Task induced dynamics of human bed nucleus of stria terminalis from direct neuronal recordings

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Abstract Submission 

Saurabh Sonkusare¹, Yingying Zhang², Qiong Ding³, Yashu Feng⁴, Linbin Wang², Violeta Casero³, Shikun Zhan⁴, Dianyou Li⁴, Bomin Sun⁴, Valerie Voon³

¹Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom, ²Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, Chi, Shanghai, China, ³Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom, Cambridge, United Kingdom, ⁴Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, Shanghai, China

Saurabh Sonkusare  
Department of Psychiatry, University of Cambridge
Cambridge, United Kingdom

Yingying Zhang  
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, Chi
Shanghai, China

Qiong Ding  
Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom
Cambridge, United Kingdom

Yashu Feng  
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai, China

Linbin Wang  
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, Chi
Shanghai, China

Violeta Casero  
Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom
Cambridge, United Kingdom

Shikun Zhan  
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai, China

Dianyou Li  
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai, China

Bomin Sun  
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai, China

Valerie Voon  
Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom
Cambridge, United Kingdom

The bed nucleus of the stria terminalis (BNST), a part of 'extended amygdala' [1], is densely connected with limbic structures, hypothalamic and brainstem nuclei. It plays a critical role in emotional processing especially fear, anxiety [2] and prosocial behaviour [3] with its dysfunction implicated in many psychiatric illnesses including major depression [4]. Yet, its functional dynamics remain poorly characterised in humans.

We acquired neuronal recordings from BNST from a cohort of 23 patients (Figure 1A) with treatment resistant depression undergoing deep brain stimulation (DBS) in a clinical trial. We employed two tasks (Figure 1B): 1) empathy for pain (painful and non-painful pictures), 2) affect task (positive and negative pictures). We first characterised task induced spectral dynamics and used permutation testing to assess condition differences. Time-frequency clusters showing condition differences were then tested for their association with depression and anxiety scores.

Behavioural ratings showed differences in painful and non-painful pictures (p<.001, Figure 2A i). Broad frequency range induced activity was seen for the empathy for pain task with condition differences in the alpha and theta frequency range activity which was greater in the painful condition (p<.001, Figure 2A ii, iii). Crucially, alpha activity correlated with baseline anxiety (r=.51, p¬FDR<.05) and depression scores (r= .55, p¬FDR<.05) and remarkably also predicted reduction in anxiety symptoms at 3-month follow up (r= .53, p¬FDR<.05). Behavioural ratings showed differences in positive and negative valence pictures (p<.011, Figure 2B i). For the affect task, early theta range (0-250 ms) activity was significantly greater for negative pictures (p<.001, Figure 2B ii, iii) and which correlated with baseline anxiety (r = .50, p¬FDR<.05) and depression scores(r= .52, p¬FDR<.05).

In a unique and rare invasive neurosurgical dataset, we investigated direct neural recordings from human BNST in two task paradigms of empathy for pain and affect picture viewing. We characterised the spectral dynamics of task-evoked activity demonstrating condition differences in the theta-alpha frequency range. Specifically, late alpha and theta activity in the empathy for pain paradigm was increased in the painful condition whilst greater early onset theta activity differentiated the negative stimuli from positive stimuli. Finally, alpha activity for empathy for the pain paradigm and theta for the affect paradigm were correlated with anxiety and depression severity with the alpha activity for empathy predicting anxiety outcomes at 3-month follow-up. Our study thus adds important informative knowledge about the functional and clinical significance of BNST essential for translational research in DBS field. These spectral characteristics can be targeted as a potential biomarker for depression and anxiety severity and predictors of therapeutic outcome.

Deep Brain Stimulation ²

Psychiatric (eg. Depression, Anxiety, Schizophrenia)

Emotional Perception ¹

Imaging Methods Other

Neurophysiology of Imaging Signals

Affective Disorders

Anxiety

ELECTROPHYSIOLOGY

Emotions

Psychiatric Disorders

Other - local field potentials, DBS