Power signatures of habenular neuronal signals in patients with bipolar or unipolar depressive disorders correlate with their disease severity

Abstract

The habenula is an epithalamic structure implicated in negative reward mechanisms and plays a downstream modulatory role in regulation of dopaminergic and serotonergic functions. Human and animal studies show its hyperactivity in depression which is curtailed by the antidepressant response of ketamine. Deep brain stimulation of habenula (DBS) for major depression have also shown promising results. However, direct neuronal activity of habenula in human studies have rarely been reported. Here, in a cross-sectional design, we acquired both spontaneous resting state and emotional task-induced neuronal recordings from habenula from treatment resistant depressed patients undergoing DBS surgery. We first characterise the aperiodic component (1/f slope) of the power spectrum, interpreted to signify excitation-inhibition balance, in resting and task state. This aperiodicity for left habenula correlated between rest and task and which was significantly positively correlated with depression severity. Time-frequency responses to the emotional picture viewing task show condition differences in beta and gamma frequencies for left habenula and alpha for right habenula. Notably, alpha activity for right habenula was negatively correlated with depression severity. Overall, from direct habenular recordings, we thus show findings convergent with depression models of aberrant excitatory glutamatergic output of the habenula driving inhibition of monoaminergic systems.

Long‐Term Recording of Subthalamic Aperiodic Activities and Beta Bursts in Parkinson's Disease

“…Recent studies have used aperiodic spectrum parameters of the LFPs in other deep brain structures such as the subcallosal cingulate (SCC) and habenula regions to monitor the severity of depression and the effects of DBS in treating depression 37,55 . For example, the exponent of the aperiodic spectrum in the right SCC increased following 6 months of SCC‐DBS therapy in patients with treatment‐resistance depression.…”

“…Recent studies have used aperiodic spectrum parameters of the LFPs in other deep brain structures such as the subcallosal cingulate (SCC) and habenula regions to monitor the severity of depression and the effects of DBS in treating depression. 37,55 For example, the exponent of the aperiodic spectrum in the right SCC increased following 6 months of SCC-DBS therapy in patients with treatment-resistance depression. Moreover, the exponent of the aperiodic spectrum in the left habenula, another target region for DBS therapy in patients with treatment-resistance depression, positively correlated with depression severity.…”

Editorial: The Habenula and Its Role in Neuropsychiatric Symptoms

“…social behavior (van Kerkhof et al, 2013 ; Ogawa and Parhar, 2021 ), circadian rhythms (Liu et al, 2021 ; Salaberry and Mendoza, 2022 ), reward processing (Lalive et al, 2022 ; Mondoloni et al, 2022 ), decision-making (Stopper et al, 2014 ; Baker et al, 2015 , 2017 ; Nuno-Perez et al, 2021 ), cognitive flexibility (Vadovičová, 2014 ; Baker et al, 2015 , 2017 ), and is implicated in the neurobiology of a number of psychiatric disorders and neuropsychiatric symptoms (Hu et al, 2020 ). Recent findings confirmed the importance of the Hb in schizophrenia (Schafer et al, 2018 ; Li et al, 2019 ; Germann et al, 2020 ; Wang et al, 2020 ), bipolar disorder (Schafer et al, 2018 ; Zhang et al, 2019 ; Germann et al, 2020 ; Sonkusare et al, 2022 ), autism (Germann et al, 2021 ; Murru et al, 2021 ), depression (Yang et al, 2018 ; Barreiros et al, 2022 ; Zhang et al, 2022 ; Young et al ), and eating disorders (Maldonado et al, 2018 ; Wills et al, 2020 ; Carlson et al, 2022 ), and implicated the Hb in neuropsychiatric symptoms such as sleep disturbances (Aizawa et al, 2013 ; Ge et al, 2021 ), and agitation/aggressive behavior (Flanigan et al, 2017 , 2020 ; Gan et al, 2019 ).…”

Structural and functional correlates of the response to deep brain stimulation at ventral capsule/ventral striatum region for treatment-resistant depression

“…Although adjusting DBS settings may lead to better clinical outcomes for TRD, where or how to optimise stimulation in VC/VS-DBS remains poorly understood 11. Recent electrophysiological studies12–15 and imaging analysis10 16 17 have provided valuable insights into the electrophysiological biomarkers and white matter pathways associated with clinical effectiveness. Thus far, the published VC/VS-DBS human data for TRD focused on clinical efficacy, whereas the neural pathways correlated with the effectiveness remain elusive.…”