No description available.

No description available.

Although it is well-established that animals will self-stimulate electric current to various diverse brain structures, the neural substrate of brain stimulation reward (BSR) has eluded identification since its discovery more than a half-century ago. We show that GABA neurons in the midbrain, hypothalamus and thalamus express connexin-36 (Cx36) gap junctions and couple electrically with dopamine application or by stimulation of the internal capsule (IC), which also supports self-stimulation. The threshold for responding for self-stimulation of the IC is the threshold for coupling between these GABA neurons, the degree of responding for IC ICSS is proportional to the magnitude of electrical coupling between these GABA neurons, and GJ blockers, including the Cx36 blocker mefloquine, increase the threshold for IC self-stimulation without affecting performance. Thus, electrical coupling between this network of GABA neurons fits the prevailing model for the elusive integrator of BSR.

Deep brain stimulation (DBS) improves the quality of life for patients suffering from neurological disorders such as Parkinson’s disease and, more recently, psychiatric/cognitive disorders such as depression and addiction. This treatment option involves the implantation of an implantable pulse generator (or neurostimulator) and leads (or electrodes) implanted deep within the human brain. Magnetic resonance imaging (MRI) is a powerful diagnostic tool that offers superior soft tissue contrast and is routinely used in clinics for neuroimaging applications. MRI is advantageous in DBS pre-surgical planning as precise lead placement within the brain is essential for optimal treatment outcomes. DBS patients can also benefit from post-surgery MRI, and studies have shown that DBS patients are more likely to require MRI within 5-10 years post-surgery. However, imaging DBS patients is restricted by substantial safety concerns that arise from localized electric charge accumulation along the implanted device during resonant radiofrequency (RF) excitation, which can potentially lead to tissue heating and bodily damage. With the technological advancement of ultra-high field (UHF) MRI systems and a growing DBS patient population, DBS MRI safety will become increasingly problematic in the future and needs to be addressed. Parallel RF transmission (pTx) is a promising technology that utilizes multiple transmit channels to generate a desired electromagnetic profile during MRI RF excitation. Several proof-of-concept studies successfully demonstrated its efficacy in creating a "safe mode" of imaging that minimizes the localized RF heating effects. However, pTx MRI systems are not easily accessible and are often custom-built and integrated onto existing MRI systems. Consequently, it adds system characterization and verification complexity to the DBS MRI safety problem. System channel count is also an important consideration as implementation costs can be very high, and the impact of system transmit channel count remains unexplored. Furthermore, in practice, DBS patients with motor-related disorders will impact the pTx MRI system’s ability to precisely generate these safe mode electromagnetic profiles. Commercial DBS devices (i.e., the neurostimulator and leads) are manufactured with fixed dimensions, and the caring surgeon typically manages the surgical orientation of the implanted DBS device and leads. Therefore, lead trajectories can vary hospital-to-hospital. As a result, standard phantoms, i.e., the ASTM International Standard, used in safety verification experiments may not be suitable for DBS MRI applications. To advance DBS patient safety in MRI, this thesis studied the implant heating effects of pTx system uncertainty, system channel count, patient motion on a novel pTx MRI research platform and its associated safe mode of imaging. It developed a new anthropomorphic heterogeneous phantom to improve safety verification experiments. / Dissertation / Doctor of Philosophy (PhD)

No description available.

Studies attempting to increase working memory (WM) capacity show promise in enhancing related cognitive functions (see Morrison & Chein, 2011 for a recent review), but have also raised criticism in the broader scientific community given the scattered findings produced by these studies (Morrison & Chein, 2011; Shipstead, Redick, & Engle, 2010, 2012). Non-invasive brain stimulation, in particular transcranial direct current stimulation, has been shown to enhance WM performance in a single session (Fregni, et al., 2005) as well as learning over time in other cognitive domains (Iuculano & Cohen Kadosh, 2013; Reis, et al., 2009). However, the extent to which tDCS might enhance learning on a WM training regime, and the extent to which learning gains might transfer outside of the training task remain unknown. To this end, participants engaged in an adaptive WM training task (previously utilized in Chein & Morrison, 2010; Richmond, Morrison, Chein, & Olson, 2011) for 10 sessions over two weeks, concurrent with either active or sham stimulation of dorsolateral prefrontal cortex. Before and after training, a battery of tests tapping domains known to relate to WM abilities was administered. Results show that tDCS reliably enhanced learning on the training task, particularly in the verbal domain. Furthermore, tDCS was shown to enhance transfer to other untrained WM tasks. These results lend support to the idea that tDCS might bolster training and transfer gains in populations with compromised WM abilities. / Psychology

Diffusion tensor imaging (DTI) is a noninvasive MRI technique used to assess white matter (WM) integrity, fiber orientation, and structural connectivity (SC) using water diffusion properties. DTI techniques are rapidly evolving and are now having a dramatic effect on depression research. Major depressive disorder (MDD) is highly prevalent and a leading cause of worldwide disability. Despite decades of research, the neurobiology of MDD remains poorly understood. MDD is increasingly viewed as a disorder of neural circuitry in which a network of brain regions involved in mood regulation is dysfunctional. In an effort to better understand the neurobiology of MDD and develop more effective treatments, much research has focused on delineating the structure of this mood regulation network. Although many studies have focused on the structural connectivity of the mood regulation network, findings using DTI are highly variable, likely due to many technical and analytical limitations. Further, structural connectivity pattern analyses have not been adequately utilized in specific clinical contexts where they would likely have high relevance, e.g., the use of white matter deep brain stimulation (DBS) as an investigational treatment for depression. In this dissertation, we performed a comprehensive analysis of structural WM integrity in a large sample of depressed patients and demonstrated that disruption of WM does not play a major role in the neurobiology of MDD. Using graph theory analysis to assess organization of neural network, we elucidated the importance of the WM network in MDD. As an extension of this WM network analysis, we identified the necessary and sufficient WM tracts (circuit) that mediate the response of subcallosal cingulate cortex DBS treatment for depression; this work showed that such analyses may be useful in prospective target selection. Collectively, these findings contribute to better understanding of depression as a neural network disorder and possibly will improve efficacy of SCC DBS.

In the present study, the Electromechanical Therapeutic Apparatus was examined to determine the extent to which its repeated use can influence intellectual performance and mood state. The Electromechanical Therapeutic Apparatus is a device designed to mildly stimulate the body and brain, while facilitating relaxation. Its three components include a rotating platform-bed; a weak, extremely-low-frequency, external-electric field; and music. In the present study, three groups were contrasted, a music-only group which served as a placebo; a group which combined motion-vestibular stimulation and music; and a group which combined motion-vestibular stimulation and music with an externalelectric field. The sample included 33 randomly selected men and women whose average age was 34.6 years.

The present thesis examines the effects of transcranial direct current stimulation and forelimb rehabilitation on motor recovery after stroke in rats. Post-stroke motor outcomes were quantified using an innovative battery of behavioural tests and high resolution, in vivo electrophysiology was employed to examine coherence of neural activity between hemispheres. It was shown that rats that received brain stimulation concurrently with forelimb rehabilitation displayed functional recovery, whereas rats that received rehabilitation alone partially regained motor function, but the improvements were not due to restitution of original movement patterns. Results from electrophysiological recordings showed that rats that received brain stimulation and rehabilitation regained pre-stroke levels of interhemispheric coherence, but rats that received rehabilitation alone did not. The present thesis suggests that transcranial direct current stimulation may be a viable adjunct therapy to increase the efficacy of physical rehabilitation with regard to post-stroke motor outcomes. Interhemishperic coherence between homotopic neuronal populations may represent a biomarker of genuine motor recovery after stroke. / ix, 75 leaves : col. ill. ; 29 cm

Associative plasticity, which involves modification of synaptic strength by coactivation of two synaptic inputs, has been demonstrated in many species. Here I explore whether it is possible to induce associative plasticity within a corticocortical pathway in the human brain using a novel protocol that activates two brain areas repeatedly with double-site transcranial magnetic stimulation (TMS). The pathway between ventral premotor cortex (PMv) and primary motor cortex (M1) which computes hand movements for precision grasp was manipulated. First, I selectively potentiated physiological connectivity between the stimulated brain areas. The effects as assessed with paired-pulse TMS were in accordance with principles of spike timing-dependent plasticity (STDP), pathwayspecific and showed a different pattern of expression during rest and during performance of a naturalistic prehension task. Furthermore, I demonstrated that effects evolved rapidly, lasted for up to three hours and were reversible. In a follow-up study, the protocol‘s effects on network interactions were investigated using functional magnetic resonance imaging (fMRI), specifically focussing on functional connectivity of network nodes within the wider parietofrontal circuit controlling reaching-and-grasping. The study demonstrated that functional connectivity was causally modified between stimulated nodes and that those changes in coupling also affected parallel, functionally-related pathways. Comparison of neurophysiological (paired-pulse TMS) and functional (fMRI) connectivity between individuals revealed a linear relationship of these connectivity indices; the first can assess the physiological nature of the interaction, whereas the latter can elucidate global network effects, making the techniques complementary. Neurophysiological interactions of ipsilesional and contralesional PMv-M1 were tested in chronic subcortical stroke patients during grasping. Patients showed a diminished facilitatory influence of ipsilesional PMv on M1 compared to healthy controls which might contribute to their motor disability. Application of paired-associative TMS “normalised“ the reduced effective influence of ipsilesional PMv on M1 and this effect correlated with the patient‘s potential to improve their dexterity.