Effect of electroconvulsive seizures on cognitive flexibility

Abstract

Electroconvulsive seizures (ECS), an animal model of electroconvulsive therapy, strongly stimulate hippocampal neurogenesis, but it is not known how this relates to the therapeutic effect or to the unwanted cognitive side effects. Recent findings suggest that neurogenesis might be important for flexible learning in changing environments. We hypothesize that animals receiving ECS treatment, which induces hippocampal neurogenesis, will show enhanced cognitive flexibility compared with controls. We have utilized a touch screen-based cognitive test (location discrimination (LD) task) to assess how five consecutive ECS treatments affect cognitive flexibility (measured as reversal of cognitive strategy) as well as spatial pattern separation ability. ECS-treated animals performed more reversals in the LD task earlier than controls over the 9 experimental weeks irrespective of spatial separation of visual stimuli, indicating an enhanced cognitive flexibility but unaffected pattern separation ability after ECS. We observed no correlation between hippocampal neurogenesis and the number of performed reversals during the last experimental week. This is the first study to elucidate the effect of ECS on cognitive flexibility. Our results indicate that ECS improves cognitive flexibility without affecting spatial pattern separation ability. Whether cognitive flexibility is enhanced via neurogenesis or other ECS-modulated processes, remains unknown. © 2016 Wiley Periodicals, Inc.

Leveraging Neuroplasticity to Enhance Adaptive Learning: The Potential for Synergistic Somatic-Behavioral Treatment Combinations to Improve Clinical Outcomes in Depression

“…While the mechanism of action of ECT remains incompletely understood, its potent effects on neuroplasticity may underlie its antidepressant effects (10,84), though critical gaps in this literature remain. Electroconvulsive seizures (the analog of ECT in animal models) affect many neuroplastic processes, including gliogenesis, increased axospinous synapses in the CA1 pyramidal layer, increase in number of mushroom spines, axonal sprouting in the dentate gyrus, neurogenesis, as well as regulation of neurotrophic factors (85,86). Cognitive flexibility, operationalized as the ability to flexibly learn new and unlearn old associations as novel situations arise, has been shown to improve following electroconvulsive seizure in rodents (86).…”

“…Electroconvulsive seizures (the analog of ECT in animal models) affect many neuroplastic processes, including gliogenesis, increased axospinous synapses in the CA1 pyramidal layer, increase in number of mushroom spines, axonal sprouting in the dentate gyrus, neurogenesis, as well as regulation of neurotrophic factors (85,86). Cognitive flexibility, operationalized as the ability to flexibly learn new and unlearn old associations as novel situations arise, has been shown to improve following electroconvulsive seizure in rodents (86). Studies of ECT in humans have also shown effects on neuroplasticity markers, including changes in hippocampal and amygdala volumes (10,84,87), peripheral brainderived neurotrophic factor (88), and default mode network connectivity (89).…”

Spatial memory impairment in Morris water maze after electroconvulsive seizures

“…We observed no difference in tonic seizure duration over the treatment course, which is in line with other studies (29). Nonetheless, both a slight increase (28) and decrease (30, 31) in ECS seizure duration over administration days have been observed. Our interpretation is that several factors such that age, weight, stimulus parameters used, and rat strain might affect the seizure duration.…”

Die Bedeutung der Elektrokonvulsionstherapie (EKT) in der multimodalen Behandlung depressiver Störungen

“…Neben dem Krampfanfall und möglicherweise auch der Suppression des Krampfanfalles als essenzielle Wirkmechanismen werden weitere diskutiert. So gibt es eine Reihe von Studien, die verschiedenste neurophysiologische und neurofunktionelle kurz-und langfristige Veränderungen durch EKT festgestellt haben: ➣ kurz-und langfristiger Anstieg neurotropher Faktoren wie BDNF (Brain Derived Nerve Factor; Okamoto et al, 2008;Piccinni et al, 2009;Rocha et al, 2016) und NGF (Nerve Growth Factor; Bilgen et al, 2014) ➣ konsekutiv Neurogenese und Neuroplastizität im Hippocampus und anderen Hirnregionen (Bolwig & Madsen, 2007;Lamont et al, 2005;Madsen, 2000;Michael et al, 2003a;Olesen et al, 2017;Otabe et al, 2014;Schloesser et al, 2015;Smith et al, 2014;Svensson et al, 2016;Tendolkar et al, 2013) ➣ kurzfristig verstärkte Freisetzung von Neurotransmittern: Dopamin , Serotonin (Baldinger et al, 2014;Ishihara & Sasa, 1999), GABA (Sanacora et al, 2003), Noradrenalin (Kelly & Cooper, 1997) ➣ Beeinflussung der Rezeptorenfunktion im Gehirn: 5-HT3 , 5-HT1A , 5-HT2A ¯ (Ishihara & Sasa, 1999) ➣ Freisetzung verschiedenster Hormone wie Prolaktin und TSH (Abrams & Sukartz, 1985;Abrams, 1992;Aperia et al, 1985), Cortisol und ACTH (Fink & Nemeroff, 1989;Florkowski et al, 1996), Endorphine (Abrams, 1992), Oxytocin (Scott et al, 1989;Whalley et al, 1987 (Abbott et al, 2013) ➣ Normalisierung bei depressiven Patient*innen im Vergleich zu psychisch Gesunden verminderter Glutamat/ Glutamin (Glx)-Konzentrationen im linken anterioren Cingulum (ACC) (Pfleiderer et al, 2003)…”