Research paperThe basal ganglia: A central hub for the psychomotor effects of electroconvulsive therapy
Introduction
Clinical Trial registration number: NCT02562846 https://clinicaltrials.gov/ct2/show/NCT02562846
Electroconvulsive therapy (ECT) is a very effective treatment for severe depression (Kho et al., 2003; UK ECT Review Group, 2003), generating a fast and positive effect not only on mood, but also on psychomotor functioning (Hickie et al., 1996; van Diermen et al., 2018), which is important because psychomotor disturbances, such as retardation and agitation, are key aspects of depression (Buyukdura et al., 2011) and their response to other antidepressant therapies is far more limited (Buyukdura et al., 2011). ECT therefore addresses an unmet therapeutic need in the field of depression, possibly by a specific and unique neurobiological mechanism that yet remains unexplained (Buyukdura et al., 2011).
A recent study by Bouckaert et al. (2016) was the first to shed some light on potential underlying pathways (Bouckaert et al., 2016). Investigating gray matter volume (GMV) changes following ECT in a group of patients with severe late-life depression together with changes in psychomotor functions, they observed that a GMV increase in the bilateral caudate nucleus, an important subcortical nucleus of the basal-ganglia complex, correlated significantly with an improvement of psychomotor functioning, as assessed by the CORE rating scale (Bouckaert et al., 2016). This finding corroborates the idea that in depression psychomotor symptoms are related to the dysfunction of the basal ganglia, a system facilitating the performance of voluntary movement through complex interactions with cortex, thalamus, and brainstem (Schrijvers et al., 2008; Sobin and Sackeim, 1997; Hickie et al., 1999; Martinot et al., 2001; Herrero et al., 2002). Functionally, the different structures of the basal ganglia generate direct and indirect motor loops that tune the activity levels of the ventrolateral and ventroanterior nuclei of the thalamus, a higher-level subcortical nucleus, which, in its turn, stimulates the motor cortex, allowing movement (Herrero et al., 2002). Moreover, the possibility that in depression alterations of the basal ganglia could be responsible for the observed psychomotor disorders, supposes a bottom-up effect, where the abnormal function of lower-level subcortical structures induces the dysfunctions of higher-level relay nuclei like the thalamus and, ultimately, the motor cortex. This idea was recently supported by Loo et al. (2008), who demonstrated that psychomotor retardation in depressed participants involves an impaired ability to drive or activate the motor cortex (Loo et al., 2008).
With these findings in mind, we propose that ECT might have an impact on psychomotor symptoms in depression by a neuroplastic effect on the basal ganglia. In an attempt to confirm this assumption, we conducted a longitudinal, structural neuroimaging study in a cohort of adult patients diagnosed with depression and explored the correlation between GMV changes and psychomotor functioning before and after patient-tailored ECT. We used the subcortical segmentation technique as implemented in Freesurfer to specifically investigate the effects of ECT on the basal ganglia. More precisely, we scrutinized those subcortical structures that are mainly included in the motor loops (caudate, putamen, and pallidum), as well as the nucleus accumbens, which is part of the limbic pathway of the basal ganglia and thought to be the functional interface between the limbic and motor systems (Salgado and Kaplitt, 2015), controlling the biological drives and motivation for action (Mogenson et al., 1980). All these structures are known to be altered in depression and implicated in past research investigating the neurobiology of psychomotor symptoms in depression (Buyukdura et al., 2011).
Section snippets
Participants
Participants were recruited from among patients being seen at the University Psychiatric Center in Duffel, Belgium. All were examined by a psychiatrist specialized in ECT and eligible participants were asked for their written informed consent before they were included in the study protocol. In case of incapacity, a close relative was asked to give informed consent. Participants had to satisfy the following inclusion criteria: age over 40 years (to thus limit age-dependent volumetric differences
Results
Table 1 summarizes patient demographic details, clinical characteristics and ECT treatment information. Table 2 summarizes the individual ECT parameters.
Discussion
To our knowledge, ours is the second study, after Bouckaert et al. (Bouckaert et al., 2016), to investigate the neurobiology of the psychomotor effects of ECT in depression by exploring the relationship between longitudinal brain-volume changes in specific subcortical nuclei and psychomotor symptoms. Considering global subcortical volumes, we observed significant post-ECT gray-matter volume (GMV) increases of the accumbens region, the putamen, and the pallidum. Furthermore, the volume increase
Conclusion
Our findings demonstrate that ECT is associated with a significant increase in gray matter volume of the accumbens nucleus, pallidum and putamen. Moreover, the positive correlation between increased accumbens volume and retardation on the one hand, and the negative correlation between increased pallidum volume and agitation on the other hand, suggest that the basal ganglia are indeed important structures in the psychomotor effect of ECT. Therefore, future research should not only investigate
Disclosures
None of the authors report any biomedical or financial interests, nor any conflicts of interest.
CRediT authorship contribution statement
Jan-Baptist Belge: Formal analysis, Writing - original draft. Linda Van Diermen: Data curation, Writing - review & editing. Didier Schrijvers: Writing - review & editing. Bernard Sabbe: Writing - review & editing. Eric Constant: Writing - review & editing. Philippe de Timary: . Sven De Keyzer: Data curation. Paul Parizel: Data curation. Kristof Vansteelandt: Formal analysis. Pascal Sienaert: Writing - review & editing. Philip van Eijndhoven: Software, Writing - review & editing.
Acknowledgments
This publication was supported by Grant Number T000218N, from the FWO.
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