1. Exploring the uncharted
Deep Brain Stimulation
investigated with dMRI
dr. ir. Bram Platel
ir. Ellen Brunenberg
prof. dr.Veerle Visser-Vandewalle
2. Deep Brain Stimulation
Deep Brain Stimulation (DBS) is type
of neuro-modulation.
It is a neuro-surgical treatment, in
which an electrode is implanted in a
specific part of the brain. Through
impulses it receives from a stimulator
it disables that part of the brain.
8. Change in behavior
In more than 50% of the treated patients a change in behavior is
noticed*
Stim Off Stim On
41% cognitive side effects
8% depression
4% mania
*Temel et al. “Behavioural changes after bilateral subthalamic
stimulation in advanced Parkinson disease: a systematic review”
Stim On Stim Off
Bejjani et al. “Transient acute depression induced
by high-frequency deep-brain stimulation”
9. Cause of the side effects
The cause of the side
effects might be that
stimulation is not limited
to the motor part of the
STN*
[Hamani et al.]
*Temel et al. Behavioural changes after bilateral subthalamic stimulation in
advanced Parkinson disease: a systematic review
14. Research Goal
Y. Temel et al. / Progress in Neurobiology 76 (2005) 393–413 399
*Temel et al. “The functional role of the subthalamic nucleus in cognitive and limbic circuits “ [Hamani et al.]
Fig. 3. Schematic illustration of the primate basal ganglia-thalamocortical associative, limbic and motor circuits. The STN has a central position in each of these
circuits. Associative circuit: the two associative circuits are the dorsolateral prefrontal circuit (DPC) and lateral orbitofrontal circuit (LOC), which are initiated from
the dorsolateral prefrontal cortex (DLPC), and lateral orbitofrontal cortex (LOFC), respectively. The second station is the dorsolateral head and the rostrocaudal axis
of the caudate nucleus. From here, this circuit is directed to the dorsomedial part of the GPi and to the rostral region of the SNr and to the anterior parts of the GPe. The
GPi and SNr project to the VA and CM nuclei of the thalamus and the DPC is closed by the thalamocortical pathway back to the DLPC and the LOC back to the LOFC.
This pathway is also known as the direct pathway. From the GPe, a projection to the STN and GPi/SNr exists. This pathway is also known as the indirect pathway. The
STN is anatomically connected with both direct, through its projection to the GPi and SNr, and indirect pathway, through its projection to the GPe. Limbic circuit:
projections from the hippocampus, the amygdala, limbic and paralimbic cortices are primarily concentrated at the level of the ventral striatum. The ventral striatum
consists basically of the nucleus accumbens, ventromedial part of the caudate-putamen and the medium-celled portion of the olfactory tubercle. The ventral striatum
projects in turn to the ventral pallidum (VP). From here the limbic circuit is directed to the MD nucleus of the thalamus. This circuit is closed by a thalamocortical
pathway to the anterior cingulated area and medial orbitofrontal cortex. The STN has reciprocal connections with the ventral pallidum. The ventral pallidum is
15. Research Goal
Y. Temel et al. / Progress in Neurobiology 76 (2005) 393–413 399
*Temel et al. “The functional role of the subthalamic nucleus in cognitive and limbic circuits “ [Hamani et al.]
Using neurological pathways to localize the
Fig. 3. Schematic illustration of the primate basal ganglia-thalamocortical associative, limbic and motor circuits. The STN has a central position in each of these
circuits. Associative circuit: the two associative circuits are the dorsolateral prefrontal circuit (DPC) and lateral orbitofrontal circuit (LOC), which are initiated from
the dorsolateral prefrontal cortex (DLPC), and lateral orbitofrontal cortex (LOFC), respectively. The second station is the dorsolateral head and the rostrocaudal axis
of the caudate nucleus. From here, this circuit is directed to the dorsomedial part of the GPi and to the rostral region of the SNr and to the anterior parts of the GPe. The
STN and to subdivide it into a motor, limbic and
GPi and SNr project to the VA and CM nuclei of the thalamus and the DPC is closed by the thalamocortical pathway back to the DLPC and the LOC back to the LOFC.
This pathway is also known as the direct pathway. From the GPe, a projection to the STN and GPi/SNr exists. This pathway is also known as the indirect pathway. The
STN is anatomically connected with both direct, through its projection to the GPi and SNr, and indirect pathway, through its projection to the GPe. Limbic circuit:
projections from the hippocampus, the amygdala, limbic and paralimbic cortices are primarily concentrated at the level of the ventral striatum. The ventral striatum
associative part.
consists basically of the nucleus accumbens, ventromedial part of the caudate-putamen and the medium-celled portion of the olfactory tubercle. The ventral striatum
projects in turn to the ventral pallidum (VP). From here the limbic circuit is directed to the MD nucleus of the thalamus. This circuit is closed by a thalamocortical
pathway to the anterior cingulated area and medial orbitofrontal cortex. The STN has reciprocal connections with the ventral pallidum. The ventral pallidum is
considered to be the major limbic circuit output region. Modulation of the STN neuronal discharge directly influences the activity of both NMDA and non-NMDA
expressing neurons in the VP. Within this concept of the limbic circuit, the STN again has a pivotal role as it is directly connected with the output of this circuit. Motor
circuit: the cortical input to the motor circuit originates mainly from the primary motor, premotor and somatosensory areas. This somatotopic glutamatergic input is
largely directed to the putamen, which projects topographically to the motor parts (ventrolateral (VL) and posterior) of the GPe and GPi and the SNr. From the GPe, a
pathway projects to the STN. The STN mainly projects to the GPi and SNr. The SNr and the GPi serve as the output nuclei of the basal ganglia. The thalamic areas
involved in the motor circuit are mainly the VL, ventroanterior (VA) and the centromedian nucleus (CM). This loop is closed by means of the thalamic projection
(glutamatergic) to the cortical areas.
30. postmortem brein 3T MRI scanner small cube around the STN 9.4 T MRI scanner
31. postmortem brein 3T MRI scanner small cube around the STN 9.4 T MRI scanner
difusion images
32. postmortem brein 3T MRI scanner small cube around the STN 9.4 T MRI scanner
difusion images
microtome
33. postmortem brein 3T MRI scanner small cube around the STN 9.4 T MRI scanner
difusion images
microtome histological staining
34. postmortem brein 3T MRI scanner small cube around the STN 9.4 T MRI scanner
difusion images
validation
microtome histological staining 3D reconstruction
35. Translation to the patient
The detailed findings of the post-mortem scans have
to be translated to regular dMRI patient data.
• Lower resolution
• Lower SNR
• Different Orientation / Shape
36. Benefits of the research
• Reduction of side effects
• More effective stimulation
• Reduced planning and surgery time
But also:
• Insight in the connectivity of the nuclei
• This may lead to improved stimulation
targets
