**6. PET, fMRI, and DBS**

Functional MRI (fMRI) is a neuroimaging modality with a wide range of application in both biomedical research and clinical studies. In addition to its high resolution for soft tissue imaging, MRI has the ability to assess physiological parameters including metabolites, diffusion, or hemodynamics [46]. Neuronal activity causes a secondary hemodynamic response, including a local vascular response, which can be measured by fMRI [47, 48]. fMRI has promoted our understanding about behavioral and translational neuroscience as it has provided human brain function maps in addition to conventional anatomical imaging.

When it comes to DBS, positron emission tomography (PET) scan is more preferred than fMRI as it provides a safer modality for studying patients during DBS intervention. PET is used for studying both mechanism and unexpected effects of DBS [49]. According to these facilities, PET has become a gold standard for imaging of in vivo neurochemistry.

Combination of fMRI and PET modalities has provided a terrific opportunity in research to understand the neurochemistry of brain and underlying biochemical nature of brain function.

### **7. Diffusion tensor imaging (DTI)**

Diffusion tensor imaging is an emerging modality that enables us to characterize microstructure of white matter and this may help with further development of targeting methods and brain stimulation therapies [50]. The technology used behind the DTI is measuring three-dimensional movement of water molecules in biological tissue. DTI calculates diffusion of water in three dimensions by fitting a tensor to each voxel of a brain diffusion-weighted MR scan [51]. Three-dimensional visualization of brain white matter pathways can be provided by DTI-based tractography [52, 53]. This has resulted in better understanding of brain anatomical structure, which can be implied in neurosurgical procedures [54, 55].

Defining accurate position of targets is a key point in neurosurgical stimulation process. The role of DTI in detailed visualization of white matter becomes more important when the conventional imaging modalities cannot reliably show the putative target location [50]. Tractography-guided neuromodulation has been tried for DBS in patients with Parkinson's disease and dystonia. This will help surgeons with finding individual anatomic variations and so achieving better results.

### **8. Less invasive stimulation modalities**

Neuromodulation carries a vast range of procedures from pharmacological interferences to the direct stimulation of brain with placed electrodes. Noninvasive brain stimulation (NIBS) devices work based on transferring electrical currents into the brain (usually cortex) through externally placed electrodes. These currents may be alternating or even created by magnetic fields [56]. In addition to its developed application in research, NIBS has dramatically entered to the clinical management of several neurologic/psychiatric disorders. Repeated trains of transcranial magnetic stimulation (rTMS) were first approved by FDA for management of major depressive disorders and obsessive-compulsive disorders, while migraine headaches are managed by single pulse TMS [56, 57].

A dynamic magnetic field is produced by TMS devices, which induces a consequent electric field through the skull and scalp. When this electric field is

**21**

and cingulotomy [71].

*Neuromodulation in the Age of Modern Neuroimaging Technologies*

delivered to the motor cortex, neurons forming the corticospinal tract are depolarized at the junction of gray and white matter. In addition, axons in superficial layers of cortex including interneurons and thalamocortical afferents can be triggered by TMS pulses. TMS has effects on various brain neurotransmitter systems including their second messengers and receptors. Also, it promotes synaptic plasticity, which is a justification for TMS use in pain management. On the other hand, some previously published researches have indicated that TMS is effective in reducing frequency of epileptic attacks in patients with medically refractory epilepsy, without imposing any additional side effects. Another pilot study holds the belief that TMS in combination with EEG is an appropriate method for developing quantitative biomarkers of cortical hyperexcitability in patients with

A considerable problem with application of rTMS is its variable effects among different patients [59, 60]. This makes the research results' replication a problem and application of rTMS to clinical therapeutic setting a controversial issue. When we use rTMS in a precise cortical area, it will equally affect all the neuronal populations and consequent behaviors involving that area [61]. Therefore, combination of EEG and rTMS seems to be an appropriate method in order to specify the rTMS effects in patients through direct measurement of cortical responses to TMS pulses [62]. This helps with measurement of TMS-evoked potentials (TEPs) and the meantime effects of TMS on the recording EEG. Various TEPs' components are a reflection of activity in a precise area of cortical neurons. So, this may result in development of more selectively targeted forms of rTMS in non-motor areas of

Transcranial direct current stimulation (tDCS) is another form of noninvasive brain stimulation techniques that is easily available and not extensive, while the exact mechanism of action has not been yet discovered [63, 64]. In this method, electrodes are placed on the scalp and they conduct weak prolonged (about 10–20 min) currents to brain tissues. Indeed, neuronal excitability is modulated in a polarity-specific manner by tDCS [65]. The modulatory effects of tDCS are the main role considered for this procedure as it shifts membrane polarity resulting to modifying the neuronal discharge. There are two subdivisions: anodal tDCS increases the rate of spontaneous neuronal firing by depolarizing resting membrane potential, while cathodal tDCS shifts the resting membrane potential to hyperpolarization, which leads into decreased cortical excitability [66]. tDCS has approved improving effects on patients with various types of anxiety disorders such as social anxiety disorders, generalized anxiety disorders, and anorexia nervosa as well as

Besides the proved applications of tDCS in previous studies, the effect of sham

tDCS has not been yet completely assessed. Some previously conducted shamcontrolled studies have reported inconsistent results with placebo response, which

**9. Neuroimaging and neurosurgical treatment of psychiatric disorders**

Progresses in neuroimaging have resulted in developing a notable amount of new indications of DBS for psychiatric disorders. Discovering new functions and relationships for internal capsule, cingulate cortex and their networks is a result of modern neuroimaging techniques. In the major part of the situations, nodes of these networks are in the regions that are responsible for functional changes in psychiatric pathology that kind of confirms the benefits of conventional capsulotomy

*DOI: http://dx.doi.org/10.5772/intechopen.92737*

major depression and chronic pain [67–69].

make this idea more important [70].

epilepsy [58].

the cortex.

### *Neuromodulation in the Age of Modern Neuroimaging Technologies DOI: http://dx.doi.org/10.5772/intechopen.92737*

*Neurostimulation and Neuromodulation in Contemporary Therapeutic Practice*

maps in addition to conventional anatomical imaging.

which can be implied in neurosurgical procedures [54, 55].

**8. Less invasive stimulation modalities**

are managed by single pulse TMS [56, 57].

Functional MRI (fMRI) is a neuroimaging modality with a wide range of application in both biomedical research and clinical studies. In addition to its high resolution for soft tissue imaging, MRI has the ability to assess physiological parameters including metabolites, diffusion, or hemodynamics [46]. Neuronal activity causes a secondary hemodynamic response, including a local vascular response, which can be measured by fMRI [47, 48]. fMRI has promoted our understanding about behavioral and translational neuroscience as it has provided human brain function

When it comes to DBS, positron emission tomography (PET) scan is more preferred than fMRI as it provides a safer modality for studying patients during DBS intervention. PET is used for studying both mechanism and unexpected effects of DBS [49]. According to these facilities, PET has become a gold standard for imaging

Combination of fMRI and PET modalities has provided a terrific opportunity in research to understand the neurochemistry of brain and underlying biochemical

Diffusion tensor imaging is an emerging modality that enables us to characterize microstructure of white matter and this may help with further development of targeting methods and brain stimulation therapies [50]. The technology used behind the DTI is measuring three-dimensional movement of water molecules in biological tissue. DTI calculates diffusion of water in three dimensions by fitting a tensor to each voxel of a brain diffusion-weighted MR scan [51]. Three-dimensional visualization of brain white matter pathways can be provided by DTI-based tractography [52, 53]. This has resulted in better understanding of brain anatomical structure,

Defining accurate position of targets is a key point in neurosurgical stimulation process. The role of DTI in detailed visualization of white matter becomes more important when the conventional imaging modalities cannot reliably show the putative target location [50]. Tractography-guided neuromodulation has been tried for DBS in patients with Parkinson's disease and dystonia. This will help surgeons with finding individual anatomic variations and so achieving better results.

Neuromodulation carries a vast range of procedures from pharmacological interferences to the direct stimulation of brain with placed electrodes. Noninvasive brain stimulation (NIBS) devices work based on transferring electrical currents into the brain (usually cortex) through externally placed electrodes. These currents may be alternating or even created by magnetic fields [56]. In addition to its developed application in research, NIBS has dramatically entered to the clinical management of several neurologic/psychiatric disorders. Repeated trains of transcranial magnetic stimulation (rTMS) were first approved by FDA for management of major depressive disorders and obsessive-compulsive disorders, while migraine headaches

A dynamic magnetic field is produced by TMS devices, which induces a consequent electric field through the skull and scalp. When this electric field is

**6. PET, fMRI, and DBS**

of in vivo neurochemistry.

nature of brain function.

**7. Diffusion tensor imaging (DTI)**

**20**

delivered to the motor cortex, neurons forming the corticospinal tract are depolarized at the junction of gray and white matter. In addition, axons in superficial layers of cortex including interneurons and thalamocortical afferents can be triggered by TMS pulses. TMS has effects on various brain neurotransmitter systems including their second messengers and receptors. Also, it promotes synaptic plasticity, which is a justification for TMS use in pain management. On the other hand, some previously published researches have indicated that TMS is effective in reducing frequency of epileptic attacks in patients with medically refractory epilepsy, without imposing any additional side effects. Another pilot study holds the belief that TMS in combination with EEG is an appropriate method for developing quantitative biomarkers of cortical hyperexcitability in patients with epilepsy [58].

A considerable problem with application of rTMS is its variable effects among different patients [59, 60]. This makes the research results' replication a problem and application of rTMS to clinical therapeutic setting a controversial issue. When we use rTMS in a precise cortical area, it will equally affect all the neuronal populations and consequent behaviors involving that area [61]. Therefore, combination of EEG and rTMS seems to be an appropriate method in order to specify the rTMS effects in patients through direct measurement of cortical responses to TMS pulses [62]. This helps with measurement of TMS-evoked potentials (TEPs) and the meantime effects of TMS on the recording EEG. Various TEPs' components are a reflection of activity in a precise area of cortical neurons. So, this may result in development of more selectively targeted forms of rTMS in non-motor areas of the cortex.

Transcranial direct current stimulation (tDCS) is another form of noninvasive brain stimulation techniques that is easily available and not extensive, while the exact mechanism of action has not been yet discovered [63, 64]. In this method, electrodes are placed on the scalp and they conduct weak prolonged (about 10–20 min) currents to brain tissues. Indeed, neuronal excitability is modulated in a polarity-specific manner by tDCS [65]. The modulatory effects of tDCS are the main role considered for this procedure as it shifts membrane polarity resulting to modifying the neuronal discharge. There are two subdivisions: anodal tDCS increases the rate of spontaneous neuronal firing by depolarizing resting membrane potential, while cathodal tDCS shifts the resting membrane potential to hyperpolarization, which leads into decreased cortical excitability [66]. tDCS has approved improving effects on patients with various types of anxiety disorders such as social anxiety disorders, generalized anxiety disorders, and anorexia nervosa as well as major depression and chronic pain [67–69].

Besides the proved applications of tDCS in previous studies, the effect of sham tDCS has not been yet completely assessed. Some previously conducted shamcontrolled studies have reported inconsistent results with placebo response, which make this idea more important [70].

### **9. Neuroimaging and neurosurgical treatment of psychiatric disorders**

Progresses in neuroimaging have resulted in developing a notable amount of new indications of DBS for psychiatric disorders. Discovering new functions and relationships for internal capsule, cingulate cortex and their networks is a result of modern neuroimaging techniques. In the major part of the situations, nodes of these networks are in the regions that are responsible for functional changes in psychiatric pathology that kind of confirms the benefits of conventional capsulotomy and cingulotomy [71].

These days, personalized medicine has become the most commonly mentioned subject in the modern medicine. All the medicine-related fields are trying to find ways that help with individualized treatment of the diseases, thus treating patients instead of diseases [72]. So, psychiatrists are following this trend and modern neuroimaging techniques may help them with finding proper treatment for each patient [73]. So far, neuroimaging was used only for checking the proper placement of electrodes and retrograde evaluation of interventional mechanisms; however, these modalities will be used for planning new treatment methods and targets for DBS in near future. Neuroimaging can provide lots of valuable data about connectivity and regional volume in each patient. Thus, it not only helps with choosing the most appropriate approach in psychiatric neurosurgery but also simplifies prediction of interventional outcomes [74–76].

Looking at the recent published studies around neuroimaging, we found out that developing neuroimaging techniques is leading to the age of "precision surgery." In this period of time, neuroimaging will change the face and approach to electrode implantation and patient selection as well as selection of surgical targets throughout individualized neuroanatomy extracted from modern neuroimaging modalities and technologies [74, 77, 78].
