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Fulltext Explainable artificial intelligence for searching frequency characteristics in Parkinson's disease tremor

Lee RE, Chan PY

Sci Rep, 2023 Oct 30;13(1):18622.
PMID: 37903843 DOI: 10.1038/s41598-023-45802-z

The distinction between Parkinson's disease (PD) and essential tremor (ET) tremors is subtle, posing challenges in differentiation. To accurately classify the PD and ET, BiLSTM-based recurrent neural networks are employed to classify between normal patients (N), PD patients, and ET patients using accelerometry data on their lower arm (L), hand (H), and upper arm (U) as inputs. The trained recurrent neural network (RNN) has reached 80% accuracy. The neural network is analyzed using layer-wise relevance propagation (LRP) to understand the internal workings of the neural network. A novel explainable AI method, called LRP-based approximate linear weights (ALW), is introduced to identify the similarities in relevance when assigning the class scores in the neural network. The ALW functions as a 2D kernel that linearly transforms the input data directly into the class scores, which significantly reduces the complexity of analyzing the neural network. This new classification method reconstructs the neural network's original function, achieving a 73% PD and ET tremor classification accuracy. By analyzing the ALWs, the correlation between each input and the class can also be determined. Then, the differentiating features can be subsequently identified. Since the input is preprocessed using short-time Fourier transform (STFT), the differences between the magnitude of tremor frequencies ranging from 3 to 30 Hz in the mean N, PD, and ET subjects are successfully identified. Aside from matching the current medical knowledge on frequency content in the tremors, the differentiating features also provide insights about frequency contents in the tremors in other frequency bands and body parts.

Matched MeSH terms: Essential Tremor*
Comparison of posterior subthalamic area deep brain stimulation for tremor using conventional landmarks versus directly targeting the dentatorubrothalamic tract with tractography

Low HL, Ismail MNBM, Taqvi A, Deeb J, Fuller C, Misbahuddin A

Clin Neurol Neurosurg, 2019 Oct;185:105466.
PMID: 31466022 DOI: 10.1016/j.clineuro.2019.105466

OBJECTIVE: To compare posterior subthalamic area deep brain stimulation (PSA-DBS) performed in the conventional manner against diffusion tensor imaging and tractography (DTIT)-guided lead implantation into the dentatorubrothalamic tract (DRTT).
PATIENTS AND METHODS: Double-blind, randomised study involving 34 patients with either tremor-dominant Parkinson's disease or essential tremor. Patients were randomised to Group A (DBS leads inserted using conventional landmarks) or Group B (leads guided into the DRTT using DTIT). Tremor (Fahn-Tolosa-Marin) and quality-of-life (PDQ-39) scores were evaluated 0-, 6-, 12-, 36- and 60-months after surgery.
RESULTS: PSA-DBS resulted in marked tremor reduction in both groups. However, Group B patients had significantly better arm tremor control (especially control of intention tremor), increased mobility and activities of daily living, reduced social stigma and need for social support as well as lower stimulation amplitudes and pulse widths compared to Group A patients. The better outcomes were sustained for up to 60-months from surgery. The active contacts of Group B patients were consistently closer to the centre of the DRTT than in Group A. Speech problems were more common in Group A patients.
CONCLUSION: DTIT-guided lead placement results in better and more stable tremor control and fewer adverse effects compared to lead placement in the conventional manner. This is because DTIT-guidance allows closer and more consistent placement of leads to the centre of the DRTT than conventional methods.

Matched MeSH terms: Essential Tremor/physiopathology; Essential Tremor/therapy*
Gamma knife thalamotomy for disabling tremor: a blinded evaluation

Lim SY, Hodaie M, Fallis M, Poon YY, Mazzella F, Moro E

Arch. Neurol., 2010 May;67(5):584-8.
PMID: 20457958 DOI: 10.1001/archneurol.2010.69

Gamma knife thalamotomy (GKT) has been used as a therapeutic option for patients with disabling tremor refractory to medications. Impressive improvement of tremor has been reported in the neurosurgical literature, but the reliability of such data has been questioned.

Matched MeSH terms: Essential Tremor/pathology; Essential Tremor/physiopathology; Essential Tremor/surgery*
Neuropharmacological potentials of β-carboline alkaloids for neuropsychiatric disorders

Ayipo YO, Mordi MN, Mustapha M, Damodaran T

Eur J Pharmacol, 2021 Feb 15;893:173837.
PMID: 33359647 DOI: 10.1016/j.ejphar.2020.173837

Neuropsychiatric disorders are diseases of the central nervous system (CNS) which are characterised by complex pathomechanisms that including homeostatic failure, malfunction, atrophy, pathology remodelling and reactivity anomaly of the neuronal system where treatment options remain challenging. β-Carboline (βC) alkaloids are scaffolds of structurally diverse tricyclic pyrido[3,4-b]indole alkaloid with vast occurrence in nature. Their unique structural features which favour interactions with enzymes and protein receptor targets account for their potent neuropharmacological properties. However, our current understanding of their biological mechanisms for these beneficial effects, especially for neuropsychiatric disorders is sparse. Therefore, we present a comprehensive review of the scientific progress in the last two decades on the prospective pharmacology and physiology of the βC alkaloids in the treatment of some neuropsychiatric conditions such as depression, anxiety, Alzheimer's disease, Parkinson's disease, brain tumour, essential tremor, epilepsy and seizure, licking behaviour, dystonia, agnosia, spasm, positive ingestive response as demonstrated in non-clinical models. The current evidence supports that βC alkaloids offer potential therapeutic agents against most of these disorders and amenable for further drug design.

Matched MeSH terms: Essential Tremor
Fulltext Functional Antagonism of Sphingosine-1-Phosphate Receptor 1 Prevents Harmaline-Induced Ultrastructural Alterations and Caspase-3 Mediated Apoptosis

Dahmardeh N, Shabani M, Basiri M, Kalantaripour TP, Asadi-Shekaari M

Malays J Med Sci, 2019 Jul;26(4):28-38.
PMID: 31496891 DOI: 10.21315/mjms2019.26.4.4

Background: There is a meaningful necessity for a targeted therapy of essential tremor (ET), as medications have not been developed specifically for ET. For nearly a century, many drugs have been applied in the treatment of tremor but the drug treatment of ET remains still unknown. Some potential therapeutic factors such fingolimod (FTY720) can be effectively used to treat ET in animals. In the present research, the effect of FTY720, the immunomodulatory sphingosine 1-phosphate (S1P) analog, on degeneration of cerebellar and olivary neurons induced by harmaline in male rats was investigated.
Methods: The animals were allotted into control dimethyl sulfoxide (DMSO), saline + harmaline [30 mg/kg, intraperitoneally, (i.p.)], harmaline + FTY720 (1 mg/kg, i.p, 1 h and 24 h before harmaline injection) groups (n = 10). The cerebellum and inferior olive nucleus (ION) were studied for neuronal degeneration using immunohistochemistry (IHC) and ultrastructural study by transmission electron microscopy (TEM) techniques.
Results: Harmaline caused neuronal cell loss, caspase-3 mediated apoptosis, astrocytosis and ultrastructural changes in cerebellar Purkinje cells and inferior olive neurons. FTY720 exhibited neuroprotective effects on cerebellar Purkinje cells and inferior olivary neurons.
Conclusion: These results suggest that FTY720 has potential efficacy for prevention of ET neurodegeneration and astrocytosis induced by harmaline in male rats.

Matched MeSH terms: Essential Tremor