Conclusions

Functional neuroimaging offers a great opportunity to noninvasively study the

underlying activities in the normal as well as diseased brain. In this dissertation, we have

investigated utilizing EEG source imaging and functional MRI in the diagnosis and

management of epilepsy and pain.

One important application of functional neuroimaging techniques in detecting and

localizing pathological activities lies in pre-surgical evaluations of patients suffering from

intractable epilepsy. In one of the studies presented here, we have proposed an ICA-based

automated method to lateralize and localize hemodynamic foci in focal epilepsy patients

for presurgical evaluation. Focal activities identified by our method were in concordance

with surgical resection in the majority of cases studied. Our findings suggest the

possibility of noninvasively and accurately localizing epileptic foci using fMRI alone in

presurgical planning. This was a feasibility study to demonstrate the value of the

proposed method. Additional features can be incorporated in the algorithm to improve

reliability and performance. A larger patient population needs to be studied to test the

broad applicability of this method. This proposed method can be easily implemented in

the current presurgical workup to provide additional information for guiding the surgical

resection.

Unlike for patients with focal epilepsy, surgical resection is not a viable treatment

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mechanism of generating wide spread epileptic activity remains poorly understood.

Therefore in order to provide benefits to these patients, there is a pressing need to

improve our understanding of the neural network and mechanism of action in order to

develop novel therapeutic approaches such as deep brain stimulation. In the second study

presented, by combining the complementary strengths of EEG and fMRI, we showed

consistent results concerning the genesis and propagation of GSWDs. EEG-informed

fMRI revealed multiple brain regions that may be involved in GSWDs. By means of

seed-based fMRI, we tested the specific network level activity and found temporal

correlation between cortical and bithalamic BOLD activities. According to the Granger

Causality analysis the mediodorsal nuclei of the thalamus serve as the main driver

throughout the initiation and the propagation of the GSWDs. Once validated, this work

can provide insight in understanding the enigmatic etiology of generalized epilepsy and

offer guidance in treatments. This work suggests the thalamus, especially the mediodorsal

nuclei, may serve as potential targets for deep brain stimulation to treat patients with

drug-resistant generalized epilepsy.

Another field of application of such noninvasive imaging techniques is to provide

better understanding of how the brain processes pain and ultimately to provide an

objective measure of pain. For the study of exogenously elicited pain, by using scalp

EEG we found that the spontaneous rhythms in all frequency bands except gamma band

were suppressed globally at the presence of tonic painful thermal stimulation. The

greatest changes were observed in the alpha power on the contralateral side to the

stimulus in the somatosensory area. Additionally, the results suggested that the degree of

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connectivity among major brain regions that responsive to pain, which was revealed

through causality analysis. Although the current finding is based on the study of sustained

pain from external stimuli in healthy subjects, it would help broaden our understanding of

cortical response to patients with chronic pain.

In addition to external pain, we also studied patients with sickle cell disease, as

they often suffer from chronic or acute pain as a result of the disease. We found that

through fMRI based functional connectivity analyses, the resting state neural network in

patients deviated from those of the healthy controls with both positive and negative

effects. The default mode network, which is a ubiquitous resting state activity believed to

be responsible for a host of cognitive functions such as memory consolidation and

introspection, is reduced in patients with SCD compared to controls. On the other hand,

insula cortex, which is a key node in the pain network, showed a marked increase in

bilateral synchrony in patients with SCD as opposed to healthy controls.

In summary, the present dissertation research developed and evaluated the

spatiotemporal imaging approaches for the non-invasive mapping of network activities in

the diseased and normal brain. Evaluations were conducted in both patient and healthy

control groups in order to test the clinical applicability of such noninvasive imaging tools.

Regarding epilepsy, two investigations have been conducted to study the localization of

hemodynamic foci in focal epilepsy patients and the widespread GSWDs of generalized

epilepsy patients. The spatial resolution has been further improved by adding the

component of fMRI through an EEG-fMRI integrated imaging framework. For the

application in pain study, two investigations were conducted to study changes in network

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with SCD. All of the results that were obtained suggest the importance of noninvasive

spatiotemporal neuroimaging approaches for solving clinical problems and for

investigating neuroscience questions. Furthermore, an improved understanding of

neurological diseases and their mechanisms would help us to develop and deliver curative

treatments of neurological diseases.