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Cited by 175Neurological disorders and treatmentsObsessive-Compulsive Spectrum DisordersTranscranial Magnetic Stimulation Studies

Deep brain stimulation for depression.

Open access
Figee, Martijn, Riva-Posse, Patricio, Choi, Ki Sueng, Bederson, Lucia, Mayberg, Helen S., Kopell, Brian H.·2022·Neurotherapeutics
DOI 10.1007/s13311-022-01270-3PMC PMC9587188
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Abstract

Deep brain stimulation has been extensively studied as a therapeutic option for treatment-resistant depression (TRD). DBS across different targets is associated with on average 60% response rates in previously refractory chronically depressed patients. However, response rates vary greatly between patients and between studies and often require extensive trial-and-error optimizations of stimulation parameters. Emerging evidence from tractography imaging suggests that targeting combinations of white matter tracts, rather than specific grey matter regions, is necessary for meaningful antidepressant response to DBS. In this article, we review efficacy of various DBS targets for TRD, which networks are involved in their therapeutic effects, and how we can use this information to improve targeting and programing of DBS for individual patients. We will also highlight how to integrate these DBS network findings into developing adaptive stimulation and optimal trial designs.

AI snapshot

Written from the paper’s full text.

TL;DR

This review summarizes deep brain stimulation (DBS) for treatment-resistant depression (TRD) across subcallosal cingulate, lateral habenula, ventral capsule/ventral striatum, medial forebrain bundle, and inferior thalamic peduncle targets. It reports variable but often substantial response rates, argues that white matter tract engagement is central to antidepressant effects, and calls for tractography-guided targeting, optimized trial designs, and biomarker-informed closed-loop stimulation.

Key findings

  • Across 38 studies and 405 patients, the most common target was the subcallosal cingulate cortex (SCC; N = 216), followed by vALIC/VC/VS (N = 85), MFB (N = 54), LHb (N = 11), and ITP (N = 1); open-label response rates were comparable at on average about 50% after adequate parameter adjustment, with first-year SCC response rates of 20–82%, VC/VS 23–75%, and MFB 0–100%.
  • Randomized sham-controlled trials often failed primary endpoints: BROADEN SCC DBS showed 20% vs 17% response at 6 months and was halted at 90/230 planned patients; RECLAIM VC/VS DBS was terminated for futility at N = 30/200 with 1-year response/remission of 20%/13%; after a 52-week open-label optimization phase, vALIC DBS showed 0% response during sham and 43.8% during active stimulation in a 12-week crossover.
  • SCC tractography findings implicated a four-bundle blueprint—bilateral forceps minor, bilateral cingulum bundles, dorsal/anterior midcingulate cortices, and medial branch of the uncinate fasciculus—and prospective tractography-based targeting in N = 11 yielded 6-month response/remission of 72.7%/54.5% and 12-month response/remission of 81.9%/54.5%.
  • Adverse events included 481 AEs with 12 suicide attempts and 6 suicides for SCC DBS, 330 AEs with 11 attempts and 3 suicides for VC/VS DBS, 434 AEs with 1 attempt and no completed suicides for MFB DBS, and 47 AEs with no attempts or suicides for ITP DBS; the review reports an overall suicide attempt rate of 6.7%, suggesting DBS for TRD does not increase suicide risk.

Methods

  • This is a review based on an electronic search through June 2022 using keywords and MeSH terms including “deep brain stimulation,” “DBS,” “depression,” “treatment resistant depression,” and “TRD”; included studies applied chronic DBS in patients with TRD, and due to limited literature, case reports, open-label studies, and randomized clinical trials were included.
  • The review screened and included 38 studies with a total of 405 patients; primary outcome measures in all but one study were HDRS-17, HDRS-24, HDRS-28, or MADRS, with HDRS response defined as ≥50% reduction and remission as score <8, and MADRS response as ≥40% reduction and remission as score ≤10.
  • For anatomical/network figures, targets were displayed in ICBM 2009b Nlin asymmetric space at 0.5 × 0.5 × 0.5 mm³ resolution, a 2.5 mm radius ball was generated at each DBS target, and normative group connectome diffusion tractography data from Lead-DBS software were used to generate connectivity profiles.

Limitations

  • Stated in the paper: the literature is limited and heterogeneous, including case reports and open-label studies; there are no head-to-head studies comparing targets; placebo-controlled results are mixed; and tractography cannot convey current direction through a bundle, disambiguate cell-specific connections, identify network nodes beyond first-level monosynaptic connections, or rely on a uniform methodology, and may require high-quality patient-specific diffusion scans rather than normative connectomic data.
  • Stated in the paper: few reviewed studies investigated different stimulation parameters, there are no fast behavioral readouts for fine-tuning DBS in TRD, and closed-loop DBS evidence is limited to case reports and does not yet demonstrate superiority over classic DBS.
  • Evident from the text: many efficacy estimates come from small, open-label, non-randomized cohorts, and when multiple studies used the same cohort, totals were calculated using the study with the largest cohort and longest follow-up; adverse event tables contain missing or “NR” data, and the review is not presented as a formal systematic meta-analysis.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1007/s13311-022-01270-3

Cites

112 of 112 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 155 cited sources checked · 0 supported · 0 flagged

  • Findingnone given

    Deep brain stimulation across different targets is associated with an average response rate of about 60% in previously refractory chronically depressed patients.

    “DBS across different targets is associated with on average 60% response rates in previously refractory chronically depressed patients.”
    Quote in the paperSubstantial claim
  • Findingnone given

    A total of 330 adverse events were reported in patients receiving ventral capsule/ventral striatum DBS.

    “A total of 330 adverse events were reported in patients receiving VC/VS DBS.”
    Quote in the paperNot a substantial claim
  • Findingcitation

    Studies of subcallosal cingulate cortex DBS for treatment-resistant depression generally use fixed frequency (130 Hz) and pulse-width (90 μs).

    “While in general, studies of SCC DBS for TRD use fixed frequency (130 Hz) and pulse-width (90 μs), three studies were specifically designed to test effects of different stimulation parameters [32][33][34].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [32] Eitan, 2018, One year double blind study of high vs low frequency subcallosal cingulate stimulation for depression, J Psychiatr Res source

      Not checked in the free run.

    • cites [33] Ramasubbu, 2013, Double-blind optimization of subcallosal cingulate deep brain stimulation for treatment-resistant depression: a pilot study, J Psychiatry Neurosci source

      Not checked in the free run.

    • cites [34] Ramasubbu, 2020, Long versus short pulse width subcallosal cingulate stimulation for treatment-resistant depression: a randomised, double-blind, crossover trial, Lancet Psychiatry source

      Not checked in the free run.

  • Findingnone given

    None of the studies testing different stimulation parameters modelled the white matter fibers differentially impacted by varying parameter settings.

    “Unfortunately, none of these studies modelled the white matter fibers differentially impacted by varying parameter settings.”
    Quote in the paperNot a substantial claim
  • Findingown data

    A total of 481 adverse events were reported in studies targeting the subcallosal cingulate cortex.

    “A total of 481 adverse events were reported in studies targeting the SCC.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 62
  • The quote only partly states this claim. 5
  • Classified as probably not a substantial claim. 16

  • May combine two claims. The quote only partly states this claim.

    Findingcitation

    Open-label trials of subcallosal cingulate cortex DBS for treatment-resistant depression have shown response rates around 55-66% and remission rates around 33-40% at 6-12 months.

    “The first open-label trial of DBS for TRD conducted by Mayberg et al. demonstrated its safety and efficacy, with a response rate (RS) at 6 months of 66% and remission (RM) rate of 33% [5].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [5] Mayberg, 2005, Deep brain stimulation for treatment-resistant depression, Neuron source

      Not checked in the free run.

    • cites [23] Lozano, 2008, Subcallosal cingulate gyrus deep brain stimulation for treatment-resistant depression, Biol Psychiatry source

      Not checked in the free run.

    • cites [24] Kennedy, 2011, Deep brain stimulation for treatment-resistant depression: follow-up after 3 to 6 years, Am J Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Findingnone given

    Response rates to DBS for treatment-resistant depression vary greatly between patients and between studies, and often require extensive trial-and-error optimization of stimulation parameters.

    “However, response rates vary greatly between patients and between studies and often require extensive trial-and-error optimizations of stimulation parameters.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Following subcallosal cingulate cortex DBS, there have been 12 suicide attempts and 6 suicides.

    “Following SCC DBS there have been 12 suicide attempts, and 6 suicides.(Table 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    The average length of the current depressive episode for patients in the BROADEN trial was 12 years, almost double the average of previous published studies.

    “Notably, the average length of the current depressive episode for these patients was 12 years, almost double the average of previous published studies”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [28] Holtzheimer, 2017, Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial, Lancet Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Following ventral capsule/ventral striatum DBS, there have been 11 suicide attempts and 3 suicides.

    “Following VC/VS DBS there have been 11 suicide attempts and 3 suicides (Table 2).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Findingnone given

    The necessary and sufficient white matter bundles within the ventral anterior limb of the internal capsule to achieve predictable good outcomes have yet to be defined.

    “The necessary and sufficient white matter bundles within the vALIC to achieve predictable good outcomes have yet to be defined.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    At last follow-up, six of seven patients preferred VC/VS stimulation over ITP stimulation, and 66.7% of these were responders.

    “However, at last follow up, six out of seven patients preferred VC/VS stimulation over ITP stimulation with 66.7% of these responding to simulation.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [76] Raymaekers, 2017, Deep brain stimulation for treatment-resistant major depressive disorder: a comparison of two targets and long-term follow-up, Transl Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Among 8 patients receiving ITP stimulation, 47 adverse events and no suicide attempts or suicides have been reported.

    “In the 8 patients receiving ITP stimulation, 47 adverse events and no suicide attempts or suicides have been reported (Table 2) (Fig. 6).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Findingnone given

    Substantial relapses after many years of sustained wellness are usually observed during unintended discontinuation.

    “Though substantial relapses after many years of sustained wellness are usually observed during unintended discontinuation”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In a case study, MFB stimulation improved depressive symptoms, but blurred vision could not be reduced by changing stimulation parameters, leading to selection of a new target.

    “Although depressive symptoms improved following stimulation, blurred vision could not be attenuated with changes in stimulation parameters and ultimately led to the selection of a new target.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [68] Blomstedt, 2017, Deep brain stimulation in the bed nucleus of the stria terminalis and medial forebrain bundle in a patient with major depressive disorder and anorexia nervosa, Clin Case Rep source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    After at least 5 months of VC/VS stimulation, 6 of 7 patients were responders and 5 were in remission, with response 85% and remission 71%.

    “After at least 5 months VC/VS stimulation 6 out of 7 patients were responders, and 5 were in remission (RS: 85%, RM: 71%).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [76] Raymaekers, 2017, Deep brain stimulation for treatment-resistant major depressive disorder: a comparison of two targets and long-term follow-up, Transl Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Frequent stimulation-related adverse events in MFB DBS include vision or eye movement disorder and blurred vision, which account for most listed adverse events.

    “Frequent stimulation-related adverse events include vision/eye movement disorder and blurred vision-accounting for the majority of listed AEs.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    A case study of combined VC/VS and SCC DBS reported remission until 75 weeks of follow-up and differential response profiles.

    “A case study of combined VC/VS and SCC DBS reports remission until 75 weeks follow-up of combined stimulation and differential response-profiles.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [77] Sheth S.A. BKR, Metzger B., Allawala A., Pirtle V., Adkinson, J.A. MJ, Mathura R.K., Oswalt D., Tsolaki E., Xiao J., Noecker A., Strutt A.M., Cohn J.F., McIntyre C.C., Mathew S.J., Borton D., Goodman W. & Pouratian N. Deep brain stimulation for depression informed by intracranial recordings. Biol Psychiatry. 2021. source

      Not checked in the free run.

  • May combine two claims.

    Findingnone given

    After MFB DBS, one attempted suicide and no completed suicides have been reported.

    “There has been one attempted and no completed suicides reported following MFB DBS.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In that 12-month randomized trial, significant response and remission rates were observed at 1 year, with response 100% and remission 50%.

    “show significant response and remission rates at 1 year (RS: 100%, RM: 50%)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [72] Coenen, 2019, Superolateral medial forebrain bundle deep brain stimulation in major depression: a gateway trial, Neuropsychopharmacology source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    After at least 3 months of ITP stimulation, 4 of 7 patients were responders and 1 was in remission, with response 57% and remission 14%.

    “After at least 3-month ITP stimulation, 4 out of 7 patients were responders, and 1 was in remission (RS: 57%, RM: 14%).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [76] Raymaekers, 2017, Deep brain stimulation for treatment-resistant major depressive disorder: a comparison of two targets and long-term follow-up, Transl Psychiatry source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingcitation

    SCC stimulation reduced mental noise and produced calmness and attention, while VC/VS stimulation produced energy and motivation.

    “SCC stimulation reduced “mental noise” and produced calmness and attention and VC/VS stimulation produced energy and motivation [77].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [77] Sheth S.A. BKR, Metzger B., Allawala A., Pirtle V., Adkinson, J.A. MJ, Mathura R.K., Oswalt D., Tsolaki E., Xiao J., Noecker A., Strutt A.M., Cohn J.F., McIntyre C.C., Mathew S.J., Borton D., Goodman W. & Pouratian N. Deep brain stimulation for depression informed by intracranial recordings. Biol Psychiatry. 2021. source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In the open-label phase of the Fenoy et al. study, at 1 year the response rate was 66% and the remission rate was 50%.

    “at 1 year (RS: 66%, RM: 50%)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [70] Fenoy, 2016, Deep brain stimulation of the medial forebrain bundle: Distinctive responses in resistant depression, J Affect Disord source

      Not checked in the free run.

    • cites [71] Fenoy, 2018, A longitudinal study on deep brain stimulation of the medial forebrain bundle for treatment-resistant depression, Transl Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Findingnone given

    Psychiatric adverse events associated with stimulation are not fully delineated and appear variable across targets.

    “psychiatric adverse events associated with stimulation are not yet fully delineated and appear variable across targets.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    Alternative measures are under study, such as scales for symptom subdimensions or analysis of movements, speech, or facial expression.

    “alternative measures are under study for example scales for symptom subdimensions or analysis of movements, speech, or facial expression [82][83][84].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [82] Jiang, 2021, Classifying major depressive disorder and response to deep brain stimulation over time by analyzing facial expressions, IEEE Trans Biomed Eng source

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    • cites [83] Scangos, 2021, State-dependent responses to intracranial brain stimulation in a patient with depression, Nat Med source

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    • cites [84] McCall, 2020, Analyzing non-verbal behavior throughout recovery in a sample of depressed patients receiving deep brain stimulation, Neurol Psychiatry Brain Res source

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  • May combine two claims.

    Findingcitation

    In one SCC DBS study, only activation of the cingulum correlated with response, though only half of participants were responders and inclusion of other fibers was unclear.

    “In one study of SCC DBS only activation of the cingulum correlated with response though only half of this trial's participants were responders and it is unclear to what extent the forceps minor, uncinate fasciculus or subcortical fibers were fully included in the surgical target [30].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] Clark, 2020, Tract-based analysis of target engagement by subcallosal cingulate deep brain stimulation for treatment resistant depression, Brain Stimul source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Symptoms return in the order of weeks when SCC DBS is turned off, whereas symptoms return in the order of days when VC/VS DBS is turned off.

    “It appears that symptoms return in the order of weeks when SCC DBS is turned off [26], whereas symptoms return on the order of days when VC/VS DBS is turned off [9].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [26] Holtzheimer, 2012, Subcallosal cingulate deep brain stimulation for treatment-resistant unipolar and bipolar depression, Arch Gen Psychiatry source

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    • cites [9] Bergfeld, 2016, Deep brain stimulation of the ventral anterior limb of the internal capsule for treatment-resistant depression: a randomized clinical trial, JAMA Psychiat source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Findingnone given

    This patient population has an average disease duration lasting many years, with a variety of associated secondary problems.

    “This patient population has an average disease duration lasting many years, with a variety of associated secondary problems.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    In psychiatric disorders, several groups are using electrophysiology to detect mood signals to select stimulation target and parameters.

    “In psychiatric disorders, there are several groups that are utilizing electrophysiology to detect mood signals to select stimulation target and parameters.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Responsive VC/VS stimulation triggered by amygdala gamma increases resulted in over 400 daily biomarker detections and acute and sustained remission of depressive symptoms.

    “This strategy resulted in over 400 daily depressive biomarker detections triggering 6-s stimulations, and acute and sustained remission of depressive symptoms.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [109] Scangos, 2021, Closed-loop neuromodulation in an individual with treatment-resistant depression, Nat Med source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    The sweet spot is in the high-frequency range of 100-150 Hz, which is also supported by animal studies.

    “the sweet spot is in the high-frequency range (100-150 Hz) [103], which is also supported by animal studies [104,105].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [103] Rudebeck PH, Rich EL, Mayberg HS. From bed to bench side: reverse translation to optimize neuromodulation for mood disorders. Proc Natl Acad Sci USA. 2019. source

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    • cites [104] Hamani, 2010, Effects of different stimulation parameters on the antidepressant-like response of medial prefrontal cortex deep brain stimulation in rats, J Psychiatr Res source

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    • cites [105] Lim LW, Prickaerts J, Huguet G, Kadar E, Hartung H, Sharp T, et al. Electrical stimulation alleviates depressive-like behaviors of rats: investigation of brain targets and potential mechanisms. Trans Psychiatry. 2015;5(3):e535-e. source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    For now, there are no fast behavioral effects with DBS at these targets as there are for tremor in Parkinson's disease.

    “for now, there are not fast behavioral effects with DBS at these targets as there are for tremor in PD.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    In the BROADEN trial, improvement between 12 and 24 months relative to the first 12 months was attributable to stimulation changes (active contacts and current) that were not permissible under study protocol in the first 12 months.

    “improvement between 12 and 24 months relative to the first 12 months was attributable to stimulation changes-changes in active contacts and current-which were not permissible under study protocol in the first 12 months.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Holtzheimer, 2017, Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial, Lancet Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The BROADEN trial of subcallosal cingulate cortex DBS for treatment-resistant depression showed no significant difference between active and sham groups at the 6-month primary endpoint, with response rates of 20% vs 17%.

    “Results at the 6-month primary endpoint showed no significant difference between active and sham groups with a low response rate in both groups (20% vs 17%).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [28] Holtzheimer, 2017, Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial, Lancet Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Activity in the subcallosal cingulate cortex increases with provocation of sad mood and decreases in response to antidepressant interventions.

    “Activity in this region increases with the provocation of sad mood [16] and decreases in response to antidepressant interventions [16][17][18][19][20].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [16] Mayberg, 1999, Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness, Am J Psychiatry source

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    • cites [17] Mayberg, 2009, Targeted electrode-based modulation of neural circuits for depression, J Clin Investig source

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    • cites [18] Siegle, 2006, Use of FMRI to predict recovery from unipolar depression with cognitive behavior therapy, Am J Psychiatry source

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  • May combine two claims.

    Premisecitation

    The RECLAIM trial of ventral capsule/ventral striatum DBS for treatment-resistant depression did not demonstrate a significant difference between active and sham groups at the 4-month primary endpoint, resulting in early termination for futility (N = 30/200).

    “Results from the primary endpoint did not demonstrate a significant difference between active and sham groups, resulting in an early termination of the study for futility (N = 30/200).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [61] Dougherty, 2015, A Randomized sham-controlled trial of deep brain stimulation of the ventral capsule/ventral striatum for chronic treatment-resistant depression, Biol Psychiat source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    DBS for obsessive-compulsive disorder showed significant benefit for OCD symptoms with an associated improvement in mood.

    “DBS for OCD showed significant benefit for OCD symptoms with an associated improvement in mood [49][50][51].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [49] Goodman, 2010, Deep brain stimulation for intractable obsessive compulsive disorder: pilot study using a blinded, staggered-onset design, Biol Psychiatry source

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    • cites [50] Greenberg, 2010, Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience, Mol Psychiatry source

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    • cites [51] Nuttin, 2003, Electrical stimulation of the anterior limbs of the internal capsules in patients with severe obsessive-compulsive disorder: anecdotal reports, Neurosurg Clin N Am source

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  • May combine two claims.

    Interpretationcitation

    The clear and well-characterized subcortical lateral habenula connections from optogenetic and functional imaging studies are of limited use for precision targeting of selective LHb white matter connections in human DBS trials, which is technically confounded by the small size of this nucleus relative to the large volume of tissue activated by conventional DBS.

    “The clear and well-characterized subcortical LHb connections from optogenetic and functional imaging studies [39] are of limited use for precision targeting of selective LHb white matter connections in human DBS trials which is technically confounded by the small size of this nucleus relative to the large volume of tissue activated by conventional DBS.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [39] Yang, 2018, Lateral habenula in the pathophysiology of depression, Curr Opin Neurobiol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Ventral capsule/ventral striatum DBS was first developed for obsessive-compulsive disorder, given positive capsulotomy outcomes for these patients.

    “Ventral capsule/ventral striatum (VC/VS) DBS was first developed for obsessive-compulsive disorder (OCD), given positive capsulotomy outcomes for these patients [48].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [48] Abelson, 2005, Deep brain stimulation for refractory obsessive-compulsive disorder, Biol Psychiatry source

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  • May combine two claims.

    Interpretationcitation

    In the Bergfeld et al. study, most patients had to be prematurely crossed over due to significantly increased depressive symptoms typically occurring within one day of crossover, raising ethical concerns around discontinuation-trials in DBS for treatment-resistant depression.

    “Of note, most patients had to be prematurely crossed over due to significantly increased depressive symptoms typically occurring within one day of crossover, raising ethical concerns around discontinuation-trials in DBS for TRD.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [9] Bergfeld, 2016, Deep brain stimulation of the ventral anterior limb of the internal capsule for treatment-resistant depression: a randomized clinical trial, JAMA Psychiat source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a subsequent retrospective analysis of an independent cohort of 19 treatment-resistant depression patients, only activation of the cingulum correlated with response at 6 months, while activation of the forceps minor negatively correlated to response.

    “In this group of patients with a lower response rate than the original study (RS: 47.4% vs 81.9%),only activation of one of the four bundles, the cingulum, correlated with response at 6 months, while activation of the forceps minor negatively correlated to response.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [30] Clark, 2020, Tract-based analysis of target engagement by subcallosal cingulate deep brain stimulation for treatment resistant depression, Brain Stimul source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a recent study of lateral habenula DBS in 6 patients with bipolar depression and 1 with unipolar depression, 3 patients were responders and 1 remitted (RS: 42.9%, RM: 14.3%).

    “Recently, LHb DBS was investigated in 6 patients with bipolar depression and 1 patient with unipolar depression [47].Three patients were responders and 1 patient remitted (RS: 42.9%, RM: 14.3%).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [47] Zhang C, Zhang Y, Luo H, Xu X, Yuan T-f, Li D, et al. Bilateral Habenula deep brain stimulation for treatment-resistant depression: clinical findings and electrophysiological features. Translational Psychiatry. 2022;12(1):52. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Another retrospective study of 17 treatment-resistant depression patients found activation of the forceps minor and uncinate fascicle but not cingulate bundle and no association between activated bundles and response, but this study did not apply tractography-based targeting.

    “Another retrospective study of 17 TRD patients (RS: 58.9%, RM: 35.5%) found activation of the forceps minor and uncinate fascicle but not cingulate bundle and no association between activated bundles and response but this study did not apply tractography-based targeting [31].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31] Aibar-Duran, 2022, Long-term results of deep brain stimulation for treatment-resistant depression: outcome analysis and correlation with lead position and electrical parameters, Neurosurgery source

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  • May combine two claims.

    Premisecitation

    The ventral capsule/ventral striatum is a central hub in the reward circuitry with dopaminergic inputs from the ventral tegmental area, and serving as a relay between prefrontal cortex (OFC, vmPFC, ACC), ventral striatum and the amygdala and hippocampus.

    “The VC/VS is a central hub in the reward circuitry with dopaminergic inputs from the ventral tegmental area (VTA), and serving as a relay between prefrontal cortex (OFC, vmPFC, ACC), ventral striatum and the amygdala and hippocampus [55,56] (Fig. 4).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [55] Nestler, 2015, Role of the brain's reward circuitry in depression: transcriptional mechanisms, Int Rev Neurobiol source

      Not checked in the free run.

    • cites [56] Rizvi, 2016, Assessing anhedonia in depression: Potentials and pitfalls, Neurosci Biobehav Rev source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The inferior thalamic peduncle connects the dorsomedial thalamus with the orbitofrontal cortex, and both regions show hypermetabolism in depressed patients.

    “The inferior thalamic peduncle (ITP) connects the dorsomedial thalamus with the orbitofrontal cortex, which both show hypermetabolism in depressed patients [73].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [73] Velasco F, Velasco M, Jimenez F, Velasco AL, Salin-Pascual R. Neurobiological background for performing surgical intervention in the inferior thalamic peduncle for treatment of major depression disorders. Neurosurgery. 2005;57(3):439–48; discussion -48. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    These patients, in addition to another cohort (N = 21), were followed for a maximum of 5 years and showed significant response and remission rates at 6 months (N = 21, RS: 42.8%, RM: 38.1%), 2 years (N = 17, RS: 64.7%, RM: 47.1%), and 5 years (N = 11, RS: 72.27%, RM: 72.7%).

    “These patients, in addition to another cohort (N = 21), were followed for a maximum of 5 years and showed significant response and remission rates at 6 months (N = 21, RS: 42.8%, RM: 38.1%), 2 years (N = 17, RS: 64.7%, RM: 47.1%), and 5 years (N = 11, RS: 72.27%, RM: 72.7%) [67].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [67] Bewernick, 2018, Deep brain stimulation of the supero-lateral branch of the medial forebrain bundle does not lead to changes in personality in patients suffering from severe depression, Psychol Med source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Placebo rates are high in medication trials for depression.

    “Though placebo rates are high in medication trials for depression [78]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [78] Jakovljevic, 2014, The placebo-nocebo response: controversies and challenges from clinical and research perspective, Eur Neuropsychopharmacol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ITP fibers continue rostrally through the ventral limb of the internal capsule and have modulatory connections to the DLPFC, OFC, ventromedial striatum, and intralaminar thalamus.

    “ITP fibers continue rostrally through the ventral limb of the internal capsule, with modulatory connections to the DLPFC, OFC, ventromedial striatum, and intralaminar thalamus [74].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [74] Kopell, 2008, Anatomy and physiology of the basal ganglia: implications for DBS in psychiatry, Neurosci Biobehav Rev source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Available evidence suggests that DBS for treatment-resistant depression is an effective, safe, and well-tolerated experimental therapeutic option.

    “Available evidence suggests that DBS for TRD is an effective, safe, and well-tolerated experimental therapeutic option for TRD.”
    • Also stated in: § Conclusion · plain
      “DBS is an effective, safe, and well-tolerated therapeutic option for TRD.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    All therapeutic DBS targets reviewed have comparable effectiveness for treating depression, although no head-to-head studies exist.

    “All therapeutic DBS targets reviewed here have comparable effectiveness for treating depression though there are no head-to-head studies to date.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The reviewed DBS studies show a suicide attempt rate of 6.7%, suggesting that DBS for treatment-resistant depression does not increase suicide risk.

    “The DBS studies reviewed here demonstrate a suicide attempt rate of 6.7%, suggesting that DBS for TRD does not increase suicide risk.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Discontinuation of stimulation is generally associated with measurable relapse, raising ethical concerns and potential non-compliance at a critical trial stage.

    “Discontinuation of stimulation is nonetheless generally associated with measurable relapse, raising ethical concerns and the potential for patients' non-compliance at this critical stage of a clinical trial.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisereasoning

    The HRDS and MADRS assess depressive symptom severity but cannot track symptoms once a patient is out of episode, when distinguishing relapse from transient mood instability matters.

    “the HRDS and MADRS are designed to assess severity of depressive symptoms but cannot be used for tracking symptoms once someone is out of episode when it is important to discriminate depression relapse from transient mood instability.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The HRDS and MADRS cannot be used to track symptoms once a patient is out of episode.

  • May combine two claims.

    Premisecitation

    VC/VS targets structurally and functionally connect to the MFB and partially to the SCC, but the SCC has selective fibers not directly connected to VC/VS or NAc.

    “DBS targets in the VC/VS region structurally and functionally connect to the MFB and partially to the SCC [91], but the SCC has selective fibers that are not directly connected to VC/VS or NAc [92,93].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [91] Salgado, 2015, The nucleus accumbens: a comprehensive review, Stereotact Funct Neurosurg source

      Not checked in the free run.

    • cites [92] Gutman, 2009, A tractography analysis of two deep brain stimulation white matter targets for depression, Biol Psychiatry source

      Not checked in the free run.

    • cites [93] Zhu, 2021, A connectomic analysis of deep brain stimulation for treatment-resistant depression, Brain Stimul source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Tractography-based surgical planning across DBS targets appears to improve outcomes but has not directly informed understanding of DBS mechanisms.

    “While tractography-based surgical planning across different DBS targets appears to improve outcomes, it has not directly informed understanding of DBS mechanisms.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    The HRDS and MADRS were designed to survey all depression symptoms globally, whereas DBS is circuit-selective and likely acts on circuit-specific symptom profiles.

    “these scales were designed to globally survey all symptoms of depression while DBS is by definition a circuit-selective intervention likely acting on circuit-specific symptom profiles.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: DBS is by definition a circuit-selective intervention that likely acts on circuit-specific symptom profiles.

  • May combine two claims.

    Premisecitation

    SCC DBS modulates NAc activity and NAc DBS modulates the SCC; both targets influence the brainstem, hypothalamus, amygdala, and OFC.

    “Nevertheless, SCC DBS modulates activity in the NAc and, conversely, NAc DBS modulates the SCC, while other regions that are influenced via both targets include the brainstem, hypothalamus, amygdala, and OFC [94][95][96].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [94] Bewernick, 2010, Nucleus accumbens deep brain stimulation decreases ratings of depression and anxiety in treatment-resistant depression, Biol Psychiatry source

      Not checked in the free run.

    • cites [95] Rauch, 2006, A functional neuroimaging investigation of deep brain stimulation in patients with obsessive-compulsive disorder, J Neurosurg source

      Not checked in the free run.

    • cites [96] Van Laere, 2006, Metabolic imaging of anterior capsular stimulation in refractory obsessive-compulsive disorder: a key role for the subgenual anterior cingulate and ventral striatum, J Nucl Med

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Generally, 30% of patients with treatment-resistant depression attempt suicide at least once in their lives.

    “Generally, 30% of patients with TRD attempt suicide at least once in their lives [86].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [86] Bergfeld, 2018, Treatment-resistant depression and suicidality, J Affect Disord source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Tractography has limitations, including inability to convey current direction through a bundle, disambiguate cell-specific connections, identify network nodes beyond first-level monosynaptic connections, and lack of uniform tract identification methodology.

    “Tractography has several limitations, including inability to con-vey information about the direction of current flow through a given bundle, inability to disambiguate cell-specific connections, inability to identify network nodes beyond first-level monosynaptic connections and lack of a uniform methodology to identify the tracts.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Notable exceptions include prospective targeting of a predefined responder map of specific white matter fibers connected to the SCC and individual tractography identification of the medial forebrain bundle.

    “Notable exceptions include prospective targeting of a predefined responder map of specific white matter fibers connected to the SCC [29], and the individual tractography identification of the medial forebrain bundle [72]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [29] Riva-Posse, 2018, A connectomic approach for subcallosal cingulate deep brain stimulation surgery: prospective targeting in treatment-resistant depression, Mol Psychiatry source

      Not checked in the free run.

    • cites [72] Coenen, 2019, Superolateral medial forebrain bundle deep brain stimulation in major depression: a gateway trial, Neuropsychopharmacology source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    In Parkinson's disease, it is more accepted that DBS selectively improves tremor and rigidity items of the MDS-UPDRS rather than freezing, gait, or apathy.

    “In Parkinson's disease (PD), it is more accepted that DBS selectively improves tremor and rigidity items of the motor Unified Parkinson's Disease Rating Scale (MDS-UPDRS) rather than freezing, gait, or apathy.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    In the MFB target, tractography is necessary for implantation and there is no responder template.

    “In this target, tractography is necessary for implantation, and there is no “responder” template.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    NAc or VC/VS stimulation does not affect the SCC monosynaptically because NAc connections go to the thalamus first and then back to frontal cortex via the ALIC.

    “NAc or VC/VS stimulation does not affect the SCC monosynaptically as NAc connections go to the thalamus first and then back to frontal cortex via the ALIC.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationnone given

    The reviewed surgical risks of DBS for treatment-resistant depression are minimal and do not differ significantly from risks of DBS for movement disorders.

    “The reviewed surgical risks of DBS for TRD are minimal and do not differ significantly from risks of DBS for movement disorders.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    Differences between active and sham groups might not be observable until stimulation parameter optimization has been achieved, which can take up to 1 year after surgery in some targets.

    “Our review suggests that differences between active and sham groups might not be observable until stimulation parameter optimization has been achieved, and that can take up to 1 year after surgery in some targets [9].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [9] Bergfeld, 2016, Deep brain stimulation of the ventral anterior limb of the internal capsule for treatment-resistant depression: a randomized clinical trial, JAMA Psychiat source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    vALIC DBS improved mood in primary OCD and was associated with enhanced striatal reward-processing and dopamine release, which may be important mechanisms for reversing anhedonia and lack of positive mood in major depression.

    “DBS of the vALIC improved mood in patients with primary OCD and was associated with enhanced striatal reward-processing and dopamine release, which may be important mechanisms for the reversal of anhedonia and lack of positive mood in major depression [52,65,100,101].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [52] Figee, 2013, Deep brain stimulation restores frontostriatal network activity in obsessive-compulsive disorder, Nat Neurosci source

      Not checked in the free run.

    • cites [65] Coenen, 2018, The anatomy of the human medial forebrain bundle: ventral tegmental area connections to reward-associated subcortical and frontal lobe regions, Neuroimage Clin source

      Not checked in the free run.

    • cites [100] Denys, 2010, Deep brain stimulation of the nucleus accumbens for treatment-refractory obsessive-compulsive disorder, Arch Gen Psychiatry source

      Not checked in the free run.

    • cites [101] Figee, 2014, Deep brain stimulation induces striatal dopamine release in obsessive-compulsive disorder, Biol Psychiatry source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation

    In the Keining et al 2013 open-label study of two patients with treatment-resistant depression, lateral habenula deep brain stimulation yielded a 100% remission rate, measured by HDRS.

    “| | Keining et al | 2013 Open label | N = 2 | N/A | 100.0% | 100.0% | HDRS |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [46] Kiening, 2013, A new translational target for deep brain stimulation to treat depression, EMBO Mol Med source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationnone given

    For closed-loop stimulation in psychiatric disorders to become a reality, reliable and accessible biomarkers of depression in TRD patients with DBS must first be determined.

    “For closed loop stimulation in psychiatric disorders to become a reality, reliable and accessible biomarkers of depression in TRD patients with DBS first have to be determined.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Interpretationreasoning

    White matter activation maps in DBS responders across targets will help determine the optimal antidepressant network for tractography-guided surgery.

    “White matter activation maps in DBS responders across targets will help determining the optimal antidepressant network that can be used for tractography-guided surgery.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationreasoning

    Progress in the field may depend on developing novel outcome measurements that capture sustained circuit-selective symptom changes and on standardizing randomized placebo-controlled designs with initial open-label parameter optimization.

    “Progress in the field may depend on the development of novel outcome measurements capturing the sustained circuit-selective symptom changes observed after DBS, and standardization of randomized placebo-controlled study designs including initial open-label parameter optimization.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    This case study does not demonstrate superiority of closed-loop VC/VS stimulation over classic VC/VS DBS or whether stimulation must be tailored to daily mood fluctuations versus prolonged depressive states.

    “it does not yet demonstrate effective superiority compared to classic VC/VS DBS or whether stimulation needs to be tailored to biomarkers of daily mood fluctuations or more prolonged depressive states.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Most trials kept medications stable during DBS because withdrawing TRD patients from treatments before experimental DBS is an ethical and safety challenge.

    “Most trials have kept medications stable during the DBS as withdrawing TRD patients from treatments prior to experimental DBS is an ethical and safety challenge.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

    Premiseown data

    In the Wang et al 2021 open-label study of one patient with treatment-resistant depression, lateral habenula deep brain stimulation yielded a 0% remission rate at 3 months, measured by HDRS.

    “| | Wang et al | 2021 Open label | N = 1 | 3 | 100.0% | 0% | HDRS |”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    Comorbid psychiatric disorders may favor specific targets, such as comorbid OCD or OC symptoms favoring VC/VS and anorexia favoring SCC stimulation.

    “Similarly, comorbid psychiatric disorders may favor the choice of specific targets in depression, i.e., comorbid OCD or significant OC symptoms may favor a VC/VS target, and depressed patients with anorexia may respond to SCC stimulation [102].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [102] Lipsman, 2017, Deep brain stimulation of the subcallosal cingulate for treatment-refractory anorexia nervosa: 1 year follow-up of an open-label trial, Lancet Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the Sartorius et al 2010 case study of one patient with treatment-resistant depression, lateral habenula deep brain stimulation yielded a 100% remission rate at 14 months, measured by HDRS.

    “| | Sartorius et al | 2010 Case study | N = 1 | 14 | 100.0% | 100.0% | HDRS |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] Sartorius, 2010, Remission of major depression under deep brain stimulation of the lateral habenula in a therapy-refractory patient, Biol Psychiatry source

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Premiseown data

    In the Wang et al 2021 open-label study of one patient with treatment-resistant depression, lateral habenula deep brain stimulation yielded a 100% response rate at 3 months, measured by HDRS.

    “| | Wang et al | 2021 Open label | N = 1 | 3 | 100.0% | 0% | HDRS |”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Longer pulse-widths were beneficial in some patients but caused more side effects, suggesting less specific stimulation delivery.

    “Although longer pulse-widths were beneficial in some patients, this also caused more side effects suggesting a less specific stimulation delivery.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based). May combine two claims.

    Interpretationreasoning

    A precision-stimulation strategy will likely produce faster and higher antidepressant responses that can be maintained or optimized by adjusting stimulation over time in a closed-loop or assisted-open-loop fashion informed by biomarkers of depressive states.

    “This precision-stimulation strategy will likely result in faster and higher antidepressant responses that can be maintained or optimized by adjusting the stimulation over time in a closed-loop or assisted-open-loop fashion informed by biomarkers of depressive states.”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Premisecitation

    In the Keining et al 2013 open-label study of two patients with treatment-resistant depression, lateral habenula deep brain stimulation yielded a 100% response rate, measured by HDRS.

    “| | Keining et al | 2013 Open label | N = 2 | N/A | 100.0% | 100.0% | HDRS |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [46] Kiening, 2013, A new translational target for deep brain stimulation to treat depression, EMBO Mol Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A case report suggests augmenting effects of SCC DBS with a monoamine oxidase inhibitor but not with other antidepressants.

    “A casereport suggests augmenting effects of SCC DBS with monoamine oxidase inhibitor but not with other antidepressants [111].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [111] Hamani, 2012, Monoamine oxidase inhibitors potentiate the effects of deep brain stimulation, Am J Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Several patients withdrawn from unhelpful medication at implant showed similar robust response to DBS, suggesting medication may not be required to achieve or augment DBS response.

    “several patients that were withdrawn from unhelpful medication at the time of implant showed similar robust response to DBS [9], suggesting that medication may not be required to achieve or augment DBS response.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [9] Bergfeld, 2016, Deep brain stimulation of the ventral anterior limb of the internal capsule for treatment-resistant depression: a randomized clinical trial, JAMA Psychiat source

      Not checked in the free run.

76 of 76

  • The authors state this as an assumption.

    The reward circuitry is related to the anhedonia symptoms of major depressive disorder.

    “This circuitry significantly overlaps with the reward-circuitry assumed to be related to the anhedonia symptoms of MDD.”

  • The paper relies on this without support.

    The ventral capsule/ventral striatum target modulates the medial forebrain bundle in addition to the anterior thalamic radiation and other pathways.

    “Notably, the VC/VS target is thought to modulate the MFB in addition to the anterior thalamic radiation (ATR) and other pathways discussed previously.”

  • The paper relies on this without support.

    Treatment-resistant depression is characterized by a lack of mood variability.

    “Since TRD is characterized by a lack of mood variability, successful treatment should restore this variability in patients.”

  • The paper relies on this without support.

    DBS is by definition a circuit-selective intervention that likely acts on circuit-specific symptom profiles.

    “while DBS is by definition a circuit-selective intervention likely acting on circuit-specific symptom profiles.”

  • The paper relies on this without support.

    The HRDS and MADRS cannot be used to track symptoms once a patient is out of episode.

    “the HRDS and MADRS are designed to assess severity of depressive symptoms but cannot be used for tracking symptoms once someone is out of episode”

  • The paper relies on this without support.

    The treatment-resistant depression patient population has an average disease duration lasting many years.

    “This patient population has an average disease duration lasting many years”

  • The paper relies on this without support.

    The four lateral habenula deep brain stimulation studies pooled in the total row are sufficiently comparable in patient population, stimulation parameters, and outcome definitions to justify aggregating their response and remission rates.

    “Total* | | | N = 11 | | 85.7% | 53.6% | |”
7 of 7

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Closed-loop procedures allow an improved control of some neurological conditions such as epilepsy, and can also be used for better control of obsessive-compulsive disorders and depression.

    “This procedures allow an improved control of some neurological conditions such as epilepsy (Ranjandish and Schmid, 2020; Farkhondeh Tale Navi et al., 2022), and can also be used for better control of obsessive-compulsive disorders and depression (Figee et al., 2022; Visser-Vandewalle et al., 2022).”

    From Toward a personalized closed-loop stimulation of the visual cortex: Advances and challenges (2022) · cites this paper as Figee et al., 2022

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Bewernick two-year remission rate conflicts with Table 1

    Major

    The text reports 9.1% remission at two years for this cohort, but Table 1 reports 45.5% for the 2012 Bewernick study at 24 months.

  • Bewernick one-year remission rate conflicts with Table 1

    Major

    The VC/VS discussion gives a 30% one-year remission rate for the 10-patient cohort, whereas Table 1 gives 50% for Bewernick et al. at 12 months.

  • MFB trial one-year remission rates disagree

    Major

    The text gives 50% remission at one year in the 16-patient randomized MFB trial, while the Table 1 entry for Coenen et al. reports 62.5% at 12 months.

  • Holtzheimer SCC outcomes conflict with Table 1

    Major

    For the 2012 Holtzheimer study at 24 months, the text reports 100% response and 92% remission, but Table 1 reports 58% response and 11% remission.

  • Original SCC cohort has two reported sizes

    Minor

    The text says the original Mayberg cohort had six patients, while Table 1 lists five for the same study.

  • RECLAIM two-year remission rate differs from Table 1

    Minor

    The text reports 20% remission at two years, while Table 1 lists 23.3% remission for the Dougherty study at 24 months.

  • Claim of no head-to-head studies contradicts reviewed comparison

    Minor

    The discussion says there are no head-to-head studies, but the paper describes a seven-patient study directly comparing VC/VS and ITP stimulation.

7 of 7

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Bewernick, 2010, Nucleus accumbens deep brain stimulation decreases ratings of depression and anxiety in treatment-resistant depression, Biol Psychiatry, 67, 110, 10.1016/j.biopsych.2009.09.013 · DOI · Paper page

Cited by

Sorted by citations

Related

Authors
Figee, M., Riva-Posse, P., Choi, K. S., Bederson, L., Mayberg, H. S., & Kopell, B. H.
Affiliations
Icahn School of Medicine at Mount Sinai (US)
Corresponding author
Figee, Martijn
ORCID
Venue
Neurotherapeutics
Publisher
Elsevier BV
Published
2022-07
Volume
19
Issue
4
Pages
1229-1245
ISSN
1878-7479 (ISSN-L)
DOI
10.1007/s13311-022-01270-3
PMC
PMC9587188
OpenAlex
W4285043264
Semantic Scholar
1fb69b72a96ebcc20085d4a3c500ad86fa028495
Cited by
175
References
112
Citations by year
2026: 50 · 2025: 46 · 2024: 45 · 2023: 30 · 2022: 3
FWCI
4.47
Type
journal article
Language
en
Open access
Licence
Locations
  • Neurotherapeutics (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Neurology › Neurological disorders and treatments
  • Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
  • Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
Keywords
deep brain stimulation, treatment-resistant depression, DBS targets, white matter tracts, tractography, antidepressant response, stimulation parameter optimization, adaptive stimulation, chronic depression
MeSH terms
Antidepressive Agents, Depression, Humans, Deep Brain Stimulation, Depressive Disorder, Treatment-Resistant, White Matter

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-08.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-08.

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