Understanding Circuits

Speech production and control is disrupted in a number of neurological diseases that involve the basal ganglia. Notably, hypophonia and hypokinetic dysarthria (characterized by decreased motor gain) are prevalent in patients with Parkinson's disease (PD). Deep brain stimulation (DBS) of the subthalamic nucleus (STN) produces predictable improvements in other motor symptoms of PD but does not result in consistent improvement in speech and can negatively impact language function. These observations and other accumulating evidence indicate an important role for the basal ganglia in speech.

PROJECT SUMMARY Speaking is one of the most complex actions that we perform, yet nearly all of us learn do it effortlessly. The ability to communicate through speech is often described as the unique and defining trait of human behavior. Despite its importance, the basic neural mechanisms that govern our ability to speak fluently remain unresolved.

Project summary/abstract Reach-to-grasp and hand manipulation will be studied in tetraplegic humans with neural recordings from multielectrode arrays (MEAs) and intracortical microstimulation (ICMS) of somatosensory cortex. Recordings will be performed within the cortical grasp circuit with MEAs implanted in two grasp-related areas, the ventral premotor cortex (PMv) and the anterior intraparietal area (AIP) of the posterior parietal cortex (PPC). ICMS will be delivered to Brodmann's area 1 (BA1) of somatosensory cortex.

ABSTRACT – (Title: Dynamic Neural Mechanisms of Audiovisual Speech Perception) Natural speech perception is multisensory; when conversing with someone that we can see, our brains combine visual (V) information from face, postural and hand gestures with auditory (A) information from the voice. The underlying speech processing is extremely rapid, with incoming AV units (e.g., syllables) arriving every few hundred milliseconds that must be encoded and passed on before the next syllable arrives.

Most current approaches to understanding the neural basis of cognitive processes are severely limited in two respects. First, most commonly used methods do not have the temporal (e.g., fMRI) or spatial (e.g., MEG/ EEG) resolution to capture the relevant dynamics. Second, even methods with high spatio-temporal resolution (intracranial EEG - icEEG) typically approach target cognitive processes in a fragmentary, un- integrated way.

 DESCRIPTION (provided by applicant): We propose to combine whole brain 2-photon imaging of neural activity in behaving larval zebrafish with detailed anatomical and connectivity information extracted from the same animals. The final goal is to generate quantitative models of brain wide neural circuits that explain the dynamic processing of sensory information as well as the generation of motor output by these circuits. Anatomical data will be generated by two complementary technologies: 1) whole brain EM data sets will be prepared from the same fish that were used for calcium imaging.

 DESCRIPTION (provided by applicant): Perceptual decision-making involves multiple cognitive components and diverse brain regions. To perform a perceptual decision, an individual must process an incoming sensory percept, retain this information in short- term memory, and choose an appropriate motor action. Research using delayed-response tasks in nonhuman primates has revealed that sensory and choice information is distributed across a hierarchy of cortical areas, with task-relevant information flowing from sensory to association to motor regions.

 DESCRIPTION (provided by applicant): Two of the most fundamental questions of sensory neuroscience are: 1) how is stimulus information represented by the activity of neurons at different levels of information processing? And 2) what features of this activity are read by the higher brain areas to guide behavior? The first question has been the subject of a large body of work across different sensory modalities. To answer the second question, one needs to establish a causal link between neuronal activity and behavior.

 DESCRIPTION (provided by applicant): The goal of the project team is to develop a robust, multi-lab research framework, enabled by large scale imaging, which will lead to principled integrative models of ethologically-relevant behaviors that incorporate a detailed knowledge of individual cell classes. The specific neurobiological question that the team will address is how the brain integrates sensory information in order to guide locomotion in a particular direction.

 DESCRIPTION (provided by applicant): Working memory, the ability to temporarily hold multiple pieces of information for mental manipulation, is central to virtually all cognitive abiliies. Working memory has been closely associated with multiple kinds of neural activity dynamics, such as persistent neural activity, activity ramps, and activity sequences. The neural circuit mechanisms of these dynamics remain unclear.