Most Parkinson’s disease patients struggle with speech problems. New research by Stanford Medicine scientists uncovers the brain connections that could be essential to preserving speech.

大多數的帕金森氏症患者，皆受到言語問題的困擾。美國史丹佛大學醫學院，科學家們的新研究揭露了，對保留語言能力至關重要的大腦連結。

Research by Stanford Medicine scientists may explain why some treatments for Parkinson’s — developed mainly to target motor symptoms — can improve speech impairments while other treatments make them worse.
由史丹佛大學醫學院，科學家們進行的研究可以解釋，為何帕金森氏症的一些療法(主要鎖定肌肉運動症狀開發的)能改善言語障礙，而其他療法使其更惡化。

Parkinson’s disease is most well-known and well-studied for its motor impairments — tremors, stiffness and slowness of movement. But less visible symptoms such as trouble with memory, attention and language, which also can profoundly impact a person’s quality of life, are less understood.

帕金森氏症以其肌肉運動障礙(顫動、僵硬及行動緩慢)，被熟知且充分被研究。不過，較少具有諸如記憶力、注意力及語言障礙等，也會極度影響一個人，生活品質的顯而易見症狀。

A new study by Stanford Medicine researchers reveals the brain mechanisms behind one of the most prevalent, yet often overlooked, symptoms of the disease — speech impairment.

一項由史丹佛大學醫學院，研究人員們進行的新研究揭露了，該種疾病最常見，不過經常被忽視的症狀之一，言語障礙背後的大腦機制。

Based on brain imaging from Parkinson’s patients, the researchers identified specific connections in the brain that may determine the extent of speech difficulties.

根據來自帕金森氏症患者的大腦造影，此些研究人員確認了，於大腦中，能決定言語困難程度的特定連結。

The findings, reported May 20 in the Proceedings of the National Academy of Sciences, could help explain why some treatments for Parkinson’s — developed mainly to target motor symptoms — can improve speech impairments while other treatments make them worse.

此些(2024年)5月20日，報導於《美國國家科學院院刊》的研究發現，可能有助於解釋，為何帕金森氏症的一些療法(主要鎖定肌肉運動症狀開發的)，能改善言語障礙，而其他療法使其惡化。

“Parkinson’s disease is a very common neurological disorder, but it’s mostly considered a motor disorder,” said Weidong Cai, PhD, clinical associate professor of psychiatry and behavioral sciences and the lead author of the new study.

該項新研究首要撰文人，精神病學暨行為科學臨床副教授，Weidong Cai博士宣稱：「帕金森氏症是一種，極常見的神經病學疾病。不過，它通常被認為是一種，肌肉運動障礙。

“There’s been lots of research on how treatments such as medications and deep brain stimulation can help improve motor function in patients, but there was limited understanding about how these treatments affect cognitive function and speech.”

一直有許多攸關諸如，藥物及深部大腦刺激等，療法如何協助改善，於患者中之肌肉運動功能的研究。不過有關此些療法，如何影響認知功能及語言能力的瞭解有限。」

Over 90% of people with Parkinson’s experience difficulties with speech, an intricate neurological process that requires motor and cognitive control. Patients may struggle with a weak voice, slurring, mumbling and stuttering.

超過90%帕金森氏症患者具有，言語困難的經歷。這是一種，需要肌肉運動及認知控制之複雜的神經病學過程。患者會掙扎面對，聲音微弱、模糊、咕噥及口吃。

“Speech is a complex process that involves multiple cognitive functions, such as receiving auditory feedback, organizing thoughts and producing the final vocal output,” Cai said.

Cai宣稱：「語音是一種，涉及諸如接收聽覺回饋、組織思想及產生最終聲音輸出之多種認知功能的複雜過程。」

The senior author of the study is Vinod Menon, PhD, professor of psychiatry and behavioral sciences and director of the Stanford Cognitive and Systems Neuroscience Laboratory.

該項研究資深撰文人是，史丹佛大學精神病學及行為科學教授，兼認知暨系統神經科學實驗室主任，Vinod Menon博士。

he researchers set out to study how levodopa, a common Parkinson’s drug that replaces the dopamine lost from the disease, affects overall cognitive function. They focused on the subthalamic nucleus, a small, pumpkin-seed-shaped region deep within the brain.

此些研究人員著手研究，左旋多巴(一種取代，因疾病失去多巴胺的常見帕金森氏症藥物)如何影響整體認知功能。他們著重於，大腦深處一個南瓜籽狀小區域的丘腦底核。

The subthalamic nucleus is known for its role in inhibiting motor activity, but there are clues to its involvement in other functions. For example, deep brain stimulation, which uses implanted electrodes to stimulate the subthalamic nucleus, has proven to be a powerful way to relieve motor symptoms for Parkinson’s patients — but a common side effect is worsened speech impairment.

丘腦底核，因其在抑制肌肉運動活動上的角色，為人所熟知。不過，有諸多其涉及其他功能的線索。譬如，使用植入電極，來刺激丘腦底核的深部大腦，已被證明會是緩解，帕金森氏症患者肌肉運動症狀的一種有效方法。不過，常見的副作用是言語障礙惡化。

In the new study, 27 participants with Parkinson’s disease and 43 healthy controls, all older than 60, took standard tests of motor and cognitive functioning. The participants with Parkinson’s took the tests while on and off their medication.

As expected, the medication improved motor functioning in the patients, with those having the most severe symptoms improving the most.

在該項新研究中，27名罹患帕金森氏症的參與者及43名健康的對照者(年齡全超過60歲)，接受了肌肉運動及認知功能的標準測試。罹患帕金森症的參與者，在其服藥及停藥時，接受了此些測試。如預期般，在此些患者中，藥物改善了肌肉運動功能。以那些具有最嚴重症狀的患者，改善最多。

The test for cognitive functioning offered a surprise. The test, known as the Symbol Digit Modalities Test, is given in two forms — oral and written. Patients are provided with nine symbols, each matched with a number — a plus sign for the number 7, for example. They are then asked to translate a string of symbols into numbers, either speaking or writing down their answers, depending on the version of the test.

認知功能測試提供了一項驚喜。該測試，被通稱為符號數字模式測試，以口頭及書面兩種形式被施予。患者被提供九個符號，每個符號匹配一個數字。例如，加號對數字7。然後，他們被要求，將一串符號翻譯成數字，取決於測試的版本，不是說出就是寫下，他們的答案。

As a group, the patients’ performance on both versions of the cognitive test was little affected by medication. But taking a closer look, the researchers noticed that the subset of patients who performed particularly poorly on the spoken version of the test without medication improved their spoken performance on the medication. Their written test scores did not change significantly.

儘管一群，患者在兩種版本的認知測試中，表現鮮少受到藥物影響。

不過，更進一步審視，此些研究人員注意到，沒服用藥物，在口語版本測試中，表現特別差的患者子群，在藥物治療中，改善了他們的口語表現。不過，他們的書寫測試情況，並無顯著變化。

“It was quite interesting to find this dissociation between the written and oral version of the same test,” Cai said.

Cai宣稱：「發現同一測試，在書面及口頭版本之間的這種離異狀況，是十分令人感興趣的。」

The dissociation suggested that the medication was not enhancing general cognitive functions such as attention and working memory, but it was selectively improving speech. “Our research unveiled a previously unrecognized impact of dopaminergic drugs on the speech function of Parkinson’s patients,” Menon said.

這種離異狀況暗示，藥物並無增強諸如，注意力及活動記憶等，一般的認知功能。不過，它選擇性改善言語能力。Menon宣稱：「我們的研究揭露了，多巴胺能的藥物，對帕金森氏症患者言語功能，一種先前未被認知的影響。」

Next, the researchers analyzed fMRI brain scans of the participants, looking at how the subthalamic nucleus interacted with brain networks dedicated to various functions, including hearing, vision, language and executive control. They found that different parts of the subthalamic nucleus interacted with different networks.

接下來，此些研究人員分析了，這些參與者之功能性磁共振造影(fMRI：functional Magnetic Resonance Imaging)的腦部掃描，探究丘腦底核與負責，包括聽力、視覺、語言及執行控制等，各種功能之大腦網絡的相互作用。他們發現，丘腦底核的不同部分與不同的網絡相互作用。

In particular, they discovered that improvements on the oral version of the test correlated with better functional connectivity between the right side of the subthalamic nucleus and the brain’s language network.

特別是，他們發現了，口語版本測試的改善和，在丘腦底核右側與大腦的語言網絡之間，更佳的功能連結相關聯。

Using a statistical model, they could even predict a patient’s improvement on the oral test based on changes in their brain’s functional connectivity.

使用統計模型，他們甚至能根據，於患者大腦功能連結的變化，預測患者在口語測試上的改善。

“Here we’re not talking about an anatomical connection,” Cai explained. Rather, functional connectivity between brain regions means the activity in these regions is closely coordinated, as if they are talking to each other.

Cai解釋：「在此，我們不是談論一種，解剖學上的聯結。」反而是，在大腦區域之間，意味著，於此些區域中之活動，如同它們互相交談般，密切協調的功能連結。

“We discovered that these medications influence speech by altering the functional connectivity between the subthalamic nucleus and crucial language networks,” Menon said. “This insight opens new avenues for therapeutic interventions tailored specifically to improve speech without deteriorating other cognitive abilities.”

Menon宣稱：「我們發現，此些藥物藉由改變，在丘腦底核與關鍵語言網路之間的功能連結，來影響言語能力。此深入瞭解，為專門用於改善言語能力，而不惡化其他認知能力的治療介入，開啟了新途徑。」

This newly identified interaction between the subthalamic nucleus and the language network could serve as a biological indicator of speech behavior — in Parkinson’s as well as other speech disorders like stuttering.

該種新近發現之丘腦底核與語言網絡之間的相互作用，除了如口吃等，其他言語障礙之外，在帕金森氏症中，也可能充當一種，言語行為的生物指標。

Such a biomarker could be used to monitor treatment outcomes and inspire new therapies. “Of course, you can directly observe the outcome of a medication by observing behavior, but I think to have a biomarker in the brain will provide more useful information for the future development of drugs,” Cai said. 

這種生物標記可能被用來，監測治療結果及導致新療法。Cai宣稱：「當然，能藉由觀察行為，來直接觀察藥物的結果。不過我認為，在大腦中，有生物標記能為未來藥物的開發，提供更多有用的資訊。」

The findings also provide a detailed map of the subthalamic nucleus, which could guide neurosurgeons performing deep brain stimulation in avoiding damage to an area critical to speech function.

此些研究發現也提供了一種，可能指導神經外科醫生們，在進行深部大腦刺激，避免對言語功能至關重要區域，造成損傷之丘腦底核的詳細圖。

“By identifying key neural maps and connections that predict speech improvement, we can craft more effective treatment plans that are both precise and personalized for Parkinson’s disease patients,” Menon said.

Menon宣稱：「藉由識別，預測改善言語能力的關鍵神經圖及連結。我們能為帕金森氏症患者精心制定，兼具精準且個人化的更有效治療計劃。」

The study received funding from the National Institutes of Health  and the Alzheimer’s Association.

該項研究獲得了，來自美國國家衛生研究院及阿茲海默症協會的資助。

網址：https://med.stanford.edu/news/all-news/2024/05/parkinsons-speech.html

翻譯：許東榮