Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of cancer treatment, significantly affecting patients’ quality of life. Current pharmacological treatments are often ineffective or poorly tolerated, necessitating alternative therapeutic approaches. Scrambler Therapy (ST), a non-invasive neuromodulation technique, has shown potential for reducing neuropathic pain, but optimal dosing regimens remain undefined.

This case study aims to evaluate the effectiveness of Scrambler Therapy in reducing pain levels and improving functional status in a patient with chemotherapy-induced peripheral neuropathy.

A single patient diagnosed with CIPN was treated with Scrambler Therapy over a series of sessions. Pain levels and functional status were measured using standardized assessment tools before, during, and after the therapy to evaluate the impact of ST on symptom relief and daily functioning.

After completing the Scrambler Therapy sessions, the patient reported significant reductions in pain intensity and notable improvements in functional status. These improvements were sustained several weeks and months following the therapy, indicating the potential long-term benefits of ST for managing CIPN.

This case study demonstrates the potential of Scrambler Therapy as an effective treatment option for reducing pain and improving functional status in patients with chemotherapy-induced peripheral neuropathy. These findings suggest that ST may provide a promising non-invasive alternative to current treatments for managing neuropathic pain in cancer patients.

Neuromodulation is emerging as a promising intervention for intractable pain syndromes. Despite heterogeneous outcomes in the literature, motor cortex stimulation (MCS) has proven effective in addressing chronic orofacial pain. Painful trigeminal neuropathy (PTN) is characterized by constant facial pain and somatosensory signs. Refractory cases, unresponsive to medical and surgical therapies, significantly impact quality of life and pose socioeconomic challenges. This article presents a retrospective case series of five MCS patients who were treated for refractory PTN in Atlantic Canada.

Since 2021, eight cases of refractory PTN from Atlantic Canada have been recruited. Demographic and clinical characteristics were collected, with primary and secondary outcomes respectively defined as a 50% Visual Analogue Scale (VAS) reduction and a 60% reduction in morphine equivalent dose per day (MED, mg/day) at 12 months post-operation. Pain intensity was assessed preoperatively and at 6- and 12-month follow-ups, along with eating habits, return to work, and global satisfaction.

Five patients with refractory PTN were implanted with MCS, all of whom achieved the primary and secondary outcomes. Preoperatively, mean VAS was 8.4 ± 1.0, reduced to 2.0 ± 1.1 at 12 months post-MCS, corresponding to a 77 ± 13% pain reduction. Average MED/day was reduced by 93 ± 13%, with 60% of participants narcotic-free at 12 months and 80% at 18 months. There were no immediate or delayed complications related to the MCS procedure.

MCS exhibits significant potential for long-term pain relief and reducing opioid consumption in refractory trigeminal pain, emphasizing the necessity for large national multicenter trials.

Binge-eating disorder (BED) is characterized by highly distressing episodes of loss-of-control over-eating. We have examined the use of repetitive transcranial magnetic stimulation (rTMS) for the treatment of people with BED and associated obesity. Such non-invasive brain stimulation (NIBS) techniques are used therapeutically in several psychiatric conditions and there is an associated scientific rationale.

Sixty participants were randomly allocated to receive 20 sessions of neuronavigated 10 Hz rTMS administered to the left dorsolateral prefrontal cortex (dlPFC) or sham treatment. Primary outcomes were the frequency of binge eating episodes (BEE) and the ‘urge to eat’ (craving) evaluated at baseline and end-of-treatment (8 weeks post-randomization). Secondary outcomes included body mass index (BMI), hunger, general and specific eating disorder psychopathology. Follow-up analyses were conducted for most outcomes at 16 weeks post-randomization. Multilevel models were used to evaluate group, time, and group-by-time interactions for the association between rTMS exposure and outcomes.

The real rTMS group (compared with sham treatment), showed a significantly greater decrease in the number of BEE at the end of treatment (Estimated Mean [EM]: 2.41 95% CI: 1.84–3.15 versus EM: 1.45 95% CI: 1.05–1.99, p = 0.02), and at follow-up (EM: 3.79 95% CI: 3–4.78 versus EM: 2.45 95% CI: 1.88–3.17, p = 0.02; group × time interaction analysis p = 0.02). No group differences were found for other comparisons.

rTMS was associated with reduced BEE during and after treatment: it suggests rTMS is a promising intervention for BED.

Novel ultrasound neuromodulation techniques allow therapeutic brain stimulation with unmet precision and non-invasive targeting of deep brain areas. Transcranial pulse stimulation (TPS), a multifrequency sonication technique, is approved for the clinical treatment of Alzheimer’s disease (AD). Here, we present the largest real-world retrospective analysis of ultrasound neuromodulation therapy in dementia (AD, vascular, mixed) and mild cognitive impairment (MCI).

The consecutive sample involved 58 patients already receiving state-of-the-art treatment in an open-label, uncontrolled, retrospective study. TPS therapy typically comprises 10 sessions (range 8–12) with individualized MRI-based target areas defined according to brain pathology and individual pathophysiology. We compared the CERAD-Plus neuropsychological test battery results before and after treatment, with the CERAD Corrected Total Score ( CTS) as the primary outcome. Furthermore, we analyzed side effects reported by patients during the treatment period.

CERAD Corrected Total Score (CTS) significantly improved (p = .017, d = .32) after treatment (Baseline: M = 56.56, SD = 18.56; Post-treatment: M = 58.65, SD = 19.44). The group of top-responders (top quartile) improved even by 9.8 points. Fewer than one-third of all patients reported any sensation during treatment. Fatigue and transient headaches were the most common, with no severe adverse events.

The findings implicate TPS as a novel and safe add-on therapy for patients with dementia or MCI with the potential to further improve current state-of-the-art treatment results. Despite the individual benefits, further randomized, sham-controlled, longitudinal clinical trials are needed to differentiate the effects of verum and placebo.

Visual release hallucinations are perceptual disturbances that occur in individuals who have experienced vision loss. Almost 50 million people worldwide are believed to experience visual release hallucinations, yet they are profoundly underdiagnosed. Although first described within the Charles Bonnet syndrome, the paradigm underlying this syndrome precludes their consideration in many populations, such as those with underlying psychiatric illness or dementia. Consequently, visual release hallucinations have rarely been studied in patients presenting with psychosis. We conducted a scoping review to determine whether visual-release hallucinations occur in psychotic patients.

The PubMed research database was searched from inception through April 2023. Cases were collected reporting on psychotic patients experiencing suspected visual release hallucinations. Individual treatment courses and responses were extracted.

Thirteen cases compiled from 11 different studies were summarized to provide baseline characteristics and overall trends in treatment response. Most patients did not remit from pharmacological management alone. All patients who received reafferentation therapy remitted, though many were not candidates. Almost half of the patients did not achieve remission.

Visual release hallucinations can manifest in psychosis and may contribute to treatment-resistant psychosis among psychiatric populations. A shift in our understanding of visual release hallucinations may aid their recognition in psychotic patients by shifting the focus toward visual release features. Recognizing release features among patients with hallucinatory conditions may open new treatment avenues for managing patients with psychosis. A preliminary screening index for visual release features is provided to support this shift.

Binge eating disorder (BED) is a common and disabling condition, typically presenting with multiple psychiatric and obesity-related comorbidities. Evidence-based treatments are either resource-intensive (psychotherapies) or have side-effects (medications): these achieve remission in around 50% of cases. Novel treatments are needed.

This randomised sham-controlled trial aimed to assess feasibility, acceptability and preliminary efficacy of at-home, self-administered transcranial direct current stimulation (tDCS) and attention bias modification training (ABMT) in adults with binge eating disorder.

Eighty-two participants with binge eating disorder were randomly allocated to real tDCS with ABMT, sham tDCS with ABMT, ABMT only or waitlist control. Intervention groups received ten sessions of their allocated treatment over 2–3 weeks. tDCS (2 mA, 20 min) was self-administered using a bilateral (anode right/cathode left) montage targeting the dorsolateral prefrontal cortex. Outcomes were assessed at baseline, post-treatment and 6-week follow-up.

Prespecified feasibility criteria (recruitment ≥80 participants and retention rate ≥75%) were exceeded, and treatment completion rates were high (98.7%). All interventions reduced binge eating episodes, eating disorder symptoms and related psychopathology between baseline and follow-up, relative to waitlist control (medium-to-large between-group effect sizes for change scores). Small-to-medium effect sizes for change scores favoured real tDCS with ABMT versus comparators, suggesting the verum intervention produces superior outcomes.

At-home, self-administered tDCS with ABMT is feasible and acceptable, and preliminary data on efficacy are promising. This approach could be a useful and scalable alternative or adjunct to established treatments for binge eating disorder. Confirmatory trials can, and should, be pursued.

This study builds on the work by Rehman et al (2022) who argued that transcranial magnetic stimulation (TMS) treatment not only helps treat depression but also decreases sleep problems such as difficulty falling asleep,staying asleep, and waking too early. The present study further explores differences in sleep onset latency, meaning the time it takes to fall asleep, and duration of sleep per night in the pre and post treatment phases of rTMS. The information regarding major attributes of sleep is critical because recent research shows that about 90% of patients with major depressive disorder (MDD) also struggle with sleep disorders (Li et al., 2022), and sleeping for less than seven hours may eventually lead to sleep deprivation (Hirshkowitz et al., 2015), with increased risk of physical and mental health problems (Sheehan et al, 2019). Sleep onset latency estimates vary from individual to individual but typical sleep latency is considered between 10 to 20 minutes (Jung et al, 2013). As it has been shown that overall sleep problems improve with rTMS, we hypothesized that self-reported sleep onset latency will decrease, and sleep duration will increase.

All participants met inclusion criteria for MDD diagnosis and completed a full course of TMS treatment (N=470; Mean age=53.45, SD=13.73). The sample was mostly male (81%) and ethnically diverse: 77.7% non-Hispanic White, 13.3% Black Americans, 1.9% Asian, 0.2 % Asian Indian, and 1.9% other ethnicities. Sleep problems were assessed using the following questions at the pre and post treatment stages: the number of minutes it takes to fall asleep and duration of sleep each night.

A Wilcoxon matched-pairs signed-rank test was conducted to determine whether there was a difference in sleep onset latency and hours of sleep per night between pre and post intervention. The results indicated a significant difference in time to fall asleep between pre and post treatment (pre-treatment M = 1.19, SD = 0.99, post-treatment M = 0.93, SD = 0.91; z = -5.01, p < .001. In addition, there was a significant increase in the minutes of sleep per night in pre (M = 6.11, SD = 2.07) compared to the post treatment (M = 6.32, SD = 1.77), z = -2.56, p = .010.

Reduced sleep is known to negatively impact mood, cognitive ability, work performance, and immune function (Besedovsky et al., 2012; Killgore, 2010; Massar et al, 2019; Vandekerckhove & Wang, 2018). Similarly, longer sleep onset latency can cause an individual to enter the first sleep stage later than expected and complete fewer sleep cycles. The results of the present study show the effectiveness of rTMS in decreasing sleep onset latency and increasing the duration of sleep. Given the comorbidity and bidirectionality between sleep disturbances and mood disorders (Fang et al., 2019; Palagini et al., 2019), further researching treatments such as rTMS to improve sleep as a means to also improve mood is crucial. We propose acquiring knowledge about sleep attributes as an essential part of clinicians’ work early on in the rTMS treatment in order to monitor an individual’s global functioning level in light of improved sleep.

Essential tremor (ET) is the most common movement disorder, characterized by bilateral action tremors of the upper extremities. Surgical interventions can be considered for severe cases that are refractory to medication. Magnetic resonance-guided focused ultrasound (MRgFUS) of the ventral intermediate nucleus of the thalamus (Vim) is a recently approved, minimally invasive treatment for unilateral tremor. While patients are generally pleased with unilateral treatment, many patients are bothered by tremor on the untreated side. Historically, bilateral thalamotomy has been associated with a higher rate of adverse events, including cognitive impairment. MRgFUS Vim thalamotomy for bilateral tremor is currently being investigated. The goal of the present study was to evaluate the effect of bilateral MRgFUS Vim thalamotomy on cognition.

Twelve patients with medication-refractory essential tremor (mean age = 68.77 +/- 11.78 years, mean education = 14.34 +/- 2.71 years, 8 male) were included in the present study. Three of the 12 patients met criteria for mild cognitive impairment (MCI). All patients successfully underwent unilateral MRgFUS thalamotomy at least 48 weeks before the second thalamotomy. A battery of neuropsychological tests was administered to patients before (considered baseline in the present study) and three months following the second thalamotomy. Baseline evaluations occurred on average 144.64 +/- 91.53 weeks (range: 55.00 - 346.58) after the first thalamotomy. The neuropsychological battery assessed domains of processing speed (Oral Symbol Digit Modalities Test, D-KEFS Color-Word Naming and Reading), attention (WAIS-IV Digit Span Forward), executive function (D-KEFS Color-Word Inhibition and Inhibition/Switching), working memory (WAIS-IV Digit Span Backward and Sequencing), verbal fluency (D-KEFS Letter Fluency and Animal Fluency), confrontation naming (Boston Naming Test), verbal memory (Hopkins Verbal Learning Test-Revised), and visuospatial perception (Judgment of Line Orientation). Alternate versions of tests were used when possible. Cognitive changes were analyzed at the group and individual level. Group level changes were assessed with paired sample t-tests (corrected for multiple comparisons). At the individual level, postoperative declines > 1.5 SD from baseline were considered clinically significant.

Participants’ baseline intellectual functioning ranged from low average to superior (as measured by the WTAR). The mean baseline score on the Montreal Cognitive Assessment was 24.58 (range: 17 - 30). At the group level, there were no significant changes in cognitive scores from baseline to follow-up (all p values > 0.635). At the individual level, one patient with MCI declined > 1.5 SD on the verbal memory composite. No other patients showed declines > 1.5 SD.

Our preliminary findings suggest that bilateral MRgFUS Vim thalamotomy is relatively safe from a cognitive perspective. However, a single patient with MCI exhibited clinically significant postoperative decline in verbal memory. Future studies with larger sample sizes are needed to investigate the factors that increase the risk of postoperative cognitive decline, including pre-existing cognitive impairment, older age, and lesion size.

Responsive neurostimulation (RNS) is a surgical intervention to reduce the frequency of seizures as an adjunctive therapy for patients with drug-resistant epilepsy (DRE). Presurgical neuropsychological evaluations capture symptoms of anxiety and depression, which occur in higher rates within the epilepsy population than in the general population; however, the effects of mood are commonly overlooked or underappreciated in the conceptualization of cognitive functioning and overall quality of life. Previous studies have shown the effects of attentional control and executive functioning on engagement in meditative states. The present study examines pre and post-meditation self-reported anxiety symptoms and the electrophysiological changes captured intracranially during meditation sessions in patients implanted with an RNS device. This study seeks to utilize presurgical neuropsychological evaluations to explore relationships between cognitive profiles and meditative state changes, and reductions in anxiety.

This study presents a series of 10 patients who underwent RNS device implantation for the treatment of DRE at Mount Sinai Hospital. All patients had at least one contact in the basolateral amygdala. Prior to surgical implantation of the RNS device, all patients completed a comprehensive neuropsychological evaluation based on the NIH Common Data Elements Battery for Epilepsy Patients. Patients in this study completed a 17-and 22-minute meditation protocol based on loving-kindness and Focal Awareness (FA) meditation. Control points and mind-wandering phases were utilized to distinguish the meditative portion of the study during intracranial recordings. All patients completed a pre- and post-meditation questionnaire adapted from the PROMIS Anxiety Short Form as well as self-ratings on meditation depth and satisfaction.

Presurgical neuropsychological evaluation of patients showed elevated levels of anxiety on the BAI (M = 18.14, SD = 12.03) and depression on the BDI-II (M = 15.57, SD = 6.92). Neuropsychological findings localized to frontal or frontotemporal deficits in 80% of the patients were captured in this study. Regarding lateralization, 50% of patients presented with bilateral weakness on neuropsychological evaluation, with the rest showing unilateral profiles. A negative correlation was observed between patient responses on pre-meditation anxiety measures and self-reported depth of engagement in meditation, r = -0.65, p = .043. When all meditation sessions were evaluated, patients displayed a reduction in anxiety levels pre- and post- meditation, t = 2.3, p = .03.

Present findings suggest a reduction in anxiety symptoms following completion of a meditation paradigm. Additionally, a relationship between anxiety and depth of engagement in meditation was identified. During each meditation session, electrocorticography data was collected and analyzed. Given the high comorbidities of anxiety and depression as well as cognitive symptoms common for individuals with epilepsy, a systems-based approach may enhance conceptualization of neuropsychological and neuropsychiatric evaluations, which may have a significant clinical impact. Evaluation of neuropsychological profiles, meditation effects, and anxiety in this population may support cross-discipline understanding of cognitive and psychiatric profiles to better inform treatment recommendations.

A fundamental challenge for people with severe mental illness (SMI) is how to deal with cognitive impairments, which are common in this population and limit daily functioning. Cognitive remediation (CR) is a psychological intervention that targets these cognitive impairments to improve everyday functioning. However, reduced neural plasticity in people with SMI might hinder newly learned cognitive skills to sustain. Transcranial Direct Current Stimulation (tDCS) can promote this neural plasticity, which could enhance learning and result in longer-lasting improvements in cognitive and daily functioning. This study aimed to investigate the acceptability of the combination of CR and tDCS for people with severe mental illness who live in residential psychiatric facilities.

We interviewed participants of the ongoing HEADDSET pilot trial. In this pragmatic, randomized, controlled pilot trial, participants (individuals with SMI, 18 years or older, living in psychiatric facilities) received CR in combination with concurrent active tDCS (n = 13) or sham tDCS (n = 13) twice weekly for 16 weeks (32 sessions in total). We invited participants who finished the trial’s training period (n = 16) to participate in the interviews. According to the Theoretical Framework of Acceptability (Sekhon et al., 2017), we assessed seven components of acceptability: Affective attitude, burden, intervention coherence, ethicality, opportunity costs, perceived effectiveness, and self-efficacy.

Twelve of the 16 participants participated in the interviews: seven completers (attended at least 20 of the 32 sessions; M = 22.7, range = 20-25) and five non-completers (M = 11.6, range = 9-15). The reasons for not completing the protocol were mainly unrelated to the training (i.e., prolonged illness, substance abuse, personal circumstances). Only one participant did not complete the training because of its intensity. Independent of whether participants completed the intervention, they were positive about the training. They reported that they liked the CR program CIRCuiTS, that participating in the training was not a burden and that, in their opinion, the training could help others. Moreover, all participants observed improvement in their cognitive functioning, and six individuals (three completers and three non-completers) observed improvements in their everyday life (e.g., fewer problems with doing groceries, being more organized, and being able to concentrate and read a book). Overall, the participants would recommend the training to others. Non-completers of the intervention would recommend the CR with tDCS, while completers neither recommended nor advised against the addition of tDCS. Participants who understood and could explain how the training works reported more improvements in daily life, were better at formulating their treatment goals, and stated that the treatment goals were more relevant to them compared to the participants who were unable to do so.

The combined intervention of CR and tDCS was acceptable to individuals with severe mental illness, the participation in the training was no burden to both completers and non-completers, and participants reported personal benefits for their cognitive functioning and everyday life. Future studies should investigate the effectiveness of the intervention in larger randomized controlled trials.

Heart rate variability (HRV) can be an indicator of the flexibility of the central and autonomic nervous systems. Heart rate variability biofeedback (HRV-BF) has been shown to validate the neuro-peripheral relationship and enhance the interaction between top-down and bottom-up processes. Few previous studies have focused on the treatment outcomes of HRV-BF in traumatic brain injury, and such studies have been mostly limited to pilot studies or case reports. The purpose of this study is to investigate the efficacy of HRV-BF for neuropsychological functioning in patients with mild traumatic brain injury (mTBI).

Forty-one patients with mTBI were referred from the neurosurgery outpatient program and randomly assigned to a psychoeducation group or a HRV-BF intervention group. The psychoeducation group received standard medical care and one 60-minute psychoeducation session after brain injury. The HRV-BF group received standard medical care and one 60-minute session of the HRV-BF intervention weekly for 10 weeks. All participants received performance-based and self-reported neuropsychological measures of memory, executive function, mood, and information processing at week 1 of injury (pretest) and week 12 (posttest).

Participants in HRV-BF improved significantly after the intervention compared with the psychoeducation group on the Verbal Learning Test, Frontal Assessment Battery, Verbal Fluency Test, Paced Auditory Serial Addition Test, Trail Making Test, Dysexecutive Questionnaire, Depression Inventory, and Checklist of Post-concussion Symptoms.

HRV-BF was found to be an efficacious and efficient intervention for improving neuropsychological functioning in patients with mTBI and a potential candidate for mTBI rehabilitation.

Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation therapy most widely used in depression, has shown evidence of secondary benefits for cognition in both neurologic and neuropsychiatric conditions. The recent development of more efficient stimulation protocols, such as accelerated high-dose intermittent theta burst (iTBS)-rTMS, has substantially reduced treatment burden by shortening the treatment course by >50%. This study aimed to establish the safety, feasibility, acceptability, and preliminary efficacy of iTBS-rTMS as a tool for bolstering cognition in individuals with amnestic mild cognitive impairment (aMCI).

Twenty-four patients with aMCI were enrolled in an open-label phase I trial of iTBS-rTMS; 2 withdrew prior to initiating treatment due to personal circumstances. All participants had received a diagnosis of MCI due to possible AD from a healthcare provider (i.e., neurologist or neuropsychologist) and met actuarial neuropsychological criteria for aMCI. This sample of older adults (range: 61.5-85.2 years, M = 74.1, SD = 5.71) was predominantly White/non-Hispanic (n = 23; Black/non-Hispanic: n = 1), roughly half female (n = 13), with a college education (range: 12-20 years, M = 15.9, SD = 2.5). Participants received 24 sessions of iTBS-rTMS to the left dorsolateral prefrontal cortex over 3 days (8 sessions each, lasting roughly 2 hours per day). Participants rated their perceptions and experience of common side effects during and after each treatment session as well as retrospectively at post-treatment and 4-week follow-up. They completed structural and functional brain MRI, neuropsychiatric evaluations, and neuropsychological assessments before and after treatment and were administered a subset of these measures at 4-week follow-up. MoCA scores were used to monitor for adverse neurocognitive effects, and the fluid cognition composite score from the NIH Toolbox Cognition Battery was used to test preliminary efficacy.

We achieved a high retention rate (95%), with 21 of the 22 participants completing all study procedures. There were no clinically significant adverse neuroradiological, neuropsychiatric, or neurocognitive effects of treatment. Participant reports indicated high tolerability and acceptability, with a modal rating of 0 (on a scale from 0=not at all to 10=extremely) for six common side effects (i.e., headache, pain, scalp irritation, facial twitching, fatigue, fear/anxiety), assessed both during and after each treatment session. They reported very low desire to quit despite some participants rating the treatment as moderately tiring. We observed significant, large effect-size (d = 0.98) improvements in fluid cognition from pre- to post-treatment.

Our findings support the safety, feasibility, and acceptability of iTBS-rTMS treatment in patients with aMCI. Further, although not explicitly dosed for efficacy, we provide preliminary evidence of improved fluid cognition as a function of treatment, highlighting the potential of this treatment for improving trans-domain cognitive impairment. These promising results can directly inform future trials aimed at optimizing treatment parameters, broadening the indication to other MCI subtypes, and testing the augmentation of established cognitive rehabilitation interventions when combined with rTMS.