Tractography‑Guided Multitarget DBS with Multiple Independent Current Control Combining Linear and Directional Electrodes in Resistant Depression and Anxiety

Introduction: Treatment‑resistant depression (TRD) is a
chronic and severe form of major depressive disorder with
limited therapeutic options. One‑third of TRD patients fail
to respond to pharmacological and psychotherapeutic in
terventions. Deep Brain Stimulation (DBS) is a promising
therapy for TRD patients, but its clinical results have been
highly variable in multiple studies focused on single target
interventions, suggesting suboptimal targeting of the circuits
implicated in TRD. Connectomics approaches have emerged
to enable an individualized planning of symptom-specific
circuits targeting in TRD with promising results. We report a
case of Multitarget DBS involving six neural tract including
subgenual cingulate cortex, Brodmann area 25 (SGC25) and
anterior limb of the internal capsule (ALIC) with distal ex
tension toward the nucleus accumbens (NAc) stimulation.
Clinical description: A 34‑year‑old woman presented with a
chronic psychiatric history dating back to age 10, when she
developed disordered eating behaviors, bulimia nervosa type
1 and later anorexia nervosa at 15 years managed with limited
success. Over the ensuing years, she experienced recurrent
major depressive episodes, generalized anxiety disorder, pa
nic attacks, social phobia, and agoraphobia. Despite multiple
evidence‑based psychiatric interventions—including cogni
tive behavioral therapy and sequential pharmacotherapy with
selective and multiple serotonin reuptake inhibitors and se
rotonin–norepinephrine reuptake inhibitors—her symptoms
remained refractory or transient improvement. At evaluation,
affective lability, anhedonia, hopeless, and intrusive anxiety
are presented persistently. Given the TRD diagnostic, a mul
tidisciplinary team recommended an innovative multitarget
DBS approach using Multiple Independent current control
(MICC).
Discussion: This case illustrates the potential of simultaneous
modulation of interconnected affective and cognitive circuits
implicated in TRD. The ALIC‑NAc target was selected to
precisely modulate anxiety and reward‑related networks, while the SGC25 was chosen to engage affective regulation
pathways including medial forebrain bundle (MFB), dorsal
longitudinal fasciculus (DLF), and anterior thalamic radia
tion (ATR), all described with antidepressant effect in DBS
for TRD. MICC technology enabled tailored stimulation ac
cording to TRD individual evolution explaining the obser
ved multidomain symptomatic improvement across scales.
At four‑month follow‑up, Hamilton Depression Rating Scale
(HDRS‑17) scores improved by 65%, Montgomery–Åsberg
Depression Rating Scale (MADRS) by 70%, with additional
improvement in Beck inventory depression and anxiety sca
les (BDI and BAI).
Conclusions: This novel single‑case study supports the fea
sibility and clinical benefit of multitarget MICC-DBS gui
ded by connectomics in TRD. Individualized modulation of
SGC25 and ALIC‑NAc may improve cognitive and anxiety
predominant symptoms in TRD patients. Further studies are
needed to replicate these findings in a well-selected cohort
of TRD patients to validate the individualized multitarget
MICC‑DBS modulation and its progressive capacity to im
prove symptoms in TRD. Coronal postoperative MRI with
tractography overlay demonstrating bilateral multitarget
DBS electrode trajectories. Directional Cartesia™ leads were
placed in the SGC25, while linear Vercise™ leads traversed
the ALIC with distal contacts in the NAc. Patient-specific
tractography highlights key white matter pathways: MFB
(blue), ATR (green), and DLF (red), confirming engagement
of fronto‑limbic and reward circuits relevant to depression
and anxiety modulation. (Figure 1)