Association between Anterior Cingulate Neurochemical Concentration and Individual Differences in Hypnotizability.

Hypnosis is the oldest form of Western psychotherapy and a powerful evidence-based treatment for numerous disorders. Hypnotizability is variable between individuals; however, it is a stable trait throughout adulthood, suggesting that neurophysiological factors may underlie hypnotic responsiveness. One brain region of particular interest in functional neuroimaging studies of hypnotizability is the anterior cingulate cortex (ACC). Here, we examined the relationships between the neurochemicals, GABA, and glutamate, in the ACC and hypnotizability in healthy individuals. Participants underwent a magnetic resonance imaging (MRI) session, whereby T1-weighted anatomical and MEGA-PRESS spectroscopy scans were acquired. Voxel placement over the ACC was guided by a quantitative meta-analysis of functional neuroimaging studies of hypnosis. Hypnotizability was assessed using the Hypnotic Induction Profile (HIP), and self-report questionnaires to assess absorption (TAS), dissociation (DES), and negative affect were completed. ACC GABA concentration was positively associated with HIP scores such that the higher the GABA concentration, the more hypnotizable an individual. An exploratory analysis of questionnaire subscales revealed a negative relationship between glutamate and the absorption and imaginative involvement subscale of the DES. These results provide a putative neurobiological basis for individual differences in hypnotizability and can inform our understanding of treatment response to this growing psychotherapeutic tool.

Hypnotic predictors of agency: Responsiveness to specific suggestions in hypnosis is associated with involuntariness in fibromyalgia.

Hypnosis is associated with alterations in the sense of agency which can play a role in its utilization as a nonpharmacological option for pain management. The goal of the current study was to examine the relationships between responsiveness to suggestions in hypnosis and alterations of the sense of agency among patients with fibromyalgia. Ninety-eight participants with fibromyalgia underwent two hypnotizability assessments followed by the Sense of Agency Rating Scale. Clinical pain measures were also collected. Involuntariness was predicted by responsiveness to control, ideomotor, and dissociation suggestions. Effortlessness was predicted by responsiveness to control and ideomotor suggestions, and age. Hypnotizability was associated with main clinical pain outcomes, but agency alterations were not. Results suggest a shared mechanism between responsiveness to specific suggestions and the sense of agency in hypnosis. We discuss theoretical and clinical implications for pain management and the need for further research.

Fast depressive symptoms improvement in bipolar I disorder after Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT): A two-site feasibility and safety open-label trial.

BACKGROUND: Although there are a few first-line treatment options for bipolar depression, none are rapid-acting. A new rTMS protocol, Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT®), has been shown to have a rapid antidepressant effect in major depressive disorder (MDD). We examined the preliminary safety, tolerability, and efficacy of SAINT for the treatment of depression in a small sample of persons with treatment-resistant bipolar I disorder. METHODS: Participants with treatment-resistant bipolar I disorder currently experiencing moderate to severe depression were treated with open-label SAINT. Resting-state functional MRI (fMRI) was used to generate individualized treatment targets for each participant based on the region of the left dorsolateral prefrontal cortex most anticorrelated with the subgenual anterior cingulate cortex. Participants were treated with 10 iTBS sessions daily, with 50-min intersession intervals, for up to 5 consecutive days. The primary outcome was change in Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to immediate follow-up after treatment. RESULTS: We treated 10 participants and found a mean reduction of 16.9 in MADRS scores, with a 50 % response rate and 40 % remission rate immediately following treatment. 60 % of participants met remission criteria within the 1-month period following treatment. No serious adverse events, manic episodes, or cognitive side effects were observed. LIMITATIONS: Our study has a limited sample size and larger samples are needed to confirm safety and efficacy. CONCLUSIONS: SAINT has shown preliminary feasibility, safety, tolerability, and efficacy in treating treatment-resistant bipolar I depression. Double-blinded sham-controlled trials with larger samples are needed to confirm safety and efficacy.

Stanford Neuromodulation Therapy (SNT): A Double-Blind Randomized Controlled Trial.

OBJECTIVE: Depression is the leading cause of disability worldwide, and half of patients with depression have treatment-resistant depression. Intermittent theta-burst stimulation (iTBS) is approved by the U.S. Food and Drug Administration for the treatment of treatment-resistant depression but is limited by suboptimal efficacy and a 6-week duration. The authors addressed these limitations by developing a neuroscience-informed accelerated iTBS protocol, Stanford neuromodulation therapy (SNT; previously referred to as Stanford accelerated intelligent neuromodulation therapy, or SAINT). This protocol was associated with a remission rate of ∼90% after 5 days of open-label treatment. Here, the authors report the results of a sham-controlled double-blind trial of SNT for treatment-resistant depression. METHODS: Participants with treatment-resistant depression currently experiencing moderate to severe depressive episodes were randomly assigned to receive active or sham SNT. Resting-state functional MRI was used to individually target the region of the left dorsolateral prefrontal cortex most functionally anticorrelated with the subgenual anterior cingulate cortex. The primary outcome was score on the Montgomery-Åsberg Depression Rating Scale (MADRS) 4 weeks after treatment. RESULTS: At the planned interim analysis, 32 participants with treatment-resistant depression had been enrolled, and 29 participants who continued to meet inclusion criteria received either active (N=14) or sham (N=15) SNT. The mean percent reduction from baseline in MADRS score 4 weeks after treatment was 52.5% in the active treatment group and 11.1% in the sham treatment group. CONCLUSIONS: SNT, a high-dose iTBS protocol with functional-connectivity-guided targeting, was more effective than sham stimulation for treatment-resistant depression. Further trials are needed to determine SNT's durability and to compare it with other treatments.

Post-stroke deficits in mediolateral foot placement accuracy depend on the prescribed walking task.

People with chronic stroke (PwCS) are susceptible to mediolateral losses of balance while walking, possibly due in part to inaccurate control of mediolateral paretic foot placement. We hypothesized that mediolateral foot placement errors when stepping to stationary or shifting visual targets would be larger for paretic steps than for steps taken by neurologically-intact individuals, hereby referred to as controls. Secondarily, we hypothesized that paretic foot placement errors would be correlated with previously identified deficits in isolated paretic hip abduction accuracy. 34 PwCS and 12 controls walked overground on an instrumented mat used to quantify foot placement location relative to parallel lines separated by various widths (10, 20, 30 cm). With stationary step width targets, foot placement errors were larger for paretic steps than for either non-paretic or control steps, most notably for the narrowest prescribed step width (mean absolute errors of 3.9, 2.3, and 1.9 cm, respectively). However, no differences in foot placement accuracy were observed immediately following visual target shifts, as all groups required multiple steps to achieve the new prescribed step width. Paretic hip abduction accuracy was moderately correlated with mediolateral foot placement accuracy when stepping to stationary targets (r = 0.49), but not shifting targets (r = 0.16). The present results suggest that a reduced ability to accurately abduct the paretic leg contributes to inaccurate paretic foot placement. However, the need to ensure mediolateral walking balance through mechanically-appropriate foot placement may often override the prescribed goal of stepping to visual targets, a concern of particular importance for narrow steps.

The Hypnotic Induction Profile (HIP) in Clinical Practice and Research.

The Hypnotic Induction Profile (HIP) was developed as a brief, yet thorough, assessment of a person's level of trait hypnotizability and their potential to experience a hypnotic state. The HIP quantitatively and qualitatively measures hynotizability by evaluating biological and sensorimotor experiences designed to assess 3 fundamental observable and measurable components of hypnosis: absorption, dissociation, and suggestibility through a guided assessment that takes 5 to 10 minutes. From conception, the HIP has been utilized in clinical settings to assess appropriateness for the use of hypnosis in treatment planning and research protocols to stratify research participants. The brevity, accessibility, and reliability of the HIP have allowed it to adapt, not only across settings but through media platforms as technology and remote delivery become increasingly incorporated in the field of hypnosis.

Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression.

OBJECTIVE: New antidepressant treatments are needed that are effective, rapid acting, safe, and tolerable. Intermittent theta-burst stimulation (iTBS) is a noninvasive brain stimulation treatment that has been approved by the U.S. Food and Drug Administration for treatment-resistant depression. Recent methodological advances suggest that the current iTBS protocol might be improved through 1) treating patients with multiple sessions per day at optimally spaced intervals, 2) applying a higher overall pulse dose of stimulation, and 3) precision targeting of the left dorsolateral prefrontal cortex (DLPFC) to subgenual anterior cingulate cortex (sgACC) circuit. The authors examined the feasibility, tolerability, and preliminary efficacy of Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), an accelerated, high-dose resting-state functional connectivity MRI (fcMRI)-guided iTBS protocol for treatment-resistant depression. METHODS: Twenty-two participants with treatment-resistant depression received open-label SAINT. fcMRI was used to individually target the region of the left DLPFC most anticorrelated with sgACC in each participant. Fifty iTBS sessions (1,800 pulses per session, 50-minute intersession interval) were delivered as 10 daily sessions over 5 consecutive days at 90% resting motor threshold (adjusted for cortical depth). Neuropsychological testing was conducted before and after SAINT. RESULTS: One participant withdrew, leaving a sample size of 21. Nineteen of 21 participants (90.5%) met remission criteria (defined as a score <11 on the Montgomery-Åsberg Depression Rating Scale). In the intent-to-treat analysis, 19 of 22 participants (86.4%) met remission criteria. Neuropsychological testing demonstrated no negative cognitive side effects. CONCLUSIONS: SAINT, an accelerated, high-dose, iTBS protocol with fcMRI-guided targeting, was well tolerated and safe. Double-blinded sham-controlled trials are needed to confirm the remission rate observed in this initial study.

Application of a Novel Force-Field to Manipulate the Relationship Between Pelvis Motion and Step Width in Human Walking.

Motion of the pelvis throughout a step predicts step width during human walking. This behavior is often considered an important component of ensuring bipedal stability, but can be disrupted in populations with neurological injuries. The purpose of this study was to determine whether a novel force-field that exerts mediolateral forces on the legs can manipulate the relationship between pelvis motion and step width, providing proof-of-concept for a future clinical intervention. We designed a force-field able to: 1) minimize the delivered mediolateral forces (Transparent mode); 2) apply mediolateral forces to assist the leg toward mechanically-appropriate step widths (Assistive mode); and 3) apply mediolateral forces to perturb the leg away from mechanically-appropriate step widths (Perturbing mode). Neurologically-intact participants were randomly assigned to either the Assistive group (n = 12) or Perturbing group (n = 12), and performed a series of walking trials in which they interfaced with the force-field. We quantified the step-by-step relationship between mediolateral pelvis displacement and step width using partial correlations. Walking in the Transparent force-field had a minimal effect on this relationship. However, force-field assistance directly strengthened the relationship between pelvis displacement and step width, whereas force-field perturbations weakened this relationship. Both assistance and perturbations were followed by short-lived effects during a wash-out period, in which the relationship between pelvis displacement and step width differed from the baseline value. The present results demonstrate that the link between pelvis motion and step width can be manipulated through mechanical means, which may be useful for retraining gait balance in clinical populations.

Post-stroke deficits in the step-by-step control of paretic step width.

BACKGROUND: Humans partially maintain gait stability by actively controlling step width based on the dynamic state of the pelvis - hereby defined as the "dynamics-dependent control of step width". Following a stroke, deficits in the accurate control of paretic leg motion may prevent use of this stabilization strategy. RESEARCH QUESTION: Do chronic stroke survivors exhibit paretic-side deficits in the dynamics-dependent control of step width? METHODS: Twenty chronic stroke survivors participated in this cross-sectional study, walking on a treadmill at their self-selected (0.57 ± 0.25 m/s; mean ± s.d.) and fastest-comfortable (0.81 ± 0.30 m/s) speeds. To quantify the dynamics-dependent control of step width, we calculated the proportion of the step-by-step variance in step width that could be predicted from mediolateral pelvis dynamics, and used partial correlations to differentiate the relative effects of pelvis displacement and velocity. Secondarily, we calculated the mean and standard deviation of more traditional gait metrics: step width; lateral foot placement; and mediolateral margin of stability (MoS). We used repeated measures ANOVA to test for significant effects of leg (paretic vs. non-paretic) and speed (self-selected vs. fastest-comfortable) on these measures. RESULTS: Relative to non-paretic steps, paretic steps exhibited a weaker (p ≤ 0.005) link between step width and pelvis dynamics, attributable to a decreased partial correlation between step width and pelvis displacement (p ≤ 0.001). Paretic steps were also placed more laterally (p < 0.0001), with a larger (p < 0.0001) and more variable (p = 0.003) MoS. The only effect of faster walking speeds was a narrower step width (p < 0.0001). SIGNIFICANCE: Pelvis displacement was less tightly linked to step width for paretic steps than for non-paretic steps, indicating a decrease in the step-by-step reactive control normally used to ensure mediolateral stability. Instead, stroke survivors placed their paretic leg farther laterally to ensure a larger MoS, behavior consistent with a greater reliance on a generalized feed-forward gait stabilization strategy.

Effects of walking speed on the step-by-step control of step width.

Young, healthy adults walking at typical preferred speeds use step-by-step adjustments of step width to appropriately redirect their center of mass motion and ensure mediolateral stability. However, it is presently unclear whether this control strategy is retained when walking at the slower speeds preferred by many clinical populations. We investigated whether the typical stabilization strategy is influenced by walking speed. Twelve young, neurologically intact participants walked on a treadmill at a range of prescribed speeds (0.2-1.2 m/s). The mediolateral stabilization strategy was quantified as the proportion of step width variance predicted by the mechanical state of the pelvis throughout a step (calculated as R2 magnitude from a multiple linear regression). Our ability to accurately predict the upcoming step width increased over the course of a step. The strength of the relationship between step width and pelvis mechanics at the start of a step was reduced at slower speeds. However, these speed-dependent differences largely disappeared by the end of a step, other than at the slowest walking speed (0.2 m/s). These results suggest that mechanics-dependent adjustments in step width are a consistent component of healthy gait across speeds and contexts. However, slower walking speeds may ease this control by allowing mediolateral repositioning of the swing leg to occur later in a step, thus encouraging slower walking among clinical populations with limited sensorimotor control.

Combining therapeutic approaches: rTMS and aerobic exercise in post-stroke depression: a case series.

Objective and importance Residual effects of stroke include well-documented functional limitations and high prevalence of depression. Repetitive transcranial magnetic stimulation (rTMS) and aerobic exercise (AEx) are established techniques that improve depressive symptoms, but a combination of the two has yet to be reported. The purpose of this case series is to examine the safety, feasibility, and impact of combined rTMS and AEx on post-stroke depression and functional mobility. Clinical presentation Three participants with a history of stroke and at least mild depressive symptoms (Patient Health Questionare-9 ≥5). Intervention Both rTMS and AEx were completed 3 times/week for 8-weeks. rTMS was applied to the left dorsolateral prefrontal cortex, 5000 pulses/session at 10 Hz, at an intensity of 120% of resting motor threshold. AEx consisted of 40 min of treadmill walking at 50-70% of heart rate reserve. Results Depressive symptoms improved in all three participants, with all demonstrating response (≥50% improvement in symptoms) and likely remission. All participants improved their Six Minute Walk Test distance and Participants 1 and 2 also improved Berg Balance Scale scores. Participants 1 and 3 improved overground walking speeds. No serious adverse events occurred with the application of rTMS or AEx and the participants' subjective reports indicated positive responses. Adherence rate for both rTMS and AEx was 98%. Conclusion Combined treatment of rTMS and AEx appears safe, feasible, and tolerable in individuals with a history of stroke and at least mild depressive symptoms. All participants had good compliance and demonstrated improvements in both depressive symptoms and walking capacity.

Effects of hip abduction and adduction accuracy on post-stroke gait.

BACKGROUND: Gait instability often limits post-stroke function, although the mechanisms underlying this instability are not entirely clear. Our recent work has suggested that one possible factor contributing to post-stroke gait instability is a reduced ability to accurately control foot placement. The purpose of the present experiments was to investigate whether post-stroke gait function is related to the ability to accurately abduct and adduct the hip, as required for accurate foot placement. METHODS: 35 chronic stroke survivors and 12 age-matched controls participated in this experiment. Participants performed hip oscillation trials designed to quantify hip abduction/adduction accuracy, in which they lay supine and moved their leg through a prescribed range of motion in time with a metronome. Stroke survivors also performed overground walking trials at their self-selected speed. FINDINGS: 28 of the 35 stroke survivors had sufficient active range of motion to perform the prescribed hip oscillation task. In comparison to controls, these 28 stroke survivors were significantly less accurate at matching the abduction target, matching the adduction target, and moving in time with the metronome. Across these stroke survivors, a multiple regression revealed that only paretic hip abduction accuracy made a unique contribution to predicting paretic step width and paretic step period, metrics of gait performance. INTERPRETATION: The present results demonstrate that the ability to accurately abduct the hip is related to post-stroke gait performance, as predicted from a model-based gait stabilization strategy. Therefore, interventions designed to improve lower limb movement accuracy may hold promise for restoring post-stroke gait stability.