Theta-gamma Phase-amplitude Coupling Research Articles

Human Cervical Epidural Spinal Electrogram Topographically Maps Distinct Volitional Movements.

Little is known about the electrophysiologic activity of the intact human spinal cord during volitional movement. We analyzed epidural spinal recordings from a total of 5 human subjects of both sexes during a variety of upper extremity movements and found that these spinal epidural electrograms contain spectral information distinguishing periods of movement, rest, and sensation. Cervical epidural electrograms also contained spectral changes time-locked with movement. We found that these changes were primarily associated with increased power in the theta (4-8 Hz) band, feature increased theta-gamma phase-amplitude coupling, and that this increase in theta power can be used to topographically map distinct upper extremity movements onto the cervical spinal cord in accordance with established myotome maps of the upper extremity. Our findings have implications for the development of neurostimulation protocols and devices focused on motor rehabilitation for the upper extremity and the approach presented here may facilitate spatiotemporal mapping of naturalistic movements.Significance statement The electrophysiology of the human spinal cord remains incompletely characterized. We build on our previous work in describing a novel method of recording spinal epidural electrograms from awake human participants by showing that SEGs (spinal electrograms) recorded from the cervical spinal cord during volitional upper extremity movements demonstrate spectral changes time-locked to movement that feature prominent increase in theta band power, theta-gamma phase-amplitude coupling, and are well delineated from pre-movement baseline. These spectral changes can also be topographically mapped to the cervical spine in a myotome distribution broadly consistent with maps generated from intraoperative stimulation studies in humans and direct stimulation experiments in monkeys. Our methodology may aid in the developing spatiotemporal maps for neurostimulation protocols to recapitulate naturalistic movements.

Individualized music induces theta-gamma phase-amplitude coupling in patients with disorders of consciousness.

This study aimed to determine whether patients with disorders of consciousness (DoC) could experience neural entrainment to individualized music, which explored the cross-modal influences of music on patients with DoC through phase-amplitude coupling (PAC). Furthermore, the study assessed the efficacy of individualized music or preferred music (PM) versus relaxing music (RM) in impacting patient outcomes, and examined the role of cross-modal influences in determining these outcomes. Thirty-two patients with DoC [17 with vegetative state/unresponsive wakefulness syndrome (VS/UWS) and 15 with minimally conscious state (MCS)], alongside 16 healthy controls (HCs), were recruited for this study. Neural activities in the frontal-parietal network were recorded using scalp electroencephalography (EEG) during baseline (BL), RM and PM. Cerebral-acoustic coherence (CACoh) was explored to investigate participants' abilitiy to track music, meanwhile, the phase-amplitude coupling (PAC) was utilized to evaluate the cross-modal influences of music. Three months post-intervention, the outcomes of patients with DoC were followed up using the Coma Recovery Scale-Revised (CRS-R). HCs and patients with MCS showed higher CACoh compared to VS/UWS patients within musical pulse frequency (p = 0.016, p = 0.045; p < 0.001, p = 0.048, for RM and PM, respectively, following Bonferroni correction). Only theta-gamma PAC demonstrated a significant interaction effect between groups and music conditions (F (2,44) = 2.685, p = 0.036). For HCs, the theta-gamma PAC in the frontal-parietal network was stronger in the PM condition compared to the RM (p = 0.016) and BL condition (p < 0.001). For patients with MCS, the theta-gamma PAC was stronger in the PM than in the BL (p = 0.040), while no difference was observed among the three music conditions in patients with VS/UWS. Additionally, we found that MCS patients who showed improved outcomes after 3 months exhibited evident neural responses to preferred music (p = 0.019). Furthermore, the ratio of theta-gamma coupling changes in PM relative to BL could predict clinical outcomes in MCS patients (r = 0.992, p < 0.001). Individualized music may serve as a potential therapeutic method for patients with DoC through cross-modal influences, which rely on enhanced theta-gamma PAC within the consciousness-related network.

Impaired Hippocampal Reactivation Preceding Robust Aβ Deposition in a Model of Alzheimer's Disease.

Current therapeutic strategies for Alzheimer's disease (AD) target amyloid-beta (Aβ) fibrils and high molecular weight protofibrils associated with plaques, but other bioactive species may directly contribute to neural systems failure in AD. Employing hippocampal electrophysiological recordings and dynamic calcium imaging across the sleep-wake cycle in young mice expressing human Aβ and Aβ oligomers, we reveal marked impairments of hippocampal function long before amyloid plaques predominate. In slow wave sleep (SWS), Aβ increased the proportion of hypoactive cells and reduced place-cell reactivation. During awake behavior, Aβ impaired theta-gamma phase-amplitude coupling (PAC) and drove excessive synchronization of place cell calcium fluctuations with hippocampal theta. Remarkably, the on-line impairment of hippocampal theta-gamma PAC correlated with the SWS impairment of place-cell reactivation. Together, these results identify toxic effects of Aβ on memory encoding and consolidation processes before robust plaque deposition and support targeting soluble Aβ-related species to treat and prevent AD.

Control of working memory by phase–amplitude coupling of human hippocampal neurons

Retaining information in working memory is a demanding process that relies on cognitive control to protect memoranda-specific persistent activity from interference1,2. However, how cognitive control regulates working memory storage is unclear. Here we show that interactions of frontal control and hippocampal persistent activity are coordinated by theta–gamma phase–amplitude coupling (TG-PAC). We recorded single neurons in the human medial temporal and frontal lobe while patients maintained multiple items in their working memory. In the hippocampus, TG-PAC was indicative of working memory load and quality. We identified cells that selectively spiked during nonlinear interactions of theta phase and gamma amplitude. The spike timing of these PAC neurons was coordinated with frontal theta activity when cognitive control demand was high. By introducing noise correlations with persistently active neurons in the hippocampus, PAC neurons shaped the geometry of the population code. This led to higher-fidelity representations of working memory content that were associated with improved behaviour. Our results support a multicomponent architecture of working memory1,2, with frontal control managing maintenance of working memory content in storage-related areas3–5. Within this framework, hippocampal TG-PAC integrates cognitive control and working memory storage across brain areas, thereby suggesting a potential mechanism for top-down control over sensory-driven processes.

Brain oscillatory processes related to sequence memory in healthy older adults

Sequence memory is subject to age-related decline, but the underlying processes are not yet fully understood. We analyzed electroencephalography (EEG) in 21 healthy older (60–80 years) and 26 young participants (20–30 years) and compared time-frequency spectra and theta-gamma phase-amplitude-coupling (PAC) during encoding of the order of visually presented items. In older adults, desynchronization in theta (4–8 Hz) and synchronization in gamma (30–45 Hz) power did not distinguish between subsequently correctly and incorrectly remembered trials, while there was a subsequent memory effect for young adults. Theta-gamma PAC was modulated by item position within a sequence for older but not young adults. Specifically, position within a sequence was coded by higher gamma amplitude for successive theta phases for later correctly remembered trials. Thus, deficient differentiation in theta desynchronization and gamma oscillations during sequence encoding in older adults may reflect neurophysiological correlates of age-related memory decline. Furthermore, our results indicate that sequences are coded by theta-gamma PAC in older adults, but that this mechanism might lose precision in aging.

Event-related theta and gamma band oscillatory dynamics during visuo-spatial sequence memory in younger and older adults.

Visuo-spatial working memory (VSWM) for sequences is thought to be crucial for daily behaviors. Decades of research indicate that oscillations in the gamma and theta bands play important functional roles in the support of visuo-spatial working memory, but the vast majority of that research emphasizes measures of neural activity during memory retention. The primary aims of the present study were (1) to determine whether oscillatory dynamics in the Theta and Gamma ranges would reflect item-level sequence encoding during a computerized spatial span task, (2) to determine whether item-level sequence recall is also related to these neural oscillations, and (3) to determine the nature of potential changes to these processes in healthy cognitive aging. Results indicate that VSWM sequence encoding is related to later (∼700 ms) gamma band oscillatory dynamics and may be preserved in healthy older adults; high gamma power over midline frontal and posterior sites increased monotonically as items were added to the spatial sequence in both age groups. Item-level oscillatory dynamics during the recall of VSWM sequences were related only to theta-gamma phase amplitude coupling (PAC), which increased monotonically with serial position in both age groups. Results suggest that, despite a general decrease in frontal theta power during VSWM sequence recall in older adults, gamma band dynamics during encoding and theta-gamma PAC during retrieval play unique roles in VSWM and that the processes they reflect may be spared in healthy aging.

Cortical hyperexcitability in mouse models and patients with amyotrophic lateral sclerosis is linked to noradrenaline deficiency.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, characterized by the death of upper (UMN) and lower motor neurons (LMN) in the motor cortex, brainstem, and spinal cord. Despite decades of research, ALS remains incurable, challenging to diagnose, and of extremely rapid progression. A unifying feature of sporadic and familial forms of ALS is cortical hyperexcitability, which precedes symptom onset, negatively correlates with survival, and is sufficient to trigger neurodegeneration in rodents. Using electrocorticography in the Sod1G86R and FusΔNLS/+ ALS mouse models and standard electroencephalography recordings in patients with sporadic ALS, we demonstrate a deficit in theta-gamma phase-amplitude coupling (PAC) in ALS. In mice, PAC deficits started before symptom onset, and in patients, PAC deficits correlated with the rate of disease progression. Using mass spectrometry analyses of CNS neuropeptides, we identified a presymptomatic reduction of noradrenaline (NA) in the motor cortex of ALS mouse models, further validated by in vivo two-photon imaging in behaving SOD1G93A and FusΔNLS/+ mice, that revealed pronounced reduction of locomotion-associated NA release. NA deficits were also detected in postmortem tissues from patients with ALS, along with transcriptomic alterations of noradrenergic signaling pathways. Pharmacological ablation of noradrenergic neurons with DSP-4 reduced theta-gamma PAC in wild-type mice and administration of a synthetic precursor of NA augmented theta-gamma PAC in ALS mice. Our findings suggest theta-gamma PAC as means to assess and monitor cortical dysfunction in ALS and warrant further investigation of the NA system as a potential therapeutic target.

Cross-frequency coupling in cortico-hippocampal networks supports the maintenance of sequential auditory information in short-term memory.

It has been suggested that cross-frequency coupling in cortico-hippocampal networks enables the maintenance of multiple visuo-spatial items in working memory. However, whether this mechanism acts as a global neural code for memory retention across sensory modalities remains to be demonstrated. Intracranial EEG data were recorded while drug-resistant patients with epilepsy performed a delayed matched-to-sample task with tone sequences. We manipulated task difficulty by varying the memory load and the duration of the silent retention period between the to-be-compared sequences. We show that the strength of theta-gamma phase amplitude coupling in the superior temporal sulcus, the inferior frontal gyrus, the inferior temporal gyrus, and the hippocampus (i) supports the short-term retention of auditory sequences; (ii) decodes correct and incorrect memory trials as revealed by machine learning analysis; and (iii) is positively correlated with individual short-term memory performance. Specifically, we show that successful task performance is associated with consistent phase coupling in these regions across participants, with gamma bursts restricted to specific theta phase ranges corresponding to higher levels of neural excitability. These findings highlight the role of cortico-hippocampal activity in auditory short-term memory and expand our knowledge about the role of cross-frequency coupling as a global biological mechanism for information processing, integration, and memory in the human brain.

Inactivation of hypocretin receptor-2 signaling in dopaminergic neurons induces hyperarousal and enhanced cognition but impaired inhibitory control

Hypocretin/Orexin (HCRT/OX) and dopamine (DA) are both key effectors of salience processing, reward and stress-related behaviors and motivational states, yet their respective roles and interactions are poorly delineated. We inactivated HCRT-to-DA connectivity by genetic disruption of Hypocretin receptor-1 (Hcrtr1), Hypocretin receptor-2 (Hcrtr2), or both receptors (Hcrtr1&2) in DA neurons and analyzed the consequences on vigilance states, brain oscillations and cognitive performance in freely behaving mice. Unexpectedly, loss of Hcrtr2, but not Hcrtr1 or Hcrtr1&2, induced a dramatic increase in theta (7–11 Hz) electroencephalographic (EEG) activity in both wakefulness and rapid-eye-movement sleep (REMS). DAHcrtr2-deficient mice spent more time in an active (or theta activity-enriched) substate of wakefulness, and exhibited prolonged REMS. Additionally, both wake and REMS displayed enhanced theta-gamma phase-amplitude coupling. The baseline waking EEG of DAHcrtr2-deficient mice exhibited diminished infra-theta, but increased theta power, two hallmarks of EEG hyperarousal, that were however uncoupled from locomotor activity. Upon exposure to novel, either rewarding or stress-inducing environments, DAHcrtr2-deficient mice featured more pronounced waking theta and fast-gamma (52–80 Hz) EEG activity surges compared to littermate controls, further suggesting increased alertness. Cognitive performance was evaluated in an operant conditioning paradigm, which revealed that DAHcrtr2-ablated mice manifest faster task acquisition and higher choice accuracy under increasingly demanding task contingencies. However, the mice concurrently displayed maladaptive patterns of reward-seeking, with behavioral indices of enhanced impulsivity and compulsivity. None of the EEG changes observed in DAHcrtr2-deficient mice were seen in DAHcrtr1-ablated mice, which tended to show opposite EEG phenotypes. Our findings establish a clear genetically-defined link between monosynaptic HCRT-to-DA neurotransmission and theta oscillations, with a differential and novel role of HCRTR2 in theta-gamma cross-frequency coupling, attentional processes, and executive functions, relevant to disorders including narcolepsy, attention-deficit/hyperactivity disorder, and Parkinson’s disease.

Phase-amplitude coupling of Go/Nogo task-related neuronal oscillation decreases for humans with insufficient sleep.

Phase-amplitude coupling (PAC) across frequency might be associated with the long-range synchronization of brain networks, facilitating the spatiotemporal integration of multiple cell assemblies for information transmission during inhibitory control. However, sleep problems may affect these cortical information transmissions based on cross-frequency PAC, especially when humans work in environments of social isolation. This study aimed to evaluate changes in the theta-beta/gamma PAC of task-related electroencephalography (EEG) for humans with insufficient sleep. Here, we monitored the EEG signals of 60 healthy volunteers and 18 soldiers in the normal environment, performing a Go/Nogo task. Soldiers also participated in the same test in isolated cabins. These measures demonstrated theta-beta PACs between the frontal and central-parietal, and robust theta-gamma PACs between the frontal and occipital cortex. Unfortunately, these PACs significantly decreased when humans experienced insufficient sleep, which was positively correlated with the behavioral performance of inhibitory control. The evaluation of theta-beta/gamma PAC of Go/Nogo task-related EEG is necessary to help understand the different influences of sleep problems in humans.

Subjective cognitive decline exhibits alterations of resting-state phase-amplitude coupling in precuneus

ObjectiveSubjective cognitive decline (SCD) is associated with increased risks for progressing to Alzheimer’s disease (AD). This study aimed to investigate phase-amplitude coupling (PAC) in individuals with SCD and healthy controls (HCs) in the baseline year and determined the predictability of cognitive changes in the clinical follow-up. MethodsResting-state magnetoencephalographic signals in 29 HCs and 23 SCD subjects were recorded in the baseline year. The parahippocampal gyrus, posterior cingulate cortex and precuneus were selected as regions of interest (ROIs). Based on the grand-averaged comodulograms, delta–beta, delta–gamma and theta–gamma PAC values were extracted from each ROI. ResultsCompared with the HCs, the SCD group showed decreased theta–gamma PAC in the precuneus. Theta–gamma PAC of the left precuneus was associated with SCD severity and performance of immediate recall in the baseline year. The SCD group was followed for 3 years and divided into SCD-Stable and SCD-Decline groups based on scores of Mini-Mental State Examination. No significant differences in PAC of the baseline year were found between SCD-Stable and SCD-Decline groups. ConclusionsThe SCD group demonstrated reduced theta–gamma PAC in the precuneus. SignificanceSubjective perception of cognitive decline is reflected by objective alterations of brain function.

Theta-gamma phase-amplitude coupling as a marker of cognitive deficits in schizophrenia

Theta-gamma phase-amplitude coupling as a marker of cognitive deficits in schizophrenia

Transcranial Alternating Current Stimulation Alters Auditory Steady-State Oscillatory Rhythms and Their Cross-Frequency Couplings.

Auditory cortical plasticity deficits in schizophrenia are evidenced with electroencephalographic (EEG)-derived biomarkers, including the 40-Hz auditory steady-state response (ASSR). Aiming to understand the underlying oscillatory mechanisms contributing to the 40-Hz ASSR, we examined its response to transcranial alternating current stimulation (tACS) applied bilaterally to the temporal lobe of 23 healthy participants. Although not responding to gamma tACS, the 40-Hz ASSR was modulated by theta tACS (vs sham tACS), with reductions in gamma power and phase locking being accompanied by increases in theta-gamma phase-amplitude cross-frequency coupling. Results reveal that oscillatory changes induced by frequency-tuned tACS may be one approach for targeting and modulating auditory plasticity in normal and diseased brains.

Eltoprazine modulated gamma oscillations on ameliorating L-dopa-induced dyskinesia in rats.

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. 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. 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. 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.

Theta-gamma phase amplitude coupling in a hippocampal CA1 microcircuit.

Phase amplitude coupling (PAC) between slow and fast oscillations is found throughout the brain and plays important functional roles. Its neural origin remains unclear. Experimental findings are often puzzling and sometimes contradictory. Most computational models rely on pairs of pacemaker neurons or neural populations tuned at different frequencies to produce PAC. Here, using a data-driven model of a hippocampal microcircuit, we demonstrate that PAC can naturally emerge from a single feedback mechanism involving an inhibitory and excitatory neuron population, which interplay to generate theta frequency periodic bursts of higher frequency gamma. The model suggests the conditions under which a CA1 microcircuit can operate to elicit theta-gamma PAC, and highlights the modulatory role of OLM and PVBC cells, recurrent connectivity, and short term synaptic plasticity. Surprisingly, the results suggest the experimentally testable prediction that the generation of the slow population oscillation requires the fast one and cannot occur without it.

Alterations in theta-gamma coupling and sharp wave-ripple, signs of prodromal hippocampal network impairment in the TgF344-AD rat model.

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

Reductions in regional theta power and fronto-parietal theta-gamma phase-amplitude coupling during gaze processing in bipolar disorder

Impaired social cognition is common in bipolar disorder (BD) and predicts poor functional outcomes. A critical determinant of social cognition is the ability to discriminate others’ gaze direction, and its alteration may contribute to functional impairment in BD. However, the neural mechanisms underlying gaze processing in BD are unclear. Because neural oscillations are crucial neurobiological mechanisms supporting cognition, we aimed to understand their role in gaze processing in BD. Using electroencephalography (EEG) data recorded during a gaze discrimination task for 38 BD and 34 controls (HC), we examined: theta and gamma power over bilateral posterior and midline anterior locations associated with early face processing and higher-level cognitive processing, and theta-gamma phase-amplitude coupling (PAC) between locations. Compared to HC, BD showed reduced midline-anterior and left-posterior theta power, and diminished bottom-up/top-down theta-gamma PAC between anterior/posterior sites. Reduced theta power and theta-gamma PAC related to slower response times. These findings suggest that altered theta oscillations and anterior-posterior cross-frequency coupling between areas associated with higher-level cognition and early face processing may underlie impaired gaze processing in BD. This is a crucial step towards translational research that may inform novel social cognitive interventions (e.g., neuromodulation to target specific oscillatory dynamics) to improve functioning in BD.

Theta-gamma phase-amplitude coupling in auditory cortex is modulated by language proficiency.

The coordination between the theta phase (3-7 Hz) and gamma power (25-35 Hz) oscillations (namely theta-gamma phase-amplitude coupling, PAC) in the auditory cortex has been proposed as an essential neural mechanism involved in speech processing. However, it has not been established how this mechanism is related to the efficiency with which a listener processes speech. Speech processing in a non-native language offers a useful opportunity to evaluate if theta-gamma PAC is modulated by the challenges imposed by the reception of speech input in a non-native language. The present study investigates how auditory theta-gamma PAC (recorded with magnetoencephalography) is modulated in both native and non-native speech reception. Participants were Spanish native (L1) speakers studying Basque (L2) at three different levels: beginner (Grade 1), intermediate (Grade 2), and advanced (Grade 3). We found that during L2 speech processing (i) theta-gamma PAC was more highly coordinated for intelligible compared to unintelligible speech; (ii) this coupling was modulated by proficiency in Basque being lower for beginners, higher for intermediate, and highest for advanced speakers (no difference observed in Spanish); (iii) gamma power did not differ between languages and groups. These findings highlight how the coordinated theta-gamma oscillatory activity is tightly related to speech comprehension: the stronger this coordination is, the more the comprehension system will proficiently parse the incoming speech input.

Cognitive impairments in a Down syndrome model with abnormal hippocampal and prefrontal dynamics and cytoarchitecture

The Dp(10)2Yey mouse carries a ∼2.3-Mb intra-chromosomal duplication of mouse chromosome 10 (Mmu10) that has homology to human chromosome 21, making it an essential model for aspects of Down syndrome (DS, trisomy 21). In this study, we investigated neuronal dysfunction in the Dp(10)2Yey mouse and report spatial memory impairment and anxiety-like behavior alongside altered neural activity in the medial prefrontal cortex (mPFC) and hippocampus (HPC). Specifically, Dp(10)2Yey mice showed impaired spatial alternation associated with increased sharp-wave ripple activity in mPFC during a period of memory consolidation, and reduced mobility in a novel environment accompanied by reduced theta-gamma phase-amplitude coupling in HPC. Finally, we found alterations in the number of interneuron subtypes in mPFC and HPC that may contribute to the observed phenotypes and highlight potential approaches to ameliorate the effects of human trisomy 21.

Neural responses to social decision-making in suicide attempters with mental disorders

BackgroundDecision-making deficits have been reported in suicide attempters and may be a neuropsychological trait of vulnerability to suicidal behavior. However, little is known about how neural activity is altered in decision-making. This study aimed to investigate the neural responses in suicide attempters with mental disorders during social decision-making. Electroencephalography (EEG) were recorded from 52 patients with mental disorders with past suicide attempts (SAs = 26) and without past suicide attempts (NSAs = 26), as well as from 22 age- and sex- matched healthy controls (HCs) during the Ultimatum Game (UG), which is a typical paradigm to investigate the responses to fair and unfair decision-making.MethodsMINI 5.0 interview and self report questionnaire were used to make mental diagnosis and suicide behavior assessment for individuals. Event-related potential (ERP) and phase-amplitude coupling (PAC) were extracted to quantify the neural activity. Furthermore, Spearman correlation and logistic regression analyses were conducted to identify the risk factors of suicidal behavior.ResultsERP analysis demonstrated that SA patients had decreased P2 amplitude and prolonged P2 latency when receiving unfair offers. Moreover, SA patients exhibited greater negative-going feedback-related negativity (FRN) to unfair offers compared to fair ones, whereas such a phenomenon was absent in NSA and HC groups. These results revealed that SA patients had a stronger fairness principle and a disregard toward the cost of punishment in social decision-making. Furthermore, theta-gamma and beta-gamma PAC were involved in decision-making, with compromised neural coordination in the frontal, central, and temporal regions in SA patients, suggesting cognitive dysfunction during social interaction. Statistically significant variables were used in logistic regression analysis. The area under receiver operating characteristic curve in the logistic regression model was 0.91 for SA/HC and 0.84 for SA/NSA.ConclusionsOur findings emphasize that suicide attempts in patients with mental disorders are associated with abnormal decision-making. P2, theta-gamma PAC, and beta-gamma PAC may be neuro-electrophysiological biomarkers associated with decision-making. These results provide neurophysiological signatures of suicidal behavior.