Theta/delta coupling across cortical laminae contributes to semantic cognition

Background: Semantic and phonological processing deficits are often present in aphasia. The degree of interdependence between the deficits has been widely studied with variable findings. Semantic variables such as category and typicality have been found to influence semantic processing in healthy individuals and persons with aphasia (PWA), but their influence on phonological processing is unknown.Aims: This study examined the nature of semantic and phonological access in aphasia by comparing adults with aphasia to healthy control participants. Semantic and phonological tasks were used to assess the difference in processing requirements between and within each group as well as examine the effects of category and typicality on different stages of semantic and phonological processing.Methods & Procedures: Thirty-two PWA and 10 neurologically healthy adults were administered nine tasks: Category Superordinate, Category Coordinate, Semantic Feature, Rhyme Judgment (No-Name), Syllable Judgment (No-Name), Phoneme Verification (No-Name), Rhyme Judgment (Name-Provided), Syllable Judgment (Name-Provided), and Phoneme Verification (Name-Provided). Accuracy and reaction time (RT) data were collected for each of these tasks and between-group and within-group differences were analysed via MANOVA/MANCOVA and hierarchical clustering analyses.Outcomes & Results: PWA performed with significantly lower accuracy than controls on phonological tasks but performed comparably on semantic tasks. Participants with aphasia were significantly slower than controls on all semantic and phonological tasks. Clustering of the nine tasks by accuracy revealed different processing requirements in the participants with aphasia compared to the control group while clustering by RT revealed similar trends in both groups in that phonological (no-name) items required the most processing time. Significant effects of category and typicality were noted in the semantic tasks but not in any of the phonological tasks.Conclusions: Individuals with aphasia demonstrated overall impaired phonological processing with relatively preserved semantic processing as compared to controls. Per accuracy and RT measures, distinct trends in processing load for semantic tasks versus phonological tasks were seen in the individuals with aphasia whereas only speed of processing and not accuracy was impacted by phonological processing load in the control group. The results align most closely with discrete serial processing models of lexical processing as category and typicality effects were robust in the semantic tasks but not in any of the phonological tasks. Alternative explanations for these results also are discussed.

Traumatic brain injury (TBI) affects neural function at the local injury site and also at distant, connected brain areas. However, the real-time neural dynamics in response to injury and subsequent effects on sensory processing and behaviour are not fully resolved, especially across a range of spatial scales. We used in vivo calcium imaging in awake, head-restrained male and female mice to measure large-scale and cellular resolution neuronal activation, respectively, in response to a mild/moderate TBI induced by focal controlled cortical impact (CCI) injury of the motor cortex (M1). Widefield imaging revealed an immediate CCI-induced activation at the injury site, followed by a massive slow wave of calcium signal activation that travelled across the majority of the dorsal cortex within approximately 30s. Correspondingly, two-photon calcium imaging in the primary somatosensory cortex (S1) found strong activation of neuropil and neuronal populations during the CCI-induced travelling wave. A depression of calcium signals followed the wave, during which we observed the atypical activity of a sparse population of S1 neurons. Longitudinal imaging in the hours and days after CCI revealed increases in the area of whisker-evoked sensory maps at early time points, in parallel to decreases in cortical functional connectivity and behavioural measures. Neural and behavioural changes mostly recovered over hours to days in our M1-TBI model, with a more lasting decrease in the number of active S1 neurons. Our results in unanaesthetized mice describe novel spatial and temporal neural adaptations that occur at cortical sites remote to a focal brain injury.

Brief optogenetic stimulation of thalamocortical axons evoked a 400 Hz wavelet, 'ripplet,' in the extracellular field potential in cortical layer 4, together with phase-locked spike bursts in fast-spiking inhibitory interneurons and alternating excitatory and inhibitory synaptic currents in excitatory cells.

The extent to which the neural systems underlying semantic processes degrade with advanced age remains unresolved, which motivated the current study of neural activation on functional magnetic resonance imaging (fMRI) during semantic judgments of associated vs. unassociated, semantic vs. rhyme, and abstract vs. rhyme word pairs. Thirty-eight older adults, 55-85years of age, performed semantic association decision tasks in a mixed event-related block fMRI paradigm involving binary judgments as to whether word pairs were related (i.e., semantically associated). As hypothesized, significantly greater activation was evident during processing of associated (vs. unassociated) word pairs in cortical areas implicated in semantic processing, including the angular gyrus, temporal cortex, and inferior frontal cortex. Cortical areas showed greater activation to unassociated (vs. associated) word pairs, primarily within a large occipital cluster. Greater activation was evident in cortical areas when response to semantic vs. phonemic word pairs. Contrasting activation during abstract vs. concrete semantic processing revealed areas of co-activation to both semantic classes, and areas that had greater response to either abstract or concrete word pairs. Neural activation across conditions did not vary as a function of greater age, indicating only minimal age-associated perturbation in neural activation during semantic processing. Therefore, the response of the semantic hubs, semantic control, and secondary association areas appear to be largely preserved with advanced age among older adults exhibiting successful cognitive aging. These findings may provide a useful clinical contrast if compared to activation among adults experiencing cognitive decline due Alzheimer's, frontal-temporal dementia, and other neurodegenerative diseases.

Semantic processing impairment in individuals with schizotypal personality disorder features: A preliminary event-related potential study

Electroencephalographic (EEG) abnormalities are seen in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) with characteristic features of cognitive impairment. The most common findings of EEG features in AD and MCI patients are increased relative power of slow oscillations (delta and theta rhythms) and decreased relative power of fast oscillations (alpha, beta and gamma rhythms). However, impairments in cognitive processes in AD and MCI are not sufficiently reflected by brain oscillatory activity in a particular frequency band. MCI patients are at high risk of progressing to AD. Cross-frequency coupling (CFC), which refers to coupling between different frequency bands, is a crucial tool for comprehending changes in brain oscillations and cognitive performance. CFC features exhibit some specificity in patients with AD and MCI, but a comparison between CFC features in individuals with these disorders is still lacking. The aim of this study was to explore changes in CFC properties in MCI and AD and to explore the relationship between CFC properties and multiple types of cognitive functional performance. We recorded resting-state EEG (rsEEG) signals in 46 MCI patients, 43 AD patients, and 43 cognitively healthy controls (HCs) and analyzed the changes in CFC as well as the relationship between CFC and scores on clinical tests of cognitive function. Multiple couplings between low-frequency oscillations and high-frequency oscillations were found to be significantly enhanced in AD patients compared to those of HCs and MCI, while delta-gamma as well as theta-gamma couplings in the right temporal and parietal lobes were significantly enhanced in MCI patients compared to HCs. Moreover, theta-gamma coupling in the right temporal lobe tended to be stronger in MCI patients than in HCs, and it was stronger in AD than in MCI. Multiple CFC properties were found to correlate significantly with various cognitive domains, especially the memory function domain. Overall, these findings suggest that AD and MCI patients must use more neural resources to maintain a resting brain state and that alterations in theta-gamma coupling in the temporal lobe become progressively obvious during disease progression and are likely to be a valuable indicator of MCI and AD pathology.

The dorsal medial prefrontal cortex and basolateral amygdala exhibit social behavior-relevant neuronal oscillations, representing unified pathophysiological mechanisms underlying social behavioral deficits.

Histamine is a neurotransmitter that modulates neuronal activity and regulates various brain functions. Histamine H3 receptor (H3R) antagonists/inverse agonists enhance its release in most brain regions, including the cerebral cortex, which improves learning and memory and exerts an antiepileptic effect. However, the mechanism underlying the effect of H3R antagonists/inverse agonists on cortical neuronal activity in vivo remains unclear. Here, we show the mechanism by which pitolisant, an H3R antagonist/inverse agonist, influenced perirhinal cortex (PRh) activity in individual neuron and neuronal population levels. We monitored neuronal activity in the PRh of freely moving mice using in vivo Ca2+ imaging through a miniaturized one-photon microscope. Pitolisant increased the activity of some PRh neurons while decreasing the activity of others without affecting the mean neuronal activity across neurons. Moreover, it increases neuron pairs with synchronous activity in excitatory-responsive neuronal populations. Furthermore, machine learning analysis revealed that pitolisant altered the neuronal population activity. The changes in the population activity were dependent on the neurons that were excited and inhibited by pitolisant treatment. These findings indicate that pitolisant influences the activity of a subset of PRh neurons by increasing the synchronous activity and modifying the population activity.

Connectivity among semantic associates: An fMRI study of semantic priming

Differential frontal activation in schizophrenia and bipolar illness during verbal fluency

A PET Study of Stimulus- and Task-Induced Semantic Processing

Working memory, a fundamental cognitive function of the brain, necessitates the evaluation of cognitive load intensity due to limited cognitive resources. Optimizing cognitive load can enhance task performance efficiency by preventing resource waste and overload. Therefore, identifying working memory load is an essential area of research. Deep learning models have demonstrated remarkable potential in identifying the intensity of working memory load. However, existing neural networks based on electroencephalogram (EEG) decoding primarily focus on temporal and spatial characteristics while neglecting frequency characteristics. Drawing inspiration from the role of cross-frequency coupling in the hippocampal region, which plays a crucial role in advanced cognitive processes such as working memory, this study proposes a Multi-Band Multi-Scale Hybrid Sinc Convolutional Neural Network (MBSincNex). This model integrates multi-frequency and multi-scale Sinc convolution to facilitate time-frequency conversion and extract time-frequency information from multiple rhythms and regions of the EEG data with the aim of effectively model the cross-frequency coupling across different cognitive domains. Due to its unique structural design, the proposed model proficiently extracts features in temporal, frequency, and spatial domains while its feature extraction capability is validated through post-hoc interpretability techniques. On our collected three-class working memory dataset, the proposed model achieved higher classification accuracy compared to other state-of-the-art methods. Furthermore, by analyzing the model's classification performance during different stages of working memory processes, this study emphasizes the significance of the encoding phase and confirms that behavioral response does not accurately reflect cognitive load.

Characteristics and classification of hippocampal theta rhythm induced by passive translational displacement

Large cortical and hippocampal pyramidal neurons are elements of neuronal circuitry that have been implicated in cross-frequency coupling (CFC) during cognitive tasks. We investigate potential mechanisms for CFC within these neurons by examining the role that the hyperpolarization-activated mixed cation current (Ih) plays in modulating CFC characteristics in multicompartment neuronal models. We quantify CFC along the soma-apical dendrite axis and tuft of three models configured to have different spatial distributions of Ih conductance density: (1) exponential gradient along the soma-apical dendrite axis, (2) uniform distribution, and (3) no Ih conductance. We simulated two current injection scenarios: distal apical 4 Hz modulation and perisomatic 4 Hz modulation, each with perisomatic, mid-apical, and distal apical 40 Hz injections. We used two metrics to quantify CFC strength—modulation index and height ratio—and we analyzed CFC phase properties. For all models, CFC was strongest in distal apical regions when the 40 Hz injection occurred near the soma and the 4 Hz modulation occurred in distal apical dendrite. The strongest CFC values were observed in the model with uniformly distributed Ih conductance density, but when the exponential gradient in Ih conductance density was added, CFC strength decreased by almost 50%. When Ih was in the model, regions with much larger membrane potential fluctuations at 4 Hz than at 40 Hz had stronger CFC. Excluding the Ih conductance from the model resulted in CFC either reduced or comparable in strength relative to the model with the exponential gradient in Ih conductance. The Ih conductance also imposed order on the phase characteristics of CFC such that minimum (maximum) amplitude 40 Hz membrane potential oscillations occurred during Ih conductance deactivation (activation). On the other hand, when there was no Ih conductance, phase relationships between minimum and maximum 40 Hz oscillation often inverted and occurred much closer together. This analysis can help experimentalists discriminate between CFC that originates from different underlying physiological mechanisms and can help illuminate the reasons why there are differences between CFC strength observed in different regions of the brain and between different populations of neurons based on the configuration of the Ih conductance.

Persistent activity in populations of neurons, time-varying activity across a neural population, or activity-silent mechanisms carried out by hidden internal states of the neural population have been proposed as different mechanisms of working memory (WM). Whether these mechanisms could be mutually exclusive or occur in the same neuronal circuit remains, however, elusive, and so do their biophysical underpinnings. While WM is traditionally regarded to depend purely on neuronal mechanisms, cortical networks also include astrocytes that can modulate neural activity. We propose and investigate a network model that includes both neurons and glia and show that glia-synapse interactions can lead to multiple stable states of synaptic transmission. Depending on parameters, these interactions can lead in turn to distinct patterns of network activity that can serve as substrates for WM.