Journal of Depression and Anxiety
Open Access

Peripheral Somatosensory Stimulation in the Treatment of Depression and Anxiety: A Clinical Trial

Leslie Ann Nussbaum^*, Tariq Mohammed Janjua, Jon Michael Pederson and Eric Spencer Nussbaum ^*Correspondence: Leslie Ann Nussbaum, Department of Medicine, National Brain Aneurysm and Tumor Center, 3033 Excelsior Blvd Ste 495, Minneapolis, Minnesota, United States of America, Email:

Author info »

Abbreviations

PSS: Peripheral Somatosensory Stimulation; GAD: General Anxiety Disorder; PHQ: Patient Health Questionnaire; CLMM: Cumulative Link Mixed Model; IQR: Interquartile Ranges; CI: Confidence Intervals

Introduction

Depression and anxiety are extremely common disorders which result in a tremendous societal burden in terms of impaired quality of life, disability, medical costs and unemployment [1,2]. It has been suggested that these conditions may be associated with impaired sensory processing, suggesting that sensory stimulation could be useful as a potential therapeutic option [3-8]. Peripheral somatosensory stimulation therapy is a non-invasive technique which may be beneficial to patients with a variety of neurological disorders. The current trial explores the use of PSS of the hand which has significant cortical sensory representation in the human brain, as a possible mechanism to improve the symptoms of anxiety and depression [9-12].

Materials and Methods

Study description

NeuroGlove is a non-invasive device that provides PSS stimulation in the form of pneumatic puffs of air directed at the volar surface of the distal forearm, the palm and the fingers. This study was designed as a prospective, single center trial enrolling ten patients to explore the effect of PSS therapy on symptoms and quality-of-life measures in patients with anxiety and depression. Men and women between the ages of 18 and 85 years with an active diagnosis of anxiety and depression who were able to provide informed consent were considered eligible for trial enrollment. Patients who were unable to comprehend or follow instructions or unable to use the device due to physical limitations of the upper extremity including fracture, joint deformity, severe spasticity/contracture or skin breakdown were excluded from participation.

Device use

Subjects were instructed to use the device at home for 1 hour of therapy per day (30 minutes using each hand) for 4 weeks. Subjects were directed to synchronize their breathing to the firing (on/off cycle) of the machine to encourage relaxation during device use. At the conclusion of the trial, compliance was determined based on patient reporting and using an internal computerized system that allowed the investigators to track device use during the course of the trial.

Patient evaluation and statistical methods

Patient response to treatment was evaluated using 3 different surveys. Survey 1 focused on patient satisfaction with the treatments and overall psychological well-being survey 2 was designed to evaluate severity of anxiety symptoms based on the General Anxiety Disorder (GAD)-7 scale (Tables 1 and 2). Survey 3 examined symptoms of depression based on the Patient Health Questionnaire-9 (PHQ) (Table 3). Patients completed survey 1 at weeks 1, 2 and 4 and completed surveys 2 and 3 at baseline and at the conclusion of the trial. Survey responses were based on a 5-pt ordinal scale. Change from baseline anxiety and depression scores were analyzed using Cumulative Link Mixed Models (CLMMs).

Table 1: Questions from survey 1-patient satisfaction questionnaire.

Table 2: Questions from survey 2 General Anxiety Disorder (GAD)-7 anxiety questionnaire.

Table 3: Questions from survey 3 Patient Health Questionnaire (PHQ)-9 depression questionnaire.

To summarize overall severity of patient status, anxiety was considered minimal (Total scores 0-4), mild (Total scores 5-9), moderate (Total scores 10-14) or severe (Total scores 15-21). Depression was graded as minimal (Total scores 0-4), mild (Total scores 5-9), moderate (Total scores 10-14), moderately severe (Total scores 15-19) or severe (Total scores 20-27).

For survey 1, simple descriptive statistics were calculated for individual scores at each time point, including median and Interquartile Ranges (IQR). A composite score of all questions using the pooled median value of patient-specific survey questions was also generated and compared between patient visits. Additionally, for in-text summaries, scores were trichotomized as ≥ 4 (positive), 3 (neutral) and <2 (negative). For trichotomized scores, counts and percentage of total were calculated.

A CLMM was used to determine the influence of time on ordinal response scores representing user satisfaction. The main CLMM was fitted using the CLMM function with the ordinal user satisfaction scores modeled as a function of time (Week) and accounting for random effects by including a subject-specific random intercept. Laplace approximation was employed to estimate the model parameters due to its suitability for handling ordinal response data. A null model was then fitted by excluding the time variable, providing a reference against which the main model could be compared. A likelihood ratio test was then performed to assess the significance of including the time variable in the main model compared to the null model, and a two-sided p-value was extracted.

For surveys 2 and 3 changes in ordinal response scores were assessed from patient-specific matched pairs using Wilcoxon’s signed-rank test to determine if there were significant improvements from baseline to week 4. A composite score of all questions using the pooled median value of patient-specific survey questions was also generated and compared between baseline and week 4. Effect sizes from Wilcoxon’s signed rank tests were reported as the median of differences alongside approximates of the 95% confidence interval. Since this nonparametric test works with ranks, it is typically not possible to derive a confidence interval with exactly 95% confidence; instead, the closest approximate was calculated, corresponding to true Confidence Intervals (CIs) calculated with 97.85% confidence; for simplicity these are reported as 95% CIs in text.

To formally analyze overall cumulative probability of improved scores across measurement times, we employed a CLMM with a logit link function. The model was specified with the following formula using the CLMM function in the ‘ordinal’ package for R: Score ～Week+(1|Subject)

Where, ‘score’ represents individual ordinal-scale responses, ‘Visit’ is the predictor variable of interest (baseline or week 4) and ‘(1|Subject)’ indicates the inclusion of random intercepts for individual subjects to account for within-subject variability. Laplace approximation was employed to estimate the model parameters. Predicted probabilities and 95% CIs for each score at a given time point were extracted from the model. Overall effect sizes from the CLMM model are reported as cumulative odds ratios.

Simple descriptive statistics were also calculated, including median and Interquartile Range (IQRs). Additionally, for in-text summaries, scores were dichotomized as ≤ 1 (positive) or >1 (negative). Bar plots were used to visually show overall odds of improved anxiety and depression outcomes and line plots were generated to show patient-specific results across time points.

Software

All analyses were conducted in RStudio (2023.06.2 Build 561), running on R version 4.2.2. CLMM analyses were performed using the ‘ordinal’ package (version 2022.16). Figures were generated using the ‘ggplot2’ package (version 3.4.0).

Results

Ten patients with a formal diagnosis and active symptoms of depression and anxiety were consented and enrolled in the trial. There were 8 women and two men; mean age was 55.8 ± 17.1 (range 29 to 75 years). All patients completed the trial. Compliance with device use was greater than 92% based on self-reporting and internal control checks at the conclusion of the trial. No patient reported an adverse event related to use of the device. All patients reported enjoying using the device and wished to keep the device at the conclusion of the trial. Two patients complained that the air was cool on their hand; others found the temperature relaxing.

Except for 1 patient who failed to complete survey 1 at Week 4, patients completed each of the surveys each week. At baseline, 1 patient had overall mild anxiety, 6 had moderate anxiety and 3 had severe anxiety. Regarding overall baseline depression scores, 1 had minimal depression, 3 had mild depression, 3 had moderate-severe depression, and 3 had severe depression.

Survey 1

Patient satisfaction: At last available follow-up, all patients (100%) had positive scores (scores 4 and 5) for wanting to use the device again (Q4), wanting to use the device in their home (Q5), recommending the device to family and friends (Q6), and having meaningful improvement in depression and anxiety symptoms (Q8). Regarding feelings of ease of use (Q1), relaxation (Q2) and positive feelings (Q7), 9 out 10 patients (90%) showed positive scores. Eight out of 10 (80%) patients reported enjoying using the device.

The pooled median score at week 1 was 4 (IQR: 4-4, min-max: 2-5) compared to 4 (IQR: 4-5, min-max: 3-5) at week 4, suggesting a typically positive outcome and slightly improved overall score over time (p<0.001; Table 4). The question that had the largest upward trend from week 1 (Q8) assessed improvement in depression and anxiety symptoms (Q8), showing a statistically significant improvement by week 4 (p<0.001). Other questions which exhibited time-dependent trends for improvement were those regarding relaxation (Q2), enjoying using the device (Q3) and wanting to use the device again (Q4). Other individual questions did not demonstrate statistically significant time-dependent improvements.

Table 4: Summary of survey 1 (patient satisfaction) responses across measurement times.

Survey 2

Anxiety symptoms: By week 4, all ten patients (100%) had no symptoms or mild symptoms (0 and 1) for being restless (Q5), becoming easily annoyed or irritable (Q6), and feeling afraid that something awful might happen (Q7). Regarding feelings nervousness/being on edge (Q1), inability to control worrying (Q3) and trouble relaxing (Q4), 9/10 patients (90%) reported mild to no symptoms. Eight out of 10 patients (80%) reported mild to no symptoms regarding worrying about too many different things (Q3).

Compared to baseline, patients had statistically significant improvements for all individual questions by week 4. The composite score was substantially improved from baseline, with an overall median score of 2 (IQR: 1.75-2.25) at baseline compared to 0 (IQR: 0-1) by week 4 (MD=-1.5 (95% CI: -1; -3), p=0.004; Table 5). Overall, the predicted probability of obtaining the best outcome (score=0) was 9% at baseline vs. 64% by week 4 (Table 6). Conversely, the predicted probability of obtaining the worst outcome (score=3) was 30% at baseline vs. 2% at week 4. The overall cumulative odds ratio was 19.3 (p<0.001), suggesting that on average, the odds of moving from one score to a lower (improved) score at week 4 compared to the baseline are 19.3 times higher. Overall likelihood of improved anxiety symptoms and patient-specific trends are displayed in Figure 1.

Table 5: Summary of survey 2 (GAD-7 anxiety) responses at baseline and at week 4.

Table 6: Cumulative link mixed model results of overall improvement in anxiety symptoms.

Figure 1: Change from baseline severity of anxiety symptoms. Relative odds of improved outcomes from baseline obtained from a CLMM model, patient specific pooled median scores at baseline and at study end.

Survey 3

Depression symptoms: By week 4, all ten patients (100%) reported being completely free symptoms (score=0) regarding moving/ speaking too slowly or being fidgety/restless (Q8). All ten patients (100%) reported positive scores (0 or 1), for little interest in activities (Q1), poor appetite or overeating (Q5), feeling bad about oneself (Q6), trouble concentrating (Q7), and thoughts about being better off dead or self-harm (Q9). Regarding feeling down, depressed, or hopeless (Q2), trouble falling/staying asleep or sleeping too much (Q3) and feeling tired or having little energy (Q4), 9/10 patients (90%) reported mild to no symptoms.

Patients had statistically significant improvements for the majority individual questions by week 4 (5/9, 67%). Although not statistically significant, patients had numerically improved scores regarding poor appetite or overeating (Q5), feeling bad about oneself (Q6), and moving/speaking too slowly or being fidgety/ restless (Q8) by week 4. For each of these questions, patients typically had mild or no symptoms, which may explain the lack of significant improvement. Regarding thoughts of being better off dead or self-harm, only 1 patient reported symptoms at baseline; this patient had improved score by week 4 (3 vs. 1), and all other patients reported no symptoms at week 4.

The composite score was substantially improved from baseline, with an overall median score of 2 (IQR: 2-3) at baseline compared to 0 (IQR: 0-0.25) by week 4 (MD=-2.0 (95% CI: 0; -3), p=0.016; Table 7), signaling typically moderate-severe depression at baseline compared vs. typically minimal to no symptoms by week 4. Overall, the predicted probability of obtaining the best outcome (score=0) was 25% at baseline vs. 83% by week 4. Conversely, the predicted probability of obtaining the worst outcome (score=3) was 31% at baseline vs. 3% at week 4 (Table 8). The overall cumulative odds ratio was 15.1 (p<0.001), suggesting that on average, the odds of moving from one score to a lower (improved) score at week 4 compared to the baseline are 15.1 times higher. Overall likelihood of improved anxiety symptoms and patient-specific trends are displayed in Figure 2.

Table 7: Summary of survey 3 (PHQ-9 patient depression questionnaire) responses at baseline and at week 4.

Table 8: Cumulative link mixed model results for overall improvement in depression symptoms.

Figure 2: Change from baseline severity of depression symptoms. Relative odds of improved outcomes from baseline obtained from a CLMM model, patient specific pooled median scores at baseline and at study end.

Discussion

A variety of physiological alterations within the brain have been associated with anxiety and depression and increasing evidence suggests that impaired sensory processing may play a critical role in these disorders [3-8]. Ayres suggested that sensory processing forms a significant basis for an individual’s physiological state [13]. Interestingly, various sensory inputs have been shown to impact symptoms in patients with depression and anxiety [14-21]. Auditory stimulation with music, olfactory stimulation with particular odors and gustatory stimulation with particular foods have all been shown to improve mood and relieve anxiety [14-17]. Transcranial magnetic stimulation and vagal nerve stimulation have also been used to ameliorate anxiety and depressive disorders [18-21]. Based on this, we hypothesized that tactile PSS might represent a straightforward therapeutic option for these conditions.

In rodent models, PSS has been shown to improve neurological outcomes following ischemic injury and to limit or even prevent stroke when applied early enough [22-24]. The mechanism for this protection remains unclear but may include enhanced neuronal reorganization encouraging neuronal recovery and/or improved regional cerebral perfusion through the recruitment of local collateral blood supply [25]. Preliminary clinical experience has suggested that PSS can improve recovery and rehabilitation in stroke survivors [26-35]. Interestingly, similar benefits have been demonstrated in patients with Parkinson’s disease, and PSS has also shown promise following traumatic brain injury and in inflammatory, auto-immune conditions such as multiple sclerosis [36-41]. Our previous work has demonstrated significant improvement in symptoms of post-traumatic stress disorder with the use of PSS [42].

In this study, we encountered a significant early response to PSS treatment as evidenced by the improvement in symptoms just one week after initiating therapy. This benefit appeared to be sustained and to further increase over the course of the study. Interestingly, multiple patients reported that PSS helped them relax and spontaneously noted an improvement in their ability to fall and remain asleep, a parameter we had not originally included in our assessment.

In regard to satisfaction with the treatment and overall sense of well-being, patients demonstrated the greatest improvement regarding depression/anxiety symptoms, relaxation, enjoying using the device and wanting to use the device again. The pooled median scores on survey 1 demonstrated significant and time-dependent overall improvement. No patients demonstrated negative survey responses by the week 4 survey.

In regard to anxiety symptoms, patients demonstrated unanimous improvement in anxiety symptoms by week 4, with all individual questions demonstrating significant improvement and composite scores substantially improved from baseline. Overall results demonstrated that patients had moderate-severe anxiety symptoms at baseline compared to minimal or no symptoms by week 4. Patients demonstrated unanimous improvement in depression symptoms by week 4, with the majority of individual questions demonstrating significant improvement and composite scores substantially improved from baseline. Results from survey 3 suggest that, on average, patients typically had moderate-severe depression symptoms at baseline compared to minimal or no symptoms by week 4. It is interesting to note that anxiety symptoms improved to a slightly greater degree than depressive symptoms, although patients reported significant improvement in both areas over the course of the trial.

Conclusion

We describe the results of a clinical trial evaluating the impact of one month of treatment with PSS on symptoms in patients with a diagnosis of depression and anxiety. All patients completed the trial and all appeared to benefit from the therapy. The improvement in symptomatology was generally apparent at one week of device use and was sustained and typically increased through the course of the trial. A significant reduction in both anxiety and depression symptoms was achieved when comparing baseline (pre-trial) and 4-week (post-trial) assessment using the GAD-7 and PHQ-9 scales. We suggest that further investigation into the potential use of PSS in the treatment of patients with depression and anxiety is warranted.

Limitations

The main limitations of our study are the small sample size and lack of an active control group. Data are also limited only to self- reported survey questions and may not capture other clinically important outcomes. Nevertheless, this trial was meant to evaluate in preliminary fashion the potential usefulness of PSS in the treatment of patients with anxiety and depression, potentially forming the basis for a larger study.

Declarations

Drs. Leslie and Eric Nussbaum are shareholders in NeuroGlove, LLC. The author declares that there has been no conflict of interests with any individual or organization in the conduct of this study and further declares that no funding has been received from anywhere for this study.

References

1. Johnston KM, Powell LC, Anderson IM, Szabo S, Cline S. The burden of treatment-resistant depression: a systematic review of the economic and quality of life literature. J Affect Disord. 2019;242:195-210.

   [Crossref] [Google Scholar] [PubMed]

2. Rehm J, Shield KD. Global burden of disease and the impact of mental and addictive disorders. Curr Psychiatry Rep. 2019;21:1-7.

   [Crossref] [Google Scholar] [PubMed]

3. Engel-Yeger B, Dunn W. The relationship between sensory processing difficulties and anxiety level of healthy adults. Br J Occup Ther. 2011;74(5):210-216.

   [Crossref] [Google Scholar]

4. Liljas AE, Jones A, Cadar D, Steptoe A, Lassale C. Association of multisensory impairment with quality of life and depression in english older adults. JAMA Otolaryngol Head Neck Surg. 2020;146(3):278-285.

   [Crossref] [Google Scholar] [PubMed]

5. Fitzgerald PJ. Gray colored glasses: is major depression partially a sensory perceptual disorder? J Affect Disord. 2013;151(2):418-422.

   [Crossref] [Google Scholar] [PubMed]

6. Acevedo BP, Aron EN, Aron A, Sangster MD, Collins N, Brown LL. The highly sensitive brain: an fMRI study of sensory processing sensitivity and response to others' emotions. Brain Behav. 2014;4(4):580-594.

   [Crossref] [Google Scholar] [PubMed]

7. Canbeyli R. Sensorimotor modulation of mood and depression: an integrative review. Behav Brain Res. 2010;207(2):249-264.

   [Crossref] [Google Scholar] [PubMed]

8. Canbeyli R. Sensory stimulation via the visual, auditory, olfactory and gustatory systems can modulate mood and depression. Eur J Neurosci. 2022;55(1):244-263.

   [Crossref] [Google Scholar] [PubMed]

9. Celnik P, Hummel F, Harris-Love M, Wolk R, Cohen LG. Somatosensory stimulation enhances the effects of training functional hand tasks in patients with chronic stroke. Arch Phys Med Rehabil. 2007;88(11):1369-1376.

   [Crossref] [Google Scholar] [PubMed]

10. Nussbaum HA, Nussbaum ES. Peripheral sensory stimulation for neurological disorders. a novel, non-invasive therapeutic option. review article. J Neurosci Neurol Surg. 2023;13:267-271.

    [Crossref]

11. Pfeifer KJ, Kromer JA, Cook AJ, Hornbeck T, Lim EA, Mortimer BJ, et al. Coordinated reset vibrotactile stimulation induces sustained cumulative benefits in parkinson’s disease. Front Physiol. 2021;12:624317.

    [Crossref] [Google Scholar] [PubMed]

12. Lucente G, Valls-Sole J, Murillo N, Rothwell J, Coll J, Davalos A, et al. Noninvasive brain stimulation and noninvasive peripheral stimulation for neglect syndrome following acquired brain injury. Neuromodulation. 2020;23(3):312-323.

    [Crossref] [Google Scholar] [PubMed]

13. Ayres AJ. Treatment of sensory integrative dysfunction. Am J Occup Ther. 1972;19(2):88.

    [Crossref] [Google Scholar] [PubMed]

14. Aalbers S, Fusar‐Poli L, Freeman RE, Spreen M, Ket JC, Vink AC, et al. Music therapy for depression. Cochrane Database Syst Rev. 2017;11(11):CD004517.

    [Crossref] [Google Scholar] [PubMed]

15. Al-Karawi D, Jubair L. Bright light therapy for nonseasonal depression: meta-analysis of clinical trials. J Affect Disord. 2016;198:64-71.

    [Crossref] [Google Scholar] [PubMed]

16. Matsubara E, Ohira T. Inhalation of Japanese cedar (Cryptomeria japonica) wood odor causes psychological relaxation after monotonous work among female participants. Biomed Res. 2018;39(5):241-249.

    [Crossref] [Google Scholar] [PubMed]

17. Meier BP, Noll SW, Molokwu OJ. The sweet life: the effect of mindful chocolate consumption on mood. Appetite. 2017;108:21-27.

    [Crossref] [Google Scholar] [PubMed]

18. Andrade P, Noblesse LH, Temel Y, Ackermans L, Lim LW, Steinbusch HW, et al. Neurostimulatory and ablative treatment options in major depressive disorder: a systematic review. Acta Neurochir. 2010;152:565-577.

    [Crossref] [Google Scholar] [PubMed]

19. Askalsky P, Iosifescu DV. Transcranial photobiomodulation for the management of depression: current perspectives. Neuropsychiatr Dis Treat. 2019;2019:3255-3272.

    [Crossref] [Google Scholar] [PubMed]

20. Conway CR, Xiong W. The mechanism of action of vagus nerve stimulation in treatment-resistant depression: current conceptualizations. Psychiatr Clin North Am. 2018;41(3):395-407.

    [Crossref] [Google Scholar] [PubMed]

21. Tao Q, Yang Y, Yu H, Fan L, Luan S, Zhang L, et al. Anatomical connectivity-based strategy for targeting transcranial magnetic stimulation as antidepressant therapy. Front Psychiatry. 2020;11:236.

    [Crossref] [Google Scholar] [PubMed]

22. Lay CC, Jacobs N, Hancock AM, Zhou Y, Frostig RD. Early stimulation treatment provides complete sensory‐induced protection from ischemic stroke under isoflurane anesthesia. Eur J Neurosci. 2013;38(3):2445-2452.

    [Crossref] [Google Scholar] [PubMed]

23. Frostig RD, Lay CC, Davis MF. A rat’s whiskers point the way toward a novel stimulus-dependent, protective stroke therapy. Neuroscientist. 2013;19(3):313-328.

    [Crossref] [Google Scholar] [PubMed]

24. Hancock AM, Lay CC, Davis MF, Frostig RD. Sensory stimulation-based complete protection from ischemic stroke remains stable at 4 months post-occlusion of MCA. J Neurol Disord. 2013;1(4):135.

    [Crossref] [Google Scholar] [PubMed]

25. Nussbaum ES, Janjua TM, Lowary J, Defillo A, Myers MT, Nussbaum LA. Peripheral sensory stimulation of the hand in the treatment of stroke. a preliminary study of safety and effectiveness.

    [Google Scholar]

26. Conforto AB, Cohen LG, Santos RL, Scaff M, Marie SK. Effects of somatosensory stimulation on motor function in chronic cortico-subcortical strokes. J Neurol. 2007;254:333-339.

    [Crossref] [Google Scholar] [PubMed]

27. Conforto AB, Dos Anjos SM, Bernardo WM, Silva AA, Conti J, Machado AG, et al. Repetitive peripheral sensory stimulation and upper limb performance in stroke: a systematic review and meta-analysis. Neurorehabil Neural Repair. 2018;32(10):863-871.

    [Crossref] [Google Scholar] [PubMed]

28. Conrad MO, Scheidt RA, Schmit BD. Effects of wrist tendon vibration on targeted upper-arm movements in poststroke hemiparesis. Neurorehabil Neural Repair. 2011;25(1):61-70.

    [Crossref] [Google Scholar] [PubMed]

29. Maeda M, Mutai H, Toya Y, Maekawa Y, Hitai T, Katai S. Effects of peripheral nerve stimulation on paralysed upper limb functional recovery in chronic stroke patients undergoing low-frequency repetitive transcranial magnetic stimulation and occupational therapy: A pilot study. Hong Kong J Occup Ther. 2020;33(1):3-11.

    [Crossref] [Google Scholar] [PubMed]

30. Nasrallah FA, Mohamed AZ, Yap HK, Lai HS, Yeow CH, Lim JH. Effect of proprioceptive stimulation using a soft robotic glove on motor activation and brain connectivity in stroke survivors. J Neural Eng. 2022;18(6):066049.

    [Crossref] [Google Scholar] [PubMed]

31. Seo NJ, Enders LR, Fortune A, Cain S, Vatinno AA, Schuster E, et al. Phase I safety trial: Extended daily peripheral sensory stimulation using a wrist-worn vibrator in stroke survivors. Transl Stroke Res. 2020;11:204-213.

    [Crossref] [Google Scholar] [PubMed]

32. Seo NJ, Woodbury ML, Bonilha L, Ramakrishnan V, Kautz SA, Downey RJ, et al. Therabracelet stimulation during task-practice therapy to improve upper extremity function after stroke: a pilot randomized controlled study. Phys Ther. 2019;99(3):319-328.

    [Crossref] [Google Scholar] [PubMed]

33. Vatinno AA, Hall L, Cox H, Fluharty A, Taylor C, Wease A, et al. Using subthreshold vibratory stimulation during poststroke rehabilitation therapy: A case series. OTJR. 2022;42(1):30-39.

    [Crossref] [Google Scholar] [PubMed]

34. Carrico C, Chelette KC, Westgate PM, Salmon-Powell E, Nichols L, Sawaki L. A randomized trial of peripheral nerve stimulation to enhance modified constraint-induced therapy after stroke. Am J Phys Med Rehabil. 2016;95(6):397.

    [Crossref] [Google Scholar] [PubMed]

35. Carrico C, Chelette KC, Westgate PM, Powell E, Nichols L, Fleischer A, et al. Nerve stimulation enhances task-oriented training in chronic, severe motor deficit after stroke: a randomized trial. Stroke. 2016;47(7):1879-1884.

    [Crossref] [Google Scholar] [PubMed]

36. Pfeifer KJ, Cook AJ, Yankulova JK, Mortimer BJ, Erickson-DiRenzo E, Dhall R, et al. Clinical efficacy and dosing of vibrotactile coordinated reset stimulation in motor and non-motor symptoms of parkinson's disease: a study protocol. Front Neurol. 2021;12:758481.

    [Crossref] [Google Scholar] [PubMed]

37. Tass PA. Vibrotactile coordinated reset stimulation for the treatment of parkinson's disease. Neural Regen Res. 2022;17(7):1495.

    [Crossref] [Google Scholar] [PubMed]

38. Tramontano M, Morone G, de Angelis S, Casagrande Conti L, Galeoto G, Grasso MG. Sensor-based technology for upper limb rehabilitation in patients with multiple sclerosis: A randomized controlled trial. Restor Neurol Neurosci. 2020;38(4):333-341.

    [Crossref] [Google Scholar] [PubMed]

39. Hall KD, Lifshitz J. Diffuse traumatic brain injury initially attenuates and later expands activation of the rat somatosensory whisker circuit concomitant with neuroplastic responses. Brain Res. 2010;1323:161-173.

    [Crossref] [Google Scholar] [PubMed]

40. Lew HL, Weihing J, Myers PJ, Pogoda TK, Goodrich GL. Dual Sensory Impairment (DSI) in Traumatic Brain Injury (TBI)–An emerging interdisciplinary challenge. NeuroRehabilitation. 2010;26(3):213.

    [Crossref] [Google Scholar] [PubMed]

41. Zheng ZT, Dong XL, Li YD, Gao WW, Zhou Y, Jiang RC, et al. Electrical stimulation improved cognitive deficits associated with traumatic brain injury in rats. Brain Behav. 2017;7(11):e00667.

    [Crossref] [Google Scholar] [PubMed]

42. Janjua TM, Pederson JM, Nussbaum ES. Peripheral somatosensory stimulation in the treatment of post-traumatic stress disorder. A clinical trial. J Neurol Dis. 2023;11:58.

    [Google Scholar]