Camptocormia in Parkinson's Disease: Systematic Review of Management Using Spine Surgery.

OBJECTIVE: Postural abnormalities are a debilitating symptom of Parkinson's disease (PD) that may require spinal intervention. Camptocormia is a unique abnormality most seen in PD, defined by a severe forward-flexion of the trunk that completely resolves when supine. The condition presents a challenge due to an undefined pathophysiology and optimal therapeutic approach in a high-risk patient population. In this study, the authors systematically reviewed the literature regarding the use of spine surgery for the treatment of camptocormia in PD. METHODS: PubMed, Embase, Web of Science, and Cochrane Library were systematically queried for studies involving spine surgery as treatment of PD-associated camptocormia. Studies involving nonsurgical management, deep brain stimulation (DBS), non-camptocormic PD patients undergoing surgery, or were out of scope were excluded. RESULTS: The search resulted in 5 studies, with a total of 19 PD patients with camptocormia who underwent spine surgery (73.7% female). The mean age was 69.5 years (range, 59 - 83), and mean PD duration was 69.5 months (range, 36 - 84). Out of 19 patients, 11 required surgical revision (57.9%), with an average of 0.68 revisions per patient (range, 0-2). Radiographic and patient-reported outcomes were inconsistently reported yet showed improvement. Ultimately, 18 patients were reported to have positive outcomes. CONCLUSION: Despite an increased risk of complication and revision that is inherent to PD patients, spine surgery has been proven as a reasonable alternative that should be prospectively studied further, as 18/19 patients had favorable outcomes.

Intraoperative 3D fluoroscopy accurately predicts final electrode position in deep brain stimulation surgery.

PURPOSE: In the absence of an intraoperative CT or MRI setup, post-implantation confirmation of electrode position in deep brain stimulation (DBS) requires patient transportation to the radiology unit, prolonging surgery time. This project aims to validate intraoperative 3D fluoroscopy (3DF), a widely available tool in Neurosurgical units, as a method to determine final electrode position. METHODS: We performed a retrospective study including 64 patients (124 electrodes) who underwent DBS at our institution. Intraoperative 3DF after electrode implantation and postoperative volumetric CT were acquired. The Euclidean coordinates of the electrode tip displayed in both imaging modalities were determined and inter-method deviations were assessed. Pneumocephalus was quantified and its potential impact in determining the electrode position analyzed. Finally, 3DF and CT-imposed exposure to radiation was compared. RESULTS: The difference between the electrode tip estimated by 3DF and CT was 0.85 ± 0.03 mm, and not significantly different (p = 0.11 for the distance to MCP assessed by both methods), but was, instead, highly correlated (p = 0.91; p < 0.0001). Even though pneumocephalus was larger in 3DF (6.89 ± 1.76 vs 5.18 ± 1.37 mm3 in the CT group, p < 0.001), it was not correlated with the difference in electrode position measured by both techniques (p = 0.17; p = 0.06). Radiation exposure from 3DF is significantly lower than CT (0.36 ± 0.03 vs 2.08 ± 0.05 mSv; p < 0.0001). CONCLUSIONS: Intraoperative 3DF is comparable to CT in determining the final DBS electrode position. Being a method with fewer radiation exposure, less expensive, faster and that avoids patient transportation outside the operation room, it is a valid tool to replace postoperative CT.

Safety and efficiency of deep brain stimulation in the elderly patients with Parkinson's disease.

AIMS: Deep brain stimulation (DBS) is not routinely performed in elderly patients (≥75 years old) to date because of concerns about complications and decreased benefit. This study aimed to evaluate the safety and efficacy of DBS in elderly patients with Parkinson's disease. METHODS: A retrospective analysis was performed using data from 40 elderly patients from four centers who were treated with neurosurgical robot-assisted DBS between September 2016 and December 2021. These patients were followed up for a minimum period of 2 years, with a subgroup of nine patients followed up for 5-7 years. Patient demographic characteristics, surgical information, pre- and postoperative motor scores, non-motor scores, activities of daily living, and complications were retrospectively analyzed. RESULTS: The mean surgical procedure duration was 1.65 ± 0.24 h, with a mean electrode implantation duration of 1.10 ± 0.23 h and a mean pulse generator implantation duration of 0.55 ± 0.07 h. The mean pneumocephalus volume, electrode fusion error, and Tao's DBS surgery scale were 16.23 ± 12.81 cm3, 0.81 ± 0.23 mm, and 77.63 ± 8.08, respectively. One patient developed a skin infection, and the device was removed. The Unified Parkinson's disease rating scale, Unified Parkinson's disease rating scale of Part III, tremor, rigidity, bradykinesia, axial, and Barthel index for activities of daily living (ADL-Barthel) scores significantly improved at the 2-year follow-up (p < 0.05). The levodopa equivalent daily dose (LEDD) was significantly reduced at the 2-year follow-up (p < 0.05). However, the Montreal cognitive assessment, Hamilton depression scale, and Hamilton anxiety scale scores did not significantly change during the 2-year follow-up (p > 0.05). Additionally, in the subgroup with a 5-year follow-up, the motor symptoms, ADL-Barthel score, and cognitive function worsened over time compared to baseline. However, there was still an improvement in motor symptoms and ADL with DBS on-stimulation compared with the off-stimulation state. The LEDD increased 5 years after surgery compared to that at baseline. Eleven patients had passed away during follow-up, the mean survival time was 38.3 ± 17.3 months after surgery, and the mean age at the time of death was 81.2 (range 75-87) years. CONCLUSION: Robot-assisted DBS surgery for the elderly patients with Parkinson's disease is accurate and safe. Motor symptoms and ADL significantly improve and patients can benefit from long-term neuromodulation, which may decrease the risk of death.

Deep brain stimulation for essential tremor in patients with ventriculomegaly.

Background: Deep brain stimulation of the nucleus ventralis intermedius (VIM-DBS) is considered a safe and effective treatment for medically intractable essential tremor (ET). However, ventriculomegaly can provide a surgical challenge, as there is an increased risk of breaching the ventricle during the procedure, with potential risk of intraventricular hemorrhage and target displacement. Case Description: In this case series, we report successful bilateral VIM-DBS in a 72-year-old and 69-year-old female ET patient with significant ventriculomegaly. VIM-DBS therapy provided an excellent tremor response. After 5 years, a ventriculoperitoneal shunt was implanted in the first patient due to an incomplete Hakim-Adams triad, with significant improvement in gait and cognition. Conclusion: To the best of our knowledge, we present the first report on VIM-DBS in ET patients with ventriculomegaly and illustrate that VIM-DBS can provide an excellent tremor response in patients with medically intractable ET, even in the context of marked ventriculomegaly.

EFFECTS OF TREADMILL GAIT TRAINING ON BALANCE IN PARKINSON'S PATIENTS AFTER DEEP BRAIN STIMULATION.

Objective: After deep brain stimulation (DBS), patients with Parkinson's disease (PD) typically still present significant gait and postural stability problems, and thus additional interventions are needed. In this way, our purpose was evaluate the comparative effectiveness of treadmill training, with and without body weight support, on balance outcomes among patients with PD after DBS. Methods: Eleven patients with PD that were using bilateral subthalamic nucleus DBS were evaluated using Time Up and Go test (TUG); Berg Balance Scale (BBS) and Static Posturography. In phase 1, all subjects participated in 8-weeks of treadmill training in conjunction with conventional physiotherapy. After six weeks (wash-out), each patient then participated in a subsequent 8-weeks of treadmill training with partial body weight support. Results: After the phase 1, there were improvements on the cognitive TUG performance (Before: 15.7 ± 1,8 sec; After: 13.7 ± 3.1 sec; p < 0.01) and an increase of anteroposterior and medio-lateral body oscillation with eyes closed. After the phase 2, there were improvements in conventional (Before: 12.3 ± 2.0 sec; After: 10.7 ± 1.7 sec; p < 0.01) and cognitive (Before: 14.6 ± 3.5 sec; After: 12.5 ± 1.6 sec; p < 0.05) TUG performances. There were no significant changes in the Berg Balance Scale following either training protocol. Conclusion: Both trainings improved static and dynamic balance and had similar results; however, supported treadmill training seemed to be a potentially superior option, as patients tended to feel safer. Level of Evidence II, therapeutic studies - investigation of treatment outcomes.

Objetivo: Mesmo após a estimulação cerebral profunda (ECP), os pacientes com doença de Parkinson (DP) muitas vezes ainda apresentam problemas significativos de marcha e estabilidade postural, e, portanto, intervenções adicionais são necessárias. Avaliar a eficácia comparativa do treinamento em esteira, com e sem suporte de peso corporal, nos resultados de equilíbrio de pacientes com DP após ECP. Métodos: Onze pacientes com DP em uso de ECP bilateral do núcleo subtalâmico foram avaliados pelos testes Time Up and Go (TUG), escala de equilíbrio de Berg (EEB) e posturografia estática. Na fase 1, todos participaram de oito semanas de treinamento em esteira em conjunto com fisioterapia convencional. Após seis semanas (wash-out), cada paciente participou de oito semanas subsequentes de treinamento em esteira com suporte parcial de peso corporal. Resultados: Depois da fase 1, houve melhora no desempenho cognitivo do TUG (antes: 15,7 ± 1,8 s; depois: 13,7 ± 3,1 s; p < 0,01) e aumento da oscilação anteroposterior e médio-lateral do corpo com os olhos fechados. Após a fase 2, os resultados do TUG convencional (antes: 12,3 ± 2,0 seg; depois: 10,7 ± 1,7 seg; p < 0,01) e cognitivo (antes: 14,6 ± 3,5 s; depois: 12,5 ± 1,6 s; p < 0,05) demonstraram melhora. Os protocolos de treinamento não causaram mudanças significativas na EEB.. Conclusão: Ambos os treinos melhoraram o equilíbrio estático e dinâmico e tiveram resultados semelhantes; no entanto, o treinamento em esteira com suporte é uma opção potencialmente superior, uma vez que os pacientes tendiam a se sentir mais seguros. Nível de Evidência II, estudos terapêuticos - investigação de resultados de tratamento.

Baseline brain volume predicts home-based transcranial direct current stimulation effects on inattention in adults with attention-deficit/hyperactivity disorder.

BACKGROUND: Home-based transcranial direct current stimulation (Hb-tDCS) is a non-invasive brain stimulation technique that utilizes low-intensity electric currents delivered via scalp electrodes to modulate brain activity. It holds significant promise for addressing inattention in adults with attention-deficit/hyperactivity disorder (ADHD). However, its effectiveness varies among individuals, and predicting outcomes remains uncertain, partially due to the influence of individual differences in ADHD-related brain anatomy. METHODS: We analyzed data from a subsample, composed by twenty-nine adult patients with ADHD, of the Treatment of Inattention Symptoms in Adult Patients with ADHD (TUNED) trial. Fourteen patients underwent active anodal right cathodal left dorsolateral prefrontal cortex (DLPFC) Hb-tDCS for 4 weeks and fifteen received sham-related tDCS intervention. Inattention outcome was evaluated at both baseline and endpoint (4th week). Baseline structural measures of the DLPFC, anterior cingulate cortex (ACC) and subcortical structures, previously associated with ADHD, were quantified. Several linear mixed models, with a three-way interaction between the fixed predictors brain volume or thickness, time, and treatment were calculated. Multiple comparison corrections were applied using the Benjamini-Hochberg method. RESULTS: Baseline volume of the left DLPFC regions middle frontal gyrus (t (25) = 3.33, p-adjusted = 0.045, Cohen's d = 1.33, 95% CI = [0.45, 2.19]), inferior frontal gyrus (orbital part) (t (25) = 3.10, p-adjusted = 0.045, Cohen's d = 1.24, 95% CI = [0.37, 2.08]), and of the left ACC supragenual (t (25) = 3.15, p-adjusted = 0.045, Cohen's d = 1.26, 95% CI = [0.39, 2.11]) presented significant association with the inattentive score improvement only in the active tDCS group. More specifically, the smaller these regions were, the more the symptoms improved following anodal right cathodal left DLPFC Hb-tDCS. CONCLUSION: Hb-tDCS was associated with greater improvement in brain areas related to attention regulation. Brain MRI can be potentially used to predict clinical response to tDCS in ADHD adults.

Analysis of diffusion changes in cerebral tissues of Parki̇nson's patients who underwent subthalamic nucleus deep brain stimulation: Correlation of improvements in motor and neuropsychiatric symptoms.

OBJECTIVE: Parkinson's disease (PD) as a neurodegenerative disorder characterized by a reduction in both the quantity and functionality of dopaminergic neurons. This succinctly highlights the central pathological feature of PD and its association with dopaminergic neuron degeneration, which underlies the motor and non-motor symptoms of the disease. This study aims to elucidate the nuances of apparent diffusion coefficient (ADC) changes in different cerebral regions by after the bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) surgery of PD, as well as to investigate their potential interactions with the motor and neuropsychiatric spectrum. METHODS: Patients who underwent STN-DBS surgery for PD between 2017 and 2019 were included in this study. The results of diffusion magnetic resonance imaging (MRI), Unified Parkinson Disease Rating Scale (UPDRS) III scores, Beck and Hamilton depression tests were recorded before and at the 3rd month of postoperative stimulation. The data obtained were evaluated with the Wilcoxon signed rank test. Result of the statistical tests were within the 95 % confidence interval and p values were significant below 0.05. RESULTS: Our study was conducted with a total of 13 patients, 8 men and 5 women. As a result of measurements made in a total of 32 different regions, especially in the motor and neuropsychiatric areas of the brain, an increase in ADC values was found in all areas. ADC changes of eight localizations such as left corpus callosum, right corona radiata, left corona radiata, hippocampus, right insula, left superior cerebellar peduncle, left caudate nucleus and left putamen were statistically significant. UPDRS III scores improved by 57 % (p <0.05), and Beck and Hamilton depression scores by 25 % and 33 %, respectively (p> 0.05). CONCLUSIONS: This article implicate that bilateral STN-DBS surgery potentially exerts beneficial effects on both motor and neuropsychiatric symptomatology in individuals with PD. We believe that this therapeutic mechanism is hypothesized to involve modulation of diffusion alterations within distinct cerebral tissues.

Non-Motor Effects of Low-Frequency Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson's Disease: A Systematic Review.

INTRODUCTION: Deep brain stimulation of the subthalamic nucleus is an effective therapy for the motor symptoms of Parkinson's disease (PD). Typically, stimulation is applied at a high frequency (≥100 Hz) to alleviate motor symptoms. However, the effects on non-motor symptoms can be variable. Low-frequency oscillations are increasingly recognized as playing an important role in the non-motor functions of the subthalamic nucleus. Therefore, it has been hypothesized that low-frequency stimulation of the subthalamic nucleus (<100 Hz) may have a direct effect on these non-motor functions, thereby preferentially impacting non-motor symptoms of PD. Despite important therapeutic implications, the literature on this topic has not been summarized. METHOD: To understand the current state of the field, we performed a comprehensive systematic review of the literature assessing the non-motor effects of low-frequency stimulation of the subthalamic nucleus in PD. We performed a supplementary meta-analysis to assess the effects of low- versus high-frequency stimulation on verbal fluency outcomes. RESULTS: Our search returned 7,009 results, of which we screened 4,199 results. A total of 145 studies were further assessed for eligibility, and a total of 21 studies met our inclusion criteria, representing 297 patients. These studies were a mix of case reports and control trials. The four clinical outcomes measured were sleep, sensory perception, cognition, and mood. A supplementary meta-analysis of six studies investigating the impact of low-frequency stimulation on verbal fluency did not find any significant results when pooling across subgroups. CONCLUSION: LFS of the STN may have benefits on a range of cognitive and affective symptoms in PD. However, current studies in this space are heterogeneous, and the effect sizes are small. Factors that impact outcomes can be divided into stimulation and patient factors. Future work should consider the interactions between stimulation location and stimulation frequency as well as how these interact depending on the specific non-motor phenotype.

Non-invasive brain stimulation for post-COVID-19 conditions: a systematic review.

Alongside the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, the number of patients with persistent symptoms following acute infection with SARS-CoV-2 is of concern. It is estimated that at least 65 million people worldwide meet criteria for what the World Health Organization (WHO) defines as "post-COVID-19 condition" - a multisystem disease comprising a wide range of symptoms. Effective treatments are lacking. In the present review, we aim to summarize the current evidence for the effectiveness of non-invasive or minimally invasive brain stimulation techniques in reducing symptoms of post-COVID-19. A total of nineteen studies were identified, one using transcutaneous vagus nerve stimulation (tVNS), another using transorbital alternating current stimulation (toACS), six studies on transcranial magnetic stimulation (TMS) and eleven studies on transcranial direct current stimulation (tDCS) for the treatment of post-COVID-19 symptoms. Existing studies report first promising results, illustrating improvement in clinical outcome parameters. Yet, the mechanistic understanding of post-COVID-19 and how brain stimulation techniques may be benefitial are limited. Directions for future research in the field are discussed.

Antibiotic-impregnated envelopes reduce the rate of surgical site infection in deep brain stimulation pulse generators: a comparative study.

BACKGROUND AND PURPOSE: Deep brain stimulation (DBS) is a surgical procedure that has been used to treat a variety of neurological disorders including Parkinson's disease, essential tremor, and dystonia. While DBS is generally considered safe and effective, surgical site infections (SSIs) are a potential complication that can lead to significant morbidity and mortality. Our objective was to investigate the use of antibiotic-impregnated envelopes (AIEs) encasing implantable pulse generators (IPGs) to reduce the rate of infection at IPG sites and the costs. METHODS: We conducted a retrospective analysis at a single center encompassing all procedures involving the placement of Implantable Pulse Generators (IPG), including both initial insertions and replacement surgeries. The study period spanned from January 2017 to May 2024. Starting in 2020, the routine utilization of AIE became standard practice at our institute for both primary DBS implantation and IPG replacements. Surgical techniques remained consistent, pre- and post-operative antibiotic protocols were standardized throughout the study period and all cases were undertaken by a single surgeon. RESULTS: 178 patients were included and the overall incidence of IPG SSIs was found to be 1.7% (1 infection in 58 patients; 20 primary IPG/38 IPG replacements) among those who received an AIE compared to 5% (6 infections in 120 patients; 36 primary IPG/84 replacement IPG) in patients where no AIE was utilized. This resulted in an odds ratio for infection that was 2.9 times higher in the absence of AIE. The decrease in infection rates was observed in both primary and replacement IPG implants. Notably, over 80% of patients with IPG infection required surgical intervention. The use of AIE further resulted in significant cost savings. CONCLUSION: To our knowledge, this is the largest series reporting the efficacy of Antibiotic impregnated envelope (AIE) in modifying infection rates associated with both initial and replacement Deep Brain Stimulation (DBS) Implantable Pulse Generators (IPGs). The implementation of AIEs led to a decrease in the occurrence of IPG-related infections, observed across both primary implantations and replacement surgeries, with associated economic benefits.

Effect of Early Levodopa Treatment on Mortality in People with Parkinson's Disease.

BACKGROUND: The ideal timing for initiating levodopa in newly diagnosed people with Parkinson's disease (PD) is uncertain due to limited data on the long-term effects of levodopa. OBJECTIVE: The aim was to investigate whether early levodopa initiation postpones mortality (primary outcome), the requirement of device-aided therapies, and the incidence of PD-related complications, such as fall-induced injuries. METHODS: Using nationwide claims data from Dutch hospitals (2012-2020), we grouped newly diagnosed PD individuals as "early initiators" (initiating levodopa within 2 years of diagnosis) or "nonearly initiators." We used the national death registry to assess mortality and health-care claims to assess PD-related complications and device-aided therapies. We used marginal structural models to compare mortality and device-aided therapy rates between groups, and a Poisson regression model to compare PD-related complication rates. RESULTS: Among 29,943 newly diagnosed PD individuals (mean age at diagnosis: 71.6, 38.5% female), there were 24,847 early and 5096 nonearly levodopa initiators. Over a median 4.25 years, 8109 (27.1%) died. The causal risk ratio for mortality was 1.04 (95% confidence interval [CI] 0.92-1.19) for early versus nonearly initiators. The risk ratio of receiving any device-aided therapy was 3.19 (95% CI 2.56-5.80). No association was observed with incidence of PD-related complications (incidence rate ratio: 1.00, 95% CI 0.96-1.05). CONCLUSIONS: Early levodopa initiation in PD does neither postpone nor accelerate mortality or PD-related complications, nor does it precipitate earlier occurrence of PD-related complications or mortality. However, we cannot exclude that the results were influenced by residual confounding due to unmeasured risk factors of mortality.

Pallidal and Thalamic Deep Brain Stimulation in the Treatment of Unilateral Dystonia: A Prospective Assessment.

BACKGROUND: The complexities of unilateral dystonia have led to exploring simultaneous (dual) globus pallidus internus (GPi) and motor ventral thalamus (Vim/Vop) deep brain stimulation (DBS), yet detailed assessments are lacking. OBJECTIVES: To assess the efficacy of GPi, Vim/Vop, and dual DBS in unilateral dystonia. METHODS: Three patients with unilateral dystonia (two idiopathic, one acquired), implanted with two DBS electrodes targeting ipsilateral Vim/Vop and GPi, were included. Three stimulation modalities were assessed. First, one electrode was activated, then the other, and finally, both electrodes were activated simultaneously. RESULTS: DBS yielded substantial symptomatic reductions in all three evaluated stimulation modalities. Patients exhibited varying responses regarding quality-of-life and depressive symptoms. Treatment satisfaction didn't align with clinical improvements, potentially affected by unrealistic expectations. CONCLUSIONS: This study contributes critical insights into GPi, Vim/Vop and simultaneous stimulation for unilateral dystonia. The safety of the procedure underscores the promise of this approach.

Deep brain stimulation of hippocampus in treatment of refractory temporal lobe epilepsy.

INTRODUCTION: Temporal lobe epilepsy (TLE) is the most common cause of focal onset seizures, affecting 40% of adolescents and adults with epilepsy. TLE is also one of the most common drug resistant forms of epilepsy. Surgical resection remains the treatment of choice for TLE, but not all patients with TLE are suitable candidates for resective neurosurgery. For such patients, deep brain stimulation (DBS) of the hippocampus remains a reversible and efficient treatment alternative. STATE OF THE ART: We undertook a systematic review of the literature on hippocampal DBS efficacy and safety in the management of patients with TLE. A search using two electronic databases, the Medical Literature, Analysis, and Retrieval System on-line (MEDLINE) and the Cochrane Central Register of Controlled Trials (CEN-TRAL), was conducted. CLINICAL IMPLICATIONS: We found 14 articles related to hippocampal DBS for the treatment of TLE. The responder rate (defined as at least 50% reduction in seizure frequency) for all patients was 83.4%, Of 99 patients treated by hippocampal DBS, 82 were regarded as responders, and 17 as non-responders. FUTURE DIRECTIONS: Hippocampal DBS appears to be a safe and efficacious treatment alternative for patients who are not candidates for temporal lobectomy or selective amygdalohippocampectomy due to serious postoperative cognitive deficits. In selected patients with TLE, this neuromodulatory therapy may be very safe and efficacious.

Deep Brain Stimulation for Consciousness Disorders; Technical and Ethical Considerations.

Disorders of Consciousness (DoC) result in profound functional impairment, adversely affecting the lives of a predominantly younger patient population. Currently, effective treatment options for those who have reached chronicity (prolonged symptom duration over 4 weeks) are extremely limited, with the majority of such cases facing life-long dependence on carers and a poor quality of life. Here we briefly review the current evidence on caseload, diagnostic and management options in the United Kingdom (UK), United States of America (USA) and the European Union (EU). We identify key differences as well as similarities in these approaches across respective healthcare systems, highlighting unmet needs in this population. We subsequently present past efforts and the most recent advances in the field of surgical modulation of consciousness through implantable neurostimulation systems. We examine the ethical dilemmas that such a treatment approach may pose, proposing mediating solutions and methodological adjustments to address these concerns. Overall, we argue that there is a strong case for the utilisation of deep brain stimulation (DBS) in the DoC patient cohort. This is based on both promising results of recent clinical trials as well as technological developments. We propose a revitalization of surgical neuromodulation for DoC with a multicenter, multidisciplinary approach and strict monitoring guidelines, in order to not only advance treatment options but also ensure the safeguarding of patients' welfare and dignity.

Transcranial Focused Ultrasound Targeting the Amygdala May Increase Psychophysiological and Subjective Negative Emotional Reactivity in Healthy Older Adults.

Background: The amygdala is highly implicated in an array of psychiatric disorders but is not accessible using currently available noninvasive neuromodulatory techniques. Low-intensity transcranial focused ultrasound (TFUS) is a neuromodulatory technique that has the capability of reaching subcortical regions noninvasively. Methods: We studied healthy older adult participants (N = 21, ages 48-79 years) who received TFUS targeting the right amygdala and left entorhinal cortex (active control region) using a 2-visit within-participant crossover design. Before and after TFUS, behavioral measures were collected via the State-Trait Anxiety Inventory and an emotional reactivity and regulation task utilizing neutral and negatively valenced images from the International Affective Picture System. Heart rate and self-reported emotional valence and arousal were measured during the emotional reactivity and regulation task to investigate subjective and physiological responses to the task. Results: Significant increases in both self-reported arousal in response to negative images and heart rate during emotional reactivity and regulation task intertrial intervals were observed when TFUS targeted the amygdala; these changes were not evident when the entorhinal cortex was targeted. No significant changes were found for state anxiety, self-reported valence to the negative images, cardiac response to the negative images, or emotion regulation. Conclusions: The results of this study provide preliminary evidence that a single session of TFUS targeting the amygdala may alter psychophysiological and subjective emotional responses, indicating some potential for future neuropsychiatric applications. However, more work on TFUS parameters and targeting optimization is necessary to determine how to elicit changes in a more clinically advantageous way.

Transcranial focused ultrasound (TFUS) is an emerging brain stimulation technique with the ability to noninvasively alter the activity of deep brain regions. Studying the potential for TFUS to alter behavioral response and processing, this study employed MRI-guided TFUS targeting the right amygdala in older adults. We found that TFUS targeting the right amygdala increased self-reported arousal in response to negative images, providing preliminary evidence that a single session of TFUS may be capable of affecting emotional reactivity.

Phase-shifted tACS can modulate cortical alpha waves in human subjects.

In the present study, we investigated traveling waves induced by transcranial alternating current stimulation in the alpha frequency band of healthy subjects. Electroencephalographic data were recorded in 12 healthy subjects before, during, and after phase-shifted stimulation with a device combining both electroencephalographic and stimulation capacities. In addition, we analyzed the results of numerical simulations and compared them to the results of identical analysis on real EEG data. The results of numerical simulations indicate that imposed transcranial alternating current stimulation induces a rotating electric field. The direction of waves induced by stimulation was observed more often during at least 30 s after the end of stimulation, demonstrating the presence of aftereffects of the stimulation. Results suggest that the proposed approach could be used to modulate the interaction between distant areas of the cortex. Non-invasive transcranial alternating current stimulation can be used to facilitate the propagation of circulating waves at a particular frequency and in a controlled direction. The results presented open new opportunities for developing innovative and personalized transcranial alternating current stimulation protocols to treat various neurological disorders. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-023-09997-1.

Optogenetic fMRI reveals therapeutic circuits of subthalamic nucleus deep brain stimulation.

While deep brain stimulation (DBS) is widely employed for managing motor symptoms in Parkinson's disease (PD), its exact circuit mechanisms remain controversial. To identify the neural targets affected by therapeutic DBS in PD, we analyzed DBS-evoked whole brain activity in female hemi-parkinsonian rats using functional magnetic resonance imaging (fMRI). We delivered subthalamic nucleus (STN) DBS at various stimulation pulse repetition rates using optogenetics, allowing unbiased examination of cell-type specific STN feedforward neural activity. Unilateral optogenetic STN DBS elicited pulse repetition rate-dependent alterations of blood-oxygenation-level-dependent (BOLD) signals in SNr (substantia nigra pars reticulata), GP (globus pallidus), and CPu (caudate putamen). Notably, this modulation effectively ameliorated pathological circling behavior in animals expressing the kinetically faster Chronos opsin, but not in animals expressing ChR2. Furthermore, mediation analysis revealed that the pulse repetition rate-dependent behavioral rescue was significantly mediated by optogenetic DBS induced activity changes in GP and CPu, but not in SNr. This suggests that the activation of GP and CPu are critically involved in the therapeutic mechanisms of STN DBS.

Effectiveness and tolerability of adjunctive transcranial direct current stimulation (tDCS) in management of treatment-resistant depression: A retrospective chart review.

Background: There is a limited number of studies from India investigating the role of transcranial direct current stimulation (tDCS) in treatment-resistant depression (TRD). This clinic-based study reports on the effectiveness of tDCS as an add-on treatment in individuals suffering from TRD. Materials and Methods: Twenty-six right-handed individuals suffering from major depressive disorder who failed to respond to adequate trials of at least two antidepressant drugs in the current episode received tDCS as an augmenting treatment. Twice daily sessions of conventional tDCS were given providing anodal stimulation at the left dorsolateral prefrontal cortex (DLPFC) and cathodal placement at the right DLPFC. A total of 20 sessions were given over 2 weeks. The outcome was assessed based on changes in scores of the Hamilton Rating Scale for Depression (HAMD) and Montgomery-Asberg Depression Rating Scale (MADRS). Results: There was a significant reduction in outcome assessment after tDCS intervention as compared to baseline, with more than 50% of the participants showing response in both scales, which increased further to approximately 77% by the end of 1 month of the follow-up period. Conclusion: Twice daily tDCS sessions with anodal stimulation of left DLPFC and cathodal stimulation of right DLPFC is an effective add-on treatment strategy in individuals with TRD.

Effects of acute hippocampal stimulation in the nonhuman primate penicillin model of temporal lobe seizures.

Asynchronous distributed multielectrode stimulation (ADMES) is a novel approach to deep brain stimulation for medication resistant temporal lobe epilepsy that has shown promise in rodent and in vitro seizure models. To further evaluate its effects on a pre-clinical model, we characterized the effect of unilateral ADMES in an NHP model of temporal lobe seizures induced by intra-hippocampal injection of penicillin (PCN). Four non-human primates were used for this study in two contemporaneous cohorts. One cohort (n = 3 hemispheres) was implanted with the Medtronic RC + S stimulation (GIN cohort) and recording system connected to two 4-contact ring electrodes to evaluate three unilateral stimulation patterns: 7 Hz Ring ADMES, 20 Hz Dual Ring, and 125 Hz Dual Ring (analog of clinical stimulation). In an additional cohort (EPC cohort, n = 2), two 12-contact segmented electrodes were implanted in the right hippocampus and connected to an externalized recording and stimulation system to allow more flexibility in the stimulation pattern. In this second cohort, 4 variations of stimulation were evaluated (7 Hz Full ADMES, 7 Hz Ring ADMES, 31 Hz Wide Ring, and 31 Hz Dual Ring). In the GIN cohort, we found an increase in seizure frequency and time spent in seizure during the 7 Hz Ring ADMES stimulation compared to the respective post-stimulation. A similar post-stimulation effect was found in the EPC cohort. We also found an increase in seizure frequency during the 7Hz full ADMES compared to the respective post-stimulation. However, we did not find a difference between pre-stimulation and stimulation conditions suggesting a possible post stimulation effect of the 7Hz hippocampal stimulation. In conclusion, in the NHP PCN model of temporal lobe seizures, acute asynchronous hippocampal stimulation was not therapeutic, however, our findings related to the post-stimulation effect can support future studies using hippocampal stimulation for the treatment of temporal lobe epilepsy.