Tag: transcranial magnetic stimulation

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Bilateral Magnetic Stimulation of the Brain Improves Symptoms of Depression

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A type of therapy that involves applying a magnetic field to both sides of the brain has been shown to be effective at rapidly treating depression in patients for whom standard treatments have been ineffective.

Our accelerated approach means we can do all of the sessions in just five days, rapidly reducing an individual’s symptoms of depression

Valerie Voon

The treatment – known as repetitive transcranial magnetic stimulation (TMS) – involves placing an electromagnetic coil against the scalp to relay a high-frequency magnetic field to the brain.

Around one in 20 adults is estimated to suffer from depression. Although treatments exist, such as anti-depressant medication and cognitive behavioural therapy (‘talking therapy’), they are ineffective for just under one in three patients.

One of the key characteristics of depression is under-activity of some regions (such as the dorsolateral prefrontal cortex) and over-activity of others (such as the orbitofrontal cortex (OFC)).

Repetitive transcranial magnetic stimulation applied to the left side of the dorsolateral prefrontal cortex (an area at the upper front area of the brain) is approved for treatment of depression in the UK by NICE and in the US by the FDA. It has previously been shown to lead to considerable improvements among patients after a course of 20 sessions, but because the sessions usually take place over 20-30 days, the treatment is not ideal for everyone, particularly in acute cases or where a person is suicidal.

In research published in Psychological Medicine, scientists from Cambridge, UK, and Guiyang, China, tested how effective an accelerated form of TMS is. In this approach, the treatment is given over 20 sessions, but with four sessions per day over a period of five consecutive days.

The researchers also tested a ‘dual’ approach, whereby a magnetic field was additionally applied to the right-hand side of the OFC (which sits below the dorsolateral prefrontal cortex).

Seventy-five patients were recruited to the trial from the Second People’s Hospital of Guizhou Province in China. The severity of their depression was measured on a scale known as the Hamilton Rating Scale of Depression.

Participants were split randomly into three groups: a ‘dual’ group receiving TMS applied first to the right- and then to the left-hand sides of the brain; a ‘single’ group receiving sham TMS to the right-side followed by active TMS applied to the left-side; and a control group receiving a sham treatment to both sides. Each session lasted in total 22 minutes.

There was a significant improvement in scores assessed immediately after the final treatment in the dual treatment group compared to the other two groups. When the researchers looked for clinically-relevant responses – that is, where an individual’s score fell by at least 50% – they found that almost half (48%) of the patients in the dual treatment group saw such a reduction, compared to just under one in five (18%) in the single treatment group and fewer than one in 20 (4%) in the control group.

Four weeks later, around six in 10 participants in both the dual and single treatment groups (61% and 59% respectively) showed clinically relevant responses, compared to just over one in five (22%) in the control group.

Professor Valerie Voon from the Department of Psychiatry at the University of Cambridge, who led the UK side of the study, said: “Our accelerated approach means we can do all of the sessions in just five days, rapidly reducing an individual’s symptoms of depression. This means it could be particularly useful in severe cases of depression, including when someone is experiencing suicidal thoughts. It may also help people be discharged from hospital more rapidly or even avoid admission in the first place.

“The treatment works faster because, by targeting two areas of the brain implicated in depression, we’re effectively correcting imbalances in two import processes, getting brain regions ‘talking’ to each other correctly.”

The treatment was most effective in those patients who at the start of the trial showed greater connectivity between the OFC and the thalamus (an area in the middle of the brain responsible for, among other things, regulation of consciousness, sleep, and alertness). The OFC is important for helping us make decisions, particularly in choosing rewards and avoiding punishment. Its over-activity in depression, particularly in relation to its role in anti-reward or punishment, might help explain why people with depression show a bias towards negative expectations and ruminations.

Dr Yanping Shu from the Guizhou Mental Health Centre, Guiyang, China, said: “This new treatment has demonstrated a more pronounced – and faster – improvement in response rates for patients with major depressive disorder. It represents a significant step forward in improving outcomes, enabling rapid discharge from hospitals for individuals with treatment-resistant depression, and we are hopeful it will lead to new possibilities in mental health care.”

Dr Hailun Cui from Fudan University, a PhD student in Professor Voon’s lab at the time of the study, added: “The management of treatment-resistant depression remains one of the most challenging areas in mental health care. These patients often fail to respond to standard treatments, including medication and psychotherapy, leaving them in a prolonged state of severe distress, functional impairment, and increased risk of suicide.

“This new TMS approach offers a beacon of hope in this difficult landscape. Patients frequently reported experiencing ‘lighter and brighter’ feelings as early as the second day of treatment. The rapid improvements, coupled with a higher response rate that could benefit a broader depressed population, mark a significant breakthrough in the field.”

Just under a half (48%) of participants in the dual treatment group reported local pain where the dual treatment was applied, compared to just under one in 10 (9%) of participants in the single treatment group. However, despite this, there were no dropouts.

For some individuals, this treatment may be sufficient, but for others ‘maintenance therapy’ may be necessary, with an additional day session if their symptoms appear to be worsening over time. It may also be possible to re-administer standard therapy as patients can then become more able to engage in psychotherapy. Other options include using transcranial direct current stimulation, a non-invasive form of stimulation using weak electrical impulses that can be delivered at home.

The researchers are now exploring exactly which part of the orbitofrontal cortex is most effective to target and for which types of depression.

The research was supported by in the UK by the Medical Research Council and by the National Institute for Health and Care Research Cambridge Biomedical Research Centre.*

Reference
Cui, H, Ding, H & Hu, L et al. A novel dual-site OFC-dlPFC accelerated repetitive transcranial magnetic stimulation for depression: a pilot randomized controlled study. Psychological Medicine; 23 Oct 2024; DOI: 10.1017/S0033291724002289

*A full list of funders is available in the journal paper.

Source: University of Cambridge. The original text of this story is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Note: Content may be edited for style and length.

Categories : NeurologyTags :

Magnetic Stimulation may Ameliorate Memory Deficits in Schizophrenia

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Schizophrenia is often accompanied by extensive impairment of memory, including prospective memory, which is the ability to remember to perform future activities. In a randomised clinical trial published in Neuropsychopharmacology Reports, researchers found that repetitive transcranial magnetic stimulation (rTMS), a non-invasive method that uses alternating magnetic fields to induce an electric current in the underlying brain tissue, may help ameliorate certain aspects of prospective memory in individuals with schizophrenia.

The trial included 50 patients with schizophrenia and 18 healthy controls. Of the 50 patients, 26 completed active rTMS and 24 completed a sham rTMS. Healthy controls received no treatment.

Investigators assessed event-based prospective memory, which is remembering to perform an action when an external event occurs, such as remembering to give a message to a friend when you next see them and also time-based prospective memory, which is remembering to perform an action at a certain time, such as remembering to attend a scheduled meeting.

Both event-based prospective memory and time-based prospective memory scores at the baseline of the trial were significantly lower in patients with schizophrenia than in controls. After rTMS treatments, the scores of event-based prospective memories in patients were significantly improved and were similar to those in controls, while patients’ scores of time-based prospective memory did not improve.

“The findings of this study may provide one therapeutic option for prospective memory in patients with schizophrenia,” said co–corresponding author Su-Xia Li, MD, PhD, of Peking University, in China.

Source: Wiley

Categories : Mental Health NeurologyTags :

The Eyes may Hold the Secret to the Greatest Benefits from TMS Therapy

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A pair of recently published studies from researchers at UCLA Health suggest that measuring changes in how pupils react to light could help predict recovery from depression and personalise transcranial magnetic stimulation (TMS) treatment of major depressive disorder.

TMS is a safe, non-invasive therapy that uses magnetic fields to stimulate parts of the brain involved in mood regulation. While TMS is proven effective, not all patients respond equally well to the therapy. The ability to predict who will benefit most could allow doctors to better customise and target treatments.

In two recent studies, UCLA scientists found that the pupil’s response to light before treatment correlated with improvements in depression symptoms over the course of therapy. Pupil size reflects activation of the autonomic nervous system, which controls involuntary functions and is negatively impacted in people with depression.

The first study, appearing in the Journal of Affective Disorders, reports on outcomes for 51 patients who underwent daily TMS sessions. Before receiving treatment, researchers measured the patients’ baseline pupillary constriction amplitude, or CA: how much the pupil shrinks when exposed to light. The pupil’s constriction is an indicator of parasympathetic nervous system function. The researchers found a significant association between baseline pupil constriction amplitude and symptom improvement, indicating that a greater constriction amplitude at baseline was associated with a better outcome. In other words, those with larger pupil constriction in response to light at baseline showed greater symptom improvement over their full treatment.

The second study, published in Brain Stimulation, went further and compared patients who were treated for depression with one of two common TMS protocols: 10Hz stimulation and intermittent theta burst stimulation (iTBS). In 10Hz stimulation, magnetic pulses are delivered in a continuous and relatively high-frequency stimulation. iTBS is a faster form of stimulation with bursts of three pulses at 50Hz, repeated with short breaks between bursts. This pattern is thought to mimic the natural rhythm of certain brain activities.

The researchers found that people with slower pupillary constriction had significantly greater improvement in depression after 10 sessions if they received iTBS rather than 10Hz treatment.

“These results suggest we may be able to use a simple test of the pupil to identify who is most likely to respond to electromagnetic stimulation of the brain to treat their depression,” said researcher Cole Citrenbaum, lead author of both studies.

Tailored TMS treatments

The researchers propose that measuring pupillary reactivity before starting TMS could guide treatment selection. “Additionally, we may be able to tailor the frequency of stimulation to the individual patient to maximise their benefit from treatment,” Citrenbaum said.

“At the present time, about 65% of patients treated with TMS have a substantial improvement in their depression,” said Dr Andrew F. Leuchter, senior author of both studies. “Our goal is to have more than 85% of patients fully recover from depression. As we better understand the complex brain activity underlying depression, we move closer to matching patients with the treatments that ensure their full recovery. Pupil testing may be one useful tool in reaching this goal.”

The studies add to growing evidence on the benefits of biologically-based personalization in treating major depression. UCLA researchers plan further trials to confirm the value of pupillometry in optimizing transcranial magnetic stimulation.

Source: University of California – Los Angeles Health Sciences

Categories : NeurologyTags :

Scientists Unravel Neurological Origins of the Placebo Effect

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Researchers at Massachusetts General Hospital (MGH) have discovered a network of brain regions activated by the placebo effect overlaps with several regions targeted by brain-stimulation therapy for depression.

The findings of this study, published in Molecular Psychiatry, will help in understanding the neurobiology of placebo effects and could inform how brain stimulation trial results are interpreted. In addition, this could provide insights on how to harness placebo effects for the treatment of a variety of conditions.

The placebo effect occurs when a patient’s symptoms improve because they expect a therapy to help (due to a variety of factors), but not from the specific effects of the treatment itself. Recent research indicates that there is a neurological basis for the placebo effect, with imaging studies identifying a pattern of changes that happen in certain brain regions when a person experiences this phenomenon.

The use of brain-stimulation techniques for patients with depression that doesn’t respond adequately to medication or psychotherapy has gained wider use in recent years. Transcranial magnetic stimulation (TMS) delivers electromagnetic pulses to the brain, and its effect on brain activity has been established over the last three decades in animal and human research studies, with several TMS devices approved by the Food and Drug Administration for treating depression. In addition, for treatment depression, deep brain stimulation (DBS, which requires an implanted device) has shown some promise.

Senior author Emiliano Santarnecchi, PhD, saw studies of brain stimulation as a unique opportunity to learn more about the neurobiology of the placebo effect. Santarnecchi and his co-investigators conducted a meta-analysis and review of neuroimaging studies involving healthy subjects and patients to create a “map” of brain regions activated by the placebo effect. They also analysed studies of people treated with TMS and DBS for depression to identify brain regions targeted by the therapies. The team found that several sites in the brain that are activated by the placebo effect overlap with brain regions targeted by TMS and DBS.

Dr Santarnecchi and his colleagues believe that this overlap has critical importance in interpreting the results of research on brain stimulation for conditions such as depression. In clinical trials, a significant portion of depression patients receiving brain stimulation improve — but so do many patients receiving placebo (sham) treatment, in which no stimulation is administered, which has led to confusion over the therapy’s benefits.

A possible explanation is “that there is a significant placebo effect when you do any form of brain stimulation intervention,” said Dr Santarnecchi. TMS involves a clinical setting, with loud clicks as the pulse is delivered. “So the patient thinks, ‘Wow, they are really activating my brain’, so you get a lot of expectation,” said Dr Santarnecchi.

Elevated placebo effects associated with brain stimulation may create problems when studying the intervention, said first author Matthew Burke, MD, a cognitive neurologist. If brain stimulation and the placebo effect overlap in activating the same brain regions, then those circuits could be maximally activated by placebo effects, which could make it difficult to show any additional benefit from TMS or DBS, said Dr Burke. If so, this could explain the disparity of results in neurostimulation treatment of depression. Screening out placebo from brain stimulation’s direct impact on brain activity will help in designing studies where the real potential of techniques such as TMS will be more easily quantified, thus improving the effect of treatment protocols.

The findings from this study also suggest broad applications for the placebo effect, said Dr Santarnecchi. “We think this is an important starting point for understanding the placebo effect in general, and learning how to modulate and harness it, including using it as a potential therapeutic tool by intentionally activating brain regions of the placebo network to elicit positive effects on symptoms,” he said.

Dr Santarnecchi and his colleagues are currently designing trials that they hope will “disentangle” the effects of brain stimulation from placebo effects and offer insights about how they can be leveraged in clinical settings.

Source: Massachusetts General Hospital