Visual word recognition, at a minimum, involves the processing of word form and lexical information. Opinions diverge on the spatiotemporal distribution of and interaction between the two types of information. Feedforward theory argues that they are processed sequentially, whereas interactive theory advocates that lexical information is processed fast and modulates early word form processing. To distinguish between the two theories, we applied stereoelectroencephalography (SEEG) to 33 human adults with epilepsy (25 males and eight females) during visual lexical decisions. The stimuli included real words (RWs), pseudowords (PWs) with legal radical positions, nonwords (NWs) with illegal radical positions, and stroked-changed words (SWs) in Chinese. Word form and lexical processing were measured by the word form effect (PW versus NW) and lexical effect (RW versus PW), respectively. Gamma-band (60 ∼ 140 Hz) SEEG activity was treated as an electrophysiological measure. A word form effect was found in eight left...

Although the anterior temporal lobe (ATL) comprises several anatomic and functional subdivisions, it is often reduced to a homogeneous theoretical entity, such as a domain-general convergence zone, or “hub,” for semantic information. Methodological limitations are largely to blame for the imprecise mapping of function to structure in the ATL. There are two major obstacles to using fMRI to identify the precise functional organization of the ATL: the difficult choice of stimuli and tasks to activate, and dissociate, specific regions within the ATL; and poor signal quality because of magnetic field distortions near the sinuses. To circumvent these difficulties, we developed a data-driven parcellation routine using resting-state fMRI data (24 females, 64 males) acquired using a sequence that was optimized to enhance signal in the ATL. Focusing on patterns of functional connectivity between each ATL voxel and the rest of the brain, we found that the ATL comprises at least 34 distinct functional parcels that are...

Episodic memory requires information to be stored and recalled in sequential order, and these processes are disrupted in schizophrenia. Hippocampal phase precession and theta sequences are thought to provide a biological mechanism for sequential ordering of experience at timescales suitable for plasticity. These phenomena have not previously been examined in any models of schizophrenia risk. Here, we examine these phenomena in a maternal immune activation (MIA) rodent model. We show that while individual pyramidal cells in the CA1 region continue to precess normally in MIA animals, the starting phase of precession as an animal enters a new place field is considerably more variable in MIA animals than in controls. A critical consequence of this change is a disorganization of the ordered representation of experience via theta sequences. These results provide the first evidence of a biological-level mechanism that, if it occurs in schizophrenia, may explain aspects of disorganized sequential processing that c...

Up-states are the best-studied example of an emergent neural dynamic regime. Computational models based on a single class of inhibitory neurons indicate that Up-states reflect bistable dynamical systems in which positive feedback is stabilized by strong inhibition and predict a paradoxical effect in which increased drive to inhibitory neurons results in decreased inhibitory activity. To date, however, computational models have not incorporated empirically defined properties of PV and SST neurons. Here we first, experimentally characterized the frequency-current (F-I) curves of pyramidal, PV, and SST neurons from mice of either sex, and confirmed a sharp difference between the threshold and slopes of PV and SST neurons. The empirically defined F-I curves were incorporated into a three-population computational model that simulated the empirically derived firing rates of pyramidal, PV, and SST neurons. Simulations revealed that the intrinsic properties were sufficient to predict that PV neurons are primarily ...

For normal cochlear function, outer hair cells (OHCs) require a precise control of intracellular Ca2+ levels. In the absence of regulatory elements such as proteinaceous buffers or extrusion pumps, OHCs degenerate, leading to profound hearing impairment. Influx of Ca2+ occurs both at the stereocilia tips and the basolateral membrane. In this latter compartment, two different origins for Ca2+ influx have been poorly explored: voltage-gated Ca2+ channels (VGCC) at synapses with type II afferent neurons, and α9α10 cholinergic nicotinic receptors at synapses with medio-olivochlear complex (MOC) neurons. Using functional imaging in mouse OHCs, we dissected Ca2+ influx individually through each of these sources, either by applying step depolarizations to activate VGCC, or stimulating MOC axons. Ca2+ ions originated in MOC synapses, but not by VGCC activation, was confined by Ca2+-ATPases most likely present in nearby synaptic cisterns. Although Ca2+ currents in OHCs are small, VGCC Ca2+ signals were comparable i...

Mediator protein complex subunit 12 (Med12) is a core component of the basal transcriptional apparatus and plays a critical role in the development of many tissues. Mutations in Med12 are associated with X-linked intellectual disability syndromes and hearing loss; however, its role in nervous system function remains undefined. Here, we show that temporal conditional deletion of Med12 in astrocytes in the adult central nervous system results in region specific alterations in astrocyte morphology. Surprisingly, behavioral studies revealed rapid hearing loss after adult deletion of Med12 that was confirmed by a complete abrogation of auditory brainstem responses. Cellular analysis of the cochlea revealed degeneration of the stria vascularis, in conjunction with disorganization of basal cells adjacent to the spiral ligament and downregulation of key cell adhesion proteins. Physiological analysis revealed early changes in endocochlear potential, consistent with strial-specific defects. Together, our studies rev...

The striatum plays critical roles in visually-guided decision making and receives dense axonal projections from midbrain dopamine neurons. However, the roles of striatal dopamine in visual decision making are poorly understood. We trained male and female mice to perform a visual decision task with asymmetric reward payoff, and we recorded the activity of dopamine axons innervating striatum. Dopamine axons in the dorsomedial striatum (DMS) responded to contralateral visual stimuli and contralateral rewarded actions. Neural responses to contralateral stimuli could not be explained by orienting behavior such as eye movements. Moreover, these contralateral stimulus responses persisted in sessions where the animals were instructed to not move to obtain reward, further indicating that these signals are stimulus-related. Lastly, we show that DMS dopamine signals were qualitatively different from dopamine signals in the ventral striatum, which responded to both ipsi- and contralateral stimuli, conforming to canoni...

In everyday life, we have no trouble categorizing objects varying in position, size, and orientation. Previous fMRI research shows that higher-level object processing regions in the human lateral occipital cortex may link object responses from different affine states (i.e. size and viewpoint) through a general linear mapping function capable of predicting responses to novel objects. In this study, we extended this approach to examine the mapping for both Euclidean (e.g. position and size) and non-Euclidean (e.g. image statistics and spatial frequency) transformations across the human ventral visual processing hierarchy, including areas V1, V2, V3, V4, ventral occipitotemporal cortex (VOT), and lateral occipitotemporal cortex (LOT). The predicted pattern generated from a linear mapping function could capture a significant amount of the changes associated with the transformations throughout the ventral visual stream. The derived linear mapping functions were not category independent, as performance was bette...

The white matter (WM) architecture of the human brain changes in response to training, though fine-grained temporal characteristics of training-induced white matter plasticity remain unexplored. We investigated white matter microstructural changes using diffusion tensor imaging at 5 different time points in 26 sighted female adults during 8-months training of tactile Braille reading. Our results show that training-induced white matter plasticity occurs both within and beyond the trained sensory modality, as reflected by fractional anisotropy (FA) increases in somatosensory and visual cortex, respectively. The observed changes followed distinct time courses, with gradual linear FA increase along the training in the somatosensory cortex and sudden visual cortex cross-modal plasticity occuring after Braille input became linguistically meaningful. WM changes observed in these areas returned to baseline after cessation of learning in line with the supply-demand model of plasticity. These results also indicate t...