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Resting-state functional magnetic resonance imaging (RS-fMRI) has been extensively utilized for noninvasive investigation of human brain activity. While studies employing simultaneous recordings of fMRI and electrophysiology have established a connection between the low-frequency fluctuation (< 0.1 Hz) observed in RS-fMRI and the local field potential (LFP), it remains unclear whether the RS-fMRI signal exhibits frequency-dependent modulation, which is a well-documented phenomenon in LFP. The present study concurrently recorded resting-state functional magnetic resonance imaging (RS-fMRI) and local field potentials (LFP) in the striatum of 8 rats before and after a pharmacological manipulation. We observed a highly similar frequency-dependent pattern of amplitude changes in both RS-fMRI and LFP following the manipulation, specifically an increase in high-frequency band amplitudes accompanied by a decrease in low-frequency band amplitudes. These findings provide direct evidence that the enhanced high-frequency fluctuations and reduced low-frequency fluctuations observed in RS-fMRI may reflect heightened neuronal activity. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) increases the risk of neurological diseases, yet how brain oscillations change as age and T2DM interact is not well characterized. To delineate the age and diabetic effect on neurophysiology, we recorded local field potentials with multichannel electrodes spanning the somatosensory cortex and hippocampus (HPC) under urethane anesthesia in diabetic and normoglycemic control mice, at 200 and 400 days of age. We analyzed the signal power of brain oscillations, brain state, sharp wave associate ripples (SPW-Rs), and functional connectivity between the cortex and HPC. We found that while both age and T2DM were correlated with a breakdown in long-range functional connectivity and reduced neurogenesis in the dentate gyrus and subventricular zone, T2DM further slowed brain oscillations and reduced theta-gamma coupling. Age and T2DM also prolonged the duration of SPW-Rs and increased gamma power during SPW-R phase. Our results have identified potential electrophysiological substrates of hippocampal changes associated with T2DM and age. The perturbed brain oscillation features and diminished neurogenesis may underlie T2DM-accelerated cognitive impairment. [ABSTRACT FROM AUTHOR]

Social behaviors such as cooperation are crucial for mammals. A deeper knowledge of the neuronal mechanisms underlying cooperation can be beneficial for people suffering from pathologies with impaired social behavior. Our aim was to study the brain activity when two animals synchronize their behavior to obtain a mutual reinforcement. In a previous work, we showed that the activity of the prelimbic cortex (PrL) was enhanced during cooperation in rats, especially in the ones leading most cooperative trials (leader rats). In this study, we investigated the specific cells in the PrL contributing to cooperative behaviors. To this end, we collected rats' brains at key moments of the learning process to analyze the levels of c-FOS expression in the main cellular groups of the PrL. Leader rats showed increased c-FOS activity in cells expressing D1 receptors during cooperation. Besides, we analyzed the levels of anxiety, dominance, and locomotor behavior, finding that leader rats are in general less anxious and less dominant than followers. We also recorded local field potentials (LFPs) from the PrL, the nucleus accumbens septi (NAc), and the basolateral amygdala (BLA). A spectral analysis showed that delta activity in PrL and NAc increased when rats cooperated, while BLA activity in delta and theta bands decreased considerably during cooperation. The PrL and NAc also increased their connectivity in the high theta band during cooperation. Thus, the present work identifies the specific PrL cell types engaged in this behavior, as well as the way this information is propagated to selected downstream brain regions (BLA, NAc). [ABSTRACT FROM AUTHOR]

Purpose: The objective is to suggest time as an important variable to consider in the network model, specifically when discussing causality. Methods: There is a consideration of the context of functional connectivity because of the time importance of observing the feature inside the neuroscience context. A network model was constructed using the Bayesian network method, utilizing a dataset consisting of three rats' local field potentials. The model took into consideration the time delay of communication among brain areas, as recorded in this study. In pursuit of this objective, the delayed mutual information method was employed to ascertain the temporal delay between local field potentials and K2 score for the purpose of model comparison. Results: Bayesian network depicted the probabilistic relationship among rat's brain areas. Delayed mutual information captured the lag among brain areas, and after its appliance on the Bayesian network model, posed better results. Conclusion: The primary novelty of this research lies in its integration of minor delays within the Bayesian network approach, accomplished through the utilization of the delayed mutual information technique prior to its implementation. The suggested methodology incorporates an essential feature that supports the analysis of functional connectivity among brain areas, thereby providing support for the dynamics of neurophysiology. [ABSTRACT FROM AUTHOR]

Despite advances in understanding the cellular and molecular processes underlying memory and cognition, and recent successful modulation of cognitive performance in brain disorders, the neurophysiological mechanisms remain underexplored. High frequency oscillations beyond the classic electroencephalogram spectrum have emerged as a potential neural correlate of fundamental cognitive processes. High frequency oscillations are detected in the human mesial temporal lobe and neocortical intracranial recordings spanning gamma/epsilon (60–150 Hz), ripple (80–250 Hz) and higher frequency ranges. Separate from other non-oscillatory activities, these brief electrophysiological oscillations of distinct duration, frequency and amplitude are thought to be generated by coordinated spiking of neuronal ensembles within volumes as small as a single cortical column. Although the exact origins, mechanisms and physiological roles in health and disease remain elusive, they have been associated with human memory consolidation and cognitive processing. Recent studies suggest their involvement in encoding and recall of episodic memory with a possible role in the formation and reactivation of memory traces. High frequency oscillations are detected during encoding, throughout maintenance, and right before recall of remembered items, meeting a basic definition for an engram activity. The temporal coordination of high frequency oscillations reactivated across cortical and subcortical neural networks is ideally suited for integrating multimodal memory representations, which can be replayed and consolidated during states of wakefulness and sleep. High frequency oscillations have been shown to reflect coordinated bursts of neuronal assembly firing and offer a promising substrate for tracking and modulation of the hypothetical electrophysiological engram. [ABSTRACT FROM AUTHOR]

• More affected (MA) STN comprises more pause-burst neurons compared to less affected. • Oscillations of pause-burst neurons in MA STN correlate with bradykinesia and rigidity. • More affected STNs feature greater oscillation power in the alpha-beta range. We aimed to establish specific biomarkers of Parkinson's disease (PD) by comparing activity of more affected (MA) and less affected (LA) subthalamic nucleus (STN) of patients with prominent clinical asymmetry. We recorded single unit activity and local field potentials (LFP) of the STN during deep brain stimulation surgeries. Neuronal firing patterns and discharge rate, as well as oscillatory features of both single cells and LFP, were analyzed. We observed notable differences in proportions of irregular-burst and pause-burst, but not tonic neurons, between the hemispheres. Oscillations of pause-burst neurons correlated significantly with the bradykinesia and rigidity scores of the corresponding hemibody. LFP derived from MA STN featured greater power in 12–15 Hz. Our results provide evidence that the increased proportion of units with prolonged pauses may be associated with PD. We also speculate that some of them may gain rhythmicity in the alpha-beta range in relation to hypokinetic symptoms, long-term disease, or both. Our findings highlight the relation between specific oscillatory features of the STN, predominance of subthalamic pause-burst units and PD pathophysiology. [ABSTRACT FROM AUTHOR]

Synaptic plasticity is an essential process encoding fine-tuned brain functions, but models to study this process in adult human systems are lacking. We aim to test whether ex vivo organotypic culture of post-mortem adult brain explants (OPABs) retain synaptic plasticity. OPABs were seeded on 3D microelectrode arrays to measure local field potential (LFP). Paired stimulation of distant electrodes was performed over three days to investigate our capacity to modulate specific neuronal connections. Long-term potentiation (LTP) or depression (LTD) did not occur within a single day. In contrast, after two and three days of training, OPABs showed a significant modulation of the paired electrodes' response compared to the non-paired electrodes from the same array. This response was alleviated upon treatment with dopamine. Our work highlights that adult human brain explants retain synaptic plasticity, offering novel approaches to neural circuitry in animal-free models. • Ex vivo culture of post-mortem brain explants (OPAB) respond to electrical stimulation. • Induction of long-term potentiation in OPAB occurs upon multiday test/training phases. • Dopamine treatment prevents focalized long-term potentiation induction in OPAB. [ABSTRACT FROM AUTHOR]

Abstract Purpose The objective is to suggest time as an important variable to consider in the network model, specifically when discussing causality. Methods There is a consideration of the context of functional connectivity because of the time importance of observing the feature inside the neuroscience context. A network model was constructed using the Bayesian network method, utilizing a dataset consisting of three rats’ local field potentials. The model took into consideration the time delay of communication among brain areas, as recorded in this study. In pursuit of this objective, the delayed mutual information method was employed to ascertain the temporal delay between local field potentials and K2 score for the purpose of model comparison. Results Bayesian network depicted the probabilistic relationship among rat’s brain areas. Delayed mutual information captured the lag among brain areas, and after its appliance on the Bayesian network model, posed better results. Conclusion The primary novelty of this research lies in its integration of minor delays within the Bayesian network approach, accomplished through the utilization of the delayed mutual information technique prior to its implementation. The suggested methodology incorporates an essential feature that supports the analysis of functional connectivity among brain areas, thereby providing support for the dynamics of neurophysiology.

Background: Synaptic plasticity is an essential process encoding fine-tuned brain functions, but models to study this process in adult human systems are lacking. Objective: We aim to test whether ex vivo organotypic culture of post-mortem adult brain explants (OPABs) retain synaptic plasticity. Methods: OPABs were seeded on 3D microelectrode arrays to measure local field potential (LFP). Paired stimulation of distant electrodes was performed over three days to investigate our capacity to modulate specific neuronal connections. Results: Long-term potentiation (LTP) or depression (LTD) did not occur within a single day. In contrast, after two and three days of training, OPABs showed a significant modulation of the paired electrodes’ response compared to the non-paired electrodes from the same array. This response was alleviated upon treatment with dopamine. Conclusion: Our work highlights that adult human brain explants retain synaptic plasticity, offering novel approaches to neural circuitry in animal-free models.

Abstract The auditory steady state response (ASSR) arises when periodic sounds evoke stable responses in auditory networks that reflect the acoustic characteristics of the stimuli, such as the amplitude of the sound envelope. Larger for some stimulus rates than others, the ASSR in the human electroencephalogram (EEG) is notably maximal for sounds modulated in amplitude at 40 Hz. To investigate the local circuit underpinnings of the large ASSR to 40 Hz amplitude-modulated (AM) sounds, we acquired skull EEG and local field potential (LFP) recordings from primary auditory cortex (A1) in the rat during the presentation of 20, 30, 40, 50, and 80 Hz AM tones. 40 Hz AM tones elicited the largest ASSR from the EEG acquired above auditory cortex and the LFP acquired from each cortical layer in A1. The large ASSR in the EEG to 40 Hz AM tones was not due to larger instantaneous amplitude of the signals or to greater phase alignment of the LFP across the cortical layers. Instead, it resulted from decreased latency variability (or enhanced temporal consistency) of the 40 Hz response. Statistical models indicate the EEG signal was best predicted by LFPs in either the most superficial or deep cortical layers, suggesting deep layer coordinators of the ASSR. Overall, our results indicate that the recruitment of non-uniform but more temporally consistent responses across A1 layers underlie the larger ASSR to amplitude-modulated tones at 40 Hz.

Background: Enhancing slow waves, the electrophysiological (EEG) manifestation of non-rapid eye movement (NREM) sleep, could potentially benefit patients with Parkinson's disease (PD) by improving sleep quality and slowing disease progression. Phase-targeted auditory stimulation (PTAS) is an approach to enhance slow waves, which are detected in real-time in the surface EEG signal. Objective: We aimed to test whether the local-field potential of the subthalamic nucleus (STN-LFP) can be used to detect frontal slow waves and assess the electrophysiological changes related to PTAS. Methods: We recruited patients diagnosed with PD and undergoing Percept™ PC neurostimulator (Medtronic) implantation for deep brain stimulation of STN (STN-DBS) in a two-step surgery. Patients underwent three full-night recordings, including one between-surgeries recording and two during rehabilitation, one with DBS+ (on) and one with DBS- (off). Surface EEG and STN-LFP signals from Percept PC were recorded simultaneously, and PTAS was applied during sleep in all three recording sessions. Results: Our results show that during NREM sleep, slow waves of the cortex and STN are time-locked. PTAS application resulted in power and coherence changes, which can be detected in STN-LFP. Conclusion: Our findings suggest the feasibility of implementing PTAS using solely STN-LFP signal for slow wave detection, thus without a need for an external EEG device alongside the implanted neurostimulator. Moreover, we propose options for more efficient STN-LFP signal preprocessing, including different referencing and filtering to enhance the reliability of cortical slow wave detection in STN-LFP recordings.

The consolidation of memory is thought to ultimately depend on the synthesis of new proteins, since translational inhibitors such as anisomycin and cycloheximide adversely affect the permanence of long‐term memory. However, when applied directly in brain, these agents also profoundly suppress neural activity to an extent that is directly correlated to the degree of protein synthesis inhibition caused. Given that neural activity itself is likely to help mediate consolidation, this finding is a serious criticism of the strict de novo protein hypothesis of memory. Here, we test the neurophysiological effects of another translational inhibitor, emetine. Unilateral intra‐hippocampal infusion of emetine suppressed ongoing local field and multiunit activity at ipsilateral sites as compared to the contralateral hippocampus in a fashion that was positively correlated to the degree of protein synthesis inhibition as confirmed by autoradiography. This suppression of activity was also specific to the circumscribed brain region in which protein synthesis inhibition took place. These experiments provide further evidence that ongoing protein synthesis is necessary and fundamental for neural function and suggest that the disruption of memory observed in behavioral experiments using translational inhibitors may be due, in large part, to neural suppression. [ABSTRACT FROM AUTHOR]

The auditory steady state response (ASSR) arises when periodic sounds evoke stable responses in auditory networks that reflect the acoustic characteristics of the stimuli, such as the amplitude of the sound envelope. Larger for some stimulus rates than others, the ASSR in the human electroencephalogram (EEG) is notably maximal for sounds modulated in amplitude at 40 Hz. To investigate the local circuit underpinnings of the large ASSR to 40 Hz amplitude-modulated (AM) sounds, we acquired skull EEG and local field potential (LFP) recordings from primary auditory cortex (A1) in the rat during the presentation of 20, 30, 40, 50, and 80 Hz AM tones. 40 Hz AM tones elicited the largest ASSR from the EEG acquired above auditory cortex and the LFP acquired from each cortical layer in A1. The large ASSR in the EEG to 40 Hz AM tones was not due to larger instantaneous amplitude of the signals or to greater phase alignment of the LFP across the cortical layers. Instead, it resulted from decreased latency variability (or enhanced temporal consistency) of the 40 Hz response. Statistical models indicate the EEG signal was best predicted by LFPs in either the most superficial or deep cortical layers, suggesting deep layer coordinators of the ASSR. Overall, our results indicate that the recruitment of non-uniform but more temporally consistent responses across A1 layers underlie the larger ASSR to amplitude-modulated tones at 40 Hz. [ABSTRACT FROM AUTHOR]

Enhancing slow waves, the electrophysiological (EEG) manifestation of non-rapid eye movement (NREM) sleep, could potentially benefit patients with Parkinson's disease (PD) by improving sleep quality and slowing disease progression. Phase-targeted auditory stimulation (PTAS) is an approach to enhance slow waves, which are detected in real-time in the surface EEG signal. We aimed to test whether the local-field potential of the subthalamic nucleus (STN-LFP) can be used to detect frontal slow waves and assess the electrophysiological changes related to PTAS. We recruited patients diagnosed with PD and undergoing Percept™ PC neurostimulator (Medtronic) implantation for deep brain stimulation of STN (STN-DBS) in a two-step surgery. Patients underwent three full-night recordings, including one between-surgeries recording and two during rehabilitation, one with DBS+ (on) and one with DBS- (off). Surface EEG and STN-LFP signals from Percept PC were recorded simultaneously, and PTAS was applied during sleep in all three recording sessions. Our results show that during NREM sleep, slow waves of the cortex and STN are time-locked. PTAS application resulted in power and coherence changes, which can be detected in STN-LFP. Our findings suggest the feasibility of implementing PTAS using solely STN-LFP signal for slow wave detection, thus without a need for an external EEG device alongside the implanted neurostimulator. Moreover, we propose options for more efficient STN-LFP signal preprocessing, including different referencing and filtering to enhance the reliability of cortical slow wave detection in STN-LFP recordings. • Phase-targeted auditory stimulation (PTAS) can be used to boost slow waves during sleep, showing therapeutic potential for diseases like Alzheimer's and Parkinson's. • The current study explored combining PTAS and DBS for Parkinson's therapy. • Concurrent surface EEG and STN-LFP in DBS-on and DBS-off conditions have identified synchronous frontal and subthalamic slow waves during NREM sleep. • PTAS effects are evident in STN-LFP data through spectral, coherence, and event-related potential analyses. • There is a potential to advance DBS therapy beyond symptomatic relief and to offer a disease-modifying therapeutic approach by improving deep sleep with PTAS. [ABSTRACT FROM AUTHOR]

Objective: To analyze the local field potentials (LFPs) in patients with focal drugresistant epilepsy (DRE) from the anterior nucleus of the thalamus (ANT) during inter-ictal state and seizure state. Method: ANT stereotactic EEG (SEEG) recordings were studied in four patients with focal temporal lobe epilepsy. SEEG data was classified as inter-ictal and ictal state and sub-categorized into electrographic (ESz), focal aware seizure (FAS), focal with impaired awareness (FIA), or focal to bilateral tonic-clonic seizure (FBTC). LFP was analyzed at 4 Hz, 8 Hz, 16 Hz, 32 Hz, high gamma (100 Hz), and ripples (200 Hz) using spectrogram analysis and a statistical comparison of normalized power spectral density (PSD) averaged during seizures versus preictal baseline segments. Result: The LFP recordings were analyzed for 162 seizures (127 ESz, 23 FAS, 6 FIA, and 6 FBTC). Based on time-frequency data (spectrogram), a broad band of activity, occurring between 2 and 6 Hz and centered at 4 Hz, and thin-band activity occurring specifically at 8 Hz on the frequency spectrogram were observed during the inter-ictal state. Statistically significant changes in LFP-PSD were seen for FAS, FIA, and FBTC. We observed a significant gain in LFP at the lower frequency band during FAS at 4 Hz, FIA, and FBTC at 4, 8, and 16 Hz while also observing increases at higher frequencies during FBTC at 100 and 200 Hz and a decrease during FAS seizures at 32 Hz. In contrast, no significant change in LFP power was seen for electrographic seizures. Interpretation: Our observations from a limited dataset indicate that all clinical seizure types, but not electrographic seizures, caused a change in ANT-LFP based on the magnitude of the associated power spectral density (PSD). Future work will be needed to validate the use of ANT-LFP at these frequencies as accurate measurements of seizure occurrence and severity. This work represents a first step toward understanding ANT thalamic LFP patterns during focal seizures and developing adaptive DBS strategies. [ABSTRACT FROM AUTHOR]

Rapid eye movement (REM) sleep, also referred to as paradoxical sleep for the striking resemblance of its electroencephalogram (EEG) to the one observed in wakefulness, is characterized by the occurrence of transient events such as limb twitches or facial and rapid eye movements. Here, we investigated the local activity of the primary somatosensory or barrel cortex (S1) in naturally sleeping head-fixed male mice during REM. Through local field potential recordings, we uncovered local appearances of spindle waves in the barrel cortex during REM concomitant with strong delta power, challenging the view of a wakefulness-like activity in REM. We further performed extra-and intracellular recordings of thalamic cells in head-fixed mice. Our data show highfrequency thalamic bursts of spikes and subthreshold spindle oscillations in approximately half of the neurons of the ventral posterior medial nucleus which further confirmed the thalamic origin of local cortical spindles in S1 in REM. Cortical spindle oscillations were suppressed, while thalamus spike firing increased, associated with rapid mouse whisker movements and S1 cortical activity transitioned to an activated state. During REM, the sensory thalamus and barrel cortex therefore alternate between high (wake-like) and low (non-REM sleep-like) activation states, potentially providing a neuronal substrate for mnemonic processes occurring during this paradoxical sleep stage. [ABSTRACT FROM AUTHOR]

BACKGROUND: Transcranial magneto-acoustical electrical stimulation (TMAES) is a non-invasive, high-precision neurofocused stimulation method based on magneto-acoustic coupling electrical effect, which can regulate the rhythmic oscillation of nerve activity, thereby affecting the brain’s movement, cognition and other functions. OBJECTIVE: To explore the effect of TMAES on beta oscillations in the neural circuits of healthy rats and Parkinson’s rats. METHODS: (1) Animal experiments: Twenty-four Wistar rats were randomly divided into four groups (n=6 per group). The rats in the normal control group received no intervention, while those in the normal stimulation group received TMAES (the average spatial peak pulse intensity: 13.33 W/cm2, fundamental frequency: 0.4 MHz, the number of fundamental wave cycles: 1000, and pulse frequency: 200 Hz). The model control group and model stimulation group were established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. After successful modeling, the rats in the model control group received sham TMAES stimulation in the prefrontal cortex, and those in the model stimulation group received TMAES in the prefrontal cortex, and the duration of stimulation was 2.0 minutes per day. After an interval of 8-10 minutes, the local field potential signals of rats were collected during the execution of T-maze test and the correct rate of behavior was recorded at the same time to compare and analyze the time-frequency distribution of local field potential signals and behavioral differences among the groups. The stimulation experiment and T-maze test were stopped when the correct rate of rats was higher than 80% for 3 consecutive days. (2) Modeling and simulation experiments: The cortical-basal ganglion circuit model under TMAES was established, and the ultrasonic emission period (5, 10, 20 ms), ultrasonic emission duty cycle (30%, 50%, 90%) and induced current density (20, 50, 100 μA/cm2) were changed respectively to compare the power spectral density values of beta oscillations in healthy rats and Parkinson’s rats under different stimulation parameters. RESULTS AND CONCLUSION: (1) Animal experiments: The spatial learning ability of the rats in the normal control group was stronger than that of the model control group (P < 0.001), the spatial learning ability of the rats in the normal stimulation group was stronger than that of the normal control group (P < 0.05), and the spatial learning ability of the rats in the model stimulation group was stronger than that of the model control group (P < 0.01). The distribution of beta oscillation energy in the normal control group was more concentrated, and the beta oscillation signal energy was reduced in the normal stimulation group compared with the normal control group. The beta oscillation energy was widely distributed and the energy value was significantly higher in the model control group and the model stimulation group than the normal control and normal stimulation groups. Moreover, the beta oscillation signal energy in the model stimulation group was significantly lower than that in the model control group. (2) Modeling and simulation experiments: the peak power spectral density of the beta band of healthy rats without stimulation (30 dB) was significantly lower than that of Parkinson’s rats (55 dB). The power spectral density value generally decreased after stimulation. The peak power spectral density in the beta band was positively correlated with the ultrasonic emission period and negatively correlated with the induced current density. In addition, the peak power spectral density value was the lowest when the duty cycle of ultrasonic emission was 50%. These findings indicate that TMAES suppresses beta oscillations in healthy and Parkinson's disease rats, thereby improving motor function and decision-making cognitive function in rats. [ABSTRACT FROM AUTHOR]

Hypoxia, especially the chronic type, leads to disruptive results in the brain that may contribute to the pathogenesis of some neurodegenerative diseases such as Alzheimer's disease (AD). The ventrolateral medulla (VLM) contains clusters of interneurons, such as the pre-Bötzinger complex (preBötC), that generate the main respiratory rhythm drive. We hypothesized that exposing animals to chronic sustained hypoxia (CSH) might develop tauopathy in the brainstem, consequently changing the rhythmic manifestations of respiratory neurons. In this study, old (20–22 months) and young (2–3 months) male rats were subjected to CSH (10 ± 0.5% O2) for ten consecutive days. Western blotting and immunofluorescence (IF) staining were used to evaluate phosphorylated tau. Mitochondrial membrane potential (MMP or ∆ψm) and reactive oxygen species (ROS) production were measured to assess mitochondrial function. In vivo diaphragm's electromyography (dEMG) and local field potential (LFP) recordings from preBötC were employed to assess the respiratory factors and rhythmic representation of preBötC, respectively. Findings showed that ROS production increased significantly in hypoxic groups, associated with a significant decline in ∆ψm. In addition, tau phosphorylation elevated in the brainstem of hypoxic groups. On the other hand, the power of rhythms declined significantly in the preBötC of hypoxic rats, parallel with changes in the respiratory rate, total respiration time, and expiration time. Moreover, there was a positive and statistically significant correlation between LFP rhythm's power and inspiration time. Our data showed that besides CSH, aging also contributed to mitochondrial dysfunction, tau hyperphosphorylation, LFP rhythms' power decline, and changes in respiratory factors. [ABSTRACT FROM AUTHOR]

Background and Objective: Emerging diseases like Parkinson or Alzheimer's, which are not curable, endanger human mental health and are challenging to research. Drug target interactions (DTI) are pivotal in the screening of candidate drugs and focus on a small pool of drug targets. Electroencephalogram shows the responses to psychotropic medicines in the brain bioelectric activity. Synaptic activity can be analyzed by using Local Field Potential recordings obtained from micro-electrodes implanted in the brain. The aim is to evaluate the effects of drug on brain bioelectric activity and increase the drug classification accuracy. The ultimate goal is to advance our understanding of how drugs affect synaptic activity and open the door to more focused treatment for neurodegenerative diseases. Methods: In this study, Pharmaco-EEG recordings are processed using Advanced neural network models, particularly Convolutional Neural Networks, to assess the effects of medications. The five different medicines used in this study are Ephedrine, Fluoxetine, Kratom, Morphine, and Saline. The signals observed are local field potential signals. To overcome some limits of DTI prediction, we propose Bidirectional Long Short-Term Memory (LSTM) for the categorization of intracranial EEG (i-EEG) data, departing from standard approaches. Similar EEG patterns are presumably caused by drugs that work by homologous pharmacological pathways, producing similar psychotropic effects. To improve accuracy and reduce training loss, our study introduces a bidirectional LSTM model for classification along with Bayesian optimization Results: High recall, precision, and F1-Scores, particularly a 95% F1-Score for morphine, ephedrine, fluoxetine, and saline, suggest good performance in predicting these drug classes. Kratom produces a somewhat lower recall of 94%, but a high F1-Score of 97% and perfect precision of 1.00. The weighted average F1-Score, macro average, and overall accuracy are all consistently high (around 97%), indicating that the model works well throughout the spectrum of drugs. Conclusions: Improved model performance was demonstrated by using a diversified dataset with five drug categories and bidirectional LSTM boosted with Bayesian optimization for hyperparameter tuning. From earlier limited-category models, it represents a substantial advancement.

Resting-state functional magnetic resonance imaging (RS-fMRI) has been extensively utilized for noninvasive investigation of human brain activity. While studies employing simultaneous recordings of fMRI and electrophysiology have established a connection between the low-frequency fluctuation (< 0.1 Hz) observed in RS-fMRI and the local field potential (LFP), it remains unclear whether the RS-fMRI signal exhibits frequency-dependent modulation, which is a well-documented phenomenon in LFP. The present study concurrently recorded resting-state functional magnetic resonance imaging (RS-fMRI) and local field potentials (LFP) in the striatum of 8 rats before and after a pharmacological manipulation. We observed a highly similar frequency-dependent pattern of amplitude changes in both RS-fMRI and LFP following the manipulation, specifically an increase in high-frequency band amplitudes accompanied by a decrease in low-frequency band amplitudes. These findings provide direct evidence that the enhanced high-frequency fluctuations and reduced low-frequency fluctuations observed in RS-fMRI may reflect heightened neuronal activity.

Hand movements are associated with modulations of neuronal activity across several interconnected cortical areas, including the primary motor cortex (M1) and the dorsal and ventral premotor cortices (PMd and PMv). Local field potentials (LFPs) provide a link between neuronal discharges and synaptic inputs. Our current understanding of how LFPs vary in M1, PMd, and PMv during contralateral and ipsilateral movements is incomplete. To help reveal unique features in the pattern of modulations, we simultaneously recorded LFPs in these areas in two macaque monkeys performing reach and grasp movements with either the right or left hand. The greatest effector-dependent differences were seen in M1, at low (≤13 Hz) and γ frequencies. In premotor areas, differences related to hand use were only present in low frequencies. PMv exhibited the greatest increase in low frequencies during instruction cues and the smallest effector-dependent modulation during movement execution. In PMd, d oscillations were greater during contralateral reach and grasp, and ß activity increased during contralateral grasp. In contrast, ß oscillations decreased in M1 and PMv. These results suggest that while M1 primarily exhibits effector-specific LFP activity, premotor areas compute more effector-independent aspects of the task requirements, particularly during movement preparation for PMv and production for PMd. The generation of precise hand movements likely relies on the combination of complementary information contained in the unique pattern of neural modulations contained in each cortical area. Accordingly, integrating LFPs from premotor areas and M1 could enhance the performance and robustness of brain-machine interfaces. [ABSTRACT FROM AUTHOR]

Brain rhythms have been postulated to play central roles in animal cognition. A prominently reported dichotomy of hippocampal rhythms links theta‐frequency oscillations (4–12 Hz) and ripples (120–250 Hz) exclusively to preparatory and consummatory behaviours, respectively. However, because of the differential power expression of these two signals across hippocampal strata, such exclusivity requires validation through analyses of simultaneous multi‐strata recordings. We assessed co‐occurrence of theta‐frequency oscillations with ripples in multi‐channel recordings of extracellular potentials across hippocampal strata from foraging rats. We detected all ripple events from an identified stratum pyramidale (SP) channel. We then defined theta epochs based on theta oscillations detected from the stratum lacunosum‐moleculare (SLM) or the stratum radiatum (SR). We found ∼20% of ripple events (in SP) to co‐occur with theta epochs identified from SR/SLM channels, defined here as theta ripples. Strikingly, when theta epochs were instead identified from the SP channel, such co‐occurrences were significantly reduced because of a progressive reduction in theta power along the SLM‐SR‐SP axis. Behaviourally, we found most theta ripples to occur during immobile periods, with comparable theta power during exploratory and immobile theta epochs. Furthermore, the progressive reduction in theta power along the SLM‐SR‐SP axis was common to exploratory and immobile periods. Finally, we found a strong theta‐phase preference of theta ripples within the fourth quadrant [3π/2 – 2π] of the associated theta oscillation. The prevalence of theta ripples expands the potential roles of ripple‐frequency oscillations to span the continuum of encoding, retrieval and consolidation, achieved through interactions with theta oscillations. Key points: The brain manifests oscillations in recorded electrical potentials, with different frequencies of oscillation associated with distinct behavioural states.A prominently reported dichotomy assigns theta‐frequency oscillations (4–12 Hz) and ripples (120–250 Hz) recorded in the hippocampus to be exclusively associated with preparatory and consummatory behaviours, respectively.Our multi‐strata recordings from the rodent hippocampus coupled with cross‐strata analyses provide direct quantitative evidence for the occurrence of ripple events nested within theta oscillations.These results highlight the need for an analysis pipeline that explicitly accounts for the specific strata where individual oscillatory power is high, in analysing simultaneously recorded data from multiple strata.Our observations open avenues for investigations involving cross‐strata interactions between theta oscillations and ripples across different behavioural states. [ABSTRACT FROM AUTHOR]

Spatial navigation through novel spaces and to known goal locations recruits multiple integrated structures in the mammalian brain. Within this extended network, the hippocampus enables formation and retrieval of cognitive spatial maps and contributes to decision making at choice points. Exploration and navigation to known goal locations produce synchronous activity of hippocampal neurons resulting in rhythmic oscillation events in local networks. Power of specific oscillatory frequencies and numbers of these events recorded in local field potentials correlate with distinct cognitive aspects of spatial navigation. Typically, oscillatory power in brain circuits is analyzed with Fourier transforms or short-time Fourier methods, which involve assumptions about the signal that are likely not true and fail to succinctly capture potentially informative features. To avoid such assumptions, we applied a method that combines manifold discovery techniques with dynamical systems theory, namely diffusion maps and Takens' time-delay embedding theory, that avoids limitations seen in traditional methods. This method, called diffusion mapped delay coordinates (DMDC), when applied to hippocampal signals recorded from juvenile rats freely navigating a Y-maze, replicates some outcomes seen with standard approaches and identifies age differences in dynamic states that traditional analyses are unable to detect. Thus, DMDC may serve as a suitable complement to more traditional analyses of LFPs recorded from behaving subjects that may enhance information yield. [ABSTRACT FROM AUTHOR]

Using rodents as a model of physiological vision studies requires adequate information about their visual cortex. Although the primary visual cortex of rats has different sub-regions, there are few studies on the different response patterns of these sub-regions. In this study, we recorded the local field potentials (LFPs) from sub-regions of the primary visual cortex (V1) of anesthetized rats. We used random dots patterns as moving stimuli presented in random sequences. Then we used machine learning methods to decode the direction and speed of the stimuli from the recorded signals. Our results revealed that there are different patterns of responses to motion stimuli across sub-regions. Although the decoding results using LFPs were not high, they were enhanced by moving to the lateral sub-regions of the V1. Our results suggested that the location of the recording areas impact reaction time, the pattern of the responses in time- and frequency- domains, and encoding the motion stimuli. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS) surgery require subsequent programming, which is complex and cumbersome. The local field potential (LFP) in the deep brain is associated with motor symptom improvement. The current study aimed to identify LFP biomarkers correlated with improved motor symptoms in PD patients after DBS and verify their guiding role in postoperative programming. Methods: Initially, the study included 36 PD patients undergoing DBS surgery. Temporary external electrical stimulation was performed during electrode implantation, and LFP signals around the electrode contacts were collected before and after stimulation. The stimulating contact at 6 months of programming was regarded as the optimal and effective stimulating contact. The LFP signal of this contact during surgery was analyzed to identify potential LFP biomarkers. Next, we randomly assigned another 30 PD patients who had undergone DBS to physician empirical programming and LFP biomarker‐guided programming groups and compared the outcomes. Results: In the first part of the study, LFP signals of electrode contacts changed after electrical stimulation. Electrical stimulation reduced gamma energy and the beta/alpha oscillation ratio. The different programming method groups were compared, indicating the superiority of beta/alpha oscillations ratio‐guided programming over physician experience programming for patients' improvement rate (IR) of UPDRS‐III. There were no significant differences in the IR of UPDRS‐III, post‐LED, IR‐PDQ39, number of programmings, and the contact change rate between the gamma oscillations‐guided programming and empirical programming groups. Conclusion: Overall, the findings reveal that gamma oscillations and the beta/alpha oscillations ratio are potential biomarkers for programming in PD patients after DBS. Instead of relying solely on spike action potential signals from single neurons, LFP biomarkers can provide the appropriate depth for electrode placement. [ABSTRACT FROM AUTHOR]

The mechanisms for spinal cord stimulation (SCS) to alleviate chronic pain are only partially known. We aimed to elucidate the roles of adenosine A1 and A3 receptors (A1R, A3R) in the inhibition of spinal nociceptive transmission by SCS, and further explored whether 2′-deoxycoformycin (dCF), an inhibitor of adenosine deaminase, can potentiate SCS-induced analgesia. We used RNAscope and immunoblotting to examine the distributions of adora1 and adora3 expression, and levels of A1R and A3R proteins in the spinal cord of rats after tibial-spared nerve injury (SNI-t). Electrophysiology recording was conducted to examine how adenosine receptor antagonists, virus-mediated adora3 knockdown, and dCF affect SCS-induced inhibition of C-fibre-evoked spinal local field potential (C-LFP). Adora1 was predominantly expressed in neurones, whereas adora3 is highly expressed in microglial cells in the rat spinal cord. Spinal application of antagonists (100 μl) of A1R (8-cyclopentyl-1,3-dipropylxanthine [DPCPX], 50 μM) and A3R (MRS1523, 200 nM) augmented C-LFP in SNI-t rats (DPCPX: 1.39 [0.18] vs vehicle: 0.98 [0.05], P =0.046; MRS1523: 1.21 [0.07] vs vehicle: 0.91 [0.03], P =0.002). Both drugs also blocked inhibition of C-LFP by SCS. Conversely, dCF (0.1 mM) enhanced SCS-induced C-LFP inhibition (dCF: 0.60 [0.04] vs vehicle: 0.85 [0.02], P <0.001). In the behaviour study, dCF (100 nmol 15 μl−1, intrathecal) also enhanced inhibition of mechanical hypersensitivity by SCS in SNI-t rats. Spinal A1R and A3R signalling can exert tonic suppression and also contribute to SCS-induced inhibition of spinal nociceptive transmission after nerve injury. Inhibition of adenosine deaminase may represent a novel adjuvant pharmacotherapy to enhance SCS-induced analgesia. [ABSTRACT FROM AUTHOR]

Neural oscillations are associated with diverse computations in the mammalian brain. The waveform shape of oscillatory activity measured in the cortex relates to local physiology and can be informative about aberrant or dynamically changing states. However, how waveform shape differs across distant yet functionally and anatomically related cortical regions is largely unknown. In this study, we capitalize on simultaneous recordings of local field potentials (LFPs) in the auditory and frontal cortices of awake, male Carollia perspicillata bats to examine, on a cycle-by-cycle basis, waveform shape differences across cortical regions. We find that waveform shape differs markedly in the fronto-auditory circuit even for temporally correlated rhythmic activity in comparable frequency ranges (i.e., in the delta and gamma bands) during spontaneous activity. In addition, we report consistent differences between areas in the variability of waveform shape across individual cycles. A conceptual model predicts higher spike-spike and spike-LFP correlations in regions with more asymmetric shapes, a phenomenon that was observed in the data: spike-spike and spike-LFP correlations were higher in the frontal cortex. The model suggests a relationship between waveform shape differences and differences in spike correlations across cortical areas. Altogether, these results indicate that oscillatory activity in the frontal and auditory cortex possesses distinct dynamics related to the anatomical and functional diversity of the fronto-auditory circuit. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests slow-wave sleep (SWS) dysfunction in Parkinson's disease (PD) is associated with faster disease progression, cognitive impairment, and excessive daytime sleepiness. Beta oscillations (8-35 Hz) in the basal ganglia thalamocortical (BGTC) network are thought to play a role in the development of cardinal motor signs of PD. The role cortical beta oscillations play in SWS dysfunction in the early stage of parkinsonism is not understood, however. To address this question, we used a within-subject design in a nonhuman primate (NHP) model of PD to record local field potentials from the primary motor cortex (MC) during sleep across normal and mild parkinsonian states. The MC is a critical node in the BGTC network, exhibits pathological oscillations with depletion in dopamine tone, and displays high amplitude slow oscillations during SWS. The MC is therefore an appropriate recording site to understand the neurophysiology of SWS dysfunction in parkinsonism. We observed a reduction in SWS quantity (p = 0.027) in the parkinsonian state compared to normal. The cortical delta (0.5-3 Hz) power was reduced (p = 0.038) whereas beta (8-35 Hz) power was elevated (p = 0.001) during SWS in the parkinsonian state compared to normal. Furthermore, SWS quantity positively correlated with delta power (r=0.43, p = 0.037) and negatively correlated with beta power (r=-0.65, p< 0.001). Our findings support excessive beta oscillations as a mechanism for SWS dysfunction in mild parkinsonism and could inform the development of neuromodulation therapies for enhancing SWS in people with PD. [ABSTRACT FROM AUTHOR]

Parkinson’s Disease (PD) is characterized by the temporary alleviation of motor symptoms following electrode implantation (or nucleus destruction), known as the microlesion effect (MLE). Electrophysiological studies have explored different PD stages, but understanding electrophysiological characteristics during the MLE period remains unclear. The objective was to examine the characteristics of local field potential (LFP) signals in the subthalamic nucleus (STN) during the hyperacute period following implantation (within 2 days) and 1 month post-implantation. 15 patients diagnosed with PD were enrolled in this observational study, with seven simultaneous recordings of bilateral STN-LFP signals using wireless sensing technology from an implantable pulse generator. Recordings were made in both on and off medication states over 1 month after implantation. We used a method to parameterize the neuronal power spectrum to separate periodic oscillatory and aperiodic components effectively. Our results showed that beta power exhibited a significant increase in the off medication state 1 month after implantation, compared to the postoperative hyperacute period. Notably, this elevation was effectively attenuated by levodopa administration. Furthermore, both the exponents and offsets displayed a decrease at 1 month postoperatively when compared to the hyperacute postoperative period. Remarkably, levodopa medication exerted a modulatory effect on these aperiodic parameters, restoring them back to levels observed during the hyperacute period. Our findings suggest that both periodic and aperiodic components partially capture distinct electrophysiological characteristics during the MLE. It is crucial to adequately evaluate such discrepancies when exploring the mechanisms of MLE and optimizing adaptive stimulus protocols. [ABSTRACT FROM AUTHOR]

The concept of receptive field (RF) is central to sensory neuroscience. Neuronal RF properties have been substantially studied in animals, while those in humans remain nearly unexplored. Here, we measured neuronal RFs with intracranial local field potentials (LFPs) and spiking activity in human visual cortex (V1/V2/V3). We recorded LFPs via macro-contacts and discovered that RF sizes estimated from low-frequency activity (LFA, 0.5–30 Hz) were larger than those estimated from low-gamma activity (LGA, 30–60 Hz) and high-gamma activity (HGA, 60–150 Hz). We then took a rare opportunity to record LFPs and spiking activity via microwires in V1 simultaneously. We found that RF sizes and temporal profiles measured from LGA and HGA closely matched those from spiking activity. In sum, this study reveals that spiking activity of neurons in human visual cortex could be well approximated by LGA and HGA in RF estimation and temporal profile measurement, implying the pivotal functions of LGA and HGA in early visual information processing. [ABSTRACT FROM AUTHOR]

ObjectiveTo analyze the local field potentials (LFPs) in patients with focal drug-resistant epilepsy (DRE) from the anterior nucleus of the thalamus (ANT) during inter-ictal state and seizure state.MethodANT stereotactic EEG (SEEG) recordings were studied in four patients with focal temporal lobe epilepsy. SEEG data was classified as inter-ictal and ictal state and sub-categorized into electrographic (ESz), focal aware seizure (FAS), focal with impaired awareness (FIA), or focal to bilateral tonic-clonic seizure (FBTC). LFP was analyzed at 4 Hz, 8 Hz, 16 Hz, 32 Hz, high gamma (100 Hz), and ripples (200 Hz) using spectrogram analysis and a statistical comparison of normalized power spectral density (PSD) averaged during seizures versus pre-ictal baseline segments.ResultThe LFP recordings were analyzed for 162 seizures (127 ESz, 23 FAS, 6 FIA, and 6 FBTC). Based on time-frequency data (spectrogram), a broad band of activity, occurring between 2 and 6 Hz and centered at 4 Hz, and thin-band activity occurring specifically at 8 Hz on the frequency spectrogram were observed during the inter-ictal state. Statistically significant changes in LFP-PSD were seen for FAS, FIA, and FBTC. We observed a significant gain in LFP at the lower frequency band during FAS at 4 Hz, FIA, and FBTC at 4, 8, and 16 Hz while also observing increases at higher frequencies during FBTC at 100 and 200 Hz and a decrease during FAS seizures at 32 Hz. In contrast, no significant change in LFP power was seen for electrographic seizures.InterpretationOur observations from a limited dataset indicate that all clinical seizure types, but not electrographic seizures, caused a change in ANT-LFP based on the magnitude of the associated power spectral density (PSD). Future work will be needed to validate the use of ANT-LFP at these frequencies as accurate measurements of seizure occurrence and severity. This work represents a first step toward understanding ANT thalamic LFP patterns during focal seizures and developing adaptive DBS strategies.

Sleep fragmentation (SF) is a common sleep problem experienced during the perioperative period by older adults, and is associated with postoperative cognitive dysfunction (POCD). Increasing evidence indicates that delta-wave activity during non-rapid eye movement (NREM) sleep is involved in sleep-dependent memory consolidation and that hippocampal theta oscillations are related to spatial exploratory memory. Recovery sleep (RS), a self-regulated state of sleep homeostasis, enhances delta-wave power and memory performance in sleep-deprived older mice. However, it remains unclear whether RS therapy has a positive effect on cognitive changes following SF in older mouse models. Therefore, this study aimed to explore whether preoperative RS can alleviate cognitive deficits in aged mice with SF. A model of preoperative 24-h SF combined with exploratory laparotomy-induced POCD was established in 18-month-old mice. Aged mice were treated with preoperative 6-h RS following SF and postoperative 6-h RS following surgery, respectively. The changes in hippocampus-dependent cognitive function were investigated using behavioral tests, electroencephalography (EEG), local field potential (LFP), magnetic resonance imaging, and neuromorphology. Mice that underwent 24-h SF combined with surgery exhibited severe spatial memory impairment; impaired cognitive performance could be alleviated by preoperative RS treatment. In addition, preoperative RS increased NREM sleep; enhanced EEG delta-wave activity and LFP theta oscillation in the hippocampal CA1; and improved hippocampal perfusion, microstructural integrity, and neuronal damage. Taken together, these results provide evidence that preoperative RS may ameliorate the severity of POCD aggravated by SF by enhancing delta slow-wave activity and hippocampal theta oscillation, and by ameliorating the reduction in regional cerebral blood flow and white matter microstructure integrity in the hippocampus.

The hippocampal-prefrontal cortex network dynamics is reported to be involved in various cognitive functions and in different mood disturbances including depression. It has been suggested that blocking orexin-1 receptors can be beneficial in depression. The purpose of this study is to determine whether orexin-1 receptor antagonists have an impact on changes in brain oscillations in the hippocampus and prefrontal cortex in a rat model of depression. Forty-eight male Wistar rats were divided into six experimental groups: control, chronic mild stress (CMS), acute SB-334867, a selective orexin-1 receptor antagonist, treated rats (SB), chronic SB-treated (CSB), CMS+SB, and CMS+CSB. Two stainless steel recording electrodes were placed in the coordinates of the hippocampus (HPC) and the prefrontal cortex (PFC). After behavioral verification of the model, local field potentials were recorded at 1 kHz sampling frequency. The absolute power of different frequency bands was obtained using the Fast Fourier Transform (FFT) function, and the power spectral density (PSD) of each frequency band was calculated for each animal. In the CMS- treated animals, the low-gamma band power increased both in the HPC and PFC (p ≤ 0.05), which were reversed by chronic SB-334867 treatment (p ≤ 0.05). The alterations in theta, and high-gamma band power were not significant in CMS treated rats, while acute and chronic SB-334867 treatment diminished the theta and high-gamma band power (p ≤ 0.05), respectively. The hippocampal-prefrontal coherence decreased in the delta (p ≤ 0.01), theta (p ≤ 0.01), and alpha (p ≤ 0.05) band range of the CMS exposed rats. It is concluded that CMS boosts the low-gamma band power, which is reversed by CSB treatment. The low-frequency band coherence is attenuated after CMS treatment.

The medial prefrontal cortex (mPFC) regulates bladder contractions via the periaqueductal grey (PAG). Subthalamic nucleus deep brain stimulation (STN-DBS) modulates urinary afferent information from PAG in Parkinson’s disease (PD). We do not know how STN-DBS modulates the activities of mPFC induced by PAG stimulation. We aim to clarify how STN-DBS modulates the neuronal activity of mPFC induced by PAG stimulation and its effects on bladder contraction Experiments were conducted under urethane anesthesia in normal (n = 9) and 6-hydroxydopamine hemi-lesioned PD rats (n = 7). Left-sided PAG stimulation and STN-DBS were applied with simultaneous bladder contraction monitoring. Local field potential (LFP) recording and collection of extracellular fluid in the mPFC were performed before stimulation, during PAG stimulation, during PAG+STN stimulation, and after stimulation. The bladder inter-contraction intervals significantly decreased with PAG stimulation with a concomitant decrease in mPFC LFP power in PD rats. Adding STN stimulation to PAG stimulation significantly increased the bladder inter-contraction intervals with a concomitant increase in mPFC LFP power in PD rats. Several mPFC catecholamine levels were modulated by PAG or PAG+STN stimulation in PD rats. The present study revealed that STN-DBS modulate the activities of mPFC induced by PAG, thereby leading to normalization of bladder contraction.

Recent results show that valuable objects can pop out in visual search, yet its neural mechanisms remain unexplored. Given the role of substantia nigra reticulata (SNr) in object value memory and control of gaze, we recorded its single-unit activity while male macaque monkeys engaged in efficient or inefficient search for a valuable target object among low-value objects. The results showed that efficient search was concurrent with stronger inhibition and higher spiking irregularity in the target-present (TP) compared with the target-absent (TA) trials in SNr. Importantly, the firing rate differentiation of TP and TA trials happened within ~100 ms of display onset, and its magnitude was significantly correlated with the search times and slopes (search efficiency). Time-frequency analyses of local field potential (LFP) after display onset revealed significant modulations of the gamma band power with search efficiency. The greater reduction of SNr firing in TP trials in efficient search can create a stronger disinhibition of downstream superior colliculus, which in turn can facilitate saccade to obtain valuable targets in competitive environments. [ABSTRACT FROM AUTHOR]

Febrile seizures during early childhood may result in central nervous system developmental disorders. However, the specific mechanisms behind the impact of febrile seizures on the developing brain are not well understood. To address this gap in knowledge, we employed a hyperthermic model of febrile seizures in 10-day-old rats and tracked their development over two months. Our objective was to determine the degree to which the properties of the hippocampal glutamatergic system are modified. We analyzed whether pyramidal glutamatergic neurons in the hippocampus die after febrile seizures. Our findings indicate that there is a reduction in the number of neurons in various regions of the hippocampus in the first two days after seizures. The CA1 field showed the greatest susceptibility, and the reduction in the number of neurons in post-FS rats in this area appeared to be long-lasting. Electrophysiological studies indicate that febrile seizures cause a reduction in glutamatergic transmission, leading to decreased local field potential amplitude. This impairment could be attributable to diminished glutamate release probability as evidenced by decreases in the frequency of miniature excitatory postsynaptic currents and increases in the paired-pulse ratio of synaptic responses. We also found higher threshold current causing hind limb extension in the maximal electroshock seizure threshold test of rats 2 months after febrile seizures compared to the control animals. Our research suggests that febrile seizures can impair glutamatergic transmission, which may protect against future seizures. [ABSTRACT FROM AUTHOR]

In recent years, several studies have shown a respiratory drive of the local field potential (LFP) in numerous brain areas so that the respiratory rhythm could be considered as a master clock promoting communication between distant brain locations. However, outside of the olfactory system, it remains unknown whether the respiratory rhythm could shape membrane potential (MP) oscillations. To fill this gap, we co-recorded MP and LFP activities in different nonolfactory brain areas, medial prefrontal cortex (mPFC), primary somatosensory cortex (S1), primary visual cortex (V1), and hippocampus (HPC), in urethane-anesthetized rats. Using respiratory cycle-by-cycle analysis, we observed that respiration could modulate both MP and spiking discharges in all recorded areas during episodes that we called respiration-related oscillations (RRo). Further quantifications revealed that RRo episodes were transient in most neurons (5 consecutive respiratory cycles in average). RRo development in MP was largely correlated with the presence of respiratory modulation in the LFP. By showing that the respiratory rhythm influenced brain activities deep to the MP of nonolfactory neurons, our data support the idea that respiratory rhythm could mediate long-range communication between brain areas. NEW & NOTEWORTHY In this study, we evidenced strong respiratory-driven oscillations of neuronal membrane potential and spiking discharge in various nonolfactory areas of the mammal brain. These oscillations were found in the medial prefrontal cortex, primary somatosensory cortex, primary visual cortex, and hippocampus. These findings support the idea that respiratory rhythm could be used as a common clock to set the dynamics of large-scale neuronal networks on the same slow rhythm. [ABSTRACT FROM AUTHOR]

Exploring the neural mechanisms of awareness is a fundamental task of cognitive neuroscience. There is an ongoing dispute regarding the role of the prefrontal cortex (PFC) in the emergence of awareness, which is partially raised by the confound between report- and awareness-related activity. To address this problem, we designed a visual awareness task that can minimize report-related motor confounding. Our results show that saccadic latency is significantly shorter in the aware trials than in the unaware trials. Local field potential (LFP) data from six patients consistently show early (200–300ms) awareness-related activity in the PFC, including event-related potential and high-gamma activity. Moreover, the awareness state can be reliably decoded by the neural activity in the PFC since the early stage, and the neural pattern is dynamically changed rather than being stable during the representation of awareness. Furthermore, the enhancement of dynamic functional connectivity, through the phase modulation at low frequency, between the PFC and other brain regions in the early stage of the awareness trials may explain the mechanism of conscious access. These results indicate that the PFC is critically involved in the emergence of awareness.

The suprachiasmatic nucleus of the hypothalamus (SCN) controls mammalian circadian rhythms. Circadian rhythms influence the dopaminergic system, and dopaminergic tone impresses the physiology and behavior of the circadian clock. However, little is known about the effect of dopamine and dopamine receptors, especially D1-like dopamine receptors (D1Rs), in regulating the circadian rhythm and the SCN neuron's activity. Therefore, the present study aimed to investigate the role of the D1Rs in SCN neural oscillations during the 24-h light–dark cycle using local field potential (LFP) recording. To this end, two groups of rats were given the SKF-38393 (1 mg/kg; i.p.) as a D1-like receptor agonist in the morning or night. LFP recording was performed for ten minutes before and two hours after the SKF-38393 injection. The obtained results showed that diurnal changes affect LFP oscillations so that delta relative power declined substantially, whereas upper-frequency bands and Lempel–Ziv complexity (LZC) index increased at night, which is consistent with rodents' activity cycles. The D1Rs agonist administration in the morning dramatically altered these intrinsic oscillations, decreasing delta and theta relative power, and most of the higher frequency bands and LZC index were promoted. Some of these effects were reversed at the night after the SKF-38393 injection. In conclusion, findings showed that the SCN's neuronal activities are regulated based on the light–dark cycle in terms of population neural oscillatory activity which could be affected by dopaminergic stimulation in a time-dependent way. [ABSTRACT FROM AUTHOR]

Objective: Thalamic deep brain stimulation (DBS) is an effective therapeutic option in patients with drug‐resistant epilepsy. Recent DBS devices with sensing capabilities enable chronic, outpatient local field potential (LFP) recordings. Whereas beta oscillations have been demonstrated to be a useful biomarker in movement disorders, the clinical utility of DBS sensing in epilepsy remains unclear. Our aim was to determine LFP features that distinguish ictal from inter‐ictal states, which may aid in tracking seizure outcomes with DBS. Methods: Electrophysiology data were obtained from DBS devices implanted in the anterior nucleus (N = 12) or centromedian nucleus (N = 2) of the thalamus. Power spectra recorded during patient/caregiver‐marked seizure events were analyzed with a method that quantitatively separates the oscillatory and non‐oscillatory/aperiodic components of the LFP using non‐parametric statistics, without the need for pre‐specification of the frequency bands of interest. Features of the LFP parameterized using this algorithm were compared with those from inter‐ictal power spectra recorded in clinic. Results: Oscillatory activity in multiple canonical frequency bands was identified from the power spectra in 86.48% of patient‐marked seizure events. Delta oscillations were present in all patients, followed by theta (N = 10) and beta (N = 9). Although there were no differences in oscillatory LFP features between the ictal and inter‐ictal states, there was a steeper decline in the 1/f slope of the aperiodic component of the LFP during seizures. Significance: Our work highlights the potential and shortcomings of chronic LFP recordings in thalamic DBS for epilepsy. Findings suggest that no single frequency band in isolation clearly differentiates seizures, and that features of aperiodic LFP activity may be clinically‐relevant biomarkers of seizures. [ABSTRACT FROM AUTHOR]

Objective: Here, we report a retrospective, single‐center experience with a novel deep brain stimulation (DBS) device capable of chronic local field potential (LFP) recording in drug‐resistant epilepsy (DRE) and explore potential electrophysiological biomarkers that may aid DBS programming and outcome tracking. Methods: Five patients with DRE underwent thalamic DBS, targeting either the bilateral anterior (n = 3) or centromedian (n = 2) nuclei. Postoperative electrode lead localizations were visualized in Lead‐DBS software. Local field potentials recorded over 12–18 months were tracked, and changes in power were associated with patient events, medication changes, and stimulation. We utilized a combination of lead localization, in‐clinic broadband LFP recordings, real‐time LFP response to stimulation, and chronic recordings to guide DBS programming. Results: Four patients (80%) experienced a >50% reduction in seizure frequency, whereas one patient had no significant reduction. Peaks in the alpha and/or beta frequency range were observed in the thalamic LFPs of each patient. Stimulation suppressed these LFP peaks in a dose‐dependent manner. Chronic timeline data identified changes in LFP amplitude associated with stimulation, seizure occurrences, and medication changes. We also noticed a circadian pattern of LFP amplitudes in all patients. Button‐presses during seizure events via a mobile application served as a digital seizure diary and were associated with elevations in LFP power. Significance: We describe an initial cohort of patients with DRE utilizing a novel sensing DBS device to characterize potential LFP biomarkers of epilepsy that may be associated with seizure control after DBS in DRE. We also present a new workflow utilizing the Percept device that may optimize DBS programming using real‐time and chronic LFP recording. [ABSTRACT FROM AUTHOR]

Aim: Parkinson's disease (PD) is a pervasive neurodegenerative disease, and levodopa (L‐dopa) is its preferred treatment. The pathophysiological mechanism of levodopa‐induced dyskinesia (LID), the most common complication of long‐term L‐dopa administration, remains obscure. Accumulated evidence suggests that the dopaminergic as well as non‐dopaminergic systems contribute to LID development. As a 5‐hydroxytryptamine 1A/1B receptor agonist, eltoprazine ameliorates dyskinesia, although little is known about its electrophysiological mechanism. The aim of this study was to investigate the cumulative effects of chronic L‐dopa administration and the potential mechanism of eltoprazine's amelioration of dyskinesia at the electrophysiological level in rats. Methods: Neural electrophysiological analysis techniques were conducted on the acquired local field potential (LFP) data from primary motor cortex (M1) and dorsolateral striatum (DLS) during different pathological states to obtain the information of power spectrum density, theta‐gamma phase–amplitude coupling (PAC), and functional connectivity. Behavior tests and AIMs scoring were performed to verify PD model establishment and evaluate LID severity. Results: We detected exaggerated gamma activities in the dyskinetic state, with different features and impacts in distinct regions. Gamma oscillations in M1 were narrowband manner, whereas that in DLS had a broadband appearance. Striatal exaggerated theta‐gamma PAC in the LID state contributed to broadband gamma oscillation, and aperiodic‐corrected cortical beta power correlated robustly with aperiodic‐corrected gamma power in M1. M1–DLS coherence and phase‐locking values (PLVs) in the gamma band were enhanced following L‐dopa administration. Eltoprazine intervention reduced gamma oscillations, theta–gamma PAC in the DLS, and coherence and PLVs in the gamma band to alleviate dyskinesia. Conclusion: Excessive cortical gamma oscillation is a compelling clinical indicator of dyskinesia. The detection of enhanced PAC and functional connectivity of gamma‐band oscillation can be used to guide and optimize deep brain stimulation parameters. Eltoprazine has potential clinical application for dyskinesia. [ABSTRACT FROM AUTHOR]

Addiction is a global concern with a high relapse rate and without effective therapeutic options. Developing new effective therapeutic strategies is impossible without discovering the disease's neurobiological basis. The present systematic review aimed to comprehensively recognize and discuss the role of local field potentials from brain areas essential in forming and storing context‐drug/food associations following the conditioned place preference (CPP) paradigm as a popular animal model of reward and addiction. Qualified studies were incorporated by a broad search of four databases, including Web of Science, Medline/PubMed, Embase, and ScienceDirect, in July 2022, and they were evaluated via appropriate methodological quality assessment tools. The current study found that drug‐seeking behavior in different stages of the CPP paradigm is accompanied by alterations in neural oscillatory activity and adaptations in connectivity among various areas such as the hippocampus, nucleus accumbens, basolateral amygdala, and prelimbic area, intensely engaged in reward‐related behaviors. These findings need to be extended by more future advanced studies to finally recognize the altered oscillatory activity patterns of large groups of cells in regions involved in reward‐context associations to improve clinical strategies such as neuromodulation approaches to modify the abnormal electrical activity of these critical brain regions and their connections for treating addiction and preventing drug/food relapse in abstinent patients. Definitions: Power is the amount of energy in a frequency band and is the squared amplitude of the oscillation.Cross‐frequency coupling refers to a statistical relationship between activities in two different frequency bands.Phase‐amplitude coupling is perhaps the most commonly used method of computing cross‐frequency coupling. Phase‐amplitude coupling involves testing for a relationship between the phase of one frequency band and the power of another, typically relatively higher, frequency band. Thus, within phase‐amplitude coupling, you refer to the "frequency for phase" and the "frequency for power."Spectral coherence has been frequently used to detect and quantify coupling between oscillatory signals of two or more brain areas. Spectral coherence estimates the linear phase‐consistency between two frequency‐decomposed signals over time windows (or trials). [ABSTRACT FROM AUTHOR]

Abstract Characterization of inter-regional interactions in brain is essential for understanding the mechanism relevant to normal brain function and neurological disease. The recently developed flexible micro (μ)-electrocorticography (μECoG) device is one prominent method used to examine large-scale cortical activity across multiple regions. The sheet-shaped μECoG electrodes arrays can be placed on a relatively wide area of cortical surface beneath the skull by inserting the device into the space between skull and brain. Although rats and mice are useful tools for neuroscience, current μECoG recording methods in these animals are limited to the parietal region of cerebral cortex. Recording cortical activity from the temporal region of cortex in mice has proven difficult because of surgical barriers created by the skull and surrounding temporalis muscle anatomy. Here, we developed a sheet-shaped 64-channel μECoG device that allows access to the mouse temporal cortex, and we determined the factor determining the appropriate bending stiffness for the μECoG electrode array. We also established a surgical technique to implant the electrode arrays into the epidural space over a wide area of cerebral cortex covering from the barrel field to olfactory (piriform) cortex, which is the deepest region of the cerebral cortex. Using histology and computed tomography (CT) images, we confirmed that the tip of the μECoG device reached to the most ventral part of cerebral cortex without causing noticeable damage to the brain surface. Moreover, the device simultaneously recorded somatosensory and odor stimulus-evoked neural activity from dorsal and ventral parts of cerebral cortex in awake and anesthetized mice. These data indicate that our μECoG device and surgical techniques enable the recording of large-scale cortical activity from the parietal to temporal cortex in mice, including somatosensory and olfactory cortices. This system will provide more opportunities for the investigation of physiological functions from wider areas of the mouse cerebral cortex than those currently available with existing ECoG techniques.

Substance use disorders (SUDs) are characterized by maladaptive signaling in the prefrontal cortex and associated regions, however precisely how these drug-induced abnormalities may be linked to drug seeking/taking behaviors is not well understood. Here, in vivo local field potential (LFP) electrophysiology was used in rats to examine the relationship between overall spontaneous (resting state) activity within the prelimbic cortex (PrL) and nucleus accumbens (NAc) core, and their functional connectivity, to cocaine taking and seeking behaviors. Adult, male Sprague-Dawley rats were trained to self-administer either intravenous cocaine (0.33 mg/inf) or water reinforcement during 6-hour daily sessions over 2 weeks; extinction sessions were completed immediately after self-administration training and following 30 days experimenter-imposed abstinence. Rest LFP recordings were completed during 3 recording periods (15 min each in a chamber different from the self-administration context) conducted (1) prior to self-administration training (rest LFP 1) (2) immediately after 2 weeks of self-administration training (rest LFP 2) and (3) following 1 month abstinence (rest LFP 3). Our findings show that resting state LFP power in the PrL recorded prior to training (Rest LFP 1) was positively correlated with total cocaine intake and escalation of cocaine seeking at the beta frequency range. Immediately after self-administration training (Rest LFP 2) power in the NAc core at gamma frequency was negatively correlated with incubation of cocaine craving. For rats trained to self-administer water, no significant correlations were observed. Together, these findings show that resting state LFP at specific timepoints in the addiction cycle can serve as unique predictors (biomarkers) of cocaine use disorders.

Introduction: Spontaneous low-frequency oscillations play a key role in brain activity. However, the underlying mechanism and origin of low-frequency oscillations remain under debate. Methods: Optical imaging and an electrophysiological recording system were combined to investigate spontaneous oscillations in the hemodynamic parameters and neuronal activity of awake and anesthetized mice after N&-nitro-L-arginine methyl ester (L-NAME) administration. Results: The spectrum of local field potential (LFP) signals was significantly changed by L-NAME, which was further corroborated by the increase in energy and spatial synchronization. The important finding was that L-NAME triggered regular oscillations in both LFP signals and hemodynamic signals. Notably, the frequency peak of hemodynamic signals can be different from that of LFP oscillations in awake mice. Discussion: A model of the neurovascular system was proposed to interpret this mismatch of peak frequencies, supporting the view that spontaneous lowfrequency oscillations arise from multiple sources. [ABSTRACT FROM AUTHOR]

During early development, brains undergo profound changes in structure at the molecular, synaptic, cellular and circuit level. At the same time, brains need to perform adaptive function. How do structurally immature brains process information? How do brains perform stable and reliable function despite massive changes in structure? The rodent olfactory system presents an ideal model for approaching these poorly understood questions. Rodents are born deaf and blind, and rely completely on their sense of smell to acquire resources essential for survival during the first 2 weeks of life, such as food and warmth. Here, we review decades of work mapping structural changes in olfactory circuits during early development, as well as more recent studies performing in vivo electrophysiological recordings to characterize functional activity patterns generated by these circuits. The findings demonstrate that neonatal olfactory processing relies on an interacting network of brain areas including the olfactory bulb and piriform cortex. Circuits in these brain regions exhibit varying degrees of structural maturity in neonatal animals. However, despite substantial ongoing structural maturation of circuit elements, the neonatal olfactory system produces dynamic network-level activity patterns that are highly stable over protracted periods during development. We discuss how these findings inform future work aimed at elucidating the circuit-level mechanisms underlying information processing in the neonatal olfactory system, how they support unique neonatal behaviors, and how they transition between developmental stages. [ABSTRACT FROM AUTHOR]

Biometric features, e.g., fingerprints, the iris, and the face, have been widely used to authenticate individuals. However, most biometrics are not cancellable, i.e., once these biometric features are cloned or stolen, they cannot be replaced easily. Unlike traditional biometrics, brain biometrics are extremely difficult to clone or forge due to the natural randomness across different individuals, which makes them an ideal option for identity authentication. Most existing brain biometrics are based on electroencephalogram (EEG), which is usually demonstrated unstable performance due to the low signal-to-noise ratio (SNR). For the first time, we propose the use of intracortical brain signals, which have higher resolution and SNR, to realize the construction of the high-performance brain biometrics. Specifically, we put forward a novel brain-based key generation approach called multidimensional Gaussian fitted bit allocation (MGFBA). The proposed MGFBA method extracts keys from the local field potential of ten rats with high reliability and high entropy. We found that with the proposed MGFBA, the average effective key length of the brain biometrics was 938 bits, while achieving high authentication accuracy of 88.1% at a false acceptance rate of 1.9%, which is significantly improved compared to conventional EEG-based approaches. In addition, the proposed MGFBA-based keys can be conveniently revoked using different motor behaviors with high entropy. Experimental results demonstrate the potential of using intracortical brain signals for reliable authentication and other security applications. [ABSTRACT FROM AUTHOR]

Delayed cerebral ischemia (DCI) is the most severe complication after subarachnoid hemorrhage (SAH), and cortical spreading depolarization (CSD) is believed to play a vital role in it. However, the dynamic changes in cerebral blood flow (CBF) in response to CSD in typical SAH models have not been well investigated. Here, SAH was established in mice with endovascular perforation. Subsequently, the spontaneous CBF dropped instantly and then returned to baseline rapidly. After KCl application to the cortex, subsequent hypoperfusion waves occurred across the groups, while a lower average perfusion level was found in the SAH groups (days 1–7). Moreover, in the SAH groups, the number of CSD decreased within day 7, and the duration and spreading velocity of the CSD increased within day 3 and day 14, respectively. Next, we continuously monitored the local field potential (LFP) in the prefrontal cortex. The results showed that the decrease in the percentage of gamma oscillations lasted throughout the whole process in the SAH group. In the chronic phase after SAH, we found that the mice still had cognitive deficits but experienced no obvious tissue damage. In summary, SAH negatively affects the CBF responses to CSD and the spontaneous LFP activity and causes long-term cognitive deficits in mice. Based on these findings, in the specific phase after SAH, DCI is induced or exacerbated more easily by potential causers of CSD in clinical practice (edema, erythrocytolysis, inflammation), which may lead to neurological deterioration. [ABSTRACT FROM AUTHOR]

Theta oscillations in the primary visual cortex (VC) have been observed during running tasks, but the mechanism behind their generation is not well understood. Some studies have suggested that theta in the VC is locally generated, while others have proposed that it is volume conducted from the hippocampus. The present study aimed to investigate the relationship between hippocampal and VC LFP dynamics. Analysis of power spectral density revealed that LFP in the VC was similar to that in the hippocampus, but with lower overall magnitude. As running velocity increased, both the power and frequency of theta and its harmonics increased in the VC, similarly to what is observed in the hippocampus. Current source density analysis triggered to theta did not identify distinct current sources and sinks in the VC, supporting the idea that theta in the VC is conducted from the adjacent hippocampus. Phase coupling between theta, its harmonics, and gamma is a notable feature in the hippocampus, particularly in the lacunosum moleculare. While some evidence of coupling between theta and its harmonics in the VC was found, bicoherence estimates did not reveal significant phase coupling between theta and gamma. Similar results were seen in the cross-region bicoherence analysis, where theta showed strong coupling with its harmonics with increasing velocity. Thus, theta oscillations observed in the VC during running tasks are likely due to volume conduction from the hippocampus. [ABSTRACT FROM AUTHOR]