Many older listeners have difficulty understanding speech in noise, when cues to speech-sound identity are less redundant. The amplitude envelope of speech fluctuates dramatically over time, and features such as the rate of amplitude change at onsets (attack) and offsets (decay), signal critical information about the identity of speech sounds. Aging is also thought to be accompanied by increases in cortical excitability, which may differentially alter sensitivity to envelope dynamics. Here, we recorded electroencephalography in younger and older human adults (of both sexes) to investigate how aging affects neural synchronization to 4 Hz amplitude-modulated noises with different envelope shapes (ramped: slow attack and sharp decay; damped: sharp attack and slow decay). We observed that subcortical responses did not differ between age groups, whereas older compared with younger adults exhibited larger cortical responses to sound onsets, consistent with an increase in auditory cortical excitability. Neural ac...

In humans, impaired response inhibition is characteristic of a wide range of psychiatric diseases and of normal aging. It is hypothesized that the right inferior frontal cortex (rIFC) plays a key role by inhibiting the motor cortex via the basal ganglia. The electroencephalography (EEG)-derived β-rhythm (15–29 Hz) is thought to reflect communication within this network, with increased right frontal β-power often observed before successful response inhibition. Recent literature suggests that averaging spectral power obscures the transient, burst-like nature of β-activity. There is evidence that the rate of β-bursts following a Stop signal is higher when a motor response is successfully inhibited. However, other characteristics of β-burst events, and their topographical properties, have not yet been examined. Here, we used a large human (male and female) EEG Stop Signal task (SST) dataset ( n = 218) to examine averaged normalized β-power, β-burst rate, and β-burst “volume” (which we defined as burst duration...

Some of us fortunate enough to have published a paper in The Journal of Neuroscience in its inaugural year (1981) have been asked to write a Progressions article addressing our views on the significance of the original work and how ideas about the topic of that work have evolved over the last 40 years. These questions cannot be effectively considered without placing them in the context of the incredible growth of the overall field of neuroscience over these last four decades. For openers, in 1981, the Nobel Prize was awarded to three neuroscience superstars: Roger Sperry, David Hubel, and Torsten Wiesel. Not a bad year to launch the Journal . With this as a backdrop, I divide this Progressions article into two parts. First, I discuss our original (1981) paper describing classical conditioning in Aplysia californica , and place our results in the context of the state of the field at the time. Second, I fast forward to the present and consider some of remarkable progress in the broad field of learning and me...

Developmental, cellular, and subcellular variations in the direction of neuronal Cl– currents elicited by GABAA receptor activation have been frequently reported. We found a corresponding variance in the GABAA receptor reversal potential (EGABA) for synapses originating from individual interneurons onto a single pyramidal cell. These findings suggest a similar heterogeneity in the cytoplasmic intracellular concentration of chloride ([Cl–]i) in individual dendrites. We determined [Cl–]i in the murine hippocampus and cerebral cortex of both sexes by (1) two-photon imaging of the Cl–-sensitive, ratiometric fluorescent protein SuperClomeleon; (2) Fluorescence Lifetime IMaging (FLIM) of the Cl–-sensitive fluorophore MEQ (6-methoxy- N -ethylquinolinium); and (3) electrophysiological measurements of EGABA by pressure application of GABA and RuBi-GABA uncaging. Fluorometric and electrophysiological estimates of local [Cl–]i were highly correlated. [Cl–]i microdomains persisted after pharmacological inhibition of c...

Quantitative estimations of spatiotemporal complexity of cortical activity patterns are used in the clinic as a measure of consciousness levels, but the cortical mechanisms involved are not fully understood. We used a version of the perturbational complexity index (PCI) adapted to multisite recordings from the ferret (either sex) cerebral cortex in vitro (sPCI) to investigate the role of GABAergic inhibition in cortical complexity. We studied two dynamical states: slow-wave activity (synchronous state) and desynchronized activity, that express low and high causal complexity respectively. Progressive blockade of GABAergic inhibition during both regimes revealed its impact on the emergent cortical activity and on sPCI. Gradual GABAA receptor blockade resulted in higher synchronization, being able to drive the network from a desynchronized to a synchronous state, with a progressive decrease of complexity (sPCI). Blocking GABAB receptors also resulted in a reduced sPCI, in particular when in a synchronous, slo...

Everyday decision-making commonly involves assigning values to complex objects with multiple value-relevant attributes. Drawing on object recognition theories, we hypothesized two routes to multiattribute evaluation: assessing the value of the whole object based on holistic attribute configuration or summing individual attribute values. In two samples of healthy human male and female participants undergoing eye tracking and functional magnetic resonance imaging (fMRI) while evaluating novel pseudo objects, we found evidence for both forms of evaluation. Fixations to and transitions between attributes differed systematically when the value of pseudo objects was associated with individual attributes or attribute configurations. Ventromedial prefrontal cortex (vmPFC) and perirhinal cortex were engaged when configural processing was required. These results converge with our recent findings that individuals with vmPFC lesions were impaired in decisions requiring configural evaluation but not when evaluating the...

Understanding speech in background noise is a difficult task. The tracking of speech rhythms such as the rate of syllables and words by cortical activity has emerged as a key neural mechanism for speech-in-noise comprehension. In particular, recent investigations have used transcranial alternating current stimulation (tACS) with the envelope of a speech signal to influence the cortical speech tracking, demonstrating that this type of stimulation modulates comprehension and therefore providing evidence of a functional role of the cortical tracking in speech processing. Cortical activity has been found to track the rhythms of a background speaker as well, but the functional significance of this neural response remains unclear. Here we use a speech-comprehension task with a target speaker in the presence of a distractor voice to show that tACS with the speech envelope of the target voice as well as tACS with the envelope of the distractor speaker both modulate the comprehension of the target speech. Because t...

Seeing a speaker's face benefits speech comprehension, especially in challenging listening conditions. This perceptual benefit is thought to stem from the neural integration of visual and auditory speech at multiple stages of processing, whereby movement of a speaker's face provides temporal cues to auditory cortex, and articulatory information from the speaker's mouth can aid recognizing specific linguistic units (e.g., phonemes, syllables). However, it remains unclear how the integration of these cues varies as a function of listening conditions. Here, we sought to provide insight on these questions by examining EEG responses in humans (males and females) to natural audiovisual (AV), audio, and visual speech in quiet and in noise. We represented our speech stimuli in terms of their spectrograms and their phonetic features and then quantified the strength of the encoding of those features in the EEG using canonical correlation analysis (CCA). The encoding of both spectrotemporal and phonetic features was ...

Mutations on γ-secretase subunits are associated with neurologic diseases. Whereas the role of γ-secretase in neurogenesis has been intensively studied, little is known about its role in astrogliogenesis. Recent evidence has demonstrated that astrocytes can be generated from oligodendrocyte precursor cells (OPCs). However, it is not well understood what mechanism may control OPCs to differentiate into astrocytes. To address the above questions, we generated two independent lines of oligodendrocyte lineage-specific presenilin enhancer 2 ( Pen-2 ) conditional KO mice. Both male and female mice were used. Here we demonstrate that conditional inactivation of Pen-2 mediated by Olig1-Cre or NG2-CreERT2 causes enhanced generation of astrocytes. Lineage-tracing experiments indicate that abnormally generated astrocytes are derived from Cre-expressing OPCs in the CNS in Pen-2 conditional KO mice. Mechanistic analysis reveals that deletion of Pen-2 inhibits the Notch signaling to upregulate signal transducer and acti...