Depression is one of the world's most common mental health conditions, affecting more than 300 million people and ranking among the leading causes of disability worldwide (World Health Organisation, 2017). For many years, depression was explained as the result of a "chemical imbalance" in the brain, however ‘this explanation captures only part of a much more complex picture. Depression is now understood as a multifactorial condition that arises through the interaction of biological, psychological, and environmental factors. These may include genetic susceptibility, changes in brain structure and function, stressful or traumatic life experiences, chronic physical illness, personality traits, and social circumstances such as isolation or financial hardship. The way these factors interact differs from person to person, meaning there is no single cause of depression or one-size-fits-all explanation for why it develops (World Health Organisation, 2025).
Advances in neuroscience have also transformed our understanding of how depression affects the brain. Rather than being caused by a shortage of a single neurotransmitter, depression is increasingly understood as a disorder involving changes in the way different brain regions communicate with one another. These disruptions can influence many aspects of daily life, including mood, motivation, concentration, memory, sleep, decision-making, and the ability to experience pleasure (Mulders et al., 2015; Drevets et al., 2008).
One of the most promising developments in this field is the understanding of neuroplasticity, the brain's ability to adapt, reorganise, and form new neural connections throughout life (Milbocker et al., 2024). This discovery has challenged the belief that the adult brain is relatively fixed, revealing instead that it remains capable of change in response to experience, learning, and treatment. As a result, researchers have been able to develop innovative therapies that harness the brain's natural capacity for change, including Transcranial Magnetic Stimulation (TMS), a non-invasive treatment that targets brain networks involved in regulating mood and modulates neuronal activity.
Neuroplasticity refers to the brain's ability to adapt, reorganise, and modify its structure and function throughout life. Rather than being a fixed organ, the brain is constantly changing in response to our experiences, thoughts, behaviours, and environment. This ability allows the brain to form new neural connections, strengthen existing ones, and weaken connections that are no longer needed, enabling us to learn, remember, adapt, and recover from change (Milbocker et al., 2024; Gazerani, P, 2025).
For much of the twentieth century, scientists believed that the brain became relatively fixed once adulthood was reached, with little capacity for significant change. Research over the past several decades has overturned this view. We now know that the adult brain remains remarkably adaptable throughout life, continuously reorganising its neural connections in response to learning, new experiences, practice, and recovery from injury (Pigott & McIernon, 2026).
Everyday activities demonstrate neuroplasticity in action. Learning a new language, mastering a musical instrument, developing a new skill, exercising regularly, or practising mindfulness all encourage the brain to strengthen and refine the neural pathways involved in those activities. Repeated use of these pathways makes communication between brain cells more efficient, while pathways that are rarely used may gradually weaken, while some unused synaptic connections are eliminated through a natural process known as synaptic pruning. In this way, the brain continually optimises itself based on how it is used (Sakai. J, 2020; Milbocker et al., 2024).
A useful way to understand neuroplasticity is to imagine a network of walking paths through a forest. The more frequently a path is used, the clearer, wider, and more efficient it becomes, as repeated travel reinforces and maintains it. In contrast, paths that are rarely used gradually become less distinct and harder to navigate as vegetation begins to grow over them. In a similar way, neural pathways in the brain that are repeatedly activated become stronger and more efficient, while those that are used less frequently may weaken over time or be reorganised as the brain adapts. Although this analogy simplifies the complexity of brain function, it captures the fundamental idea that the brain is shaped by experience and patterns of use.
The brain’s ongoing ability to reorganise itself underpins many of the brain's most important functions. Neuroplasticity allows us to acquire new knowledge, store memories, solve problems, adapt to changing environments, recover from brain injury, and regulate our emotions. It also plays a central role in mental health. Evidence suggests that depression is associated with reduced neuroplasticity in brain networks involved in mood, cognition, and reward processing. Understanding how these networks can be strengthened or reshaped has become one of the most promising areas of modern neuroscience and has led to the development of innovative treatments, including TMS, which aims to promote healthier and more balanced patterns of brain activity.
Depression is much more than simply feeling sad. While sadness is a normal human emotion that everyone experiences from time to time, depression is a medical condition that affects the brain in ways that can significantly change a person's thoughts, emotions, behaviour, and physical wellbeing. It influences the way different regions of the brain communicate with one another, altering how we process information, regulate emotions, make decisions, and respond to everyday experiences. These changes can make routine tasks feel overwhelming and can reduce a person's ability to experience pleasure, motivation, or hope. Understanding depression as a condition that involves changes in brain function helps explain why it is not something that people can simply "snap out of" through willpower alone (NHS, 2025).
Brain imaging studies suggest that depression disrupts communication between networks involved in emotion regulation, decision-making, attention, motivation, and reward processing. Rather than working together efficiently, some brain networks become underactive while others become overactive. This imbalance can make it more difficult to regulate emotions, think clearly, and experience positive feelings (NeuroLaunch, 2026). As a result, many people with depression experience persistent negative thoughts, difficulty concentrating, reduced motivation, a loss of interest or enjoyment in activities they once loved, and feelings of hopelessness or emotional numbness. These symptoms are not simply a matter of willpower; they reflect measurable changes in how the brain is functioning.
One of the brain regions most extensively studied in depression is the prefrontal cortex, located at the front of the brain. This area acts as one of the brain's "control centres," playing a crucial role in regulating emotions, making decisions, planning, focusing attention, solving problems, and controlling impulsive reactions. It also helps us evaluate situations rationally and regulate our responses to stressful or emotionally challenging events. Research suggests that in many people with depression, activity within parts of the prefrontal cortex is reduced. As a result, the brain may become less effective at regulating negative emotions and shifting attention away from distressing thoughts. At the same time, regions involved in processing emotions, such as the amygdala, often show increased activity, particularly in response to negative or threatening information. This imbalance means that emotional centres of the brain can exert a stronger influence while the brain's regulatory systems become less able to moderate those responses. Consequently, negative experiences may feel more intense, stressful situations may be harder to cope with, and patterns of rumination or persistent negative thinking can become more difficult to interrupt (Zhang et al., 2018).
Over time, these patterns of brain activity can become increasingly established, reinforcing cycles of negative thinking, low mood, and withdrawal. The promising news is that the brain is not fixed. Thanks to neuroplasticity, the brain's ability to reorganise and form new connections, these patterns can change. Understanding how depression affects the brain helps explain why recovery takes time, but also why treatments and healthy lifestyle changes can gradually help the brain build healthier, more resilient pathways.
Many effective treatments for depression are thought to work, at least in part, by supporting neuroplasticity. Rather than simply reducing symptoms in isolation, these approaches help the brain develop more adaptive patterns of communication across the networks involved in mood, thinking, and behaviour (Wang et al., 2023). Although neuroplasticity is essential for learning and recovery, it can also reinforce unhelpful patterns of brain activity, such as persistent negative thinking in depression. Many treatments therefore aim not simply to increase neuroplasticity, but to promote more adaptive patterns of neural change.
For example, Cognitive Behavioural Therapy (CBT) helps individuals identify and challenge unhelpful thought patterns while developing more adaptive cognitive and behavioural responses to difficult situations. Repeated practice of these strategies has been associated with changes in neural activity and connectivity in brain networks involved in emotional regulation and cognitive control (Goldapple et al., 2004). Similarly, regular physical activity has been shown to increase levels of brain-derived neurotrophic factor (BDNF), a protein that supports neuronal growth, survival, and synaptic plasticity, and is linked to improved brain function in systems involved in mood, learning, and memory (Szuhany et al., 2015). Other lifestyle factors also contribute to this process. Good-quality sleep supports the brain’s ability to repair, reorganise, and consolidate neural connections, while social connection, effective stress management, and appropriate medical treatments, including medication when indicated, all help create conditions in which the brain can function more effectively (Tononi and Cirelli., 2014; Pickersgill et al., 2022). These approaches may work together to support the brain’s natural capacity to adapt and recover (Rajkumar, 2024)
Importantly, this understanding has shifted how researchers conceptualise recovery. Depression is not seen solely as a fixed or irreversible condition, but rather as a state in which brain networks can change over time. As new neural connections form and existing pathways are strengthened, the brain can gradually become better at regulating emotions, processing experiences, and responding to stress. This shift in perspective has also influenced treatment development, leading to therapies that aim to directly target brain activity and promote healthier network functioning. One such treatment studied is TMS, a non-invasive technique that uses targeted magnetic pulses to stimulate brain regions involved in mood regulation (Lefaucheur, 2020). In the next section, we’ll explore how TMS works and why it has become an increasingly important option in the treatment of depression.
TMS is a non-invasive brain stimulation treatment that uses electromagnetic pulses, to induce small, targeted electrical currents in specific brain regions. These currents temporarily modulate the excitability of neurons in the stimulated area, most commonly the dorsolateral prefrontal cortex, a region strongly implicated in mood regulation, cognitive control, and decision-making. Depending on the stimulation protocol (such as the frequency or pattern of stimulation), TMS can increase or decrease cortical excitability (Chaudhary, 2025).
Unlike surgical interventions or invasive neuromodulation techniques, TMS does not require anaesthesia or incisions, and it is generally well tolerated, with individuals remaining awake, alert, and able to resume normal daily activities immediately after each session. Treatment is typically delivered in outpatient clinical settings over several weeks, involving daily weekday sessions using repetitive TMS (rTMS). Evidence suggests that repeated sessions produce cumulative changes in cortical excitability and brain network activity over time, rather than producing a single immediate effect after one treatment (Cleveland Clinic, 2026).
One leading hypothesis is that the therapeutic effects of TMS are linked to neuroplasticity, the brain's ability to change and reorganise itself by forming and modifying connections between nerve cells (Pascual-Leone et al., 2005; Lefaucheur et al., 2020). When the TMS pulses are delivered repeatedly over multiple treatment sessions, they may lead to longer-lasting changes in cortical excitability and brain network function. Rather than affecting only the stimulated brain region, TMS is thought to influence larger-scale neural networks involved in mood regulation, particularly those connecting regions responsible for cognitive and emotional processing. These networks often show altered functional connectivity in people with depression (Fox et al., 2012). By repeatedly stimulating targeted brain regions, TMS may help normalise patterns of functional connectivity within these networks over time (Fitzsimmons et al., 2024). In this way, TMS is thought to produce its effects, at least in part, by promoting neuroplastic changes within brain networks involved in mood regulation. Although researchers are still investigating the precise biological mechanisms underlying these changes, evidence suggests that improvements in brain network function and connectivity play an important role in the antidepressant effects of TMS (Lefaucheur et al., 2020).
The science of neuroplasticity offers an encouraging message: the brain is not fixed. Throughout our lives, it continues to adapt, reorganise, and form new connections in response to our experiences, learning, and treatment. This remarkable ability creates opportunities for recovery, resilience, and positive change, even in conditions such as depression where brain networks may have become disrupted. Although no single treatment is effective for everyone, growing knowledge of how depression affects brain networks is transforming the way researchers understand and treat the condition. This understanding is opening new possibilities for treatments that aim to support the brain's natural capacity for adaptation and recovery.
As neuroscience continues to advance, our understanding of depression is becoming increasingly detailed. This growing knowledge has the potential to lead to more personalised, targeted, and effective treatments that consider the unique ways depression affects everyone's brain. Although many questions remain, research into neuroplasticity is providing new insights into how recovery occurs and offering hope that future treatments will continue to improve outcomes for people living with depression.
Written by Holly, Smart TMS Newcastle Practitioner
Chaudhary, U. (2025). Non-invasive brain stimulation techniques: TMS, tDCS, and tACS methods. In Expanding senses using neurotechnology: Volume 1—Foundation of brain-computer interface technology (pp. 281–324). Springer Nature Switzerland.
Cleveland Clinic. (2026, January 29). Transcranial magnetic stimulation (TMS): What it is. https://my.clevelandclinic.org/health/treatments/17827-transcranial-magnetic-stimulation-tms
Drevets, W. C., Price, J. L., & Furey, M. L. (2008). Brain structural and functional abnormalities in mood disorders: Implications for neurocircuitry models of depression. Brain Structure and Function, 213(1–2), 93–118. https://doi.org/10.1007/s00429-008-0189-x
Fitzsimmons, S. M., Oostra, E., Postma, T. S., van der Werf, Y. D., & van den Heuvel, O. A. (2024). Repetitive transcranial magnetic stimulation–induced neuroplasticity and the treatment of psychiatric disorders: State of the evidence and future opportunities. Biological Psychiatry, 95(6), 592-600.
Fox, M. D., Buckner, R. L., White, M. P., Greicius, M. D., & Pascual-Leone, A. (2012). Efficacy of transcranial magnetic stimulation targets for depression is related to intrinsic functional connectivity to the subgenual cingulate. Biological Psychiatry, 72(7), 595–603. https://doi.org/10.1016/j.biopsych.2012.04.028
Gazerani, P. (2025). The neuroplastic brain: Current breakthroughs and emerging frontiers. Brain Research, 1858, 149643. https://doi.org/10.1016/j.brainres.2025.149643
Goldapple, K., Segal, Z., Garson, C., Lau, M., Bieling, P., Kennedy, S., & Mayberg, H. (2004). Modulation of cortical-limbic pathways in major depression: Treatment-specific effects of cognitive behavior therapy. Archives of General Psychiatry, 61(1), 34–41. https://doi.org/10.1001/archpsyc.61.1.34
Kita, A., Ishida, T., Kita, N., et al. (2025). Exploring the capabilities of repetitive transcranial magnetic stimulation in major depressive disorder: Dynamic causal modeling of the neural network. Translational Psychiatry, 15, 257. https://doi.org/10.1038/s41398-025-03480-7
Lefaucheur, J.-P., Aleman, A., Baeken, C., Benninger, D. H., Brunelin, J., Di Lazzaro, V., Filipović, S. R., Grefkes, C., Hasan, A., Merabet, L., Nardone, R., Nyffeler, T., Pascual-Leone, A., Rossi, S., Sahlsten, H., & Ziemann, U. (2020). Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014–2018). Clinical Neurophysiology, 131(2), 474–528. https://doi.org/10.1016/j.clinph.2019.11.002
Milbocker, K. A., Smith, I. F., & Klintsova, A. Y. (2024). Maintaining a dynamic brain: A review of empirical findings describing the roles of exercise, learning, and environmental enrichment in neuroplasticity from 2017–2023. Brain Plasticity, 9(1–2), 75–95. https://doi.org/10.3233/BPL-230151
Mulders, P. C. R., van Eijndhoven, P. F. P., Schene, A. H., Beckmann, C. F., & Tendolkar, I. (2015). Resting-state functional connectivity in major depressive disorder: A review. Neuroscience & Biobehavioral Reviews, 56, 330–344. https://doi.org/10.1016/j.neubiorev.2015.07.014
National Health Service. (2023, July 5). Depression in adults – Overview. https://www.nhs.uk/mental-health/conditions/depression-in-adults/overview/
NeuroLaunch. (2026). What part of the brain is affected by depression? https://neurolaunch.com/what-part-of-the-brain-is-affected-by-depression/
Pascual-Leone, A., Amedi, A., Fregni, F., & Merabet, L. B. (2005). The plastic human brain cortex. Annual Review of Neuroscience, 28, 377–401. https://doi.org/10.1146/annurev.neuro.27.070203.144216
Pickersgill, J. W., Turco, C. V., Ramdeo, K., Rehsi, R. S., Foglia, S. D., & Nelson, A. J. (2022). The combined influences of exercise, diet and sleep on neuroplasticity. Frontiers in Psychology, 13, Article 831819. https://doi.org/10.3389/fpsyg.2022.831819
Pigott, L. E., & McIernon, S. (2026, January 27). Scientists once thought the brain couldn't be changed. Now we know different. The Conversation. https://theconversation.com/scientists-once-thought-the-brain-couldnt-be-changed-now-we-know-different-271252
Rajkumar, R. P. (2024). The advantages of combining therapies in treating psychiatric patients. Brain Sciences, 14(7), 708. https://doi.org/10.3390/brainsci14070708
Sakai, J. (2020). How synaptic pruning shapes neural wiring during development and, possibly, in disease. Proceedings of the National Academy of Sciences, 117(28), 16096–16099. https://doi.org/10.1073/pnas.2010281117
Szuhany, K. L., Bugatti, M., & Otto, M. W. (2015). A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor. Journal of Psychiatric Research, 60, 56–64. https://doi.org/10.1016/j.jpsychires.2014.10.003
Thut, G., & Pascual-Leone, A. (2010). Integrating TMS with EEG to study brain oscillations and network dynamics. Brain Topography, 22(4), 215–218.
Tononi, G., & Cirelli, C. (2014). Sleep and the price of plasticity. Neuron, 81(1), 12–34. https://doi.org/10.1016/j.neuron.2013.12.025
Wang, Y. B., Song, N. N., Ding, Y. Q., & Zhang, L. (2023). Neural plasticity and depression treatment. IBRO neuroscience reports, 14, 160-184.
World Health Organization. (2017, March 30). Depression: Let's talk says WHO, as depression tops list of causes of ill health. "Depression: let’s talk" says WHO, as depression tops list of causes of ill health
World Health Organization. (2025). Depressive disorder (depression). https://www.who.int/news-room/fact-sheets/detail/depression
Zhang, F. F., Peng, W., Sweeney, J. A., Jia, Z. Y., & Gong, Q. Y. (2018). Brain structure alterations in depression: Psychoradiological evidence. CNS Neuroscience & Therapeutics, 24(11), 994–1003. https://doi.org/10.1111/cns.12835