Natural antisense transcript of Period2, Per2AS, regulates the amplitude of the mouse circadian clock.

In mammals, a set of core clock genes form transcription-translation feedback loops to generate circadian oscillations. We and others recently identified a novel transcript at the Period2 (Per2) locus that is transcribed from the antisense strand of Per2 This transcript, Per2AS, is expressed rhythmically and antiphasic to Per2 mRNA, leading to our hypothesis that Per2AS and Per2 mutually inhibit each other's expression and form a double negative feedback loop. By perturbing the expression of Per2AS, we found that Per2AS transcription, but not transcript, represses Per2 However, Per2 does not repress Per2AS, as Per2 knockdown led to a decrease in the Per2AS level, indicating that Per2AS forms a single negative feedback loop with Per2 and maintains the level of Per2 within the oscillatory range. Per2AS also regulates the amplitude of the circadian clock, and this function cannot be solely explained through its interaction with Per2, as Per2 knockdown does not recapitulate the phenotypes of Per2AS perturbation. Overall, our data indicate that Per2AS is an important regulatory molecule in the mammalian circadian clock machinery. Our work also supports the idea that antisense transcripts of core clock genes constitute a common feature of circadian clocks, as they are found in other organisms.

Small-molecule CEM3 strengthens single-cell oscillators in the suprachiasmatic nucleus.

A robust endogenous clock is required for proper function of many physiological processes. The suprachiasmatic nucleus (SCN) constitutes our central circadian clock and allows us to adapt to daily changes in the environment. Aging can cause a decline in the amplitude of circadian rhythms in SCN and peripheral clocks, which contributes to increased risk of several chronic diseases. Strengthening clock function would therefore be an effective strategy to improve health. A high-throughput chemical screening has identified clock-enhancing molecule 3 (CEM3) as small molecule that increases circadian rhythm amplitude in cell lines and SCN explants. It is, however, currently not known whether CEM3 acts by enhancing the amplitude of individual single-cell oscillators or by enhancing synchrony among neurons. In view of CEM3's potential, it is of evident importance to clarify the mode of action of CEM3. Here, we investigated the effects of CEM3 on single-cell PERIOD2::LUCIFERASE rhythms in mouse SCN explants. CEM3 increased the amplitude in approximately 80%-90% of the individual cells in the SCN without disrupting the phase and/or period of their rhythms. Noticeably, CEM3's effect on amplitude is independent of the cell's initial amplitude. These findings make CEM3 a potential therapeutic candidate to restore compromised amplitude in circadian rhythms and will boost the development of other molecular approaches to improve health.

Anatomical and behavioural correlates of auditory perception in developmental dyslexia.

Developmental dyslexia is typically associated with difficulties in basic auditory processing and in manipulating speech sounds. However, the neuroanatomical correlates of auditory difficulties in developmental dyslexia (DD) and their contribution to individual clinical phenotypes are still unknown. Recent intracranial electrocorticography findings associated processing of sound amplitude rises and speech sounds with posterior and middle superior temporal gyrus (STG), respectively. We hypothesize that regional STG anatomy will relate to specific auditory abilities in DD, and that auditory processing abilities will relate to behavioral difficulties with speech and reading. One hundred and ten children (78 DD, 32 typically developing, age 7-15 years) completed amplitude rise time and speech in noise discrimination tasks. They also underwent a battery of cognitive tests. Anatomical MRI scans were used to identify regions in which local cortical gyrification complexity correlated with auditory behavior. Behaviorally, amplitude rise time but not speech in noise performance was impaired in DD. Neurally, amplitude rise time and speech in noise performance correlated with gyrification in posterior and middle STG, respectively. Furthermore, amplitude rise time significantly contributed to reading impairments in DD, while speech in noise only explained variance in phonological awareness. Finally, amplitude rise time and speech in noise performance were not correlated, and each task was correlated with distinct neuropsychological measures, emphasizing their unique contributions to DD. Overall, we provide a direct link between the neurodevelopment of the left STG and individual variability in auditory processing abilities in neurotypical and dyslexic populations.

Altered brain function in classical trigeminal neuralgia patients: ALFF, ReHo, and DC static- and dynamic-frequency study.

The present study aimed to clarify the brain function of classical trigeminal neuralgia (CTN) by analyzing 77 CTN patients and age- and gender-matched 73 healthy controls (HCs) based on three frequency bands of the static and dynamic amplitude of low-frequency fluctuation, regional homogeneity, and degree centrality (sALFF, sReHo, sDC, dALFF, dReHo, and dDC). Compared to HCs, the number of altered brain regions was different in three frequency bands, and the classical frequency band was most followed by slow-4 in CTN patients. Cerrelellum_8_L (sReHo), Cerrelellum_8_R (sDC), Calcarine_R (sDC), and Caudate_R (sDC) were found only in classical frequency band, while Precuneus_L (sALFF) and Frontal_Inf_Tri_L (sReHo) were found only in slow-4 frequency band. Except for the above six brain regions, the others overlapped in the classical and slow-4 frequency bands. CTN seriously affects the mental health of patients, and some different brain regions are correlated with clinical parameters. The static and dynamic indicators of brain function were complementary in CTN patients, and the changing brain regions showed frequency specificity. Compared to slow-5 frequency band, slow-4 is more consistent with the classical frequency band, which could be valuable in exploring the pathophysiology of CTN.

Comparison of the effects of peritoneal dialysis and hemodialysis on spontaneous brain activity in CKD patients: an rs-fMRI study.

OBJECTIVE: To compare the effects of peritoneal dialysis and hemodialysis on spontaneous brain activity in patients with end-stage renal disease. METHODS: A total of 52 dialysis patients with end-stage renal disease, including 25 patients with chronic kidney disease undergoing hemodialysis (HD-CKD) and 27 patients with chronic kidney disease undergoing peritoneal dialysis (PD-CKD), and 49 healthy controls (normal control) were included. All participants underwent neuropsychological testing (Mini-Mental State Examination and Montreal cognitive assessment) and resting-state functional magnetic resonance imaging. Fractional amplitude of low frequency fluctuations and Regional Homogeneity algorithms were employed to evaluate spontaneous brain activity. Statistical analysis was performed to discern differences between the groups. RESULTS: When compared with the normal control group, the PD-CKD group exhibited significant alterations in fractional amplitude of low frequency fluctuations in various cerebellum regions and other brain areas, while the HD-CKD group showed decreased fractional amplitude of low frequency fluctuations in the bilateral pericalcarine cortex. The Regional Homogeneity values in the PD-CKD group were notably different than those in the normal control group, particularly in regions such as the bilateral caudate nucleus and the right putamen. CONCLUSION: Both peritoneal dialysis and hemodialysis modalities impact brain activity, but manifest differently in end-stage renal disease patients. Understanding these differences is crucial for optimizing patient care.

The Epworth sleepiness scale may have more advantages than the multiple sleep latency test in assessing sleepiness in patients with obstructive sleep apnea.

This study aimed to analyze the brain function of severe obstructive sleep apnea patients with various sleepiness assessment methods and explore the brain imaging basis for the differences between these methods. This study included 30 severe obstructive sleep apnea patients and 19 healthy controls. Obstructive sleep apnea patients were divided into a subjective excessive daytime sleepiness group and a subjective non-excessive daytime sleepiness group according to the Epworth sleepiness scale. Moreover, they were divided into an objective excessive daytime sleepiness group and an objective non-excessive daytime sleepiness group according to the multiple sleep latency test. The fractional amplitude of low-frequency fluctuation was used to assess the features of brain function. Compared with healthy controls, participants in the subjective excessive daytime sleepiness group exhibited higher fractional amplitude of low-frequency fluctuation signals in the right thalamus, left cerebellar lobe 6, left putamen, and pallidum. Participants in the objective excessive daytime sleepiness group showed higher fractional amplitude of low-frequency fluctuation signals in the right thalamus and lower fractional amplitude of low-frequency fluctuation signals in the right superior frontal gyrus, the dorsolateral and superior frontal gyrus, and the medial orbital. We concluded that the thalamus may be involved in subjective and objective sleepiness regulation. Functional abnormalities in the putamen and pallidum may be involved in subjective sleepiness, whereas the frontal lobe may be involved in objective sleepiness.

A Redundant Cortical Code for Speech Envelope.

Animal communication sounds exhibit complex temporal structure because of the amplitude fluctuations that comprise the sound envelope. In human speech, envelope modulations drive synchronized activity in auditory cortex (AC), which correlates strongly with comprehension (Giraud and Poeppel, 2012; Peelle and Davis, 2012; Haegens and Zion Golumbic, 2018). Studies of envelope coding in single neurons, performed in nonhuman animals, have focused on periodic amplitude modulation (AM) stimuli and use response metrics that are not easy to juxtapose with data from humans. In this study, we sought to bridge these fields. Specifically, we looked directly at the temporal relationship between stimulus envelope and spiking, and we assessed whether the apparent diversity across neurons' AM responses contributes to the population representation of speech-like sound envelopes. We gathered responses from single neurons to vocoded speech stimuli and compared them to sinusoidal AM responses in auditory cortex (AC) of alert, freely moving Mongolian gerbils of both sexes. While AC neurons displayed heterogeneous tuning to AM rate, their temporal dynamics were stereotyped. Preferred response phases accumulated near the onsets of sinusoidal AM periods for slower rates (<8 Hz), and an over-representation of amplitude edges was apparent in population responses to both sinusoidal AM and vocoded speech envelopes. Crucially, this encoding bias imparted a decoding benefit: a classifier could discriminate vocoded speech stimuli using summed population activity, while higher frequency modulations required a more sophisticated decoder that tracked spiking responses from individual cells. Together, our results imply that the envelope structure relevant to parsing an acoustic stream could be read-out from a distributed, redundant population code.SIGNIFICANCE STATEMENT Animal communication sounds have rich temporal structure and are often produced in extended sequences, including the syllabic structure of human speech. Although the auditory cortex (AC) is known to play a crucial role in representing speech syllables, the contribution of individual neurons remains uncertain. Here, we characterized the representations of both simple, amplitude-modulated sounds and complex, speech-like stimuli within a broad population of cortical neurons, and we found an overrepresentation of amplitude edges. Thus, a phasic, redundant code in auditory cortex can provide a mechanistic explanation for segmenting acoustic streams like human speech.

The Hierarchy of Coupled Sleep Oscillations Reverses with Aging in Humans.

A well orchestrated coupling hierarchy of slow waves and spindles during slow-wave sleep supports memory consolidation. In old age, the duration of slow-wave sleep and the number of coupling events decrease. The coupling hierarchy deteriorates, predicting memory loss and brain atrophy. Here, we investigate the dynamics of this physiological change in slow wave-spindle coupling in a frontocentral electroencephalography position in a large sample (N = 340; 237 females, 103 males) spanning most of the human life span (age range, 15-83 years). We find that, instead of changing abruptly, spindles gradually shift from being driven by slow waves to driving slow waves with age, reversing the coupling hierarchy typically seen in younger brains. Reversal was stronger the lower the slow-wave frequency, and starts around midlife (age range, ∼40-48 years), with an established reversed hierarchy between 56 and 83 years of age. Notably, coupling strength remains unaffected by age. In older adults, deteriorating slow wave-spindle coupling, measured using the phase slope index (PSI) and the number of coupling events, is associated with blood plasma glial fibrillary acidic protein levels, a marker for astrocyte activation. Data-driven models suggest that decreased sleep time and higher age lead to fewer coupling events, paralleled by increased astrocyte activation. Counterintuitively, astrocyte activation is associated with a backshift of the coupling hierarchy (PSI) toward a "younger" status along with increased coupling occurrence and strength, potentially suggesting compensatory processes. As the changes in coupling hierarchy occur gradually starting at midlife, we suggest there exists a sizable window of opportunity for early interventions to counteract undesirable trajectories associated with neurodegeneration.SIGNIFICANCE STATEMENT Evidence accumulates that sleep disturbances and cognitive decline are bidirectionally and causally linked, forming a vicious cycle. Improving sleep quality could break this cycle. One marker for sleep quality is a clear hierarchical structure of sleep oscillations. Previous studies showed that sleep oscillations decouple in old age. Here, we show that, rather, the hierarchical structure gradually shifts across the human life span and reverses in old age, while coupling strength remains unchanged. This shift is associated with markers for astrocyte activation in old age. The shifting hierarchy resembles brain maturation, plateau, and wear processes. This study furthers our comprehension of this important neurophysiological process and its dynamic evolution across the human life span.

Two Oscillatory Correlates of Attention Control in the Alpha-Band with Distinct Consequences on Perceptual Gain and Metacognition.

Behavioral consequences and neural underpinnings of visuospatial attention have long been investigated. Classical studies using the Posner paradigm have found that visual perception systematically benefits from the use of a spatially informative cue pointing to the to-be-attended spatial location, compared with a noninformative cue. Lateralized α amplitude modulation during visuospatial attention shifts has been suggested to account for such perceptual gain. However, recent studies on spontaneous fluctuations of prestimulus α amplitude have challenged this notion. These studies showed that spontaneous fluctuations of prestimulus α amplitude were associated with the subjective appreciation of stimulus occurrence, while objective accuracy was instead best predicted by the frequency of α oscillations, with faster prestimulus α frequency accounting for better perceptual performance. Here, in male and female humans, by using an informative cue in anticipation of lateralized stimulus presentation, we found that the predictive cue not only modulates preparatory α amplitude but also α frequency in a retinotopic manner. Behaviorally, the cue significantly impacted subjective performance measures (metacognitive abilities [meta-d']) and objective performance gain (d'). Importantly, α amplitude directly accounted for confidence levels, with ipsilateral synchronization and contralateral desynchronization coding for high-confidence responses. Crucially, the contralateral α amplitude selectively predicted interindividual differences in metacognitive abilities (meta-d'), thus anticipating decision strategy and not perceptual sensitivity, probably via excitability modulations. Instead, higher perceptual accuracy both within and across participants (d') was associated with faster contralateral α frequency, likely by implementing higher sampling at the attended location. These findings provide critical new insights into the neural mechanisms of attention control and its perceptual consequences.SIGNIFICANCE STATEMENT Prior knowledge serves the anticipation of sensory input to reduce sensory ambiguity. The growing interest in the neural mechanisms governing the integration of sensory input into our internal representations has highlighted a pivotal role of brain oscillations. Here we show that distinct but interacting oscillatory mechanisms are engaged during attentional deployment: one relying on α amplitude modulations and reflecting internal decision processes, associated with subjective perceptual experience and metacognitive abilities; the other relying on α frequency modulations and enabling mechanistic sampling of the sensory input at the attended location to influence objective performance. These insights are crucial for understanding how we reduce sensory ambiguity to maximize the efficiency of our conscious experience, but also in interpreting the mechanisms of atypical perceptual experiences.

Speech Reception in Young Children with Autism Is Selectively Indexed by a Neural Oscillation Coupling Anomaly.

Communication difficulties are one of the core criteria in diagnosing autism spectrum disorder (ASD), and are often characterized by speech reception difficulties, whose biological underpinnings are not yet identified. This deficit could denote atypical neuronal ensemble activity, as reflected by neural oscillations. Atypical cross-frequency oscillation coupling, in particular, could disrupt the joint tracking and prediction of dynamic acoustic stimuli, a dual process that is essential for speech comprehension. Whether such oscillatory anomalies already exist in very young children with ASD, and with what specificity they relate to individual language reception capacity is unknown. We collected neural activity data using electroencephalography (EEG) in 64 very young children with and without ASD (mean age 3; 17 females, 47 males) while they were exposed to naturalistic-continuous speech. EEG power of frequency bands typically associated with phrase-level chunking (δ, 1-3 Hz), phonemic encoding (low-γ, 25-35 Hz), and top-down control (ß, 12-20 Hz) were markedly reduced in ASD relative to typically developing (TD) children. Speech neural tracking by δ and θ (4-8 Hz) oscillations was also weaker in ASD compared with TD children. After controlling gaze-pattern differences, we found that the classical θ/γ coupling was replaced by an atypical ß/γ coupling in children with ASD. This anomaly was the single most specific predictor of individual speech reception difficulties in ASD children. These findings suggest that early interventions (e.g., neurostimulation) targeting the disruption of ß/γ coupling and the upregulation of θ/γ coupling could improve speech processing coordination in young children with ASD and help them engage in oral interactions.SIGNIFICANCE STATEMENT Very young children already present marked alterations of neural oscillatory activity in response to natural speech at the time of autism spectrum disorder (ASD) diagnosis. Hierarchical processing of phonemic-range and syllabic-range information (θ/γ coupling) is disrupted in ASD children. Abnormal bottom-up (low-γ) and top-down (low-ß) coordination specifically predicts speech reception deficits in very young ASD children, and no other cognitive deficit.

Neurovascular coupling in eye-open-eye-close task and resting state: Spectral correspondence between concurrent EEG and fMRI.

Neurovascular coupling serves as an essential neurophysiological mechanism in functional neuroimaging, which is generally presumed to be robust and invariant across different physiological states, encompassing both task engagement and resting state. Nevertheless, emerging evidence suggests that neurovascular coupling may exhibit state dependency, even in normal human participants. To investigate this premise, we analyzed the cross-frequency spectral correspondence between concurrently recorded electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data, utilizing them as proxies for neurovascular coupling during the two conditions: an eye-open-eye-close (EOEC) task and a resting state. We hypothesized that given the state dependency of neurovascular coupling, EEG-fMRI spectral correspondences would change between the two conditions in the visual system. During the EOEC task, we observed a negative phase-amplitude-coupling (PAC) between EEG alpha-band and fMRI visual activity. Conversely, in the resting state, a pronounced amplitude-amplitude-coupling (AAC) emerged between EEG and fMRI signals, as evidenced by the spectral correspondence between the EEG gamma-band of the midline occipital channel (Oz) and the high-frequency fMRI signals (0.15-0.25 Hz) in the visual network. This study reveals distinct scenarios of EEG-fMRI spectral correspondence in healthy participants, corroborating the state-dependent nature of neurovascular coupling.

Population coding of time-varying sounds in the nonlemniscal inferior colliculus.

The inferior colliculus (IC) of the midbrain is important for complex sound processing, such as discriminating conspecific vocalizations and human speech. The IC's nonlemniscal, dorsal "shell" region is likely important for this process, as neurons in these layers project to higher-order thalamic nuclei that subsequently funnel acoustic signals to the amygdala and nonprimary auditory cortices, forebrain circuits important for vocalization coding in a variety of mammals, including humans. However, the extent to which shell IC neurons transmit acoustic features necessary to discern vocalizations is less clear, owing to the technical difficulty of recording from neurons in the IC's superficial layers via traditional approaches. Here, we use two-photon Ca2+ imaging in mice of either sex to test how shell IC neuron populations encode the rate and depth of amplitude modulation, important sound cues for speech perception. Most shell IC neurons were broadly tuned, with a low neurometric discrimination of amplitude modulation rate; only a subset was highly selective to specific modulation rates. Nevertheless, neural network classifier trained on fluorescence data from shell IC neuron populations accurately classified amplitude modulation rate, and decoding accuracy was only marginally reduced when highly tuned neurons were omitted from training data. Rather, classifier accuracy increased monotonically with the modulation depth of the training data, such that classifiers trained on full-depth modulated sounds had median decoding errors of ∼0.2 octaves. Thus, shell IC neurons may transmit time-varying signals via a population code, with perhaps limited reliance on the discriminative capacity of any individual neuron.NEW & NOTEWORTHY The IC's shell layers originate a "nonlemniscal" pathway important for perceiving vocalization sounds. However, prior studies suggest that individual shell IC neurons are broadly tuned and have high response thresholds, implying a limited reliability of efferent signals. Using Ca2+ imaging, we show that amplitude modulation is accurately represented in the population activity of shell IC neurons. Thus, downstream targets can read out sounds' temporal envelopes from distributed rate codes transmitted by populations of broadly tuned neurons.

Multimodal data fusion reveals functional and neurochemical correlates of Parkinson's disease.

BACKGROUND: Neurotransmitter deficits and spatial associations among neurotransmitter distribution, brain activity, and clinical features in Parkinson's disease (PD) remain unclear. Better understanding of neurotransmitter impairments in PD may provide potential therapeutic targets. Therefore, we aimed to investigate the spatial relationship between PD-related patterns and neurotransmitter deficits. METHODS: We included 59 patients with PD and 41 age- and sex-matched healthy controls (HCs). The voxel-wise mean amplitude of the low-frequency fluctuation (mALFF) was calculated and compared between the two groups. The JuSpace toolbox was used to test whether spatial patterns of mALFF alterations in patients with PD were associated with specific neurotransmitter receptor/transporter densities. RESULTS: Compared to HCs, patients with PD showed reduced mALFF in the sensorimotor- and visual-related regions. In addition, mALFF alteration patterns were significantly associated with the spatial distribution of the serotonergic, dopaminergic, noradrenergic, glutamatergic, cannabinoid, and acetylcholinergic neurotransmitter systems (p < 0.05, false discovery rate-corrected). CONCLUSIONS: Our results revealed abnormal brain activity patterns and specific neurotransmitter deficits in patients with PD, which may provide new insights into the mechanisms and potential targets for pharmacotherapy.

Neurovascular coupling alteration in drug-naïve Parkinson's disease: The underlying molecular mechanisms and levodopa's restoration effects.

BACKGROUND: Parkinson's disease (PD) patients exhibit an imbalance between neuronal activity and perfusion, referred to as abnormal neurovascular coupling (NVC). Nevertheless, the underlying molecular mechanism and how levodopa, the standard treatment in PD, regulates NVC is largely unknown. MATERIAL AND METHODS: A total of 52 drug-naïve PD patients and 49 normal controls (NCs) were enrolled. NVC was characterized in vivo by relating cerebral blood flow (CBF) and amplitude of low-frequency fluctuations (ALFF). Motor assessments and MRI scanning were conducted on drug-naïve patients before and after levodopa therapy (OFF/ON state). Regional NVC differences between patients and NCs were identified, followed by an assessment of the associated receptors/transporters. The influence of levodopa on NVC, CBF, and ALFF within these abnormal regions was analyzed. RESULTS: Compared to NCs, OFF-state patients showed NVC dysfunction in significantly lower NVC in left precentral, postcentral, superior parietal cortex, and precuneus, along with higher NVC in left anterior cingulate cortex, right olfactory cortex, thalamus, caudate, and putamen (P-value <0.0006). The distribution of NVC differences correlated with the density of dopaminergic, serotonin, MU-opioid, and cholinergic receptors/transporters. Additionally, levodopa ameliorated abnormal NVC in most of these regions, where there were primarily ALFF changes with limited CBF modifications. CONCLUSION: Patients exhibited NVC dysfunction primarily in the striato-thalamo-cortical circuit and motor control regions, which could be driven by dopaminergic and nondopaminergic systems, and levodopa therapy mainly restored abnormal NVC by modulating neuronal activity.

Neural adaptation of the reward system in primary dysmenorrhea.

Introduction: The brain's reward system (RS) reacts differently to pain and its alleviation. This study examined the correlation between RS activity and behavior during both painful and pain-free periods in individuals with primary dysmenorrhea (PDM) to elucidate their varying responses throughout the menstrual cycle. Methods: Ninety-two individuals with PDM and 90 control participants underwent resting-state functional magnetic resonance imaging (rsfMRI) scans during their menstrual and peri-ovulatory phases. Regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) analyses were used to evaluate RS responses. Psychological evaluations were conducted using the McGill Pain Questionnaire and the Pain Catastrophizing Scale. Results: ReHo analysis showed higher values in the left putamen and right amygdala of the PDM group during the peri-ovulatory phase compared to the menstrual phase. ALFF analysis revealed lower values in the putamen of the PDM group compared to controls, regardless of phase. ReHo and ALFF values in the putamen, amygdala, and nucleus accumbens were positively correlated with pain scales during menstruation, while ALFF values in the ventral tegmental area inversely correlated with pain intensity. Those with severe PDM (pain intensity ≥7) displayed distinct amygdala ALFF patterns between pain and pain-free phases. PDM participants also had lower ReHo values in the left insula during menstruation, with no direct correlation to pain compared to controls. Discussion: Our study highlights the pivotal role of the RS in dysmenorrhea management, exhibiting varied responses between menstrual discomfort and non-painful periods among individuals with PDM. During menstruation, the RS triggers mechanisms for pain avoidance and cognitive coping strategies, while it transitions to processing rewards during the peri-ovulatory phase. This demonstrates the flexibility of the RS in adapting to the recurring pain experienced by those with PDM.

Altered dynamic amplitude of low-frequency fluctuation in individuals at high risk for Alzheimer's disease.

The brain's dynamic spontaneous neural activity is significant in supporting cognition; however, how brain dynamics go awry in subjective cognitive decline (SCD) and mild cognitive impairment (MCI) remains unclear. Thus, the current study aimed to investigate the dynamic amplitude of low-frequency fluctuation (dALFF) alterations in patients at high risk for Alzheimer's disease and to explore its correlation with clinical cognitive assessment scales, to identify an early imaging sign for these special populations. A total of 152 participants, including 72 SCD patients, 44 MCI patients and 36 healthy controls (HCs), underwent a resting-state functional magnetic resonance imaging and were assessed with various neuropsychological tests. The dALFF was measured using sliding-window analysis. We employed canonical correlation analysis (CCA) to examine the bi-multivariate correlations between neuropsychological scales and altered dALFF among multiple regions in SCD and MCI patients. Compared to those in the HC group, both the MCI and SCD groups showed higher dALFF values in the right opercular inferior frontal gyrus (voxel P < .001, cluster P < .05, correction). Moreover, the CCA models revealed that behavioural tests relevant to inattention correlated with the dALFF of the right middle frontal gyrus and right opercular inferior frontal gyrus, which are involved in frontoparietal networks (R = .43, P = .024). In conclusion, the brain dynamics of neural activity in frontal areas provide insights into the shared neural basis underlying SCD and MCI.

Differences in resting-state brain activity in first-episode drug-naïve major depressive disorder patients with and without suicidal ideation.

Despite altered brain activities being associated with suicidal ideation (SI), the neural correlates of SI in major depressive disorder (MDD) have remained elusive. We enrolled 82 first-episode drug-naïve MDD patients including 41 with SI and 41 without SI, as well as 41 healthy controls (HCs). Resting-state functional and structural MRI data were collected. The measures of fractional amplitude of low-frequency fluctuation (fALFF) and grey matter volume (GMV) were calculated and compared. Compared with HCs, patients with SI exhibited increased fALFF values in the right rectus gyrus and left medial superior frontal gyrus, middle frontal gyrus and precuneus. Decreased GMV in the right parahippocampal gyrus, insula and middle occipital gyrus and increased GMV in the left superior frontal gyrus were detected in patients with SI. In addition, patients without SI demonstrated increased fALFF values in the right superior frontal gyrus and decreased fALFF values in the right postcentral gyrus. Decreased GMV in the left superior frontal gyrus, right medial superior frontal gyrus, opercular part of inferior frontal gyrus, postcentral gyrus, fusiform gyrus and increased left supplementary motor area, superior occipital gyrus, right anterior cingulate gyrus and superior temporal gyrus were revealed in patients with SI. Moreover, in comparison with patients without SI, increased fALFF values were identified in the left precuneus of patients with SI. However, no significant differences were found in GMV between patients with and without SI. These findings might be helpful for finding neuroimaging markers predicting individual suicide risk and detecting targeted brain regions for effective early interventions.

Data-driven MEG analysis to extract fMRI resting-state networks.

The electrophysiological basis of resting-state networks (RSN) is still under debate. In particular, no principled mechanism has been determined that is capable of explaining all RSN equally well. While magnetoencephalography (MEG) and electroencephalography are the methods of choice to determine the electrophysiological basis of RSN, no standard analysis pipeline of RSN yet exists. In this article, we compare the two main existing data-driven analysis strategies for extracting RSNs from MEG data and introduce a third approach. The first approach uses phase-amplitude coupling to determine the RSN. The second approach extracts RSN through an independent component analysis of the Hilbert envelope in different frequency bands, while the third new approach uses a singular value decomposition instead. To evaluate these approaches, we compare the MEG-RSN to the functional magnetic resonance imaging (fMRI)-RSN from the same subjects. Overall, it was possible to extract RSN with MEG using all three techniques, which matched the group-specific fMRI-RSN. Interestingly the new approach based on SVD yielded significantly higher correspondence to five out of seven fMRI-RSN than the two existing approaches. Importantly, with this approach, all networks-except for the visual network-had the highest correspondence to the fMRI networks within one frequency band. Thereby we provide further insights into the electrophysiological underpinnings of the fMRI-RSNs. This knowledge will be important for the analysis of the electrophysiological connectome.

Dynamic evolution of frontal-temporal network connectivity in temporal lobe epilepsy: A magnetoencephalography study.

Temporal lobe epilepsy (TLE) frequently involves an intricate, extensive epileptic frontal-temporal network. This study aimed to investigate the interactions between temporal and frontal regions and the dynamic patterns of the frontal-temporal network in TLE patients with different disease durations. The magnetoencephalography data of 36 postoperative seizure-free patients with long-term follow-up of at least 1 year, and 21 age- and sex-matched healthy subjects were included in this study. Patients were initially divided into LONG-TERM (n = 18, DURATION >10 years) and SHORT-TERM (n = 18, DURATION ≤10 years) groups based on 10-year disease duration. For reliability, supplementary analyses were conducted with alternative cutoffs, creating three groups: 0 < DURATION ≤7 years (n = 11), 7 < DURATION ≤14 years (n = 11), and DURATION >14 years (n = 14). This study examined the intraregional phase-amplitude coupling (PAC) between theta phase and alpha amplitude across the whole brain. The interregional directed phase transfer entropy (dPTE) between frontal and temporal regions in the alpha and theta bands, and the interregional cross-frequency directionality (CFD) between temporal and frontal regions from the theta phase to the alpha amplitude were further computed and compared among groups. Partial correlation analysis was conducted to investigate correlations between intraregional PAC, interregional dPTE connectivity, interregional CFD, and disease duration. Whole-brain intraregional PAC analyses revealed enhanced theta phase-alpha amplitude coupling within the ipsilateral temporal and frontal regions in TLE patients, and the ipsilateral temporal PAC was positively correlated with disease duration (r = 0.38, p <.05). Interregional dPTE analyses demonstrated a gradual increase in frontal-to-temporal connectivity within the alpha band, while the direction of theta-band connectivity reversed from frontal-to-temporal to temporal-to-frontal as the disease duration increased. Interregional CFD analyses revealed that the inhibitory effect of frontal regions on temporal regions gradually increased with prolonged disease duration (r = -0.36, p <.05). This study clarified the intrinsic reciprocal connectivity between temporal and frontal regions with TLE duration. We propose a dynamically reorganized triple-stage network that transitions from balanced networks to constrained networks and further develops into imbalanced networks as the disease duration increases.

Impact of Electric Field Magnitude in the Left Dorsolateral Prefrontal Cortex on Changes in Intrinsic Functional Connectivity Using Transcranial Direct Current Stimulation: A Randomized Crossover Study.

This study investigated whether the electric field magnitude (E-field) delivered to the left dorsolateral prefrontal cortex (L-DLPFC) changes resting-state brain activity and the L-DLPFC resting-state functional connectivity (rsFC), given the variability in tDCS response and lack of understanding of how rsFC changes. Twenty-one healthy participants received either 2 mA anodal or sham tDCS targeting the L-DLPFC for 10 min. Brain imaging was conducted before and after stimulation. The fractional amplitude of low-frequency fluctuation (fALFF), reflecting resting brain activity, and the L-DLPFC rsFC were analyzed to investigate the main effect of tDCS, main effect of time, and interaction effects. The E-field was estimated by modeling tDCS-induced individual electric fields and correlated with fALFF and L-DLPFC rsFC. Anodal tDCS increased fALFF in the left rostral middle frontal area and decreased fALFF in the midline frontal area (FWE p < 0.050), whereas sham induced no changes. Overall rsFC decreased after sham (positive and negative connectivity, p = 0.001 and 0.020, respectively), with modest and nonsignificant changes after anodal tDCS (p = 0.063 and 0.069, respectively). No significant differences in local rsFC were observed among the conditions. Correlations were observed between the E-field and rsFC changes in the L-DLPFC (r = 0.385, p = 0.115), left inferior parietal area (r = 0.495, p = 0.037), and right lateral visual area (r = 0.683, p = 0.002). Single-session tDCS induced resting brain activity changes and may help maintain overall rsFC. The E-field in the L-DLPFC is associated with rsFC changes in both proximal and distally connected brain regions to the L-DLPFC.