(searched for: doi:10.3410/m4-22)
Journal of Clinical Medicine, Volume 9; https://doi.org/10.3390/jcm9103260
Major depression contributes significantly to the global disability burden. Since the first clinical study of deep brain stimulation (DBS), over 406 patients with depression have now undergone this neuromodulation therapy, and 30 animal studies have investigated the efficacy of subgenual cingulate DBS for depression. In this review, we aim to provide a comprehensive overview of the progress of DBS of the subcallosal cingulate in humans and the medial prefrontal cortex, its rodent homolog. For preclinical animal studies, we discuss the various antidepressant-like behaviors induced by medial prefrontal cortex DBS and examine the possible mechanisms including neuroplasticity-dependent/independent cellular and molecular changes. Interestingly, the response rate of subcallosal cingulate Deep brain stimulation marks a milestone in the treatment of depression. DBS among patients with treatment-resistant depression was estimated to be approximately 54% across clinical studies. Although some studies showed its stimulation efficacy was limited, it still holds great promise as a therapy for patients with treatment-resistant depression. Overall, further research is still needed, including more credible clinical research, preclinical mechanistic studies, precise selection of patients, and customized electrical stimulation paradigms.
Published: 3 February 2020
Proceedings of the National Academy of Sciences, Volume 117, pp 3808-3818; https://doi.org/10.1073/pnas.1910842117
The amygdala is central to the pathophysiology of many psychiatric illnesses. An imprecise understanding of how the amygdala fits into the larger network organization of the human brain, however, limits our ability to create models of dysfunction in individual patients to guide personalized treatment. Therefore, we investigated the position of the amygdala and its functional subdivisions within the network organization of the brain in 10 highly sampled individuals (5 h of fMRI data per person). We characterized three functional subdivisions within the amygdala of each individual. We discovered that one subdivision is preferentially correlated with the default mode network; a second is preferentially correlated with the dorsal attention and fronto-parietal networks; and third subdivision does not have any networks to which it is preferentially correlated relative to the other two subdivisions. All three subdivisions are positively correlated with ventral attention and somatomotor networks and negatively correlated with salience and cingulo-opercular networks. These observations were replicated in an independent group dataset of 120 individuals. We also found substantial across-subject variation in the distribution and magnitude of amygdala functional connectivity with the cerebral cortex that related to individual differences in the stereotactic locations both of amygdala subdivisions and of cortical functional brain networks. Finally, using lag analyses, we found consistent temporal ordering of fMRI signals in the cortex relative to amygdala subdivisions. Altogether, this work provides a detailed framework of amygdala–cortical interactions that can be used as a foundation for models relating aberrations in amygdala connectivity to psychiatric symptoms in individual patients.
Stereotactic and Functional Neurosurgery, Volume 97, pp 404-406; https://doi.org/10.1159/000504680
This case report presents a 54-year-old Parkinson´s disease patient who underwent a DBS implantation to the subthalamic nuclei bilaterally. Shortly after the operation, the subcutaneous pocket of the generator filled with a liquid. Repeated aspirations did not show any bacterial contamination, and an infection was not found. In the sample, a beta-trace protein was detected that proved the presence of cerebrospinal fluid. A lumbar drain was immediately placed, and a chest compression bandage was fastened for 7 days. After removing the lumbar drain and the compression bandage, no additional liquid was observed, and the wound healed without any other complication. We present an unusual adverse event related to DBS surgery and suggest an effective treatment that has led to uncomplicated healing.
Published: 30 March 2019
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Micromachines, Volume 9; https://doi.org/10.3390/mi9110595
We demonstrate a method of neurostimulation using implanted, free-floating, inter-neural diodes. They are activated by volume-conducted, high frequency, alternating current (AC) fields and address the issue of instability caused by interconnect wires in chronic nerve stimulation. The aim of this study is to optimize the set of AC electrical parameters and the diode features to achieve wireless neurostimulation. Three different packaged Schottky diodes (1.5 mm, 500 µm and 220 µm feature sizes) were tested in vivo (n = 17 rats). A careful assessment of sciatic nerve activation as a function of diode–dipole lengths and relative position of the diode was conducted. Subsequently, free-floating Schottky microdiodes were implanted in the nerve (n = 3 rats) and stimulated wirelessly. Thresholds for muscle twitch responses increased non-linearly with frequency. Currents through implanted diodes within the nerve suffer large attenuations (~100 fold) requiring 1–2 mA drive currents for thresholds at 17 µA. The muscle recruitment response using electromyograms (EMGs) is intrinsically steep for subepineurial implants and becomes steeper as diode is implanted at increasing depths away from external AC stimulating electrodes. The study demonstrates the feasibility of activating remote, untethered, implanted microscale diodes using external AC fields and achieving neurostimulation.
Depression and Anxiety, Volume 35, pp 992-1000; https://doi.org/10.1002/da.22832
Background Definition of response is critical when seeking to establish valid predictors of treatment success. However, response at the end of study or endpoint only provides one view of the overall clinical picture that is relevant in testing for predictors. The current study employed a classification technique designed to group subjects based on their rate of change over time, while simultaneously addressing the issue of controlling for baseline severity. Methods A set of latent class trajectory analyses, incorporating baseline level of symptoms, were performed on a sample of 344 depressed patients from a clinical trial evaluating the efficacy of cognitive behavior therapy and two antidepressant medications (escitalopram and duloxetine) in patients with major depressive disorder. Results Although very few demographic and illness‐related features were associated with response rate profiles, the aggregated effect of candidate genetic variants previously identified in large pharmacogenetic studies and meta‐analyses showed a significant association with early remission as well as nonresponse. These same genetic scores showed a less compelling relationship with endpoint response categories. In addition, consistent nonresponse throughout the study treatment period was shown to occur in different subjects than endpoint nonresponse, which was verified by follow‐up augmentation treatment outcomes. Conclusions When defining groups based on the rate of change, controlling for baseline depression severity may help to identify the clinically relevant distinctions of early response on one end and consistent nonresponse on the other.
Psychiatric Clinics of North America, Volume 41, pp 485-503; https://doi.org/10.1016/j.psc.2018.04.009
The authors conducted a meta-review of meta-analyses published in the past decade on therapeutic neuromodulation (ie, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, vagus nerve stimulation and deep brain stimulation) for major depression. Active repetitive transcranial magnetic stimulation and transcranial direct current stimulation have been generally associated with small to moderate effect sizes vis-à-vis their efficacy and with similar acceptability compared with sham. Vagus nerve stimulation and deep brain stimulation (although more challenging to investigate) have demonstrated preliminary effectiveness, particularly during longer-term follow-up.
Journal of Neurosurgery, Volume 127, pp 360-369; https://doi.org/10.3171/2016.6.jns152946
OBJECTIVEAs the number of deep brain stimulation (DBS) procedures performed under general anesthesia (“asleep” DBS) increases, it is more important to assess the rates of adverse events, inpatient lengths of stay (LOS), and 30-day readmission rates in patients undergoing these procedures compared with those in patients undergoing traditional “awake” DBS without general anesthesia.METHODSAll patients in an institutional database who had undergone awake or asleep DBS procedures performed by a single surgeon between August 2011 and August 2014 were reviewed. Adverse events, inpatient LOS, and 30-day readmissions were analyzed.RESULTSA total of 490 electrodes were placed in 284 patients, of whom 126 (44.4%) underwent awake surgery and 158 (55.6%) underwent asleep surgery. The most frequent overall complication for the cohort was postoperative mental status change (13 patients [4.6%]), followed by hemorrhage (4 patients [1.4%]), seizure (4 patients [1.4%]), and hardware-related infection (3 patients [1.1%]). Mean LOS for all 284 patients was 1.19 ± 1.29 days (awake: 1.06 ± 0.46 days; asleep: 1.30 ± 1.67 days; p = 0.08). Overall, the 30-day readmission rate was 1.4% (1 awake patient, 3 asleep patients). There were no significant differences in complications, LOS, and 30-day readmissions between awake and asleep groups.CONCLUSIONSBoth awake and asleep DBS can be performed safely with low complication rates. The authors found no significant differences between the 2 procedure groups in adverse events, inpatient LOS, and 30-day readmission rates.
Cerebral Cortex, Volume 28, pp 1760-1770; https://doi.org/10.1093/cercor/bhx086
The brain-derived neurotrophic factor (BDNF) is critical for brain development, and the functional BDNF Val66Met polymorphism is implicated in risk for mood disorders. The objective of this study was to determine how the Val66Met polymorphism influences amygdala–cortical connectivity during neurodevelopment and assess the relevance for mood disorders. Age- and sex-specific effects of the BDNF Val66Met polymorphism on amygdala–cortical connectivity were assessed by examining covariance of amygdala volumes with thickness throughout the cortex in a sample of Caucasian youths ages 8–22 that were part of the Philadelphia Neurodevelopmental Cohort (n = 339). Follow-up analyses assessed corresponding BDNF genotype effects on resting-state functional connectivity (n = 186) and the association between BDNF genotype and major depressive disorder (MDD) (n = 2749). In adolescents, amygdala–cortical covariance was significantly stronger in Met allele carriers compared with Val/Val homozygotes in amygdala–cortical networks implicated in depression; these differences were driven by females. In follow-up analyses, the Met allele was also associated with stronger resting-state functional connectivity in adolescents and increased likelihood of MDD in adolescent females. The BDNF Val66Met polymorphism may confer risk for mood disorders in females through effects on amygdala–cortical connectivity during adolescence, coinciding with a period in the lifespan when onset of depression often occurs, more commonly in females.
European Neuropsychopharmacology, Volume 26, pp 684-692; https://doi.org/10.1016/j.euroneuro.2016.02.005
In major depressive disorder (MDD), electrophysiological and imaging studies provide evidence for a reduced neural activity in parietal and dorsolateral prefrontal regions. In the present study, neural correlates and temporal dynamics of visual affective perception have been investigated in patients with unipolar depression in a pre/post treatment design using magnetoencephalography (MEG). Nineteen in-patients and 19 balanced healthy controls passed MEG measurement while passively viewing pleasant, unpleasant and neutral pictures. After a 4-week treatment with electroconvulsive therapy or 4-week waiting period without intervention respectively, 16 of these patients and their 16 corresponding controls participated in a second MEG measurement. Before treatment neural source estimations of magnetic fields evoked by the emotional scenes revealed a general bilateral parietal hypoactivation in depressed patients compared to controls predominately at early and mid-latency time intervals. Successful ECT treatment, as reflected by a decline in clinical scores (Hamilton Depression Scale; HAMD) led to a normalization of this distinct parietal hypoactivation. Effective treatment was also accompanied by relatively increased neural activation at right temporo-parietal regions. The present study indicates dysfunctional parietal information processing and attention processes towards emotional stimuli in MDD patients which can be returned to normal by ECT treatment. Since convergent neural hypoactivations and treatment effects have recently been shown in MDD patients before and after pharmacological therapy, this electrophysiological correlate might serve as a biomarker for objective treatment evaluation and thereby potentially advance treatment options and support the prediction of individual treatment responses.
Operative Neurosurgery, Volume 11, pp 190-199; https://doi.org/10.1227/neu.0000000000000659
Although numerous studies have focused on the efficacy of deep brain stimulation (DBS) for movement disorders, less is known about surgical adverse events, especially over longer time intervals. Here, we analyze adverse events in 510 consecutive cases from a tertiary movement disorders center at up to 10 years postoperatively. We conducted a retrospective review of adverse events from craniotomies between January 2003 and March 2013. The adverse events were categorized into 2 broad categories—immediate perioperative and time-dependent postoperative events. Across all targets, perioperative mental status change occurred in 18 (3.5%) cases, and symptomatic intracranial hemorrhage occurred in 4 (0.78%) cases. The most common hardware-related event was skin erosion in 13 (2.5%) cases. The most frequent stimulation-related event was speech disturbance in 16 (3.1%) cases. There were no significant differences among surgical targets with respect to the incidence of these events. Time-dependent postoperative events leading to the revision of a given DBS electrode for any reason occurred in 4.7% ± 1.0%, 9.3% ± 1.4%, and 12.4% ± 1.5% of electrodes at 1, 4, and 7 years postoperatively, respectively. Staged bilateral DBS was associated with approximately twice the risk of repeat surgery for electrode replacement vs unilateral surgery (P = .020). These data provide low incidences for adverse events in a large series of DBS surgeries for movement disorders at up to 10 years follow-up. Accurate estimates of adverse events will better inform patients and caregivers about the potential risks and benefits of surgery and provide normative data for process improvement.
Published: 6 November 2014
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Published: 1 November 2014
Biofeedback, Volume 42, pp 115-120; https://doi.org/10.5298/1081-5937-42.3.04
Implementing a viable biofeedback program into an integrative mental health inpatient rehabilitation program has its appeals and its challenges. This article describes the biofeedback program within the Sierra Tucson inpatient rehabilitation hospital. The fact that the field of biofeedback provides a dynamic system of training, education, and empowerment can yield creative programmatic solutions toward integrating this therapy to coalesce within a greater integrative mental health system. A brief outline of the challenges to consider when implementing such a program is offered, along with further discussion regarding the Sierra Tucson program's model and methods.
Journal of Affective Disorders, Volume 167, pp 251-258; https://doi.org/10.1016/j.jad.2014.06.022
Typically, transcranial direct current stimulation (tDCS) treatments for depression have used bifrontal montages with anodal (excitatory) stimulation targeting the left dorsolateral prefrontal cortex (DLPFC). There is limited research examining the effects of alternative electrode montages. This pilot study aimed to examine the feasibility, tolerability and safety of two alternative electrode montages and provide preliminary data on efficacy. The montages, Fronto-Occipital (F-O) and Fronto-Cerebellar (F-C), were designed respectively to target midline brain structures and the cerebellum. The anode was placed over the left supraorbital region and the cathode over the occipital and cerebellar region for the F-O and F-C montages respectively. Computational modelling was used to determine the electric fields produced in the brain regions of interest compared to a standard bifrontal montage. The two montages were evaluated in an open label study of depressed participants (N=14). Mood and neuropsychological functioning were assessed at baseline and after four weeks of tDCS. Computational modelling revealed that the novel montages resulted in greater activation in the anterior cingulate cortices and cerebellum than the bifrontal montage, while activation of the DLPFCs was higher for the bifrontal montage. After four weeks of tDCS, overall mood improvement rates of 43.8% and 15.9% were observed under the F-O and F-C conditions, respectively. No significant neuropsychological changes were found. The clinical pilot was open-label, without a control condition and computational modelling was based on one healthy participant. Results found both montages safe and feasible. The F-O montage showed promising antidepressant potential.
Published: 27 August 2014
Deep Brain Stimulation: Technology and Applications (Volume 2) pp 64-75; https://doi.org/10.2217/ebo.13.577
Published: 22 April 2014
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Psychiatric Annals, Volume 44, pp 131-137; https://doi.org/10.3928/00485713-20140306-04
Psychiatry and Clinical Neurosciences, Volume 68, pp 606-611; https://doi.org/10.1111/pcn.12166
Aim The purpose of this study was to evaluate the efficacy of vagus nerve stimulation (VNS) as a therapeutic option for treatment‐resistant depression (TRD), with follow‐up periods of 1, 3 and 5 years after VNS surgery. Methods We examined 27 consecutive patients with unipolar TRD. Depressive symptoms were evaluated both at baseline and at follow‐up after the surgery by means of the 21‐item Hamilton Rating Scale for Depression (HAM‐D 21). Results The mean HAM‐D preoperative score was 25.6. Twenty‐two patients were evaluated after 1 year of treatment, and the mean improvement of the HAM‐D score was of 10.3. Five patients (20%) went into complete remission (HAM‐D < 7) after 1 year, six patients (22.3%) were considered responders (50% reduction of HAM‐D scoring) and eight patients had score reduction of less then 20%. Nineteen patients were evaluated after 24–36 months: the average improvement on the HAM‐D score was of 12.1 points (47.2%). One patient went into complete remission and eight patients (42.1%) were responders. Up to the present date, seven patients have undergone re‐evaluation at 48–60 months from surgery showing an average score reduction of 14.2. Two more patients obtained complete remission, while four of them did not have any improvement since their last follow‐up control visit. Conclusion VNS antidepressant was successful in 20% of TRD patients, although some patients required several months to obtain clinical improvement or remission of symptomatology. Nonetheless this procedure can be considered as a useful option in treating TRD.