Brain Disorders: Electroconvulsive Therapy vs Transcranial Magnetic Stimulation.

Shock Therapy: A barbaric treatment no longer in use?
Previous treatments of mental illnesses are often now viewed as extreme. Back in the 1800’s the use of primitive treatment to cut away a section of the patient’s skull to release the ‘evil spirits’ from their body was a common treatment of mental disorders. A tranquilizing chair was also often adopted, where the individual would have to place their head inside a box to reduce blood flow to their brain (Griggs, 2014). Yes, this seems outrageous, terrifying and barbaric in today’s society. In modern day medicine however, the use of biomedical treatments such as electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS or rTMS) can actually be used to treat mental disorders, and have shown to be particularly successful in treatment-resistant depression. The unusual historical treatments have often led to the common misconception of ECT in that it is invasive and unsafe, however this is no longer viewed as the case.  These two approaches have actually revolutionized the treatment of depression, and now recent research also supports the use of TMS in those with autism and epilepsy, which will be discussed in this essay.

The History of Electroconvulsive Therapy
Italian neurologists Ugo Cerletti and Lucio Bini developed electroconvulsive therapy. Cerletti was an epilepsy specialist who knew that an electric shock across the head would lead to seizures. He thought that induced convulsions could be used to treat schizophrenia, however these convulsions were far too severe. Along with Kalinowski, a German physician, the researchers developed experiments to test brief electric shocks on humans. Around 10 – 20 ECT shocks on alternate days produced improvement in patients with acute-onset schizophrenia. Another side effect, which appeared to be beneficial, was the retrograde amnesia it caused, as it meant that patients did not report bad experiences towards the therapy. In further use, the treatment was found to be highly effective in depression (Sabbatini, 2016). Today ECT is executed under anesthesia, where small electrical currents are passed through the brain to specific areas via electrodes on the patient’s skull. This targeted therapy makes for an improvement on the previously used treatments such as drugs, as the side effects are minimal. The misconceptions associated with ECT were due to its improper use in its early days. It was often used to control psychiatric patients, whilst conscious and mostly without consent. Various media has depicted ECT in this way, such as the movie/novel One Flew Over the Cuckoos Nest – which is not how the treatment is used (Lilienfeld and Arkowitz, 2014).

ECT Success in Depression
ECT is currently one of the most successful therapies for severe depression, and sometimes in bipolar disorder, however less frequently in other mental disorders. In a meta-analysis by Pagnin et al (2004), ECT was shown to be the superior treatment in comparison to placebos, simulated ECT (a procedure were shocks are not given) and antidepressants, including tricyclic antidepressants and monoamine oxidase inhibitors. Tew et al (1999) found that even older patients with more severe depression and cognitive impairment could tolerate the use of ECT as equally as the younger patients with severe major depression, and even showed some improvement in results.

How does ECT work?
This is one thing we are unsure about, there are many theories postulated however the specific mechanisms leading to improvement in depressive disorders are unknown. It is possible that ECT increases the monoamine neurotransmitters, such as dopamine and serotonin, which are thought to be reduced in those with depression. Another theory is that the treatment stimulates the release of hormones from the hypothalamus or pituitary, as the hypothalamic-pituitary-adrenal axis is thought to be disturbed in depression. The treatment is also thought to have an anti-convulsant nature, rising the threshold for seizures and decreasing their duration. The final theory is that the efficacy of the treatment is due to an increase in synaptogenesis and neurogenesis.

Research by Madsen at al (2000) suggests that ECT leads to an increase in neurogenesis. Rats in this study were either given single electroconvulsive seizures, or a series of 10. Bromodeoxyuridine (BrdU) was administered to the rats; this is a marker commonly used to highlight newly born cells – an indicator of neurogenesis. This marker was used in combination with a specific neuronal marker and co-staining could therefore indicate these new cells were specifically neurons. One month following a single electroconvulsive seizure, there was a 3-fold increase in cells stained with BrdU in the dentate gyrus of the rat’s hippocampus (Figure 1), thus supporting the neurogenesis theory of ECT.


Figure 1: A single electroconvulsive seizure (ECS) stimulates cell proliferation. Double immunofluoroscence images showing a rat dentate gyrus from (top) a sham-treated animal and (bottom) an ECS treated-animal. Bromodeoxyuridine (BrdU) was injected six times with 12-hour intervals, starting 72 hours after ECS. Animals survived 1 month after the ECS treatment. Red cells are positive for the mitotic marker BrdU, and green cells are positive for the neuronal marker NeuN. Scale bar, 50 μm (Madsen et al 2000).

Transcranial Magnetic Stimulation: An advancement of ECT
TMS is another brain stimulation technique, which uses magnetic field (similar to that used in an MRI). It is non-invasive and unlike ECT the patients do not have to be under anesthesia. The magnetic currents pass through the brain and skull to induce currents in the brain tissue underlying a coil placed on the scalp of the individual. Similarly to ECT, TMS is a targeted therapy leading to fewer side effects than commonly used medications. This technique does have possible use as a therapeutic method, as it has been shown to be successful in depression. At the American psychiatric association’s annual meeting in 2013 they showed that TMS induced improvement in depression, and these results were maintained throughout the 12-month study, suggesting that the effects of TMS are long lasting. More recently however, TMS has been successfully used as a diagnostic tool for many disorders such as depression, epilepsy and autism (Narayana et al 2015). In epilepsy it has been used to determine the changes in the excitability of neurons in the brains of patients, and how this has altered after treatment with anti-epileptic drugs. TMS can then be applied to these epilepsy patients therapeutically as low-frequency TMS can reduce cortical excitability- it is a very promising treatment approach for people with treatment-resistant refractory epilepsy (Narayana et al 2015). Again, similarly to ECT the biology behind why TMS works is not completely understood. 

Autistic Spectrum Disorder – an upcoming use of TMS
Autistic Spectrum disorder has been considered a possible candidate for the therapeutic use of TMS. Autism affects around 700,000 people in the UK alone. It is a disorder that causes an individual to present with deficits in social interaction and communication across multiple contexts (according to DSM-5).  Advances within Neuroscience have allowed us to determine differences in the brains of those with autistic spectrum disorder, one such variation is that people with autism have larger brain sizes – possibly due to larger numbers of neurons. There is thought to be a lack of communication between various regions in the brain, which could explain why those with autism have difficulties integrating different cognitive functions. Although TMS has been used effectively in the treatment of depression, its use in autism is relatively novel and still being studied.

John Elder Robison, an individual with autistic spectrum disorder, was involved in a six-month study where he received weekly TMS treatments. He revealed that this treatment gave him empathy he had never felt before and the ability to perceive music in a way he had never experienced. To read more about John’s experience, his book ‘switched on’ is available, which details his use of TMS treatment and its effects.

Both of these techniques, ECT and TMS have been very successful in the treatment of depression, and particularly TMS as a diagnostic tool and potential therapeutic tool for many other brain disorders. These brain stimulation techniques hold many advantages over more commonly used treatments such as pharmacotherapy and unquestionably over the tranquilizing chair and primitive treatment. These treatments are not dangerous and could possibly change the way we diagnose and treat specific disorders, including autism, which there is currently few treatments for.

Author: Abbie Byford 

Editor: Molly Campbell



Griggs, R. 2014. Concise introduction to psychology. Worth Pub.

Sabbatini, R. 2016. The History of Shock Therapy in Psychiatry. [Online].

Pagnin, D et al. 2004. Efficacy of ECT in Depression: A Meta-Analytic Review. The Journal of ECT. 20(1),pp.13-20.

Lilienfeld, S. and Arkowitz, H. 2014. The Truth about Shock Therapy. [Online].

Tew, J et al. 1999. Acute Efficacy of ECT in the Treatment of Major Depression in the Old-Old. Am J Psychiatry. 156(12),pp.1865–1870.

Madsen, T el al. 2000. Increased neurogenesis in a model of electroconvulsive therapy. Biological Psychiatry. 47(12),pp.1043-1049.

Narayana, S et al. 2015. Clinical Applications of Transcranial Magnetic Stimulation in Pediatric Neurology. Journal of Child Neurology. 30(9),pp.1111-1124.




A Neuroscience Insight into Anxiety Disorders.

I read an article recently in a magazine aimed at individuals my age titled ‘Generation Anxiety’, and this sparked a series of thoughts and questions. The mental health charity Mind reported that 1 in 4 individuals in the UK will experience a mental health problem each year. 1 in 4. A quarter. That’s a lot. Of the listed mental health issues, 4.6 in 100 people will experience anxiety related problems this year.

What is anxiety?
Anxiety disorders describe pathological worry that actually stems from our cave man impulses, our ‘fight or flight response’ to put it simply. In the case of anxiety however an individual may not necessarily have a scenario to trigger such response, it occurs without stimuli, or with stimuli that wouldn’t necessarily be considered as dangerous. The DSM 5 (the diagnostic and statistical manual of mental health disorders) divides pathological anxiety into 3 categories: Obsessive compulsive related disorders, trauma and stressor related disorders and anxiety disorders (Calhoon et al). The stimuli differ for these diagnoses, but in all cases the cognitive and behavioral symptoms of anxiety adversely affect normal functioning.

Having read the initial statistics, I was shocked at how many people are actually affected by this condition. Having read the criteria for diagnosis, I was less shocked, because I most definitely can appreciate how easily worry can spiral and affect an individual in a pathological sense. At the end of the day, life can be very worrying; we are faced with stress every day be it through studying, through work, through financial stresses, all the things that make being an adult quite a burden. As a neuroscience student, I then began to question: what is happening in the brains of individuals for which this worry is becoming pathological? In addition to, why, despite the high incidence of individuals suffering, are there relatively few therapeutic targets identified for treatment? I wanted to explore these questions and present to you the answers from a neuroscience perspective.

Firstly, I encountered this statement from a source discussing mindfulness that I really quite liked:

The underlying mechanism of any mental illness is adaptive and present throughout the human population. A mental disorder is not a new and aberrant development of the human mind but an under- or over-representation of a native mechanism’ (Matthew, 2014).

The brain is complex, and with its complexity it poses the possibility of developing new ‘alternate’ circuits, new mechanisms of neurotransmission with far too much, or less, of the signalling molecule required.

When considering this, anxiety is a sum of its parts. So what has neuroscience taught us?

The Amygdala:
If you keep up to date with our blog you may have read a previous article discussing the role of the amygdala in fear responses. The amygdala is regarded as the ‘central hub’ for the circuitry that creates the sense of fear in our brains. Upon presentation of a threat, the lateral nucleus of the amygdala is activated, and through connections to the central nucleus of the amygdala initiates defensive behavioural mechanisms, freezing being the best example. Connections from the lateral amygdala to the basal amygdala to the nucleus accumbens enable defensive actions, such as avoidance, to be regulated. Don’t worry if the terminology baffles you, the schematic diagram (Figure 1) is a visual representation of these circuits.


Figure 1: A schematic of the circuits underlying defensive reactions and actions (LeDoux and Pine, 2016).

In accordance, individuals with lesions to the amygdala (i.e. damage) fail to show bodily reactions to threat. Imaging studies illustrate that in healthy individuals, a posing threat activates the amygdala, but in the case of an anxiety suffer there is exaggerated amygdala activation. In healthy individuals, cortical areas down-regulate the amygdala, however this capacity is destabilised in individuals with anxiety disorders (LeDoux and Pine, 2016).

Furthermore, a really interesting piece of research by Qin et al (2014) adopted structural and functional MRI to investigate the brain structure of young children who had been diagnosed with early childhood anxiety. Even in children as young as 7-9, MRI illustrated an enlarged amygdala volume, specifically the basolateral amygdala. Findings also showed increased connectivity between the amygdala and distributed brain systems implicated in attention and emotion perception. Machine algorithms suggest that the levels of childhood anxiety could be reliably predicted via amygdala morphometry and intrinsic functional connectivity.

The Bed Nucleus of the Stria Terminalis (BNST):
In neuroscience, one of the techniques in research that I find the most fascinating is optogenetics. This is where neuroscientists transfect cells with genes and render them responsive to light – you can physically turn on and turn off a gene through the presentation of a light stimulus. Two very elegant studies, Jennings et al (2013) and Kim et al (2013) have adopted optogenetics to examine the role of the BNST in anxiety disorders.

Jennings et al looked at the role of the ventral BNST (vBNST) in regulating motivated behaviour and generating anxiety. Interestingly, the study showed that learned anxiety associated with specific environments led to an increase in the activity of some vBNST neurons, and a decrease in activity of others – in accordance with the vBNST consisting functionally distinct cell populations. The vBNST cell populations were found to synapse with neurons of the ventral tegmental area (VTA) that is involved in motivated behaviour and also addiction. Cells that were found to be excited by anxiety-inducing environments excited the VTA cell to which they were synaptically linked, and this activity increased anxiety and decreased reward seeking behaviour. Consistent results were found in vBNST neurons that were inhibited by anxiety seeking behaviour, and activating these connections encouraged reward-seeking behaviour and a reduction in anxiety levels. It must be considered however in these findings that the neurons were artificially excited to induce a state of anxiety – findings might differ in natural anxiety states. Nonetheless this research illustrates nicely that the BNST neuronal population, particularly the ventral neurons, are involved in anxiety. It might be the interplay of these neuronal populations that creates a specific level of anxiety.

Kim et al (2013) investigated whether the cells of the two subregions of the dorsal BNST, the oval nucleus and the anterodorsal BNST regulate anxiety. Their research showed that oval nucleus neurons promoted anxiety, whereas inputs from the amygdala activated the anterodorsal BNST and reduced anxiety. The inhibition of the anterodorsal BNST regions therefore enhanced anxiety. In mice models, the anterodorsal BNST neurons were more active when the mouse was in a safe, familiar environment when compared to an anxiety enhancing one.

The proposed mechanisms from this study are illustrated in figure 2.


Figure 2: A schematic illustrating the collective findings of Kim and Jennings et al (2013) and the proposed mechanisms underlying anxiety based on their research.

Collectively, these findings suggest evidence that in individuals with anxiety, there are physical structural changes to the brain, producing circuitry alterations that act overall to enhance fear.

For some people, particularly anxiety sufferers themselves, such evidence might be quite daunting; the idea that the brain can actually change its circuitry to produce pathology is quite hard to appreciate. For some, it might be reassuring, as it fights the stigma that unfortunately some associate with mental health conditions as being ‘not real’ – if a structural brain change doesn’t convince you then frankly I’m not sure what will. Regardless of which category you fall into, I would like to point you in the direction of neuroscience research that, using animal models, implies that these alterations can actually be corrected, or silenced, using select methods.

For example, a 2013 study investigated exposure therapy, an element of cognitive behavioural therapy (CBT) and its effects on the structure of the mouse brain. The research showed that exposure therapy silenced and stimulated remodelling of the perisomatic inhibitory synapse. This synapse enables one group of neurons to silence another, and the number of these synapses specifically increased around the fear neurons aforementioned in the amygdala. In the study, mice were placed in a box and exposed to a fear-stimulating situation. A control group did not receive the exposure therapy, whereas a comparison group did. In the exposure therapy group, the mice were placed in the box without the fear inducing situation repeatedly, and this led to a decreased response to the fear stimuli (Trouche et al., 2013). This research nicely demonstrates how the physiological changes in the brain present as behavioural changes. The study also suggested potential new drug targets for improving exposure therapy in humans, which has been found to show a varying success rate thus far.

I hope you will appreciate that the scope of research into anxiety and mental health in neuroscience is extremely large, and thus extends far beyond the content of this article. However, what I do hope to have shown you is how neuroscience research can greatly enhance our understanding of the underlying mechanisms that lead to disorders of the brain such as anxiety, and how these mechanisms produce the behaviour and symptoms that present clinically in sufferers.

Author: Molly Campbell


  2. Calhoon, G.G. and Tye, K.M. 2015. Resolving the neural circuits of anxiety. Nature Neuroscience. 18(10), pp. 1394–1404.
  3. Matthew (2014) The Neuroscience of anxiety disorders. Available at: (Accessed: 19 January 2017).
  4. LeDoux, J.E. and Pine, D.S. 2016. Using Neuroscience to help understand fear and anxiety: A Two-System framework. American Journal of Psychiatry. 173(11), pp. 1083–1093.
  5. Qin, S., Young, C., Duan, X., Chen, T., Supekar, K. and Menon, V. 2013. Amygdala subregional structure and intrinsic functional connectivity predicts individual differences in anxiety during early childhood. Biological psychiatry. 75(11), pp. 892–900.
  6. Jennings, J., Sparta, Stamatakis, A., Ung, R., Pleil, K., Kash, T. and Stuber, G. 2013. Distinct extended amygdala circuits for divergent motivational states. Nature. 496(7444), pp. 224–8.
  7. Kim, S., Adhikari, A., Lee, S., Marshel, J., Kim, C., Mallory, C., Lo, M., Pak, S., Mattis, J., Lim, B., Malenka, R., Warden, Neve, R., Tye, K. and Deisseroth, K. 2013. Diverging neural pathways assemble a behavioural state from separable features in anxiety. Nature. 496(7444), pp. 219–23.
  8. Trouche, S., Sasaki, J.M., Tu, T. and Reijmers, L.G. 2013. Fear extinction causes target-specific remodeling of perisomatic inhibitory synapses. Neuron. 80(4). pp. 1-22.