Medical Neurobiology Commons^™

The Climate Of Neurofeedback: Scientific Rigour And The Perils Of Ideology, Robert T. Thibault, Michael Lifshitz, Amir Raz

Psychology Faculty Articles and Research

Over the last six decades, an in-group with ideological and financial stakes has been conducting sub-par research to develop an ostensibly effective clinical intervention: EEG-neurofeedback. More recently, however, a string of independent studies featuring increased scientific rigour and tighter experimental controls has challenged the foundation on which EEG-neurofeedback stands. Earlier this year, Brain published one of the most robust EEG-neurofeedback experiments to date (Schabus et al., 2017), which sparked a flurry of correspondence concerning the therapeutic value of neurofeedback (Fovet et al., 2017; Schabus, 2017); notably, a parallel discussion continues in Lancet Psychiatry …

Role Of Microglial Amylin Receptors In Mediating Beta Amyloid (Aβ)-Induced Inflammation, Wen Fu, Vlatka Vukojevic, Aarti Patel, Rania Soudy, David Mactavish, David Westaway, Kamaljit Kaur, Valeri Goncharuk, Jack Jhamandas

Pharmacy Faculty Articles and Research

Background: Neuroinflammation in the brain consequent to activation of microglia is viewed as an important component of Alzheimer’s disease (AD) pathology. Amyloid beta (Aβ) protein is known to activate microglia and unleash an inflammatory cascade that eventually results in neuronal dysfunction and death. In this study, we sought to identify the presence of amylin receptors on human fetal and murine microglia and determine whether Aβ activation of the inflammasome complex and subsequent release of cytokines is mediated through these receptors.

Methods: The presence of dimeric components of the amylin receptor (calcitonin receptor and receptor activity modifying protein 3) …

Trkb-Enhancer Facilitates Functional Recovery After Traumatic Brain Injury, John Marshall, Joanna Szmydynger-Chodobska, Mengia S. Rioult-Pedotti, Kara Lau, Andrea T. Chin, Siva K. Reddy Kotla, Rakesh Tiwari, Keykavous Parang, Steven W. Threlkeld, Adam Chodobski

Pharmacy Faculty Articles and Research

Brain-derived neurotrophic factor (BDNF), a key player in regulating synaptic strength and learning, is dysregulated following traumatic brain injury (TBI), suggesting that stimulation of BDNF signaling pathways may facilitate functional recovery. This study investigates whether CN2097, a peptidomimetic ligand which targets the synaptic scaffold protein, postsynaptic density protein 95, to enhance downstream signaling of tropomyosin-related kinase B, a receptor for BDNF, can improve neurological function after TBI. Moderate to severe TBI elicits neuroinflammation and c-Jun-N-terminal kinase (JNK) activation, which is associated with memory deficits. Here we demonstrate that CN2097 significantly reduces the post-traumatic synthesis of proinflammatory mediators and inhibits the …

Efficient Synthesis Of Cn2097 Using In Situ Activation Of Sulfhydryl Group, Shaban Darwish, Keykavous Parang, John Marshall, Dennis J. Goebel, Rakesh Tiwari

Pharmacy Faculty Articles and Research

CN2097 (R₇Cs-sCYK[KTE(β-Ala)]V) is a rationally designed peptidomimetic that shows effectiveness in preclinical models for the treatment of neurological disorders, such as Angelman syndrome, traumatic brain injury (TBI), and stroke. Because of its potential therapeutic activity for the treatment of human CNS disorders, there was an urgent need to develop an efficient strategy for large-scale synthesis of CN2097. The synthesis of CN2097 was accomplished using Fmoc/tBu solid phase chemistry in multiple steps. Two different peptide fragments (activated polyarginine peptide Npys-sCR₇ and CYK[KTE(β-Ala)]V) were synthesized, followed by solution phase coupling in water. Activation of the polyarginine (CR₇) …

Neurofeedback Or Neuroplacebo?, Robert T. Thibault, Michael Lifshitz, Amir Raz

Psychology Faculty Articles and Research

This scientific commentary refers to ‘Better than sham? A double-blind placebo-controlled neurofeedback study in primary insomnia’, by Schabus et al.. (doi:10.1093/brain/awx011).

Role Of Corpus Callosum Integrity In Arm Function Differs Based On Motor Severity After Stroke, Jill Campbell Stewart, Pritha Dewanjee, George Tran, Erin Burke Quinlan, Lucy Dodakian, Alison Mckenzie, Jill See, Steven C. Cramer

Physical Therapy Faculty Articles and Research

While the corpus callosum (CC) is important to normal sensorimotor function, its role in motor function after stroke is less well understood. This study examined the relationship between structural integrity of the motor and sensory sections of the CC, as reflected by fractional anisotropy (FA), and motor function in individuals with a range of motor impairment level due to stroke. Fifty-five individuals with chronic stroke (Fugl-Meyer motor score range 14 to 61) and 18 healthy controls underwent diffusion tensor imaging and a set of motor behavior tests. Mean FA from the motor and sensory regions of the CC and from …

Regulation Of Sleep Plasticity By A Thermo-Sensitive Circuit In Drosophila., Angelique Lamaze, Arzu Öztürk-Çolak, Robin Fischer, Nicolai Peschel, Kyunghee Koh, James E.C. Jepson

Department of Neuroscience Faculty Papers

Sleep is a highly conserved and essential behaviour in many species, including the fruit fly Drosophila melanogaster. In the wild, sensory signalling encoding environmental information must be integrated with sleep drive to ensure that sleep is not initiated during detrimental conditions. However, the molecular and circuit mechanisms by which sleep timing is modulated by the environment are unclear. Here we introduce a novel behavioural paradigm to study this issue. We show that in male fruit flies, onset of the daytime siesta is delayed by ambient temperatures above 29 °C. We term this effect Prolonged Morning Wakefulness (PMW). We show that …

Cerebellar Tdcs: A Novel Approach To Augment Language Treatment Post-Stroke, Rajani Sebastian, Sadhvi Saxena, Kyrana Tsapkini, Andreia V. Faria, Charltien Long, Amy Wright, Cameron Davis, Donna C. Tippett, Antonios P. Mourdoukoutas, Marom Bikson, Pablo Celnik, Argye E. Hillis

Publications and Research

People with post-stroke aphasia may have some degree of chronic deficit for which current rehabilitative treatments are variably effective. Accumulating evidence suggests that transcranial direct current stimulation (tDCS) may be useful for enhancing the effects of behavioral aphasia treatment. However, it remains unclear which brain regions should be stimulated to optimize effects on language recovery. Here, we report on the therapeutic potential of right cerebellar tDCS in augmenting language recovery in SMY, who sustained bilateral MCA infarct resulting in aphasia and anarthria. We investigated the effects of 15 sessions of anodal cerebellar tDCS coupled with spelling therapy using a randomized, …

Distinct Neural Bases Of Disruptive Behavior And Autism Symptom Severity In Boys With Autism Spectrum Disorder., Y.J. Daniel Yang, Denis G Sukhodolsky, Jiedi Lei, Eran Dayan, Kevin A. Pelphrey, Pamela Ventola

Pediatrics Faculty Publications

BACKGROUND: Disruptive behavior in autism spectrum disorder (ASD) is an important clinical problem, but its neural basis remains poorly understood. The current research aims to better understand the neural underpinnings of disruptive behavior in ASD, while addressing whether the neural basis is shared with or separable from that of core ASD symptoms.

METHODS: Participants consisted of 48 male children and adolescents: 31 ASD (7 had high disruptive behavior) and 17 typically developing (TD) controls, well-matched on sex, age, and IQ. For ASD participants, autism symptom severity, disruptive behavior, anxiety symptoms, and ADHD symptoms were measured. All participants were scanned while …

Cyclic Ac253, A Novel Amylin Receptor Antagonist, Improves Cognitive Deficits In A Mouse Model Of Alzheimer’S Disease, Rania Soudy, Aarti Patel, Wen Fu, Kamaljit Kaur, David Mactavish, David Westaway, Rachel Davey, Jeffrey Zajac, Jack Jhamandas

Pharmacy Faculty Articles and Research

Introduction: Amylin receptor serves as a portal for the expression of deleterious effects of amyloid b-protein (Ab), a key pathologic hallmark of Alzheimer’s disease. Previously, we showed that AC253, an amylin receptor antagonist, is neuroprotective against Ab toxicity in vitro and abrogates Ab-induced impairment of hippocampal long-term potentiation.

Methods: Amyloid precursor protein–overexpressing TgCRND8 mice received intracerebroventricularly AC253 for 5 months. New cyclized peptide cAC253 was synthesized and administered intraperitoneally three times a week for 10 weeks in the same mouse model. Cognitive functions were monitored, and pathologic changes were quantified biochemically and immunohistochemically.

Results: AC253, when administered …