Development of neuronal timescales in human cortical organoids and rat hippocampus dissociated cultures.

To support complex cognition, neuronal circuits must integrate information across multiple temporal scales, ranging from milliseconds to decades. Neuronal timescales describe the duration over which activity within a network persists, posing a putative explanatory mechanism for how information might be integrated over multiple temporal scales. Little is known about how timescales develop in human neural circuits or other model systems, limiting insight into how the functional dynamics necessary for cognition emerge. In our work, we show that neuronal timescales develop in a non-linear fashion in both human cortical organoids and dissociated rat hippocampus cultures. We use spectral parameterization of spiking activity to extract an estimate of neuronal timescale that is unbiased by co-evolving oscillations. Cortical organoid timescales begin to increase around month 6 post-differentiation. We complement these findings with an analysis of timescales in rodent hippocampal dissociated cultures over development and see that timescales decrease from in vitro days 13-23 before stabilizing. We speculate that cortical organoid development over the duration studied here reflects an earlier stage of a generalized developmental timeline in contrast to the rodent hippocampal cultures, potentially accounting for differences in timescale developmental trajectories. The fluctuation of timescales might be an important developmental feature that reflects the changing complexity and information capacity in developing neuronal circuits.

Internal Representations Are Prioritized by Frontoparietal Theta Connectivity and Suppressed by alpha Oscillation Dynamics: Evidence from Concurrent Transcranial Magnetic Stimulation EEG and Invasive EEG.

Control over internal representations requires the prioritization of relevant information and suppression of irrelevant information. The frontoparietal network exhibits prominent neural oscillations during these distinct cognitive processes. Yet, the causal role of this network-scale activity is unclear. Here, we targeted theta-frequency frontoparietal coherence and dynamic alpha oscillations in the posterior parietal cortex using online rhythmic transcranial magnetic stimulation (TMS) in women and men while they prioritized or suppressed internally maintained working memory (WM) representations. Using concurrent high-density EEG, we provided evidence that we acutely drove the targeted neural oscillation and TMS improved WM capacity only when the evoked activity corresponded with the desired cognitive process. To suppress an internal representation, we increased the amplitude of lateralized alpha oscillations in the posterior parietal cortex contralateral to the irrelevant visual field. For prioritization, we found that TMS to the prefrontal cortex increased theta-frequency connectivity in the prefrontoparietal network contralateral to the relevant visual field. To understand the spatial specificity of these effects, we administered the WM task to participants with implanted electrodes. We found that theta connectivity during prioritization was directed from the lateral prefrontal to the superior posterior parietal cortex. Together, these findings provide causal evidence in support of a model where a frontoparietal theta network prioritizes internally maintained representations and alpha oscillations in the posterior parietal cortex suppress irrelevant representations.

Progesterone modulates theta oscillations in the frontal-parietal network.

The neuroactive metabolites of the steroid hormones progesterone (P4) and testosterone (T) are GABAergic modulators that influence cognition, yet, the specific effect of P4 and T on brain network activity remains poorly understood. Here, we investigated if a fundamental oscillatory network activity pattern, often related to cognitive control, frontal midline theta (FMT) oscillations, are modulated by steroids hormones, P4 and T. We measured the concentration of P4 and T using salivary enzyme immunoassay and FMT oscillations using high-density electroencephalography (EEG) during eyes-open resting-state in 55 healthy women and men. Electrical brain activity was analyzed using Fourier analysis, aperiodic signal fitting, and beamformer source localization. Steroid hormone concentrations and biological sex were used as predictors for scalp and source-estimated amplitude of theta oscillations. Elevated concentrations of P4 predicted increased amplitude of FMT oscillations across both sexes, and no relationship was found with T. The positive correlation with P4 was specific to the frontal midline electrodes and survived correction for the background aperiodic signal of the brain. Using source localization, FMT oscillations were localized to the frontal-parietal network (FPN). Additionally, theta amplitude within the FPN, but not the default mode network, positively correlated with P4 concentration. Our results suggest that P4 concentration modulates brain activity via upregulation of theta oscillations in the FPN.

Active and Passive Rhythmic Music Therapy Interventions Differentially Modulate Sympathetic Autonomic Nervous System Activity.

Dysregulation of the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in psychiatric disorders. Music therapy (MT) has been shown to modulate heart-rate variability (HRV) and salivary stress markers, physiological markers of the ANS and HPA axes, respectively. Given the prominent role of arousal and stress physiology in many psychiatric disorders, MT has the potential to provide therapeutic benefits in psychiatry. Active MT requires patients to engage rhythmically with music; in contrast, passive MT requires patients to listen to music, eliminating the rhythmic movement seen in active MT. Yet, it remains unknown whether active or passive MT differentially modulates arousal and stress physiology. We contrasted the effects of active and passive MT experiences to examine the differential impact of rhythmic movement on the ANS and HPA axes in healthy participants. Individuals (N = 16) participated in a crossover study of 40 min of an active MT and a passive MT intervention. HRV recordings and saliva samples were collected both before and after each intervention. The high-frequency component (HF) and the ratio of low-frequency to high-frequency components (LF/HF) were calculated as cardiac markers of parasympathetic and sympathetic ANS activation, respectively. Saliva samples were analyzed for alpha-amylase and cortisol, markers of the sympathetic ANS and HPA axes, respectively. Active MT and passive MT interventions differentially modulated LF/HF, where active MT decreased LF/HF and passive MT increased LF/HF. These results indicate that MT affects the ANS and suggests that differences in engagement between active MT and passive MT lead to a differential modulation of the sympathetic ANS.

Intrinsic Rhythmicity Predicts Synchronization-Continuation Entrainment Performance.

Rhythmic entrainment-defined as a stable temporal relationship between external periodic signals and endogenous rhythmic processes-allows individuals to coordinate with environmental rhythms. However, the impact of inter-individual differences on entrainment processes as a function of the tempo of external periodic signals remain poorly understood. To better understand the effects of endogenous differences and varying tempos on rhythmic entrainment, 20 young healthy adults participated in a spontaneous motor tempo (SMT) task and synchronization-continuation tasks at three experimental tempos (50, 70, and 128 bpm; 1200, 857, and 469 ms inter onset interval (IOI)). We hypothesized that SMT task performance and tempo would influence externally paced synchronization-continuation task behavior. Indeed, intrinsic rhythmicity assessed through the SMT task predicted performance in the externally paced task, allowing us to characterize differences in entrainment behavior between participants with low and high endogenous rhythmicity. High rhythmicity individuals, defined by better SMT performance, deviated from externally paced pulses sooner than individuals with low rhythmicity, who were able to maintain externally paced pulses for longer. The magnitude of these behavioral differences depended on the experimental tempo of the synchronization-continuation task. Our results indicate that differences in intrinsic rhythmicity vary between individuals and relate to tempo-dependent entrainment performance.