Semantic processing is an amodal process with modality-specific information integrated in supramodal “convergence zones” or “semantic hub” with executive mechanisms that tailor semantic representation in a task-appropriate way. One unsolved question is how frontal control region dynamically interacts with temporal representation region in semantic integration. The present study addressed this issue by using inhibitory double-pulse transcranial magnetic stimulation over the left inferior frontal gyrus (IFG) or left posterior middle temporal gyrus (pMTG) in one of eight 40 ms time windows (TWs) (3 TWs before and 5 TWs after the identification point of speech), when human participants (12 females, 14 males) were presented with semantically congruent or incongruent gesture-speech pairs but merely identified the gender of speech. We found a TW-selective disruption of gesture-speech integration, indexed by the semantic congruency effect (i.e., a cost of reaction time because of semantic conflict), when stimulati...

There is a growing body of research demonstrating that the cerebellum is involved in language understanding. Early theories assumed that the cerebellum is involved in low-level language processing. However, those theories are at odds with recent work demonstrating cerebellar activation during cognitive tasks. Using natural language stimuli and an encoding model framework, we performed an fMRI experiment on 3 men and 2 women, where subjects passively listened to 5 h of natural language stimuli, which allowed us to analyze language processing in the cerebellum with higher precision than previous work. We used these data to fit voxelwise encoding models with five different feature spaces that span the hierarchy of language processing from acoustic input to high-level conceptual processing. Examining the prediction performance of these models on separate BOLD data shows that cerebellar responses to language are almost entirely explained by high-level conceptual language features rather than low-level acoustic ...

Kelly C. Harris, Jayne B. Ahlstrom, James W. Dias, Lilyana B. Kerouac, Carolyn M. McClaskey, et al. (see pages [10293–10304][1]) Difficulty understanding conversation is a common complaint in older people. Sometimes hearing loss stems from loss of cochlear hair cells, as indicated by elevated

Aging is often associated with cognitive decline and recurrent cellular and molecular impairments. While life-long caloric restriction (CR) may delay age-related cognitive deterioration as well as the onset of neurological disease, recent studies suggest that late-onset, short-term intermittent fasting (IF), may show comparable beneficial effects as those of life-long CR to improve brain health. We used a new optogenetic aging model to study the effects of late-onset (>18 months), short-term (4-6 weeks) IF on age-related changes in GABAergic synaptic transmission, intracellular calcium (Ca2+) buffering and cognitive status. We utilized male mice from a bacterial artificial chromosome (BAC) transgenic mouse line with stable expression of the channelrhodopsin-2 (ChR2) variant H134R [VGAT-ChR2(H134R)-EYFP] in a reduced synaptic preparation that allows for specific optogenetic light stimulation on GABAergic synaptic terminals across aging. We performed quantal analysis using the method of failures in this mode...

The primary somatosensory cortex (S1) plays a critical role in processing multiple somatosensations, but the mechanism underlying the representation of different submodalities of somatosensation in S1 remains unclear. Using in vivo two-photon calcium imaging that simultaneously monitors hundreds of layer 2/3 pyramidal S1 neurons of awake male mice, we examined neuronal responses triggered by mechanical, thermal, or pruritic stimuli. We found that mechanical, thermal, and pruritic stimuli activated largely overlapping neuronal populations in the same somatotopic S1 subregion. Population decoding analysis revealed that the local neuronal population in S1 encoded sufficient information to distinguish different somatosensory submodalities. Although multimodal S1 neurons responding to multiple types of stimuli exhibited no spatial clustering, S1 neurons preferring mechanical and thermal stimuli tended to show local clustering. These findings demonstrated the coding scheme of different submodalities of somatosen...

When listening to speech, our brain responses time lock to acoustic events in the stimulus. Recent studies have also reported that cortical responses track linguistic representations of speech. However, tracking of these representations is often described without controlling for acoustic properties. Therefore, the response to these linguistic representations might reflect unaccounted acoustic processing rather than language processing. Here, we evaluated the potential of several recently proposed linguistic representations as neural markers of speech comprehension. To do so, we investigated EEG responses to audiobook speech of 29 participants (22 females). We examined whether these representations contribute unique information over and beyond acoustic neural tracking and each other. Indeed, not all of these linguistic representations were significantly tracked after controlling for acoustic properties. However, phoneme surprisal, cohort entropy, word surprisal, and word frequency were all significantly tra...

Neurotoxic HIV-1 viral proteins contribute to the development of HIV-associated neurocognitive disorder (HAND), the prevalence of which remains high (30–50%) with no effective treatment available. Estrogen is a known neuroprotective agent; however, the diverse mechanisms of estrogen action on the different types of estrogen receptors is not completely understood. In this study, we determined the extent to which and mechanisms by which 17α-estradiol (17αE2), a natural less-feminizing estrogen, offers neuroprotection against HIV-1 gp120-induced neuronal injury. Endolysosomes are important for neuronal function, and endolysosomal dysfunction contributes to HAND and other neurodegenerative disorders. In hippocampal neurons, estrogen receptor α (ERα) is localized to endolysosomes and 17αE2 acidifies endolysosomes. ERα knockdown or overexpressing an ERα mutant that is deficient in endolysosome localization prevents 17αE2-induced endolysosome acidification. Furthermore, 17αE2-induced increases in dendritic spine ...

The cerebral cortex, basal ganglia and motor thalamus form circuits important for purposeful movement. In Parkinsonism, basal ganglia neurons often exhibit dysrhythmic activity during, and with respect to, the slow (∼1 Hz) and beta-band (15-30 Hz) oscillations that emerge in cortex in a brain state-dependent manner. There remains, however, a pressing need to elucidate the extent to which motor thalamus activity becomes similarly dysrhythmic after dopamine depletion relevant to Parkinsonism. To address this, we recorded single-neuron and ensemble outputs in the basal ganglia-recipient zone (BZ) and cerebellar-recipient zone (CZ) of motor thalamus in anesthetized male dopamine-intact rats and 6-OHDA-lesioned rats during two brain states, respectively defined by cortical slow-wave activity and activation. Two forms of thalamic input zone-selective dysrhythmia manifested after dopamine depletion: (1) BZ neurons, but not CZ neurons, exhibited abnormal phase-shifted firing with respect to cortical slow oscillati...

Space-specific neurons in the owl's midbrain form a neural map of auditory space, which supports sound-orienting behavior. Previous work proposed that a population vector (PV) readout of this map, implementing statistical inference, predicts the owl's sound localization behavior. This model also predicts the frontal localization bias normally observed and how sound-localizing behavior changes when the signal-to-noise ratio varies, based on the spread of activity across the map. However, the actual distribution of population activity and whether this pattern is consistent with premises of the PV readout model on a trial-by-trial basis remains unknown. To answer these questions, we investigated whether the population response profile across the midbrain map in the optic tectum of the barn owl matches these predictions using in vivo multielectrode array recordings. We found that response profiles of recorded subpopulations are sufficient for estimating the stimulus interaural time difference using responses f...

Invited reviewers are asked to identify colleagues who assisted with review. JNeurosci would like to acknowledge the hard work of these collaborating reviewers and thank them for their service to the journal. Andrin Abegg Julia Abitbol Tobias Ackels Elie Adam Kadidia Adula Blanca Aldana Mor