Manipulating facial musculature with functional electrical stimulation as an intervention for major depressive disorder: a focused search of literature for a proposal.

BACKGROUND: Major Depressive Disorder (MDD) is associated with interoceptive deficits expressed throughout the body, particularly the facial musculature. According to the facial feedback hypothesis, afferent feedback from the facial muscles suffices to alter the emotional experience. Thus, manipulating the facial muscles could provide a new "mind-body" intervention for MDD. This article provides a conceptual overview of functional electrical stimulation (FES), a novel neuromodulation-based treatment modality that can be potentially used in the treatment of disorders of disrupted brain connectivity, such as MDD. METHODS: A focused literature search was performed for clinical studies of FES as a modulatory treatment for mood symptoms. The literature is reviewed in a narrative format, integrating theories of emotion, facial expression, and MDD. RESULTS: A rich body of literature on FES supports the notion that peripheral muscle manipulation in patients with stroke or spinal cord injury may enhance central neuroplasticity, restoring lost sensorimotor function. These neuroplastic effects suggest that FES may be a promising innovative intervention for psychiatric disorders of disrupted brain connectivity, such as MDD. Recent pilot data on repetitive FES applied to the facial muscles in healthy participants and patients with MDD show early promise, suggesting that FES may attenuate the negative interoceptive bias associated with MDD by enhancing positive facial feedback. Neurobiologically, the amygdala and nodes of the emotion-to-motor transformation loop may serve as potential neural targets for facial FES in MDD, as they integrate proprioceptive and interoceptive inputs from muscles of facial expression and fine-tune their motor output in line with socio-emotional context. CONCLUSIONS: Manipulating facial muscles may represent a mechanistically novel treatment strategy for MDD and other disorders of disrupted brain connectivity that is worthy of investigation in phase II/III trials.

Use of non-invasive neurostimulation for rehabilitation in functional movement disorders.

Functional movement disorders (FMD) are a subtype of functional neurological disorders which involve abnormal movements and include multiple phenomenologies. There is a growing interest in the mechanism, diagnosis, and treatment of these disorders. Most of the current therapeutic approaches rely on psychotherapy and physiotherapy conducted by a multidisciplinary team. Although this approach has shown good results in some cases, FMD cause a great burden on the health system and other treatment strategies are urgently needed. In this review, we summarize past studies that have applied non-invasive neurostimulation techniques, such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS) and peripheral nerve stimulation as a treatment for FMD. There is an increasing number of studies related to TMS including randomized controlled trials; however, the protocols amongst studies are not standardized. There is only preliminary evidence for the efficacy of non-invasive neuromodulation in reducing FMD symptoms, and further studies are needed. There is insufficient evidence to allow implementation of these techniques in clinical practice.

Utility of transcranial magnetic stimulation in the assessment of spinal cord injury: Current status and future directions.

Comprehensive assessment following traumatic spinal cord injury (SCI) is needed to improve prognostication, advance the understanding of the neurophysiology and better targeting of clinical interventions. The International Standards for Neurological Classification of Spinal Cord Injury is the most common clinical examination recommended for use after a SCI. In addition, there are over 30 clinical assessment tools spanning across different domains of the International Classification of Functioning, Disability, and Health that have been validated and recommended for use in SCI. Most of these tools are subjective in nature, have limited value in predicting neurologic recovery, and do not provide insights into neurophysiological mechanisms. Transcranial magnetic stimulation (TMS) is a non-invasive neurophysiology technique that can supplement the clinical assessment in the domain of body structure and function during acute and chronic stages of SCI. TMS offers a better insight into neurophysiology and help in better detection of residual corticomotor connectivity following SCI compared to clinical assessment alone. TMS-based motor evoked potential and silent period duration allow study of excitatory and inhibitory mechanisms following SCI. Changes in muscle representations in form of displacement of TMS-based motor map center of gravity or changes in the map area can capture neuroplastic changes resulting from SCI or following rehabilitation. Paired-pulse TMS measures help understand the compensatory reorganization of the cortical circuits following SCI. In combination with peripheral stimulation, TMS can be used to study central motor conduction time and modulation of spinal reflexes, which can be used for advanced diagnostic and treatment purposes. To strengthen the utility of TMS in SCI assessment, future studies will need to standardize the assessment protocols, address population-specific concerns, and establish the psychometric properties of TMS-based measurements in the SCI population.

Multi-center, single-blind randomized controlled trial comparing functional electrical stimulation therapy to conventional therapy in incomplete tetraplegia.

Background: Loss of upper extremity function after tetraplegia results in significant disability. Emerging evidence from pilot studies suggests that functional electrical stimulation (FES) therapy may enhance recovery of upper extremity function after tetraplegia. The aim of this trial was to determine the effectiveness of FES therapy delivered by the Myndmove stimulator in people with tetraplegia. Methods: A multi-center, single-blind, parallel-group, two-arm, randomized controlled trial was conducted comparing FES to conventional therapy in adults (≥18 years) with C4-C7 traumatic incomplete tetraplegia between 4 and 96 months post-injury, and with a baseline spinal cord injury independence measure III -self-care (SCIM III-SC) score of ≤10. Participants were enrolled at four SCI-specialized neurorehabilitation centers in the U.S. and Canada. Participants were stratified by center and randomized in a 1:1 ratio to receive either 40 sessions of FES or conventional therapy targeting upper extremities over a 14-week period. Blinded assessors measured SCIM III, Toronto Rehabilitation Institute Hand Function Test, and Graded Redefined Assessment of Strength, Sensibility, and Prehension at baseline, after 20th session, after 40th session or 14 weeks after 1st session, and at 24 weeks after 1st session. The primary outcome measure was change in SCIM III-SC from baseline to end of the treatment. Based on the primary outcome measure, a sample size of 60 was calculated. Seventeen participants' progress in the study was interrupted due to the COVID-19 lockdown. The protocol was modified for these participants to allow them to complete the study. Results: Between June 2019 to August 2021, 51 participants were randomized to FES (n = 27) and conventional therapy (n = 24). Both groups gained a mean of 2 points in SCIM-SC scores at the end of treatment, which was a clinically meaningful change. However, there was no statistically significant difference between the groups on any outcomes. Conclusion: Forty sessions of FES therapy delivered by the MyndMove stimulator are as effective as conventional therapy in producing meaningful functional improvements that persist after therapy is completed. Limitations of this study include the impact of COVID-19 limiting the ability to recruit the target sample size and per-protocol execution of the study in one-third of the participants. Registration: This trial is registered at www.ClinicalTrials.gov, NCT03439319.

Evaluating the efficacy of functional electrical stimulation therapy assisted walking after chronic motor incomplete spinal cord injury: effects on bone biomarkers and bone strength.

OBJECTIVES: To determine the efficacy of functional electrical stimulation therapy assisted walking (FES-T) compared to a conventional aerobic and resistance training (CONV) with respect to bone biomarkers and lower extremity bone strength outcomes among adults with chronic motor incomplete spinal cord injury (SCI). DESIGN: Parallel group randomized controlled trial ( www.clinicaltrials.gov - NCT0020196819). Site: Tertiary academic rehabilitation centre in Canada. METHODS: Adults with chronic (≥18 months) motor incomplete SCI (C2-T12 AIS C-D) were consented and randomized to FES-T or CONV training for 45 minutes thrice-weekly for 4 months. Osteocalcin (OC), ß-cross laps (CTX) and sclerostin were assessed at baseline, and 4 months. Similarly, total hip, distal femur and proximal tibia region bone mineral density (BMD) via DXA (4500A, Hologic Inc. Waltham, MA, USA) and tibia bone quality via pQCT (Stratec XCT-2000, Mezintecknik, Pforzheim, Germany) were assessed at baseline, 4, and 12 months. Between group differences were analyzed using repeated measures general linear models. RESULTS: Thirty-four participants (17 FES-T, 17 CONV) consented and were randomized, 27 participants completed the 4-month intervention and 12-month outcome assessments. Participants in the FES-T arm had a decrease in CTX and a significant increase in OC at intervention completion (P<0.05). Significant biomarker changes were not observed in the CONV group. No within or between group differences from baseline were observed in sclerostin or bone strength. CONCLUSIONS: Four months of FES-T improved bone turnover (increase in OC and decrease in CTX) but not bone strength among individuals with chronic SCI. Future, long term FES-T may augment lower extremity bone strength.