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Deep Brain Stimulation (DBS) of Nucleus Accumbens (NAc) for Treatment-Resistant Depression (4 Case Reports)

Deep Brain Stimulation (DBS) for Treatment-Resistant Depression (TRD) explores the cutting-edge intersection of technology and neuroscience, offering hope to those for whom traditional treatments have failed.

By targeting specific brain areas, such as the nucleus accumbens, DBS attempts to modulate the underlying neural circuits associated with depression.

A recent review analyzed case reports documenting significant improvement in clinical depression as a result of stimulating a brain structure called the “nucleus accumbens” (NAc).


  1. Treatment-Resistant Depression: TRD is a severe form of major depressive disorder that does not respond to conventional treatment methods, including medication and psychotherapy.
  2. Deep Brain Stimulation: DBS is an investigational therapy for TRD, involving the implantation of electrodes in specific brain regions to deliver targeted electrical impulses.
  3. Nucleus Accumbens & Connectivity: The nucleus accumbens area is a focal point for DBS in TRD due to its central role in the brain’s reward circuitry, with structural and functional connectivity analyses revealing insights into the mechanisms of symptom improvement.
  4. Longitudinal & Retrospective Analysis: Studies, including a longitudinal, retrospective analysis of four female patients, highlight the potential of DBS in achieving remission in TRD cases, underscoring the importance of further research in larger cohorts and over longer periods.

Source: European Archives of Psychiatry & Clinical Neuroscience (2023)

What is Deep Brain Stimulation (DBS)?

Deep Brain Stimulation (DBS) is an advanced neurosurgical procedure that has shown promise in treating various neurological and psychiatric disorders, including Treatment-Resistant Depression (TRD).

The mechanism of DBS involves the delivery of electrical impulses to specific brain areas to modulate abnormal neural circuits that contribute to disease symptoms.

In the context of depression, targeting the nucleus accumbens is particularly beneficial due to its central role in the brain’s reward system and emotional regulation.

Modulating Neural Circuits

DBS for depression involves the surgical implantation of electrodes in targeted brain regions.

These electrodes are connected to a pulse generator, typically placed under the skin in the chest, which sends controlled electrical impulses to the brain.

The precise mechanism by which DBS alleviates depression is not fully understood, but it is believed to involve the modulation of dysfunctional neural circuits.

By adjusting the electrical impulses, DBS can change the activity of specific brain areas and neural pathways involved in mood regulation, potentially resetting the brain’s reward and emotional processing systems to alleviate depressive symptoms.

(Case Report: Depression Treated with Deep Brain Focused Ultrasound)

Why target the nucleus accumbens (NAc) with DBS for depression?

Reward Processing

The nucleus accumbens has been identified as a key node in the mesolimbic pathway, a neural circuit that mediates reward perception and emotional responses.

In depression, this reward system is often dysregulated, leading to symptoms such as anhedonia and low motivation.

Targeting the nucleus accumbens with DBS aims to directly modulate this dysregulation, potentially restoring normal reward processing and emotional responses.

Connectivity to Emotional Regulation Networks

The nucleus accumbens is interconnected with various other brain regions involved in mood regulation, including the prefrontal cortex, amygdala, and hippocampus.

By modulating activity in the nucleus accumbens, DBS can have downstream effects on these connected regions, contributing to an overall improvement in mood and emotional stability.

Major Findings: DBS of the Nucleus Accumbens for Treatment-Resistant Depression (2023 Cases)

Leserri et al. reviewed cases of Deep Brain Stimulation (DBS) for Treatment-Resistant Depression (TRD), specifically targeting the nucleus accumbens – below are the major findings.

1. Remission Rate & Clinical Improvement

  • 66% Remission Rate: A notable finding from this study is the 66% remission rate observed at the 1-year follow-up among the participants. This demonstrates the potential of DBS targeting the nucleus accumbens in inducing significant clinical improvement in TRD patients who had previously not responded to conventional treatments.
  • Sustained Response: For one patient, remission was not only achieved but sustained for an extended period, highlighting the durability of DBS effects in certain cases.

2. Structural Connectivity Insights

  • Connection to Brodmann Area 25: The study uncovered a consistent structural connectivity between the nucleus accumbens and Brodmann area 25 in the patient with the longest remission phase. This area is critically involved in emotional regulation and has been implicated in depression, suggesting its importance in the therapeutic mechanism of DBS.
  • Pathway to Prefrontal Cortex: Enhanced structural connectivity to the prefrontal cortex was observed, particularly in areas associated with executive function and mood regulation. This finding aligns with the hypothesis that effective DBS may modulate broader neural networks beyond the immediate target area.

3. Functional Connectivity Insights

  • Patient-Specific R-Maps: The creation of patient-specific R-maps, correlating functional connectivity with symptom improvement, is a groundbreaking aspect of this study. These maps revealed that functional connections between the nucleus accumbens and specific regions in the prefrontal cortex were significantly associated with clinical improvements.
  • Variability Across Patients: The study also noted variability in functional connectivity patterns across patients, underscoring the personalized nature of DBS effects and the necessity for tailored treatment approaches.

DBS of the Nucleus Accumbens for Depression (2023 Cases)

The primary objective of this study was to evaluate the efficacy and mechanisms of DBS in the nucleus accumbens for patients with TRD.

It sought to correlate clinical improvements with changes in structural and functional connectivity, hypothesizing that specific connectivity patterns may predict therapeutic success.


The study included four female patients diagnosed with TRD, undergoing DBS targeting the nucleus accumbens.

Each participant had a history of non-response to multiple conventional treatments, including antidepressants, psychotherapy, and electroconvulsive therapy.

  • Structural Connectivity: Analyzed using probabilistic tractography derived from diffusion MRI, allowing for the mapping of white matter tracts from the nucleus accumbens to various brain regions.
  • Functional Connectivity: Assessed by combining patient-specific stimulation volumes with a normative functional connectome, estimated through functional MRI (fMRI).
  • Clinical Outcomes: Measured via standardized depression rating scales at baseline and during follow-up sessions, enabling the evaluation of DBS efficacy over time.


  • A notable remission rate of 66% was observed at the 1-year follow-up, indicating DBS’s potential in alleviating symptoms of TRD.
  • Structural Connectivity: A consistent structural connectivity to Brodmann area 25 was observed in the patient with the longest remission phase, suggesting its importance in DBS therapy for TRD.
  • Functional Connectivity: Patient-specific R-maps highlighted significant correlations between symptom improvement and connectivity in the prefrontal cortex, although these findings varied across patients.


  • Small Sample Size: With only four participants, the study’s findings are preliminary and require validation in larger cohorts.
  • Lack of Longitudinal Imaging Data: The absence of repeated imaging sessions throughout the follow-up period limits the ability to directly correlate changes in connectivity with clinical outcomes.
  • Open-Label Design: The absence of a control group and the open-label nature of the study introduce potential biases, including placebo effects.
  • Generalizability: The exclusive focus on female patients with TRD may limit the applicability of findings to the broader population of individuals with depression.

Pursuing Deep Brain Stimulation for Depression (The Steps)

For individuals with refractory or Treatment-Resistant Depression (TRD), pursuing Deep Brain Stimulation (DBS) of the nucleus accumbens or other brain regions represents a path towards potential relief when traditional treatments have failed.

This process involves a multidisciplinary approach, combining the expertise of psychiatrists, neurosurgeons, and other specialists to determine the most suitable intervention for each individual.

1. Initial Consultation & Evaluation

The journey typically begins with a comprehensive evaluation by a psychiatrist or a team specializing in TRD.

This assessment confirms the diagnosis of TRD, ensuring that the individual has undergone multiple treatment attempts, including medications, psychotherapy, and possibly electroconvulsive therapy (ECT), without sufficient improvement.

A detailed psychiatric and medical history, along with a review of previous treatments, helps to establish the severity and persistence of the depression.

2. Multidisciplinary Team Assessment

Once TRD is confirmed, the individual may be referred to a specialized center with expertise in DBS.

A multidisciplinary team, including neurologists, neurosurgeons, psychiatrists, and neuropsychologists, conducts a thorough evaluation.

This assessment determines the patient’s suitability for DBS, considering factors such as the presence of any contraindications to surgery, the individual’s overall health, and the potential for benefiting from DBS.

3. Informed Consent & Preoperative Planning

Patients who are deemed suitable candidates for DBS undergo a detailed informed consent process.

They receive information about the procedure, potential risks, benefits, and the postoperative care required.

Preoperative planning involves neuroimaging studies, such as MRI and CT scans, to map the brain’s structure for precise targeting of the DBS electrodes.

4. Targeting the Nucleus Accumbens (or Other Regions)

The nucleus accumbens is a key target for DBS in TRD due to its central role in the brain’s reward system and its connectivity with mood regulation networks.

Targeting this region aims to modulate the dysfunctional neural circuits associated with depression, potentially restoring normal mood and emotional responses.

5. Postoperative Care and Follow-up

After DBS surgery, patients require careful monitoring and follow-up to adjust the stimulation parameters for optimal therapeutic effects.

This process involves regular visits with the DBS team to fine-tune the device settings based on the patient’s response and any side effects experienced.

Psychological support and continued psychiatric care are essential components of postoperative care, ensuring the patient’s overall well-being and adjustment to life with DBS.

Other Deep Brain Stimulation Targets that May Help Treat Refractory Depression

Subcallosal Cingulate

The subcallosal cingulate gyrus is another common target for DBS in TRD.

It plays a significant role in emotional regulation and has shown promising results in reducing depressive symptoms in several studies.

Targeting this area can modulate the activity of connected brain regions involved in depression.

Ventral Capsule/Ventral Striatum (VC/VS)

The VC/VS is targeted for its involvement in emotional regulation and its extensive connections with the prefrontal cortex and limbic system.

DBS in this region has been explored for both depression and obsessive-compulsive disorder (OCD), with some patients experiencing significant improvements.

Medial Forebrain Bundle (MFB)

The MFB is a newer target for DBS in TRD, chosen for its role in the brain’s reward system and its direct connections between the ventral tegmental area and the nucleus accumbens.

Early studies targeting the MFB have shown rapid and robust antidepressant effects, making it a promising area for future research.

Conclusion: Deep Brain Stimulation of Nucleus Accumbens for Depression

This study underscores the potential of Deep Brain Stimulation (DBS) targeting the nucleus accumbens as a viable treatment option for individuals with Treatment-Resistant Depression (TRD), offering new hope to those for whom conventional therapies have been ineffective.

By examining the structural and functional connectivity changes associated with DBS, the research provides invaluable insights into the mechanisms underlying its therapeutic effects, highlighting the importance of personalized treatment approaches based on detailed brain mapping.

Although the findings from this small cohort are preliminary, they pave the way for larger, more comprehensive studies that could further validate and refine DBS as a treatment for TRD.

The variability in clinical outcomes and connectivity patterns observed across patients underscores the complexity of depression as a neural network disorder and the need for targeted interventions.

Future research should focus on optimizing DBS protocols, exploring additional brain regions for stimulation, and integrating multimodal treatment strategies to enhance efficacy.

Overall, this study contributes significantly to our understanding of DBS in TRD, marking an important step towards developing more effective and personalized treatments for one of psychiatry’s most challenging conditions.


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