Biology subjects

Greenlee, J. D.

Publications and source records attributed to Greenlee, J. D..

6 recordsLinked to original sources

bioRxiv2025

Distinct Temporal Patterns of Human Neural Firing in the Subthalamic Nucleus During Speech and Orofacial Movement

Clinical studies, along with electrophysiological findings, provide evidence that the subthalamic nucleus (STN) contributes to speech production. These studies have reported that the STN encodes diverse aspects of speech, comprising speech motor planning and execution, timing, and linguistic features such as phonetic content. However, none of these studies have included an orofacial non-speech motor task to evaluate speech-specificity of STN activity. Here, we examined the modulation of STN neurons while participants engaged in two speech tasks (sentence repetition and syllable repetition) as well as two non-speech orofacial movement tasks (jaw movement and tongue protrusion) in awake patients with Parkinsons disease undergoing deep brain stimulation implantation surgery. A total of 51 single- and multi-unit neural clusters were captured. A Poisson generalized linear model (GLM) was implemented to understand the temporal dynamics of STN activity. A larger proportion of clusters was modulated during speech (22%) than during orofacial movement (12%) and a substantial subset of STN neural clusters responded to overlapping speech and orofacial tasks (27%). The findings suggest that STN can encode both motor and linguistic aspects of speech production. Graphical abstractThe subthalamic nucleus (STN) shows neural modulation during speech production, a process which requires motor planning, execution, and phonological functions. By comparing STN spiking activity during speech tasks (sentence and syllable repetition) and non-speech orofacial tasks (jaw movement and tongue protrusion), we identified task-specific modulation patterns in STN neurons. The STN contains distinct neural populations engaged during speech and orofacial movements. Among all recorded clusters, 22% responded exclusively to speech, 12% exclusively to orofacial movements, 27% to both, and 39% were non-responsive. We demonstrated that STN activity at single- and multi-unit levels is specific to speech production and is influenced by task-specific motor and linguistic demands, highlighting a role for STN in integrating motor control and speech production. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/693637v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@1ec3c60org.highwire.dtl.DTLVardef@6fe46forg.highwire.dtl.DTLVardef@1fe733corg.highwire.dtl.DTLVardef@3f736b_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

Identifying critical language planning regions with direct electrical brain stimulation

Many brain areas exhibit activity correlated with language planning1-9, but the impact of these dynamics on spoken interaction remains unclear. Here we use direct electrical stimulation to transiently perturb cortical function in neurosurgical patient-volunteers performing a question-answer task10. Stimulating structures involved in speech motor function evoked diverse articulatory deficits, while perturbations of caudal inferior and middle frontal gyri - which exhibit preparatory activity during conversational turn-taking - led to response errors. Perturbation of the same planning-related frontal regions slowed inter-speaker timing, while faster responses could result from stimulation of sites located in other areas. Taken together, these findings further indicate that caudal inferior and middle frontal gyri constitute a critical planning network essential for interactive language use1.

neuroscience↗

bioRxiv2023

Exercise modulates human hippocampal-cortical ripple dynamics

Physical exercise acutely improves hippocampus-dependent memory. Whereas animal studies have offered cellular- and synaptic-level accounts of these effects, human neuroimaging studies show that exercise improves hippocampal-cortical connectivity at the macroscale level. However, the neurophysiological basis of exercise-induced effects on hippocampal-cortical circuits remains unknown. Experimental evidence supports that hippocampal sharp wave-ripples (SWR) play a critical role in learning and memory. Coupling between SWRs in the hippocampus and neocortex may reflect modulations in inter-regional connectivity required by mnemonic processes. Here, we examine the hypothesis that exercise modulates hippocampal-cortical ripple dynamics in the human brain. We performed intracranial recordings in epilepsy patients undergoing pre-surgical evaluation, during awake resting state, before and after an exercise session. Exercise increased ripple rate in the hippocampus. Exercise also enhanced the coupling and phase-synchrony between cortical ripples in the limbic and the default mode (DM) cortical networks and hippocampal SWRs. Further, higher heart rate during exercise, reflecting exercise intensity, was related to a subsequent increase in resting state ripples across specific cortical networks including the DMN. These results offer the first direct evidence that a single exercise session elicits changes in ripple events, a well-established neurophysiological marker of mnemonic processing. The characterization and anatomical distribution of the described modulation points to hippocampal ripples as a potential mechanism by which exercise elicits its reported short-term effects in cognition.

neuroscience↗

bioRxiv2022

Immediate neural network impact after the loss of a semantic hub

The human brain extracts meaning from the world using an extensive neural system for semantic knowledge. Whether such broadly distributed systems1-3 crucially depend on or can compensate for the loss of one of their highly interconnected hubs4-6 is controversial4. The strongest level of causal evidence for the role of a brain hub is to evaluate its acute network-level impact following disconnection and any rapid functional compensation that ensues. We report rare neurophysiological data from two patients who underwent awake intracranial recordings during a speech prediction task immediately before and after neurosurgical treatment that required disconnection of the left anterior temporal lobe (ATL), a crucial hub for semantic knowledge4-6. Informed by a predictive coding framework, we tested three sets of hypotheses including diaschisis causing disruption in interconnected sites7 and incomplete or complete compensation by other language-critical and speech processing sites8-10. Immediately after ATL disconnection, we observed highly specific neurophysiological alterations in the recorded fronto-temporal network, including abnormally magnified high gamma responses to the speech sounds in auditory cortex. We also observed evidence for rapid compensation, seen as focal increases in effective connectivity involving language-critical sites in the inferior frontal gyrus and speech processing sites in auditory cortex. However, compensation was incomplete, in part because after ATL disconnection speech prediction signals were depleted in auditory cortex. This study provides direct causal evidence for a semantic hub in the human brain and shows striking neural impact and a rapid attempt at compensation in a neural network after the loss of one of its hubs.

neuroscience↗

bioRxiv2021

Oxaliplatin Resistance in Colorectal Cancer Enhances TRAIL Sensitivity Via Death Receptor 4 Upregulation and Lipid Raft Localization

Colorectal cancer (CRC) remains a leading cause of cancer death, and its mortality is associated with metastasis and chemoresistance. We demonstrate that oxaliplatin-resistant CRC cells are sensitized to TRAIL-mediated apoptosis. Oxaliplatin-resistant cells exhibited transcriptional downregulation of caspase-10, but this had minimal effects on TRAIL sensitivity following CRISPR-Cas9 deletion of caspase-10 in parental cells. Sensitization effects in oxaliplatin-resistant cells were found to be a result of increased DR4, as well as significantly enhanced DR4 palmitoylation and translocation into lipid rafts. Raft perturbation via nystatin and resveratrol significantly altered DR4/raft colocalization and TRAIL sensitivity. Blood samples from metastatic CRC patients were treated with TRAIL liposomes, and a 57% reduction of viable CTCs was observed. Increased DR4/lipid raft colocalization in CTCs was found to correspond with increased oxaliplatin resistance and increased efficacy of TRAIL liposomes. To our knowledge, this is the first study to investigate the role of lipid rafts in primary CTCs. Impact StatementOxaliplatin-resistant colorectal cancer cells exhibit unregulated death receptor 4 expression with increased receptor palmitoylation and translocation into lipid rafts, increasing their sensitivity to apoptosis via TRAIL.

cancer biology↗

bioRxiv2020

Differential causal involvement of human auditory and frontal cortices in vocal motor control

Speech motor control requires integration of sensory and motor information. Bidirectional communication between frontal and auditory cortices is crucial for speech production, self-monitoring and motor control. We used cortical direct electrical stimulation (DES) to functionally dissect audio-motor interactions underlying speech production and motor control. Eleven neurosurgical patients performed a visually cued vocal task in which a short auditory feedback perturbation was introduced during vocalization. We evaluated the effect of DES on vocal initiation, voice fundamental frequency (F0) and feedback-dependent motor control. DES of frontal sites modulated vocal onset latencies. Stimulation of different inferior frontal gyrus sites elicited either shortening or prolongation of vocal latencies. DES distinctly modulated voice F0 at different vocalization stages. Frontal and temporal areas played an important role in setting voice F0 in the first 250 ms of an utterance, while Heschls gyrus was involved later when auditory input is available for self-monitoring. Vocal responses to pitch-shifted auditory feedback were mostly reduced by DES of non-core auditory cortices. Overall, we demonstrate that vocal planning and initiation are driven by frontal cortices, while feedback-dependent control relies predominantly on non-core auditory cortices. Our findings represent direct evidence of the role played by different auditory and frontal regions in vocal motor control.

neuroscience↗