Zafer Keser

The medial forebrain bundle as a deep brain stimulation target for treatment resistant depression: A review of published data.

INTRODUCTION Despite a wide variety of therapeutic interventions for major depressive disorder (MDD), treatment resistant depression (TRD) remains to be prevalent and troublesome in clinical practice. In recent years, deep brain stimulation (DBS) has emerged as an alternative for individuals suffering from TRD not responding to combining antidepressants, multiple adjunctive strategies and electroconvulsive therapy (ECT). Although the best site for TRD-DBS is still unclear, pilot data suggests that the medial forebrain bundle (MFB) might be a key target to accomplish therapeutic efficacy in TRD patients. OBJECTIVE To explore the anatomic, electrophysiologic, neurocognitive and treatment data supporting the MFB as a target for TRD-DBS. RESULTS The MFB connects multiple targets involved in motivated behavior, mood regulation and antidepressant response. Specific phenomenology associated with TRD can be linked specifically to the superolateral branch (sl) of the MFB (slMFB). TRD patients who received DBS-slMFB reported high response/remission rates with an improvement in functioning and no significant adverse outcomes in their physical health or neurocognitive performance. DISCUSSION The slMFB is an essential component of a network of structural and functional pathways connecting different areas possibly involved in the pathogenesis of mood disorders. Therefore, the slMFB should be considered as an exciting therapeutic target for DBS therapy to achieve a sustained relief in TRD patients. CONCLUSION There is an urgent need for clinical trials exploring DBS-slMFB in TRD. Further efforts should pursue measuring baseline pro-inflammatory cytokines, oxidative stress, and cognition as possible biomarkers of DBS-slMFB response in order to aid clinicians in better patient selection.

Diffusion tensor imaging of the human cerebellar pathways and their interplay with cerebral macrostructure

Cerebellar white matter (WM) connections to the central nervous system are classified functionally into the Spinocerebellar (SC), vestibulocerebellar (VC), and cerebrocerebellar subdivisions. The SC pathways project from spinal cord to cerebellum, whereas the VC pathways project from vestibular organs of the inner ear. Cerebrocerebellar connections are composed of feed forward and feedback connections between cerebrum and cerebellum including the cortico-ponto-cerebellar (CPC) pathways being of cortical origin and the dentate-rubro-thalamo-cortical (DRTC) pathway being of cerebellar origin. In this study we systematically quantified the whole cerebellar system connections using diffusion tensor magnetic resonance imaging (DT-MRI). Ten right-handed healthy subjects (7 males and 3 females, age range 20–51 years) were studied. DT-MRI data were acquired with a voxel size = 2 mm × 2 mm × 2 mm at a 3.0 Tesla clinical MRI scanner. The DT-MRI data were prepared and analyzed using anatomically-guided deterministic tractography methods to reconstruct the SC, DRTC, fronto-ponto-cerebellar (FPC), parieto-ponto-cerebellar (PPC), temporo-ponto-cerebellar (TPC) and occipito-ponto-cerebellar (OPC). The DTI-attributes or the cerebellar tracts along with their cortical representation (Brodmann areas) were presented in standard Montréal Neurological Institute space. All cerebellar tract volumes were quantified and correlated with volumes of cerebral cortical, subcortical gray matter (GM), cerebral WM and cerebellar GM, and cerebellar WM. On our healthy cohort, the ratio of total cerebellar GM-to-WM was ~3.29 ± 0.24, whereas the ratio of cerebral GM-to-WM was approximately 1.10 ± 0.11. The sum of all cerebellar tract volumes is ~25.8 ± 7.3 mL, or a percentage of 1.6 ± 0.45 of the total intracranial volume (ICV).

Distinguishing and quantification of the human visual pathways using high-spatial-resolution diffusion tensor tractography.

Quantification of the living human visual system using MRI methods has been challenging, but several applications demand a reliable and time-efficient data acquisition protocol. In this study, we demonstrate the utility of high-spatial-resolution diffusion tensor fiber tractography (DTT) in reconstructing and quantifying the human visual pathways. Five healthy males, age range 24-37years, were studied after approval of the institutional review board (IRB) at The University of Texas Health Science Center at Houston. We acquired diffusion tensor imaging (DTI) data with 1-mm slice thickness on a 3.0-Tesla clinical MRI scanner and analyzed the data using DTT with the fiber assignment by continuous tractography (FACT) algorithm. By utilizing the high-spatial-resolution DTI protocol with FACT algorithm, we were able to reconstruct and quantify bilateral optic pathways including the optic chiasm, optic tract, optic radiations free of contamination from neighboring white matter tracts.

Transcranial direct current stimulation (tDCS) of the primary motor cortex and robot-assisted arm training in chronic incomplete cervical spinal cord injury: A proof of concept sham-randomized clinical study

BACKGROUND After cervical spinal cord injury, current options for treatment of upper extremity motor functions have been limited to traditional approaches. However, there is a substantial need to explore more rigorous alternative treatments to facilitate motor recovery. OBJECTIVE To demonstrate whether anodal-primary motor cortex (M1) excitability enhancement (with cathodal-supra orbital area) (atDCS) combined with robot-assisted arm training (R-AAT) will provide greater improvement in contralateral arm and hand motor functions compared to sham stimulation (stDCS) and R-AAT in patients with chronic, incomplete cervical spinal cord injury (iCSCI). METHODS In this parallel-group, double-blinded, randomized and sham-controlled trial, nine participants with chronic iCSCI (AIS C and D level) were randomized to receive 10 sessions of atDCS or stDSC combined with R-AAT. Feasibility and tolerability was assessed with attrition rate and occurrence of adverse events, Changes in arm and hand function were assessed with Jebson Taylor Hand Function Test (JTHFT). Amount of Use Scale of Motor Activity Log (AOU-MAL), American Spinal Injury Association Upper Extremity Motor Score and Modified Ashworth Scale (MAS) at baseline, after treatment, and at two-month follow-up. RESULTS None of the participants missed a treatment session or dropped-out due to adverse events related to the treatment protocol. Participants tended to perform better in JTHFT and AOU-MAL after treatment. Active group at post-treatment and two-month follow-up demonstrated better arm and hand performance compared to sham group. CONCLUSION These preliminary findings support that modulating excitatory input of the corticospinal tracts on spinal circuits may be a promising strategy in improving arm and hand functions in persons with incomplete tetraplegia. Further study is needed to explore the underlying mechanisms of recovery.

Mapping the trajectory of the stria terminalis of the human limbic system using high spatial resolution diffusion tensor tractography

The human limbic system is composed of gray and white matter structures which have been known to have a role in core processes such as motivation, memory, emotion, social behavior, self-awareness as well as certain primitive instincts. Multiple functional studies investigated some of these brain tasks in human brain limbic system. However, the underlying fine fiber pathways of the limbic system including the trajectory of the stria terminalis have not been delineated separately by prior diffusion weighted imaging. The ability to trace the underlying fiber anatomy noninvasively using diffusion tensor tractography (DTT) would be helpful to study the neurophysiology of these tracts in different functions in future functional studies. Few studies have focused on the stria terminalis using diffusion tensor tractography. Yet, the trajectory of the stria terminalis and some fine subtrajectories of the fornix have not been elucidated by prior DTT studies. We decided to further investigate these fine neuronal trajectory using tractography and high spatial resolution diffusion tensor imaging on 3T. Fifteen healthy right-handed men (age range 24-37 years) were studied. We delineated the detailed trajectories of the stria terminalis and fornix bilaterally in fifteen normal adult human brains. Using a high resolution DTT technique, we demonstrate for the first time, the trajectory of stria terminalis as well as detailed precommissural and postcommissural connectivity of the forniceal columns.

Limbic Pathway Correlates of Cognitive Impairment in Multiple Sclerosis

Distinct injuries to various limbic white matter pathways have been reported to be associated with different aspects of cognitive dysfunction in multiple sclerosis (MS). Diffusion tensor imaging (DTI) offers a noninvasive method to map tissue microstructural organization. We utilized quantitative magnetic resonance imaging methods to analyze the main limbic system—white matter structures in MS patients with cognitive impairment (CI).

Lifespan Gyrification Trajectories of Human Brain in Healthy Individuals and Patients with Major Psychiatric Disorders

Cortical gyrification of the brain represents the folding characteristic of the cerebral cortex. How the brain cortical gyrification changes from childhood to old age in healthy human subjects is still unclear. Additionally, studies have shown regional gyrification alterations in patients with major psychiatric disorders, such as major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ). However, whether the lifespan trajectory of gyrification over the brain is altered in patients diagnosed with major psychiatric disorders is still unknown. In this study, we investigated the trajectories of gyrification in three independent cohorts based on structural brain images of 881 subjects from age 4 to 83. We discovered that the trajectory of gyrification during normal development and aging was not linear and could be modeled with a logarithmic function. We also found that the gyrification trajectories of patients with MDD, BD and SCZ were deviated from the healthy one during adulthood, indicating altered aging in the brain of these patients.

Entorhinal Cortex Thickness across the Human Lifespan.

Human entorhinal cortex (ERC) connects the temporal neocortex with hippocampus and is essential for memory retrieval and navigation. Markedly, there have been only few quantitative MRI works on the ERC geometric measurements in pediatric and adult healthy subjects across the lifespan. Here, we sought to fill this gap in knowledge by quantifying the ERC thickness in a very large cohort of subjects spanning 9 decades of life.

Quantitative Mapping of Human Brain Vertical-Occipital Fasciculus.

The vertical‐occipital fasciculus (VOF), historically named as “the fasciculus occipitalis verticalis of Wernicke,” has been recently brought to the attention of the neuroscience community. In this study, we delineated and quantified this tract with deterministic diffusion tensor imaging protocol.

Neuropharmacology of Poststroke Motor and Speech Recovery

Almost 7 million adult Americans have had a stroke. There is a growing need for more effective treatment options as add-ons to conventional therapies. This article summarizes the published literature for pharmacologic agents used for the enhancement of motor and speech recovery after stroke. Amphetamine, levodopa, selective serotonin reuptake inhibitors, and piracetam were the most commonly used drugs. Pharmacologic augmentation of stroke motor and speech recovery seems promising but systematic, adequately powered, randomized, and double-blind clinical trials are needed. At this point, the use of these pharmacologic agents is not supported by class I evidence.