High-density EEG of auditory steady-state responses during stimulation of basal forebrain parvalbumin neurons.
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ABSTRACT:
SUBMITTER: Hwang E
PROVIDER: S-EPMC7478973 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:High-density electroencephalographic (hdEEG) recordings are widely used in human studies to determine spatio-temporal patterns of cortical electrical activity. How these patterns of activity are modulated by subcortical arousal systems is poorly understood. Here, we couple selective optogenetic stimulation of a defined subcortical cell-type, basal forebrain (BF) parvalbumin (PV) neurons, with hdEEG recordings in mice (Opto-hdEEG). Stimulation of BF PV projection neurons preferentially generated time-locked gamma oscillations in frontal cortices. BF PV gamma-frequency stimulation potently modulated an auditory sensory paradigm used to probe cortical function in neuropsychiatric disorders, the auditory steady-state response (ASSR). Phase-locked excitation of BF PV neurons in advance of 40 Hz auditory stimuli enhanced the power, precision and reliability of cortical responses, and the relationship between responses in frontal and auditory cortices. Furthermore, synchronization within a frontal hub and long-range cortical interactions were enhanced. Thus, phasic discharge of BF PV neurons changes cortical processing in a manner reminiscent of global workspace models of attention and consciousness.
| S-EPMC6532347 | biostudies-literature
Project description:The ability to rapidly arouse from sleep is important for survival. However, increased arousals in patients with sleep apnea and other disorders prevent restful sleep and contribute to cognitive, metabolic, and physiologic dysfunction [1, 2]. Little is currently known about which neural systems mediate these brief arousals, hindering the development of treatments that restore normal sleep. The basal forebrain (BF) receives inputs from many nuclei of the ascending arousal system, including the brainstem parabrachial neurons, which promote arousal in response to elevated blood carbon dioxide levels, as seen in sleep apnea [3]. Optical inhibition of the terminals of parabrachial neurons in the BF impairs cortical arousals to hypercarbia [4], but which BF cell types mediate cortical arousals in response to hypercarbia or other sensory stimuli is unknown. Here, we tested the role of BF parvalbumin (PV) neurons in arousal using optogenetic techniques in mice. Optical stimulation of BF-PV neurons produced rapid transitions to wakefulness from non-rapid eye movement (NREM) sleep but did not affect REM-wakefulness transitions. Unlike previous studies of BF glutamatergic and cholinergic neurons, arousals induced by stimulation of BF-PV neurons were brief and only slightly increased total wake time, reminiscent of clinical findings in sleep apnea [5, 6]. Bilateral optical inhibition of BF-PV neurons increased the latency to arousal produced by exposure to hypercarbia or auditory stimuli. Thus, BF-PV neurons are an important component of the brain circuitry that generates brief arousals from sleep in response to stimuli, which may indicate physiological dysfunction or danger to the organism.
| S-EPMC7757019 | biostudies-literature
Project description:Neuronal activity can modify Alzheimer's disease pathology. Overexcitation of neurons can facilitate disease progression whereas the induction of cortical gamma oscillations can reduce amyloid load and improve cognitive functions in mouse models. Although previous studies have induced cortical gamma oscillations by either optogenetic activation of cortical parvalbumin-positive (PV+) neurons or sensory stimuli, it is still unclear whether other approaches to induce gamma oscillations can also be beneficial. Here we show that optogenetic activation of PV+ neurons in the basal forebrain (BF) increases amyloid burden, rather than reducing it. We applied 40 Hz optical stimulation in the BF by expressing channelrhodopsin-2 (ChR2) in PV+ neurons of 5xFAD mice. After 1-h induction of cortical gamma oscillations over three days, we observed the increase in the concentration of amyloid-β42 in the frontal cortical region, but not amyloid-β40. Amyloid plaques were accumulated more in the medial prefrontal cortex and the septal nuclei, both of which are targets of BF PV+ neurons. These results suggest that beneficial effects of cortical gamma oscillations on Alzheimer's disease pathology can depend on the induction mechanisms of cortical gamma oscillations.
| S-EPMC7508947 | biostudies-literature
Project description:Cortical gamma band oscillations (GBO, 30-80 Hz, typically ∼40 Hz) are involved in higher cognitive functions such as feature binding, attention, and working memory. GBO abnormalities are a feature of several neuropsychiatric disorders associated with dysfunction of cortical fast-spiking interneurons containing the calcium-binding protein parvalbumin (PV). GBO vary according to the state of arousal, are modulated by attention, and are correlated with conscious awareness. However, the subcortical cell types underlying the state-dependent control of GBO are not well understood. Here we tested the role of one cell type in the wakefulness-promoting basal forebrain (BF) region, cortically projecting GABAergic neurons containing PV, whose virally transduced fibers we found apposed cortical PV interneurons involved in generating GBO. Optogenetic stimulation of BF PV neurons in mice preferentially increased cortical GBO power by entraining a cortical oscillator with a resonant frequency of ∼40 Hz, as revealed by analysis of both rhythmic and nonrhythmic BF PV stimulation. Selective saporin lesions of BF cholinergic neurons did not alter the enhancement of cortical GBO power induced by BF PV stimulation. Importantly, bilateral optogenetic inhibition of BF PV neurons decreased the power of the 40-Hz auditory steady-state response, a read-out of the ability of the cortex to generate GBO used in clinical studies. Our results are surprising and novel in indicating that this presumptively inhibitory BF PV input controls cortical GBO, likely by synchronizing the activity of cortical PV interneurons. BF PV neurons may represent a previously unidentified therapeutic target to treat disorders involving abnormal GBO, such as schizophrenia.
| S-EPMC4371918 | biostudies-literature
Project description:Deviant auditory steady-state responses (aSSRs) in the gamma range (30-90?Hz) may be translational biomarkers for schizophrenia (SZ). This study tests whether aSSR deviations are (i) specific to SZ across the psychosis dimension, (ii) specific to particular frequency bands, and (iii) present in bipolar I disorder without psychosis (BDNP). METHODS:Beta (20-), low- (40-), and high-gamma (80-Hz) aSSRs were measured with EEG and compared across 113 SZ, 105 schizoaffective disorder (SAD), 99 bipolar disorder with psychosis (BDP), 68 BDNP, and 137 healthy comparison subjects (HC). Standard aSSR measures (single-trial power [STP] and inter-trial phase coherence [ITC]), as well as evoked responses to stimulus onsets/offsets and pre-stimulus power, were quantified. Multivariate canonical discriminant analysis was used to summarize variables that efficiently and maximally differentiated groups. RESULTS:(i) Psychosis groups showed reduced responses on ITC 20?Hz, STP/ITC 40?Hz, STP/ITC 80?Hz, indicating dimensional reductions in aSSR across the psychosis spectrum not specific to aSSR frequency. For the 40- and 80-Hz ITCs there was greater reduction in SZ compared to SAD, possibly indexing cortical disruptions linked to psychosis without mood symptoms. (ii) All probands had elevated pre-stimulus power, possibly compromising neural entrainment to the steady-state stimuli. (iii) Onset/Offset and 80?Hz ITC responses were most important for group discrimination and showed dimensional reduction across the schizo-bipolar spectrum. CONCLUSIONS:Deviant aSSRs were found across the schizo-bipolar spectrum at multiple frequencies with psychosis status and severity linked to greatest reductions at low and high gamma.
| S-EPMC6661193 | biostudies-literature
Project description:AimsThe basal forebrain (BF) plays an essential role in wakefulness and cognition. Two subtypes of BF gamma-aminobutyric acid (GABA) neurons, including somatostatin-expressing (GABASOM ) and parvalbumin-positive (GABAParv ) neurons, function differently in mediating the natural sleep-wake cycle. Since the loss of consciousness induced by general anesthesia and the natural sleep-wake cycle probably share similar mechanisms, it is important to clarify the accurate roles of these neurons in general anesthesia procedure.MethodsBased on two transgenic mouse lines expressing SOM-IRES-Cre and PV-IRES-Cre, we used a combination of genetic activation, inactivation, and chronic ablation approaches to further explore the behavioral and electroencephalography (EEG) roles of BFSOM and BFParv neurons in general anesthesia. After a single intravenous injection of propofol and the induction and recovery times of isoflurane anesthesia, the anesthesia time was compared. The changes in cortical EEG under different conditions were also compared.ResultsActivation of BF GABASOM neurons facilitates both the propofol and isoflurane anesthesia, manifesting as a longer anesthesia duration time with propofol anesthesia and a fast induction time and longer recovery time with isoflurane anesthesia. Moreover, BF GABASOM -activated mice displayed a greater suppression of cortical electrical activity during anesthesia, showing an increase in δ power bands or a simultaneous decrease in high-frequency power bands. However, only a limited and nuanced effect on propofol and isoflurane anesthesia was observed with the manipulated BF GABAParv neurons.ConclusionsOur results suggested that BF GABASOM neurons play a critical role in propofol and isoflurane general anesthesia, while BF GABAParv neurons appeared to have little effect.
| S-EPMC8193699 | biostudies-literature
Project description:Auditory evoked steady-state responses are increasingly being used as a marker of brain function and dysfunction in various neuropsychiatric disorders, but research investigating the test-retest reliability of this response is lacking. The purpose of this study was to assess the consistency of the auditory steady-state response (ASSR) across sessions. Furthermore, the current study aimed to investigate how the reliability of the ASSR is impacted by stimulus parameters and analysis method employed. The consistency of this response across two sessions spaced approximately 1 week apart was measured in nineteen healthy adults using electroencephalography (EEG). The ASSR was entrained by both 40 Hz amplitude-modulated white noise and click train stimuli. Correlations between sessions were assessed with two separate analytical techniques: a) channel-level analysis across the whole-head array and b) signal-space projection from auditory dipoles. Overall, the ASSR was significantly correlated between sessions 1 and 2 (p<0.05, multiple comparison corrected), suggesting adequate test-retest reliability of this response. The current study also suggests that measures of inter-trial phase coherence may be more reliable between sessions than measures of evoked power. Results were similar between the two analysis methods, but reliability varied depending on the presented stimulus, with click train stimuli producing more consistent responses than white noise stimuli.
| S-EPMC3899078 | biostudies-literature
Project description:The basal forebrain (BF) strongly regulates cortical activation, sleep homeostasis, and attention. Many BF neurons involved in these processes are GABAergic, including a subpopulation of projection neurons containing the calcium-binding protein, parvalbumin (PV). However, technical difficulties in identification have prevented a precise mapping of the distribution of GABAergic and GABA/PV+ neurons in the mouse or a determination of their intrinsic membrane properties. Here we used mice expressing fluorescent proteins in GABAergic (GAD67-GFP knock-in mice) or PV+ neurons (PV-Tomato mice) to study these neurons. Immunohistochemical staining for GABA in GAD67-GFP mice confirmed that GFP selectively labeled BF GABAergic neurons. GFP+ neurons and fibers were distributed throughout the BF, with the highest density in the magnocellular preoptic area (MCPO). Immunohistochemistry for PV indicated that the majority of PV+ neurons in the BF were large (>20 ?m) or medium-sized (15-20 ?m) GFP+ neurons. Most medium and large-sized BF GFP+ neurons, including those retrogradely labeled from the neocortex, were fast-firing and spontaneously active in vitro. They exhibited prominent hyperpolarization-activated inward currents and subthreshold "spikelets," suggestive of electrical coupling. PV+ neurons recorded in PV-Tomato mice had similar properties but had significantly narrower action potentials and a higher maximal firing frequency. Another population of smaller GFP+ neurons had properties similar to striatal projection neurons. The fast firing and electrical coupling of BF GABA/PV+ neurons, together with their projections to cortical interneurons and the thalamic reticular nucleus, suggest a strong and synchronous control of the neocortical fast rhythms typical of wakefulness and REM sleep.
| S-EPMC3627393 | biostudies-literature
Project description:The latency of the auditory steady-state response (ASSR) may provide valuable information regarding the integrity of the auditory system, as it could potentially reveal the presence of multiple intracerebral sources. To estimate multiple latencies from high-order ASSRs, we propose a novel two-stage procedure that consists of a nonparametric estimation method, called apparent latency from phase coherence (ALPC), followed by a heuristic sequential forward selection algorithm (SFS). Compared with existing methods, ALPC-SFS requires few prior assumptions, and is straightforward to implement for higher-order nonlinear responses to multi-cosine sound complexes with their initial phases set to zero. It systematically evaluates the nonlinear components of the ASSRs by estimating multiple latencies, automatically identifies involved ASSR components, and reports a latency consistency index. To verify the proposed method, we performed simulations for several scenarios: two nonlinear subsystems with different or overlapping outputs. We compared the results from our method with predictions from existing, parametric methods. We also recorded the EEG from ten normal-hearing adults by bilaterally presenting superimposed tones with four frequencies that evoke a unique set of ASSRs. From these ASSRs, two major latencies were found to be stable across subjects on repeated measurement days. The two latencies are dominated by low-frequency (LF) (near 40 Hz, at around 41-52 ms) and high-frequency (HF) (> 80 Hz, at around 21-27 ms) ASSR components. The frontal-central brain region showed longer latencies on LF components, but shorter latencies on HF components, when compared with temporal-lobe regions. In conclusion, the proposed nonparametric ALPC-SFS method, applied to zero-phase, multi-cosine sound complexes is more suitable for evaluating embedded nonlinear systems underlying ASSRs than existing methods. It may therefore be a promising objective measure for hearing performance and auditory cortex (dys)function.
| S-EPMC7835249 | biostudies-literature
Project description:The auditory steady-state response (ASSR) has been traditionally recorded with few electrodes and is often measured as the voltage difference between mastoid and vertex electrodes (vertical montage). As high-density EEG recording systems have gained popularity, multi-channel analysis methods have been developed to integrate the ASSR signal across channels. The phases of ASSR across electrodes can be affected by factors including the stimulus modulation rate and re-referencing strategy, which will in turn affect the estimated ASSR strength. To explore the relationship between the classical vertical-montage ASSR and whole-scalp ASSR, we applied these two techniques to the same data to estimate the strength of ASSRs evoked by tones with sinusoidal amplitude modulation rates of around 40, 100, and 200 Hz. The whole-scalp methods evaluated in our study, with either linked-mastoid or common-average reference, included ones that assume equal phase across all channels, as well as ones that allow for different phase relationships. The performance of simple averaging was compared to that of more complex methods involving principal component analysis. Overall, the root-mean-square of the phase locking values (PLVs) across all channels provided the most efficient method to detect ASSR across the range of modulation rates tested here. Graphical abstract Image 1 Highlights • The auditory steady-state response (ASSR) measures frequency-specific responses.• ASSR pre-processing and quantification techniques were compared using human data.• Choice of EEG reference affects measured strength and phase of ASSR.• Mastoid channels are not electrically neutral when measuring ASSR.• The all-channel RMS phase locking value is most efficient to detect ASSR.
| S-EPMC9647176 | biostudies-literature