Search

Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative disease resulting in memory loss and cognitive decline. Synaptic dysfunction is an early hallmark of the disease whose effects on whole-brain functional architecture can be identified using resting-state functionalMRI (rsfMRI). Insights into mechanisms of early, whole-brain network alterations can help our understanding of the functional impact of AD's pathophysiology. Methods: Here, we obtained rsfMRI data in the TgF344-AD rat model at the pre- and early-plaque stages. This model recapitulates the major pathological and behavioral hallmarks of AD. We used co-activation pattern (CAP) analysis to investigate if and how the dynamic organization of intrinsic brain functional networks states, undetectable by earliermethods, is altered at these early stages. Results: We identified and characterized six intrinsic brain states as CAPs, their spatial and temporal features, and the transitions between the different states. At the pre-plaque stage, the TgF344-AD rats showed reduced co-activation of hub regions in the CAPs corresponding to the default mode-like and lateral cortical network. Default mode-like network activity segregated into two distinct brain states, with one state characterized by high co-activation of the basal forebrain. This basal forebrain co-activation was reduced in TgF344-AD animals mainly at the pre-plaque stage. Brain state transition probabilities were altered at the pre-plaque stage between states involving the defaultmode-like network, lateral cortical network, and basal forebrain regions. Additionally, while the directionality preference in the network-state transitions observed in the wild-type animals at the pre-plaque stage had diminished at the early-plaque stage, TgF344-AD animals continued to show directionality preference at both stages. Discussion: Our study enhances the understanding of intrinsic brain state dynamics and how they are impacted at the early stages of AD, providing a nuanced characterization of the early, functional impact of the disease's neurodegenerative process. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a severe neurodegenerative disorder caused by the accumulation of toxic proteins, amyloid-beta (Aβ) and tau, which eventually leads to dementia. Disease-modifying therapies are still lacking, due to incomplete insights into the neuropathological mechanisms of AD. Synaptic dysfunction is known to occur before cognitive symptoms become apparent and recent studies have demonstrated that imbalanced synaptic signaling drives the progression of AD, suggesting that early synaptic dysfunction could be an interesting therapeutic target. Synaptic dysfunction results in altered oscillatory activity, which can be detected with electroencephalography and electrophysiological recordings. However, the majority of these studies have been performed at advanced stages of AD, when extensive damage and cognitive symptoms are already present. The current study aimed to investigate if the hippocampal oscillatory activity is altered at pre-plaque stages of AD. The rats received stereotactic surgery to implant a laminar electrode in the CA1 layer of the right hippocampus. Electrophysiological recordings during two consecutive days in an open field were performed in 4-5-month-old TgF344-AD rats when increased concentrations of soluble Aβ species were observed in the brain, in the absence of Aβ-plaques. We observed a decreased power of high theta oscillations in TgF344-AD rats compared to wildtype littermates. Sharp wave-ripple (SWR) analysis revealed an increased SWR power and a decreased duration of SWR during quiet wake in TgF344-AD rats. The alterations in properties of SWR and the increased power of fast oscillations are suggestive of neuronal hyperexcitability, as has been demonstrated to occur during presymptomatic stages of AD. In addition, decreased strength of thetagamma coupling, an important neuronal correlate of memory encoding, was observed in the TgF344-AD rats. Theta-gamma phase amplitude coupling has been associated with memory encoding and the execution of cognitive functions. Studies have demonstrated that mild cognitive impairment patients display decreased coupling strength, similar to what is described here. The current study demonstrates altered hippocampal network activity occurring at pre-plaque stages of AD and provides insights into prodromal network dysfunction in AD. The alterations observed could aid in the detection of AD during presymptomatic stages. [ABSTRACT FROM AUTHOR]

One of the main challenges in brain research is to link all aspects of brain function: on a cellular, systemic, and functional level. Multimodal neuroimaging methodology provides a continuously evolving platform. Being able to combine calcium imaging, optogenetics, electrophysiology, chemogenetics, and functional magnetic resonance imaging (fMRI) as part of the numerous efforts on brain functional mapping, we have a unique opportunity to better understand brain function. This review will focus on the developments in application of these tools within fMRI studies and highlight the challenges and choices neurosciences face when designing multimodal experiments. [ABSTRACT FROM AUTHOR]

Random dot kinematograms (RDKs) have recently been used to train subjects with cortical scotomas to perform direction of motion discrimination, partially restoring visual motion perception. To study the recovery of visual perception, it is important to understand how visual areas in normal subjects and subjects with cortical scotomas respond to RDK stimuli. Studies in normal subjects have shown that blood oxygen level-dependent (BOLD) responses in human area hV5/MT+ increase monotonically with coherence, in general agreement with electrophysiology studies in primates. However, RDK responses in prior studies were obtained while the subject was performing fixation, not a motion discrimination condition. Furthermore, BOLD responses were gauged against a baseline condition of uniform illumination or static dots, potentially decreasing the specificity of responses for the spatial integration of local motion signals (motion coherence). Here, we revisit this question starting from a baseline RDK condition of no coherence, thereby isolating the component of BOLD response due specifically to the spatial integration of local motion signals. In agreement with prior studies, we found that responses in the area hV5/MT+ of healthy subjects were monotonically increasing when subjects fixated without performing a motion discrimination task. In contrast, when subjects were performing an RDK direction of motion discrimination task, responses in the area hV5/MT+ remained flat, changing minimally, if at all, as a function of motion coherence. A similar pattern of responses was seen in the area hV5/MT+ of subjects with dense cortical scotomas performing direction of motion discrimination for RDKs presented inside the scotoma. Passive RDK presentation within the scotoma elicited no significant hV5/MT+ responses. These observations shed further light on how visual cortex responses behave as a function of motion coherence, helping to prepare the ground for future studies using these methods to study visual system recovery after injury. [ABSTRACT FROM AUTHOR]

In the adult visual system, topographic reorganization of the primary visual cortex (V1) after retinal lesions has been extensively investigated. In contrast, the plasticity of higher order extrastriate areas following retinal lesions is less well studied. Here, we used fMRI to study reorganization of visual areas V2/V3 following the induction of permanent, binocular, homonymous retinal lesions in 4 adult macaque monkeys. We found that the great majority of voxels that did not show visual modulation on the day of the lesion in the V2/V3 lesion projection zone (LPZ) demonstrated significant visual modulations 2 weeks later, and the mean modulation strength remained approximately stable thereafter for the duration of our observations (4–5 months). The distribution of eccentricities of visually modulated voxels inside the V2/V3 LPZ spanned a wider range post-lesion than pre-lesion, suggesting that neurons inside the LPZ reorganize by receiving input either from the foveal or the peripheral border of the LPZ, depending on proximity. Overall, we conclude that area V2/V3 of adult rhesus macaques displays a significant capacity for topographic reorganization following retinal lesions markedly exceeding the corresponding capacity of area V1. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), a neurodegenerative disorder marked by accumulation of extracellular amyloid-β (Aβ) plaques leads to progressive loss of memory and cognitive function. Resting-state fMRI (RS-fMRI) studies have provided links between these two observations in terms of disruption of default mode and task-positive resting-state networks (RSNs). Important insights underlying these disruptions were recently obtained by investigating dynamic fluctuations in RS-fMRI signals in old TG2576 mice (a mouse model of amyloidosis) using a set of quasi-periodic patterns (QPP). QPPs represent repeating spatiotemporal patterns of neural activity of predefined temporal length. In this article, we used an alternative methodology of co-activation patterns (CAPs) that represent instantaneous and transient brain configurations that are likely contributors to the emergence of commonly observed RSNs and QPPs. We followed a recently published approach for obtaining CAPs that divided all time frames, instead of those corresponding to supra-threshold activations of a seed region as done traditionally, to extract CAPs from RS-fMRI recordings in 10 TG2576 female mice and eight wild type littermates at 18 months of age. Subsequently, we matched the CAPs from the two groups using the Hungarian method and compared the temporal (duration, occurrence rate) and the spatial (lateralization of significantly co-activated and co-deactivated voxels) properties of matched CAPs. We found robust differences in the spatial components of matched CAPs. Finally, we used supervised learning to train a classifier using either the temporal or the spatial component of CAPs to distinguish the transgenic mice from the WT. We found that while duration and occurrence rates of all CAPs performed the classification with significantly higher accuracy than the chance-level, blood oxygen level-dependent (BOLD) signals of significantly activated voxels from individual CAPs turned out to be a significantly better predictive feature demonstrating a near-perfect classification accuracy. Our results demonstrate resting-state co-activation patterns are a promising candidate in the development of a diagnostic, and potentially, prognostic RS-fMRI biomarker of AD. [ABSTRACT FROM AUTHOR]

Sensory input is inherently ambiguous but our brains achieve remarkable perceptual stability. Prior experience and knowledge of the statistical properties of the world are thought to play a key role in the stabilization process. Individual differences in responses to ambiguous input and biases toward one or the other interpretation could modulate the decision mechanism for perception. However, the role of perceptual bias and its interaction with stimulus spatial properties such as regularity and element density remain to be understood. To this end, we developed novel bi-stable moving visual stimuli in which perception could be parametrically manipulated between two possible mutually exclusive interpretations: transparently or coherently moving. We probed perceptual stability across three composite stimulus element density levels with normal or degraded regularity using a factorial design. We found that increased density led to the amplification of individual biases and consequently to a stabilization of one interpretation over the alternative. This effect was reduced for degraded regularity, demonstrating an interaction between density and regularity. To understand how prior knowledge could be used by the brain in this task, we compared the data with simulations coming from four different hierarchical models of causal inference. These models made different assumptions about the use of prior information by including conditional priors that either facilitated or inhibited motion direction integration. An architecture that included a prior inhibiting motion direction integration consistently outperformed the others. Our results support the hypothesis that direction integration based on sensory likelihoods maybe the default processing mode with conditional priors inhibiting integration employed in order to help motion segmentation and transparency perception. [ABSTRACT FROM AUTHOR]

Discovering neural correlates of subjective perception and dissociating them from sensory input has fascinated neuroscientists for a long time. Bistable and multistable perception phenomena have exhibited great experimental potential to address this question. Here, we performed electrophysiological recordings from single neurons in lateral intraparietal area (LIP) of rhesus macaques during stimulus and perceptual transitions induced by binocular flash suppression (BFS). LIP neurons demonstrated transient bursts of activity after stimulus presentation and stimulus or perceptual switches but only a minority of cells demonstrated stimulus and perceptual selectivity. To enhance LIP neural selectivity, we performed a second experiment in which the competing stimuli were associated with asymmetric rewards. We found that transient and sustained activities substantially increased while the proportion of stimulus selective neurons remained approximately the same, albeit with increased selectivity magnitude. In addition, we observed mild increases in the proportion of perceptually selective neurons which also showed increase magnitude of selectivity. Importantly, the increased selectivity of cells after the reward manipulation was not directly reflecting the reward size per se but an enhancement in stimulus differentiation. Based on our results, we conjecture that LIP contributes to perceptual transitions and serves a modulatory role in perceptual selection taking into account the stimulus behavioral value. [ABSTRACT FROM AUTHOR]

Despite being commonly referenced throughout neuroscientific research on songbirds, reports of hemispheric specialization in the processing of song remain controversial. The notion of such asymmetries in songbirds is further complicated by evidence that both cerebral hemispheres in humans may be specialized for different aspects of speech perception. Some studies suggest that the auditory neural substrates in the left and right hemispheres of humans process temporal and spectral elements within speech sounds, respectively. To determine whether songbirds process their conspecific songs in such a complementary, bilateral manner, we performed functional magnetic resonance imaging (fMRI) on 15 isoflurane anesthetized adult male zebra finches (Taeniopygia guttata) while presenting them with (1) non-manipulated, (2) spectrally-filtered (reduced spectral structure), and (3) temporally-filtered (reduced temporal structure) conspecific song. Our results revealed sensitivity of both primary (Field L) and secondary (caudomedial nidopallium, NCM) auditory regions to changes in spectral and temporal structure of song. On the one hand, temporally-filtered song elicited a bilateral decrease in neural responses compared to the other stimulus types. On the other hand, spectrally filtered song elicited significantly greater responses in left Field L and NCM than temporally filtered or non-manipulated song while concurrently reducing the response relative to non-manipulated song in the right auditory forebrain. The latter hemispheric difference in sensitivity to manipulations of spectral structure in song, suggests that there is an asymmetry in spectral and temporal domain processing in the zebra finch auditory forebrain bearing some resemblance to what has been observed in human auditory cortex. [ABSTRACT FROM AUTHOR]

Using functional magnetic resonance imaging in awake behaving monkeys we investigated how species-specific vocalizations are represented in auditory and auditory-related regions of the macaque brain. We found clusters of active voxels along the ascending auditory pathway that responded to various types of complex sounds: inferior colliculus (IC), medial geniculate nucleus (MGN), auditory core, belt, and parabelt cortex, and other parts of the superior temporal gyrus (STG) and sulcus (STS). Regions sensitive to monkey calls were most prevalent in the anterior STG, but some clusters were also found in frontal and parietal cortex on the basis of comparisons between responses to calls and environmental sounds. Surprisingly, we found that spectrotemporal control sounds derived from the monkey calls ("scrambled calls") also activated the parietal and frontal regions. Taken together, our results demonstrate that species-specific vocalizations in rhesus monkeys activate preferentially the auditory ventral stream, and in particular areas of the antero-lateral belt and parabelt. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various reports within the issue on topics including the interaction between binocular rivalry and selective attention, the role of visual adaptation for alternations of binocular rivalry, and influence of fear expression to perceptual dominance during rivalry.