Deep brain stimulation of the central thalamus restores arousal and motivation in a zolpidem-responsive patient with akinetic mutism after severe brain injury.

After severe brain injury, zolpidem is known to cause spectacular, often short-lived, restorations of brain functions in a small subgroup of patients. Previously, we showed that these zolpidem-induced neurological recoveries can be paralleled by significant changes in functional connectivity throughout the brain. Deep brain stimulation (DBS) is a neurosurgical intervention known to modulate functional connectivity in a wide variety of neurological disorders. In this study, we used DBS to restore arousal and motivation in a zolpidem-responsive patient with severe brain injury and a concomitant disorder of diminished motivation, more than 10 years after surviving hypoxic ischemia. We found that DBS of the central thalamus, targeted at the centromedian-parafascicular complex, immediately restored arousal and was able to transition the patient from a state of deep sleep to full wakefulness. Moreover, DBS was associated with temporary restoration of communication and ability to walk and eat in an otherwise wheelchair-bound and mute patient. With the use of magnetoencephalography (MEG), we revealed that DBS was generally associated with a marked decrease in aberrantly high levels of functional connectivity throughout the brain, mimicking the effects of zolpidem. These results imply that 'pathological hyperconnectivity' after severe brain injury can be associated with reduced arousal and behavioral performance and that DBS is able to modulate connectivity towards a 'healthier baseline' with lower synchronization, and, can restore functional brain networks long after severe brain injury. The presence of hyperconnectivity after brain injury may be a possible future marker for a patient's responsiveness for restorative interventions, such as DBS, and suggests that lower degrees of overall brain synchronization may be conducive to cognition and behavioral responsiveness.

Audiovisual Modulation in Mouse Primary Visual Cortex Depends on Cross-Modal Stimulus Configuration and Congruency.

The sensory neocortex is a highly connected associative network that integrates information from multiple senses, even at the level of the primary sensory areas. Although a growing body of empirical evidence supports this view, the neural mechanisms of cross-modal integration in primary sensory areas, such as the primary visual cortex (V1), are still largely unknown. Using two-photon calcium imaging in awake mice, we show that the encoding of audiovisual stimuli in V1 neuronal populations is highly dependent on the features of the stimulus constituents. When the visual and auditory stimulus features were modulated at the same rate (i.e., temporally congruent), neurons responded with either an enhancement or suppression compared with unisensory visual stimuli, and their prevalence was balanced. Temporally incongruent tones or white-noise bursts included in audiovisual stimulus pairs resulted in predominant response suppression across the neuronal population. Visual contrast did not influence multisensory processing when the audiovisual stimulus pairs were congruent; however, when white-noise bursts were used, neurons generally showed response suppression when the visual stimulus contrast was high whereas this effect was absent when the visual contrast was low. Furthermore, a small fraction of V1 neurons, predominantly those located near the lateral border of V1, responded to sound alone. These results show that V1 is involved in the encoding of cross-modal interactions in a more versatile way than previously thought.SIGNIFICANCE STATEMENT The neural substrate of cross-modal integration is not limited to specialized cortical association areas but extends to primary sensory areas. Using two-photon imaging of large groups of neurons, we show that multisensory modulation of V1 populations is strongly determined by the individual and shared features of cross-modal stimulus constituents, such as contrast, frequency, congruency, and temporal structure. Congruent audiovisual stimulation resulted in a balanced pattern of response enhancement and suppression compared with unisensory visual stimuli, whereas incongruent or dissimilar stimuli at full contrast gave rise to a population dominated by response-suppressing neurons. Our results indicate that V1 dynamically integrates nonvisual sources of information while still attributing most of its resources to coding visual information.

Imagery and retrieval of auditory and visual information: neural correlates of successful and unsuccessful performance.

Remembering past events - or episodic retrieval - consists of several components. There is evidence that mental imagery plays an important role in retrieval and that the brain regions supporting imagery overlap with those supporting retrieval. An open issue is to what extent these regions support successful vs. unsuccessful imagery and retrieval processes. Previous studies that examined regional overlap between imagery and retrieval used uncontrolled memory conditions, such as autobiographical memory tasks, that cannot distinguish between successful and unsuccessful retrieval. A second issue is that fMRI studies that compared imagery and retrieval have used modality-aspecific cues that are likely to activate auditory and visual processing regions simultaneously. Thus, it is not clear to what extent identified brain regions support modality-specific or modality-independent imagery and retrieval processes. In the current fMRI study, we addressed this issue by comparing imagery to retrieval under controlled memory conditions in both auditory and visual modalities. We also obtained subjective measures of imagery quality allowing us to dissociate regions contributing to successful vs. unsuccessful imagery. Results indicated that auditory and visual regions contribute both to imagery and retrieval in a modality-specific fashion. In addition, we identified four sets of brain regions with distinct patterns of activity that contributed to imagery and retrieval in a modality-independent fashion. The first set of regions, including hippocampus, posterior cingulate cortex, medial prefrontal cortex and angular gyrus, showed a pattern common to imagery/retrieval and consistent with successful performance regardless of task. The second set of regions, including dorsal precuneus, anterior cingulate and dorsolateral prefrontal cortex, also showed a pattern common to imagery and retrieval, but consistent with unsuccessful performance during both tasks. Third, left ventrolateral prefrontal cortex showed an interaction between task and performance and was associated with successful imagery but unsuccessful retrieval. Finally, the fourth set of regions, including ventral precuneus, midcingulate cortex and supramarginal gyrus, showed the opposite interaction, supporting unsuccessful imagery, but successful retrieval performance. Results are discussed in relation to reconstructive, attentional, semantic memory, and working memory processes. This is the first study to separate the neural correlates of successful and unsuccessful performance for both imagery and retrieval and for both auditory and visual modalities.

Modality-specific and modality-independent components of the human imagery system.

Imagery research typically deals with the commonalities and differences between imagery and perception. As such, it is usually confined to one specific modality. Yet, it is likely that some of the underlying processes are shared between different sensory modalities while others are modality-specific. In this fMRI study, we used a balanced design that allowed for a direct comparison between imagery and perception in visual and auditory modalities, and also for a link between subjective imagery experience and brain activation. Results indicated a selective role for the "default mode network" as a modality-independent "core" imagery network. In addition, results identified areas in the visual and auditory association cortices that contributed to mental imagery in a modality-specific fashion. Interestingly during mental imagery, primary visual and auditory cortices showed modality-specific suppression of activity. This is the first fMRI study to characterize both modality-specific and modality-independent components of the human imagery system.