PROJECT SUMMARY
Actions are not mediated solely by cortical processes but rely on communication within basal ganglia-
thalamocortical loops. Speech is one example, although how the basal ganglia participate in this uniquely
human behavior is not clear, due to a lack of empirical data. For instance, the leading computational model of
speech production ignores the hyperdirect cortical pathway to the subthalamic nucleus (STN), a basal ganglia
node that has been implicated in multiple cognitive processes relevant to speech production (e.g. action
selection and suppression, behavioral switching, gain modulation, motor learning). Recognizing that deep
brain stimulation (DBS) surgery offers the only opportunity to directly measure neural activity in the human
basal ganglia, we initiated studies to understand how motor and linguistic speech information is encoded
within the STN-sensorimotor cortical network. We established a novel experimental paradigm, where
electrocorticography (ECoG) is recorded simultaneously with STN single unit activity and local field potentials
(LFP), during DBS surgery in which patients are awake and speaking. We discovered that STN neuron activity is
dynamic during speech production, exhibiting behaviorally-selective inhibition and excitation of separate
populations of neurons. At the population level, we found that STN activity tracks with specific articulatory
motor features and with gain adjustment in articulatory movements. In addition, our data suggest a role for
the STN in speech planning, in that STN activity appears to be modulated prior to speech onset. These findings
led us to expand ECoG coverage to additionally record from areas involved in speech perception (superior
temporal gyrus) and planning (inferior frontal gyrus). Given the evidence in nonhuman primates for an
auditory basal ganglia-thalamocortical loop and the known hyperdirect projections from broad areas of frontal
cortex to the STN, we propose that hyperdirect pathways from both speech perception and speech planning
areas of cortex project to the STN and contribute to speech control. Supporting this idea, we have recorded
evoked potentials after STN stimulation that are consistent with antidromic activation not only in
sensorimotor cortex, but also from the inferior frontal gyrus (IFG) and superior temporal gyrus (STG). Our
principal hypothesis is that interactions between the STN and functionally distinct cortical regions contribute
to multiple aspects of speech, at the levels of perception, planning and modulation. Aim 1 uses stimulation
and functional connectivity measures to map the cortical-STN speech network. Aim 2, in parallel, probes
proposed basal ganglia functions relevant to speech, by simultaneously recording neural activity and speech
acoustics during an auditory repetition tasks that employs the Lombard Effect to selectively perturb speech
production. The resulting data will inform modifications to current models of speech production, which
subsequently will be tested with cue and response-locked intraoperative stimulation in Aim 3.