Recovering from depression with repetitive transcranial magnetic stimulation (rTMS): a systematic review and meta-analysis of preclinical studies

Abstract

Repetitive transcranial magnetic stimulation (rTMS) has gained growing interest for the treatment of major depression (MDD) and treatment-resistant depression (TRD). Most knowledge on rTMS comes from human studies as preclinical application has been problematic. However, recent optimization of rTMS in animal models has laid the foundations for improved translational studies. Preclinical studies have the potential to help identify optimal stimulation protocols and shed light on new neurobiological-based rationales for rTMS use. To assess existing evidence regarding rTMS effects on depressive-like symptoms in rodent models, we conducted a comprehensive literature search in accordance with PRISMA guidelines (PROSPERO registration number: CRD42019157549). In addition, we conducted a meta-analysis to determine rTMS efficacy, performing subgroup analyses to examine the impact of different experimental models and neuromodulation parameters. Assessment of the depressive-like phenotype was quite homogeneous whilst rTMS parameters among the 23 included studies varied considerably. Most studies used a stress-induced model. Overall, results show a largely beneficial effect of active rTMS compared to sham stimulation, as reflected in the statistically significant recovery of both helplessness (SDM 1.34 [1.02;1.66]) and anhedonic (SDM 1.87 [1.02;2.72]) profiles. Improvement of the depressive-like phenotype was obtained in all included models and independently of rTMS frequency. Nonetheless, these results have limited predictive value for TRD patients as only antidepressant-sensitive models were used. Extending rTMS studies to other MDD models, corresponding to distinct endophenotypes, and to TRD models is therefore crucial to test rTMS efficacy and to develop cost-effective protocols, with the potential of yielding faster clinical responses in MDD and TRD.

A Role of BDNF in the Depression Pathogenesis and a Potential Target as Antidepressant: The Modulator of Stress Sensitivity “Shati/Nat8l-BDNF System” in the Dorsal Striatum

“…Changes in structures and function in the PFC caused by altered dysfunction of the neuronal circuit have been reported in human studies. The methods for the treatment of depression treatment include electrical stimulation, including transcranial direct-current stimulation (tDCS) [ 61 ] and electroconvulsive therapy (ECT) [ 62 ], or magnetic stimulation including magnetic seizure therapy (MST) [ 63 ] and repetitive transcranial magnetic stimulation (rTMS) [ 64 ] to transiently induce neuronal activity. Deep brain stimulation (DBS) also enables the invasive region-specific regulation of neuronal activity using implanted electrodes [ 65 ].…”

Neuromodulators generate multiple context-relevant behaviors in a recurrent neural network by shifting activity flows in hyperchannels

“…For comparison, we considered the effect of electrical modulation, which influences circuit dynamics by altering current inputs into target neurons. Experimentally and clinically, electrical modulation is increasingly used in the form of optogenetics [Deisseroth, 2015], deep-brain stimulation (DBS) [Krauss et al, 2021] (Figure 8A), and transcranial magnetic stimulation [Risio et al, 2020, Gouveia et al, 2019]; the latter two providing much needed alternatives when traditional pharmacologic treatments fail. We used our model to ask whether electrical modulation alters network activity in an analogous manner to chemical neuromodulation or operates through an independent mechanism.…”

“…To fully characterize how networks respond to electrical stimulation, further exploration with different target regions and varied wave forms is warranted. Such experimentation in clinical use has led to major advancements in efficacy of DBS [Krauss et al, 2021] and TMS [Risio et al, 2020]. Future work utilizing wave forms and target areas mimicking and extending from clinically-used parameters will help fully characterize the effects of electrical stimulation on neural networks.…”

Transcranial Magnetic Stimulation in Psychiatry: Is There a Need for Electric Field Standardization?

“…It is important to emphasize, however, that in vitro preparations are not comparable to the complex in vivo situation and do not allow for a straightforward translation to treating the diseased human brain. Nevertheless, careful standardization of stimulus parameters—specifically, electric field strength and direction—seems mandatory for a systematic assessment of factors that may affect the outcome of a given (standardized) therapeutic rTMS protocol in suitable animal models (De Risio et al, 2020 ) as well as human rTMS studies.…”