Ultrasonic Modification of Human Brain Structures for Treatment of Neurological Disorders

ABSTRACT Viral infection of the central nervous system (CNS) can result in perturbation of cell-to-cell communication involving the extracellular matrix (ECM). ECM integrity is maintained by a dynamic balance between the synthesis and proteolysis of its components, mainly as a result of the action of matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs). An MMP/TIMP imbalance may be critical in triggering neurological disorders, in particular in virally induced neural disorders. In the present study, a mouse model of brain infection using a neurotropic strain of canine distemper virus (CDV) was used to study the effect of CNS infection on the MMP/TIMP balance and cytokine expression. CDV replicates almost exclusively in neurons and has a unique pattern of expression (cortex, hypothalamus, monoaminergic nuclei, hippocampus, and spinal cord). Here we show that although several mouse brain structures were infected, they exhibited a differential pattern in terms of MMP, TIMP, and cytokine expression, exemplified by (i) a large increase in pro-MMP9 levels, in particular in the hippocampus, which occurred mainly in neurons and was associated with in situ gelatinolytic activity, (ii) specific and significant upregulation of MT1-MMP mRNA expression in the cortex and hypothalamus, (iii) an MMP/TIMP imbalance, suggested by the upregulation of TIMP-1 mRNA in the cortex, hippocampus, and hypothalamus and of TIMP-3 mRNA in the cortex, and (iv) a concomitant region-specific large increase in expression of Th1-like cytokines, such as gamma interferon, tumor necrosis factor alpha, and interleukin 6 (IL-6), contrasting with weaker induction of Th2-like cytokines, such as IL-4 and IL-10. These data indicate that an MMP/TIMP imbalance in specific brain structures, which is tightly associated with a local inflammatory process as shown by the presence of immune infiltrating cells, differentially impairs CNS integrity and may contribute to the multiplicity of late neurological disorders observed in this viral mouse model.

Download Full-text

First evidence of long-term effects of transcranial pulse stimulation (TPS) on the human brain

Journal of Translational Medicine ◽

10.1186/s12967-021-03222-5 ◽

2022 ◽

Vol 20 (1) ◽

Author(s):

Eva Matt ◽

Lisa Kaindl ◽

Saskia Tenk ◽

Anicca Egger ◽

Teodora Kolarova ◽

...

Keyword(s):

Human Brain ◽

Brain Stimulation ◽

Longitudinal Design ◽

Brain Structures ◽

Brain Network ◽

Long Term Effects ◽

Sensorimotor Network ◽

Functional Brain Network ◽

Pulse Stimulation

Abstract Background With the high spatial resolution and the potential to reach deep brain structures, ultrasound-based brain stimulation techniques offer new opportunities to non-invasively treat neurological and psychiatric disorders. However, little is known about long-term effects of ultrasound-based brain stimulation. Applying a longitudinal design, we comprehensively investigated neuromodulation induced by ultrasound brain stimulation to provide first sham-controlled evidence of long-term effects on the human brain and behavior. Methods Twelve healthy participants received three sham and three verum sessions with transcranial pulse stimulation (TPS) focused on the cortical somatosensory representation of the right hand. One week before and after the sham and verum TPS applications, comprehensive structural and functional resting state MRI investigations and behavioral tests targeting tactile spatial discrimination and sensorimotor dexterity were performed. Results Compared to sham, global efficiency significantly increased within the cortical sensorimotor network after verum TPS, indicating an upregulation of the stimulated functional brain network. Axial diffusivity in left sensorimotor areas decreased after verum TPS, demonstrating an improved axonal status in the stimulated area. Conclusions TPS increased the functional and structural coupling within the stimulated left primary somatosensory cortex and adjacent sensorimotor areas up to one week after the last stimulation. These findings suggest that TPS induces neuroplastic changes that go beyond the spatial and temporal stimulation settings encouraging further clinical applications.

Download Full-text

Cellular resolution anatomical and molecular atlases for prenatal human brains

10.1101/2021.07.14.452297 ◽

2021 ◽

Author(s):

Song-Lin Ding ◽

Joshua J. Royall ◽

Phil Lesnar ◽

Benjamin A.C. Facer ◽

Kimberly A. Smith ◽

...

Keyword(s):

Human Brain ◽

Hippocampal Formation ◽

Marker Gene ◽

Brain Structures ◽

Marker Genes ◽

Subcortical Structures ◽

Cellular Resolution ◽

Reliable Marker ◽

Human Brains ◽

Developmental Features

Increasing interest in studies of prenatal human brain development, particularly using new single-cell genomics and anatomical technologies to create cell atlases, creates a strong need for accurate and detailed anatomical reference atlases. In this study, we present two cellular-resolution digital anatomical atlases for prenatal human brain at post-conceptional weeks (PCW) 15 and 21. Both atlases were annotated on sequential Nissl-stained sections covering brain-wide structures on the basis of combined analysis of cytoarchitecture, acetylcholinesterase staining and an extensive marker gene expression dataset. This high information content dataset allowed reliable and accurate demarcation of developing cortical and subcortical structures and their subdivisions. Furthermore, using the anatomical atlases as a guide, spatial expression of 37 and 5 genes from the brains respectively at PCW 15 and 21 was annotated, illustrating reliable marker genes for many developing brain structures. Finally, the present study uncovered several novel developmental features, such as the lack of an outer subventricular zone in the hippocampal formation and entorhinal cortex, and the apparent extension of both cortical (excitatory) and subcortical (inhibitory) progenitors into the prenatal olfactory bulb. These comprehensive atlases provide useful tools for visualization, targeting, imaging and interpretation of brain structures of prenatal human brain, and for guiding and interpreting the next generation of cell census and connectome studies.

Download Full-text

Volitional Control of Individual Neurons in the Human Brain

10.1101/2020.05.05.079038 ◽

2020 ◽

Author(s):

Kramay Patel ◽

Chaim N. Katz ◽

Suneil K. Kalia ◽

Milos R. Popovic ◽

Taufik A. Valiante

Keyword(s):

Human Brain ◽

Firing Rate ◽

Phase Locking ◽

Brain Structures ◽

Human Memory ◽

Skill Learning ◽

Oscillation Phase ◽

Improved Performance ◽

Beta Frequency ◽

Interconnected Structure

AbstractCan the human brain, a complex interconnected structure of over 80 billion neurons learn to control itself at the most elemental scale – a single neuron. We directly linked the firing rate of a single (direct) neuron to the position of a box on a screen, which participants tried to control. Remarkably, all subjects upregulated the firing rate of the direct neuron in memory structures of their brain. Learning was accompanied by improved performance over trials, simultaneous decorrelation of the direct neuron to local neurons, and direct neuron to beta frequency oscillation phase-locking. Such previously unexplored neuroprosthetic skill learning within memory related brain structures, and associated beta frequency phase-locking implicates the ventral striatum. Our demonstration that humans can volitionally control neuronal activity in mnemonic structures, may provide new ways of probing the function and plasticity of human memory without exogenous stimulation.

Download Full-text

Morphological Studies on Brain Structures of the NZB Mouse: An Animal Model for the Aging Human Brain?

Advances in Applied Neurological Sciences - Senile Dementia of the Alzheimer Type ◽

10.1007/978-3-642-70644-8_29 ◽

1985 ◽

pp. 355-365 ◽

Cited By ~ 11

Author(s):

K. Zilles

Keyword(s):

Animal Model ◽

Human Brain ◽

Brain Structures ◽

Morphological Studies

Download Full-text

Mind and Matter

Mind Shift ◽

10.1093/oso/9780198801634.003.0002 ◽

2021 ◽

pp. 19-31

Author(s):

John Parrington

Keyword(s):

Human Brain ◽

Rene Descartes ◽

Brain Structures ◽

Human Mind ◽

Black Box ◽

Human Consciousness ◽

Common Thread ◽

René Descartes

This chapter discusses different views on the basis of human consciousness. A major problem with much popular speculation about the biological roots of consciousness is that those who advocate a gene-based view of consciousness often appear to have little understanding of modern genetics, while speculation about how brain structures shape that consciousness often bear little resemblance to emerging knowledge about the complexity of an actual human brain. There is a common thread here, which is that idealised genes and brains have been substituted for real ones. Unfortunately, because of this tendency, it is not clear how much we have really advanced forwards from René Descartes and his belief that the human mind was an unknowable entity, or for that matter, the behaviourists with their view that the human mind could be treated as a black box. In contrast, to understand human consciousness, there is a need to understand real genes, real brains, and how these have evolved in humans compared to other species.

Download Full-text

P2-142 Tissue slice cultures from human brain autopsies and biopsies: alzheimer's disease and other neurological disorders

Neurobiology of Aging ◽

10.1016/s0197-4580(04)80889-3 ◽

2004 ◽

Vol 25 ◽

pp. S265

Author(s):

Ronald W. Verwer ◽

Rawien Balesar ◽

Lei Wu ◽

Elisabeth F. Boiten ◽

Arja A. Sluiter ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Human Brain ◽

Neurological Disorders ◽

Tissue Slice

Download Full-text

Antibodies to normal and Alzheimer human brain structures from non-immunised mice of various ages

FEBS Letters ◽

10.1016/0014-5793(87)81243-7 ◽

1987 ◽

Vol 217 (1) ◽

pp. 62-64 ◽

Cited By ~ 2

Author(s):

James Simpson ◽

Ian H. Milne ◽

John O. Gardner ◽

Celia M. Yates ◽

Keith James ◽

...

Keyword(s):

Human Brain ◽

Brain Structures

Download Full-text

Realistic modeling of ephaptic fields in the human brain

10.1101/688101 ◽

2019 ◽

Cited By ~ 2

Author(s):

Giulio Ruffini ◽

Ricardo Salvador ◽

Ehsan Tadayon ◽

Roser Sanchez-Todo ◽

Alvaro Pascual-Leone ◽

...

Keyword(s):

Human Brain ◽

Electric Fields ◽

Neuronal Activity ◽

Direct Interaction ◽

Pyramidal Cells ◽

Brain Structures ◽

Relative Orientation ◽

Transcranial Brain Stimulation ◽

Potential Perturbation ◽

Human Function

AbstractSeveral decades of research suggest that weak electric fields may influence neural processing, including those induced by neuronal activity and recently proposed as substrate for a potential new cellular communication system, i.e., ephaptic transmission. Here we aim to map ephaptic activity in the human brain and explore its trajectory during aging by characterizing the macroscopic electric field generated by cortical dipoles using realistic finite element modeling. We find that modeled endogenous field magnitudes are comparable to those in measurements of weak but functionally relevant endogenous fields and to those generated by noninvasive transcranial brain stimulation, therefore possibly able to modulate neuronal activity. Then, to evaluate the role of self-generated ephaptic fields in the human cortex, we adapt an interaction approximation that considers the relative orientation of neuron and field to derive the membrane potential perturbation in pyramidal cells. Building on this, we define a simplified metric (EMOD1) that weights dipole coupling as a function of distance and relative orientation between emitter and receiver and evaluate it in a sample of 401 realistic human brain models from subjects aged 16-83. Results reveal that ephaptic modulation follows gyrification patterns in the human brain, and significantly decreases with age, with higher involvement of sensorimotor regions and medial brain structures. By providing the means for fast and direct interaction between neurons, ephaptic modulation likely contributes to the complexity of human function for cognition and behavior, and its modification across the lifespan and in response to pathology.

Download Full-text

New chemical biopsy tool for spatially resolved profiling of human brain tissue in vivo

Scientific Reports ◽

10.1038/s41598-021-98973-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Joanna Bogusiewicz ◽

Katarzyna Burlikowska ◽

Kamil Łuczykowski ◽

Karol Jaroch ◽

Marcin Birski ◽

...

Keyword(s):

Human Brain ◽

Grey Matter ◽

Solid Phase ◽

Imaging Techniques ◽

Brain Structures ◽

Limited Information ◽

Human Brain Tissue ◽

Sampling Device ◽

Spatially Resolved

AbstractIt is extremely challenging to perform chemical analyses of the brain, particularly in humans, due to the restricted access to this organ. Imaging techniques are the primary approach used in clinical practice, but they only provide limited information about brain chemistry. Solid-phase microextraction (SPME) has been presented recently as a chemical biopsy tool for the study of animal brains. The current work demonstrates for the first time the use of SPME for the spatially resolved sampling of the human brain in vivo. Specially designed multi-probe sampling device was used to simultaneously extract metabolites from the white and grey matter of patients undergoing brain tumor biopsies. Samples were collected by inserting the probes along the planned trajectory of the biopsy needle prior to the procedure, which was followed by metabolomic and lipidomic analyses. The results revealed that studied brain structures were predominantly composed of lipids, while the concentration and diversity of detected metabolites was higher in white than in grey matter. Although the small number of participants in this research precluded conclusions of a biological nature, the results highlight the advantages of the proposed SPME approach, as well as disadvantages that should be addressed in future studies.

Download Full-text