to-rostral axis, mirroring the flow in sensory information from caudal to rostral regions, and visual processing continues to develop into childhood. Examining both typical and atypical development will offer critical mechanistic insight not otherwise available in the adult stable state. This article is categorized under: Psychology > Attention.

Functional Interactions between Entorhinal Cortical Pathways Modulate Theta Activity in the Hippocampus.

Simple SummaryThe activity in the hippocampus is characterized by a strong oscillation at theta frequency that organizes the neuronal firing. We have recently shown that different theta oscillations are present in the hippocampus, opening the possibility to multiple interactions between theta rhythms. In this work, we analyzed the functional connectivity between theta generators during the exploration of a known environment with or without a novel stimulus. The directionality of the interactions was determined using tools based on Granger causality and transfer entropy. We found significant interactions between activity components originated in CA3 and in layers II and III of the entorhinal cortex. During exploration with a novel stimulus, the connectivity from the entorhinal cortex layer II increased, while the influence of CA3 decreased. These results suggest that the entorhinal cortex layer II may drive theta interactions and synchronization in the hippocampus during novelty exploration.Theta oscillations organize neuronal firing in the hippocampus during context exploration and memory formation. Recently, we have shown that multiple theta rhythms coexist in the hippocampus, reflecting the activity in their afferent regions in CA3 (Schaffer collaterals) and the entorhinal cortex layers II (EC-II, perforant pathway) and III (EC-III, temporoammonic pathway). Frequency and phase coupling between theta rhythms were modulated by the behavioral state, with synchronized theta rhythmicity preferentially occurring in tasks involving memory updating. However, information transmission between theta generators was not investigated. Here, we used source separation techniques to disentangle the current generators recorded in the hippocampus of rats exploring a known environment with or without a novel stimulus. We applied analytical tools based on Granger causality and transfer entropy to investigate linear and non-linear directed interactions, respectively, between the theta activities. Exploration in the novelty condition was associated with increased theta power in the generators with EC origin. We found a significant directed interaction from the Schaffer input over the EC-III input in CA1, and a bidirectional interaction between the inputs in the hippocampus originating in the EC, likely reflecting the connection between layers II and III. During novelty exploration, the influence of the EC-II over the EC-III generator increased, while the Schaffer influence decreased. These results associate the increase in hippocampal theta activity and synchrony during novelty exploration with an increase in the directed functional connectivity from EC-II to EC-III.

Prenatal Exposure to Tobacco and Alcohol Alters Development of the Neonatal Auditory System

Prenatal exposures to alcohol (PAE) and tobacco (PTE) are known to produce adverse neonatal and childhood outcomes including damage to the developing auditory system. Knowledge of the timing, extent, and combinations of these exposures on effects on the developing system is limited. As part of the physiological measurements from the Safe Passage Study, Auditory Brainstem Responses (ABRs) and Transient Otoacoustic Emissions (TEOAEs) were acquired on infants at birth and one-month of age. Research sites were in South Africa and the Northern Plains of the U.S. Prenatal information on alcohol and tobacco exposure was gathered prospectively on mother/infant dyads. Cluster analysis was used to characterize three levels of PAE and three levels of PTE. Repeated-measures ANOVAs were conducted for newborn and one-month-old infants for ABR peak latencies and amplitudes and TEOAE levels and signal-to-noise ratios. Analyses controlled for hours of life at test, gestational age at birth, sex, site, and other exposure. Significant main effects of PTE included reduced newborn ABR latencies from both ears. PTE also resulted in a significant reduction of ABR peak amplitudes elicited in infants at 1-month of age. PAE led to a reduction of TEOAE amplitude for 1-month-old infants but only in the left ear. Results indicate that PAE and PTE lead to early disruption of peripheral, brainstem, and cortical development and neuronal pathways of the auditory system, including the olivocochlear pathway.

New Cortical Neurodegenerative Pathways in the Hypertensive Rat Brain.

Hypertension is a risk factor for neurodegenerative diseases. We hypothesized that chronic hypertension underlies neurodegeneration. In this study, we examined the expression of brain cortical proteins involved in homeostasis, apoptosis, and brain functions in Spontaneously Hypertensive Rats (SHR) compared with normotensive Wistar-Kyoto (WKY) rats. We used paraffin-embedded brain sections of 8-month-old SHR and WKY rats, immunohistochemically stained and analyzed by image processing. In SHR, cytochrome c oxidase subunit 7A increased, indicative of hypoxia; heat shock protein 40, the chaperon for refolding proteins, decreased, leading to accumulation of misfolded proteins; the levels of both voltage-gated sodium channels, Na1.2, 1.6, decreased, reflecting attenuation of the action potential, causing axonal injury; autophagy-related protein 4A (Atg4a), an essential protein of autophagy, decreased, reducing the removal of misfolded proteins; demyelination, the hallmark of neurodegeneration, was shown; modulation of both histone deacetylases 2 and histone acetyltransferase 1 was shown, indicative of altered regulation of gene transcription; increased activated (cleaved) caspase-3, indicative of apoptosis. These new findings suggest that chronic hypertension induces hypoxia and oxidative stress, axonal injury, accelerates the accumulation of misfolded proteins and apoptosis, pathways preceding neurodegeneration.

Card posting does not rely on visual orientation: A challenge to past neuropsychological dissociations

A common set of tasks frequently employed in the neuropsychological assessment of patients with visuomotor or perceptual deficits are the card-posting and the perceptual orientation matching tasks. In the posting task, patients have to post a card (or their hand) through a slot of varying orientations while the matching task requires them to indicate the slot's orientation as accurately as possible. Observations that damage to different areas of the brain (dorsal vs. ventral stream) is associated with selective impairment in one of the tasks - but not the other - has led to the suggestion that different cortical pathways process visual orientation information for perception versus action. In three experiments, we show that this conclusion may be premature as posting does not seem to rely on the processing of visual orientation information but is instead performed using obstacle avoidance strategies that require an accurate judgement of egocentric distances between the card's and the slot's edges. Specifically, we found that while matching is susceptible to the oblique effect (i.e., common perceptual orientation bias with higher accuracy for cardinal than oblique orientations), this was not the case for posting, neither in immediate nor in memory-guided conditions. In contrast to matching, posting errors primarily depended on biomechanical demands and reflected a preference for performing efficient and comfortable movements. Thus, we suggest that previous dissociations between perceptual and visuomotor performance in letter posting tasks are better explained by impairments in egocentric and allocentric spatial processing than by independent visual processing systems.

Prolonged development of long-term potentiation at lateral entorhinal cortex synapses onto adult-born neurons.

Critical period plasticity at adult-born neuron synapses is widely believed to contribute to the learning and memory functions of the hippocampus. Experience regulates circuit integration and for a transient interval, until cells are ~6 weeks old, new neurons display enhanced long-term potentiation (LTP) at afferent and efferent synapses. Since neurogenesis declines substantially with age, this raises questions about the extent of lasting plasticity offered by adult-born neurons. Notably, however, the hippocampus receives sensory information from two major cortical pathways. Broadly speaking, the medial entorhinal cortex conveys spatial information to the hippocampus via the medial perforant path (MPP), and the lateral entorhinal cortex, via the lateral perforant path (LPP), codes for the cues and items that make experiences unique. While enhanced critical period plasticity at MPP synapses is relatively well characterized, no studies have examined long-term plasticity at LPP synapses onto adult-born neurons, even though the lateral entorhinal cortex is uniquely vulnerable to aging and Alzheimer's pathology. We therefore investigated LTP at LPP inputs both within (4-6 weeks) and beyond (8+ weeks) the traditional critical period. At immature stages, adult-born neurons did not undergo significant LTP at LPP synapses, and often displayed long-term depression after theta burst stimulation. However, over the course of 3-4 months, adult-born neurons displayed increasingly greater amounts of LTP. Analyses of short-term plasticity point towards a presynaptic mechanism, where transmitter release probability declines as cells mature, providing a greater dynamic range for strengthening synapses. Collectively, our findings identify a novel form of new neuron plasticity that develops over an extended interval, and may therefore be relevant for maintaining cognitive function in aging.

Severity of Lesions Involving the Cortical Cholinergic Pathways May Be Associated With Cognitive Impairment in Subacute Ischemic Stroke.

Purpose: Impairment of cortical cholinergic pathways (CCP) is an important risk factor for chronic vascular cognitive impairment. However, this phenomenon has rarely been studied in post-stroke cognitive impairment (PSCI). We investigated the relationship between PSCI and CCP lesions assessed by structural magnetic resonance imaging (MRI).Patients and methods: We prospectively enrolled 103 patients within 7 days of ischemic stroke onset. CCP was measured by the cholinergic pathways hyperintensities scale (CHIPS), which semiquantitatively grades MR lesions strategically located on the CCP identified in human brains. We also measured other MRI parameters, including the location and volumes of acute infarcts, cerebral microbleeds, medial temporal lobe atrophy, and white matter lesions. Neuropsychological assessments were performed using the 60-min modified vascular dementia battery (VDB) at 3 months after the index stroke, and PSCI was defined according to VDB as well as ADL.Results: Of all 103 patients, 69 men (67.0%) and 34 women (33.0%) with a mean age of 57.22 ± 12.95 years, 55 patients (53.4%) were judged to have PSCI at 3 months, including 43 (41.7%) patients with PSCI-no dementia and 12 (11.7%) patients with poststroke dementia. According to the VBD assessment, the most commonly impaired cognitive domain was visuomotor speed (27.2%) followed by verbal memory (25.2%). Univariate analysis showed that patients with PSCI were older; had higher informant questionnaire on cognitive decline in the elderly (IQCODE) scores; had more frequent previous stroke history and atrial fibrillation; and had higher CHIPS scores, more severe white matter lesions, and medial temporal lobe atrophy. PSCI patients also had higher depression scores at 3 months. In the multivariate regression analysis, age, IQCODE score, CHIPS score, and Hamilton depression rating scale score were independent predictors of PSCI. Ordinal regression analysis for risk factors of poor functional outcomes revealed that IQCODE scores and cognitive function status were related to mRS score at 3 months after stroke.Conclusion: In patients with early subacute ischemic stroke, the severity of lesions involving the CCP may be associated with cognitive impairment at 3 months.Clinical Trial Registration: Chinese Clinical Trial Registry, identifier: ChiCTR1800014982.