Neuromodulation for Depression: Insights Gained from Neuroimaging and Computational Models

Major depressive disorder (MDD) is a public health concern worldwide, affecting a sixth of the American population. Neuromodulation therapies have been employed to treat severe cases of treatment resistant depression. These procedures attempt to modulate activity in cortical regions that represent nodes in brain circuits believed to be involved in MDD. One challenge in neuromodulation trials has been the difficulty in quantifying outcome variability. We sought to understand the effects of neuromodulation therapies and their sources of variability while adding an objective perspective to assess clinical improvement in neuropsychiatric disorders such as depression. The goal of my dissertation was to investigate the neuronal circuitry of MDD patients who were treated using neuromodulation. Our primary measures were behavior scores and results from functional neuroimaging. The specific aims of this study were to answer three fundamental questions: 1) What is the role of stimulation parameters in patient response to chronic epidural cortical stimulation (EpCS) for MDD? 2) What functional changes result from repetitive transcranial magnetic stimulation (rTMS) for MDD? 3) How does stimulation of different targets in the depressive circuit affect antidepressive response? Our results suggest that combining neuroimaging with computational tools can increase the predictive power to determine who is likely to respond to a specific neuromodulation treatment course. We demonstrated the significance of stimulation parameters (location, polarity, duration) and the engagement of crucial nodes of the depressive circuit in order to achieve a sustained clinical improvement. Additionally, we showed that it is possible to affect deeper brain regions by targeting superficial areas that are easier to access with noninvasive modalities. The approaches highlighted in this dissertation can provide valuable insights about patients evaluated for neuromodulation for depression

Photocatalytic Application of Bismuth Based Semiconducting Nanoparticles and their Heterostructures towards Selective Organic Transformations and Degradation of Persistent Organic Pollutants

In this thesis, Bi based complex oxides and sulphide semiconductor nanomaterials have been synthesized by combustion synthesis route. The Bi based materials have been coupled with low band gap metal sulphide materials to form heterojunction photocatalytic systems with improved visible light absorption and photon harvesting efficiency. The photocatalytic activity of the heterostructure systems have been studied for degradation of organic pollutants from aqueous sources and selective organic transformation reactions under visible light illumination. Bismuth tungstate (Bi2WO6) nanoparticles were synthesized by combustion synthesis method using different N-containing organic compounds as fuels (urea, glycine, hexamethylenetetramine (HMTA), malonic acid dihydrazide (MDH)). Glycine as fuel was effective for synthesis of phase pure Bi2WO6 nanoparticles. Employing HMTA and MDH as fuel lead to mixed phase complex oxide system with Bi14W2O27 as minor (impurity) phase. The nature of the fuel significantly influences the particle size and morphology. The Bi2WO6 nanoparticles were used as an efficient photocatalyst for the visible light driven chemoselective oxidation of substituted thiophenols to disulfide using air as oxidant. Structurally diverse diphenyl disulfide moieties were obtained in high yield and excellent selectivity within a time span of 6 h of visible light irradiation. The Bi2WO6 nanoparticles were also synthesized by amorphous citrate process and subsequently modified by dispersing CuS to form CuS/Bi2WO6 (CuSBTA) heterojunction materials. XRD study indicated the existence of hexagonal covellite CuS and orthorhombic Russellite Bi2WO6 phase in the heterojunction materials. During hydrothermal treatment, the Cu2+ ions substituted for the W6+ ions in the Bi2WO6 lattice to form a substitutional solid solution (Bi2CuxW1-xO6-2x). The CuS and Bi2WO6 phases existed in distinct nanorod and nanosheet morphologies, respectively. During hydrothermal treatment, significant morphological reorganization of the Bi2WO6 phase took place leading to the formation of flower like hierarchical nanostructures. The CuSBTA materials possess characteristic features of a type-II heterojunction exhibiting narrow band gap, enhanced visible light absorption and efficient charge separation properties. The heterojunction materials were evaluated as visible light active photocatalyst for complete degradation of Congo red dye using H2O2 as oxidant. The CuSBTA materials exhibited higher apparent rate constant (Kapp) and greater efficiency for Congo red degradation compared to pure Bi2WO6 material. A series of type-II heterojunction nanomaterials were synthesized by coupling Bi2W2O9 with CdS and CuS. Initially, phase pure Bi2W2O9 with orthorhombic crystalline structure was prepared by a facile combustion synthesis route using urea as a fuel. The CuS and CdS nanoparticles were dispersed over Bi2W2O9 matrix by using a hydrothermal route. The heterojunction materials were characterized using XRD, XPS, FTIR, UV-Vis-DRS, PL, FESEM and HRTEM study. Pure Bi2W2O9 exhibited micron-size plate-like particles. The occurrence of ultrafine CdS nanoparticles with diameter between 8-15 nm well dispersed over Bi2W2O9 plates is noticed for CdS/Bi2W2O9 materials. For CuS/ Bi2W2O9 materials, Cu2+ ions replaced partially W6+ ions in Bi2W2O9 lattice to form Bi2CuxW2-xO9-2x as a nonstoichiometric solid solution phase. Under hydrothermal treatment, the desegregation of the Bi2W2O9 plates to nanosheets and the concurrent formation of CuS nanorods were noticed leading to their hierarchical reorganisation to microspherical structures. Both the heterojunction materials, exhibited improved visible light absorption, enhanced charge carrier separation and suitable band alignment characteristic of a type-II heterojunction. The CdS/Bi2W2O9 heterojunctions were evaluated as visible light active photocatalyst for aerobic oxidation of amines to imines. Structurally and functionally diverse amine molecules were oxidized to the corresponding imines with excellent selectivity in a short span of time. The CuS/Bi2W2O9 heterojunction materials were studied as an efficient photocatalyst for the degradation of diuron pesticide under visible light irradiation achieving 95% mineralization within 3 h. Mechanistic study indicated that the mineralization of diuron occurred in a cascade manner over the catalyst surface involving dechlorination, alkyl oxidation and oxidative ring-opening steps. A visible light promoted photocatalytic route has been developed for mineralization of alachlor pesticide using type-II CuS/BiFeO3 heterojunction materials. The heterojunctions were synthesized by a two-step process involving synthesis of BiFeO3 by combustion route followed by deposition of CuS material by hydrothermal route. Microscopically, the heterojunction materials contained BiFeO3 nanoplates and CuS nanorods. Optical property study and photocurrent measurement suggested that these materials show excellent absorption in visible region with superior charge carrier mobility and separation compared to the individual components. The CuS/BiFeO3 materials showed high efficiency for mineralization of alachlor pesticide under visible light illumination achieving >95% degradation within 60 min. The mechanism of alachlor degradation over the catalyst surface was elucidated using GCMS and radical scavenger experiments. A series of α-Fe2O3-Bi2S3 heterojunction materials were prepared by a one-step autocombustion method employing thiourea as fuel and characterized using XRD, UV–Vis-DRS, FTIR, PL, XPS, FESEM, TEM and HRTEM analytical techniques. XRD study indicated presence of rhombohedral α-Fe2O3 and orthorhombic Bi2S3 in the heterojunction materials. The heterojunctions displayed better optical absorption in the visible region. Microscopic studies indicated presence of well dispersed α-Fe2O3 nanorods in a continuous Bi2S3 matrix. The α-Fe2O3 nanorods were typically 30–50 nm in diameter and 120–150 nm in length growing isotopically in different direction from a single nucleation point. The calculated band positions of both components indicated a facile electrons transfer from the conduction band of α-Fe2O3 to Bi2S3 whereas migration of holes occurs in the reverse direction yielding a type-II heterojunction. The α-Fe2O3 -Bi2S3 heterojunctions materials were evaluated as selective and efficient photocatalyst for the hydrogen transfer reduction of nitroarenes under visible light illumination. Structurally diverse nitroarenes could be selectively reduced to the corresponding amines in high yield and purity using α-Fe2O3 -Bi2S3 as photocatalyst

Exploring Determinants of Adherence to Medical Regimens in Patients with Chronic Conditions Beyond Hypertension and Diabetes

Chronic diseases are significantly increasing globally and increasing premature deaths among population. CDC has defined chronic diseases are the conditions that last 1 year or more and require ongoing medical support or limit the daily activities or both. Diabetes and hypertension are popular chronic diseases. But there are many others are also now increasing. The current study was conducted to find out the prevalence of noncompliance among chronic diseases like thyroid diseases, Asthma, COPD, Orthopedic problems and epilepsy. Also to understand the determinants factors among them. It was a hospital based cross sectional study. The sample size was calculated and it was 36 for each disease. Total 40 study participants of each disease were included. It was randomly selected the individuals diagnosed with the mentioned chronic diseases who have been diagnosed and on treatment for more than 3 years from hospital. Result: A total of 200 patients participated in the study. The study included 40 patients from each chronic disease that is thyroid disorders, COPD, Orthopedic problems, Asthma and Epilepsy. The rural population comprised 69% of the total study group. The prevalence of medical noncompliance was found in 56.5% of all the patients. People having the disease for longer period of time were more non-compliant. The study revealed that family support and regular follow up with doctor are two important determinate factors which has positive impact on compliance. Conclusion: Noncompliance to medication regimen among chronic disease patients is an important issue for public health consideration. This current study recorded an overall noncompliance level of 57.5%. The factors identified as contributing to medication noncompliance in this study were regular follow-ups, family support, adequate knowledge regarding their disease and importance of taking medication with or without symptoms

Antiurolithiatic activity of trans-cinnamic acid against ethylene glycol induced renal calculi in rats

Urolithiasis is a complex process characterized by supersaturation and retention of salts within the kidney and also a debilitating problem worldwide. Here, we have investigated antiurolithiatic effect of trans-cinnamic acid (t-CA) against ethylene glycol (EG) induced urolithiasis in rats. Urolithiasis was induced in Wistar albino rats using 0.75% v/v EG in drinking water for 28 days. t-CA was administered @200 and 400 mg/kg along with EG for 28 days. Biochemical, urine and histopathological analysis were performed to observe the calcium oxalate (CaC2O4) deposits and renal tissue damage. The EG group showed significant rise in urine oxalate, calcium, phosphate, and renal tissues oxalates, as compared to normal group. Serum creatinine and uric acid levels were also increased significantly in EG-treated group. Histopathological studies showed marked renal tissue damage and the presence of CaC2O4 crystals. Further, treatment of t-CA significantly ameliorated oxalate, calcium, magnesium, phosphate (urine) and creatinine, uric acid (serum) in EG-induced urolithiasis after 28 days. Moreover, t-CA-treated groups showed reversal of renal tissue damage and reduced level of CaC2O4. Interestingly, t-CA @400 mg/kg, was more effective in preventing the urolithiasis and regeneration of renal tissues in rats

Proceedings of the 11th Annual Deep Brain Stimulation Think Tank: pushing the forefront of neuromodulation with functional network mapping, biomarkers for adaptive DBS, bioethical dilemmas, AI-guided neuromodulation, and translational advancements

The Deep Brain Stimulation (DBS) Think Tank XI was held on August 9–11, 2023 in Gainesville, Florida with the theme of “Pushing the Forefront of Neuromodulation”. The keynote speaker was Dr. Nico Dosenbach from Washington University in St. Louis, Missouri. He presented his research recently published in Nature inn a collaboration with Dr. Evan Gordon to identify and characterize the somato-cognitive action network (SCAN), which has redefined the motor homunculus and has led to new hypotheses about the integrative networks underpinning therapeutic DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers, and researchers (from industry and academia) can freely discuss current and emerging DBS technologies, as well as logistical and ethical issues facing the field. The group estimated that globally more than 263,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. This year's meeting was focused on advances in the following areas: cutting-edge translational neuromodulation, cutting-edge physiology, advances in neuromodulation from Europe and Asia, neuroethical dilemmas, artificial intelligence and computational modeling, time scales in DBS for mood disorders, and advances in future neuromodulation devices

Proceedings of the Eighth Annual Deep Brain Stimulation Think Tank: Advances in Optogenetics, Ethical Issues Affecting DBS Research, Neuromodulatory Approaches for Depression, Adaptive Neurostimulation, and Emerging DBS Technologies

We estimate that 208,000 deep brain stimulation (DBS) devices have been implanted to address neurological and neuropsychiatric disorders worldwide. DBS Think Tank presenters pooled data and determined that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. The DBS Think Tank was founded in 2012 providing a space where clinicians, engineers, researchers from industry and academia discuss current and emerging DBS technologies and logistical and ethical issues facing the field. The emphasis is on cutting edge research and collaboration aimed to advance the DBS field. The Eighth Annual DBS Think Tank was held virtually on September 1 and 2, 2020 (Zoom Video Communications) due to restrictions related to the COVID-19 pandemic. The meeting focused on advances in: (1) optogenetics as a tool for comprehending neurobiology of diseases and on optogenetically-inspired DBS, (2) cutting edge of emerging DBS technologies, (3) ethical issues affecting DBS research and access to care, (4) neuromodulatory approaches for depression, (5) advancing novel hardware, software and imaging methodologies, (6) use of neurophysiological signals in adaptive neurostimulation, and (7) use of more advanced technologies to improve DBS clinical outcomes. There were 178 attendees who participated in a DBS Think Tank survey, which revealed the expansion of DBS into several indications such as obesity, post-traumatic stress disorder, addiction and Alzheimer’s disease. This proceedings summarizes the advances discussed at the Eighth Annual DBS Think Tank