Jun 12, 2026
Intermittent Theta-Burst Stimulation for Depressive Symptoms in Parkinson Disease
A Randomized Clinical Trial
JAMA Netw Open
Published Online: May 20, 2026
2026;9;(5):e2613580. doi:10.1001/jamanetworkopen.2026.13580
Miaomiao Hou, MD1; Bingjie Tian, PhD2; Chen Qi, PhD1 et al
Key Points
Question Can the ultra-brief intermittent theta-burst stimulation (iTBS) protocol provide a time-efficient and effective alternative to standard high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) for treating depressive symptoms in Parkinson disease (PD)?
Findings In this randomized clinical trial including 54 patients with PD and depressive symptoms, both iTBS and HF-rTMS produced significant and comparable reductions in depressive symptoms compared with sham stimulation.
Meaning This study suggests that the ultra-brief iTBS protocol achieved antidepressant efficacy comparable with that of standard HF-rTMS in PD while reducing treatment time, offering a pragmatic and patient-centered advancement for clinical management.
Importance Depressive symptoms in patients with Parkinson disease (PD) are common and burdensome. High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) targeting the left dorsolateral prefrontal cortex (DLPFC-L) is effective but time intensive, limiting practicality.
Objective To evaluate the antidepressant efficacy and neurofunctional effects of the ultra-brief intermittent theta-burst stimulation (iTBS) protocol for patients with PD depression (PD-D) compared with active HF-rTMS and sham stimulation.
Design, Setting, and Participants This triple-arm, randomized, sham-controlled single-center clinical trial was conducted at Xinhua Hospital, Shanghai Jiao Tong University School of Medicine in China from August 1, 2024, to January 31, 2025. Patients with PD aged 50 to 80 years with 24-item Hamilton Depression Rating Scale (HAMD-24) scores of 8 to 20 were randomized 1:1:1 to iTBS, HF-rTMS, or sham iTBS. Outcomes were assessed at baseline, week 1, week 2, and week 6. Data analysis was finalized in February 2026.
Interventions Ten daily sessions over 2 weeks: active iTBS (3 minutes and 20 seconds), active HF-rTMS (20 minutes), or sham iTBS.
Main Outcomes and Measures The primary outcome was the HAMD-24 score at week 2. Secondary outcomes included anxiety (measured by the 14-item Hamilton Anxiety Rating Scale [HAMA-14]), motor symptoms (measured by the Movement Disorder Society–Unified Parkinson Disease Rating Scale), quality of life (measured by the 8-item Parkinson’s Disease Questionnaire [PDQ-8]), and prefrontal hemodynamics (measured using functional near-infrared spectroscopy). Primary analysis followed the principle of intention to treat.
Results Of 54 randomized participants (mean [SD] age, 70.1 [5.3] years; 29 men [53.7%]), 50 (92.6%) completed the trial. Linear mixed-effects models revealed a significant group × time interaction for the HAMD-24 (F6,145 = 4.84; P < .001). At week 2, both active interventions were superior to sham (HAMD-24 score mean difference: iTBS, −4.97 [95% CI, −7.71 to −2.23]; P < .001; and HF-rTMS, −5.73 [95% CI, −8.95 to −2.51]; P < .001). Effects persisted at week 6 (HAMD-24 score mean difference: iTBS vs sham, −6.05 [95% CI, −9.26 to −2.83]; P < .001; and HF-rTMS vs sham, −5.57 [95% CI, −9.36 to −1.78]; P = .002), with no between-group differences. Both interventions improved PDQ-8 scores at week 2 (mean difference: iTBS vs sham, −2.33 [95% CI, −3.33 to −1.33]; P < .001; and HF-rTMS vs sham, −2.43 [95% CI, −4.60 to −0.26]; P = .02). iTBS also alleviated anxiety (mean difference: HAMA-14 score vs sham, −4.04 [95% CI, −7.73 to −0.35; P = .03). Active stimulations increased DLPFC-L activation (estimated adjusted difference: iTBS vs sham, 151.18 [95% CI, 51.24-251.11]; P = .004; and HF-rTMS vs sham, 173.26 [95% CI, 71.92-274.60]; P = .001) and reduced time in low-efficiency connectivity states (iTBS: median change, −0.12 [IQR, −0.29 to 0.02]; false discovery rate–corrected P = .045; and HF-rTMS: −0.12 [IQR, −0.32 to 0]; false discovery rate–corrected P = .02).
Conclusions and Relevance In this randomized clinical trial of patients with PD-D, the ultra-brief iTBS achieved antidepressant efficacy comparable with that of standard HF-rTMS while markedly reducing treatment time, supporting its use as a pragmatic therapy for PD-D. This study suggests the promise of symptom-stratified neuromodulation for personalized treatment protocols.
Trial Registration Chinese Clinical Trial Registry Identifier: ChiCTR2100044421
Introduction
Depressive symptoms affect 20% to 50%1 of patients with Parkinson disease (PD), worsening quality of life, motor function, and cognitive trajectory.2 Although selective serotonin reuptake inhibitors are first-line pharmacotherapy, their adverse effects (eg, nausea and headache) often limit tolerability.3,4 High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) over the left dorsolateral prefrontal cortex (DLPFC-L) offers an effective alternative with guideline support.5-7 However, the standard 20-minute session duration of HF-rTMS poses a practical barrier for patients with PD, who frequently contend with complex medication regimens, mobility challenges, and time-intensive care schedules.
Intermittent theta-burst stimulation (iTBS) condenses therapeutic stimulation into an ultra-brief 3-minute session while using potent plasticity mechanisms.8 Although iTBS has demonstrated efficacy comparable with that of HF-rTMS in major depressive disorder,9 its use for PD depression (PD-D) remains unknown.
Therefore, we conducted this 3-arm, randomized, sham-controlled clinical trial to evaluate the clinical use of iTBS for PD-D. We aimed to determine whether the ultra-brief iTBS protocol could achieve antidepressant efficacy comparable with that of the standard HF-rTMS and to examine the underlying neural mechanisms. Using functional near-infrared spectroscopy (fNIRS) during a verbal fluency task (VFT),10 we measured prefrontal cortical activation via oxygenated hemoglobin (HbO) concentration changes, and we complemented this with dynamic functional connectivity analysis to capture temporal network dynamics. We hypothesized that both active interventions would be superior to sham stimulation in alleviating depressive symptoms and that the clinical response to iTBS would be underpinned by measurable modulation of prefrontal network dynamics. Confirmation of these hypotheses would position iTBS as a pragmatic, patient-centered advancement in the management of PD-D.
Methods
Study Design
This double-blind, 3-arm, randomized, sham-controlled clinical trial compared iTBS, HF-rTMS, and sham stimulation for PD-D (trial protocol in Supplement 1). The protocol consisted of 10 daily sessions over 2 consecutive weeks, with clinical assessments at baseline, on the day of session 5 (week 1) and session 10 (week 2), as well as 4 weeks after session 10 ended (week 6) (eFigure 1A in Supplement 2). This study was conducted at Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine in China from August 1, 2024, to January 31, 2025. The Ethics Committee of Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine approved the experiments, and written informed consent was obtained from all the participants. The study protocol was preregistered with the Chinese Clinical Trial Register (ChiCTR2100044421). This 3-arm, randomized, sham-controlled clinical trial followed the Consolidated Standards of Reporting Trials (CONSORT) reporting guideline.
Jun 11, 2026
Mouse study targets GluN2B receptor subunit in movement-control neurons
Written by Marisa Wexler, MS | June 8, 2026
- Many people with Parkinson’s disease develop dyskinesia, or uncontrolled movements, after long-term levodopa treatment.
- In a mouse model, dyskinesia was linked to abnormal levels of the GluN2B receptor subunit in specific movement-control neurons.
- An experimental gene therapy strategy that reduced GluN2B levels in mice prevented and eased dyskinesia without reducing levodopa’s benefits.
Levodopa, a standard treatment for Parkinson’s disease, can cause uncontrolled movements called dyskinesia — and this side effect may be driven by changes in a specific receptor component in certain brain cells, a new study shows.
Scientists found that an experimental gene therapy strategy aimed at decreasing levels of this receptor component in those specific brain cells could blunt dyskinesia’s development and substantially ease established dyskinesia in a mouse model.
“This is a way that we might be able to control dyskinesia with a completely novel strategy,” D. James Surmeier, PhD, senior author of the study at Northwestern University, said in a university news story. “Nearly 80 percent of Parkinson’s disease patients will develop dyskinesia. At present, we have a very limited set of tools to help these patients right now. This work points to the possibility of a non-invasive gene therapy that would be transformative.”
The study, “Cell- and state-specific plasticity of striatal glutamatergic synapses is critical to the expression of levodopa-induced dyskinesia,” was published in Neuron.
Levodopa treatment can trigger dyskinesia
Parkinson’s is a neurological disorder marked by the degeneration and death of brain cells that make dopamine, a signaling molecule that’s key for coordinating movements. Low dopamine levels ultimately drive Parkinson’s symptoms.
Levodopa and its derivatives primarily work by being converted into dopamine in the brain. These medications have for decades been a gold standard of Parkinson’s treatment, and they can be highly effective for easing disease symptoms — but as with any medical treatment, levodopa can cause side effects. In particular, many people who take levodopa long term develop dyskinesia, defined by jerky, uncontrollable movements.
Although it’s well-established that levodopa can trigger dyskinesia, the precise molecular mechanisms by which this drug causes this side effect have been obscure.
Working in a mouse model, researchers found that repeated levodopa treatment that induced dyskinesia led to molecular abnormalities in a subset of brain cells called indirect pathway spiny projection neurons, or iSPNs. Under normal circumstances, these nerve cells are thought to help the brain prevent unwanted movements.
The researchers specifically found that dyskinesia was linked to increased levels of N-methyl-D-aspartate (NMDA) receptors containing a specific subunit called GluN2B in iSPNs. NMDA receptors normally help nerve cells communicate with each other, but changes in these receptors can disrupt nerve-to-nerve communication.
“Connections between neurons dictate when they become active and how they perform their duties in controlling movement. In late-stage [Parkinson’s] patients, levodopa begins to ‘scramble’ these connections, which we think leads to uncontrolled movement or dyskinesia,” Surmeier said. “When we induce dyskinesia, we see this change in NMDA receptors in this subset of striatal neurons thought to be responsible for suppression of unwanted movement.”
Jun 10, 2026
Medically reviewed by Meredith Goodwin, MD, FAAFP — Written by The Healthline Editorial Team — Updated on June 16, 2025
Key takeaways
- Parkinson’s disease can impair driving ability due to its effects on vision, motor function, memory, and spatial awareness, though the degree and timing vary for each individual.
- People with Parkinson’s can remain safe while driving by managing their symptoms, getting regular evaluations, and making certain adjustments to their driving habits.
- Even if driving is no longer an option, individuals with Parkinson’s can maintain independence through alternative transportation and support services.
Parkinson’s disease is a central nervous system disorder that causes certain cells in your brain to decline over time. This can affect your movement, reaction times, memory, and visual-spatial perception. It may also lead to dementia.
All of these challenges can interfere with a person’s ability to drive.
Yet it may take many months or years after diagnosis for Parkinson’s to interfere with activities of daily living, including the ability to drive a vehicle.
It’s important to know when driving will become a concern and what you can do once it’s no longer safe to get behind the wheel.
There is no one-size-fits-all answer for how long you can drive with Parkinson’s or how your condition is affecting your driving now. Many people can drive long after they first receive a diagnosis, while others will need to stop driving sooner.
It depends on:
- the person
- progression of the disease
- how severe the symptoms are
Some Parkinson’s symptoms that specifically interfere with safe driving may include:
- tremors, or uncontrollable shaking, in the hands and arms
- lack of coordination
- decreased reaction times
- attention deficits
- visual impairment
- muscle stiffness
- daytime sleepiness, often due to nighttime sleeping issues
- drowsiness, dizziness, or blurred vision resulting from Parkinson’s medications
Driving may be riskier than it might seem, because your symptoms may become more or less severe depending on the particular day.
Even the earliest stages of Parkinson’s can affect a person’s driving.
That said, people who aren’t experiencing cognitive impairments (such as vision changes or visuospatial processing issues) might be able to drive for many years.
A 2018 review of studies found that in 50 studies, people with Parkinson’s were 6 times more likely to fail an on-the-road driving test compared with people who did not have the condition. Those with Parkinson’s were also more than 2 1/2 times as likely to crash in a simulated test.
Jun 9, 2026
A Parkinson's journey is rarely straightforward and varies from patient to patient
Written by Mary Beth Skylis | June 4, 2026
Before my dad’s Parkinson’s diagnosis in 2013, my understanding of the disease was limited. I knew someone from church who had it, mainly because their tremors made it extremely visible. But I knew little about the disease’s nuances, such as who is most likely to be diagnosed with it, how people experience it differently, and how its treatment isn’t simple.
Based on my experience over the years, the following are five common misconceptions about Parkinson’s that I’ve encountered:
1. Tremors are always a part of having Parkinson’s: Because tremors are one of the most recognizable Parkinson’s symptoms, it’s easy to assume that one must experience them in order to have the disease. While my dad has always experienced this symptom, not everyone does.
2. Parkinson’s affects only older people: As Parkinson’s News Today notes, “most people with Parkinson’s first start to notice symptoms when they are age 60 or older. In about 10% to 20% of cases, however, Parkinson’s begins before a person turns 50. These cases are commonly referred to as early-onset or young-onset Parkinson’s.” My dad was diagnosed at about age 60, but the disease clearly can affect a wide range of ages.
Jun 8, 2026
Last updated Aug. 1, 2025, by Patricia Weiser, PharmD Fact-checked by Patrícia Silva, PhD
Cognitive changes Tips Brain exercises Helpful tools
Cognitive changes are a common part of living with Parkinson’s disease. These shifts in memory, attention, or decision-making may start subtly but can grow more noticeable over time.
The good news is that with the right tools, habits, and support, it’s possible to stay mentally engaged. From lifestyle strategies to targeted brain exercises for Parkinson’s, there are practical steps you can take to support long-term cognitive health.
Cognitive changes in Parkinson’s
Parkinson’s disease doesn’t just affect movement — it can also affect how you think, focus, and remember things.
These changes are often linked to the loss of dopamine, a brain chemical that helps with both movement and mental function. Parkinson’s may also affect other brain chemicals, like norepinephrine and acetylcholine, which play a role in memory and attention.
Cognitive symptoms tend to be mild at first and often become more noticeable over time. They may include:
- trouble concentrating or staying organized
- challenges with decision-making or planning
- changes in memory, such as forgetting how to do familiar tasks
- slower processing or delayed verbal responses
- trouble finding words or remembering names of everyday items
- problems with spatial awareness and perception, especially in low light
- difficulty with slurred speech or word confusion.
Other mental health symptoms like depression, anxiety, and apathy often overlap with cognitive changes. These conditions can show up at any stage and may make memory and attention problems feel worse.
Talk with your healthcare team as soon as you or a loved one notices any changes. Early support can make a big difference.
Jun 5, 2026
Multiple states are now considering legislation to ban the herbicide
Written by Doc Irish | June 2, 2026
There are moments when a disease stops being only a medical story and becomes a public trust story. A prevention story. A question of whether the people who know enough to act will do so in time. I think Parkinson’s disease is having one of those moments now.
For years, many of us living with Parkinson’s have been told some version of the same unsatisfying sentence: We do not know what caused it. Parkinson’s is complicated. Genes, aging, and biology matter. No one should pretend that one chemical explains every diagnosis. But uncertainty is not ignorance. And it is certainly not an excuse for paralysis.
The Parkinson’s Foundation says genetics contribute to about 10% to 15% of Parkinson’s cases, while environmental factors, including pesticide exposure, can influence risk. That leaves millions of us living in the gray zone between “we do not know” and “we should have known enough to do more.”
Paraquat sits squarely in that gray zone. This highly toxic herbicide has been linked in multiple studies and advocacy campaigns to increased Parkinson’s risk. Its use is already banned in more than 70 countries, including China, where it is still manufactured and exported, yet remains legal in the United States. Advocates, scientists, patients, and families have warned about it. Still, the chemical remains in use.
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